Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Antineoplastic Combined Chemotherapy Protocols: The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae".Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Etoposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.Lung Neoplasms: Tumors or cancer of the LUNG.Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.DeoxycytidineCombined Modality Therapy: The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.Vinblastine: Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)DNA Adducts: The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.Paclitaxel: A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.Cell Line, Tumor: A cell line derived from cultured tumor cells.Head and Neck Neoplasms: Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)Carboplatin: An organoplatinum compound that possesses antineoplastic activity.Ifosfamide: Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Vomiting: The forcible expulsion of the contents of the STOMACH through the MOUTH.Carcinoma, Squamous Cell: A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Carcinoma, Non-Small-Cell Lung: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Taxoids: A group of diterpenoid CYCLODECANES named for the taxanes that were discovered in the TAXUS tree. The action on MICROTUBULES has made some of them useful as ANTINEOPLASTIC AGENTS.Infusions, Intravenous: The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.LeukopeniaDose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Testicular Neoplasms: Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms.Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.Neoplasm Staging: Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.Vindesine: Vinblastine derivative with antineoplastic activity against CANCER. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols (ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS).Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Oxonic Acid: Antagonist of urate oxidase.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Carcinoma, Small Cell: An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1286-7)Neutropenia: A decrease in the number of NEUTROPHILS found in the blood.Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.Tegafur: Congener of FLUOROURACIL with comparable antineoplastic action. It has been suggested especially for the treatment of breast neoplasms.Stomach Neoplasms: Tumors or cancer of the STOMACH.Neoplasms, Germ Cell and Embryonal: Neoplasms composed of primordial GERM CELLS of embryonic GONADS or of elements of the germ layers of the EMBRYO, MAMMALIAN. The concept does not refer to neoplasms located in the gonads or present in an embryo or FETUS.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Germinoma: A malignant neoplasm of the germinal tissue of the GONADS; MEDIASTINUM; or pineal region. Germinomas are uniform in appearance, consisting of large, round cells with vesicular nuclei and clear or finely granular eosinophilic-staining cytoplasm. (Stedman, 265th ed; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1642-3)Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals.Neoplasm Recurrence, Local: The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Esophageal Neoplasms: Tumors or cancer of the ESOPHAGUS.Mesothelioma: A tumor derived from mesothelial tissue (peritoneum, pleura, pericardium). It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. (Dorland, 27th ed)Chemotherapy, Adjuvant: Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.Antiemetics: Drugs used to prevent NAUSEA or VOMITING.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Maximum Tolerated Dose: The highest dose of a biologically active agent given during a chronic study that will not reduce longevity from effects other than carcinogenicity. (from Lewis Dictionary of Toxicology, 1st ed)Epirubicin: An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.Pleural Neoplasms: Neoplasms of the thin serous membrane that envelopes the lungs and lines the thoracic cavity. Pleural neoplasms are exceedingly rare and are usually not diagnosed until they are advanced because in the early stages they produce no symptoms.Urologic Neoplasms: Tumors or cancer of the URINARY TRACT in either the male or the female.Thrombocytopenia: A subnormal level of BLOOD PLATELETS.Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.Carcinoma: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)Antimetabolites, Antineoplastic: Antimetabolites that are useful in cancer chemotherapy.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.GuanineCyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.Platinum Compounds: Inorganic compounds which contain platinum as the central atom.Radiation-Sensitizing Agents: Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.Induction Chemotherapy: Initial drug treatment designed to bring about REMISSION INDUCTION. It is typically a short-term and high-dose drug treatment that is followed by CONSOLIDATION CHEMOTHERAPY and then MAINTENANCE CHEMOTHERAPY.Neoadjuvant Therapy: Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment.Hematologic Diseases: Disorders of the blood and blood forming tissues.Uterine Cervical Neoplasms: Tumors or cancer of the UTERINE CERVIX.Osteosarcoma: A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level.Thiosulfates: Inorganic salts of thiosulfuric acid possessing the general formula R2S2O3.Dose Fractionation: Administration of the total dose of radiation (RADIATION DOSAGE) in parts, at timed intervals.

Tumour ablation and hepatic decompensation rates in multi-agent chemoembolization of hepatocellular carcinoma. (1/7975)

Thirty-seven cirrhotic patients with 62 hepatocellular carcinoma (HCC) foci--most Child-Pugh class B or C and/or with large, inoperable tumours--underwent 148 sessions of transcatheter arterial chemoembolization (TACE) using lipiodol, doxorubicin and cisplatin. Treatment efficacy was assessed by serial hepatic arteriography in 34/37 (91.9%) patients and abdominal CT scanning in 3/37 (8.1%) patients. Child-Pugh status was determined prior to each treatment session. Varying degrees of control of tumour neovascularity occurred for a median 390 days (range 90 to > 1680 days) in 33/34 (97.1%) patients in whom progress hepatic arteriography was performed. Ablation of tumour neovascularity occurred in 6/6 (100%), 4/12 (33.3%) and 6/16 (37.5%) patients with HCC diameters < 4 cm, 4-7 cm and > 8 cm, respectively (p < 0.02). Significantly more sessions were required for ablation of larger tumours (p < 0.05). Recurrent HCC was detected in 50% of patients after a median 240 days (range 60-1120 days). Deterioration in Child-Pugh status followed a session of TACE on 19/148 (12.8%) occasions but resulted in unscheduled hospitalization on only 4/148 (2.7%) occasions, the highest incidence (8.3%) in Child-Pugh C patients. Actuarial survival was 27/36 (75.0%) at 6 months, 17/34 (50.0%) at 12 months, 14/34 (41.2%) at 18 months, 9/31 (29.0%) at 24 months and 4/27 (14.8%) at 36 months. Multi-agent TACE with lipiodol, doxorubicin and cisplatin provides a useful anti-tumour effect, even in cirrhotic patients with large HCCs. The incidence of clinically significant deterioration in hepatic function due to ischaemia of non-tumorous liver is acceptably low, even in Child-Pugh C patients.  (+info)

Intensive weekly chemotherapy is not effective in advanced pancreatic cancer patients: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). (2/7975)

Twenty-two patients, with locally advanced unresectable and/or metastatic pancreatic carcinoma, received weekly administration of cisplatin 40 mg m(-2), 5-fluorouracil 500 mg m(-2), epidoxorubicin 35 mg m(-2), 6S stereoisomer of leucovorin 250 mg m(-2) and glutathione 1.5 mg m(-2), supported by a daily administration of lenograstim at a dose of 5 microg kg(-1). Nineteen patients were men and three were women. Median age was 63 years (range 47-70). At study entry, pain was present in 15 out of 22 patients (68%) with a mean value of Scott-Huskisson scale of 27.6+/-23.8, whereas a weight loss >10% was present in 15 patients. After eight weekly treatments, three partial responses were achieved for a response rate of 13% (95% CI 0-26%), five patients had stable disease and 14 progressed on therapy. Pain was present in 9 out of 22 patients (40%) with a mean value of Scott-Huskisson scale of 12.3+/-18.4. Eight patients (36%) (three partial response and five stable disease) had a positive weight change. Toxicity was mild: WHO grade III or IV toxicity was recorded in terms of anaemia in 7 out of 188 cycles (3.7%), of neutropenia in 9 out of 188 cycles (4.7%) and of thrombocytopenia in 3 out of 188 cycles (1.5%). Median survival of all patients was 6 months. The outcome of this intensive chemotherapy regimen does not support its use in pancreatic cancer.  (+info)

Role of dexamethasone dosage in combination with 5-HT3 antagonists for prophylaxis of acute chemotherapy-induced nausea and vomiting. (3/7975)

Dexamethasone (20 mg) or its equivalent in combination with 5-HT3 antagonists appears to be the gold-standard dose for antiemetic prophylaxis. Additional to concerns about the use of corticosteroids with respect to enhanced tumour growth or impaired killing of the tumour cells, there is evidence that high-dosage dexamethasone impairs the control of delayed nausea and emesis, whereas lower doses appear more beneficial. To come closer to the most adequate dose, we started a prospective, single-blind, randomized trial investigating additional dosage of 8 or 20 mg dexamethasone to tropisetron (Navoban), a 5-HT3 receptor antagonist, in cis-platinum-containing chemotherapy. After an interim analysis of 121 courses of chemotherapy in 69 patients, we have been unable to detect major differences between both treatment alternatives. High-dose dexamethasone (20 mg) had no advantage over medium-dose dexamethasone with respect to objective and subjective parameters of acute and delayed nausea and vomiting. In relation to concerns about the use of corticosteroids in non-haematological cancer chemotherapy, we suggest that 8 mg or its equivalent should be used in combination with 5-HT3 antagonists until further research proves otherwise.  (+info)

MycN sensitizes neuroblastoma cells for drug-induced apoptosis. (4/7975)

Amplification of the MYCN gene is found in a large proportion of neuroblastoma and considered as an adverse prognostic factor. To investigate the effect of ectopic MycN expression on the susceptibility of neuroblastoma cells to cytotoxic drugs we used a human neuroblastoma cell line harboring tetracycline-controlled expression of MycN. Neither conditional expression of MycN alone nor low drug concentrations triggered apoptosis. However, when acting in concert, MycN and cytotoxic drugs efficiently induced cell death. Apoptosis depended on mitochondrial permeability transition and activation of caspases, since the mitochondrion-specific inhibitor bongkrekic acid and the caspase inhibitor zVAD-fmk almost completely abrogated apoptosis. Loss of mitochondrial transmembrane potential and release of cytochrome c from mitochondria preceded activation of caspase-8 and caspase-3 and cleavage of PARP. CD95 expression was upregulated by treatment with cytotoxic drugs, while MycN cooperated with cytotoxic drugs to increase sensitivity to CD95-induced apoptosis and enhancing CD95-L expression. MycN overexpression and cytotoxic drugs also synergized to induce p53 and Bax protein expression, while Bcl-2 and Bcl-X(L) protein levels remained unchanged. Since amplification of MYCN is usually associated with a poor prognosis, these findings suggest that dysfunctions in apoptosis pathways may be a mechanism by which MycN-induced apoptosis of neuroblastoma cells is inhibited.  (+info)

A novel trinuclear platinum complex overcomes cisplatin resistance in an osteosarcoma cell system. (5/7975)

Multinuclear platinum compounds have been designed to circumvent the cellular resistance to conventional platinum-based drugs. In an attempt to examine the cellular basis of the preclinical antitumor efficacy of a novel multinuclear platinum compound (BBR 3464) in the treatment of cisplatin-resistant tumors, we have performed a comparative study of cisplatin and BBR 3464 in a human osteosarcoma cell line (U2-OS) and in an in vitro selected cisplatin-resistant subline (U2-OS/Pt). A marked increase of cytotoxic potency of BBR 3464 in comparison with cisplatin in U2-OS cells and a complete lack of cross-resistance in U2-OS/Pt cells were found. A detailed analysis of the cisplatin-resistant phenotype indicated that it was associated with reduced cisplatin accumulation, reduced interstrand cross-link (ICL) formation and DNA platination, microsatellite instability, and reduced expression of the DNA mismatch repair protein PMS2. Despite BBR 3464 charge and molecular size, in U2-OS and U2-OS/Pt cells, BBR 3464 accumulation and DNA-bound platinum were much higher than those observed for cisplatin. In contrast, the frequency of ICLs after exposure to BBR 3464 was very low. The time course of ICL formation after drug removal revealed a low persistence of these types of DNA lesions induced by BBR 3464, in contrast to an increase of DNA lesions induced by cisplatin, suggesting that components of the DNA repair pathway handle the two types of DNA lesions differently. The cellular response of HCT116 mismatch repair-deficient cells was consistent with a lack of influence of mismatch repair status on BBR 3464 cytotoxicity. Because BBR 3464 produces high levels of lesions different from ICLs, likely including intra-strand cross-links and monoadducts, the ability of the triplatinum complex to overcome cisplatin resistance appears to be related to a different mechanism of DNA interaction (formation of different types of drug-induced DNA lesions) as compared with conventional mononuclear complexes rather than the ability to overcome specific cellular alterations.  (+info)

Testicular cancer: an oncological success story. (6/7975)

Testicular cancer has become a model for a curable neoplasm. Our studies with cisplatin combination chemotherapy allow us to conclude that: (a) short-duration intensive induction therapy with the most active agents in optimal dosage is more important than maintenance therapy; (b) modest dose escalation increases toxicity without improving therapeutic efficacy; (c) it is possible to develop curative salvage therapy for refractory germ cell tumors; and (d) preclinical models predicting synergism, such as vinblastine + bleomycin or cisplatin + etoposide have clinical relevance. Finally, testicular cancer has also become a model for new drug development. Cisplatin was approved by the Food and Drug Administration for testis and ovarian cancer, and etoposide and ifosfamide were approved for refractory germ cell tumors. The success of these studies confirms the importance of the continued search for new investigational drugs in all solid tumors.  (+info)

Multimodality therapy for locally advanced and limited stage IV breast cancer: the impact of effective non-cross-resistance late-consolidation chemotherapy. (7/7975)

To determine the effectiveness of non-cross-resistant late-consolidation chemotherapy in locally advanced breast cancer (LABC) and stage IV breast cancer, we review our experience with two regimens. Between 1985 and 1991, we enrolled 56 patients with LABC, who were treated with a doxorubicin-based adjuvant regimen, followed by a late-consolidation non-cross-resistant regimen containing methotrexate, 5-fluorouracil, cisplatin, and cyclophosphamide. Between 1985 and 1996, a total of 45 patients with limited stage IV breast cancer underwent surgical excision of all evaluable disease, making them metastatic (stage IV) with no evaluable disease. Surgery was followed by a doxorubicin-containing regimen and then a late-consolidation non-cross-resistant regimen, which was either methotrexate, 5-fluorouracil, cisplatinum, and cyclophosphamide or 5-fluorouracil, mitomycin, etoposide, and cisplatin. Twenty-four patients with limited bone metastases that were unresectable were treated with a doxorubicin-containing regimen, radiation therapy to all sites of disease, and then one of the two late non-cross-resistant regimens. With a median follow-up of 84 months, 78% of patients with LABC are alive, and 68% are free of disease. After a median follow-up of 44 months, 53% of patients with stage IV with no evaluable disease are alive and free of disease. The use of non-cross-resistant late-consolidation chemotherapy is an effective strategy in the treatment of patients with LABC and selected patients with limited stage IV breast cancer.  (+info)

Modification of non-conservative double-strand break (DSB) rejoining activity after the induction of cisplatin resistance in human tumour cells. (8/7975)

The induction of collateral radioresistance after the development of cisplatin resistance is a well-documented phenomenon; however, the exact processes that are responsible for the cisplatin-induced radioresistance remain to be elucidated. There was no obvious difference in the level of radiation-induced DNA double strand breaks (DSBs), in DSB rejoining rates, or the level of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) in the cisplatin- and radiation-sensitive 2780/WT and cisplatin-resistant 2780/CP cell lines. However, there was a significantly (P < 0.01) lower level of DSB misrejoining activity within nuclear protein extracts derived from the cisplatin- and radiation-sensitive 2780/WT and OAW42/WT tumour cell lines than in similar extracts from their cisplatin- (and radiation-) resistant 2780/CP and OAW42/CP counterparts. All of the DSB misrejoining events involved deletions of between 134 and 444 bp that arose through illegitimate recombination at short repetitive sequences, such as those that arise through non-homologous repair (NHR). These data further support the notion that the radiosensitivity of DSB repair proficient human tumour cell lines may be partly determined by the predisposition of these cell lines to activate non-conservative DSB rejoining pathways. Furthermore, our data suggest that the induction of acquired cisplatin resistance is associated with a two- to threefold decrease in the activity of a non-conservative DSB rejoining mechanism that appears to be a manifestation of NHR.  (+info)

