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Cancer Chemotherapy and Pharmacology

Lei Zhan, Jun Li, Bing Wei
Autophagy captures and degrades intracellular components such as proteins and organelles to sustain metabolism and homeostasis. Rapidly accumulating attention is being paid to the role of autophagy in the development of cancer, which makes autophagy attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that autophagy dysregulation is causal in many cases of cancer, with autophagy acting as tumor suppressors or tumor promoters, and autophagy inhibitor or promoter has shown promise in preclinical studies...
September 17, 2018: Cancer Chemotherapy and Pharmacology
Joan Maurel, Santiago Sánchez-Cabús, Berta Laquente, Lydia Gaba, Laura Visa, Joan Fabregat, Ignacio Povés, Susana Roselló, Roberto Díaz-Beveridge, Marta Martín-Richard, Javier Rodriguez, Luis Sabater, Carles Conill, María Cambray, Ana Reig, Juan Ramón Ayuso, Carlos Valls, Antonio Ferrández, Josep Antoni Bombí, Angels Ginés, Xabier García-Albéniz, Laureano Fernández-Cruz
BACKGROUND: Neoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients. METHODS: Patients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000 mg/m2 /week) plus daily erlotinib (ERL) (100 mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300 mg/m2 /week), ERL 100 mg/day and concomitant radiotherapy (45 Gy)...
September 17, 2018: Cancer Chemotherapy and Pharmacology
Koki Goto, Ryusei Matsuyama, Yusuke Suwa, Sayaka Arisaka, Toshiaki Kadokura, Mari Sato, Ryutaro Mori, Takafumi Kumamoto, Masataka Taguri, Itaru Endo
PURPOSE: To assess the predictive ability of the maximum chemiluminescence intensity (CImax ) for severe neutropenia (SN) during neoadjuvant chemo(radio)therapy [NAC(RT)] in patients with advanced pancreatic or biliary tract cancer. METHODS: Clinicopathological variables and blood test data before NAC(RT) were evaluated in 64 patients with advanced pancreatic or biliary tract cancer who received gemcitabine plus tegafur/gimeracil/oteracil as NAC(RT). RESULTS: Thirty-nine patients (60...
September 14, 2018: Cancer Chemotherapy and Pharmacology
Arabinda Das, Fraser Henderson, Stephen Lowe, Gerald C Wallace, William A Vandergrift, Scott M Lindhorst, Abhay K Varma, Libby K Infinger, Pierre Giglio, Narendra L Banik, Sunil J Patel, David Cachia
PURPOSE/INTRODUCTION: Glioblastoma (GB) remains incurable despite aggressive chemotherapy, radiotherapy, and surgical interventions; immunotherapies remain experimental in clinical practice. Relevant preclinical models that can accurately predict tumor response to therapy are equally challenging. This study aimed to validate the effect of the naturally occurring agent diallyl trisulfide (DATS) in human GB in relevant pre-clinical models. METHODS: Ex vivo slice culture, in vivo cell line derived orthotopic xenograft and patient-derived orthotopic xenograft (PDX) animal models of GB were utilized to assess efficacy of treatment with DATS...
September 12, 2018: Cancer Chemotherapy and Pharmacology
Z Liu, J Martin, L Orme, B Seddon, J Desai, W Nicholls, D Thomson, D Porter, G McCowage, C Underhill, N Cranswick, M Michael, M Zacharin, A Herschtal, J Sivasuthan, D M Thomas
PURPOSE: For many cancers, adolescents and young adults (AYA) have worse outcomes than for children and adults. Many factors may contribute to the AYA survival gap, including differences in biology, therapeutic intent, and adherence to therapy. It has been observed that male AYAs have poorer outcomes than females. The purpose of this work was to test the proposition that gender-related pharmacologic factors may account for a component of the AYA survival gap. PATIENTS AND METHODS: A prospective, multi-institutional pharmacologic study of 79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment...
September 11, 2018: Cancer Chemotherapy and Pharmacology
Elena Fountzilas, Elangovan Krishnan, Filip Janku, Siqing Fu, Daniel D Karp, Aung Naing, Vivek Subbiah, David S Hong, Sarina A Piha-Paul, David J Vining, Apostolia-Maria Tsimberidou
BACKGROUND: We investigated hepatic arterial infusion (HAI) oxaliplatin combined with capecitabine +/- bevacizumab in advanced cancer with predominant liver involvement. METHODS: Patients received HAI oxaliplatin (140 mg/m2 ) and escalating doses of capecitabine (500, 750, and 1000 mg/m2 ), with (Group 1) or without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used, followed by an expansion phase. RESULTS: From 9/2009 to 2/2014, 61 patients (34 men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17)...
