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Gemcitabine toxicity

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https://www.readbyqxmd.com/read/28106283/therapeutic-potential-of-curcumin-in-treatment-of-pancreatic-cancer-current-status-and-future-perspectives
#1
Mina Hosseini, Seyed Mahdi Hassanian, Elham Mohamamdazade, Soodabeh ShahidSales, Mina Maftouh, Hasan Fayazbakhsh, Majid Khazaei, Amir Avan
Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28099809/a-gemcitabine-based-peptide-conjugate-with-improved-metabolic-properties-and-dual-mode-of-efficacy
#2
Theodoros Karampelas, Eleni Skavatsou, Orestis Argyros, Demosthenes Fokas, Constantin Tamvakopoulos
Gemcitabine is a clinically established anticancer agent potent in various solid tumors but limited by its rapid metabolic inactivation and off-target toxicity. We have previously generated a metabolically superior to gemcitabine molecule (GSG) by conjugating gemcitabine to a gonadotropin releasing hormone receptor (GnRH-R) ligand peptide, and showed that GSG was efficacious in a castration resistant prostate cancer (CRPC) animal model. The current manuscript provides an in-depth metabolic and mechanistic study of GSG, coupled with toxicity assays that strengthen the potential role of GSG in the clinic...
January 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28093003/outcome-for-patients-with-relapsed-refractory-aggressive-lymphoma-treated-with-gemcitabine-and-oxaliplatin-with-or-without-rituximab-a-retrospective-multicentre-study
#3
Vijay Dhanapal, Menaka Gunasekara, Chia Lianwea, Robert Marcus, Corinne De Lord, Stella Bowcock, Stephen Devereux, Piers Patten, Deborah Yallop, David Wrench, Paul Fields, Shireen Kassam
The treatment of relapsed aggressive lymphoma remains a challenge. Platinum-containing chemotherapy is standard of care. Gemcitabine/oxaliplatin (Gem-Ox) with or without rituximab (R) is an outpatient regimen with a favorable toxicity profile. This retrospective 'real world' study reports outcomes for 44 unselected patients with relapsed/refractory aggressive lymphoma treated with Gem-Ox ± R. 41% had primary refractory disease. The overall response rate (ORR) was 43% with a complete response (CR) of 30%...
January 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28089829/resveratrol-and-capsaicin-used-together-as-food-complements-reduce-tumor-growth-and-rescue-full-efficiency-of-low-dose-gemcitabine-in-a-pancreatic-cancer-model
#4
Véronique Vendrely, Evelyne Peuchant, Etienne Buscail, Isabelle Moranvillier, Benoit Rousseau, Aurélie Bedel, Aurélia Brillac, Hubert de Verneuil, François Moreau-Gaudry, Sandrine Dabernat
Pancreatic adenocarcinoma, highly resistant to all current anti-cancer treatments, necessitates new approaches promoting cell death. We hypothesized that combined actions of several Bioactive Food Components (BFCs) might provide specific lethal effect towards tumor cells, sparing healthy cells. Human tumor pancreatic cell lines were tested in vitro for sensitivity to resveratrol, capsaicin, piceatannol, and sulforaphane cytotoxic effects. Combination of two or three components showed striking synergetic effect with gemcitabine in vitro...
January 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28089484/dosimetric-parameters-correlate-with-duodenal-histopathologic-damage-after-stereotactic-body-radiotherapy-for-pancreatic-cancer-secondary-analysis-of-a-prospective-clinical-trial
#5
Vivek Verma, Audrey J Lazenby, Dandan Zheng, Abhijeet R Bhirud, Quan P Ly, Chandrakanth Are, Aaron R Sasson, Chi Lin
PURPOSE: Prospectively assess relationships between dosimetric parameters and histopathologic/clinical duodenal toxicities in patients on a phase I trial for pancreatic cancer. METHODS: Forty-six borderline resectable/unresectable patients were enrolled on a prospective trial testing neoadjuvant gemcitabine/5-fluorouracil followed by SBRT (5 daily fractions of 5-8Gy) and concurrent nelfinavir. Post-SBRT surgery was performed in 13 resectable patients, which constituted the patient population herein...