TY - JOUR. T1 - O6-methylguanine DNA methyltransferase repairs platinum-DNA adducts following cisplatin treatment and predicts prognoses of nasopharyngeal carcinoma. AU - Chen, Shang Hung. AU - Kuo, Ching Chuan. AU - Li, Chien Feng. AU - Cheung, Chun Hei Antonio. AU - Tsou, Tsui Chun. AU - Chiang, Huai Chih. AU - Yang, Yun Ning. AU - Chang, Shin Lun. AU - Lin, Li Ching. AU - Pan, Hsin Yi. AU - Chang, Kwang Yu. AU - Chang, Jang Yang. PY - 2015/9/1. Y1 - 2015/9/1. N2 - Cisplatin (CDDP) is an important anti-cancer drug commonly used in various human cancers, including nasopharyngeal carcinoma (NPC). How to overcome the drug resistance of CDDP provides opportunities to improve clinical outcomes of NPC. O6-methylguanine-DNA methyltransferase (MGMT) has been well-characterized to be a therapeutic determinant of O6-alkylguanine alkylating drugs. However, the underlying mechanism and clinical relevance between MGMT and CDDP remain poorly defined in NPC. In this study, we showed that MGMT-proficient ...
TY - JOUR. T1 - Ras-mediated activation of ERK by cisplatin induces cell death independently of p53 in osteosarcoma and neuroblastoma cell lines. AU - Woessmann, Willi. AU - Chen, Xinbin. AU - Borkhardt, Arndt. PY - 2002. Y1 - 2002. N2 - Activation of the mitogen-activated protein kinases ERK1/2 by the chemotherapeutic agent cisplatin has been shown to result in either survival or cell death. The downstream mediators of these opposing effects are unknown, as are the upstream signaling molecules. Activation of ERK is required for accumulation and phosphorylation of p53 following cisplatin treatment. We studied the role of ERK activation after cisplatin treatment under p53-negative and p53-positive conditions using a tetracycline-dependent expression vector in Saos-2 osteosarcoma cells. Dose-dependent activation of ERK first occurred 3-6 h after a 2-h cisplatin incubation and declined after 12-24 h in several tumor cell lines. Incubation of cell lines with the MEK1 inhibitors PD98059 or UO126 ...
TY - JOUR. T1 - The effects of the antioxidant α-tocopherol succinate on cisplatin-induced ototoxicity in HEI-OC1 auditory cells. AU - Kim, Sung Kyun. AU - Im, Gi Jung. AU - An, Yun Suk. AU - Lee, Se Hee. AU - Jung, Hak Hyun. AU - Park, Sang Yoo. PY - 2016/7/1. Y1 - 2016/7/1. N2 - Conclusion: D-α-tocopherol succinate significantly reduced a cisplatin-induced hair cell loss in HEI-OC1 cell lines. These effects were mediated by its scavenging activity against reactive oxygen species (ROS) and inhibition of apoptosis. Objectives: Alpha-tocopherol is a class of methylated phenols, known as fat-soluble antioxidants, and is a different form of vitamin E, which reduces free radicals and acts as an antioxidant. We hypothesized that the antioxidative effect of α-tocopherol could protect against cisplastin-induced cytotoxicity, and thus evaluated its effects on cisplatin-induced ototoxicity in HEI-OC1 auditory cells. Methods: HEI-OC1 cells were pretreated with D-α-tocopherol succinate at a ...
In the present work, we studied the molecular mechanisms by which sodium butyrate sensitizes cancer cells towards cisplatin. HeLa cells were treated with 5 mM butyrate, with 8 μM cis-diaminedichloroplatinum II (cisplatin), or with both. Cells treated with both agents showed approximately two-fold increase of the mortality rate in comparison with cells treated with cisplatin only. Accordingly, the life span of albino mice transfected with Ehrlich ascites tumor was prolonged almost two-fold by treatment with cisplatin and butyrate in comparison with cisplatin alone. This showed that the observed synergism of cisplatin and butyrate was not limited to specific cell lines or in vitro protocols, but was also expressed in vivo during the process of tumor development. DNA labeling and fluorescence activated cell sorting experiments showed that cisplatin treatment inhibited DNA synthesis and arrested HeLa cells at the G1/S transition and early S phase of the cell cycle. Western blotting and chromatin ...
Background: Cisplatin is a commonly used anti-cancer drug. However, its use is associated with severe side effects including ototoxicity that affects a large fraction of cisplatin-treated patients. Approved therapies that reduce cisplatin-induced ototoxicity are lacking. Among the candidate therapeutics, dexamethasone stands out. There is extensive experience of its use in combination with cisplatin for the prevention of chemotherapy-induced nausea and vomiting indicating that dexamethasone does not affect the anti-cancer effects of cisplatin. Objective: The objective of this study is to assess the potential of dexamethasone for the prevention of cisplatin-induced ototoxicity by a systematic analysis of the available evidence. Results: We identified 16 relevant original research articles. The analyzed studies reported conflicting results on the effects of dexamethasone on cisplatin-induced ototoxicity. However, studies in which dexamethasone was used prior to cisplatin treatment and directly ...
Our study analyzes the effect of magnesium supplementation on nephrotoxicity in patients receiving cisplatin for head and neck cancer. We retrospectively reviewed the medical records of patients with head and neck cancer who received two doses of cisplatin (80 mg/m2) and 5-fluorouracil (800 mg/m2) 3 weeks apart from August 2008 to October 2012. The regimen prior to 2011 (crystalloid-only) involved the administration of 1000 mL of lactated Ringers solution on the day prior to cisplatin infusion and 2000 mL of continuous infusion of saline on the day of cisplatin infusion. The regimen after 2011 (magnesium-supplemented) did not involve hydration on the day before cisplatin administration but used 1000 mL of 0.9% saline with magnesium sulfate (20 mEq) administered for 3 hours before cisplatin infusion. Sixty-five patients were treated with the crystalloid-only regimen and 56 patients with the magnesium-supplemented regimen. The mean creatinine clearance in the magnesium-supplemented group decreased by 4.9
The efficacy of treatment with a combination of radiotherapy and chemotherapy in the yeast Saccharomyces cerevisiae as suitable eukaryotic model is demonstrated by following the induction and repair of DNA double-strand breaks. These may be induced by ionizing radiation. Furthermore, the chemotherapeutic agent cisplatin may induce DNA double-strand breaks through cellular repair mechanisms. The aim of this study is to investigate the induction and repair of DNA double-strand breaks after a combination of treatment with cisplatin and radiation versus radiation alone under hypoxic conditions.The number of induced double-strand breaks caused by radiation under hypoxic conditions is dependent on dose. Following combined treatment with cisplatin and radiation, the radiation-induced double-strand breaks simply add to those induced by cisplatin. We identified no difference in the repair kinetics of double-strand breaks following radiation between cells treated with cisplatin and those not treated with ...
This study assigned subjects to either cisplatin/vinorelbine or cisplatin/pemetrexed chemotherapy using a genomic based expression profile to determine chemotherapy sensitivity in completely resected early stage non-squamous non-small-cell lung cancer (NSCLC). The vinorelbine-sensitive tumors group received Vinorelbine followed by cisplatin, while the pemetrexed-sensitive tumors group received pemetrexed followed by cisplatin. The primary objective of this trial was to determine whether genomic-based adjuvant chemotherapy treatment increased the 2-year progression-free survival rate in completely resected patients with NSCLC compared to historic controls. Secondary objectives included: 1) estimation of the percentage of completely resected NSCLC tumors that can be adequately analyzed and used to direct specific adjuvant chemotherapy; 2) estimation of the proportion of patients who are assigned to treatment with vinorelbine and pemetrexed; 3) evaluation of drug sensitivity patterns of cisplatin ...
This study determined the in vitro permeability of cisplatin through isolated human sclera as delivered by a collagen matrix vehicle. Short-term and long-term intraocular levels of cisplatin were also measured in the rabbit eye after a subconjunctival injection. Cisplatin in either a collagen matrix vehicle or a control balanced salt solution (BSS) vehicle was applied to human sclera mounted in a specially designed in vitro perfusion chamber. The amount of cisplatin that diffused across the sclera was measured in hourly samples for 24 h using atomic absorption spectrometry. In vivo studies were also performed in Dutch Belted rabbits given subconjunctival injections of cisplatin in collagen matrix or in BSS. Eyes were enucleated at 1.5 h and 2 weeks after injection, frozen, and dissected to determine the intraocular cisplatin concentrations. Cisplatin had a peak in vitro scleral permeability constant of 8.3+/-1.2 x 10(-6) and 20.1+/-1.8 x 10(-6) cm/s, delivered in collagen matrix and in BSS, respectively
The impact of cumulative dose of cisplatin on clinical outcomes of nasopharyngeal carcinoma (NPC) patients who received intensity-modulated radiotherapy (IMRT) was evaluated. This study included 491 consecutive patients with histologically confirmed NPC who were treated with concurrent chemoradiotherapy with IMRT. The patients were divided into three groups: low- (cumulative dose ≤100 mg/m2), medium- (cumulative dose |100 mg/m2 and ≤200 mg/m2), and high- (cumulative dose |200 mg/m2) dose groups. Subgroups of patients included pre-treatment levels of Epstein-Barr Virus DNA (EBV DNA) |4000 copies/ml and pre-treatment EBV DNA ≥4000 copies/ml. To test for independent significance, the Kaplan-Meier with the log-rank test and the Cox proportional hazards model were used. The 5-year overall survival (OS) rates of the low-, medium-, and high-dose groups were 64.1 %, 91.1 %, and 89.4 %, respectively (P = 0.002). Based on multivariate analysis, patients who were in the medium- and high-dose groups had
Gemcitabine and cisplatin treatment were administered to patients with advanced-stage, non-small-cell lung cancer. During phase II studies, the treatment is performed using a 28-day cycle, with gemcitabine administered on days 1, 8, and 15. Although it is advised that cisplatin not be administered...
TY - JOUR. T1 - Peripheral neuroglial death induced by cisplatin administration in newborn rats. AU - Sugimoto, Tomosada. AU - Takeyama, Akihiro. AU - Fujita, Masako. AU - Ichikawa, Hiroyuki. AU - Takano-Yamamoto, Teruko. PY - 2001/1/22. Y1 - 2001/1/22. N2 - To determine the target of cytotoxicity of cisplatin (CDDP), we injected newborn rats with 2mg/kg CDDP and examined the trigeminal ganglion for possible cell death. A nick translation method for DNA fragmentation revealed CDDP-induced glial cell death. DNA fragmentation was detected in both Schwann cells and satellite cells. Satellite cell death was observed as early as 0.5 day after injection, most frequent at 1-3 days and subsided thereafter. The incidence of neuronal death was very low and comparable to that observed in vehicle control rats. CDDP has selective toxicity to peripheral glial cells, though the damage did not culminate in cell death in adults. The glial toxicity may contribute to clinical symptoms of CDDP neuropathy.. AB - To ...
To the editor: We wish to call to your readers attention an unexpectedly severe and disabling neurotoxicity due to very-high-dose cisplatin therapy for cancer of the ovary. The attainment of complete remission, proven by second-look surgery, is the first step toward achieving prolonged survival and cure of stage III cancer of the ovary. Recently, Ozols and associates (1) have reported that administration of very high doses of cisplatin (200 mg/m2 body surface area over 5 consecutive days) has achieved frequent tumor regression in patients with advanced cancer of the ovary previously refractory to conventional doses of cisplatin. To improve complete ...
Drug resistance is still a major obstacle for efficient treatment of hepatocellular carcinoma (HCC) during the cisplatin-based chemotherapy. Recent studies have demonstrated that CD133 positive population of cancer cells are responsible for multiple drug resistance. We are supposed to take strategies to sensitize CD133+ HCC cells to cisplatin treatment. In the present study, CD133+ HCC cells showed significant cisplatin-resistance compared to the CD133- HCC cells. Downregulation of miR-124 was observed in CD133+ HCC cells. However, enforced expression of miR-124 can increase the sensitivity of CD133+ HCC cells to cisplatin treatment in vitro and in vivo. Mechanically, overexpression of miR-124 was found to inhibit the expression of SIRT1 and thus promoted the generation of ROS and phosphorylation of JNK. As the results, overexpression of miR-124 expanded the apoptosis in cisplatin-treated CD133+ HCC cells. We then demonstrated that
The combination of pemetrexed and cisplatin shows good clinical activity against mesothelioma and lung cancer. In order to study the potential cellular basis for this, and provide leads as to how to optimize the combination, we studied the schedule-dependent cytotoxic effects of pemetrexed and cisplatin against four human cancer cell lines in vitro. Tumor cells were incubated with pemetrexed and cisplatin for 24 h at various schedules. The combination effects after 5 days were analyzed by the isobologram method. Both simultaneous exposure to pemetrexed and cisplatin for 24 h and sequential exposure to cisplatin for 24 h followed by pemetrexed for 24 h produced antagonistic effects in human lung cancer A549, breast cancer MCF7, and ovarian cancer PA1 cells and additive effects in colon cancer WiDr cells. Pemetrexed for 24 h followed by cisplatin for 24 h produced synergistic effects in MCF7 cells, additive/synergistic effects in A549 and PA1 cells, and additive effects in WiDr cells. Cell cycle ...
Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin
TY - JOUR. T1 - Use of organotypic cultures of Cortis organ to study the protective effects of antioxidant molecules on cisplatin-induced damage of auditory hair cells. AU - Kopke, Richard D.. AU - Liu, Wei. AU - Gabaizadeh, Ramin. AU - Jacono, Andrew. AU - Feghali, Joseph. AU - Spray, David. AU - Garcia, Phil. AU - Steinman, Howard. AU - Malgrange, Bridgitte. AU - Ruben, Robert J.. AU - Rybak, Leonard. AU - Van De Water, Thomas R.. PY - 1997/9/1. Y1 - 1997/9/1. N2 - Hypothesis: Cisplatin causes the generation of reactive oxygen species (ROS), which interferes with the antioxidant defense system of Cortis organ and results in damage to the hair cells. Background: Cisplatin is a widely used chemotherapeutic agent with the dose-limiting side effect of ototoxicity. Evidence is accumulating that cisplatin interferes with the antioxidant defense system of Cortis organ. Methods: Organotypic explants of P-3 rat organ of Corti were the in vitro model system. Presence of intact auditory hair cells and ...
TY - JOUR. T1 - Effect of miR-29 on cisplatin sensitivity of ovarian cancer cells. AU - Yu, Pei Ning. AU - Lin, Wen-Chi. AU - Kuo, Chih Chi. AU - Huang, Rui-Lan. AU - Yan, Ming De. AU - Shih, Yu Lueng. AU - Chou, Yu Ching. AU - Lai, Hung-Cheng. AU - Lin, Ya Wen. PY - 2014/11/21. Y1 - 2014/11/21. N2 - Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, ILIn clinical practice, the main dilemma to a successful ovarian cancer therapy is the development of drug resistance. The mounting evidence demonstrated that microRNAs (miRNAs) not only controlled cell proliferation, invasion and metastasis but also therapeutic resistance of ovarian cancer cell. Recently, we isolated CP70sps(CP70 side population spheres) from CP70 ovarian cancer cell line and proved that CP70sps exhibited more resistant to cisplatin than CP70. This phenomenon was correlated to other study which supported that side population of cancer cells was responsible for chemoresistance. In this study, we ...
