PRIMARY OBJECTIVES:. I. To determine the maximum tolerated dose of intraperitoneal (IP) paclitaxel when given concurrently with fixed dose intravenous (IV) doxorubicin (doxorubicin hydrochloride) and IV cisplatin.. II. To determine the maximum tolerated dose of IP paclitaxel when given concurrently with fixed dose IV doxorubicin hydrochloride and IP cisplatin.. III. To determine the feasibility of an IV/IP based doxorubicin hydrochloride, paclitaxel, and cisplatin chemotherapy regimen in patients with advanced endometrial cancer.. OUTLINE: This is a dose-escalation study of paclitaxel.. Patients receive doxorubicin hydrochloride IV over 30 minutes followed by cisplatin IV over 1 hour on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim subcutaneously (SC) on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.. Patients then receive doxorubicin hydrochloride IV and cisplatin IV or IP ...
We investigated in vivo the chemotherapeutic anthracycline agents doxorubicin and its ability to activate mitochondrial-mediated, receptor-mediated and endoplasmic/sarcoplasmic reticulum-mediated apoptosis transduction pathways in cardiac tissue from male and female rats. We administered a single low dose of doxorubicin (10 mg/kg of body weight, i.p.) and then isolated mitochondrial and cytosolic proteins one and four days later from the heart. Caspase-3 protein content and caspase-3 activity were significantly increased after day four of doxorubicin treatment in both male and female rats. However, while males had DNA fragmentation at day one but not day four following doxorubicin administration, females showed no significant increase in DNA fragmentation at either time. Caspase-12, localized in the SR, is considered a central caspase, and its activation by cleavage via calpain indicates activation of the SR-mediated pathway of apoptosis. Cleaved caspase-12 content and calpain activity significantly
Pegylated liposomal doxorubicin (PLD) is the first antineoplastic drug derived from the new technology of liposome formulation to be introduced in clinical practice. The low myocardium uptake of this formulation accounts for its reduced cardiac toxicity, confirmed both in preclinical models and in humans. Preclinical data have shown activity in NSCLC xenografts. This Phase II study is to explore the efficacy and toxicity of Pegylated liposomal doxorubicin and Carboplatin in patients with previously untreated non-small cell lung cancer (NSCLC) not amenable to radiotherapy or surgical treatment ...
The efficacy of liposomal doxorubicin for treating Kaposis sarcoma (KS) in patients infected with human immunodeficiency virus (HIV) was studied. Eight men with HIV infection and KS were to be given liposomal doxorubicin 20 mg/sq m i.v. monthly for six months and 10 mg/sq m i.v. monthly thereafter, depending on the response. They were assessed for the onset, extent, and duration of clinical response; relapse; adverse effects; development of new opportunistic infections; quality of life; and survival. Five patients had a clinical complete response (i.e., complete resolution of the manifestations of KS, as determined by physical examination but not confirmed by biopsy) and three patients had a partial response to the induction regimen of liposomal doxorubicin. Relapse occurred in all patients in whom therapy was stopped; reinstatement of therapy elicited a partial response. Neutropenia occurred in two patients; filgrastim therapy enabled the liposomal doxorubicin therapy to continue uninterrupted.
Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine). An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids.
Verapamil reversed resistance to doxorubicin in a human multiple myeloma cell line selected for multiple drug resistance. The drug-resistant cell line 8226/DOX40 is known to have reduced intracellular drug accumulation associated with the overexpression of P-glycoprotein when compared to the sensitive parent cell line 8226/S. Verapamil alone was minimally cytotoxic in both cell lines, but reversed doxorubicin resistance in a dose-related manner in 8226/DOX40. A similar dose-response relationship was observed for verapamil in increasing net intracellular doxorubicin accumulation. This increased net accumulation was secondary to block of enhanced doxorubicin efflux by verapamil from resistant cells. In contrast, verapamil did not alter initial doxorubicin accumulation over the first 60 s when incubated with resistant cells. Addition of verapamil to the 8226/DOX40 cells enhanced the formation of doxorubicin-induced DNA single strand breaks, double strand breaks, and DNA-protein cross-links. ...
