TY - JOUR. T1 - Oxaliplatin-induced neuropathy. T2 - a tale of two electrolytes. AU - Babiker, Hani M.. AU - Green, Myke R.. AU - Nelson, Mark A. AU - Elquza, Emad -. PY - 2015/6/1. Y1 - 2015/6/1. KW - Calcium/magnesium. KW - Oxaliplatin. KW - Sensory neurotoxicity. UR - http://www.scopus.com/inward/record.url?scp=84940006306&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84940006306&partnerID=8YFLogxK. U2 - 10.1007/s00520-015-2702-0. DO - 10.1007/s00520-015-2702-0. M3 - Article. C2 - 25801447. AN - SCOPUS:84940006306. VL - 23. SP - 1483. EP - 1485. JO - Supportive Care in Cancer. JF - Supportive Care in Cancer. SN - 0941-4355. IS - 6. ER - ...

Background The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned interim analysis of CLASSIC (median followup 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial. Methods CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II-IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m(2) twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m(2) on day 1) for 6 months or observation alone. Randomisation was stratified by ...

TY - JOUR. T1 - Oxaliplatin-induced liver injury mimicking metastatic tumor on images. T2 - A case report. AU - Uchino, Kaori. AU - Fujisawa, Masayoshi. AU - Watanabe, Takanori. AU - Endo, Yoshikatsu. AU - Nobuhisa, Tetsuji. AU - Matsumoto, Yusuke. AU - Kai, Kyohei. AU - Sato, Shiso. AU - Notohara, Kenji. AU - Matsukawa, Akihiro. PY - 2013/10. Y1 - 2013/10. N2 - Oxaliplatin-based chemotherapy is widely used for advanced colorectal cancer treatment, but it occasionally induces liver injury that is characterized histologically by sinusoidal dilatation, hepatic plate atrophy and/or venular obstruction. Most of the patients do not reveal apparent radiological abnormalities, however. Here, we report the case of a 47-year-old man with a radiologically detectable mass-forming oxaliplatin-induced sinusoidal injury that mimicked multiple liver tumors. These mass lesions were found on computed tomography images after the administration of six cycles of folinic acid, fluorouracil and oxaliplatin therapy as ...

Author: Dan Xing, Yu-Qin Chen, Dong-Chang Wang, Yun-Xia Zhao and Gang Chen. Publishing Date: 2016. E-ISSN: 1011-601X. Volume 29 Issue 6. ABSTRACT:. To investigate the combined effects of indomethacin and oxaliplatin on expressions of epidermal growth factor receptor (EGFR), E-cadherin (E-cad), intercellular adhesion molecule-1 (ICAM-1) and CD44v6 related to lymph node metastasis of human lung cancer cell lines. Human lung adenocarcinoma A549 cells were inoculated subcutaneously into the left armpit of nude mice to establish human lung cancer xenografts. The mice were randomly divided into control group, indomethacin group, oxaliplatin group and combination therapy group, which were treated with sterile distilled water, indomethacin, oxaliplatin and indomethacin combined with oxaliplatin, respectively. After 42 days, the mice were sacrificed. The immunohistochemistry and reverse transcription polymerase chain reaction were used to detect the expressions of EGFR, E-cad, ICAM-1 and CD44v6 in tumor ...

Primary Objective: 1. To assess the radical resection rate in subjects treated with S1/ Oxaliplatin chemotherapy plus Apatinib conversion therapy in subjects

TY - JOUR. T1 - The mechanism of the actions of oxaliplatin on ion currents and action potentials in differentiated NG108-15 neuronal cells. AU - Wu, Sheng-Nan. AU - Chen, Bing Shuo. AU - Wu, Yung Han. AU - Peng, Hsung. AU - Chen, Li Tzong. PY - 2009/7/1. Y1 - 2009/7/1. N2 - Oxaliplatin (OXAL) is a platinum-based chemotherapeutic agent which is effective against advanced or metastatic gastrointestinal cancer. However, the mechanisms responsible for the development of the neuropathy induced by this agent remain unclear. In this study, we attempted to evaluate the possible effects of OXAL on ion currents and action potentials (APs) in NG108-15 cells differentiated with dibutyryl cyclic-AMP. Application of OXAL decreased the peak amplitude of voltage-gated Na+ current (INa) with no change in the overall current-voltage relations of the currents. This agent also produced a concentration-dependent slowing of INa inactivation. A further application of ranolazine reversed OXAL-induced slowing of INa ...

Fingerprint Dive into the research topics of XPF protein levels determine sensitivity of malignant melanoma cells to oxaliplatin chemotherapy: Suitability as a biomarker for patient selection. Together they form a unique fingerprint. ...