A statistically significant (p=0.0039) increase in IL6 was shown in the blood plasma of the cisplatin animals (131.9±31.91 pg/ml) compared to the vehicle animals (38.00±6.748 pg/ml). There were no significant differences between cisplatin and vehicle animals in dorsal horn neurones or astrocytes at either time point. Microglia cell counts in the dorsal horn were significantly decreased at the juvenile time point in the Cisplatin treatment group. Cisplatin induced significant increases in dorsal horn expression of Aβ-fibre and non-peptidergic C-fibre terminations at both time-points, in the Cisplatin treatment group. TrkA expression in dorsal horn peptidetgic C-fibre terminations was increased at both time-points, however, CGRP expression was only initially increased at the juvenile time-point but showed no difference to the veh at the adult time-point. Interneuron expression was increased at both time-points ...
Patients. Twenty-eight cancer patients were included in this study and were treated with locoregional standard radiotherapy and simultaneous cisplatin-containing chemotherapy. They gave their written informed consent to be included in this study, which was approved by the local ethics committee. Patients were irradiated for intrathoracic, pelvic, or head and neck tumors in 21, 4, and 3 cases, respectively. All patients received cisplatin-containing chemotherapy concurrent with radiotherapy at weekly or longer intervals. The cisplatin doses per application ranged from 20 to 50 mg/m2 and were given at days 0 and 7 of each 21- to 28-d cycle. Cisplatin was given according to three schedules, either as cisplatin monochemotherapy or, for non-small cell lung cancer patients (n = 14), as cisplatin 50 mg/m2 and navelbine 15 mg/m2 doublet at days 0 and 7 after the start of radiotherapy (day −1). For small-cell lung cancer patients (n = 4), it was given as cisplatin 45 to 50 mg/m2 at days 0 and 7 ...
An unanswered question in first line treatment of non small cell lung cancer (NSCLC) is whether the administration of more than 2 active drugs provides greater efficacy than a two-drug combination. Docetaxel/gemcitabine combination is a well tolerated regimen, which has comparable efficacy to docetaxel/cisplatin or vinorelbine/cisplatin. In a recent phase II study in first line treatment of advanced or metastatic NSCLC, the sequential administration of vinorelbine/cisplatin followed by docetaxel/gemcitabine produced a response rate of 45.8% and a 1-year survival rate of 51%. The addition of bevacizumab to a platinum-based regimen provided a survival benefit in patients with advanced or metastatic NSCLC ...
Cisplatin-based chemotherapy is the standard therapy used for the treatment of several types of cancer. However, its efficacy is largely limited by the acquired drug resistance. To date, little is known about the RNA expression changes in cisplatin-resistant cancers. Identification of the RNAs related to cisplatin resistance may provide specific insight into cancer therapy. In the present study, expression profiling of 7 cancer cell lines was performed using oligonucleotide microarray analysis data obtained from the GEO database. Bioinformatic analyses such as the Gene Ontology (GO) and KEGG pathway were used to identify genes and pathways specifically associated with cisplatin resistance. A signal transduction network was established to identify the core genes in regulating cancer cell cisplatin resistance. A number of genes were differentially expressed in 7 groups of cancer cell lines. They mainly participated in 85 GO terms and 11 pathways in common. All differential gene interactions in the ...
Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic ...
Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic ...
Background. Erythropoietin (Epo) is a growth factor whose synthesis mainly takes place in the kidney. Epo has been shown to support the growth not only of erythroid progenitor cells but also of certain other cell types. We attempted to establish whether Epo enhances the recovery from acute renal failure induced by cisplatin.. Methods. Sprague‐Dawley rats were randomized into three groups. In the cisplatin group, animals received one intraperitoneal injection of cisplatin (6 mg/kg) and a daily injection of placebo for 9 days. In the cisplatin+Epo group, animals received intrapertoneal cisplatin and a daily injection of Epo (100 IU/kg) for 9 days. In the control group, animals received both placebo preparations alone. Para‐aminohippuric acid and inulin clearances were determined after 4 and 9 days to evaluate renal blood flow and glomerular filtration rate. In addition, light microscopy and immunohistochemistry examinations were performed, and in situ proliferating cell nuclear antigen (PCNA) ...
Objective: To study the therapeutic efficacy of intraperitoneal perfusion of Compound Matrine injection and Cisplatin on malignant ascites. Methods: Forty- two patients of malignant ascites were randomly divided into treatment group and control group. 22 patients were treated with Compound Matrine injection and Cisplatin intraperitoneal perfusion( treatment group),and 20 patients were treated with Cisplatin intraperitoneal perfusion only( control group). The changes in volume of ascites and treatment side effects were observed. Results: The objective response rate( CR and PR) of treatment group and control group were 90. 9% and 65. 0% respectively,and the difference was significant( P 0. 05). The treatment group had a slighter side effect on abdominal pain,gastrointestinal rection and bone marrow depression,and the difference was significant( P 0. 05). Conclusion: The results suggest that intraperitoneal perfusion of Compound Matrine injection and Cisplatin is safe and effective in treating malignant
Using a combination of tandem affinity purification tagging and mass spectrometry, we characterized a novel, evolutionarily conserved protein phosphatase 4 (PP4)-containing complex (PP4cs, protein phosphatase 4, cisplatin-sensitive complex) that plays a critical role in the eukaryotic DNA damage response. PP4cs is comprised of the catalytic subunit PP4C; a known regulatory subunit, PP4R2; and a novel protein that we termed PP4R3. The Saccharomyces cerevisiae PP4R3 ortholog Psy2 was identified previously in a screen for sensitivity to the DNA-damaging agent and anticancer drug cisplatin. We demonstrated that deletion of any of the PP4cs complex orthologs in S. cerevisiae elicited cisplatin hypersensitivity. Furthermore human PP4R3 complemented the yeast psy2 deletion, and Drosophila melanogaster lacking functional PP4R3 (flfl) exhibited cisplatin hypersensitivity, suggesting a highly conserved role for PP4cs in DNA damage repair. Finally we found that PP4R3 may target PP4cs to the DNA damage ...
705 The treatment of alkylating cytotoxic drug cisplatin is often limited by high incidence rate of resistance. In the present study, the potential involvement of the transcription factor Nrf2 in determination of cisplatin cytotoxicity has been investigated. Nrf2-deficient murine embryonic fibroblasts showed increased cell death, cytotoxicity, and apoptosis in response to cisplatin treatment compared to wild-type cells. Cisplatin-resistant human ovarian cancer SK-OV cells, which are retaining 25-fold higher levels of GSH than murine fibroblasts, could be sensitized by inhibition of Nrf2. Transfection with Nrf2 siRNA into SK-OV cells resulted in severe degree of GSH depletion and exacerbated cytotoxicity following cisplatin treatment compared to scrambled RNA control. In conclusion, we propose that the Nrf2 pathway, which plays a protective role in normal cells, can be a potential target to control cancer cell resistance to oxidants, cytotoxic chemicals, and radiation. ...
The standard of care for resected stage II - IIIA non-small-cell lung cancer includes adjuvant chemotherapy based on the results of randomized trials using cisplatin regimens. A recent meta-analysis (Lung Adjuvant Cisplatin Evaluation) showed no surv
The administration of cisplatin is limited due to its nephrotoxic side effects, and prevention of this nephrotoxicity of cisplatin is difficult. Mesenchymal stem cell (MSC)-derived exosomes have been implicated as a novel therapeutic approach for tissue injury. In this study, we demonstrated that the pretreatment of human umbilical cord MSC-derived exosomes (hucMSC-Ex) can prevent the development of cisplatin-induced renal toxicity by activation of autophagy in vitro and in vivo. In vitro, rat renal tubular epithelial (NRK-52E) cells were pre-incubated with exosomes from hucMSC or HFL1 (human lung fibroblast cells; as control) for 30 min, and 3-methyladenine (an autophagic inhibitor) and rapamycin (an autophagic inducer) for 1 h before cisplatin treatment for 8 h, respectively. Cells were harvested for apoptosis assay, enzyme-linked immunosorbent assay (ELISA), Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). In vivo, we constructed cisplatin-induced acute kidney injury rat
Malignant melanoma causes the highest mortality rate in skin cancers. Although cisplatin has proved efficacious in the treatment of various solid tumors, melanoma seems particularly resistant to this chemotherapeutic drug. Reports show that melanoma patients whose tumors express nitric oxide (NO) synthase and/or nitrotyrosine are often faced with poor prognosis. Moreover, it has been shown that NO produced by melanoma cells sustains lower sensitivity to cisplatin toxicity in vitro. Because inflammatory products such as NO and reactive oxygen species (ROS) are associated with the genesis and evolution of cancer, we hypothesized that these oxidative species may regulate key components of the response of melanoma to cisplatin. Using a system for controlled delivery of NO to simulate the NO levels believed to occur during inflammation, we showed that human melanoma (A375) cells pre-exposed to submicromolar NO concentrations were protected from a subsequent challenge with cisplatin. This protection ...
The antiapoptotic factor Livin has been considered critical for tumor progression and poor prognosis for variant types of tumors. However, there are only limited reports regarding its expression and biological functions in colon cancer. Here, we examined Livin expression in four colon cancer cell lines (HCT116, RKO, KM12C, and SW620) in the presence or absence of cisplatin that was used as a model reagent. We found the different response to cisplatin was related to endogenous Livin expression level. From among a panel of apoptosis-related factors (p53, Bcl-2, Bcl-XL, BAX, and survivin), the expression of Livin was upregulated after cisplatin treatment in a dose-dependent manner. Both immunocytochemistry and nuclear cytoplasmic fractionation indicated Livin remained in the cytoplasm after treatment with cisplatin. In an attempt to explore the mechanism, we found the elevated expression of Livin was not due to the decreased degradation by proteosome but was enhanced at the mRNA level. Besides, ...
The latest results from the groups research to create a DNA targeting, light activated anticancer drug will be presented at the 231st American Chemical Society national meeting in Atlanta on March 26-30. Chemistry professor Karen J. Brewer reports that the group has developed supramolecular complexes that combine light-absorbing PDT agents and cisplatin like units. Previous anticancer molecules created by the group have contained platinum-based molecules that bind DNA. They have also developed new light activated systems able to photocleave DNA. This report combines these two approaches to target the drug to DNA using cisplatin like units, directing the light activation to tumor cells and the sub-cellular target, DNA. "In the past, our light activated systems had to find the DNA within the cell, an often inefficient process. Now we have added the DNA targeting drug," Brewer said. "We were working on cisplatin analogs before, so we have tied it to light activated systems." Cisplatin begins its ...
Abstract: Cisplatin is a widely used chemotherapeutic drug which causes ototoxicity. Previous studies from this laboratory using the rat have shown that cisplatin ototoxicity may be mediated by the production of free oxygen radicals. The ototoxic effects of cisplatin can be reduced by treatment with reducing agents such as diethyldithiocarbamate, methylthiobenzoic acid, ebselen, D-methionine, or sodium thiosulfate. The injury to the inner ear caused by cisplatin is potentiated by noise exposure. The greatest degree of cochlear damage in the guinea pig was observed when noise exposure precedes the administration of cisplatin [G. Laurell, Ann. Otol. 101, 969--976 (1992)]. These findings could be explained by an increase in oxidative stress produced by noise exposure, which could predispose to further injury by subsequent cisplatin administration. [Work supported by NIH ...
The results of the study revealed a true potential for these chemicals, or similar more advanced chemicals, to aid in chemotherapy. During cisplatin treatment massive apoptosis occurs. In the experiment, the group that was just given cisplatin treatment the RPTC cell apoptosis was 53%, but when treated with SAHA prior to the cisplatin treatment the cell apoptosis was reduced significantly to 21%. Similarly, when RPTC cells were treated with TSA the cisplatin was reduced by 17%. Both chemicals inhibit the negative apoptosis that the cisplatin treatment causes. This part of the experiment was conducted over a short period of time. For practical use the success of SAHA and TSA needs to be long-term the experimenters also observed its success over an extended period. Forty-eight hours after cisplatin treatment the morphology and amount of cell protein recovered was observed for each of the experimental and control groups. In the group of RPTC cells that were just issued the cisplatin treatment the ...
Treatment of multifunctional diseases such as cancer typically cannot be achieved by therapeutic agents that inhibit a single target.1 Single agent therapeutics often lead to development of drug resistance as well as limited accessibility of drug to tumour tissue due to intra-tumour heterogeneity.2 Moreover, in order to achieve therapeutically relevant concentrations within the tumour, high systemic doses of chemotherapy agents need to be administered, often resulting in severe toxic side effects.3 This is the case with drugs such as cisplatin and other platinum derivative drugs that are widely used in the treatment of ovarian cancer and head and neck squamous cell carcinoma (HNSCC).4,5 The primary mechanism of action of cisplatin is through DNA damage.6 However, several cellular pathways are activated by cisplatin exposure, including DNA repair pathways that remove the damage and result in the emergence of drug resistance.7 It has been shown that a combination of multiple anticancer drugs can ...
Cisplatin (cis-diamminedichloroplatinum II, CDDP) is a chemotherapeutic agent that induces nephrotoxicity associated with oxidative/nitrosative stress. Sulforaphane (SFN) is an isothiocyanate produced by the enzymatic action of myrosinase on glucorophanin, a glucosinolate contained in cruciferous vegetables. SFN is able to induce cytoprotective enzymes through the transcription factor Nrf2. The purpose of this study was to evaluate whether SFN induces a cytoprotective effect on the CDDP-induced nephrotoxicity. Preincubation of LLC-PK1 cells with 0.5-5 microM SFN by 24 h was able to prevent, in a concentration-dependent way, CDDP-induced cell death. Immunofluorescent staining confirmed the nuclear translocation of Nrf2 after treatment with SFN. In the in vivo studies, CDDP was given to Wistar rats as a sole i.p. injection at a dose of 7.5 mg/kg. SFN (500 microg/kg i.v.) was given two times (24 h before and 24 after CDDP-injection). Animals were killed three days after CDDP-injection.. SFN ...
By targeting mitochondria with the anticancer drug cisplatin, chemists have developed a new way to kill cancer cells that have shown resistance to cisplatin.. Cisplatin is a chemotherapy drug given to more than half of all cancer patients. The drug kills cells very effectively by damaging nuclear DNA, but if tumors become resistant to cisplatin they often grow back.. A new study from MIT and the University of Toronto offers a possible way to overcome that resistance. The researchers found that when cisplatin was delivered to cellular structures called mitochondria. DNA in this organelle was damaged, leading to cancer cell death. Moreover, the mitochondrial-targeted drug could overcome cisplatin resistance.. "These results suggest that the mitochondria can be an important target for platinum-based drugs," says Robert Radford, an MIT postdoc and an author of a paper describing the findings in the October 31 online edition of the journal Biology & Chemistry.. Mitochondria-targeting cisplatin might ...
