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Phase 3 cancer

Shengnan Guo, Yuanyuan Wang, Yu Gao, Yinxu Zhang, Mingzi Chen, Minghao Xu, Lu Hu, Yu Jing, Fangyu Jing, Chen Li, Qingjun Wang, Zhitu Zhu
BACKGROUND High mobility group-box 3 (HMGB3) has been shown to affect tumor initiation and progression. This research aimed to investigate the role of HMGB3 in gastric cancer (GC) cell proliferation, migration, invasion, chemoresistance, and its potential molecular mechanisms. MATERIAL AND METHODS GC MGC803 and BGC823 cells were transfected with siRNA targeting the HMGB3 gene. The expressions of HMGB3 protein in MGC803 and BGC823 cells after transfection were detected by Western blot assays. We detected cell proliferation and cell cycle by MTT and flow cytometry assay...
October 24, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Ying Liu, Yang Qi, Zhi-Hui Bai, Chen-Xu Ni, Qi-Hui Ren, Wei-Heng Xu, Jing Xu, Hong-Gang Hu, Lei Qiu, Jian-Zhong Li, Zhi-Gao He, Jun-Ping Zhang
AIM: Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, which has shown chemopreventive potential against various cancers. In this study, we evaluated the anticancer efficacy of a novel derivative of matrine, (6aS, 10S, 11aR, 11bR, 11cS)-10- methylamino-dodecahydro- 3a,7a-diaza-benzo (de) (MASM), against human hepatocellular carcinoma (HCC) cells and their corresponding sphere cells in vitro and in vivo. METHODS: Human HCC cell lines (Hep3B and Huh7) were treated with MASM...
October 24, 2016: Acta Pharmacologica Sinica
Feixiong Cheng, Junfei Zhao, Ariella B Hanker, Monica Red Brewer, Carlos L Arteaga, Zhongming Zhao
PURPOSE: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in human breast cancer. Furthermore, PIK3CA mutations are commonly associated with resistance to anti-epidermal growth factor receptor 2 (HER2) or anti-estrogen receptor (ER) agents in HER2 or ER positive (HER2(+)/ER(+)) breast cancer. Hence, deciphering the underlying mechanisms of PIK3CA mutations in HER2(+)/ER(+) breast cancer would provide novel insights into elucidating resistance to anti-HER2/ER therapies...
October 22, 2016: Breast Cancer Research and Treatment
Sihem Ait-Oudhia, Donald E Mager
Cancer is a complex disease that is characterized by an uncontrolled growth and spread of abnormal cells. Drug development in oncology is particularly challenging and is associated with one of the highest attrition rates of compounds despite substantial investments in resources. Pharmacokinetic and pharmacodynamic (PK/PD) modeling seeks to couple experimental data with mathematical models to provide key insights into factors controlling cytotoxic effects of chemotherapeutics and cancer progression. PK/PD modeling of anti-cancer compounds is equally challenging, partly based on the complexity of biological and pharmacological systems...
October 22, 2016: Journal of Pharmacokinetics and Pharmacodynamics
B Gyawali, T Shimokata, M Ando, K Honda, Y Ando
BACKGROUND: Sorafenib is a multikinase-tyrosine kinase inhibitor commonly used in a variety of cancers. There are concerns about the increased risk of serious adverse events (SAEs) and fatal adverse events (FAEs) with sorafenib. We performed an up-to-date meta-analysis of all phase 3 randomized controlled trials (RCTs) of sorafenib to quantify the increased risk of SAEs and FAEs. PATIENTS AND METHODS: We carried out a systematic search of electronic databases for studies published from inception to February 2016 without any restrictions...
October 22, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Thai H Ho, Rafael Nunez-Nateras, Yue-Xian Hou, Alan H Bryce, Donald W Northfelt, Amylou C Dueck, Bryan Wong, Melissa L Stanton, Richard W Joseph, Erik P Castle
BACKGROUND: Prostate tissue expresses 2 estrogen receptor (ER) isoforms, ER-α and ER-β, and estrogen-based therapies have shown activity in preclinical studies. Raloxifene, a selective ER modulator, has inhibited the growth of prostate cancer xenograft models and was tested in a phase II trial of castration-resistant prostate cancer (CRPC), with some patients achieving stable disease. However, no studies have examined the safety of the combination of bicalutamide plus raloxifene for CRPC...
