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https://www.readbyqxmd.com/read/29345044/preclinical-characterisation-of-absorption-distribution-metabolism-and-excretion-properties-of-tak-063
#1
Kimio Tohyama, Miyako Sudo, Akio Morohashi, Suguru Kato, Junzo Takahashi, Yoshihiko Tagawa
TAK-063 is currently being developed to treat schizophrenia. In this study, we investigated the absorption, distribution, metabolism and excretion (ADME) properties of TAK-063 using several paradigms. Following oral administration of TAK-063 at 0.3 mg/kg, bioavailability of TAK-063 was 27.4% in rats and 49.5% in dogs with elimination half-lives of 3.1 hr in rats and 3.7 hr in dogs. TAK-063 is a highly permeable compound without P-glycoprotein (P-gp) or breast cancer resistance protein substrate liability and can be readily absorbed into systemic circulation via the intestine...
January 17, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29341164/patient-derived-organoid-models-help-define-personalized-management-of-gastrointestinal-cancer
#2
REVIEW
M R Aberle, R A Burkhart, H Tiriac, S W M Olde Damink, C H C Dejong, D A Tuveson, R M van Dam
BACKGROUND: The prognosis of patients with different gastrointestinal cancers varies widely. Despite advances in treatment strategies, such as extensive resections and the addition of new drugs to chemotherapy regimens, conventional treatment strategies have failed to improve survival for many tumours. Although promising, the clinical application of molecularly guided personalized treatment has proven to be challenging. This narrative review focuses on the personalization of cancer therapy using patient-derived three-dimensional 'organoid' models...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29340015/apatinib-alone-or-combined-with-radiotherapy-in-metastatic-prostate-cancer-results-from-a-pilot-multicenter-study
#3
Feng Zhao, Wei Tian, Ming Zeng, Jianling Xia, Honglin Hu, Xinbao Hao, Liangfu Han, Hao Liu, Yangke He, Xueqiang Zhu, Liang Liang, Rui Ao, Min Wei, Lili Deng, Yuquan Wei
Background: To study safety and efficacy of apatinib in combination of radiotherapy in patients with symptomatic bony disease prostate cancer(SBPC), based on the potential synergistic antitumor activity between apatinib and Radiation Therapy (RT). Patients and methods: In phase I dose escalation part, 18 patients received apatinib dose at 250 mg every other day, 250 mg daily and 500 mg daily. In phase II part, the 250 mg daily cohorts were expanded to 20 patients in combination of RT (6 Gy/fraction, 5 fraction in total), one patient lost followed up and excluded the study, comparing with RT alone cohort with 10 patients, ratio of RT to RT + apatinib was 1 to 2...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339926/using-a-chronic-hepatitis-b-registry-to-support-population-level-liver-cancer-prevention-in-sydney-australia
#4
Monica C Robotin, Ximena Masgoret, Mamta Porwal, David Goldsbury, Chee Khoo, Jacob George
Background: Approximately 1% of Australians have chronic hepatitis B (CHB), which disproportionately affects people born in hepatitis B-endemic countries. Currently, approximately half of the people affected remain undiagnosed and antiviral treatment uptake is suboptimal (~5%). This increases the likelihood of developing end-stage disease complications, particularly hepatocellular cancer (HCC), and largely accounts for the significant increases in HCC incidence and mortality in Australia over the last decades...
2018: Clinical Epidemiology
https://www.readbyqxmd.com/read/29337443/-update-in-surgical-oncology
#5
Daniel Clerc, Didier Roulin, Nicolas Demartines, Emmanuel Melloul
In 2017, data from large multicentre randomized controlled trials assessed the safety of minimally invasive techniques for liver or esophagus resection with similar oncologic outcome compared to open approach. Patients also benefit from progress in medical oncology in particular with the development of new targeted therapies, offering surgery to patients with initially non-resectable disease. The increase in complete tumor response after neoadjuvant treatment allows more conservative approaches, like organ preserving surgery for rectal cancer...