TY - JOUR. T1 - Cisplatin nephrotoxicity as a model of chronic kidney disease. AU - Shi, Mingjun. AU - McMillan, Kathryn L.. AU - Wu, Junxia. AU - Gillings, Nancy. AU - Flores, Brianna. AU - Moe, Orson W. AU - Hu, Ming C. PY - 2018/6/1. Y1 - 2018/6/1. N2 - Cisplatin (CP)-induced nephrotoxicity is widely accepted as a model for acute kidney injury (AKI). Although cisplatin-induced chronic kidney disease (CKD) in rodent has been reported, the role of phosphate in the cisplatin-induced CKD progression is not described. In this study, we gave a single peritoneal injection of CP followed by high (2%) phosphate diet for 20 weeks. High dose CP (20 mg/Kg) led to high mortality; whereas a lower dose (10 mg/Kg) resulted in a full spectrum of AKI with tubular necrosis, azotemia, and 0% mortality 7 days after CP injection. After consuming a high phosphate diet, mice developed CKD characterized by low creatinine clearance, interstitial fibrosis, hyperphosphatemia, high plasma PTH and FGF23, low plasma ...
The purpose of this investigation was to evaluate the efficacy of cisplatin chemotherapy in BRCA1 mutation carriers with metastatic breast cancer. In a phase II, open-label study, 20 patients with metastatic breast cancer who carried a mutation in BRCA1 were treated with cisplatin 75 mg/m2 intravenously every 3 weeks as part of a 21-day cycle for 6 cycles. Restaging studies to assess response were performed after cycles 2 and 6, and every three months thereafter. Between July 2007 and January 2009, 20 patients were enrolled. Baseline characteristics were as follows: 65% had prior adjuvant chemotherapy, 55% had prior chemotherapy for metastatic breast cancer; mean age was 48 years (ranges 32 to 70); 30% estrogen receptor (ER) or progesterone receptor (PR)+, 70% ER/PR/Human Epidermal Growth Factor Receptor 2 (HER2)- and 0% HER2+. Overall response rate was 80%; nine patients experienced a complete clinical response (45%) and seven experienced a partial response (35%). Overall survival was 80% at one year,
Cisplatin, the most common chemotherapeutic drug for the treatment of advanced stage cervical cancers has limitations in terms of drugs resistance observed in patients partly due to functional DNA damage repair (DDR) processes in the cell. Mediator of DNA damage checkpoint 1 (MDC1) is an important protein in the Ataxia telangiectasia mutated (ATM) mediated double stranded DNA break (DSB) repair pathway. In this regard, we investigated the effect of MDC1 change in expression on the cisplatin sensitivity in cervical cancer cells. Through modulation of MDC1 expression in the cervical cancer cell lines; Hela, SiHa and Caski, we found that all the three cell lines silenced for MDC1 exhibited higher sensitivity to cisplatin treatment with inefficiency in accumulation of p γH2AX, Ser 139 foci and increased accumulation of pChk2 Thr 68 at the damaged chromatin followed by enhanced apoptosis. Further, we observed the increased p53 Ser 15 phosphorylation in the MDC1 depleted cells. Our studies suggest that MDC1
Like other forms of radiotherapy or chemotherapy, administration of cisplatin causes DNA damage and activates the cellular DDR pathway. In this study, we report that in some oral/laryngeal SCC cell lines, expression of several DDR factors, including ATM, Mre11, and H2AX, is significantly reduced. We showed that DDR signaling is partially defective in these cells, in correlation with chemoresistance to cisplatin. These findings are in line with several previous studies in head and neck cancer. For example, Parikh and colleagues have previously shown that partial loss of the chromosome 11q21-23 region that harbors Mre11, ATM, and H2AX genes frequently occurs in oral SCCs (25). Although the sensitivity of these cells to cisplatin was not examined, the authors reported that these cells exhibit decreased sensitivity to ionizing radiation in clonogenic survival assays (25). Moreover, independent studies discovered reduced ATM expression in a portion of head and neck cancer cases, in correlation with ...
The emergence of cisplatin resistance is a major stumbling block to the successful treatment of ovarian cancer. To effectively treat or overcome the problem, one has to understand the various mechanisms behind the resistance to cisplatin. Study of various platinum resistance models has shown several putative cisplatin resistance mechanisms including: (a) decreased platinum accumulation; (b) increased drug inactivation; (c) enhanced platinum-DNA adduct repair capacity; and (d) an increased ability to tolerate platinum-DNA damage (7, 8, 9, 10, 11, 12 , 22 , 23) .. Recent evidence from our laboratory indicated that the ability of cells to repair DNA damage may be a critical determinant of cisplatin sensitivity and resistance in our cisplatin resistance model (13) . In our model system, NER activity was higher in resistant cells as determined by a single lesion assay, and the amount of ERCC1 RNA expression was also elevated in cells resistant to platinum. Moreover, complementation of ERCC1 and XPF ...
We investigated the possible role of miR-143 in the development of cisplatin resistance in human gastric cancer cell line. miR-143 was detected by quantitative real-time PCR. Cisplatin resistance...
This open label Phase I study involves treating subjects with advanced cancer with BAY80-6946 in combination with either gemcitabine or cisplatin plus g
Importance: The Canadian Cancer Trials Group study HN.6 is the largest randomized clinical trial to date comparing the concurrent administration of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies with radiotherapy (RT) to standard chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Objective: To compare progression-free survival (PFS) in patients with LA-SCCHN treated with standard-fractionation RT plus high-dose cisplatin vs accelerated-fractionation RT plus the anti-EGFR antibody panitumumab. Design, Setting, and Participants: A randomized phase 3 clinical trial in 17 Canadian centers. A total of 320 patients were randomized between December 2008 and November 2011. Interventions: Patients with TanyN+M0 or T3-4N0M0 LA-SCCHN were randomized 1:1 to receive standard-fractionation RT (70 Gy/35 over 7 weeks) plus cisplatin at 100 mg/m2 intravenous for 3 doses (arm A) vs accelerated-fractionation RT (70 Gy/35 over 6 weeks) plus panitumumab
Epidermal growth factor receptor overexpression is associated with poor outcomes in urothelial carcinoma (UC). Cetuximab (CTX) exhibited an antitumor effect in in vivo UC models. The efficacy of gemcitabine/cisplatin (GC) with or without CTX in patients with advanced UC was evaluated.. ...
The effect of single-drug cis-diamminedichloroplatinum (CDDP) treatment on the distribution of T-lymphocyte subsets and monocytes was determined using monoclonal antibodies and a flow cytometry technique. Thirty-nine patients with radically operated ovarian carcinoma received postoperative treatment with six cycles of CDDP 50 mg/m2, and were examined either before, during, or after chemotherapy. During treatment, the number of OKT4+ (mainly T-helper) cells was reduced, whereas the number of OKT8+ (mainly T-suppressor/cytotoxic) cells was increased. Four to six months after the CDDP treatment was ended, these aberrations were no longer seen. The number of 1D5+ cells (monocytes) was not influenced by the treatment. It is concluded that no long-lasting change in the distribution of immunocompetent cells could be detected after this regimen of CDDP treatment.
TY - JOUR. T1 - Protective Role of Natural Products in Cisplatin-Induced Nephrotoxicity. AU - Ridzuan, Nurul Raudzah Adib. AU - Rashid, Norhashima Abd. AU - Othman, Faizah. AU - Budin, Siti Balkis. AU - Pa Pa Hlaing @ Farida Hussan, Khin. AU - Teoh, Seong Lin. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Cisplatin is a widely used antineoplastic agent for the treatment of metastatic tumors, advanced bladder cancer and many other solid tumors. However, at higher doses, toxicities such as nephrotoxicity may appear. Cisplatin leads to DNA damage and subsequently renal cell death. Besides that, oxidative stress is also implicated as one of the main causes of nephrotoxicity. Several studies showed that numerous natural products: ginseng, curcumin, licorice, honey and pomegranate were able to reduce the oxidative stress by restoring the levels of antioxidant enzymes and also at the same time act as an anti-inflammatory agent. Furthermore, pre-treatment with vitamin supplementation, such as vitamin C, E and ...
TY - JOUR. T1 - Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. AU - Yoshioka, H.. AU - Shimokawa, M.. AU - Seto, T.. AU - Morita, S.. AU - Yatabe, Y.. AU - Okamoto, I.. AU - Tsurutani, J.. AU - Satouchi, M.. AU - Hirashima, T.. AU - Atagi, S.. AU - Shibata, K.. AU - Saito, H.. AU - Toyooka, S.. AU - Yamamoto, N.. AU - Nakagawa, K.. AU - Mitsudomi, T.. PY - 2019/12/1. Y1 - 2019/12/1. N2 - Background: Primary analysis of the phase III study WJTOG 3405 demonstrated superiority of progression-free survival (PFS) for gefitinib (G) in patients treated with the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) gefitinib compared with cisplatin plus docetaxel (CD) as the first-line treatment of stage IIIB/IV or postoperative recurrent EGFR mutation-positive ...
This study is a randomized Phase 3 study comparing pemetrexed and cisplatin combination to gemcitabine and cisplatin for the treatment of Non Small Cell
We found that vandetanib augmented the antitumor activity of cisplatin with concurrent radiation in preclinical models of human cisplatin and radiation-resistant HNSCC in vitro and in vivo. Vandetanib plus cisplatin effectively radiosensitized HNSCC cells both in vitro and in vivo. Vandetanib alone or in combination with cisplatin and/or radiation inhibited the phosphorylation of EGFR and its downstream mediators, Akt and MAPK, both in vitro and in vivo. Treatment with vandetanib, cisplatin, and radiation led to reductions in tumor size and cervical lymph node metastases and prolonged survival in an orthotopic nude mouse model by inducing apoptosis in tumor and endothelial cells.. Chemoradiotherapy with cisplatin remains a standard treatment for patients with HNSCC, with the aim of improving organ preservation as well as patient survival (31). However, resistance to cisplatin or radiation leading to treatment failure and locoregional recurrence is a critical problem. In addition, cisplatin ...
Comparison of weekly administration of cisplatin versus three courses of cisplatin 100 mg-m2 for definitive radiochemotherapy of locally advanced head-and-neck cancers. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The efficacy of bevacizumab plus cetuximabbased chemotherapy remains unclear in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the anticancer efficacy of a bevacizumabcetuximab-cisplatin triple-agent combination in treating mouse HNSCC. SCC-VII tumor-bearing C3H mice were treated with bevacizumab, cetuximab and cisplatin either alone or in various combinations. In vivo results showed that the largest delay in tumor growth and the maximum increase in survival were not in the triple-agent combination therapy, but in the bevacizumab plus cisplatin therapy. TUNEL assay showed that the apoptosis indices in bevacizumab plus cisplatin group and a triple-agent combination group were 31.6±12.0% and 6.9±1.3%, respectively. Western blot showed that down-regulation of Bcl-2 and up-regulation of cleaved caspase-3 contributed to the anticancer effect of a triple-agent combination and bevacizumab plus cisplatin. Moreover, the maximum level of cleaved caspase-3 ...
This study has demonstrated that GC may affect the cytotoxicity of cisplatin in the GR-rich human carcinoma cell line, SiHa. Since GC is commonly co-administered with cisplatin, this influence of GC on cytotoxicity may affect the response to cisplatin treatment in carcinoma patients.. GC mediates its effects by binding to and activation of GR. Activated GR exerts its cellular effect by either transactivating its downstream GRE-containing genes or interacting with other transcriptional factors. In the former transactivation mechanism, GC binds to its cytoplasmic receptor, dimerizes, enters the nucleus, and finally binds to GREs to transactivate the target genes, such as tyrosine aminotransferase and alanine aminotransferase (Beato et al. 1995). However, some major effects of GC, including its anti-inflammatory and immunosuppressive effects, are achieved by regulating genes that do not contain GREs in their promoters (McEwan et al. 1997, Van der Burg et al. 1997, Cato & Wade 1996). This finding ...
BACKGROUND: Renal toxicity is a clinical problem that affects 28 - 42% of patients undergoing treatment with cisplatin. Renal toxicity can be minimized by high volume hydration with mannitol diuresis. Recent reports have shown that cisplatin induces depletion of Mg and that Mg supplementation can reduce renal toxicity. We hypothesized that Mg infusion combined with low volume hydration may not be sufficient to overcome cisplatin-induced renal toxicity.. METHODS: In total, 85 patients with lung cancer receiving their first cycle of cisplatin-based chemotherapy at the Osaka City University Hospital were classified into three groups: those administered high volume hydration without Mg infusion (high-volume Mg-), high volume hydration with Mg infusion (high-volume Mg+), and with low volume hydration with Mg infusion (low-volume Mg+). Serum creatinine (sCr) and creatinine clearance (CrCl) were examined before and after treatment with cisplatin. Multivariable analysis was carried out to identify the ...
Background: Cisplatin with definitive radiotherapy (RT) is considered the standard of care for cervical cancer; however, older women are frequently undertreated and have worse outcomes compared with younger patients. Because women aged ≥65 years have been disproportionately underrepresented in clinical trials, uncertainties exist regarding how much they benefit from the addition of cisplatin to RT. Patients and Methods: Women aged ≥65 years with nonmetastatic cervical cancer treated with definitive external-beam RT and brachytherapy were identified in the SEER-Medicare database. Death attributable to cervical cancer (cancer-specific mortality [CSM]) was evaluated against competing risks of death using Grays test. Propensity score analysis and the Fine-Gray multivariable regression model were used to adjust for baseline differences, including comorbidity. Results: The total cohort comprised 826 patients, of whom 531 (64%) received cisplatin, 233 (28%) were FIGO stage I, 374 (45%) were stage ...
miR-145 was reproducibly elevated in all the resistant sub-lines tested within one of the experimental sets; however, modulation of miR-145 levels alone in these cells did not affect their response to cisplatin. A potential target of miR-145 is cyclin dependent kinase 6 (CDK6), an important regulator of cell proliferation. Both mRNA and protein levels of CDK6 are down regulated in the resistant sub-lines. An inhibitor of CDK4/6 (PD0332991) protected cells from cisplatin cytotoxicity. ...
Intraperitoneal cisplatin versus no further treatment: 8-year results of EORTC 55875, a randomized phase III study in ovarian cancer patients with a pathologically complete remission after platinum-based intravenous chemotherapy ...