We present the preliminary toxicity data from the MRC COIN trial, a phase III randomised controlled trial of first-line therapy in advanced colorectal cancer, with particular reference to the addition of cetuximab to an oxaliplatin-fluoropyrimidine combination. A total of 804 patients were randomised between March 2005 and July 2006 from 78 centres throughout the United Kingdom. Patients were allocated to oxaliplatin plus fluoropyrimidine chemotherapy with or without the addition of weekly cetuximab. The choice of fluoropyrimidine (either 5-fluorouracil (5FU) or capecitabine) was decided by the treating physician and patient before randomisation. Toxicity data were collected from all patients. Two hundred and three patients received 5FU plus oxaliplatin (OxMdG, 25%), 333 oxaliplatin+capecitabine (Xelox, 41%), 102 received OxMdG+cetuximab (OxMdG+C, 13%) and 166 Xelox+cetuximab (21%). Percent grade 3/4 toxicities included diarrhoea 6, 15, 13 and 25%, nausea/vomiting 3, 7, 7 and 14% for OxMdG, Xelox, OxMdG

Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer.. Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≥2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir.. Results. Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and ...

This 2 arm study will compare the efficacy and safety of intermittent oral Xeloda plus Eloxatin (oxaliplatin) with that of fluorouracil/leucovorin in patients who have had surgery for colon cancer and no previous chemotherapy. Patients will be randomized to receive either 1) XELOX (Xeloda 1000mg/m2 po bid on days 1-15 + oxaliplatin) in 3 week cycles or 2)5-fluorouracil + leucovorin in 4 or 8 week cycles. The anticipated time on study treatment is until disease progression and the target sample size is 500+ individuals ...

This 2 arm study will compare the efficacy and safety of intermittent oral Xeloda plus Eloxatin (oxaliplatin) with that of fluorouracil/leucovorin in patients who have had surgery for colon cancer and no previous chemotherapy. Patients will be randomized to receive either 1) XELOX (Xeloda 1000mg/m2 po bid on days 1-15 + oxaliplatin) in 3 week cycles or 2)5-fluorouracil + leucovorin in 4 or 8 week cycles. The anticipated time on study treatment is until disease progression and the target sample size is 500+ individuals ...

The International Duration Evaluation of Adjuvant chemotherapy (IDEA) collaboration found evidence to support the noninferiority of 3 versus 6 months oxaliplatin-based adjuvant therapy for capecitabine plus oxaliplatin for patients with stage III colon cancer.

Combined olaparib and oxaliplatin inhibits tumor proliferation and induces G2/M arrest and γ-H2AX foci formation in colorectal cancer Kaiwu Xu,1* Zhihui Chen,2* Yi Cui,1 Changjiang Qin,2 Yulong He,2 Xinming Song2 1Endoscopy Center, 2Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Background: Poly (ADP-ribose) polymerase 1 (PARP1) has an important role in homologous recombination repair. The purpose of this study was to investigate the effect of PARP1 inhibitor on oxaliplatin treatment for colorectal cancer (CRC). Methods: A cell counting kit-8 assay was used to determine the sensitivity of CRC cells to olaparib and/or oxaliplatin. The gene and protein expressions of PARP1 and the gamma histone variant H2AX (γH2AX) were measured by real-time quantitative polymerase chain reaction and western blotting, respectively. The γH2AX

Oxaliplatin-based regimens induce a potential risk of hypersensitivity reaction (HSR), with incidence varying from 10% to 25% and lack of clearly identified risk factors. The present study aimed to assess incidence and risk factors in HSR. All patients treated with oxaliplatin in the Medical Oncology Department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) from October 2004 to January 2011 were enrolled. Incidence and severity of HSR were analyzed retrospectively and the potential clinicopathological covariates were tested on univariate and multivariate analysis. A total of 1,221 doses of oxaliplatin were administered for 191 patients, 8.9% of whom experienced an HSR. Seventeen HSRs were observed, with 1.6% grade 3 and no grade 4 events. The first reaction appeared after a median of 3 oxaliplatin infusions. Using univariate analysis, HSR was associated with younger age (mean age, 56.2 years; p = 0.04), female gender (p = 0.01) and prior exposure to platinum salts (p = 0.02). No

The levels of PVT1-214, microRNA (miR)-128, and interferon regulatory factor-1 (IRF-1) in CRC tissues and cell lines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Log-rank test was applied to evaluate the role of high PVT1-214 levels in shortening the overall survival of CRC patients. Chi-square test was to assess the relation between PVT1-214 expression and clinicopathological features of CRC patients. CCK8 assays tested the cell proliferation of oxaliplatin-resistant CRC cells (HCT116/Oxa and SW480/Oxa) with PVT1-214 knockdown. The underlying regulatory mechanism between PVT1-214 and miR-128 was predicted by bioinformatics and verified by RNA transfection, qRT-PCR and western blotting. Chromatin immunoprecipitation (ChIP) assay was done to examine the relationship between or IRF-1 and the PVT1-214 gene ...

