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Cancer Chemotherapy and Pharmacology

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https://www.readbyqxmd.com/read/28634650/a-randomized-phase-ii-study-of-gemcitabine-plus-z-360-a-cck2-receptor-selective-antagonist-in-patients-with-metastatic-pancreatic-cancer-as-compared-with-gemcitabine-plus-placebo
#1
Makoto Ueno, Chung Pin Li, Masafumi Ikeda, Hiroshi Ishii, Nobumasa Mizuno, Taketo Yamaguchi, Tatsuya Ioka, Do Youn Oh, Wataru Ichikawa, Takuji Okusaka, Yutaka Matsuyama, Daichi Arai, Li Tzong Chen, Young Suk Park, Junji Furuse
BACKGROUND: We investigated the efficacy and safety of 60, 120, or 240 mg of Z-360, which is a highly potent cholecystokinin2-receptor-selective antagonist, combined with gemcitabine in patients with metastatic pancreatic cancer. METHODS: Patients were randomly assigned in a 1:1:1:1 ratio to one of four treatment groups. Patients received 1000 mg/m(2) gemcitabine for each cycle and Z-360 tablets of 60 mg (GZ 60 mg group), 120, 240 mg or placebo tablets (Gem group) orally twice daily...
June 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28634649/assessment-of-cabozantinib-treatment-on-qt-interval-in-a-phase-3-study-in-medullary-thyroid-cancer-evaluation-of-indirect-qt-effects-mediated-through-treatment-induced-changes-in-serum-electrolytes
#2
Dale R Miles, Steven A Lacy, David R Wada, Steve Milwee, Yifah Yaron, Linh T Nguyen
PURPOSE: This study evaluated factors impacting QTc interval in a phase 3 trial of cabozantinib in progressive, metastatic, medullary thyroid cancer (MTC). METHODS: Electrocardiogram (12-lead ECG) measurements were obtained at screening, and at pre-dose, and 2, 4, and 6 h post-dose on Days 1 and 29 in a phase 3 study in patients with MTC treated with cabozantinib (140 mg/day). Central tendency analyses were conducted on baseline-corrected QTc values. Linear and nonlinear mixed-effects models were used to evaluate potential factors affecting the QTc interval, including serum electrolytes, patient demographics, and cabozantinib concentration...
June 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28623449/differential-effects-of-thiopurine-methyltransferase-tpmt-and-multidrug-resistance-associated-protein-gene-4-mrp4-on-mercaptopurine-toxicity
#3
Chengcheng Liu, Laura J Janke, Jun J Yang, William E Evans, John D Schuetz, Mary V Relling
PURPOSE: Mercaptopurine plays a pivotal role in treatment of acute lymphoblastic leukemia (ALL) and autoimmune diseases, and inter-individual variability in mercaptopurine tolerance can influence treatment outcome. Thiopurine methyltransferase (TPMT) and multi-drug resistant Protein 4 (MRP4) have both been associated with mercaptopurine toxicity in clinical studies, but their relative contributions remain unclear. METHODS: We studied the metabolism of and tolerance to mercaptopurine in murine knockout models of Tpmt, Mrp4, and both genes simultaneously...
June 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28612092/involvement-of-cytochrome-p450-in-cisplatin-treatment-implications-for-toxicity
#4
REVIEW
Júlia Coelho França Quintanilha, Vanessa Marcilio de Sousa, Marília Berlofa Visacri, Laís Sampaio Amaral, Roseane Maria Maia Santos, Tomás Zambrano, Luis Antonio Salazar, Patricia Moriel
PURPOSE: The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity. METHODS: This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review. RESULTS: The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28612091/intracellular-vorinostat-accumulation-and-its-relationship-to-histone-deacetylase-activity-in-soft-tissue-sarcoma-patients
#5
Jürgen Burhenne, Lu Liu, Christoph E Heilig, Andreas D Meid, Margarete Leisen, Thomas Schmitt, Bernd Kasper, Walter E Haefeli, Gerd Mikus, Gerlinde Egerer
PURPOSE: In the regulation of chromatin-structure and histone function, histone deacetylases (HDACs) are key enzymes and thus modulators of epigenetic regulation and gene expression. Accesses of the HDAC inhibitor vorinostat to intracellular compartments are essential to exert epigenetic effects. METHODS: In ten sarcoma patients receiving oral Zolinza (400 mg qd) vorinostat concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were quantified using validated LC/MS/MS assays to determine intracellular and extracellular pharmacokinetic data...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28608259/js-k-a-gst-activated-nitric-oxide-donor-prodrug-enhances-chemo-sensitivity-in-renal-carcinoma-cells-and-prevents-cardiac-myocytes-toxicity-induced-by-doxorubicin
#6
Mingning Qiu, Longzhi Ke, Sai Zhang, Xin Zeng, Zesong Fang, Jianjun Liu
PURPOSE: Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. METHODS: The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins...