Real-time monitoring of cisplatin cytotoxicity on three-dimensional spheroid tumor cells NamHuk Baek,1,* Ok Won Seo,1,* Jaehwa Lee,1 John Hulme,2 Seong Soo A An2 1Department of Research and Development, NanoEntek Inc., Seoul, 2Department of BioNano Technology, Gachon University, Gyeonggi-do, Korea *These authors contributed equally to this work Abstract: Three-dimensional (3D) cell cultivation is a powerful technique for monitoring and understanding diverse cellular mechanisms in developmental cancer and neuronal biology, tissue engineering, and drug development. 3D systems could relate better to in vivo models than two-dimensional (2D) cultures. Several factors, such as cell type, survival rate, proliferation rate, and gene and protein expression patterns, determine whether a particular cell line can be adapted to a 3D system. The 3D system may overcome some of the limitations of 2D cultures in terms of cell-cell communication and cell networks, which are essential for understanding differentiation,
Cooley, M.E.; Davis, L.E.; DeStefano, M.; Abrahm, J., 1994: Cisplatin: a clinical review. Part I--Current uses of cisplatin and administration guidelines
https://www.wiseguyreports.com/sample-request/1001034-global-cisplatin-industry-situation-and-prospects-research-report-2017. For the sake of making you deeply understand the Cisplatin industry and meeting you needs to the report contents, Global Cisplatin Industry Situation and Prospects Research report will stands on the report readers perspective to provide you a deeply analysis report with the integrity of logic and the comprehensiveness of contents. We promise that we will provide to the report reader a professional and in-depth industry analysis no matter you are the industry insider、potential entrant or investor.. Firstly, the report provides a basic overview of the industry including definitions, classifications, applications and industry chain structure. The Cisplatin market analysis is provided for the international market including development history, competitive landscape analysis, and major regions development status.. Secondly, development policies and plans are discussed as ...
A phase II study was conducted to assess the response rate and toxicity profile of the combination of irinotecan (CPT-11, Camptosar) and cisplatin (Platinol) administered weekly to patients with untreated advanced 1
From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. Results: ...
In the present study, we observed that the Golgi-SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) GS28 forms a complex with p53 in HEK (human embryonic kidney)-293 cells. Given that p53 represents a tumour suppressor that affects the sensitivity of cancer cells to various chemotherapeutic drugs, we examined whether GS28 may influence the level of sensitivity to the DNA-damaging drug cisplatin. Indeed, knockdown of GS28 using short-hairpin RNA (shGS28) induced resistance to cisplatin in HEK-293 cells. On the other hand, overexpression of GS28 sensitized HEK-293 cells to cisplatin, whereas no sensitization effect was noted for the mitotic spindle-damaging drugs vincristine and taxol. Accordingly, we observed that knockdown of GS28 reduced the accumulation of p53 and its pro-apoptotic target Bax. Conversely, GS28 overexpression induced the accumulation of p53 and Bax as well as the pro-apoptotic phosphorylation of p53 on Ser46. Further experiments showed that ...
Thirty-one patients were recruited according to the Simons two-stage design method. The median age was 62 years (range, 41-74) and the primary site was oropharynx; 11 (35%), hypopharynx; 18 (58%), larynx; 2 (7%). Twenty-four patients (77%) completed chemoradiotherapy as planned, and 9 patients (29%) completed adjuvant TPF chemotherapy. Thirty patients were evaluated for response without 1 early death before post-treatment assessment, and the response rates were CR, 10%; PR, 66.7%; SD, 6.7%; PD, 16.6%. At a median follow-up of 31 months (range, 4.5-113), the median time to progression and overall survival was 13.2 months (95% CI, 7.6-22.4) and 39.9 months (95% CI, 15.7-), respectively. The estimated overall survival with functional larynx at 3 years was 35.5% (95% CI, 20.9-53.4). The most common grade 3 or 4 adverse events during the treatment were lymphocytopenia (100%), mucositis (77%), pain (45%), hyponatremia (32%) and leukocytopenia (13%). Toxicities related to the kidney were minimal and ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Goksel, T Hatipoglu, ON Ozturk, C Gorguner, M Kiyik, M Yilmaz, U Guzelant, A Tasbakan, S Tabakoglu, E Firat, H Tutar, U Cikrikicioglu, S Akkoclu, A Soyer, S Cakir, E Itil, O Sanal, S, A prospective, multicentre clinical trial comparing cisplatin plus gemcitabine with cisplatin plus etoposide in patients with locally advanced and metastatic non-small cell lung cancer, RESPIROLOGY Volume: 10 Issue: 4 Pages: 456-463 Published: SEP 2005 (September 2005) ...
To report the experience of treating selected fit patients with locally advanced head-and-neck squamous cell carcinoma with three cycles of induction TPF (docetaxel 75 mg/m(2), cisplatin 75 mg/m(2), 5...
This randomized phase III trial is studying cisplatin, radiation therapy, and tirapazamine to see how well they work compared to cisplatin and radi
This cisplatin-resistant cell line has been developed by chronic exposure of the parent cisplatin-sensitive A2780 cell line (ECACC No. 93112519) to increasing concentrations of cisplatin. A2780cis is cross-resistant to melphalan, adriamycin and irradiation. An increased ability to repair DNA damage as well as cytogenetic abnormalities has been observed. In order to retain resistance cisplatinum has to be added to the media every 2-3 passages. In addition to this matched pair of drug-sensitive/resistant cell lines an adriamycin-resistant cell line, A2780adr (ECACC No. 93112520), has been isolated from the same parental line A2780 ...
Source: Oncology Report. Adding chemotherapy to radiotherapy improved 10-year survival of resectable head and neck carcinomas among high-risk patients who had microscopically involved resection margins and/or extracapsular spread of disease - but not in high-risk patients who only had tumor in multiple lymph nodes.. The findings come from a long-term update and unplanned subset analysis of 410 evaluable patients from the RTOG (Radiation Therapy Oncology Group) 9501 phase III study, which previously showed no overall survival advantage from the addition of cisplatin chemotherapy to radiation.. The new data are "good news," according to lead author Dr. Jay Cooper, director of Maimonides Cancer Center in Brooklyn, N.Y.. "We now can eradicate some advanced head and neck tumors that we couldnt before by adding chemotherapy to radiation therapy. At the same time, we can spare other patients who would not do better with the addition of chemotherapy from its side effects," he said at a head and neck ...
Cisplatin (CDDP) has been widely used as a chemotherapeutic agent for solid tumors. The most common side effect of CDDP is nephrotoxicity, and many efforts have been made in the laboratory and the clinic to employ candidate adjuvants to CDDP to minimize this adverse influence. Many synthetic and herbal antioxidants as well as trace elements have been investigated for this purpose in recent years and a variety of positive and negative results have been yielded. However, no definitive supplement has so far been proposed to prevent CDDP-induced nephrotoxicity; however, this condition is gender related and the sex hormone estrogen may protect the kidney against CDDP damage. In this review, the results of research related to the effect of different synthetic and herbal antioxidants supplements are presented and discussed with suggestions included for future work.
MacDonagh L, Gallagher MF, Ffrench B, Gasch C et al, Targeting aldehyde dehygrogenase 1 (ALDH1) to circumvent cisplatin resistance in NSCLC, OncoTarget, 2017 ...
The present study investigated the protective effect of extracts prepared from grape, coriander, roselle and fennel in a rat model of kidney dysfunction induced by intraperitoneal cisplatin. Mixture of ethanol and petroleum ether extracts was prepared from a given plant. Six groups of rats were...
3S Corporation is supplier, distributor and exporter for Cisplatin 10 Mg Injection in India. To buy Cisplatin 10 Mg or know its price contact us.
P&U Cisplatin is a medicine available in a number of countries worldwide. A list of US medications equivalent to P&U Cisplatin is available on the Drugs.com website.
Data on 6,500 pesticides, insecticides and herbicides including toxicity, water pollution, ecological toxicity, uses and regulatory status.
Your condition will be monitored carefully while you are receiving this medicine. You will need important blood work done while you are taking this medicine.. This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.. In some cases, you may be given additional medicines to help with side effects. Follow all directions for their use.. Call your doctor or health care professional for advice if you get a fever, chills or sore throat, or other symptoms of a cold or flu. Do not treat yourself. This drug decreases your bodys ability to fight infections. Try to avoid being around people who are sick.. This medicine may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding.. Be careful brushing and flossing your teeth or using a toothpick ...
Introduction: Chemotherapy regimen gemcitabin/cisplatin is indicated in the treatment of non-small cell lung cancer (NSCLC), stage IIIb and IV with good performance status (according to leading National Comprehensive Cancer Network (NCCN) guideline).. Aim of the study: To compare the hematological toxicity of gemcitabine/cisplatin between elderly and patients younger than 65 years of age.. Patients and methods: In our study we observed 253 chemotherapy-naive patients divided into two groups according to their ages: younger then 65 years of age (194 patients) and patients older then 65 years of age (59 patients). Both groups of patients had received chemotherapy regimen: gemcitabine (1000mg/m2 iv. day 1. and day 8.),and cisplatin (50mg/m2 iv. day 1. and day 8.) in three weeks regimen-four cycles.. Results: Hematological toxicity were register in 26/194 (13,4%) younger patients compared to 15/59 (25,3%) older patients. Statistical analysis showed significant difference in apperance of ...
The extent of intratumoral heterogeneity, the subclonal structures and the mechanisms of treatment-induced clonal selection by cisplatin was investigated in the squamous cell carcinoma cell line model FaDu. We picked 96 single cell-derived clones from the cisplatin-sensitive parental FaDu cell line. After expansion as separate cultures, these clones were tested for their sensitivity to CDDP. By this approach, we isolated individual cell clones that were primarily resistant (clones 5 & 78) and others that showed high sensitivity to CDDP (clones 46 & 54). Basal mRNA expression levels associated with CDDP sensitivity / resistance were determined in two independent microarray analyses.
This pilot phase I trial studies the side effects and best way to give sirolimus, gemcitabine hydrochloride, and cisplatin in treating patients at high risk for cholangiocarcinoma recurrence after liver transplant or surgery. Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sirolimus with gemcitabine hydrochloride and cisplatin may be an effective treatment for patients with a high risk of cancer recurrence after a liver transplant or surgery ...
Se supervisará su condición atentamente mientras reciba este medicamento. Tendrá que hacerse análisis de sangre periódicos mientras está tomando este medicamento.. Este medicamento puede hacerle sentir un malestar general. Esto es normal ya que la quimioterapia afecta tanto a las células sanas como a las células cancerosas. Si presenta alguno de los efectos secundarios, infórmelos. Sin embargo, continúe con el tratamiento aun si se siente enfermo, a menos que su médico le indique que lo suspenda.. En algunos casos, podrá recibir medicamentos adicionales para ayudarle con los efectos secundarios. Siga las instrucciones para usarlos.. Consulte a su médico o a su profesional de la salud por asesoramiento si tiene fiebre, escalofríos, dolor de garganta o cualquier otro síntoma de resfrío o gripe. No se trate usted mismo. Este medicamento puede reducir la capacidad del cuerpo para combatir infecciones. Trate de no acercarse a personas que estén enfermas.. Este medicamento puede ...
We included 314 eligible pts (3-weekly schedule, N = 127; weekly schedule, N = 187). Median cumulative cisplatin dose was 200 mg/m2 (IQR 150-300) for pts treated with a 3-weekly schedule and 160 mg/m2 (120-240) for the weekly schedule, consequently more pts treated with a 3-weekly schedule reached a cumulative dose ,200 mg/m2 (75.6% vs. 47.1%, p , 0.001). This association was also observed in multivariable analysis adjusted for age and sex (OR 3.46, 95% confidence interval [CI], 2.1 - 5.7). The 3-weekly regimen led to a higher rate of renal toxicity (33.1% vs. 20.9%, p = 0.022), but not ototoxicity (15% vs. 12.8%). In the landmark analysis, we could not confirm that a cisplatin dose ,200 mg/m2 is associated with better survival (HR 1.3, 95% CI 0.8 -1.9).. ...
Backgrounds: Cisplatin (CDDP) is a choice of anti-cancer drug for cancer chemotherapy with serious side effects such as nephrotoxicity. It seems that age is an important factor influencing the side effects of CDDP. This study was designed to determine the role of age and gender simultaneously in CDDP induced renal toxicity. Methods: 40 Wistar male and female rats were assigned as 6 groups in 3 different age categories (10, 16, and 20 weeks old). The single dose of CDDP (7.5 mg/kg, ip) was administrated, and a week later measurements were performed. Results: Body weight changes in male (not in female) animals aged 16 and 20 weeks were more than 10 weeks old animals (P|0.05). In male rats, the serum levels of creatinine (Cr) and blood urea nitrogen (BUN), and Cr-clearance in aged 10 weeks, normalized kidney weight (KW) in aged 20 weeks, and serum nitrite, aspartate aminotransferase (AST) and malondialdehyde (MDA) levels and kidney tissue damage score (KTDS) in rats aged 16 weeks were significantly
Glutathione therapy can reduce the toxicity of some chemo agents. In one study (Tedeschi), the toxicity of cisplatin, an effective drug in the treatment of solid tumors, was greatly reduced. It is proposed in this article that glutathione is a promising antidote. Glutathione is a safe compound that prevents cisplatin-induced nephrotoxicity without affecting its antitumor activity. This would enhance the ability to use higher doses of cisplatin and improve efficacy against certain tumors. The advantage of the combination of glutathione with high doses of cisplatin was demonstrated by the impressive response rate in the treatment of ovarian cancer ...
Cisplatin, platinum-based chemotherapy, is one of the most widely used chemotherapy medicines. Learn about how it works, side effects, and who uses it here.
Overall, 21 pts have been treated (18/3 pts in IRP/ARP, respectively) and 71 cycles administered (median: 3 cycles, range 1-9). In IRP three DL were explored (range 200-400 mcg/m2 nemorubicin + 40-60 mg/m2 cisplatin). One DLT (thrombocytopenia) was reported at the first DL 200 mcg/m2 nemorubicin + 40 mg/m2 cisplatin. One other DLT (fatigue) occurred at the fourth DL (600 mcg/m2 nemorubicin + 60 mg/m2 cisplatin), currently under expansion. Common drug-related adverse events were transient liver transaminases increase (all pts, max grade [G] 3), neutropenia/thrombocytopenia (5 pts, G2-3), fatigue (5 pts, G1-2), nausea/vomiting (4 pts, max G3 in one case), ototoxicity (1 pts, G3). Across dose levels, confirmed partial responses were reported in 3/11 currently evaluable pts (27%), stable disease , 3 months in 5/11 pts (45.4%) and progressive disease in the remaining 3 pts. In ARP one DL has been explored (200 mcg/m2 nemorubicin + 60 mg/m2 cisplatin): no DLTs were reported; one pts has stable disease ...
