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Cancer Chemotherapy and Pharmacology

Jie Weng, Mengyun Tu, Bo Yang, Zhiyi Wang
No abstract text is available yet for this article.
March 15, 2018: Cancer Chemotherapy and Pharmacology
Weiwei Chen, Jiajia An, Jiwei Guo, Yan Wu, Lijuan Yang, Juanjuan Dai, Kaikai Gong, Shuang Miao, Sichuan Xi, Jing Du
PURPOSE: Sodium selenite (SS) has been widely reported to induce apoptosis in various cancer cell types. However, the underlying molecular mechanisms governing SS-mediated repression of lung cancer stem cells remain largely undefined. METHODS: In vitro assays of cell proliferation, clonal formation, apoptosis, migration and cancer stemness cell sphere formation were performed to examine the inhibitory effects of SS on lung adenocarcinoma (LAD) cells with or without the overexpression of SRY-related high-mobility-group box 2 (SOX2)...
March 15, 2018: Cancer Chemotherapy and Pharmacology
Emma Dean, Udai Banerji, Jan H M Schellens, Matthew G Krebs, Begona Jimenez, Emilie van Brummelen, Chris Bailey, Ed Casson, Diana Cripps, Marie Cullberg, Stephen Evans, Andrew Foxley, Justin Lindemann, Paul Rugman, Nigel Taylor, Guy Turner, James Yates, Peter Lawrence
PURPOSE: AZD5363 is a potent pan-AKT inhibitor originally formulated as a capsule; a tablet was developed for patient convenience and manufacturing ease. This study assessed the PK comparability of both formulations (Part A) and the effect of food (Part B) on the PK/safety of the tablet. METHODS: Adults with advanced solid tumours received AZD5363 480 mg bid in a partially fasted state by tablet (Week 1) and capsule (Week 2) in a '4-days-on/3-days-off' schedule (Part A)...
March 14, 2018: Cancer Chemotherapy and Pharmacology
Peng Yin, Guizhen Song, Zhenhua Jiang
PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the most commonly diagnosed cancers worldwide with significantly high prevalence in Southern China. Chemoprevention of cancer with alkylating agent compounds could potentially reverse, suppress, or prevent cancer progression. Cisplatin (CIS) is an antineoplastic or cytotoxic platinum-based drug used for chemotherapy of different types of human cancers such as NPC. Nevertheless, the effects of CIS on the migration and invasion of human NPC cells and the underlying molecular mechanisms have not yet been fully scrutinized...
March 14, 2018: Cancer Chemotherapy and Pharmacology
Mengyan Deng, Linna Li, Jianchun Zhao, Shoujun Yuan, Wenbao Li
PURPOSE: MBRI-001 is a novel synthetic derivative of plinabulin. In this study, our purpose is to investigate the inhibition effects of MBRI-001 on human hepatocellular carcinoma as monotherapy or in combination with sorafenib. METHODS: HCCLM3 and Bel-7402 cell lines were used for activity evaluation in vitro. The anti-proliferative activity of MBRI-001 was assessed by MTT assay. The morphological change of microtubules was determined by immunofluorescence assay...
March 12, 2018: Cancer Chemotherapy and Pharmacology
Anthony B El-Khoueiry, Robert O'Donnell, Thomas J Semrad, Philip Mack, Suzette Blanchard, Nathan Bahary, Yixing Jiang, Yun Yen, John Wright, Helen Chen, Heinz-Josef Lenz, David R Gandara
PURPOSE: The insulin-like growth factor (IGF) pathway is activated in hepatocarcinogenesis. Cixutumumab is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). Given the cross-talk between the IGF and VEGF pathways, we performed a phase I study of the combination of cixutumumab and sorafenib in hepatocellular cancer (HCC). METHODS: Eligible patients with no prior systemic therapy for advanced HCC and Child-Pugh A to B7 were treated with sorafenib 400 mg BID and escalating doses of cixutumumab (2, 4, or 6 mg/kg IV weekly) in a 3 + 3 design...
March 8, 2018: Cancer Chemotherapy and Pharmacology
David Kudlowitz, Alejandro Velastegui, Fernanda Musa, Franco Muggia
PURPOSE: We report here on the tolerance of a carboplatin-'divided dose' paclitaxel (given on days 1 and 11) regimen in chemotherapy-naïve patients with resected and staged endometrial epithelial neoplasms deemed at high-risk of recurrence or early stage epithelial high-grade serous tubo-ovarian adenocarcinomas after risk-reducing surgery. More recently, we applied this regimen as neoadjuvant chemotherapy for advanced ovarian cancer presentations. METHODS: A retrospective chart review of patients receiving this day 1, 11 paclitaxel regimens in combination with carboplatin at AUC 6 every 3 weeks since 2004 was carried out by the second author with subsequent updates by the first and third authors...