博士論文本文 以下に掲載：International Journal of Nanomedicine 9(1) pp.3005-3012 2014. Dove press. 共著者：Takayoshi Ueno, Kazuhira Endo

Oxaliplatin drug for Colon Cancer: Read about the availability, dosage, administration and side effects of Oxaliplatin while treating colon cancer.

Roilas comments came as the SENRI Trial results were presented including a new gender analysis (1),(2). He said: Until now we said that NK1 antagonists have no role in the prevention of emesis in oxaliplatin chemotherapy, classified as having a moderate emetogenic risk only.. The multicentre, open label, randomised phase III SENRI Trial evaluated the NK1 antagonist aprepitant for the prevention of nausea and vomiting induced by oxaliplatin-based chemotherapy in Japanese patients with colorectal cancer. Patients were randomised in a 1:1 ratio to the control group (5-HT3 receptor antagonist + dexamethasone) or aprepitant group (5-HT3 receptor antagonist + dexamethasone + aprepitant or fosaprepitant (3)) in the first course. All patients were treated with aprepitant/fosaprepitant in the second course. The primary endpoint was the rate of patients with no emesis. The results presented today also include a new analysis of the potential effect of gender on treatment response.. The trial enrolled ...

Oxaliplatin-based chemotherapy is used to treat patients with esophageal adenocarcinoma (EAC), but no biomarkers are currently available for patient selection. We performed a prospective, clinical trial to identify potential biomarkers associated with clinical outcomes. Tumor tissue was obtained from 38 patients with resectable EAC before and after 2 cycles of oxaliplatin-fluorouracil chemotherapy. Pre-treatment mRNA expression of 280 DNA repair (DNAR) genes was tested for association with histopathological regression at surgery, disease-free survival (DFS) and overall survival (OS). High expression of 13 DNA damage repair genes was associated with DFS less than one year (P | 0.05); expression of 11 DNAR genes were associated with worse OS (P | 0.05). From clinical associations with outcomes, two genes, ERCC1 and EME1, were identified as candidate biomarkers. In cell lines in vitro, we showed the mechanism of action related to repair of oxaliplatin-induced DNA damage by depletion and knockout of protein

To investigate acquired resistance to oxaliplatin, we selected two resistant clones from the HCT116 cell line. We found that the resistant phenotype was associated with resistance to oxaliplatin-induced apoptosis as demonstrated by FACS analysis and by Western blotting of caspase 3 activation. In ad …

To characterize the cellular action mechanism of Debio 0507, we compared the major DNA adducts formed by Debio 0507- and oxaliplatin-treated HCT116 human colon carcinoma cells by a combination of inductively coupled plasma mass spectrometry (ICP-MS) and ultraperformance liquid chromatography mass spectrometry (UPLC-MS/MS). HCT116 cells were treated with IC50 doses of Debio 0507 or oxaliplatin for 3 days. Total cellular Pt-DNA adducts were determined by ICP-MS. The DNA was digested, and the major Pt-DNA adducts formed by both drugs were characterized by UPLC/MS/MS essentially as described previously for cisplatin (Baskerville-Abraham et al. in Chem Res Toxicol 22:905-912, 2009). The Pt level/deoxynucleotide was 7.4/104 for DNA from Debio 0507-treated cells and 5.5/104 for oxaliplatin-treated cells following a 3-day treatment at the IC50 for each drug. UPLC-MS/MS in the positive ion mode confirmed the major Pt-DNA adducts formed by both drugs were dach-Pt-d(GpG) (904.2 m/z → 610 m/z and 904.2 m/z →

Supplementary Materials? CAM4-8-276-s001. selectively depleted MDSCs, especially Mo\MDSCs, but only minimally affected T cells. In addition, sublethal doses of oxaliplatin eliminated the immunosuppressive capacity of MDSCs and induced the differentiation of MDSCs into mature cells. Oxaliplatin treatment diminished the expression of the immunosuppressive functional mediators arginase 1 (ARG1) and NADPH oxidase 2 (NOX2) in MDSCs, while an MDSC\depleting agent, gemcitabine, did not downregulate these factors significantly. Oxaliplatin\conditioned MDSCs had no tumor\promoting activity in vivo. In addition, oxaliplatin modulated the intracellular NF\B signaling in MDSCs. Thus, oxaliplatin has the potential to be used as an immunoregulatory agent as well as a cytotoxic drug in cancer treatment. (ratio)?=?(% CFSElow/% Ezetimibe biological activity CFSEhigh), % specific lysis?=?[1???(assessments were performed to compare differences between two groups using SigmaPlot 12.5 software. Values of iNOSin ...

