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Cancer Chemotherapy and Pharmacology

Jia-Feng Huang, Chun-Jie Wen, Guo-Zhi Zhao, Yi Dai, Ying Li, Lan-Xiang Wu, Hong-Hao Zhou
PURPOSE: Doxorubicin is one of the most active agents in the first-line therapy for metastatic breast cancer, but its utility is partially limited by the frequent emergence of doxorubicin resistance. In this study, we aimed to investigate the role of ATP-binding cassette sub-family B, member 4 (ABCB4) in acquired doxorubicin resistance in breast cancer cells, as well as its potential mechanism. METHODS: In doxorubicin-sensitive and -resistant breast cancer cell lines MCF-7 and MDA-MB-231, the expression levels of ABCB4 were detected using real-time quantitative PCR and Western blot analysis, the DNA methylation and histone acetylation status of ABCB4 gene were investigated by bisulfite-sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) assays, and the doxorubicin sensitivity and intracellular doxorubicin accumulation were observed using cell cytotoxicity assay and flow cytometry...
May 18, 2018: Cancer Chemotherapy and Pharmacology
Hoi-Wing Leung, Chun-Hay Ko, Grace Gar-Lee Yue, Ingrid Herr, Clara Bik-San Lau
BACKGROUND AND PURPOSE: Cancer stem-like cells (CSC) are regarded as the source of tumour origins, metastasis and drug resistance, and limits current treatment regimens. Previously, we reported the first study of the anti-angiogenic and anti-tumour activities of 4-vinylphenol. To further examine the therapeutic role of 4-vinylphenol, the inhibitory effects of 4-vinylphenol on cancer stemness, drug resistance and metastasis in breast cancer were investigated in the present study. STUDY DESIGN AND METHODS: We enriched parental MDA-MB-231 cells with CSCs in serum-free medium to give spheroids...
May 18, 2018: Cancer Chemotherapy and Pharmacology
Benjamin Anon, Bérenger Largeau, Alban Girault, Aurélie Chantome, Morgane Caulet, Clémence Perray, Driffa Moussata, Christophe Vandier, Chantal Barin-Le Guellec, Thierry Lecomte
INTRODUCTION: Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN. MATERIALS AND METHODS: We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density...
May 17, 2018: Cancer Chemotherapy and Pharmacology
Orsolya Rusz, Orsolya Papp, Laura Vízkeleti, Béla Ákos Molnár, Kristóf Csaba Bende, Gábor Lotz, Balázs Ács, Zsuzsanna Kahán, Tamás Székely, Ágnes Báthori, Csilla Szundi, Janina Kulka, Zoltán Szállási, Anna-Mária Tőkés
PURPOSE: To determine the associations between lysosomal-associated transmembrane protein 4b (LAPTM4B) gene copy number and response to different chemotherapy regimens in hormone receptor negative (HR-) primary breast carcinomas. PATIENTS AND METHODS: Two cohorts were analyzed: (1) 69 core biopsies from HR-breast carcinomas treated with neoadjuvant chemotherapy (anthracycline based in 72.5% of patients and non-anthracycline based in 27.5% of patients). (2) Tissue microarray (TMA) of 74 HR-breast carcinomas treated with adjuvant therapy (77...
May 16, 2018: Cancer Chemotherapy and Pharmacology
Peter N Morcos, Eveline Nueesch, Felix Jaminion, Elena Guerini, Joy C Hsu, Walter Bordogna, Bogdana Balas, Francois Mercier
PURPOSE: Alectinib is a selective and potent anaplastic lymphoma kinase (ALK) inhibitor that is active in the central nervous system (CNS). Alectinib demonstrated robust efficacy in a pooled analysis of two single-arm, open-label phase II studies (NP28673, NCT01801111; NP28761, NCT01871805) in crizotinib-resistant ALK-positive non-small-cell lung cancer (NSCLC): median overall survival (OS) 29.1 months (95% confidence interval [CI]: 21.3-39.0) for alectinib 600 mg twice daily (BID). We investigated exposure-response relationships from final pooled phase II OS and safety data to assess alectinib dose selection...
May 10, 2018: Cancer Chemotherapy and Pharmacology
Hisao Imai, Hiroyuki Minemura, Tomohide Sugiyama, Yutaka Yamada, Kyoichi Kaira, Kenya Kanazawa, Takashi Kasai, Takayuki Kaburagi, Koichi Minato
PURPOSE: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations...
May 8, 2018: Cancer Chemotherapy and Pharmacology
Taro Koba, Seigo Minami, Yu Nishijima-Futami, Kentaro Masuhiro, Hiromi Kimura, Shinji Futami, Moto Yaga, Masahide Mori, Hiroyuki Kagawa, Takeshi Uenami, Satoshi Kohmo, Tomoyuki Otsuka, Suguru Yamamoto, Kiyoshi Komuta, Takashi Kijima
PURPOSE: We conducted a phase II trial to evaluate the efficacy and safety of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS: Patients with advanced or recurrent untreated non-squamous NSCLC received split-dose cisplatin (40 mg/m2 , days 1 and 8) plus pemetrexed (500 mg/m2 , day 1) tri-weekly. After four cycles of induction, patients without disease progression received pemetrexed maintenance until disease progression or unacceptable toxicity...