Objective: The present study was designed to investigate the cardioprotective potential of Galangin on Doxorubicin induced cardiotoxicity in rats.. Methods: Albino rats used in this experiment were pretreated with vehicle, Galangin (100 & 200µg/kg) and Vit-C (20 mg/kg) for 28 days. On 25th day, a single dose of Doxorubicin (10 mg/kg, i. p) was administered to groups. After 72 h of Doxorubicin administration, ECG, serum and tissues biomarkers were evaluated. Histopathological examination of the heart was performed.. Results: Doxorubicin treated rats exhibited abnormal ECG pattern followed by significant increase in CK-MB, LDH, SGOT, SGPT and LPO level and decrease in GSH, CAT, TT when compared to control rats. Pretreatment with different doses of Galangin and Vit-C significantly reduced the serum biomarkers and increased the tissue antioxidant level when compared to Doxorubicin alone treated groups. Moreover, pretreatment also improved Doxorubicin induced changes in ECG pattern and ...
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BACKGROUND: We aimed to define the maximum tolerated dose (MTD) and characterize the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Caelyx trade mark ) and weekly paclitaxel (wPTX), and to investigate pharmacokinetics of PLD in this combination. METHODS: A phase I study was performed with an initial dose of 50 mg/m(2) wPTX and 30 mg/m(2) PLD. The paclitaxel dose was escalated in increments of 10 mg/m(2) and PLD in increments of 5 mg/m(2) until the MTD was reached. The pharmacokinetics of PLD were studied at the highest achieved dose levels. RESULTS: Forty-four cancer patients were enrolled. The MTD was 30/90 and 35/80 mg/m(2) for PLD/wPTX. Dose-limiting toxicities included treatment delay for neutropenia grade 3, febrile neutropenia, palmar-plantar erythrodysesthesia and deep venous thrombosis. Toxicity below the MTD was mild: skin toxicity grade 1-2 developed at high cumulative doses and vascular thrombotic events occurred in two patients with predisposing factors. No ...
Preclinical studies have reported that a single treadmill session performed 24h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24h prior to treatment changes this response. Breast cancer patients were randomized to either 30min of vigorous-intensity exercise 24h prior to the first doxorubicin treatment (n=13), or no vigorous exercise for 72h prior to treatment (control, n=11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24-48h after the treatment. Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p≤0.01). Whereas systemic vascular resistance ...
Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Doxorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Doxorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific ...
Various researches about doxorubicin work mechanism have done. Anthracyclin antibiotic like doxorubicin has cytotoxic action mechanism through four mechanism, that are: (1) Inhibition of topoisomerase II. (2) Intercalation of DNA so that cause DNA and RNA synthesis inhibition. (3) Cell membrane binding which cause ion flow and transport. (4) Formation of semiquinon free radicals and oxygen free radicals through iron dependent processes and reductive process that is mediated enzyme. This free radicals mechanism has known responsible in cardiotoxicity cause antracyclin antibiotic (Bruton et al, 2005). Doxorubicin can intercalation with DNA, it will directly affect transcription and replication. Doxorubicin can form complex tripartite with topoisomerase II and DNA. Topoisomerase II is an enzyme dependent ATP that work to bind DNA and cause double-stand break in the tip 3phosphate so that allowing strand exchange and streamlining the supercoiled DNA. The streamlining of this strand is followed by ...
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In the present study, we explored sexual dimorphism of doxorubicin cardiotoxicity and energetic and signaling pathways that could be involved in these differences. Two clinically relevant cumulative doses of doxorubicin, either 14 mg/kg after 7 injections or 8 mg/kg after 4 injections were administrated to investigate sex differences in the cardiotoxicity of doxorubicin. Doxorubicin treatment resulted in sex differences characterized in males by (1) important weight loss and decrease in survival rate, (2) strong alterations of myocardial function, (3) decrease in energy signaling pathways, (4) downregulation of mitochondrial biogenesis, (5) decrease in cardiolipin content, (6) decrease in mitochondrial DNA content, and (7) and alteration of mitochondrial respiration. No sex differences were found for the oxidative stress response or for death markers, whereas mitochondrial dysfunction and mitochondrial protein expression were associated with early cardiotoxicity in males.. Several clinical ...