June 12, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28601972/tak-228-formerly-mln0128-an-investigational-dual-torc1-2-inhibitor-plus-paclitaxel-with-without-trastuzumab-in-patients-with-advanced-solid-malignancies
#7
Howard A Burris, C D Kurkjian, L Hart, S Pant, P B Murphy, S F Jones, R Neuwirth, C G Patel, F Zohren, J R Infante
PURPOSE: This phase I trial evaluated the safety, pharmacokinetic profile, and antitumor activity of investigational oral TORC1/2 inhibitor TAK-228 plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. METHODS: Sixty-seven patients received TAK-228 6-40 mg via three dosing schedules; once daily for 3 days (QDx3d QW) or 5 days per week (QDx5d QW), and once weekly (QW) plus paclitaxel 80 mg/m(2) (dose-escalation phase, n = 47) and with/without trastuzumab 2 mg/kg (expansion phase, n = 20)...
June 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28601971/genetic-variability-in-the-regulation-of-the-expression-cluster-of-mdr-genes-in-patients-with-breast-cancer
#8
Matvey M Tsyganov, Maxim B Freidin, Marina K Ibragimova, Irina V Deryusheva, Polina V Kazantseva, Elena M Slonimskaya, Nadezhda V Cherdyntseva, Nikolai V Litviakov
PURPOSE: We aimed to investigate the association between the polymorphism and expression patterns of multiple drug resistance genes (MDR) in breast cancer (BC). MATERIALS AND METHODS: The MDR gene expression levels were measured in tumor tissues of 106 breast cancer patients using quantitative real-time PCR. Affymetrix CytoScan™ HD Array chips were used to assess genotypes. Pairwise correlation analysis for ABCB1, ABCC1, ABCC2 and ABCG2 gene expression levels was carried out to reveal co-expression clusters...
June 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28600629/knockdown-of-long-non-coding-rna-kcnq1ot1-depressed-chemoresistance-to-paclitaxel-in-lung-adenocarcinoma
#9
Kaiming Ren, Ran Xu, Jingshan Huang, Jungang Zhao, Wenjun Shi
Lung cancer, with the highest morbidity and second highest death rates, is one of the most common cancers in both males and females worldwide. Lung adenocarcinoma (LAD) is the main lung cancer class. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) gene is an lncRNA which had been reported high-expression in colorectal cancer. In this study, the expression of KCNQ1OT1 was confirmed to be highly expressed in LAD tissues and cells contrast to control tissues and cells, and high KCNQ1OT1 expression correlated to malignant behaviors of LAD, including big tumor size, poor differentiation, positive lymphatic metastasis and high TNM stages...
June 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28597043/prognostic-factors-in-patients-with-advanced-biliary-tract-cancer-treated-with-first-line-gemcitabine-plus-cisplatin-retrospective-analysis-of-740-patients
#10
Bum Jun Kim, Jaewon Hyung, Changhoon Yoo, Kyu-Pyo Kim, Seong-Joon Park, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Jin-Hong Park, Hyungwoo Cho, Baek-Yeol Ryoo, Heung-Moon Chang
PURPOSE: Biliary tract cancer (BTC) is a heterogeneous group of diseases comprising intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer. Although gemcitabine plus cisplatin (GEMCIS) was established as the standard first-line chemotherapy based on the ABC-02 trial, more data are needed to define the clinical course of BTC and its prognostic factors with the standard GEMCIS treatment. METHODS: Between April 2010 and June 2016, 740 patients with histologically documented cholangiocarcinoma and gallbladder cancer were treated with first-line GEMCIS in Asan Medical Center, Seoul, Korea...