As described herein, vandetanib is able to inhibit the activity of various human renal transporters in vitro. The results indicate that vandetanib is a significantly more potent inhibitor of [3H]MPP+ and [14C]metformin uptake by MATE1-HEK and MATE2K-HEK cells than by OCT2-HEK cells under the same conditions. Vandetanib can also modulate cisplatin-induced cytotoxicity in vitro by inhibiting MATE1 and MATE2K (Table 2). Moreover, vandetanib exhibits substrate-dependent inhibition (Table 1).. First, we examined the selectivity and inhibition potency of vandetanib in HEK293 cells stably transfected with five different renal transporters. Vandetanib did not affect the uptake by OAT1 and OAT3 up to a concentration of 100 µM (Fig. 1). In contrast, marked inhibition of uptake in MATE1-HEK and MATE2K-HEK cells was observed (Table 1). Given that vandetanib had no effect on either MPP+ or metformin uptake by OCT2-HEK cells at a clinically relevant concentration (i.e., 1.7 µM), and that vandetanib ...
improves median overall survival compared to treatment with cisplatin alone.1 With incidence rates expected to double over the next 20 years in many countries2, new and effective treatments are a welcome addition, concluded an eminent panel of international speakers at a symposium sponsored by Hospira at the 35th congress of the European Society for Medical Oncology (ESMO), Milan.. Mesothelioma is a form of cancer that affects the mesothelium, a thin membrane that lines the inner surface of the chest wall where it is known as the pleura. It also surrounds the organs found within this cavity, for example the heart and lungs.3 Speakers at the symposium highlighted that whilst ...
What you need to know before starting Cisplatin + Gemzar + Avastin treatment for Non-Small Cell Lung Cancer, how its given and possible side effects. Get free tools to track your health.
TY - JOUR. T1 - Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer. AU - DeVore, Russell F.. AU - Johnson, David H.. AU - Crawford, Jeffrey. AU - Garst, Jennifer. AU - Dimery, Isaiah W.. AU - Eckardt, John. AU - Eckhardt, S. Gail. AU - Elfring, Gary L.. AU - Schaaf, Larry J.. AU - Hanover, Cristy K.. AU - Miller, Langdon L.. PY - 1999/9. Y1 - 1999/9. N2 - Purpose: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small- cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. Patients and Methods: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m2) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m2) after CPT-11 administration on day 1. Results: Fifty-two patients were enrolled, including 33 men ...
Cisplatin is one of the most widely used chemical drugs for anticancer treatment. Recent studies have focused on the ability of cisplatin to retain the high mobility group box 1 (HMGB1) protein in cisplatin-DNA adducts, thereby preventing its release from the nucleus. Because HMGB1 is a powerful inflammatory mediator in many diseases, the aim of this study is to evaluate the therapeutic effect of cisplatin acute liver failure. In this study, low-dose cisplatin was administered to treat PMA-induced macrophage-like cells induced by PMA and rats with acute liver failure. We found that cell viability and liver injury were greatly improved by cisplatin treatment. The extracellular levels of HMGB1, TNF-α and IFN-γ were also significantly decreased by the administration of cisplatin. During inflammation, nuclear HMGB1 translocates from the nucleus to the cytoplasm. The administration of cisplatin reduced the cytoplasmic levels of HMGB1 and increased nuclear HMGB1 levels in vitro and in vivo. In conclusion,
Explore the TECENTRIQ® (atezolizumab) site map and navigate to more information for HCPs about advanced urothelial carcinoma and metastatic non-small cell lung cancer. TECENTRIQ INDICATIONS: Locally advanced or metastatic urothelial carcinoma. TECENTRIQ (atezolizumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who: Are not eligible for cisplatin-containing chemotherapy, or Have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Metastatic non-small cell lung cancer. TECENTRIQ is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following
Today, the U.S. Food and Drug Administration (FDA) granted regular approval to pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. The FDA also granted accelerated approval to pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.. KEYNOTE-045. The regular approval for the second-line indication was based on data from the KEYNOTE-045 trial, a multicenter, randomized, active-controlled trial in patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy. Patients were randomly assigned (1:1) to receive either pembrolizumab 200 mg every 3 weeks (n = 270) or investigators choice of a chemotherapy regimen (paclitaxel [n ...
Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting. Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon. Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P | 0.05)
Eighty-two patients with metastatic germ cell tumors (GCT) treated with two-drug therapy consisting of etoposide and cisplatin were evaluated for late relapse. Good-risk GCT was defined using Memorial Sloan-Kettering Cancer Center (MSKCC) criteria. Etoposide was given at 100 mg/m2 on days 1 to 5 and cisplatin was given at 20 mg/m2 on days 1 to 5; therapy was recycled at 21 days with delays up to 7 days for a leukocyte count of less than 3000/microliters or a platelet count of less than 100,000/microliters. Drug doses were not attenuated for myelosuppression. Seventy-six of 82 evaluable patients achieved a complete response (CR). Seventy-two patients had a CR to chemotherapy alone. Forty-six (56%) patients had excision of residual abnormalities: 11 had teratoma in the resected specimen, 31 had necrotic debris or fibrosis, and 4 had a CR after chemotherapy plus complete excision of residual viable GCT. Six patients had an incomplete response to chemotherapy; one of these patients had unresectable ...
In a study reported in the Journal of Clinical Oncology, Shaikh et al, of the Childrens Oncology Group, found that event-free survival rates were not maintained with the use of reduced and compressed cisplatin-based regimens in children and adolescents with intermediate-risk extracranial malignant germ cell tumors.. Study Details. In a phase III single-arm trial, 210 patients with intermediate-risk disease (stages II-IV testicular, II-III ovarian, I-II extragonadal, or I gonadal tumors with subsequent recurrence) had cisplatin, etoposide, and bleomycin treatment reduced from the standard of 4 to 3 cycles and compressed from 5 to 3 days/cycle. A parametric comparator model specified that the observed 4-year event-free survival rate should not be significantly , 92%; a one-sided P value ≤ .10 defined statistical significance. A post hoc analysis compared results with a comparable group of patients treated with four cycles in two prior studies.. Event-Free Survival. Among 210 eligible patients ...
Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. Use was made of nerve conduction studies and needle electromyography (EMG) to assess motor nerve excitability in cancer patients during their first treatment cycle with platinum-based chemotherapy in this study. Twenty-nine adult cancer patients had a neurophysiological assessment either before oxaliplatin plus capecitabine, on days 2 to 4 or 14 to 20 after oxaliplatin plus capecitabine, or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin, undertaken by a neurophysiologist who was blinded to patient and treatment details. Patients completed a symptom questionnaire at the end of the treatment cycle. Abnormal spontaneous high frequency motor fibre action potentials were detected in 100% of patients (n = 6) and 72% of muscles (n = 22) on days 2 to 4 post-oxaliplatin, and in 25% of patients (n = 8) and 13% of
Four courses of PVP16B (cisplatin plus etoposide [VP-16] plus bleomycin) has been standard chemotherapy for disseminated germ cell tumors at Indiana University and the Southeastern Cancer Study Group (SECSG) since 1984. We began a random prospective phase III study in patients with favorable-prognosis (minimal and moderate extent) disseminated germ cell tumors comparing four courses of PVP16B over 12 weeks to the identical dose PVP16B administered in three courses over 9 weeks. The categories of minimal and moderate disease constitute approximately two thirds of all disseminated germ cell tumors that require chemotherapy. One hundred eighty-four patients entered this trial, and all patients have a minimal follow-up of 1 year. Overall, 106 of 107 (99%) minimal extent and 73 of 77 moderate patients (95%) achieved an initial disease-free status (NED), confirming the favorable prognostic categories. Eighty-six of 88 patients (98%) randomized to three courses and 93 of 96 randomized to four courses ...
Examples: iron pentacarbonyl, titanium tetrachloride, cisplatin Usually, organometallic compounds are considered to contain the ... Cisplatin). The field, which incorporates many aspects of biochemistry, includes many kinds of compounds, e.g., the phosphates ...
When cisplatin forms interstrand crosslinks (5'-GC), there is a severe distortion to the DNA helix due to a shortened distance ... "Cisplatin". National Cancer Institute. Retrieved 2017-10-09. Cimino, G. D.; Gamper, H. B.; Isaacs, S. T.; Hearst, J. E. (1985 ... When cisplatin generates DNA crosslinks, it more frequenlty forms 1,2-intrastrand crosslinks (5'-GG), but also forms 1,3- ... Cisplatin (cis-diamminedichloroplatinum(II)) and its derivatives mostly act on adjacent guanines at their N7 positions. The ...
"Cisplatin". Science & Research (Drugs). United States Food and Drug Administration. Reuther LO, Vainer B, Sonne J, Larsen NE ( ... Genetic variants of TPMT have also been associated with cisplatin-induced ototoxicity in children. TPMT is now listed as a ... "Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy". Nat. Genet. ... pharmacogenomic biomarker for adverse drug reactions to cisplatin by the FDA. GRCh38: Ensembl release 89: ENSG00000137364 - ...
Several chemotherapeutic agents, for example Cisplatin, are associated with acute and chronic kidney injuries. Newer agents ... Cisplatin nephrotoxicity. In: UpToDate, Palevsky PM (Ed), UpToDate, Waltham, MA, 2013. http://www.uptodate.com/contents/ ... cisplatin-nephrotoxicity Robinson, Emily S.; Khankin, Eliyahu V.; Karumanchi, S. Ananth; Humphreys, Benjamin D. (1 November ...
Unlike cisplatin, carboplatin may be susceptible to alternative mechanisms. Some results show that cisplatin and carboplatin ... It may be used for some types of testicular cancer but cisplatin is generally more effective. Relative to cisplatin, the ... or the like-cisplatin hypothesis. Activation, or the unlike-cisplatin hypothesis. The former is more accepted owing to the ... 1 ratio compared to cisplatin; that is, for a dose that usually requires a particular dose of cisplatin, four times as much ...
TMEM205 has been shown to be involved in Cisplatin resistance. Cisplatin is a Chemotheraputic drug that is commonly used to ... In addition to being involved in Cisplatin resistance there is growing evidence that the protein is also involved in the ... Shen DW, Gottesman MM (March 2012). "RAB8 enhances TMEM205-mediated cisplatin resistance". Pharmaceutical Research. 29 (3): 643 ... is associated with cisplatin resistance". Journal of Cellular Physiology. 225 (3): 822-8. doi:10.1002/jcp.22287. PMC 2971691 . ...
Cisplatin, or cis-diamminedichloroplatinum(II) is the first of a series of square planar platinum(II)-containing chemotherapy ... Side effects of cisplatin include nausea and vomiting, hair loss, tinnitus, hearing loss, and nephrotoxicity.) The ... Compounds containing platinum, such as cisplatin, oxaliplatin and carboplatin, are applied in chemotherapy against certain ... Taguchi, Takashi; Nazneen, Arifa; Abid, M. Ruhul; Razzaque, Mohammed S. (2005). "Cisplatin-Associated Nephrotoxicity and ...
Cleft lip and palate transmembrane protein 1-like protein (CLPTM1-like protein), also known as cisplatin resistance-related ... CRR9p is associated with cisplatin-induced apoptosis. CLPTM1L, which lies within a cancer susceptibility locus on chromosome 5 ...
Cisplatin-induced ototoxicity is dose-dependent, typically occurring with doses greater than 60 mg/m2, and tend to occur when ... Cisplatin and related agents are absorbed by the cochlear hair cells and result in ototoxicity through the production of ... January 2009). "Cisplatin and oxaliplatin toxicity: importance of cochlear kinetics as a determinant for ototoxicity". Journal ... Gratton, Michael Anne; Salvi, Richard J; Kamen, Barton A; Saunders, Samuel S (1990-12-01). "Interaction of cisplatin and noise ...
... and cisplatin, which is used in chemotherapy. Amikacin should not be used with neuromuscular blocking agents, as they can ...
Cisplatin was the first to be developed. Cisplatin is particularly effective against testicular cancer; the cure rate was ... In this form of chemotherapy, popular drugs include cisplatin and carboplatin, but several have been proposed or are under ... Poklar N, Pilch DS, Lippard SJ, Redding EA, Dunham SU, Breslauer KJ (July 1996). "Influence of cisplatin intrastrand ... As studied mainly on cisplatin, but presumably for other members as well, platinum-based antineoplastic agents cause ...
Basu, A. (2010). "Cellular Responses to Cisplatin-Induced DNA Damage". Journal of Nucleic Acids. 2010: 1-16. doi:10.4061/2010/ ...
CISPLATIN 115. CITALOPRAM HYDROBROMIDE 116. CLARITHROMYCIN 117. CLAVULANIC ACID 118. CLIDINIUM BROMIDE ...
2003). "Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A". Biochem. ... LUC7 like 3 pre-mRNA splicing factor (LUC7L3), also known as Cisplatin resistance-associated overexpressed protein, or CROP, is ... This gene encodes a cisplatin resistance-associated overexpressed protein (CROP). The N-terminal half of the CROP contains ... 2000). "CROP/Luc7A, a novel serine/arginine-rich nuclear protein, isolated from cisplatin-resistant cell line". FEBS Lett. 465 ...
Aziridines include thiotepa, mytomycin and diaziquone (AZQ). Cisplatin and derivatives include cisplatin, carboplatin and ... Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin. On the other hand, therapies ... Rybak LP, Mukherjea D, Jajoo S, Ramkumar V (Nov 2009). "Cisplatin ototoxicity and protection: clinical and experimental studies ... such as bleomycin and cisplatin), to enter the cancer cells. Hence, greater effectiveness of antitumor treatment is achieved. ...
Cisplatin resistance occurs when cancer cells develop an enhanced ability to reverse such damage by removing the cisplatin from ... The cisplatin-resistant cells upregulate expression of the excision repair cross-complementing (ERCC1) gene and protein. Some ... In ovarian cancer, the ATP7B gene encodes for a copper efflux transporter, found to be upregulated in cisplatin-resistant cell ... Platinum-based chemotherapies, such as cisplatin, target tumour cells by cross-linking their DNA strands, causing mutation and ...
Commonly used drugs include cisplatin, vincristine, and methotrexate. Side effects include anemia (causing fatigue, weakness), ...
"Investigation into ubiquitin signalling in response to cisplatin". Discovery Research Portal. University of Dundee. Retrieved 2 ... predicted to be a part of the ubiquitin ligase family and involved with DNA repair mechanisms after treatment with cisplatin, a ...
Cisplatin ("Platinol") was given instead of carboplatin ("Paraplatin"). He resides in Rome, New York with his second wife, ...
Aziridines include thiotepa, mytomycin and diaziquone (AZQ). Cisplatin and derivatives include cisplatin, carboplatin and ... Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin.[90] On the other hand, ... such as bleomycin and cisplatin), to enter the cancer cells. Hence, greater effectiveness of antitumor treatment is achieved. ... Instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by ...
... to better understand how cisplatin invades tumor cells and interferes with their activity. The interaction of Cisplatin and DNA ... Cisplatin is one of the most frequently used chemotherapy medications for many forms of cancer. It was discovered in the 1960s ... Cisplatin : chemistry and biochemistry of a leading anticancer drug. Zürich: Verlag Helvetica Chimica Acta. pp. 456-458. ISBN ... Its proprietary drug candidates included BTP-114, a cisplatin prodrug, and BTP-277, a targeting ligand designed to bond ...
Examples of radiosensitizing drugs include: Cisplatin, Nimorazole, and Cetuximab. The effect of radiotherapy on control of ...
Treatment with cisplatin, etoposide, and bleomycin has been described. Before modern chemotherapy, this type of neoplasm was ...