January 12, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28086830/sigma-2-receptor-agonist-derivatives-of-1-cyclohexyl-4-3-5-methoxy-1-2-3-4-tetrahydronaphthalen-1-yl-propyl-piperazine-pb28-induce-cell-death-via-mitochondrial-superoxide-production-and-caspase-activation-in-pancreatic-cancer
#6
Maria Laura Pati, John R Hornick, Mauro Niso, Francesco Berardi, Dirk Spitzer, Carmen Abate, William Hawkins
BACKGROUND: Despite considerable efforts by scientific research, pancreatic cancer is the fourth leading cause of cancer related mortalities. Sigma-2 receptors, which are overexpressed in several tumors, represent promising targets for triggering selective pancreatic cancer cells death. METHODS: We selected five differently structured high-affinity sigma-2 ligands (PB28, PB183, PB221, F281 and PB282) to study how they affect the viability of diverse pancreatic cancer cells (human cell lines BxPC3, AsPC1, Mia PaCa-2, and Panc1 and mouse Panc-02, KCKO and KP-02) and how this is reflected in vivo in a tumor model...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28079819/efficacy-and-toxicity-of-different-concurrent-chemoradiotherapy-regimens-in-the-treatment-of-advanced-cervical-cancer-a-network-meta-analysis
#7
Zhan-Zhao Fu, Kun Li, Yong Peng, Yue Zheng, Li-Yan Cao, Yun-Jie Zhang, Yong-Mei Sun
OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of different concurrent chemoradiotherapy (CCRT) regimens in the treatment of advanced cervical cancer (CC) by adopting a network meta-analysis. METHODS: We searched PubMed and Cochrane Library from the inception of these databases to September 2016, and all cohort studies (CSs) related to different CCRT regimens in the treatment of CC were included. A network analysis was adopted to compare the combination of direct and indirect evidence, to analyze the odds ratio (OR), and to draw a surface under the cumulative ranking curve of the efficacy and toxicity of different CCRT regimens for CC...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28079805/toxicities-of-different-first-line-chemotherapy-regimens-in-the-treatment-of-advanced-ovarian-cancer-a-network-meta-analysis
#8
Chang-Ping Qu, Gui-Xia Sun, Shao-Qin Yang, Jun Tian, Jin-Ge Si, Yi-Feng Wang
BACKGROUND: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. METHODS: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemotherapy regimens were included...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28078124/advanced-biliary-tract-cancer-clinical-outcomes-with-abc-02-regimen-and-analysis-of-prognostic-factors-in-a-tertiary-care-center-in-the-united-states
#9
Rishi Agarwal, Arun Sendilnathan, Nabeela Iffat Siddiqi, Shuchi Gulati, Abhimanyu Ghose, Changchun Xie, Olugbenga Olanrele Olowokure
BACKGROUND: Gemcitabine plus cisplatin (GC) is currently the standard regimen for advanced biliary tract cancers (BTC) based on the outcomes in ABC-02 trial. Multiple factors can affect outcomes in these patients. This retrospective review evaluates the University of Cincinnati experience with GC in advanced intrahepatic (IHC)/extrahepatic cholangiocarcinoma (EHC) and gall bladder carcinoma (GBC). METHODS: In this study approved by University of Cincinnati IRB, retrospective analysis of advanced BTC patients seen between 01/2008 and 01/2015 was done...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28072706/a-randomized-multicenter-phase-iii-study-of-gemcitabine-combined-with-capecitabine-versus-gemcitabine-alone-as-first-line-chemotherapy-for-advanced-pancreatic-cancer-in-south-korea
#10
Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seungmin Bang, Seung Woo Park, Ho Gak Kim, Myung Hwan Noh, Sang Hyub Lee, Yong-Tae Kim, Hyo Jung Kim, Chang Duck Kim, Dong Ki Lee, Kwang Bum Cho, Chang Min Cho, Jong Ho Moon, Dong Uk Kim, Dae Hwan Kang, Young Koog Cheon, Ho Soon Choi, Tae Hyeon Kim, Jae Kwang Kim, Jieun Moon, Hye Jung Shin, Si Young Song
BACKGROUND: This phase III trial compared the efficacy and safety of gemcitabine plus capecitabine (GemCap) versus single-agent gemcitabine (Gem) in advanced pancreatic cancer as first-line chemotherapy. METHODS: A total of 214 advanced pancreatic cancer patients were enrolled from 16 hospitals in South Korea between 2007 and 2011. Patients were randomly assigned to receive GemCap (oral capecitabine 1660 mg/m plus Gem 1000 mg/m by 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break every 4 weeks) or Gem (by 30-minute intravenous infusion weekly for 3 weeks every 4 weeks)...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28063799/phase-ii-trial-of-dose-dense-pemetrexed-gemcitabine-and-bevacizumab-in-patients-with-advanced-non-small-cell-lung-cancer