Danish researchers identified a microRNA shown to predict whether a patient with colorectal cancer would be resistant to oxaliplatin treatment, a discovery that holds promise of improving both current treatment options and development of future treatment strategies.

To evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) for elderly patients with untreated metastatic gastric cancer

Brief introduction of FOLFOX regimen chemotherapy,At present, the common chemotherapy regimen is FOLFOX, and there are 2 different methods of administration:1, mFOLFOX6 solution time: Asha L

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A Multicenter, Randomized Phase II Trial Assessing the Activity of Gemcitabine - Oxaliplatin Chemotherapy Alone or in Combination with Cetuximab in Pati

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First-line chemotherapy for metastatic colorectal cancer commonly involves 5-FU in combination with either oxaliplatin or irinotecan. Currently, the efficacy of second-line therapy with either oxaliplatin or irinotecan is limited. For example, the response rate for second-line single-agent oxaliplatin is only 10% (33). Clearly, there is a need for more effective chemotherapy for patients who relapse after or have poor response to first-line treatment. There are a variety published and ongoing clinical trials studying gefitinib as monotherapy (34) or in combination with anthracyclines, taxanes, or platinum-based therapies (35, 36). There are also a significant number of recent studies evaluating capecitabine in combination with cyclophosphamide and methotrexate (37), oxaliplatin (38, 39), oxaliplatin and erlotinib (40), paclitaxel (41), gemcitabine (42, 43), gemcitabine and vinorelbine (44), and vinorelbine (45). The utility of this regimen was explored in an initial attempt to develop new ...

Kaplan-Meier curves according to first-line treatment (oxaliplatin-based regimen) with/without bevacizumab. (A) Progresion-free survival (PFS), (B) Overall surv

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Title: A randomised phase II study of pre-operative or peri-operative docetaxel, oxaliplatin, capecitabine (DOX) regimen in patients with locally advanc

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Background Oxaliplatin is effective in adjuvant and first-line colorectal cancer chemotherapy. Oxaliplatin-induced severe chronic neurotoxicity is the main dose-limiting adverse event. No standard treatment for oxaliplatin-induced chronic neurotoxicity has been identified.. Materials and methods We conducted a prospective pilot clinical trial to explore whether neurotropin has neuroprotective effects on chronic neurotoxicity. From May 1 2010 to July 1 2011, 80 stage II and III colorectal cancer patients who were eligible to receive oxaliplatin-based chemotherapy voluntarily enrolled in the trial. The patients were randomly divided into 2 groups, one of which received neurotropin treatment.. Results The patients in the control group experienced significantly ≥ grade 2 and ≥ grade 3 neurotoxicity (by NCI CTCAE grading) than did those in the neurotropin group (60.9% vs. 38%, for at least grade 2 neurotoxicity, P = 0.001; 39% vs. 2.7%, for at least grade 3 neurotoxicity, P < 0.001). If ...

The acute peripheral neuropathy induced by oxaliplatin treatment occurs very frequently and is aggravated by exposure to cold. Goshajinkigan (GJG), a traditional Japanese (,i,kampo,/i,) medicine, was recently shown to be effective against oxaliplatin-induced acute neuropathy. However, because the effects of GJG and its mechanism in relation to those of its ingredients and its mechanism are not well understood, we examined the effects of GJG on acute neuropathy. Further, we investigated whether GJG affects the functions and gene expressions of transient receptor potential (TRP) channels using a rat model of oxaliplatin-induced neuropathy. Administration of oxaliplatin increased withdrawal responses from cold stimulation, and GJG or calcium gluconate/magnesium sulfate significantly inhibited the oxaliplatin-induced cold hypersensitivity. Application of menthol, a TRPA1/TRPM8 agonist, or allyl isothiocyanate (AITC), a selective TRPA1 agonist, to the hind paw of oxaliplatin-treated rats enhanced the ...