September 4, 2018: Cancer Chemotherapy and Pharmacology
Eleanor Bishop, Tracey D Bradshaw
Autophagy is a tightly controlled process comprising lysosomal degradation and recycling of cellular proteins and organelles. In cancer, its paradoxical dual role of cytoprotection and cytotoxicity is context-dependent and controversial. Autophagy primarily acts as a mechanism of tumour suppression, by maintenance of genomic integrity and prevention of proliferation and inflammation. This, combined with immune-surveillance capabilities and autophagy's implicated role in cell death, acts to prevent tumour initiation...
September 4, 2018: Cancer Chemotherapy and Pharmacology
Michael Moloney, David Faulkner, Emma Link, Danny Rischin, Ben Solomon, Annette M Lim, John R Zalcberg, Michael Jefford, Michael Michael
PURPOSE: 5-Fluorouracil (5FU) drug exposure correlates with treatment response and toxicity in cancer patients. Dosing is based upon body surface area which does not correlate with 5FU pharmacokinetics (PK)/pharmacodynamics. Therapeutic drug monitoring has enabled real-time 5FU dose adjustments: reducing toxicity with increased efficacy. The aim of this study was to assess feasibility of a 5FU monitoring service utilising a commercial kit in a quaternary cancer centre and to compare PK parameters to previously published studies...
September 3, 2018: Cancer Chemotherapy and Pharmacology
Ayako Iida-Ueno, Masaru Enomoto, Sawako Uchida-Kobayashi, Atsushi Hagihara, Yuga Teranishi, Hideki Fujii, Hiroyasu Morikawa, Yoshiki Murakami, Akihiro Tamori, Le Thi Thanh Thuy, Norifumi Kawada
PURPOSE: This study aimed to identify a biomarker for predicting the response to sorafenib in patients with hepatocellular carcinoma (HCC). METHODS: Of 100 patients with unresectable HCC who received sorafenib treatment in our institute (Cohort A), 48 had stored plasma samples collected within 28 days before the start of treatment (Cohort B). Concentrations of 18 plasma cytokines were measured in plasma samples using a sandwich immunoassay with multiplexed fluorescent bead-based technology...
September 3, 2018: Cancer Chemotherapy and Pharmacology
Udai Banerji, Nivedita Sain, Swee Y Sharp, Melanie Valenti, Yasmin Asad, Ruth Ruddle, Florence Raynaud, Michael Walton, Suzanne A Eccles, Ian Judson, Ann L Jackman, Paul Workman
The corresponding author of this article has informed us of concerns about the immunoblots in Fig. 2 which were carried out in the collaborating laboratory of Professor Ann Jackman.
September 1, 2018: Cancer Chemotherapy and Pharmacology
Vassilios Aslanis, Jianping Zhang, Barbara Lomeli, Kai Grosch, Taoufik Ouatas
PURPOSE: Eltrombopag is indicated in patients with severe aplastic anemia (SAA) refractory to prior immunosuppressive therapy. The combination of eltrombopag and immunosuppressive therapy (such as cyclosporine) is currently being evaluated in patients with treatment-naive SAA. Cyclosporine is a human breast cancer resistance protein (BCRP) inhibitor, and can potentially alter plasma exposure to eltrombopag, a BCRP substrate. This phase 1, open-label, randomized, 3-period, crossover study evaluated the effect of cyclosporine on the pharmacokinetics of eltrombopag in healthy adults...
August 31, 2018: Cancer Chemotherapy and Pharmacology
Hironaga Satake, Tamotsu Sagawa, Koshi Fujikawa, Yukimasa Hatachi, Hisateru Yasui, Masahito Kotaka, Takeshi Kato, Akihito Tsuji
PURPOSE: Optimal salvage chemotherapy for patients with treated advanced/metastatic gastric cancer (AGC) is unknown. Irinotecan is commonly used in Japan. Ramucirumab, a human IgG-1 monoclonal antibody targeting the extracellular domain of VEGF receptor 2, is the first molecularly targeted agent proven to be effective in second-line therapy for AGC in combination with chemotherapy. We sought to determine the maximum tolerated dose (MTD) and recommended dose (RD) of ramucirumab plus irinotecan for AGC previously treated with fluoropyrimidine with/without platinum and taxane...
August 30, 2018: Cancer Chemotherapy and Pharmacology
Yong Cao, Yan Lin, Dongxu Wang, Di Pan, Ying Zhang, Yu Jin, Changqing Zheng
PURPOSE: Cancer cells alter regular metabolic pathways in order to sustain rapid proliferation. One example of metabolic remodeling in cancerous tissue is the upregulation of pyruvate kinase isoenzyme M2 (PKM2), which is involved in aerobic glycolysis. Indeed, PKM2 has previously been identified as a tumor biomarker and as a potential target for cancer therapy. Here, the role of PKM2 in the anticancer efficacy of 5-fluorouracil (5-FU) was evaluated in colorectal cancer (CRC). METHODS: HCT116, SW480 and HT-29 cells were used by transfection with lentiviral vectors expressing short hairpin RNA (shRNA) against PKM2...