May 4, 2018: Cancer Chemotherapy and Pharmacology
Nikolai Litviakov, Matvey Tsyganov, Irina Larionova, Marina Ibragimova, Irina Deryusheva, Polina Kazantseva, Elena Slonimskaya, Irina Frolova, Eugeniy Choinzonov, Nadezhda Cherdyntseva, Julia Kzhyshkowska
PURPOSE: High activity of enzyme TOP2a in tumor cells is known to be associated with sensitivity to anthracycline chemotherapy, but 20% of such patients do not show clinical response. Tumor microenvironment, including tumor-associated macrophages (TAM), is an essential factor defining the efficiency of chemotherapy. In the present study, we analyzed the expression of M2 macrophage markers, YKL-39 and CCL18, in tumors of breast cancer patients received anthracycline-based NAC. METHODS: Patients were divided into two groups according to the level of doxorubicin sensitivity marker TOP2a: DOX-Sense and DOX-Res groups...
May 4, 2018: Cancer Chemotherapy and Pharmacology
Qianqian Yu, Tao Zhang, Conghua Xie, Hong Qiu, Bo Liu, Liu Huang, Ping Peng, Jueping Feng, Jigui Chen, Aihua Zang, Xianglin Yuan
PURPOSE: To investigate the association between UDP-glucuronosyltransferase (UGT)1A polymorphisms and irinotecan-treatment efficacy in a Chinese population with metastatic colorectal cancer (mCRC). METHODS: The present study was based on a prospective multicenter trial of Chinese mCRC patients treated with irinotecan-based chemotherapy (NCT01282658, registered at ). Fifteen single-nucleotide polymorphisms (SNPs) in four UGT1A genes were selected for genotyping in 164 patients...
May 4, 2018: Cancer Chemotherapy and Pharmacology
Egbert F Smit, Edward B Garon, Martin Reck, Federico Cappuzzo, Paolo Bidoli, Roger B Cohen, Ling Gao, Lisa M O'Brien, Pablo Lee, Annamaria Zimmermann, David R Ferry, Allen S Melemed, Maurice Pérol
PURPOSE: Ramucirumab plus docetaxel improved survival in REVEL, a randomized phase 3 trial for patients with Stage IV non-small cell lung cancer after standard platinum-based chemotherapy. This exploratory analysis evaluated the exposure-response relationship of ramucirumab from REVEL. METHODS: Patients received ramucirumab (10 mg/kg) or placebo plus docetaxel (75 mg/m2 ) every 3 weeks. Pharmacokinetic samples were collected. A population pharmacokinetic analysis predicted ramucirumab minimum concentration after first-dose administration (Cmin,1 ) and average concentration at steady state (Cave,ss )...
May 2, 2018: Cancer Chemotherapy and Pharmacology
Takeshi Wada, Kentaro Ando, Atsuhiko T Naito, Yuji Nakamura, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Xin Cao, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Yuji Nakazato, Atsushi Sugiyama
PURPOSE: Cancer chemotherapies have improved the prognosis of cancer patients in recent years; however, their side effects on the cardiovascular systems have emerged as a major concern in the field of both cardiology and oncology. In particular, multi-targeted tyrosine kinase inhibitors are known to induce various types of cardiovascular adverse events including hypertension, QT-interval prolongation and heart failure, but their underlying mechanisms remain elusive. To explore how to better predict such drug-induced cardiovascular adverse events, we assessed the electropharmacological effects of sunitinib using the halothane-anesthetized dogs (n = 5), while plasma concentrations of cardiac enzymes including aspartate aminotransferase, lactate dehydrogenase, creatinine kinase and cardiac troponin I  were measured...
May 2, 2018: Cancer Chemotherapy and Pharmacology
Qi Zhang, Xiao-Ting Li, Yue Chen, Jia-Qi Chen, Jian-Yun Zhu, Yu Meng, Xiao-Qian Wang, Yuan Li, Shan-Shan Geng, Chun-Feng Xie, Jie-Shu Wu, Cai-Yun Zhong, Hong-Yu Han
Unfortunately, the online published article has error in Figure 4. The correct Figure 4 is given here.
April 30, 2018: Cancer Chemotherapy and Pharmacology
Jessica Lee, John P Curtin, Franco M Muggia, Bhavana Pothuri, Leslie R Boyd, Stephanie V Blank
PURPOSE: To evaluate the outcomes of intraperitoneal chemotherapy (IP) compared with those of intravenous chemotherapy (IV) in patients with advanced ovarian cancer after neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or primary debulking surgery (PDS). METHODS: Patients with advanced epithelial ovarian carcinoma treated with PDS or NACT and IDS from 2006 to 2015 were identified. Comparative statistics were used to evaluate covariates, and survival rates were calculated using the Kaplan-Meier method and compared with log-rank tests...
