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Cancer Chemotherapy and Pharmacology

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https://www.readbyqxmd.com/read/28534209/the-renal-safety-and-efficacy-of-combined-gemcitabine-plus-cisplatin-and-gemcitabine-plus-carboplatin-chemotherapy-in-chinese-patients-with-a-solitary-kidney-after-nephroureterectomy
#1
Peng Sun, Cong Xue, Li-Ren Li, Cui Shao, Xin An, Ried Thomas, Wei Yang, Ying-Fei Deng, Wen-Qi Jiang, Yan-Xia Shi
PURPOSE: The renal safety of cisplatin-based chemotherapy has not been investigated in patients with urothelial carcinoma of the upper urinary tract (UUT-UC) who retain a solitary kidney after nephroureterectomy. This study aimed to assess and compare the renal safety and efficacy of gemcitabine-cisplatin (GP) and gemcitabine-carboplatin (GC) in these patients. METHODS: The medical records of patients diagnosed with urothelial carcinoma at the Sun Yat-Sen University Cancer Center between January 2005 and December 2015 were retrospectively reviewed...
May 22, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28528358/dna-topoisomerase-targeting-chemotherapeutics-what-s-new
#2
REVIEW
Selma M Cuya, Mary-Ann Bjornsti, Robert C A M van Waardenburg
To resolve the topological problems that threaten the function and structural integrity of nuclear and mitochondrial genomes and RNA molecules, human cells encode six different DNA topoisomerases including type IB enzymes (TOP1 and TOP1mt), type IIA enzymes (TOP2α and TOP2β) and type IA enzymes (TOP3α and TOP3β). DNA entanglements and the supercoiling of DNA molecules are regulated by topoisomerases through the introduction of transient enzyme-linked DNA breaks. The covalent topoisomerase-DNA complexes are the cellular targets of a diverse group of cancer chemotherapeutics, which reversibly stabilize these reaction intermediates...
May 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28523597/prognostic-value-of-chemotherapy-resistant-ck19mrna-positive-circulating-tumor-cells-in-patients-with-advanced-metastatic-non-small-cell-lung-cancer
#3
G Milaki, I Messaritakis, F Koinis, A Kotsakis, S Apostolaki, E K Dermitzaki, M Perraki, D Hatzidaki, V Georgoulias
BACKGROUND: The detection of circulating tumor cells (CTCs) is of prognostic significance in several tumor types. The present study evaluated the detection and the clinical relevance of CK19mRNA(+) CTCs in patients with advanced/metastatic non-small cell lung cancer before and after front-line chemotherapy. PATIENTS AND METHODS: Peripheral blood was obtained from 642 patients with treatment-naïve unresectable stage IIIB and IV non-small cell lung cancer and from 455 patients after the completion of 1st line chemotherapy...
May 18, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28523596/pharmacokinetics-and-safety-of-vismodegib-in-patients-with-advanced-solid-malignancies-and-hepatic-impairment
#4
Ghassan K Abou-Alfa, Lionel D Lewis, Patricia LoRusso, Michael Maitland, Priya Chandra, Sravanthi Cheeti, Dawn Colburn, Sarah Williams, Brian Simmons, Richard A Graham
PURPOSE: Vismodegib is a Hedgehog pathway inhibitor approved for the treatment of advanced basal cell carcinoma. Currently, the pharmacokinetics (PK) and safety of vismodegib in patients with hepatic dysfunction are unknown and are the objective of this study. METHODS: Patients with advanced solid malignancies and hepatic impairment were enrolled into one of four cohorts: normal [bilirubin (bili) < upper limit of normal (ULN)], mild (ULN < bili ≤ 1...
May 18, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28510802/phase-i-ii-study-of-bi-weekly-xeliri-plus-bevacizumab-treatment-in-patients-with-metastatic-colorectal-cancer-resistant-to-oxaliplatin-based-first-line-chemotherapy
#5
Tsunekazu Mizushima, Mutsumi Fukunaga, Toshinori Sueda, Masataka Ikeda, Takeshi Kato, Ho Min Kim, Toshihiro Kudo, Kohei Murata, Junichi Nishimura, Taishi Hata, Chu Matsuda, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
PURPOSE: We aimed to determine the recommended dose for bi-weekly XELIRI plus bevacizumab for second-line chemotherapy and examined its safety and efficacy in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy. METHODS: Irinotecan and bevacizumab were administered as a continuous intravenous infusion on Day 1 at 150 mg/mm(2) and 5 mg/kg, respectively. Capecitabine was orally administered in two divided doses on Days 2-8...