January 10, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29336888/lxr-apoe-activation-restricts-innate-immune-suppression-in-cancer
#6
Masoud F Tavazoie, Ilana Pollack, Raissa Tanqueco, Benjamin N Ostendorf, Bernardo S Reis, Foster C Gonsalves, Isabel Kurth, Celia Andreu-Agullo, Mark L Derbyshire, Jessica Posada, Shugaku Takeda, Kimia N Tafreshian, Eric Rowinsky, Michael Szarek, Roger J Waltzman, Elizabeth A Mcmillan, Connie Zhao, Monica Mita, Alain Mita, Bartosz Chmielowski, Michael A Postow, Antoni Ribas, Daniel Mucida, Sohail F Tavazoie
Therapeutic harnessing of adaptive immunity via checkpoint inhibition has transformed the treatment of many cancers. Despite unprecedented long-term responses, most patients do not respond to these therapies. Immunotherapy non-responders often harbor high levels of circulating myeloid-derived suppressor cells (MDSCs)-an immunosuppressive innate cell population. Through genetic and pharmacological approaches, we uncovered a pathway governing MDSC abundance in multiple cancer types. Therapeutic liver-X nuclear receptor (LXR) agonism reduced MDSC abundance in murine models and in patients treated in a first-in-human dose escalation phase 1 trial...
January 9, 2018: Cell
https://www.readbyqxmd.com/read/29336009/gefitinib-for-advanced-non-small-cell-lung-cancer
#7
REVIEW
Esther Ha Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
BACKGROUND: The role of gefitinib for the treatment of advanced non-small cell lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the available evidence from all randomised trials. OBJECTIVES: To determine the effectiveness and safety of gefitinib as first-line, second-line or maintenance treatment for advanced NSCLC. SEARCH METHODS: We performed searches in CENTRAL, MEDLINE and Embase from inception to 17 February 2017...
January 16, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29335858/effects-of-aidi-injection-with-western-medical-therapies-on-quality-of-life-for-patients-with-primary-liver-cancer-a-systematic-review-and-meta-analysis
#8
Li Liu, Jian Liang, Xin Deng
OBJECTIVE: To evaluate the effects of Aidi Injection (, AD) in combination with Western medical therapies (WMT) in patients with primary liver cancer (PLC). METHODS: Randomized controlled trials (RCTs) comparing AD plus WMT with WMT alone were retrieved from inception to March 2013 by retrieving the literature database thoroughly and systematically. The extracted data from included studies were analyzed and synthesized by Review Manager 5.2 software. The Cochrane risk of bias tool was used to assess the quality of included studies, and Begg's and Egger's tests were used to evaluate the potential presence of publication bias...
January 15, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29334698/endoscopic-ultrasound-and-the-liver-current-applications-and-beyond
#9
REVIEW
Neil D Shah, Todd H Baron
The diagnosis and management of many gastrointestinal conditions has been augmented by the development of endoscopic ultrasound. Its role in the diagnosis and management of liver disease has been somewhat limited, but with the rapid development of therapeutic advancements it has quickly emerged as a useful tool in the management of complex hepatic conditions. This includes its use in the management of complications of portal hypertension as well as its use in liver lesions and cancer. In this paper, we review case studies, case series and trials for hepatic applications of endoscopic ultrasound to provide an overview of its utilization in this field and demonstrating its more novel applications for future use...
January 15, 2018: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/29334610/phase-ii-study-of-dovitinib-in-patients-with-castration-resistant-prostate-cancer-kcsg-gu11-05
#10
Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park
Purpose: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and Methods: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500mg/day (5-days-on/2-days-off schedule)...
January 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29322091/a-retroviral-replicating-vector-encoding-cytosine-deaminase-and-5-fc-induces-immune-memory-in-metastatic-colorectal-cancer-models
#11
Kader Yagiz, Maria E Rodriguez-Aguirre, Fernando Lopez Espinoza, Tiffany T Montellano, Daniel Mendoza, Leah A Mitchell, Carlos E Ibanez, Noriyuki Kasahara, Harry E Gruber, Douglas J Jolly, Joan M Robbins
Treatment of tumors with Toca 511, a gamma retroviral replicating vector encoding cytosine deaminase, followed by 5-fluorocytosine (5-FC) kills tumors by local production of 5-fluorouracil (5-FU). In brain tumor models, this treatment induces systemic anti-tumor immune responses and long-term immune-mediated survival. Phase 1 Toca 511 and Toca FC (extended-release 5-FC) clinical trials in patients with recurrent high-grade glioma show durable complete responses and promising survival data compared to historic controls...