The optimal cardiac toxicity prevention strategy for doxorubicin would include an agent that improves the efficacy of the doxorubicin-based cancer therapy and prevents cardiac toxicity. In our experiments, pretreatment with GGA blocked doxorubicin cardiac toxicity by maintaining systolic function and decreasing cell death in the heart. Most remarkably, GGA also contributed to doxorubicins chemotherapy efficacy in MDA-MB-231 xenografts in parallel with protecting the heart. GGAs antineoplastic effect is likely due to its inhibition of RHO family proteins in both the heart and cancer cells, and we selected MDA-MB-231 for these experiments because of the endogenous high RHO activity in these cells. Because GGA has been used in Japan since 1984 to prevent stomach ulcers and has a long history of safety and lack of adverse effects, we suggest that this novel approach to prevention of doxorubicin toxicity should be further investigated.. By comparison, dexrazoxane, an iron chelator used to reduce ...
A total of 10 patients with histologically proved carcinoma in situ of the bladder had remission of tumor after topical chemotherapy with doxorubicin hydrochloride for 24 months. Of the 10 patients 3 suffered new areas of carcinoma in situ 9 to 12 months after termination of intravesical chemotherapy. Furthermore, 1 of these 3 patients had a distal ureteral tumor. Fibrosis of the submucosal tissue was observed in every patient but a decrease in bladder capacity was observed in only 1 with prior radiotherapy. ...
RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride, docetaxel, and doxorubicin hydrochloride, work in different ways to stop the g
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Patient information for DOXORUBICIN HYDROCHLORIDE 2 MG/ML SOLUTION FOR INFUSION Including dosage instructions and possible side effects.
From March 1996 to March 1998, 106 patients with untreated metastatic breast cancer (MBC) were treated with docetaxel (Taxotere) (100 mg/m²) and doxorubicin (75 mg/m²) on an alternating cycle-by-cycle (doxorubicin, docetaxel, doxorubicin, etc) or sequential (four cycles of docetaxel, then four cycles of doxorubicin) basis, every 3 weeks, for a maximum of eight cycles. 1
Background. Prognosis of acute lymphoblastic leukemia in elderly is poor. The GRAALL-SA1 phase II trial randomly compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients ≥55 years with Philadelphia chromosome-negative ALL. Design and Methods. Sixty patients received either continuous infusion-Doxorubicin (12 mg/m²/d) and continuous infusion-vincristine (0.4 mg/day) on day1-4 or liposomal-Doxorubicin (40 mg/m2;) and standard vincristine (2 mg) on day1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. Endpoints were safety, outcome and prognostic factors. Results. Myelosupression was reduced in the Peg-Dox arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and less erythrocytes transfusions (P=0.04). Grade 3/4 infections and gram-negative bacteremia were reduced in the Peg-Dox arm (P=0.04 and 0.02, respectively). There was a trend toward less ...
Anthracyclines such as, doxorubicin (DOX) are an effective class of antineoplastic agents. Despite its efficacy in the treatment of a variety of cancers including breast cancer, the clinical use of DOX is limited by cardiac side effects. While it has been shown that DOX alters myocardial fatty acid metabolism, it is poorly understood whether variations in myocardial triacylglycerol (TG) metabolism contribute to DOX-induced cardiotoxicity. Since TG catabolism in the heart is primarily controlled by adipose triglyceride lipase (ATGL), this study examined the influence of DOX on cardiac ATGL expression and TG levels as well as the consequence of forced-expression of ATGL in the setting of DOX-induced cardiotoxicity. To do this, wild type (WT) mice and mice with cardiomyocyte-specific ATGL over-expression (MHC-ATGL) received weekly intraperitoneal injections of saline or DOX (8mg/kg) for four weeks. Heart rate, heart weight to tibia length ratio and DOX-induced body weight loss were comparable ...
|strong|Resveratrol enhances the sensitivity of doxorubicin-mediated cell proliferation invasion and migration in human breast cancer cell lines.|/stron ...