May 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28508095/estimation-of-glomerular-filtration-rate-in-cancer-patients-with-abnormal-body-composition-and-relation-with-carboplatin-toxicity
#6
M Bretagne, A Jouinot, J P Durand, O Huillard, P Boudou Rouquette, C Tlemsani, J Arrondeau, G Sarfati, F Goldwasser, J Alexandre
PURPOSE: Carboplatin clearance is correlated with glomerular filtration rate (GFR) and usually estimated with creatinine clearance using Cockcroft-Gault (CG) formula. Because plasma creatinine level is highly correlated with muscle mass, we hypothesized that an abnormal body composition with a low lean body mass (LBM) percentage [(LBM/weight) × 100] may result in inadequate carboplatin dosing. Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We aimed to investigate the influence of total LBM and LBM percentage on GFR calculation, using creatinine (CrCl) or cystatin C (GFRcysC-creat) in cancer patients...
May 15, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28502039/possible-involvement-of-the-lipoxygenase-and-leukotriene-signaling-pathways-in-cisplatin-mediated-renal-toxicity
#7
Osama A Alkhamees, Abdulaziz S Alroujayee, Hatem M Abuohashish, Fatima S Alrojayee, Mohammed M Ahmed
PURPOSE: The present study examined the possible involvement of the lipoxygenase (LOX) pathway in cisplatin (CPT)-induced nephrotoxicity. METHODS: Wistar albino rats were challenged with CPT IP injection (7.5 mg/kg) and were sacrificed after one week. Signs of renal dysfunction, including urea and creatinine clearance levels and renal histological structure, were investigated. Gene and protein expression levels of different LOX pathway enzymes and products, including 5-LOX, 12-LOX, 15-LOX, 5-LOX activating protein (FLAP), leukotriene A4 hydrolase (LTA4 hydrolase), leukotriene C4 synthase (LTC4 synthase), LTB4 receptor, and cysteinyl (cys) LT receptor types 1 and 2, were also determined in the kidneys using real-time PCR and western blotting, respectively...
May 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28500557/cellular-effect-and-efficacy-of-carfilzomib-depends-on-cellular-net-concentration-gradient
#8
Julia Schäfer, Lukas Welti, Anja Seckinger, Jürgen Burhenne, Dirk Theile, Johanna Weiss
PURPOSE: The cellular interrelation between intracellular concentrations of unbound carfilzomib, a second-generation proteasome inhibitor, and subsequent proteasome inhibition and effect on cell viability are unknown and were evaluated for two different exposure regimens: A high dose bolus regime of 500 nM for 1 h followed by 47 h in drug-free media vs. 48-h continuous exposure to 10 nM. METHODS: Eight multiple myeloma cell lines were exposed to either one of the two exposure regimens...
May 12, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28493032/is-there-any-predictor-for-hypersensitivity-reactions-in-gynecologic-cancer-patients-treated-with-paclitaxel-based-therapy
#9
Tadashi Aoyama, Masashi Takano, Morikazu Miyamoto, Tomoyuki Yoshikawa, Hiroaki Soyama, Kento Kato, Hiroki Ishibashi, Hideki Iwahashi, Masaya Nakatsuka, Isao Yajima, Yukihiro Shimizu, Yusuke Aizawa, Yuki Suguchi, Miki Moriiwa, Tomoko Goto, Hidenori Sasa, Isao Nagaoka, Hitoshi Tsuda, Kenichi Furuya
PURPOSE: Recently, generic drugs of paclitaxel have been commonly used mainly by economic reasons; however, predictive factors for toxicities are not fully determined. Hypersensitivity reaction (HSR) is one of the most important adverse events in the paclitaxel-based therapy, and sometimes leads to lethal condition. The aim of the study was to identify predictors for HSR in patients treated with paclitaxel-based regimens. METHODS: All the patients treated with chemotherapy including paclitaxel at our hospital between 1998 and 2013 were retrospectively evaluated...
May 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28488026/carfilzomib-and-lenalidomide-response-related-to-vegf-and-vegfr2-germline-polymorphisms
#10
Tristan M Sissung, Cody J Peer, Neha Korde, Sham Mailankody, Dickran Kazandjian, David J Venzon, Ola Landgren, William D Figg
The combination of carfilzomib, lenalidomide, and dexamethasone (CRd) has induced deep responses in patients with newly diagnosed multiple myeloma. While vascular endothelial growth factor (VEGF) pathway polymorphisms have been associated with clinical outcomes for antiangiogenesis agents, we explored associations between such polymorphisms and CRd clinical response. The VEGF-1498C>T (rs833061) and VEGFR2 V297I (rs2305948) were associated with CRd response (OR ≤ 0.10, P ≤ 0.009), whereas VEGF-1498C>T and VEGFR2 Q472H (rs1870377) were associated with minimum residual disease negativity (P ≤ 0...