"Cisplatin Archived April 5, 2007, at the Wayback Machine.". General Chemistry Curriculum Supplement. Accessed April 21, 2007 ... the discoverer of cancer-fighting drug cisplatin. In addition to faculty, Michigan State has around 6,000 administration and ...
In SCLC, cisplatin and etoposide are most commonly used. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, ... Typically, two drugs are used, of which one is often platinum-based (either cisplatin or carboplatin). Other commonly used ... The combination of vinorelbine and cisplatin is more effective than older regimens. Adjuvant chemotherapy for people with stage ...
It has also been shown to circumvent acquired cisplatin resistance in breast cancer cells under in invitro conditions. ... January 2010). "FOXM1 confers acquired cisplatin resistance in breast cancer cells". Molecular Cancer Research. 8 (1): 24-34. ...
Cisplatin is the most widely used chemotherapeutic agent for OS management, it significantly enhances the survival rate. ... SENSITIZATION OF HUMAN OSTEOSARCOMA CELL LINE 143B WITH CALCITRIOL FOR CISPLATIN THERAPY. dc.contributor.advisor. Garimella, ... Our hypothesis is pretreatment of OS cells with calcitriol would sensitize them for cisplatin therapy leading to decrease in ... Objective: Our primary objective is to investigate effects of calcitriol in combination with cisplatin on the osteosarcoma cell ...
Cisplatin is one of the drugs acclimated in chemotherapy analysis for mesothelioma patients. Anon it has been accumulated with ... Tags: drugs, acclimated, patients, mesothelioma, amusement, biologic, alimta, cancers, broadly, gemcitabine, cisplatin, ...
Ptac2S is more effective than Platinol (cisplatin) at reducing the growth rate of sarcomatoid malignant pleural mesothelioma in ... cisplatin) and either Alimta (pemetrexed) or Tomudex (raltitrexed). But survival rates are still low, with only half of ...
In various trials, chemotherapy drugs such as cisplatin and pemetrexed have been used as the sole treatment for patients with ...
Currently, there is only a single chemotherapy regimen (Alimta® (pemetrexed) in conjunction with Cisplatin) approved by the ...
... dexamethasone cyclophosphamide etoposide and cisplatin, cyclophosphamide lung ...
Reduce cisplatin by 25%. 30 to less than 50. Reduce fluorouracil by 25% and cisplatin by 50% or consider substituting ... Cisplatin. Commence prehydration for cisplatin:. *administer 10 mmol magnesium sulphate (MgSO4) in 1000 mL sodium chloride 0.9 ... Arm 1 (TPF): docetaxel 75mg/m2 and cisplatin 100 mg/m2 on day 1 followed by fluorouracil 1000 mg/m2/day from day 1 to day 4 Arm ... ciSplatin. 100 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes. ...
Gill KRS, Gross SA, Al-Haddad M, Patel T, Scolapio JS.Cisplatin induced ischemic colitis: a case report. American Journal of ... Cisplatin. React. Wkly. 1175, 11 (2007). https://doi.org/10.2165/00128415-200711750-00037 ...
Yang Q, et al. Concurrent chemoradiotherapy versus intensitymodulated radiotherapy alone for elderly nasopharyngeal carcinoma patients with pre-treatment Epstein-Barr virus DNA: A cohort study in an endemic area with long-term follow-up. Journal of Cancer 9: 3023-3031, No. 17, 30 Jul 2018. Available from: URL: http://doi.org/10.7150/jca.26145 - ChinaCrossRefPubMedPubMedCentralGoogle Scholar ...
Cisplatin Injection: learn about side effects, dosage, special precautions, and more on MedlinePlus ... Cisplatin may cause severe allergic reactions, especially if you have received more than one dose of cisplatin injection. If ... Before taking cisplatin,. *tell your doctor and pharmacist if you are allergic to cisplatin, carboplatin (Paraplatin), any ... If you become pregnant while receiving cisplatin, call your doctor. Cisplatin may harm the fetus. ...
This page contains brief information about cisplatin and a collection of links to more information about the use of this drug, ... Cisplatin is approved to be used alone or with other drugs to treat:. *Bladder cancer that cannot be treated with surgery or ... More About Cisplatin. Definition from the NCI Drug Dictionary - Detailed scientific definition and other names for this drug. ... MedlinePlus Information on Cisplatin - A lay language summary of important information about this drug that may include the ...
Get an overview of CISPLATIN (injection, solution), including warnings and precautions, directions, and the names of other ...
A list of US medications equivalent to P&U Cisplatin is available on the Drugs.com website. ... P&U Cisplatin is a medicine available in a number of countries worldwide. ... Ingredient matches for P&U Cisplatin. Cisplatin. Cisplatin is reported as an ingredient of P&U Cisplatin in the following ... P&U Cisplatin. P&U Cisplatin may be available in the countries listed below. ...
2 hours before every cisplatin infusion) beginning one day before the cisplatin dose, was found to be protective for cisplatin- ... Cisplatin is not absorbed through intact skin, however dermal exposure to cisplatin has resulted in skin irritation (Khan et al ... Cisplatin is not absorbed through intact skin, however dermal exposure to cisplatin has resulted in skin irritation, (Khan et ... 1990) Cisplatin neurotoxicity. N Engl J Med 322 (2):126-127 NIOSH. (1995) Cisplatin, RTECS-TP25000 C2 (95-2) Expires 09/95 ...
Etoposide and cisplatin chemotherapy, known as EP (or sometimes PE), is used to treat many cancers. Find out more about the ... Cisplatin can affect your hearing. You may have a hearing test before you start treatment. You may get ringing in your ears. ... After this, they will give you cisplatin as a drip over a longer period of time. They usually run the drip through a pump, ... Cisplatin can affect how your kidneys work. You will have blood tests before and during treatment to check this. ...
Cisplatin rated 8.0/10 vs Vincristine rated 9.0/10 in overall patient satisfaction. ... Compare Cisplatin vs Vincristine head-to-head for uses, ratings, cost, side effects, interactions and more. ...
If cisplatin accidentally seeps out of the vein into which it is injected, it may damage some tissues and cause scarring. Tell ... Cisplatin may lower your bodys resistance and there is a chance you might get the infection the immunization is meant to ... Cisplatin can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. ... While you are being treated with cisplatin, and after you stop treatment with it, do not have any immunizations (vaccinations) ...
Cisplatin (Platinol, CDDP) chemotherapy side effects, how its given, how it works, precautions and self care tips for treatent ... If cisplatin escapes from the vein it can cause tissue damage. The nurse or doctor who gives cisplatin must be carefully ... Cisplatin side effects will improve after therapy is complete.. *Cisplatin side effects may be quite manageable. There are many ... How Cisplatin Is Given:. *Cisplatin is administered through a vein (intravenously or IV) as an infusion. ...
cisplatin (UNII: Q20Q21Q62J) (cisplatin - UNII:Q20Q21Q62J) cisplatin. 1 mg in 1 mL. ... The active ingredient, cisplatin USP, is a yellow to orange crystalline powder. Cisplatin is a heavy metal complex containing a ... Cisplatin is mutagenic in bacteria and produces chromosome aberrations in animal cells in tissue culture. In mice cisplatin is ... Cisplatin Injection is a clear, colorless, sterile aqueous solution. Each 100 mL amber vial of Cisplatin Injection contains: 1 ...
Cisplatin: The Invention of an Anticancer Drug by Andri Smith. *Anti-cancer Agents: A treatment of Cisplatin and their ... Cisplatin resistanceEdit. Cisplatin combination chemotherapy is the cornerstone of treatment of many cancers. Initial platinum ... "Cisplatin". International Drug Price Indicator Guide. Retrieved 8 December 2016.. *^ British national formulary: BNF 69 (69 ed ... Cisplatin". Annals of Internal Medicine. 100 (5): 704-13. doi:10.7326/0003-4819-100-5-704. PMID 6370067.. ...
Cisplatin is used together with other medications to treat bladder cancer, testicular cancer, or ovarian cancer. Cisplatin may ... Cisplatin is a cancer medication that interferes with the growth of cancer cells and slows their growth and spread in the body ... How is cisplatin given?. Cisplatin is injected into a vein through an IV. You will receive this injection in a clinic or ... What other drugs will affect cisplatin?. Cisplatin can harm your kidneys. This effect is increased when you also use certain ...
Interaction of Cisplatin with Glutathione. When cancer cells are exposed to cisplatin, the platinum atom in cisplatin is ... How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced ... Efflux of cisplatin from the cells by the ATP-dependent transporters, ATP7A and ATP7B. [. 3. ]. Cisplatin binds to cellular ... Cisplatin increased p53 and decreased XIAP in cisplatin-sensitive ovarian cancer 2008 cells but not in cisplatin-resistant ...
Cisplatin and fluorouracil (5FU) chemotherapy treats cancers of the gullet (oesophagus), head and neck, and anus. It may also ... How cisplatin and 5FU is given. You will have cisplatin and 5FU in the chemotherapy day unit or during a short stay in hospital ... What is cisplatin and 5FU?. Cisplatin and fluorouracil (5FU) is a combination chemotherapy treatment used to treat cancers of ... Your course of cisplatin and 5FU. You usually have a course of several cycles of treatment over a few months. Cisplatin and 5FU ...
... with fecal pellets before chemotherapy reduces intestinal damage and systemic inflammation in response to cisplatin. ... Bacteriotherapy Heals Cisplatin Damage * NHLBI selects Moffitt Cancer Center as one of the Cell Therapies Processing Facilities ... Bacteriotherapy Heals Cisplatin Damage * S100A9-Induced Overexpression of Pd-1/Pd-L1 Contributes to Ineffective Hematopoiesis ... The new study indicates that cisplatin induces significant changes in the repertoire of intestinal commensal bacteria, which ...
Cisplatin: The Invention of an Anticancer Drug by Andri Smith Anti-cancer Agents: A treatment of Cisplatin and their analogues ... It is suggested that an antibody reacting with a cisplatin-red-cell membrane is responsible for hemolysis. Cisplatin interferes ... cisplatin is used in Auger therapy. Often, medical practitioners and researchers must be careful about how long cisplatin ... so it is not primarily due to the cisplatin. Hemolytic anemia can be developed after several courses of cisplatin. ...
  • At the moment the mesothelioma treatment that does the best job of lengthening patients' lives is a combination of Platinol (cisplatin) and either Alimta (pemetrexed) or Tomudex (raltitrexed). (bionewsfeeds.com)
  • The dose response of cisplatin with and without calcitriol (100nM) pretreatment was studied in osteosarcoma cell lines 143B-MM, 143-P and control murine osteoblast MC3T3-E1. (ku.edu)
  • Our hypothesis is pretreatment of OS cells with calcitriol would sensitize them for cisplatin therapy leading to decrease in concentration for IC50. (ku.edu)
  • Results: Calcitriol does not sensitize the 143B-P and 143B-MM OS cells for cisplatin therapy. (ku.edu)
  • The clinically acquired resistance can be caused by decreased drug accumulation which includes reduced uptake or increased efflux of cisplatin, increased drug detoxification by cellular thiols, increased DNA repair or tolerance of cisplatin-damaged DNA and the ability of the cancer cells to evade cisplatin-induced cell death. (hindawi.com)
  • While triggering apoptosis through interfering with DNA replication remains the primary mechanism of cisplatin, this has not been found to contribute to neurological side effects. (wikipedia.org)
  • We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. (hindawi.com)
  • Cisplatin, like many other chemotherapeutic drugs, can induce apoptosis. (hindawi.com)
  • Thus, the signaling pathways that regulate apoptosis have significant impact on deciding cellular responsiveness to cisplatin. (hindawi.com)
  • Our observations revealed that EGCG increases the sensitization of cisplatin to cervical cancer cells by inhibiting cell survival and inducing apoptosis. (frontiersin.org)
  • Inhibition of caspase activity by caspase-9 inhibitor (z-LEHD-fmk) or by overexpression of Bcl-2 potently inhibited apoptosis induced by cisplatin. (cdc.gov)
  • Since Bcl-2 is overexpressed in many cancer cell types and resistance to cisplatin-induced apoptosis is a major limitation for effective therapy, the knowledge from this study could be beneficial to the design of more effective therapy for cancer treatment. (cdc.gov)
  • Green coffee administration in cisplatin-induced renal apoptosis groups produced significant lower levels of BUN, creatinine, uric acid and H 2 O 2 (24.4 ± 4.14, 1.730 ± 0.2830, 5.50 ± 0.850 and 0.51 ± 0.12 respectively) as compared with cisplatin-induced renal apoptosis group not administrated green coffee (27.4 ± 6, 2.04 ± .31, 7.00 ± 1.25 and 1.1 ± 0.16 respectively). (scirp.org)
  • Green coffee improved the general condition of cisplatin-induced renal apoptosis rats due to its antioxidant and anti-apoptotic effects. (scirp.org)
  • Here we report caspase-2 and caspase-9 dynamics during cisplatin-induced HeLa apoptosis using Double Fluorescence Resonance Energy Transfer (FRET) technique. (spie.org)
  • RPTC cells underwent apoptosis during cisplatin treatment, which was increased when Hsf1 was knocked down. (medworm.com)
  • Transfection or restoration of Hsf1 into Hsf1-knockdown cells suppressed cisplatin-induced apoptosis, further supporting a cytoprotective role of Hsf1 and its associated heat shock response. (medworm.com)
  • Transfection of CryAB into Hsf1-knockdown cells diminished their sensitivity to cisplatin-induced apoptosis, suggesting that CryAB may be a key mediator of the cytoprotective effect of Hsf1. (medworm.com)
  • Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. (jci.org)
  • C and D ) Effects of MAPK inhibitors on cisplatin-induced apoptosis in wild-type and Pkcd -/- kidney proximal tubular cells. (jci.org)
  • Although NO favored increased expression and phosphorylation of p53, it also increased the expression of the p53 inhibitor MDM2, which may have counteracted p53-induced apoptosis upon cisplatin treatment. (mit.edu)
  • Furthermore, NO displayed the remarkable ability to overcome the effect of U0126, a MEK inhibitor, and promoted continuous phosphorylation of ERK1/2 (and hence cell survival), in contrast to cells not exposed to NO. Results also demonstrated that cisplatin-induced apoptosis was substantially decreased by the antioxidant precursor N-acetylcysteine (NAC). (mit.edu)
  • Increased expression of mesenchymal markers and actin-cytoskeleton regulators, as well as low apoptosis index, in TUR specimens was associated with pathologic progression on cisplatin-based NAC. (urotoday.com)
  • Cisplatin has been used as a first-line therapy for several cancers, including testicular, ovarian, cervical, head, and neck and small-cell lung cancers either alone or in combination with other anticancer agents. (hindawi.com)
  • Indeed, cisplatin is one of the most successful anticancer agents, effective against a wide range of solid tumors. (pnas.org)
  • This host-guest chemistry could open the way to relatively unexplored methods of drug delivery, which circumvent the malicious side effects and drug resistance associated with cisplatin and other anticancer therapeutics. (rsc.org)
  • Other drugs (such as the aminoglycoside antibiotic class) may also cause ototoxicity, and the administration of this class of antibiotics in patients receiving cisplatin is generally avoided. (wikipedia.org)
  • Find Clinical Trials for Cisplatin - Check for trials from NCI's list of cancer clinical trials now accepting patients. (cancer.gov)
  • Not all cisplatin side effects are listed above, some that are rare (occurring in less than 10% of patients) are not listed here. (chemocare.com)
  • Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625 mg/m(2) twice daily orally, streptozocin (Strep) 1.0 g/m(2) intravenously on day 1, with or without cisplatin (Cis) 70 mg/m(2) intravenously on day 1. (nih.gov)
