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Impact of obesity on accumulation of the toxic irinotecan metabolite, SN-38, in mice.

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OBJECTIVE Our aim is to investigate the impact of high fat diet-induced obesity on plasma concentrations of the toxic irinotecan metabolite, SN-38, in mice. METHODS Diet-induced obese (DIO, 60% kcal fed) and lean mice (10% kcal fed) were treated orally with a single dose of 10mg/kg irinotecan to

Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study.

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BACKGROUND Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy. METHODS Survival outcomes and toxicity data

Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese.

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OBJECTIVE Despite the rising prevalence of obesity, there is paucity of information describing how doses of anticancer drugs should be adjusted in clinical practice. Here, we assessed the pharmacokinetics of eight anticancer drugs in adults and evaluated the potential utility of alternative weight

Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases.

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BACKGROUND The objective was to evaluate the effect of preoperative administration of newer chemotherapeutic agents (irinotecan and oxaliplatin) on development of steatohepatitis, which could limit surgical options. METHODS Thirty-seven patients were referred for resection of hepatic colorectal

Glucagon-like peptide-1 receptor activation inhibits growth and augments apoptosis in murine CT26 colon cancer cells.

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Obesity, accompanying or independent of type 2 diabetes mellitus (T2DM), is associated with higher rates of malignancy. Hence, there is considerable interest in understanding whether therapies used to treat obese patients with T2DM impact cancer cell growth. Glucagon-like peptide-1 (GLP-1) is

Efficacy and toxicity of a virus-directed enzyme prodrug therapy purging method: preclinical assessment and application to bone marrow samples from neuroblastoma patients.

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Autologous stem cell transplantation is used to rescue cancer patients from myelosuppression caused by high-dose chemotherapy. However, autologous grafts often contain tumor cells that can contribute directly to relapse. Current purging methods are useful when fewer than 1% tumor cells contaminate

Blood transfusions and steatohepatitis are independent risk factors for complications following liver resection for colorectal cancer liver metastases.

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The aim of the present study was to evaluate the risk factors for postoperative complications following liver resection for colorectal cancer liver metastases. Patients who underwent hepatic resection for colorectal cancer liver metastases were stratified according to chemotherapy administration and

Prospective evaluation of accuracy of liver biopsy findings in the identification of chemotherapy-associated liver injuries.

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OBJECTIVE To evaluate the accuracy of liver biopsy findings in preoperative assessment of chemotherapy-associated liver injuries (CALIs). DESIGN Prospective study. SETTING Tertiary care referral hospital. PATIENTS From July 1, 2007, to January 31, 2011, all patients with colorectal metastases

Association Between Changes in Body Composition and Neoadjuvant Treatment for Pancreatic Cancer.

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UNASSIGNED Sarcopenia and sarcopenic obesity have been associated with poor outcomes in unresectable pancreatic cancer (PC). Neoadjuvant treatment (NT) is used increasingly to improve resectability; however, its effects on fat and muscle body composition have not been characterized. UNASSIGNED To

Optimization of cancer chemotherapy on the basis of pharmacokinetics and pharmacodynamics: from patients enrolled in clinical trials to those in the 'real world'.

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Cytotoxic anticancer drugs are the most challenging therapeutic agents among all medicines with relatively narrow efficacy profiles. Therefore, medical oncologists have to practically manage the risk of severe toxic effects to optimize treatment outcomes. Dose and treatment-schedule recommendations

Carboxylesterase-2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs.

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Orlistat has been the most used anti-obesity drug and the mechanism of its action is to reduce lipid absorption by inhibiting gastrointestinal lipases. These enzymes, like carboxylesterases (CESs), structurally belong to the α/β hydrolase fold superfamily. Lipases and CESs are functionally related

Barking up the wrong genome--we are not alone.

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OBJECTIVE Pharmacogenetic studies, to help us understand variability in human drug response, have hitherto focussed largely on our own germline mutations, and in the context of anticancer and antimicrobial drugs, also on mutations of the tumour cell or invader microorganism. Here, we wish to draw

Marginal effects of glucose, insulin and insulin-like growth factor on chemotherapy response in endothelial and colorectal cancer cells.

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Resistance to chemotherapy is a major clinical issue for patients with colorectal cancer. Obesity has been associated with a poorer outcome and is a possible mechanism of resistance. The aim of the present study was to investigate the effect of obesity-related factors on the cell response to

Histological patterns in drug-induced liver disease.

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The diagnosis of drug-induced liver injury (DILI) is a challenging problem, often confounded by incomplete clinical information and the difficulty of eliciting exposure to herbal products, over-the-counter agents and toxins. The task is further rendered difficult on biopsy, as drugs can mimic all

Diagnosis and management of pancreatic cancer.

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Pancreatic cancer remains the fourth leading cause of cancer-related deaths in the United States. Risk factors include family history, smoking, chronic pancreatitis, obesity, diabetes mellitus, heavy alcohol use, and possible dietary factors. Because more than two-thirds of adenocarcinomas occur in

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