June 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28597042/cisplatin-induces-expression-of-drug-resistance-related-genes-through-c-jun-n-terminal-kinase-pathway-in-human-lung-cancer-cells
#11
Li Xu, Yingya Fu, Youlun Li, Xiaoli Han
PURPOSE: Change of multidrug resistance-related genes (e.g., lung resistance protein, LRP) and overexpression of anti-apoptotic genes (Bcl-2, Bcl-Xl, XIAP, Survivin) are responsible for cisplatin resistance. In our study, we investigated the mechanism by which cisplatin induces LRP, Bcl-2, Bcl-xL, XIAP, and Survivin expression in human lung adenocarcinoma A549 cells and human H446 small cell lung cancer cells at mRNA and protein levels. METHODS: In our study, cell proliferation was assessed with CCK-8 assays, and cell apoptosis was assessed with flow cytometric analysis and Annexin-V/PI staining...
June 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28597041/efficacy-and-safety-of-postoperative-bio-chemoradiotherapy-using-cetuximab-and-docetaxel-for-high-risk-head-and-neck-cancer-patients-in-japan
#12
Goshi Nishimura, Osamu Shiono, Daisuke Sano, Kenichiro Yabuki, Yasuhiro Arai, Yoshihiro Chiba, Teruhiko Tanabe, Nobuhiko Oridate
PURPOSE: To confirm the efficacy and safety of cetuximab and docetaxel in postoperative radiotherapy for high-risk head and neck cancer patients who cannot to be administered high-dose cisplatin. PATIENTS AND METHODS: The eligibility criteria required stage III-IVB head and neck cancer patients who had undergone total resection, and for whom pathological evaluation revealed positive or close margins in the primary site and/or extracapsular nodal extension and/or two or more nodal metastases...
June 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28597040/phase-ii-study-of-induction-gemcitabine-and-s-1-followed-by-chemoradiotherapy-and-systemic-chemotherapy-using-s-1-for-locally-advanced-pancreatic-cancer
#13
Kentaro Sudo, Ryusuke Hara, Kazuyoshi Nakamura, Emiri Kita, Akiko Tsujimoto, Taketo Yamaguchi
PURPOSE: S-1 has systemic activity for locally advanced pancreatic cancer (LAPC). Here, the efficacy and safety of induction gemcitabine (GEM) and S-1 (GS) followed by chemoradiotherapy (CRT) and systemic chemotherapy using S-1 for LAPC were assessed. METHODS: The treatment consisted of four cycles of induction GS (S-1 60, 80, or 100 mg/day based on body surface area for 14 days every 3 weeks plus GEM 1000 mg/m(2) on days 8 and 15), followed by S-1 (80, 100, or 120 mg/day based on body surface area on days 1-14 and 22-35) and concurrent radiotherapy (50...
June 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28597039/clinical-significance-of-systemic-chemotherapy-after-curative-resection-of-metachronous-pulmonary-metastases-from-colorectal-cancer
#14
Sungwoo Park, Byung Woog Kang, Soo Jung Lee, Shinkyo Yoon, Yee Soo Chae, Jong Gwang Kim, Kyung Hee Lee, Sung Ae Koh, Hong Suk Song, Keon Uk Park, Jin Young Kim, Mi Hwa Heo, Hun Mo Ryoo, Yoon Young Cho, Jungmin Jo, Jung Lim Lee, Sun Ah Lee
PURPOSE: The use of systemic chemotherapy after resection remains controversial in patients with resectable metachronous pulmonary metastases from colorectal cancer (CRC). This retrospective study compared systemic chemotherapy with observation alone after resection of pulmonary metastases from CRC. METHODS: Between 2001 and 2015, 91 patients with metachronous pulmonary metastases underwent curative surgical resection at five centers. Patients with stage IV at diagnosis were excluded...
June 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28597038/the-cardiac-glycoside-oleandrin-induces-apoptosis-in-human-colon-cancer-cells-via-the-mitochondrial-pathway
#15
Li Pan, Yuming Zhang, Wanlu Zhao, Xia Zhou, Chunxia Wang, Fan Deng
PURPOSE: Evidence indicates that the cardiac glycoside oleandrin exhibits cytotoxic activity against several different types of cancer. However, the specific mechanisms underlying oleandrin-induced anti-tumor effects remain largely unknown. The present study examined the anti-cancer effect and underlying mechanism of oleandrin on human colon cancer cells. METHODS: The cytotoxicity and IC50 of five small molecule compounds (oleandrin, neriifolin, strophanthidin, gitoxigenin, and convallatoxin) in human colon cancer cell line SW480 cells and normal human colon cell line NCM460 cells were determined by cell counting and MTT assays, respectively...