  • Non-randomized, open-label, single center trial to assess efficacy (as measured by overall response rate (ORR) by RECIST 1.1 of disulfiram and cisplatin in patients with multiple relapsed/refractory germ cell tumors (GCTs). (clinicaltrials.gov)
  • To find out if SS1(dsFV)PE38, together with pemetrexed and cisplatin is safe and tolerable in patients with mesothelioma. (mesothelioma.com)
  • To see if SS1(dsFV)PE38 given with pemetrexed and cisplatin has any effect on patients tumors. (mesothelioma.com)
  • HOUSTON -- In patients with anal canal carcinoma, a rare malignancy, cisplatin-based induction therapy did not pan out, a randomized trial revealed. (medpagetoday.com)
  • The optimal schedule would correspond to the delivery of gemcitabine upon awakening and cisplatin near mid-activity in cancer patients. (nature.com)
  • Cisplatin and other platinum-based chemotherapeutic agents are routinely used in treating numerous tumor types with approximately 500,000 patients including 2,000 children treated each year in the United States. (cnbc.com)
  • The hsp90B-MAST1-CHIP signaling axis and its relationship with cisplatin response were clinically validated in cancer patients. (jci.org)
  • 9 patients with thymoma-associated MG complicated with hypertension and/or diabetes after thymectomy were administered 75 mg/m2 of docetaxel and 70 mg/m2 of cisplatin on day 1. (degruyter.com)
  • This new approach provides hope for patients with cisplatin-resistant invasive bladder cancers. (medindia.net)
  • Patients may experience an allergic-type reaction within minutes of cisplatin administration consisting of wheezing, difficulty breathing and low blood pressure. (unm.edu)
  • Uncommonly, patients experience a type of allergic reaction to cisplatin. (unm.edu)
  • Ulrich Gatzemeier, MD, of Hamburg, said that patients treated with paclitaxel/cisplatin had higher response rates and longer time to disease progression than those on high-dose cisplatin. (cancernetwork.com)
  • Patients were randomized to single-agent high-dose cisplatin (100 mg/m²) or combination paclitaxel and standard-dose cisplatin (paclitaxel 175 mg/m² by 3-hr infusion, followed by cisplatin 80 mg/m²). (cancernetwork.com)
  • As might be expected, patients were significantly less able to tolerate the high-dose cisplatin regimen (median of 3 courses) than the standard-dose combination regimen (median of 5 courses). (cancernetwork.com)
  • Dr. Gatzemeier reported overall response rates in patients with measurable disease of 26% for cisplatin/paclitaxel vs 17% for high-dose cisplatin (P = .0001). (cancernetwork.com)
  • Dr. Gatzemeier said that there was crossover to second-line therapy when disease progressed, and that some patients on single-agent cisplatin did receive a taxane. (cancernetwork.com)
  • In the knowledge of late adjuvant chemotherapy-related over-mortality it is therefore critical to identify subsets of patients who would or would never benefit from adjuvant cisplatin. (biomedsearch.com)
  • Seventeen patients with intraperitoneal tumors were treated by 4-hour intraperitoneal dialysis with cisplatin alone, or in combination with an intravenous neutralizing agent, sodium thiosulfate. (annals.org)
  • Determine the maximum tolerated dose (MTD) of gemcitabine in combination with cisplatin and pelvic radiotherapy in these patients. (bioportfolio.com)
  • Among the 448 patients in the study, median overall survival was 12.1 months for the Alimta-treated patients vs 9.3 months for the cisplatin-only arm, a 30% increase with Alimta. (cancernetwork.com)
  • At 1 year, 50.3% of Alimta-treated patients were alive, compared with 38% treated with cisplatin alone. (cancernetwork.com)
  • Among the 331 patients who received the full folic acid and B 12 supplementation, the median overall survival was 13.3 months in the Alimta group vs 10.0 months in the cisplatin-only arm. (cancernetwork.com)
  • Adverse events among the fully supplemented participants consistently occurred more often in the Alimta-group than in the cisplatin-only patients. (cancernetwork.com)
  • A Norwegian study that looked back at the treatments and outcomes of men with testicular cancer found that patients with certain inherited genetic makeups either had an increased tendency to lose hearing or were protected from hearing loss when treated with cisplatin. (curetoday.com)
  • All patients being treated with cisplatin are at an increased risk of experiencing ear toxicities. (medicineshoppe.com)
  • In lung cancer, cisplatin-based chemotherapy remained the first line regimen for advanced lung cancer patients especially those without EGFR mutation. (aacrjournals.org)
  • To estimate the response rate and overall survival of patients with metastatic or unresectable adenocarcinomas of the urothelial tract or urachal remnant who are treated with combination chemotherapy consisting of 5-FU, leucovorin, gemcitabine and cisplatin. (mdanderson.org)
  • In preparation for a clinical trial in which chemotherapy would be administered intraoperatively, the question of exposure to healthcare personnel arose, therefore, the purpose of this study was to perform an evaluation of healthcare personnel exposure to cisplatin during a mock demonstration of intraperitoneal chemotherapy administration. (cdc.gov)
  • MCL induced GSH depletion and severe cell death in KLF4-overexpressing MCF-7 cells following exposure to cisplatin. (sigmaaldrich.com)
  • Cisplatin is also used alone or in combination with other medications to treat bladder cancer that can not be treated with surgery or radiation therapy alone. (medlineplus.gov)
  • An Oncofetal Glycosaminoglycan Modification Provides Therapeutic Access to Cisplatin-resistant Bladder Cancer. (medindia.net)
  • Day one - you have etoposide as a drip (infusion) over an hour and cisplatin as a drip (infusion). (macmillan.org.uk)
  • Cisplatin is administered through a vein (intravenously or IV) as an infusion. (chemocare.com)
  • Before and/or after the cisplatin infusion, extra IV fluids are given and care is taken to ensure adequate hydration before both during and after cisplatin, to protect your kidney function. (chemocare.com)
  • Cisplatin also has been used as an infusion into the abdominal cavity (contains the abdominal organs). (chemocare.com)
  • Your nurse will give you cisplatin through a drip (infusion). (macmillan.org.uk)
  • You have cisplatin as a drip into your bloodstream (intravenously). (cancerresearchuk.org)
  • Cisplatin can be given intravenously (into a vein), or intraperitoneally (into the peritoneum of the abdominal cavity). (unm.edu)
  • Cisplatin is usually used intravenously and is given in conjunction with a process called "diuresis. (marvistavet.com)
  • Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. (sigmaaldrich.com)
  • In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. (sigmaaldrich.com)
  • Cisplatin interferes with DNA replication, which kills the fastest proliferating cells, which in theory are carcinogenic. (wikipedia.org)
  • Our recent financing enables us to expand the scope of our development efforts, and the clinical evaluation of OTO-104 for the prevention of cisplatin-induced hearing loss is a priority based on the high unmet medical need, attractive market potential, and preclinical proof-of-concept presented in this publication," said David A. Weber, Ph.D., president and CEO of Otonomy. (cnbc.com)
  • Read user comments about the side effects, benefits, and effectiveness of cisplatin intravenous. (webmd.com)
  • Day 1 - Intravenous (through a vein) infusions of pemetrexed and cisplatin. (mesothelioma.com)
  • Cisplatin therapy can cause hearing loss for men with testicular cancer, but preventive measures are emerging. (curetoday.com)
  • In addition, from 40 to 60 percent of testicular cancer survivors who have used cisplatin-based chemotherapy experience tinnitus, or a continuous, high-pitched sound in the ears. (curetoday.com)
  • There are about 300,000 testicular cancer survivors worldwide, as well as millions of survivors of other cancers who have been treated with cisplatin-based chemotherapy. (curetoday.com)
  • The ototoxicity of both the aminoglycosides and cisplatin may be related to their ability to bind to melanin in the stria vascularis of the inner ear or the generation of reactive oxygen species. (wikipedia.org)
  • Because inflammatory products such as NO and reactive oxygen species (ROS) are associated with the genesis and evolution of cancer, we hypothesized that these oxidative species may regulate key components of the response of melanoma to cisplatin. (mit.edu)
  • Cisplatin may cause serious kidney problems. (medlineplus.gov)
  • To help understand mechanisms involved in the development of kidney injury, cisplatin rodent model has been developed. (hindawi.com)
  • The investigation of the development of CKI was not gaining any attention, although it was known that cisplatin can have long term effects on the structure and function of the rat kidney after single [ 10 - 12 ] or multiple [ 13 - 15 ] administration. (hindawi.com)
  • Cisplatin can cause kidney damage. (marvistavet.com)
  • B ) Cisplatin-induced MAPK activation in primary cultures of wild-type and Pkcd -/- kidney proximal tubular cells. (jci.org)
  • Kidney proximal tubular cells isolated from ( C ) wild-type and ( D ) Pkcd -/- mice were incubated for 24 hours with 50 μM cisplatin in the absence (-) or presence (+) of 5 μM U0126, 10 μM SP600125, or 10 μM SB203580. (jci.org)
  • or induction chemotherapy with cisplatin and 5FU followed by radiation. (medpagetoday.com)
  • To determine the maximum tolerated dose of cisplatin when given concurrently with radiation therapy for participants with Stage II or III breast cancer who have undergone breast conserving surgery. (knowcancer.com)
  • The aim of this study is to evaluate the feasibility of hypofractionated radiation therapy and concomitant chemotherapy with cisplatin for locally advanced head and neck cancer in a high volume brazilian center. (clinicaltrials.gov)
  • To evaluate if concomitant cisplatin and hypofractionated radiation therapy wold be feasible in a brazilian population. (clinicaltrials.gov)
  • In the presence of radiation, both gold and platinum of cisplatin, serve as high atomic number radiosensitizers leading to the emission of ionizing photoelectrons and Auger electrons. (rsc.org)
  • Here you can see the latest Cisplatin Gemcitabine Hydrochloride Radiation Therapy Pancreatic Cancer articles that have been published worldwide. (bioportfolio.com)
  • We have published hundreds of Cisplatin Gemcitabine Hydrochloride Radiation Therapy Pancreatic Cancer news stories on BioPortfolio along with dozens of Cisplatin Gemcitabine Hydrochloride Radiation Therapy Pancreatic Cancer Clinical Trials and PubMed Articles about Cisplatin Gemcitabine Hydrochloride Radiation Therapy Pancreatic Cancer for you to read. (bioportfolio.com)
  • In addition to the medical data, news and clinical trials, BioPortfolio also has a large collection of Cisplatin Gemcitabine Hydrochloride Radiation Therapy Pancreatic Cancer Companies in our database. (bioportfolio.com)
  • You can also find out about relevant Cisplatin Gemcitabine Hydrochloride Radiation Therapy Pancreatic Cancer Drugs and Medications on this site too. (bioportfolio.com)
  • Combining cisplatin with gemcitabine may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells. (bioportfolio.com)
  • The addition of nimotuzumab to weekly cisplatin-radiation improves outcomes inclusive of OS in HPV negative oropharyngeal cancers. (brightsurf.com)
  • The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin. (nih.gov)
  • The authors reported colostomy rates of 10% with the mitomycin regimen and 19% with the cisplatin therapy ( P =0.02). (medpagetoday.com)
  • Through a metabolism-related kinome RNAi screen, we identified inositol-trisphosphate 3-kinase B (ITPKB) as a critical enzyme that contributes to cisplatin-resistant tumor growth. (jci.org)
  • We demonstrated that inositol 1,3,4,5-tetrakisphosphate (IP4), the product of ITPKB, plays a critical role in redox homeostasis upon cisplatin exposure by reducing cisplatin-induced ROS through inhibition of a ROS-generating enzyme, NADPH oxidase 4 (NOX4), which promotes cisplatin-resistant tumor growth. (jci.org)
  • 0.05) more effective in retarding tumor growth than nonradioactive cisplatin. (lu.se)
  • This resulted in enhanced synergy between cisplatin and radiotherapy mediated cytotoxicity, and photo/Auger electron mediated radiosensitisation leading to complete ablation of the tumour cells in an in vitro model system. (rsc.org)
  • Because HMGB1 is a powerful inflammatory mediator in many diseases, the aim of this study is to evaluate the therapeutic effect of cisplatin acute liver failure. (mdpi.com)
  • After this, they will give you cisplatin as a drip over a longer period of time. (macmillan.org.uk)
  • Hydrogen peroxide mediates the apoptotic effect of cisplatin by downregulating bcl-2 through ubiquitin-proteasomal degradation. (cdc.gov)
  • The antitumor activity of cisplatin is believed to be due to its interaction with chromosomal DNA [ 4 ]. (hindawi.com)
  • HeLa cells were used to control the effect of cilastatin on the tumoricidal activity of cisplatin. (biomedsearch.com)
  • There is no relationship between the presence or severity of Cisplatin side effects and effectiveness of cisplatin. (chemocare.com)
  • KB-3-1 cisR and A549 cisR cells with flag-CHIP and MAST1 knockdown or WT/2KR overexpression were treated with increasing concentrations of cisplatin in the presence of 17-AAG for 48 hours. (jci.org)
  • Our results show that cisplatin can be inactivated by this protein with the aid of 2 solvent-accessible and reactive cysteines. (pnas.org)
  • Because cisplatin binds covalently to protein, labeling remains strong through subsequent steps used in downstream mass cytometry staining protocols. (fluidigm.com)
  • Recent studies have focused on the ability of cisplatin to retain the high mobility group box 1 (HMGB1) protein in cisplatin-DNA adducts, thereby preventing its release from the nucleus. (mdpi.com)
  • Cisplatin administration increased expression of the apoptotic protein caspase-3. (scirp.org)
  • Herein, we have demonstrated that EGCG works synergistic with cisplatin in inhibiting growth of cervical cancer cells. (frontiersin.org)
  • In addition, cisplatin is used in Auger therapy. (wikipedia.org)
  • Slight changes in liver function and histopathology are also observed following cisplatin therapy. (inchem.org)
  • Cisplatin side effects will improve after therapy is complete. (chemocare.com)
  • Microbiota Reconstitution Restores Intestinal Integrity After Cisplatin Therapy. (moffitt.org)
  • This effect is used in cancer therapy, and cisplatin may operate on a similar principle. (eurekalert.org)
  • The hypocalcaemia seems to occur in those with low serum magnesium secondary to cisplatin, so it is not primarily due to the cisplatin. (wikipedia.org)
  • Since the growth of normal body cells may also be affected by cisplatin, other effects will also occur. (mayoclinic.org)
  • Bone marrow suppression can also occur on cisplatin. (marvistavet.com)
  • Using a system for controlled delivery of NO to simulate the NO levels believed to occur during inflammation, we showed that human melanoma (A375) cells pre-exposed to submicromolar NO concentrations were protected from a subsequent challenge with cisplatin. (mit.edu)
  • One of the most effective chemotherapy drugs against cancer is cisplatin because it attaches to cancer DNA and disrupts repair. (innovations-report.com)
  • Many scientists are creating alternative drugs or cisplatin analogs in attempts to find treatments without side effects. (innovations-report.com)
  • Cisplatin belongs to a group of drugs called alkylating agents. (unm.edu)
  • RATIONALE: Drugs used in chemotherapy, such as topotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from divid. (bioportfolio.com)
  • RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. (bioportfolio.com)
  • Cisplatin is in a group of drugs called platinum-containing alkylating agents. (medicineshoppe.com)
  • TMPT is an enzyme involved in the breakdown of cisplatin and other drugs from the body. (medicineshoppe.com)