Purpose Anthracyclines (including doxorubicin) are still the backbone of commonly used breast cancer chemotherapy regimens. Despite increasing use of doxorubicin and cyclophosphamide (AC) combinations...
This phase IIb trial investigated the efficacy and tolerability of adding vintafolide [EC 145] to pegylated doxorubicin liposomal in patients with
Doxorubicin - Get up-to-date information on Doxorubicin side effects, uses, dosage, overdose, pregnancy, alcohol and more. Learn more about Doxorubicin
There are direct and indirect indications that PEGylated liposomal doxorubicin (Doxil), a widely used anticancer nanomedicine, has a subclinical immune suppressive effect. As an example of a seemingly bad pharmacological property turning out to be "not-so-ugly", but actually beneficial, the authors highlight the potential benefits of Doxils immune suppressive effect. ... read more These include (1) the decreased uptake of the drug by the MPS which may entail enhanced tumor uptake, and, hence, improved therapeutic efficacy; (2) the use of slow infusion protocols in reducing the risk of hypersensitivity (infusion) reactions; and (3), possible protection against hypersensitivity reactions to co-administered reactogenic drugs. To consider immune suppression as useful represents a paradigm shifts in nanotoxicology and anticancer chemotherapy. show less ...
Multidrug resistance (MDR) is a prime reason for numerous failed oncotherapy approaches. In the present study, we investigated whether Alisol F 24 acetate (ALI) could reverse the MDR of MCF-7/DOX cells, a multidrug-resistant human breast cancer cell line. We found that ALI was a potent P-glycoprotein (P-gp) inhibitor, in the Caco-2-monolayer cell model. ALI showed a significant and concentration-dependent cytotoxic effect on MCF-7/DOX cells in combination with doxorubicin by increasing intracellular accumulation and inducing nuclear migration of doxorubicin. However, ALI had no such effect on MCF-7 cells. In addition, ALI also promoted doxorubicin-induced early apoptosis of MCF-7/DOX cells in a time-dependent manner. These results suggest that ALI can enhance chemosensitivity of doxorubicin and reinforce its anti-cancer effect by increasing its uptake, especially inducing its nuclear accumulation in MCF-7/DOX cells. Therefore, ALI could be developed as a potential MDR-reversing agent in cancer
Young cancer patients may occasionally face infertility and premature gonadal failure. Apart from its direct effect on follicles and oocytes, chemotherapy may induce ovarian toxicity via an impact on the entire ovary. The role of doxorubicin in potential ovarian failure remains obscure. Our intention was to elucidate doxorubicin-related toxicity within ovaries. Female mice were injected intraperitoneally with 7.5 or 10 mg/kg doxorubicin and their ovaries were visualized in vivo by high resolution MRI, one day and one month following treatment. Ovaries of other treated mice were excised and weighed at the same post-treatment intervals. Ovarian histological sections were stained for TUNEL or active caspase-3 and follicles were counted and categorized. Ovulation rates were evaluated in superovulated female mice treated with doxorubicin. A single injection of doxorubicin resulted in a major reduction in both ovarian size and weight that lasted even one month post treatment. A dramatic reduction in ovulation
Consumer information about the medication DOXORUBICIN - INJECTION (Adriamycin, Rubex), includes side effects, drug interactions, recommended dosages, and storage information. Read more about the prescription drug DOXORUBICIN - INJECTION.
The characterization of cells that have survived treatment with Adriamycin (MCF-7A), FUdR (MCF-7F), or cells that were subjected to sequential treatment with Adriamycin and FUdR (MCF-7 A/F) was performed to determine whether populations of cells surviving these treatments present different phenotypes than parental, untreated MCF-7 cells. Cells were treated with several concentrations of each of the chemotherapeutic agents. Cell populations from cultures treated with the highest concentrations of Adriamycin or FUdR, still containing viable cells after the period of treatment, were selected. The survivors of the initial Adriamycin treatment were those that remained alive after 5 days of Adriamycin treatment at a concentration of 25 ng/ml, and the survivors of the FUdR treatment were those that survived 3 days of treatment at a concentration of 10 μg/ml of FUdR. These were the highest concentrations in which cells survived, under the conditions used. The MCF-7 A/F cells were developed by treating ...