June 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28597037/erratum-to-population-pharmacokinetic-modelling-of-doxorubicin-and-doxorubicinol-in-children-with-cancer-is-there-a-relationship-with-cardiac-troponin-profiles
#16
Kuhan Kunarajah, Stefanie Hennig, Ross L G Norris, Michael Lobb, Bruce G Charles, Ross Pinkerton, Andrew S Moore
No abstract text is available yet for this article.
June 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28585036/differential-expression-pattern-of-protein-markers-for-predicting-chemosensitivity-of-dexamethasone-based-chemotherapy-of-b-cell-acute-lymphoblastic-leukemia
#17
Nasrin Dehghan-Nayeri, Peyman Eshghi, Kourosh Goudarzi Pour, Mostafa Rezaei-Tavirani, Mir Davood Omrani, Ahmad Gharehbaghian
Dexamethasone is considered as a direct chemotherapeutic agent in the treatment of pediatric acute lymphoblastic leukemia (ALL). Beside the advantages of the drug, some problems arising from the dose-related side effects are challenging issues during the treatment. Accordingly, the classification of patients to dexamethasone sensitive and resistance groups can help to select optimizing the therapeutic dose with the lowest adverse effects particularly in sensitive cases. For this purpose, we investigated inhibited proliferation and induced cytotoxicity in NALM-6 cells, as sensitive cells, after dexamethasone treatment...
June 5, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28585035/ugt1a1-6-polymorphisms-are-correlated-with-irinotecan-induced-neutropenia-a-systematic-review-and-meta-analysis
#18
Xue Zhang, Jia-Fu Yin, Jiao Zhang, Shu-Jia Kong, Hong-Yin Zhang, Xue-Mei Chen
Irinotecan (IRI) chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. Neutropenia is a life-threatening side effect of irinotecan, and UDP glucuronosyltransferases (UGTs) gene polymorphisms could predict the side effects in cancer patients and then reduce IRI-induced toxicity by preventative treatment or a decrease in dose. Both UGT1A1*6 and *28 were reliably demonstrated to be risk factors for IRI-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients...
June 5, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28577239/population-pharmacokinetic-analyses-of-the-effect-of-carboplatin-pretreatment-on-olaparib-in-recurrent-or-refractory-women-s-cancers
#19
Cody J Peer, Jung-Min Lee, Jeffrey Roth, Louis Rodgers, Jeffers Nguyen, Christina M Annunziata, Lori Minasian, Elise C Kohn, William D Figg
PURPOSE: Combining olaparib with carboplatin was recently shown to be active in both BRCA and non-BRCA mutant cancers in a recent phase I/Ib combination trial. The optimal drug sequence recommended was carboplatin 1-day before olaparib. However, carboplatin pre-treatment induced a ~50% faster olaparib clearance. METHODS: To further explore this drug interaction, a population pharmacokinetic (PK) model was designed that included a lag time parameter, a second absorption compartment from tablet formulation, a single distribution/elimination compartment, and covariance among the clearance and volume parameters...
June 2, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28567478/%C3%AE-iii-tubulin-enhances-efficacy-of-cabazitaxel-as-compared-with-docetaxel
#20
Gregoriy Smiyun, Olga Azarenko, Herbert Miller, Alexander Rifkind, Nichole E LaPointe, Leslie Wilson, Mary Ann Jordan
Cabazitaxel is a novel taxane approved for treatment of metastatic hormone-refractory prostate cancer in patients pretreated with docetaxel. Cabazitaxel, docetaxel, and paclitaxel bind specifically to tubulin in microtubules, disrupting functions essential to tumor growth. High levels of βIII-tubulin isotype expression are associated with tumor aggressivity and drug resistance. To understand cabazitaxel's increased efficacy, we examined binding of radio-labeled cabazitaxel and docetaxel to microtubules and the drugs' suppression of microtubule dynamic instability in vitro in microtubules assembled from purified bovine brain tubulin containing or devoid of βIII-tubulin...
May 31, 2017: Cancer Chemotherapy and Pharmacology
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