We aimed at validating the role of genetic variants identified by a recent genome-wide association study (GWAS) as determinants of chronic oxaliplatin-induced peripheral neurotoxicity (OXAIPN). Eight polymorphisms (rs10486003, rs2338, rs843748, rs797519, rs4936453, rs12023000, rs17140129, and rs6924 …

Oxaliplatin, the third-generation platinum compound, has evolved as one of the most important therapeutic agents in colorectal cancer chemotherapy. The main limiting factor in oxaliplatin treatment is painful neuropathy that is difficult to treat. This side effect has been studied for several years, but its full mechanism is still inconclusive, and effective treatment does not exist. Data suggest that oxaliplatins initial neurotoxic effect is peripheral and oxidative stress-dependent. A spinal target is also suggested in its mechanism of action. The flavonoids rutin and quercetin have been described as cell-protecting agents because of their antioxidant, antinociceptive, and anti-inflammatory actions. We proposed a preventive effect of these agents on oxaliplatin-induced painful peripheral neuropathy based on their antioxidant properties. Oxaliplatin (1 mg/kg, i.v.) was injected in male Swiss mice, twice a week (total of nine injections). The development of sensory alterations, such as thermal and

TY - JOUR. T1 - Oxaliplatin induces mitotic catastrophe and apoptosis in esophageal cancer cells. AU - Ngan, Chew Yee. AU - Yamamoto, Hirofumi. AU - Takagi, Akimitsu. AU - Fujie, Yujiro. AU - Takemasa, Ichiro. AU - Ikeda, Masataka. AU - Takahashi-Yanaga, Fumi. AU - Sasaguri, Toshiyuki. AU - Sekimoto, Mitsugu. AU - Matsuura, Nariaki. AU - Monden, Morito. PY - 2008/1/1. Y1 - 2008/1/1. N2 - The platinum-based chemotherapeutic agent oxaliplatin displays a wide range of antitumor activities. However, the underlying molecular responses to oxaliplatin in esophageal cancer remain largely unknown. In the present study, we investigated the effect of oxaliplatin on two esophageal cancer cell lines, squamous cell carcinoma (TE3) and adenocarcinoma (TE7). Following cell-cycle arrest at G2 phase after oxaliplatin treatment, TE3 cells died via apoptosis and TE7 cells died via mitotic catastrophe. Survivin was inhibited more in TE7 cells compared with TE3 cells, but inhibition of survivin using small ...

Peripheral neurotoxicity is a debilitating condition that afflicts up to 90% of patients with colorectal cancer receiving oxaliplatin-containing therapy. Although emerging evidence has highlighted the importance of various solute carriers to the toxicity of anticancer drugs, the contribution of these proteins to oxaliplatin-induced peripheral neurotoxicity remains controversial. Among candidate transporters investigated in genetically engineered mouse models, we provide evidence for a critical role of the organic cation transporter 2 (OCT2) in satellite glial cells in oxaliplatin-induced neurotoxicity, and demonstrate that targeting OCT2 using genetic and pharmacological approaches ameliorates acute and chronic forms of neurotoxicity. The relevance of this transport system was verified in transporter-deficient rats as a secondary model organism, and translational significance of preventive strategies was demonstrated in preclinical models of colorectal cancer. These studies suggest that ...

Colorectal cancer (CRC) is a leading cause of cancer death globally and new biomarkers and treatments are severely needed. Here, we employed HCT116 and LoVo human CRC cells made resistant to either SN38 or oxaliplatin, to investigate whether altered expression of the high affinity glutamate transporters Solute Carrier (SLC)-1A1 and -1A3 (EAAT3, EAAT1) is associated with the resistant phenotypes. Analyses included real-time quantitative PCR, immunoblotting and immunofluorescence analyses, radioactive tracer flux measurements, and biochemical analyses of cell viability and glutathione content. Results were evaluated using one- and two-way ANOVA and Students two-tailed t-test, as relevant. In SN38-resistant HCT116 and LoVo cells, SLC1A1 expression was down-regulated ~60 % and up-regulated ~4-fold, respectively, at both mRNA and protein level, whereas SLC1A3 protein was undetectable. The changes in SLC1A1 expression were accompanied by parallel changes in DL-Threo-β-Benzyloxyaspartic acid (TBOA)-sensitive,

Taiho Pharmaceutical Co., Ltd. (HQ: Tokyo, President: Masayuki Kobayashi) announced today that the results of a Phase III clinical trial of TS-1 conducted in Japan on metastatic colorectal cancer (SOFT* Study) were published in the digital version of The Lancet Oncology, a leading medical journal in the field of oncology research.. The SOFT Study enrolled 512 patients with metastatic colorectal cancer to verify that the SOX/Bev regimen (TS-1/oxaliplatin plus bevacizumab) is non-inferior to mFOLFOX6/Bev (modified regimen of 5-FU/l-LV/oxaliplatin plus bevacizumab), which is one of the standard regimens. The primary endpoint was progression-free survival (PFS). Median PFS was 11.5 months in the mFOLFOX6/Bev group and 11.7 months in the SOX/Bev group (hazard ratio 1.04, non-inferiority p value 0.014). Adverse events of Grade 3 or higher (Common Terminology Criteria for Adverse Events) in the SOX/Bev group were sensory neuropathy (10.0%), diarrhea (9.2%), neutropenia (8.8%), hypertension (6.0%), ...