We examined the use of flavopiridol in potentiating the effects of doxorubicin on the growth of malignant sarcoma both in vitro and in vivo. Preclinically, we documented in MPNST cells that flavopiridol potentiates doxorubicin, when compared with single agents alone. Furthermore, we showed that flavopiridol is active in vivo both as a single agent and in combination with doxorubicin in liposarcoma xenograft with amplified CDK4.. Given these findings, we conducted a phase I dose-escalation clinical trial of flavopiridol plus doxorubicin in patients with advanced sarcomas. Biologically active and therapeutic doses of flavopiridol (90 mg/m2; 50 mg/m2 bolus followed by 40 mg/m2 infusion) and doxorubicin (60 mg/m2) were combined without reaching an MTD. The achieved dose of flavopiridol was similar to that shown to be tolerable in combination with other chemotherapies and the PK at most of the dose levels tested were in the active range based on preclinical data (13, 26). Hematologic DLTs, ...
Liposomes with internal small molecule chemotherapeutics and external ligands specific to cancer-associated cell surface receptors are a promising strategy for next generation anti-cancer therapeutics. The ligands facilitate tight, specific interactions with targeted cancer cells, and upon internalization, deliver their toxic payload locally. In particular, we study liposomal doxorubicin with attached F3 ligand specific to nucleolin overexpressing cancer cells. We build a kinetic model to capture this process and parameterize it with binding, internalization, and cell killing assays in five cell lines. We study the similarities and differences between the liposomes effect on the cell lines, manifesting as model parameter differences in accessible surface area/receptor density, liposome internalization and processing rate, and cell-killing activity. This enables the examination of tunable aspects of drug design like ligand strength and density and further general studies of potency and ...
Doxorubicine hydrochloride PCH is a medicine available in a number of countries worldwide. A list of US medications equivalent to Doxorubicine hydrochloride PCH is available on the Drugs.com website.
This phase I/II trial is studying the side effects and best dose of oblimersen when given together with doxorubicin and docetaxel and to see how well th
Nausea, hair loss, and weight gain are just a few of the common side effects of doxorubicin. This eMedTV segment lists other common doxorubicin side effects, as well as more serious side effects that you should report to your doctor right away.
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What is Doxorubicin nasal spray used for? Consumer medicine information. This leaflet answers some common questions about Doxorubicin
Doxorubicin is routinely used in combination with cisplatin for the treatment of ovarian cancer (11), and although initially successful, therapy often ultimately fails because of acquired resistance to one or both of these agents. A series of compounds with both DNA intercalation and cross-linking potential was investigated against the A2780 human ovarian cancer cell line, the MDR1 overexpressing variant (2780AD), and the 2780/cp70 cell line, which is defective in the hMLH1 subunit with consequent loss of DNA mismatch repair activity. The results from the cytotoxicity investigation highlighted mechanisms of resistance that distinguished the chloroethylaminoanthraquinones from the noncovalent binding hydroxyethylaminoanthraquinones. All of the compounds tested, with the exception of ZP289M, were found to be of the same order of potency as doxorubicin in the A2780 cell line, but showed a wide-ranging variation in the extent of cross-resistance in the doxorubicin-resistant cell line 2780AD (Table ...
The cardiotoxicity sometimes seen with doxorubicin may be caused by the effects of chemotherapy on the enzyme topoisomerase-IIβ.
The move follows the results of a trial, published in the Lancet* today, showing that the drug doxorubicin can be safely omitted from treatment without affecting patients chances of survival.. Wilms tumour is a type of kidney cancer that affects around 80 children a year in the UK, most under the age of seven. Until now, about one half of these patients would have received doxorubicin as part of their treatment, which carries a small risk of heart problems in later life. Now only about one quarter of children at the greatest risk of relapse need the drug.. Doxorubicin is helpful in treating many types of cancer. But with around nine in 10 of children with Wilms tumour now cured, doctors wanted to find out whether it could be safely left out from the treatment of those who had a low chance of relapse, without affecting survival chances.. As part of the study, which was led by Kathy Pritchard-Jones, consultant oncologist at GOSH and researcher at the UCL Institute of Child Health, 583 children ...