March 30, 2018: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29316037/development-of-a-recombinant-murine-tumor-model-using-hepatoma-cells-expressing-hepatitis-c-virus-hcv-non-structural-antigens
#12
K Young, K Haq, S MacLean, R Dudani, S M Elahi, R Gilbert, R Weeratna, L Krishnan
Hepatitis C virus (HCV) chronically infects 2-3% of the world's population, causing liver disease and cancer with prolonged infection. The narrow host range of the virus, being restricted largely to human hepatocytes, has made the development of a relevant infection and reliable model to evaluate the efficacy of vaccines a challenge. We have developed a novel approach to accomplish this by generating a murine hepatoma cell line stably expressing non-structural HCV antigens which can be used in vitro or in vivo to test HCV vaccine efficacies...
January 6, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29307930/hepatocyte-specific-contrast-agent-enhanced-magnetic-resonance-cholangiography-perioperative-evaluation-of-the-biliary-tree
#13
Luciana Carmen Zattar-Ramos, Regis Otaviano Franca Bezerra, Luis Tenório de Brito Siqueira, Marcos Roberto Menezes, Claudia da Costa Leite, Giovanni Guido Cerri
A large number of gadolinium chelates have recently been tested in clinical trials. Some of those have already been approved for clinical use in the United States and Europe. Thus, new diagnostic perspectives have been incorporated into magnetic resonance imaging studies. Among such gadolinium chelates are hepatobiliary-specific contrast agents (HSCAs), which, due to their property of being selectively taken up by hepatocytes and excreted by the biliary ducts, have been widely used for the detection and characterization of focal hepatic lesions...
November 2017: Radiologia Brasileira
https://www.readbyqxmd.com/read/29299827/apical-lymph-nodes-in-the-distant-metastases-and-prognosis-of-patients-with-stage-iii-colorectal-cancer-with-adequate-lymph-node-retrieval-following-folfox-adjuvant-chemotherapy
#14
Hsiang-Lin Tsai, Yi-Ting Chen, Yung-Sung Yeh, Ching-Wen Huang, Cheng-Jen Ma, Jaw-Yuan Wang
The aim of the study was to assess apical lymph nodes (APNs) for predicting distant metastases in patients with stage III colorectal cancer (CRC) curatively treated with FOLFOX adjuvant chemotherapy and adequate lymph node retrieval. We investigated the correlation between APN metastasis and clinical outcomes. This retrospective study examined 97 patients. All patients were followed until death, loss to follow-up, or May 2017. Clinicopathological variables, including the APN status, were assessed. Multivariate logistic regression model was used to identify the independent risk factors for APN and distant metastases, and Cox proportional regression model was used to evaluate the association between APN metastasis and oncologic outcomes...
January 3, 2018: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29290261/does-nivolumab-for-progressed-metastatic-lung-cancer-fulfill-its-promises-an-efficacy-and-safety-analysis-in-20-general-hospitals
#15
Kurt G Tournoy, Michiel Thomeer, Paul Germonpré, Sofie Derijcke, Rebecca De Pauw, Daniëlla Galdermans, Karl Govaert, Elke Govaerts, Rob Schildermans, Isabelle Declercq, Nele De Brucker, Karin Pat, Rika Van Herreweghe, Luc Van Zandweghe, Luc Vanmaele, Valerie Van Damme, Heidi Marien, Sofie De Craene, Isabelle Fabry, Patrick Alexander, Piet Vercauter, Ingel Demedts
OBJECTIVES: In patients with refractory or recurrent non-small-cell lung cancer (NSCLC) after first line chemotherapy, phase III trials showed superiority of nivolumab, an IgG4 programmed death-1 immune-checkpoint-inhibitor antibody, over docetaxel. We evaluated case mix, effectiveness and safety of nivolumab upon implementation in general practice. MATERIALS AND METHODS: In 20 general hospitals, all consecutive NSCLC patients treated with nivolumab within the medical need program (inclusion period 12 months) in Flanders - Belgium were evaluated...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29274197/increased-recurrence-rates-of-hepatocellular-carcinoma-after-daa-therapy-in-a-hepatitis-c-infected-egyptian-cohort-a-comparative-analysis
#16
Mohamed El Kassas, Anna L Funk, Mohamed Salaheldin, Yusuke Shimakawa, Mohammed Eltabbakh, Kévin Jean, Adel El Tahan, Ahmad T Sweedy, Shimaa Afify, Naglaa Fa Youssef, Gamal Esmat, Arnaud Fontanet
In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV infected population from one Egyptian specialized HCC management center starting from the time of successful HCC intervention...