March 7, 2018: Cancer Chemotherapy and Pharmacology
Keiji Kurata, Kimikazu Yakushijin, Atsuo Okamura, Motohiro Yamamori, Hiroya Ichikawa, Rina Sakai, Yu Mizutani, Seiji Kakiuchi, Yoshiharu Miyata, Akihito Kitao, Shinichiro Kawamoto, Hiroshi Matsuoka, Tohru Murayama, Hironobu Minami
PURPOSE: Mycophenolate mofetil (MMF) is increasingly used among Japanese patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Because pharmacokinetic data for MMF in the Asian population are limited, we conducted this investigation. METHODS: Intravenous MMF (1000 mg/dose) was administered to 10 patients along with cyclosporine or tacrolimus for 10 days after allo-SCT; it was administered every 8 h in peripheral blood stem cell- and bone marrow-transplanted patients, and every 12 h in cord blood-transplanted patients...
March 6, 2018: Cancer Chemotherapy and Pharmacology
Yoshinori Munemoto, Mitsuro Kanda, Koji Oba, Ho Min Kim, Hiroyoshi Takemoto, Tadamichi Denda, Naoki Nagata, Nao Takano, Mutsumi Fukunaga, Masato Kataoka, Yukihiko Tokunaga, Junichi Sakamoto, Hideyuki Mishima
PURPOSE: Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted...
March 5, 2018: Cancer Chemotherapy and Pharmacology
Motoo Nomura, Atsushi Otsuka, Michio Yoshimura, Yumi Nonomura, Yo Kaku, Shigemi Matsumoto, Manabu Muto
BACKGROUND: The objective of this study was to evaluate the efficacy and safety of concurrent immune checkpoint inhibitor therapy and radiotherapy (immunoradiotherapy) in patients with metastatic melanoma after progression on nivolumab. PATIENTS AND METHODS: A retrospective review was performed on 16 consecutive patients with metastatic melanoma treated with concurrent immunoradiotherapy after progression on nivolumab. Best responses to immunoradiotherapy were assessed either inside or outside of the radiation fields...
March 3, 2018: Cancer Chemotherapy and Pharmacology
Suguru Yamada, Tsutomu Fujii, Yukihiro Yokoyama, Hiroki Kawashima, Osamu Maeda, Kojiro Suzuki, Tohru Okada, Eizaburo Ono, Junpei Yamaguchi, Nao Takano, Hideki Takami, Masamichi Hayashi, Yukiko Niwa, Yoshiki Hirooka, Yoshiyuki Ito, Shinji Naganawa, Yuichi Ando, Masato Nagino, Hidemi Goto, Yasuhiro Kodera
PURPOSE: For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen. METHODS: Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined...
March 3, 2018: Cancer Chemotherapy and Pharmacology
Kazuki Takasaki, Morikazu Miyamoto, Masashi Takano, Hiroaki Soyama, Tadashi Aoyama, Hiroko Matsuura, Kento Kato, Takahiro Sakamoto, Mika Kuwahara, Hideki Iwahashi, Hiroki Ishibashi, Tomoyuki Yoshikawa, Kenichi Furuya
PURPOSE: To compare a cohort of patients with platinum-resistant recurrent ovarian cancer (PROC) treated with bevacizumab and gemcitabine (Bev-Gem) to that of patients treated only with gemcitabine (Gem). METHODS: Between 2011 and 2017, we identified the Bev-Gem and Gem PROC groups. The regimen included 1000 mg/m2 of Gem on days 1, 8, and 15, and 15 mg/m2 of Bev on day 1, every 4 weeks. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of the administration of Bev-Gem or Gem until disease progression or death...
March 2, 2018: Cancer Chemotherapy and Pharmacology
Diaddin Hamdan, François Darrouzain, Theodora Bejan-Angoulvant, Charles Isorni, Laurent Zelek, Gilles Paintaud, Anne Janin, Guilhem Bousquet
PURPOSE: Trastuzumab is the most widely prescribed anti-HER2 humanized monoclonal antibody. Cardiac toxicity is the only limiting toxicity of trastuzumab and it is of particular concern in patients with complete response, since the drug needs to be stopped, with a risk of disease relapse. To date, no pharmacological data on trastuzumab cardiotoxicity in patients have been made available. Here, we provide proof of concept, demonstrating that it was possible to prevent trastuzumab-induced cardiotoxicity by modifying the drug administration schedule...
March 1, 2018: Cancer Chemotherapy and Pharmacology
Jie Cui, Min-Cong Wang, Ya-Min Zhang, Ming-Zhi Ren, Shi-Xiong Wang, Ke-Jun Nan, Li-Ping Song
OBJECTIVE: To investigate the potential radiosensitization of S-1 and gefitinib in human non-small cell lung cancer (NSCLC) in vitro and in vivo. METHODS: The impact of radiation, 5-fluorouracil (5-Fu), and gefitinib on the proliferation and apoptosis of human NSCLC A549, H1299, H1975, and HCC827 cells was examined by MTT and flow cytometry. The effect of radiation, 5-Fu, and gefitinib on the clonogenicity of H1975 and HCC827 cells was determined by colony formation assay...