April 27, 2018: Cancer Chemotherapy and Pharmacology
Laurent Claret, Christina Pentafragka, Sanja Karovic, Binsheng Zhao, Lawrence H Schwartz, Michael L Maitland, Rene Bruno
PURPOSE: To compare lesion-level and volumetric measures of tumor burden with sum of the longest dimensions (SLD) of target lesions on overall survival (OS) predictions using time-to-growth (TTG) as predictor. METHODS: Tumor burden and OS data from a phase 3 randomized study of second-line FOLFIRI ± aflibercept in metastatic colorectal cancer were available for 918 patients out of 1216 treated (75%). A TGI model that estimates TTG was fit to the longitudinal tumor size data (nonlinear mixed effect modeling) to estimate TTG with: SLD, sum of the measured lesion volumes (SV), individual lesion diameters (ILD), or individual lesion volumes (ILV)...
April 26, 2018: Cancer Chemotherapy and Pharmacology
A A van Zweeden, C J van Groeningen, R J Honeywell, E Giovannetti, R Ruijter, C H Smorenburg, G Giaccone, H M W Verheul, G J Peters, Hans J van der Vliet
PURPOSE: Preclinical research and prior clinical observations demonstrated reduced toxicity and suggested enhanced efficacy of cisplatin due to folic acid and vitamin B12 suppletion. In this randomized phase 2 trial, we evaluated the addition of folic acid and vitamin B12 to first-line palliative cisplatin and gemcitabine in patients with advanced esophagogastric cancer (AEGC). METHODS: Patients with AEGC were randomized to gemcitabine 1250 mg/m2 (i.v. days 1, 8) and cisplatin 80 mg/m2 (i...
April 25, 2018: Cancer Chemotherapy and Pharmacology
Hiroyoshi Koide, Masayuki Tsujimoto, Yurie Katsube, Megumi Ochiai, Ayako Hojo, Taku Furukubo, Satoshi Izumi, Tomoyuki Yamakawa, Daisuke Shima, Tetsuya Minegaki, Kohshi Nishiguchi
PURPOSE: Pharmacokinetics and pharmacodynamics of irinotecan have been reported to be altered in cancer patients with end-stage kidney disease (ESKD). Carboxylesterase (CES) has an important role in metabolism of irinotecan to its active metabolite, SN-38, in human liver. The purpose of the present study was to investigate whether CES activity was altered in ESKD patients. METHODS: The present study investigated the effects of uremic serum, uremic toxins, and fatty acids on the hydrolysis of irinotecan and a typical CES substrate, p-nitrophenyl acetate (PNPA), in human liver microsomes...
April 24, 2018: Cancer Chemotherapy and Pharmacology
Jing Du, Yuanqiao He, Peng Li, Weiquan Wu, Youwei Chen, Hongjun Ruan
Cytokines play important roles in tumorigenesis and progression of cancer cells, while their functions in drug resistance remain to be illustrated. We successfully generated doxorubicin (Dox)-resistant CRC HCT-116 and SW480 cells (namely HCT-116/Dox and SW480/Dox, respectively). Cytokine expression analysis revealed that IL-8, while not FGF-2, EGF, TGF-β, IL-6, or IL-10, was significantly increased in Dox-resistant CRC cells as compared with their corresponding parental cells. Targeted inhibition of IL-8 via siRNAs or its inhibitor reparixin can increase the Dox sensitivity of HCT-116/Dox and SW480/Dox cells...
April 24, 2018: Cancer Chemotherapy and Pharmacology
Steven Lacy, Bei Yang, Jace Nielsen, Dale Miles, Linh Nguyen, Matt Hutmacher
PURPOSE: An integrated population pharmacokinetic (popPK) model was developed to describe the pharmacokinetics (PK) of tyrosine kinase inhibitor cabozantinib in healthy volunteers (HVs) and patients with various cancer types and to identify any differences in cabozantinib PK across these populations. METHODS: Plasma concentration data used to develop the popPK model were obtained from nine clinical trials (8072 concentrations from 1534 HVs or patients) of cabozantinib in HVs and patients with renal cell carcinoma (RCC), medullary thyroid carcinoma (MTC), glioblastoma multiforme, castration-resistant prostate cancer, or other advanced malignancies...
April 23, 2018: Cancer Chemotherapy and Pharmacology
Kohei Fujita, Naohiro Uchida, Osamu Kanai, Misato Okamura, Koichi Nakatani, Tadashi Mio
PURPOSE: After approval of anti-programmed cell death (PD)-1 antibodies, treatment for non-small cell lung cancer (NSCLC) has drastically changed. However, even in patients with favorable effects, therapeutic efficacy does not last long. Recently, retreatment with anti-PD-1 antibody has received attention. The aim of this study was to evaluate the efficacy and safety of retreatment with pembrolizumab in NSCLC patients previously treated with nivolumab. PATIENTS AND METHODS: We retrospectively reviewed NSCLC patients retreated with pembrolizumab who were previously treated with nivolumab...
April 19, 2018: Cancer Chemotherapy and Pharmacology
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