August 28, 2018: Cancer Chemotherapy and Pharmacology
Laeeq Malik, James Cooper
PURPOSE: Efforts are underway in improving the informed consent process. The success of these efforts to improve quality of informed consent forms (ICFs) for phase I oncology trials has not been previously measured. METHODS: We reviewed and compared ICFs of all phase I trials for metastatic cancer conducted between 1986 and 1999 and 2000-2015 periods at our institution. Information pertaining to ICF length, study purpose description, research regimen/methods, potential risks and benefits was extracted...
August 27, 2018: Cancer Chemotherapy and Pharmacology
Min Huang, Hong Zhu, Cheng Yi, Juan Yan, Lijia Wei, Xi Yang, Shouchun Chen, Ying Huang
PURPOSE: Pancreatic cancer is a malignant tumor of the digestive system with poor prognosis and high mortality, and the treatment of pancreatic cancer still remains a major challenge. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis selectively in cancer cells while causing virtually no damage to normal cells, which is promising for cancer therapy. However, many primary tumors and cancer cell lines including various human pancreatic cancer cell lines were found to be resistant to TRAIL-induced apoptosis...
August 24, 2018: Cancer Chemotherapy and Pharmacology
Kelong Tao, Meng He, Feng Tao, Guangen Xu, Minfeng Ye, Yuanyuan Zheng, Yaoqing Li
Gastric cancer is the third leading cause of cancer-related mortalities worldwide and mostly incurable. It remains an urgent need for novel strategies in the management of patients with advanced gastric cancer. Chimeric antigen receptor (CAR) T therapy has shown unprecedented clinical success in hematological malignancies and potential utility is going on various solid tumors like gastric cancer. In this study, a broad expression of NKG2D ligands was observed in gastric cancer cell lines, making them suitable targets for gastric cancer therapy...
August 21, 2018: Cancer Chemotherapy and Pharmacology
Sandeepraj Pusalkar, Mihaela Plesescu, Neeraj Gupta, Michael Hanley, Karthik Venkatakrishnan, Jing-Tao Wu, Cindy Xia, Xiaoquan Zhang, Swapan Chowdhury
PURPOSE: This metabolite profiling and identification analysis (part of a phase I absorption, distribution, metabolism, and excretion study) aimed to define biotransformation pathways and evaluate associated inter-individual variability in four patients with advanced solid tumors who received [14 C]-ixazomib. METHODS: After administration of a single 4.1-mg oral dose of [14 C]-ixazomib (total radioactivity [TRA] ~ 500 nCi), plasma (at selected timepoints), urine, and fecal samples were collected before dosing and continuously over 0-168-h postdose, followed by intermittent collections on days 14, 21, 28, and 35...
August 20, 2018: Cancer Chemotherapy and Pharmacology
Isabel Sousa, Filipa Rodrigues, Hugo Prazeres, Raquel T Lima, Paula Soares
Liposomal therapies opened the chapter of nanomedicine, in 1995, with the approval of liposomal doxorubicin (Doxil® ) for the treatment of numerous types of cancer. For the first time, liposomes permitted the employment of potent chemotherapeutic agents with improved pharmacokinetic and pharmacodynamic profiles, with less undesired side effects. Liposomal therapies allow the drug encapsulation and more selective delivery in the tumor bed, particularly due to the enhanced permeation and retention effect. These unique characteristics explain why liposomal therapies are being increasingly considered as alternatives in cancer therapy and represent an important research field with the recent approval for clinical use and emergent formulations in clinical trials...
August 16, 2018: Cancer Chemotherapy and Pharmacology
Hisham Qosa, Brittany R Avaritt, Neil R Hartman, Donna A Volpe
PURPOSE: Hyperbilirubinemia has been observed in patients treated with tyrosine kinase inhibitor (TKI) drugs. Therefore, it would be beneficial to understand whether there is a relationship between inhibition of uridine-5'-diphosphate glucuronosyltransferase (UGT) 1A1 activity and observed bilirubin elevations in TKI drug-treated patients. UGT1A1 is responsible for the glucuronidation of bilirubin which leads to its elimination in the bile. METHODS: To examine this question, an in vitro glucuronidation assay was developed to determine the inhibitory effect of TKI drugs employing human liver microsomes (HLM) with varying UGT1A1 activity...
August 13, 2018: Cancer Chemotherapy and Pharmacology
Negin Farshchian, Avisa Alavi, Sahel Heydarheydari, Nasrin Moradian
OBJECTIVE: One of the complications of chemotherapy is peripheral neuropathy. Various studies have shown that potent norepinephrine and serotonin reuptake inhibitors such as gabapentin, venlafaxine and duloxetine have therapeutic effects on neuropathy. The aim of this study was to compare the effects of venlafaxine vs. duloxetine on chemotherapy-induced peripheral neuropathy. METHODS: In this clinical trial, cancer patients who were suffering from chemotherapy-induced peripheral neuropathy comprised the study population...
August 13, 2018: Cancer Chemotherapy and Pharmacology
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