TY - JOUR. T1 - The effect of prophylactic calcium and magnesium infusions on the incidence of neurotoxicity and clinical outcome of oxaliplatin-based systemic treatment in advanced colorectal cancer patients. AU - Knijn, N.. AU - Tol, J.. AU - Koopman, M.. AU - Werter, M. J.B.P.. AU - Imholz, A. L.T.. AU - Valster, F. A.A.. AU - Mol, L.. AU - Vincent, Andrew. AU - Teerenstra, S.. AU - Punt, C. J.A.. PY - 2011/2/1. Y1 - 2011/2/1. N2 - Background: Peripheral sensory neurotoxicity is a frequent and potentially debilitating side effect of oxaliplatin treatment. Calcium and magnesium (Ca/Mg) infusions are frequently used to prevent this toxicity. However, concerns about a negative impact of Ca/Mg infusions on outcome have been raised. We retrospectively assessed the effect of Ca/Mg infusions on the incidence of neurotoxicity and on clinical outcome in advanced colorectal cancer (ACC) patients treated in the phase III CAIRO2 study. Materials and methods: Seven hundred and fifty five previously ...

Oxaliplatin can induce peripheral neuropathy (OXIPN) as an adverse side effect in cancer patients. Until now, no effective preventive or therapeutic drug has b...

Background Metastatic colorectal cancer (mCRC) is a heterogeneous disease where prognosis is dependent both on tumor biology and host factors. Total circulating cell-free DNA (cfDNA) has shown to harbor prognostic information in mCRC, although less is known about the biological correlates of cfDNA levels in this patient group. The primary objective was to evaluate the prognostic value of pretreatment cfDNA in patients receiving the first-line oxaliplatin-based chemotherapy for mCRC, by using a predefined upper limit of normal (ULN) from a cohort of presumed healthy individuals. The secondary objective was to model cfDNA levels as a function of predefined tumor and host factors. Patients and methods This was a retrospective post hoc study based on a prospective multicenter phase III trial, the NORDIC-VII study. DNA was purified from 547 plasma samples and cfDNA quantified by a droplet digital PCR assay (B2M, PPIA) with controls for lymphocyte contamination. Main clinical end point was overall ...

ZALTRAP, in combination with fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. See Important Safety Information and full Prescribing Information.

TY - JOUR. T1 - Novel separation method for highly sensitive speciation of cancerostatic platinum compounds by HPLC-ICP-MS. AU - Hann, S.. AU - Stefánka, Zs. AU - Lenz, K.. AU - Stingeder, G.. PY - 2005/1/1. Y1 - 2005/1/1. N2 - A high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC ICP-MS) method is presented for analysis of cisplatin, monoaquacisplatin, diaquacisplatin, carboplatin, and oxaliplatin in biological and environmental samples. Chromatographic separation was achieved on pentafluorophenylpropyl-functionalized silica gel. For cisplatin, carboplatin, and oxaliplatin limits of detection of 0.09, 0.10, and 0.15 μg L -1, respectively, were calculated at m/z 194, using aqueous standard solutions. (3 μL injection volume). The method was utilized for model experiments studying the stability of carboplatin and oxaliplatin at different chloride concentrations simulating wastewater and surface water conditions. It was found that a high fraction of ...

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Oxaliplatin and protracted infusion of 5FU in patients with advanced or relapsed 5FU pretreated colorectal cancer. The purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5- fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg m(-2)) was given every 2 weeks and PVI 5-FU (300 mg m(-2) day(-1)) was administered. Median age of patients was 61 years. 17 patients had ,2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response ...