May 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28444427/population-pharmacokinetic-modelling-of-doxorubicin-and-doxorubicinol-in-children-with-cancer-is-there-a-relationship-with-cardiac-troponin-profiles
#11
Kuhan Kunarajah, Stefanie Hennig, Ross L G Norris, Michael Lobb, Bruce G Charles, Ross Pinkerton, Andrew S Moore
PURPOSE: Anthracyclines are a mainstay of the treatment of several childhood malignancies, but their utility is limited by dose-related cardiotoxicity. This study is aimed to explore the link between exposure of paediatric cancer patients to doxorubicin and its metabolite doxorubicinol, and cardiac troponin I (cTnI). METHODS: In a prospective pilot study plasma doxorubicin, doxorubicinol, and cTnI concentrations were measured in samples from children undergoing cancer chemotherapy...
April 25, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28391354/low-plasma-concentration-of-gefitinib-in-patients-with-egfr-exon-21-l858r-point-mutations-shortens-progression-free-survival
#12
Yuji Okuda, Kazuhiro Sato, Kazuhisa Sudo, Yukiyasu Hasegawa, Mariko Asano, Hajime Miura, Masahide Takeda, Masaaki Sano, Hiroyuki Watanabe, Hiroyuki Kobayashi, Takenori Niioka, Masatomo Miura, Hiroshi Ito
PURPOSE: The relationship between the pharmacokinetics and effects of gefitinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) is unknown. In this study, we examined the correlation between gefitinib plasma concentration and progression-free survival (PFS) in patients with two common types of EGFR mutations: a deletion in exon 19 and point mutations in exon 21 L858R. METHODS: The retrospective analysis examined 40 patients who were administered 250 mg of gefitinib daily...
April 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28391353/wbp2-modulates-g1-s-transition-in-er-%C3%A2-breast-cancer-cells-and-is-a-direct-target-of-mir-206
#13
Yong-Qiang Ren, Hui-Jun Wang, Yong-Qing Zhang, Yan-Bing Liu
PURPOSE: The mechanisms underlying the oncogenic properties of WW domain binding protein 2 (WBP2) in breast cancer have not been fully understood. In this study, we explored the role of WBP2 in cell cycle regulation in ER+ breast cancer cells and how it is regulated in the cancer cells. METHODS: The association between WBP2 expression and prognosis in ER+ breast cancer was assessed by data mining in Breast Cancer Gene-Expression Miner v4.0. Cell cycle was assessed by PI staining and flow cytometry...
April 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28391352/the-impact-of-a-solitary-kidney-on-tolerability-to-gemcitabine-plus-cisplatin-chemotherapy-in-urothelial-carcinoma-patients-a-retrospective-study
#14
Masahiro Kondo, Yuji Hotta, Ryosuke Ando, Takahiro Yasui, Kazunori Kimura
PURPOSE: There is little information on tolerability to cisplatin-based chemotherapies in patients with a solitary kidney after nephroureterectomy. We evaluated the impact of having a solitary kidney on tolerability to gemcitabine plus cisplatin (GC) chemotherapy in urothelial carcinoma patients. METHODS: We retrospectively reviewed medical records of patients treated between August 2007 and November 2015. Eligible patients had received GC as first-line chemotherapy, including as neoadjuvant and adjuvant treatment...
April 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28391351/curcumin-inhibits-prostate-cancer-by-targeting-pgk1-in-the-foxd3-mir-143-axis
#15
Hongwen Cao, Hongjie Yu, Yigeng Feng, Lei Chen, Fang Liang
PURPOSE: Curcumin is a potent antitumor agent. The objective of this study was to explore the interaction between curcumin and PGK1, an oncogene in the FOXD3/miR-143 axis, in prostate cancer therapy. METHODS: MiRNA microarray analysis was used to identify miRNAs upregulated by curcumin treatment. MiR-143 was dramatically upregulated by curcumin. Cells were treated with antimiR-143 in combination to curcumin, followed by examining cell viability and migration. Bioinformatics analysis was used to investigate target genes of miR-143...
April 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28389780/computed-determination-of-the-in-vitro-optimal-chemocombinations-of-sphaeropsidin-a-with-chemotherapeutic-agents-to-combat-melanomas
#16
Aude Ingels, Carina Dinhof, Abhishek D Garg, Lucia Maddau, Marco Masi, Antonio Evidente, Walter Berger, Bieke Dejaegher, Véronique Mathieu
PURPOSE: Evasion to new treatments of advanced melanoma is still associated with a poor prognosis. Choosing the best combination of agents that can bypass resistance mechanisms remains a challenge. Sphaeropsidin A (Sph A) is a fungal bioactive secondary metabolite previously shown to force melanoma cells to undergo apoptosis via cell volume dysregulation. This work studied its in vitro combination with cytotoxic chemotherapeutics in a rational manner. METHODS: Four melanoma cell lines harboring different sensitivity levels to pro-apoptotic stimuli were used to build a predictive response surface model allowing the determination of the optimal in vitro combinations of Sph A with two drugs, i...