September 8, 2016: Clinical Genitourinary Cancer
Ali Farzin, Mohammadhossein Fathi, Rahmatollah Emadi
Hyperthermia and local drug delivery have been proposed as potential therapeutic approaches for killing cancer cells. The development of bioactive materials such as Hardystonite (HT) with magnetic and drug delivery properties can potentially meet this target. This new class of magnetic bioceramic can replace the widely used magnetic iron oxide nanoparticles, whose long-term biocompatibility is not clear. Magnetic HT can be potentially employed to develop new ceramic scaffolds for bone surgery and anticancer therapies...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
S Zappavigna, M Scuotto, A M Cossu, D Ingrosso, M De Rosa, C Schiraldi, R Filosa, M Caraglia
BACKGROUND: Embelin is a potent dual inhibitor of 5-lipoxigenase (5-LOX) and microsomal prostaglandin E2 synthase (mPGES)-1 that suppresses proliferation of human glioma cells and induces apoptosis by inhibiting XIAP and NF-κB signaling pathway. Synthetic structural modification yielded the derivative 3-((decahydronaphthalen-6-yl)methyl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione (RF-Id), an embelin constrained analogue, with improved efficiency against 5-LOX in human neutrophils and anti-inflammatory activity in vivo...
October 22, 2016: Journal of Experimental & Clinical Cancer Research: CR
Majid Zaki Dizaji, Seyed H Ghaffari, Elham Hosseini, Nasrin Alizadeh, Shahrbano Rostami, Majid Momeny, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
AIM: Survivin, an inhibitor of apoptosis protein, is overexpressed in most cancers and is associated with chemotherapy resistance, increased tumor recurrence and shorter patient survival. Several survivin splice variants have been described, and none of their expressions have been defined in acute promyelocytic leukemia (APL). METHODS: Expression of the survivin gene isoforms (survivin, -2α, -2B, -ΔΕx3 and -3B) were analyzed in 50 peripheral blood and 19 bone marrow samples that were collected at different phases of the disease (diagnostic, remission and relapse) in APL patients treated with arsenic trioxide (ATO) as a front-line therapy...
October 22, 2016: Asia-Pacific Journal of Clinical Oncology
Britton Trabert, Ronald C Eldridge, Ruth M Pfeiffer, Meredith S Shiels, Troy J Kemp, Chantal Guillemette, Patricia Hartge, Mark E Sherman, Louise A Brinton, Amanda Black, Anil K Chaturvedi, Allan Hildesheim, Sonja I Berndt, Mahboobeh Safaeian, Ligia Pinto, Nicolas Wentzensen
Inflammation is proposed to increase risk of developing endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating inflammation markers and endometrial cancer risk. In a nested case-control study within the PLCO Screening Trial we measured serum levels of 64 inflammation-related biomarkers in 284 incident endometrial cancer cases and 284 matched controls. Using multivariable logistic regression inflammation markers were evaluated individually and combined into a cross-validated inflammation score...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
Ana M Denis-Bacelar, Sarah J Chittenden, David P Dearnaley, Antigoni Divoli, Joe M O'Sullivan, V Ralph McCready, Bernadette Johnson, Yong Du, Glenn D Flux
PURPOSE: To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit. METHODS: Clinical data from 57 patients who received 2.5-5.1 GBq of (186)Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed...
October 21, 2016: European Journal of Nuclear Medicine and Molecular Imaging
Nancy Chan, Amy Willis, Naomi Kornhauser, Maureen M Ward, Sharrell B Lee, Eleni Nackos, Bo Ri Seo, Ellen Chuang, Tessa Cigler, Anne Moore, Diana Donovan, Marta Vallee Cobham, Veronica Fitzpatrick, Sarah Schneider, Alysia Wiener, Jessica Guillaume-Abraham, Elnaz Anjom, Richard Zelkowitz, J David Warren, Maureen E Lane, Claudia Fischbach, Vivek Mittal, Linda Vahdat
PURPOSE: Bone marrow derived progenitor cells; including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways model the tumor microenvironment. We hypothesized that copper depletion (CD) using tetrathiomolybdate (TM) would reduce EPCs in high risk for relapse breast cancer (BC) patients (pts). We investigated the effect of TM on the tumor microenvironment in preclinical models. EXPERIMENTAL DESIGN: Stage 2 triple negative BC (TNBC), Stage 3 and stage 4 without any evidence of disease, (NED) BC pts, received oral TM to maintain ceruloplasmin (Cp) between 8-17mg/dL for 2 years or until relapse...
October 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Chao-Ming Hung, Ying-Chao Lin, Liang-Chih Liu, Sheng-Chu Kuo, Chi-Tang Ho, Tzong-Der Way
CWF-145, a synthetic 2-phenyl-4-quinolone derivative exerted potent cytotoxicity against prostate cancer. CWF-145 inhibited prostate cancer cell lines PC-3, DU-145 and LNCap. It had a very low IC50 about 200 nM against castrate-resistant prostate cancer (CRPC) PC-3. We found that CWF-145 had a similar effect to clinical trial antimitotic agents in cancer cells and normal cells. CWF-145 arrested cell cycle at G2/M phase by binding to the β-tubulin at the colchicine-binding site then disrupted microtubule polymerization...