December 23, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29262510/-a-prospective-pilot-study-of-combined-intra-operative-radiotherapy-for-centrally-located-hepatocellular-carcinomas
#17
Y H Liu, L M Wang, J X Wu, W Q Rong, F Wu, M H Li, Y Zhang, S T Lin, Y L Zheng, Q F Feng
Objective: To carry out a prospective cohort study of combined intra-operative radiotherapy for centrally located hepatocellular carcinomas (HCC) and to observe the safety and postoperative complications. Methods: A total of 79 patients with centrally located HCC who underwent hepatectomy were divided into two groups: experimental group (combined with targeted intra-operative radiotherapy, 32 cases) and control group (single surgical operation, 47 cases). Patients in the experimental group received intra-operative electron radiotherapy after tumor resection, while patients in the control group received to intra-operative electron radiotherapy...
December 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/29258858/emerging-biomarkers-for-immunomodulatory-cancer-treatment-of-upper-gastrointestinal-pancreatic-and-hepatic-cancers
#18
REVIEW
Belinda Lee, Ryan Hutchinson, Hui-Li Wong, Jeanne Tie, Tracy Putoczki, Ben Tran, Peter Gibbs, Michael Christie
Carcinomas of the oesophagus, stomach, pancreas and liver are common and account for a disproportionately high number of cancer deaths. There is a need for new treatment options for patients with advanced disease. Immunomodulatory treatments including immune checkpoint blockade offer a promising new approach, with efficacy shown in other solid tumour types. However, only a small proportion of patients with carcinomas of the oesophagus, stomach, pancreas and liver have responded to single agent checkpoint inhibitors, and there is a need for markers that are predictive of response to guide treatment of individual patients...
December 16, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29250323/strategies-for-prevention-of-gastrointestinal-cancers-in-developing-countries-a-systematic-review
#19
Ahmad Zia Shams, Ulrike Haug
Background: Gastrointestinal cancers account for one third of total cancer incidence and mortality in developing countries. To date, there is no systematic synthesis of evidence regarding strategies to prevent gastrointestinal cancers in developing countries. We aimed to provide a systematic overview of studies evaluating strategies for prevention or early detection of the three most common gastrointestinal cancers (gastric, liver and colorectal cancer) in developing countries. Methods: We searched MEDLINE, Web of Science and WHO Global Index Medicus databases for relevant articles published until October 2016 using combinations of the search terms "gastrointestinal", "digestive system", "gastric", "liver", "colorectal", "cancer", "prevention", "early detection" and "developing country" (including names)...
December 2017: Journal of Global Health
https://www.readbyqxmd.com/read/29248731/pharmacokinetic-profile-of-pbrm-in-rodents-a-first-selective-covalent-inhibitor-of-17%C3%AE-hsd1-for-breast-cancer-and-endometriosis-treatments
#20
René Maltais, Alexandre Trottier, Jenny Roy, Diana Ayan, Nicolas Bertrand, Donald Poirier
The development of a covalent inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a promising approach for the treatment of hormone-dependent breast cancer and endometriosis. After reporting the steroid derivative PBRM as a first potent covalent inhibitor of 17β-HSD1 without estrogenic activity, we are now interested in studying its pharmaceutical behavior. The metabolism study in a human liver microsomal preparation showed a gradual transformation of PBRM into PBRM-O, an oxidized ketonic form of PBRM at position C17...
December 14, 2017: Journal of Steroid Biochemistry and Molecular Biology
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