#11
Bryan J Schneider, Gregory P Kalemkerian, Shirish M Gadgeel, Manuel Valdivieso, Deborah M Hackstock, Wei Chen, Lance K Heilbrun, John C Ruckdeschel, Antoinette J Wozniak
INTRODUCTION: Platinum-based chemotherapy is standard for untreated, advanced non-small-cell lung cancer (NSCLC). We investigated the activity and tolerability of the novel combination of dose-dense pemetrexed, gemcitabine, and bevacizumab in patients with advanced NSCLC. METHODS: This multicenter phase II trial evaluated the safety and efficacy of the combination of pemetrexed (400 mg/m(2)), gemcitabine (1200 mg/m(2)), and bevacizumab (10 mg/kg), given every 14 days in patients with untreated, advanced NSCLC...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28062705/novel-p21-activated-kinase-4-pak4-allosteric-modulators-overcome-drug-resistance-and-stemness-in-pancreatic-ductal-adenocarcinoma
#12
Amro Aboukameel, Irfana Muqbil, William Senapedis, Erkan Baloglu, Yosef Landesman, Sharon Shacham, Michael Kauffman, Philip A Philip, Ramzi M Mohammad, Asfar S Azmi
The p21-activated kinase 4 (PAK4) is a key downstream effector of the Rho family GTPases and is found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC) cells but not in normal human pancreatic ductal epithelia (HPDE). Gene copy number amplification studies in PDAC patient cohorts confirmed PAK4 amplification making it an attractive therapeutic target in PDAC. We investigated the antitumor activity of novel PAK4 allosteric modulators (PAM) on a panel of PDAC cell lines and chemotherapy-resistant flow-sorted PDAC cancer stem cells (CSC)...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28042876/the-chk1-inhibitor-mk-8776-increases-the-radiosensitivity-of-human-triple-negative-breast-cancer-by-inhibiting-autophagy
#13
Zhi-Rui Zhou, Zhao-Zhi Yang, Shao-Jia Wang, Li Zhang, Ju-Rui Luo, Yan Feng, Xiao-Li Yu, Xing-Xing Chen, Xiao-Mao Guo
MK-8776 is a recently described inhibitor that is highly selective for checkpoint kinase 1 (Chk1), which can weaken the DNA repair capacity in cancer cells to achieve chemo-sensitization. A number of studies show that MK-8776 enhances the cytotoxicity of hydroxyurea and gemcitabine without increasing normal tissue toxicities. Thus far, there is no evidence that MK-8776 can be used as a radiotherapy sensitization agent. In this study, we investigated the effects of MK-8776 on the radiosensitivity of 3 human triple-negative breast cancer (TNBC) cell lines MDA-MB-231, BT-549 and CAL-51...
January 2, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28036270/induction-chemotherapy-for-the-treatment-of-non-endemic-locally-advanced-nasopharyngeal-carcinoma
#14
Lina Zhao, Man Xu, Wen Jiang, Haitao Pan, Jian Zang, Shanquan Luo, Jianhua Wang, Yongchun Zhou, Mei Shi
BACKGROUND: The role of induction chemotherapy is less clear in non-endemic locally advanced nanopharyngeal carcinomas (NPC). RESULTS: With a total of 233 eligible patients and a median follow-up of 36 months, 3-year overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) were 84.5%, 94.9%, 78.6% and 69.2%, respectively. The overall failure rate was 21.0% and distant metastasis occurred in 17...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030863/real-world-clinical-practice-of-intensified-chemotherapies-for-metastatic-pancreatic-cancer-results-from-a-pan-european-questionnaire-study
#15
Nha Le, Alessio Vinci, Marvin Schober, Sebastian Krug, Muhammad A Javed, Thomas Kohlmann, Malin Sund, Albrecht Neesse, Georg Beyer
INTRODUCTION: Recently, FOLFIRINOX and gemcitabine + nab-paclitaxel have been introduced as a novel intensified chemotherapy regimen for patients with metastasized pancreatic cancer. This study aims to analyze the real-world clinical practice with FOLFIRINOX and gemcitabine + nab-paclitaxel across Europe. METHODS: Invitations to participate in an anonymous web-based questionnaire were sent via e-mail to 5,420 doctors in 19 European countries through the network of national gastroenterological, oncological, surgical and pancreatic societies as well as the European Pancreatic Club...