April 7, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28378028/up-regulation-of-autophagy-is-a-mechanism-of-resistance-to-chemotherapy-and-can-be-inhibited-by-pantoprazole-to-increase-drug-sensitivity
#17
Qian Tan, A M Joshua, M Wang, R G Bristow, B G Wouters, C J Allen, Ian F Tannock
BACKGROUND: Autophagy is a survival mechanism that allows recycling of cellular breakdown products, particularly in stressed cells. Here we evaluate the hypotheses that up-regulation of autophagy is a common mechanism of resistance to chemotherapy, and that drug resistance can be reversed by inhibiting autophagy with a proton pump inhibitor. METHODS: We exposed human PC3, LNCaP and MCF7 cells to seven clinically-used chemotherapy drugs ± pantoprazole, examined the up-regulation of autophagy and the effect on cellular proliferation by Western Blots, MTS assay and colony-forming assay...
April 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28378027/a-phase-ii-trial-of-neoadjuvant-chemoradiotherapy-with-intensity-modulated-radiotherapy-combined-with-gemcitabine-and-s-1-for-borderline-resectable-pancreatic-cancer-with-arterial-involvement
#18
Yuichi Nagakawa, Yuichi Hosokawa, Hidetsugu Nakayama, Yatsuka Sahara, Chie Takishita, Tetsushi Nakajima, Yousuke Hijikata, Kazuhiko Kasuya, Kenji Katsumata, Koichi Tokuuye, Akihiko Tsuchida
PURPOSE: Chemoradiotherapy using intensity-modulated radiotherapy (IMRT) is expected to provide a powerful alternative to conventional chemotherapy with a low incidence of adverse events. This study evaluated the efficacy of intensity modulated radiotherapy in combination with gemcitabine and S-1 as neoadjuvant chemoradiotherapy (NACRT) for borderline-resectable pancreatic cancer with arterial involvement (BR-A). METHODS: A total of 27 patients with BR-A were enrolled in this study between February 2012 and September 2015...
April 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28364288/co-administration-of-proton-pump-inhibitors-ameliorates-nephrotoxicity-in-patients-receiving-chemotherapy-with-cisplatin-and-fluorouracil-a-retrospective-cohort-study
#19
Kenji Ikemura, Kosuke Oshima, Tomoyuki Enokiya, Akiharu Okamoto, Hiroyasu Oda, Toshiro Mizuno, Hajime Ishinaga, Yuichi Muraki, Takuya Iwamoto, Kazuhiko Takeuchi, Naoyuki Katayama, Masahiro Okuda
PURPOSE: The nephrotoxicity of cisplatin (CDDP) is its dose-limiting side effect, and is caused by renal accumulation of CDDP mainly via organic cation transporter 2 (OCT2). Because proton pump inhibitors (PPIs) are known to inhibit OCT2 activity, PPI might ameliorate CDDP-induced nephrotoxicity. In the present study, we retrospectively investigated the effect of co-administration of PPI on CDDP-induced nephrotoxicity. METHODS: We analyzed the impact of PPI on the development of nephrotoxicity in 133 patients who received CDDP and fluorouracil (5-FU) therapy for the treatment of esophageal cancer or head and neck cancer...
March 31, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28361167/potential-drug-drug-interactions-with-abiraterone-in-metastatic-castration-resistant-prostate-cancer-patients-a-prevalence-study-in-france
#20
Clément Bonnet, Pascaline Boudou-Rouquette, Esther Azoulay-Rutman, Olivier Huillard, Jean-Louis Golmard, Edith Carton, Gaëlle Noé, Michel Vidal, Galdric Orvoen, Anne Chah Wakilian, Clémentine Villeminey, Benoit Blanchet, Jérôme Alexandre, François Goldwasser, Audrey Thomas-Schoemann
PURPOSE: Abiraterone acetate combined with prednisone improves survival in metastatic castration-resistant prostate cancer (mCRPC) patients. This oral anticancer agent may result in drug-drug interactions (DDI). We aimed to evaluate the prevalence of DDI with abiraterone and the possible determinants for the occurrence of these DDI. METHODS: We performed a single centre retrospective review from electronic medical records of mCRPC patients treated with abiraterone from 2011 to 2015...
March 30, 2017: Cancer Chemotherapy and Pharmacology
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