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05 Apr 2017. A short-term fast appears to counteract increases in blood sugar caused by common cancer drugs and protect healthy cells in mice from becoming too vulnerable to chemotherapy, according to new research from the University of Southern California.. Valter Longo, USC Leonard Davis School of Gerontology professor and director of the USC Longevity Institute, examined the effects of short-term fasting on mice being treated with the drug doxorubicin.. The study appeared online in the journal PLoS Biology on March 30, 2017.. Mice received the doxorubicin alone or in combination with either dexamethasone or rapamycin, which are both commonly administered during chemotherapy to manage side effects but are also known to increase blood glucose levels.. The mice who received a drug combination showed worse side effects from the chemotherapy, including greater damage to cells in the heart, than the mice who received doxorubicin alone, Longo said.. This combination [doxorubicin with dexamethasone ...
Evidence-based information on doxorubicin from hundreds of trustworthy sources for health and social care. Make better, quicker, evidence based decisions. Evidence search provides access to selected and authoritative evidence in health, social care and public health.
Evidence-based information on doxorubicin from hundreds of trustworthy sources for health and social care. Make better, quicker, evidence based decisions. Evidence search provides access to selected and authoritative evidence in health, social care and public health.
DOXIL (Doxorubicin, liposomal) drug information & product resources from MPR including dosage information, educational materials, & patient assistance.
Cancer treatment with doxorubicin (DOX) can induce cumulative dose-dependent cardiotoxicity. Currently, there are no specific biomarkers that can identify patients at risk during the initial doses of chemotherapy. The aim of this study was to examine plasma cytokines/chemokines and potential cardiovascular biomarkers for the prediction of DOX-induced cardiotoxicity. Plasma samples were collected before (T0), and after the first (T1) and the second (T2) cycles of DOX-based chemotherapy of 27 breast cancer patients, including five patients who presented with ,10% decline of left ventricular ejection fraction (LVEF), five patients with LVEF decline of 5-10%, and 17 patients who maintained normal LVEF at the end of chemotherapy (240 mg/m2 cumulative dose of DOX from four cycles of treatment ...
In dit onderzoek zijn een aantal analytische, farmaceutische en farmacokinetische aspecten bestudeerd van het cytostaticum doxorubicine verpakt in twee verschillende typen liposomen. De fluid-state DXR-liposomen zijn instabiel gedurende de eerste zes maanden na bereiding m.b.t. farmaconlek en chemische stabiliteit van het DXR, maar de dispersie blijft stabiel m.b.t. de deeltjesgrootte van de liposomen. Na twaalf maanden is echter ook de stabiliteit m.b.t. de deeltjesgrootte verminderd. De gel-state DXR-liposomen zijn stabiel gedurende de eerste zes maanden. Na twaalf maanden is de stabiliteit m.b.t. de deeltjesgrootte echter afgenomen. De chemische stabiliteit is op dit tijdstip veel beter dan die van de fluid-state DXR-liposomen. In geen van beide typen DXR-liposomen is groei van aerobe bacterien aangetroffen. Het biologische deel is gericht op het verwerven van meer inzicht in het mechanisme achter de verbetering van de therapeutische index bereikt met DXR-liposomen. M.b.v. een ...
First, lets look at the clear failure to replicate (#2). The original paper reported the effects of a tumor-penetrating peptide (short protein), iRGD peptide, which in the paper increased cellular uptake of the chemotherapy agent doxorubicin in a xenograft model of prostate cancer. A xenograft model involves injecting human tumor cells into immunosuppressed mice and measuring their growth and the ability of the intervention tested to inhibit or reverse that growth. Basically, the Replication Study failed to find statistically significant differences in the penetrance of doxorubicin into the tumor cells, the tumor weight for mice treated with DOX and iRGD compared to DOX alone, or a measure of programmed cell death (apoptosis).. Neither of the two studies reported to be replicated (#1 and #3) was exactly a resounding replication, either. For example, in #3, the results were mixed, as described in an accompanying commentary. In the original paper, for example, the authors noted that cimetidine ...