2016: Digestion
https://www.readbyqxmd.com/read/28029039/stimuli-sensitive-biodegradable-and-amphiphilic-block-copolymer-gemcitabine-conjugates-self-assemble-into-a-nanoscale-vehicle-for-cancer-therapy
#16
Zhenyu Duan, Yanhong Zhang, Hongyan Zhu, Ling Sun, Hao Cai, Bijin Li, Qiyong Gong, Zhongwei Gu, Kui Luo
The availability and the stability of current anticancer agents, particularly water-insoluble drugs, are still far from satisfactory. A widely used anticancer drug, gemcitabine (GEM), is so poorly stable in circulation that some polymeric drug-delivery systems have been under development for sometimes to improve its therapeutic indexes. Herein, we designed, prepared and characterized a biodegradable amphiphilic block N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-GEM conjugate-based nanoscale and stimuli-responsive drug delivery vehicle...
December 28, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28028360/dilemma-of-first-line-regimens-in-metastatic-pancreatic-adenocarcinoma
#17
REVIEW
Marwan Ghosn, Tony Ibrahim, Tarek Assi, Elie El Rassy, Hampig Raphael Kourie, Joseph Kattan
Pancreatic cancer is one of the deadliest cancers, ranking fourth among cancer-related deaths. Despite all the major molecular advances and treatment breakthroughs, mainly targeted therapies, the cornerstone treatment of metastatic pancreatic cancer (mPC) remains cytotoxic chemotherapy. In 2016, more than 40 years after the introduction of gemcitabine in the management of mPC, the best choice for first-line treatment has not yet been fully elucidated. Two main strategies have been adopted to enhance treatment efficacy...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28007550/gemcitabine-selective-cytotoxicity-induction-of-inflammation-and-effects-on-urothelial-function
#18
Stefanie E Farr, Russ Chess-Williams, Catherine M McDermott
Intravesical gemcitabine has recently been introduced for the treatment of superficial bladder cancer and has a favourable efficacy and toxicity profile in comparison to mitomycin c (MMC), the most commonly used chemotherapeutic agent. The aim of this study was to assess the cytotoxic potency of gemcitabine in comparison to MMC in urothelial cell lines derived from non-malignant (UROtsa) and malignant (RT4 and T24) tissues to assess selectivity. Cells were treated with gemcitabine or mitomycin C at concentrations up to the clinical doses for 1 or 2h respectively (clinical duration)...
December 19, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28002342/effects-of-sequential-paclitaxel-carboplatin-followed-by-gemcitabine-based-chemotherapy-compared-with-paclitaxel-carboplatin-therapy-administered-to-patients-with-advanced-epithelial-ovarian-cancer-a-retrospective-strobe-compliant-study
#19
Fei Wang, Xuelian Du, Xiaoxia Li, Naifu Liu, Hao Yu, Xiugui Sheng
We aimed to compare the efficacy of paclitaxel and carboplatin followed by gemcitabine-based combination chemotherapy with paclitaxel-carboplatin for treating advanced epithelial ovarian cancer in this retrospective, STROBE-compliant study. Patients' tolerance to treatment was also assessed.We retrospectively analyzed the records of 178 women who underwent initial optimal debulking surgery between January 2003 and December 2011 to treat FIGO stage IIIc epithelial ovarian cancer. Patients in arm 1 (n = 88) received 4 cycles of paclitaxel and carboplatin followed by 2 to 4 cycles of gemcitabine-based combination chemotherapy...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27998964/phase-2-placebo-controlled-double-blind-trial-of-dasatinib-added-to-gemcitabine-for-patients-with-locally-advanced-pancreatic-cancer
#20
T R J Evans, E Van Cutsem, M J Moore, I S Bazin, A Rosemurgy, G Bodoky, G Deplanque, M Harrison, B Melichar, D Pezet, A Elekes, E Rock, C Lin, L Strauss, P J O'Dwyer
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in 2 of 8 patients with gemcitabine-refractory PDAC. PATIENTS AND METHODS: This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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