October 18, 2016: Chemico-biological Interactions
Arndt Vogel, Josefine Römmler-Zehrer, Jack Shiansong Li, Desmond McGovern, Alfredo Romano, Michael Stahl
BACKGROUND: The phase 3 MPACT trial in patients with metastatic pancreatic cancer demonstrated superior efficacy of nab-paclitaxel (nab-P) + gemcitabine (Gem) vs Gem monotherapy for all endpoints examined including overall survival, the primary endpoint. In the MPACT trial, patients were treated until progressive disease (PD) or unacceptable toxicity. The current exploratory analysis investigated outcomes of patients from the MPACT trial who were treated until PD, in order to understand how to maximize treatment benefit from nab-P + Gem...
October 21, 2016: BMC Cancer
Hideomi Yamashita, Ryousuke Takenaka, Kae Okuma, Kuni Ootomo, Keiichi Nakagawa
BACKGROUND: A prospective study was performed on the use of chemoradiotherapy (CRT) for esophageal cancer (EC) with involved-field radiation therapy (IFRT), based on 18-fluorodeoxyglucose positron-emission tomography. Prognostic factors for overall survival (OS) were analyzed. METHODS: Eligible patients included 63 adults with newly diagnosed, untreated, inoperable stage I-IV EC with lymph node metastases. Patients received 80 mg/m(2) nedaplatin per day on day 1, 800 mg/m(2) 5-fluorouracil on days 1-4 intravenously repeated every 28 days for two to four cycles, and combined IFRT...
September 2016: Thoracic Cancer
Kambiz Rahbar, Hojjat Ahmadzadehfar, Clemens Kratochwil, Uwe Haberkorn, Michael Schäfers, Markus Essler, Richard P Baum, Harshad R Kulkarani, Matthias Schmidt, Peter Bartenstein, Andreas Pfestroff, Ulf Lützen, Marlies Marx, Vikas Prasad, Winfried Brenner, Alexander Heinzel, Juri Ruf, Philipp Tobias Meyer, Martin Heuschkel, Maria Eveslage, Martin Bögemann, Wolfgang Peter Fendler, Bernd Joachim Krause
: (177)Lutetium labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of (177)Lu-PSMA-617 in a large cohort of patients. METHODS: 145 patients (median age 73 years, range 43-88) with mCRPC were treated with (177)Lu-PSMA-617 in 12 therapy centres between February 2014 and July 2015 with one to four therapy cycles and an activity range of 2 to 8 GBq per cycle...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
H H Yoon, J C Bendell, F S Braiteh, I Firdaus, P A Philip, A L Cohn, N Lewis, D M Anderson, E Arrowsmith, J D Schwartz, L Gao, Y Hsu, Y Xu, D Ferry, S R Alberts, Z A Wainberg
BACKGROUND: We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ). PATIENTS AND METHODS: Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks...
October 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
S Kanda, K Goto, H Shiraishi, E Kubo, A Tanaka, H Utsumi, K Sunami, S Kitazono, H Mizugaki, H Horinouchi, Y Fujiwara, H Nokihara, N Yamamoto, H Hozumi, T Tamura
BACKGROUND: The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible...
October 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Matthew I Milowsky, Matthew D Galsky, Michael J Morris, Daniel J Crona, Daniel J George, Robert Dreicer, Kin Tse, Jesika Petruck, Iain J Webb, Neil H Bander, David M Nanus, Howard I Scher
BACKGROUND: This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer. PATIENTS AND METHODS: A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165mg/m(2); 12 patients); every 2 weeks (120, 168, 236, and 330mg/m(2); 15 patients); every 3 weeks (330 and 426mg/m(2); 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330mg/m(2); 17 patients)...
October 17, 2016: Urologic Oncology
Keun-Wook Lee, Bum Jun Kim, Mi-Jung Kim, Hye Sook Han, Jin Won Kim, Young Iee Park, Sook Ryun Park
Purpose: This study evaluated the re-challenge of S-1 or cisplatin in combination with docetaxel in metastatic gastric cancer (MGC) that had progressed on a cisplatin plus either S-1 or capecitabine regimen. Materials and Methods: Patients with progressive disease after first-line cisplatin plus S-1 or capecitabine were randomized to receive 3-week cycles of docetaxel 75 mg/m² intravenously (IV) on D1 (D), docetaxel 60 mg/m² IV plus cisplatin 60 mg/m² IV on D1 (DC), or docetaxel 60 mg/m² IV D1 plus oral S-1 30 mg/m² b...
October 18, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
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