1]. Comella P, Casaretti R, Sandomenico C, Avallone A, Franco L. Role of oxaliplatin in the treatment of colorectal cancer. Ther Clin Risk Manag. 2009;5(1):229-38.. [2]. Hsu HH, Chen MC, Baskaran R, Lin YM, Day CH, Lin YJ, Tu CC, Vijaya Padma V, Kuo WW, Huang CY. Oxaliplatin resistance in colorectal cancer cells is mediated via activation of ABCG2 to alleviate ER stress induced apoptosis. J Cell Physiol. 2018 Jul;233(7):5458-5467. doi: 10.1002/jcp.26406. Epub 2018 Jan 23... [3]. Mohammadian M, Zeynali S, Azarbaijani AF, Khadem Ansari MH, Kheradmand F. Cytotoxic effects of the newly-developed chemotherapeutic agents 17-AAG in combination with oxaliplatin and capecitabine in colorectal cancer cell lines. Res Pharm Sci. 2017;12(6):517-525. [4]. Sonowal H, Pal PB, Wen JJ, Awasthi S, Ramana KV, Srivastava SK. Aldose reductase inhibitor increases doxorubicin-sensitivity of colon cancer cells and decreases cardiotoxicity. Sci Rep. 2017;7(1):3182. Published 2017 Jun 9. doi:10.1038/s41598-017-03284-w. ...

High BMI is a well-known risk factor for the development and recurrence of several solid tumours, including CRC. Obesity is associated with increased levels of vascular endothelial growth factor (VEGF). Bevacizumab is the main targeted therapy for inhibiting tumour angiogenesis by blocking the VEGF/VEGF receptor pathway. Elevated VEGF in obese patients might provoke resistance to anti-VEGF therapy. We evaluated the efficacy of bevacizumab on TTP among mCRC patients through stratifying them according to their BMI. Patients with mCRC who had been treated with fluoropyrimidine-based combination chemotherapy with bevacizumab were included in the study. Patients were assigned according to their BMI before initiation of therapy (group A: BMI < 25 kg/m(2), group B: BMI >= 25 kg/m(2)). Multivariate analysis was performed to evaluate the risk of tumour progression. Between April 2007 and June 2011, 80 patients were treated with chemotherapy and bevacizumab as first-line therapy (n = 37 for group A, n = ...

TY - JOUR. T1 - A multicenter, phase I/II trial of biweekly S-1, leucovorin, oxaliplatin and gemcitabine in metastatic pancreatic adenocarcinoma-TCOG T1211 study. AU - Chiang, Nai Jung. AU - Tsai, Kelvin K.. AU - Hsiao, Chin Fu. AU - Yang, Shih Hung. AU - Hsiao, Hui Hua. AU - Shen, Wen Chi. AU - Hsu, Chiun. AU - Lin, Yu Lin. AU - Chen, Jen Shi. AU - Shan, Yan Shen. AU - Chen, Li Tzong. PY - 2020/1. Y1 - 2020/1. N2 - Background: This phase I/II study evaluated the feasibility and efficacy of S-1, leucovorin, oxaliplatin and gemcitabine (SLOG), a triplet regimen, for treating patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Methods: Patients with chemo-naive, metastatic PDAC were eligible to receive fixed-rate infusion (10 mg/m2/min) of gemcitabine of 800 mg/m2 followed by 85 mg/m oxaliplatin of 85 mg/m2 on day 1 plus oral S-1 and leucovorin (20 mg/m2) twice daily from days 1 to 7 in a 2-week cycle. The dose of S-1 would be escalated from 20, 30, 35 to 40 mg/m2 in a 3 + 3 designed ...

Purpose: Understanding the roles of mammalian autophagy in cancer highlights recent advances in the pharmacologic manipulation of autophagic pathways as a therapeutic strategy for cancer. However, autophagy status and corresponding functions in hepatocellular carcinoma (HCC) after therapeutic stress remain to be clarified. This study was to determine whether the autophagic machinery could be activated after chemotherapy and the contribution of autophagy to tolerance of oxaliplatin in HCC.. Experimental Design: Autophagy activation and cell death induced by oxaliplatin were examined in two HCC cell lines as well as in vivo using an HCC model in nude mice. HCC tissue samples with or without locoregional chemotherapy before surgery were also examined by immunohistochemical and electron microscopic analysis.. Results: Autophagy was functionally activated in HCC cell lines and xenografts after oxaliplatin treatment. Suppression of autophagy using either pharmacologic inhibitors or RNA interference of ...

For more than 20 years, BroadcastMed has been innovating digital strategies for healthcare organizations. The company was first in the world to broadcast live surgeries on the internet using its ORLive solution which provides an intimate look inside the operating room.. ...