February 26, 2018: Cancer Chemotherapy and Pharmacology
Valentina Citi, Marzia Del Re, Alma Martelli, Vincenzo Calderone, Maria Cristina Breschi, Romano Danesi
BACKGROUND: Everolimus is the hydroxyethyl derivative of sirolimus and a strong inhibitor of mammalian target of rapamycin (mTOR). This drug has immunosuppressive and anticancer activities and the present in vitro study was aimed at identifying the cellular and molecular profiles of breast cancer cells predictive of sensitivity to everolimus. MATERIALS AND METHODS: MCF-7, T-47D, ZR-75-1, CAMA-1, HCC-1500 and MCF-10A cells were used and viability was assessed using WST-1 dye...
February 23, 2018: Cancer Chemotherapy and Pharmacology
Lauriane Goldwirt, Kevin Beccaria, Alain Ple, Hélène Sauvageon, Samia Mourah
PURPOSE: Central nervous system (CNS) dissemination occurs in 4.1% of mantle cell lymphoma (MCL) patients and clinically significant CNS involvement in chronic lymphocytic leukemia (CLL) patients reaches 4%. Ibrutinib, an orally administered Bruton's tyrosine kinase (BTK) inhibitor, has shown substantial activity in CLL or MCL patients with CNS localization, and in primary central nervous system lymphoma (PCNSL). The drug efficacy to treat primary or secondary CNS impairments relies on its brain distribution through the blood-brain barrier (BBB), the aim of the present work was to study the brain distribution of ibrutinib using an in vivo mice model...
February 23, 2018: Cancer Chemotherapy and Pharmacology
Concetta Panebianco, Kaarel Adamberg, Madis Jaagura, Massimiliano Copetti, Andrea Fontana, Signe Adamberg, Kaia Kolk, Raivo Vilu, Angelo Andriulli, Valerio Pazienza
BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-related death. We aimed to evaluate whether gemcitabine treatment shapes the gut microbiota in a model of PDAC xenografted mice. MATERIALS AND METHODS: Pancreatic cancer xenograft mice were subjected to gemcitabine injection once per week for 3 weeks to assess the tumor volume as compared to control mice injected with normal saline solution. The composition of fecal microbiota, the activation of NF-kB pathway in cancer tissues and the serum metabolomics were further analyzed...
February 22, 2018: Cancer Chemotherapy and Pharmacology
Frederik Marmé, Carlos Gomez-Roca, Kristina Graudenz, Funan Huang, John Lettieri, Carol Peña, Zuzana Jirakova Trnkova, Jan Eucker
Combining sorafenib and eribulin mesylate may provide synergistic antitumor activities with limited overlapping toxicities. This phase 1b, open-label, dose-escalation study evaluated safety, pharmacokinetics, maximum tolerated dose/recommended phase 2 dose (MTD/RP2D), and preliminary efficacy of sorafenib plus standard-dose eribulin mesylate in patients with advanced, metastatic, or refractory tumors. Patients received sorafenib 200 mg twice daily (BID; n = 5), 600 mg/day (n = 8), and 400 mg BID (MTD; n = 27)...
February 21, 2018: Cancer Chemotherapy and Pharmacology
Anthony B El-Khoueiry, John Sarantopoulos, Cindy L O'Bryant, Kristen K Ciombor, Huiping Xu, Melissa O'Gorman, Jayeta Chakrabarti, Tiziana Usari, Bassel F El-Rayes
PURPOSE: This phase 1 study evaluated the effect of hepatic impairment on pharmacokinetics and safety of crizotinib in patients with advanced cancer. METHODS: Patients were dosed according to hepatic function classified by modified National Cancer Institute Organ Dysfunction Working Group criteria and group assignment [normal (A1 and A2), mild (B), moderate (C1 and C2), or severe (D)]. Primary pharmacokinetic endpoints included area under the concentration-time curve as daily exposure (AUCdaily ) and maximum plasma concentration (Cmax ) at steady state...
February 21, 2018: Cancer Chemotherapy and Pharmacology
Takahiro Nakayama, Yasuaki Sagara, Tsutomu Takashima, Nobuki Matsunami, Norikazu Masuda, Yasuo Miyoshi, Tetsuya Taguchi, Toyokazu Aono, Toshikazu Ito, Tatsuo Kagimura, Shinzaburo Noguchi
PURPOSE: This phase II study evaluated the efficacy and safety of anastrozole concurrent with tegafur/uracil (UFT) as neoadjuvant therapy for ER-positive postmenopausal breast cancer. METHODS: Postmenopausal Japanese women with ER-positive, HER2-negative, T2,N0-1,M0 breast cancer seen at tertiary hospitals were eligible for this open-label, randomized, multicenter study. Patients were randomized 1:1 by minimization to orally receive either anastrozole (1 mg once daily) plus UFT (tegafur/uracil combination in 1:4 molar ratio; 270 mg/m2 /day in two divided doses) or anastrozole (as above) alone for 24 weeks...
February 21, 2018: Cancer Chemotherapy and Pharmacology
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