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Compared to the FOLFOXIRI group, in the FOLFOXIRI plus bev group more patients had ECOG PS 0 (p < 0.001) and synchronous disease (p = 0.031), less patients had received a prior adjuvant chemotherapy (p = 0.012), had the primary tumor resected (p < 0.001) and a high Kohne score (p < 0.001). In the FOLFOXIRI plus bev group a significantly longer PFS (median PFS: 12.1 vs 9.8 months, HR: 0.75 [95%CI: 0.58-0.96], p = 0.022) was reported, as well as a strong trend toward longer OS (median OS: 31.0 vs 23.4 months, HR: 0.76 [95%CI: 0.57-1.02], p = 0.067). No significant differences in terms of RECIST RR (65% vs. 56%; Odds Ratio: 1.19 [95%CI: 0.73-1.95], p = 0.494), early response rate (cut-off: 20%; 63% vs 58%; Odds Ratio: 1.19 [95%CI: 0.69-2.07], p = 0.532) and deepness of response (42.2% vs 53.8%, p = 0.486) were reported. ...

Connie K. Ho for redOrbit.com - Your Universe Online. Researchers at the Massachusetts Institute of Technology (MIT) recently revealed a new platinum compound that could eliminate cancer cells more effectively than cisplatin, a popular chemotherapy anticancer drug. Drugs that have platinum are the most widely used most powerful cancer drugs. On the downside, these agents have toxic side effects and the cancer cells can eventually become resistant; as such, the new discovery is exciting for researchers to explore new treatment possibilities.. Researchers hope that the new compound will prove to be affective in fighting cancer.. I´ve long believed that there´s something special about platinum and its ability to treat cancer, noted MIT chemistry professor Stephen J. Lippard, who has studied platinum drugs, in a prepared statement. We might have a chance of applying platinum to a broader range of cancer types, more successfully.. The project is described in a paper featured in the Proceedings ...

What: The purpose of this study is to evaluate the effects of an oral drug called celecoxib when combined with FOLFOX chemotherapy in patients with colon cancer who have previously been treated with surgery. FOLFOX chemotherapy is a standard treatment used to prevent colon cancer from coming back and consists of three drugs: 5-fluorouracil, leucovorin and oxaliplatin. This study will also look at whether receiving FOLFOX for 6 treatments is as good as 12 treatments in preventing colon cancer from returning. Currently, the standard of care for colon cancer is 12 treatments with FOLFOX. This trial will explore whether 6 treatments are as effective as 12 treatments and whether side effects can be reduced with fewer treatments ...

What: The purpose of this study is to evaluate the effects of an oral drug called celecoxib when combined with FOLFOX chemotherapy in patients with colon cancer who have previously been treated with surgery. FOLFOX chemotherapy is a standard treatment used to prevent colon cancer from coming back and consists of three drugs: 5-fluorouracil, leucovorin and oxaliplatin. This study will also look at whether receiving FOLFOX for 6 treatments is as good as 12 treatments in preventing colon cancer from returning. Currently, the standard of care for colon cancer is 12 treatments with FOLFOX. This trial will explore whether 6 treatments are as effective as 12 treatments and whether side effects can be reduced with fewer treatments ...

Therapy with platinum compounds is limited by strong side effects, resistance development and insufficient tumor accumulation. Aim of this project in cooperation with Christian Kowol (Group of Prof. Bernhard K. Keppler, University of Vienna) is to enhance tumor-targeting of platinum drugs via binding of an albumin-affine ligand (maleimide). To this end, the first maleimide-containing platinum (IV) drugs have been synthesized, which after reduction release free (unmodified) oxaliplatin. First results indicate that the rapid albumin binding of the new compounds results in enhanced tumor accumulation and increased anticancer activity. ...

Based on the results of 3 adjuvant trials (MOSAIC,20 NSABP-C-07,21 and XELOXA22), oxaliplatin-based combinational chemotherapy is considered the standard of care for patients with stage III colon cancer, offering a 4% overall survival (OS) benefit over 5FU/LV at 6 years. However, the additional benefit of oxaliplatin in older patients appears to be attenuated. Subset analyses of MOSAIC and NSABP C-07 trials showed no significant benefit in OS with the addition of oxaliplatin in patients age 70 or older (MOSAIC mortality hazard ratio [HR] = 1.10; 95% confidence interval [CI], 0.73-1.65; for NSABP-C-07, HR = 1.32; 95% CI, 1.03-1.70).20,21 In contrast, a subgroup analysis of XELOXA, a study that evaluated the use of oral capecitabine in combination with oxaliplatin versus bolus 5FU/LV, the benefits of disease-free survival (DFS) were maintained regardless of age, but no significant OS benefit was shown.22 In an analysis using the ACCENT23 database of 2575 patients age ≥70 years using ...

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McLennan, Alistair J. (1983) Cyclopentadienyl platinum complexes and organic group transfer reactions. PhD thesis, University of Glasgow. Full text available as ...