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https://www.readbyqxmd.com/read/28817753/efficacy-and-safety-of-durvalumab-in-locally-advanced-or-metastatic-urothelial-carcinoma-updated-results-from-a-phase-1-2-open-label-study
#1
Thomas Powles, Peter H O'Donnell, Christophe Massard, Hendrik-Tobias Arkenau, Terence W Friedlander, Christopher J Hoimes, Jae Lyun Lee, Michael Ong, Srikala S Sridhar, Nicholas J Vogelzang, Mayer N Fishman, Jingsong Zhang, Sandy Srinivas, Jigar Parikh, Joyce Antal, Xiaoping Jin, Ashok K Gupta, Yong Ben, Noah M Hahn
Importance: The data reported herein were accepted for assessment by the US Food and Drug Administration for Biologics License Application under priority review to establish the clinical benefit of durvalumab as second-line therapy for locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent US approval. Objective: To report a planned update of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC. Design, Setting, and Participants: This is an ongoing phase 1/2 open-label study of 191 adult patients with histologically or cytologically confirmed locally advanced/metastatic UC whose disease had progressed on, were ineligible for, or refused prior chemotherapy from 60 sites in 9 countries as reported herein...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28817737/myc-mediates-cancer-stem-like-cells-and-emt-changes-in-triple-negative-breast-cancers-cells
#2
Shuping Yin, Vino T Cheryan, Liping Xu, Arun K Rishi, Kaladhar B Reddy
Women with triple negative breast cancer (TNBC) have poor prognosis compared to other breast cancer subtypes. There were several reports indicating racial disparity in breast cancer outcomes between African American (AA) and European American (EA) women. For example, the mortality rates of AA breast cancer patients were three times higher than of EA patients, even though, the incidence is lower in AA women. Our in vitro studies indicate that cancer stem-like cells (CSCs) derived from AA TNBC cell lines have significantly higher self-renewal potential (mammosphere formation) than CSCs derived from EA cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28816757/therapeutic-drug-monitoring-during-induction-of-anti-tumor-necrosis-factor-therapy-in-inflammatory-bowel-disease-defining-a-therapeutic-drug-window
#3
Konstantinos Papamichael, Niels Vande Casteele, Marc Ferrante, Ann Gils, Adam S Cheifetz
Anti-tumor necrosis factor (TNF) therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, up to 30% of patients with IBD show no clinical benefit and are defined as having a primary nonresponse. Primary nonresponse to a biologic can be attributed to either pharmacokinetic or pharmacodynamic issues, such as those involved in secondary loss of response. Pharmacokinetic issues are linked to undetectable or subtherapeutic drug concentrations because of either an accelerated non-immune-mediated clearance or immunogenicity and the development of antidrug antibodies, whereas pharmacodynamic issues are likely related to "non-TNF driven" disease...
September 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28816748/therapeutic-drug-monitoring-during-induction-of-anti-tumor-necrosis-factor-therapy-in-inflammatory-bowel-disease-defining-a-therapeutic-drug-window
#4
Konstantinos Papamichael, Niels Vande Casteele, Marc Ferrante, Ann Gils, Adam S Cheifetz
Anti-tumor necrosis factor (TNF) therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, up to 30% of patients with IBD show no clinical benefit and are defined as having a primary nonresponse. Primary nonresponse to a biologic can be attributed to either pharmacokinetic or pharmacodynamic issues, such as those involved in secondary loss of response. Pharmacokinetic issues are linked to undetectable or subtherapeutic drug concentrations because of either an accelerated non-immune-mediated clearance or immunogenicity and the development of antidrug antibodies, whereas pharmacodynamic issues are likely related to "non-TNF driven" disease...
August 14, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28816713/radiation-therapy-to-the-primary-in-metastatic-prostate-cancer-palliation-only-or-altering-tumor-biology
#5
Pierre Blanchard, Alberto Bossi, Karim Fizazi
PURPOSE OF REVIEW: Despite improvement in systemic treatment, the prognosis of men with de novo metastatic prostate cancer remains poor. Treating the local disease may not only reduce the occurrence of local urologic symptoms, but also slow the metastatic process, either by reducing the seeding from the primary tumor or by altering the microenvironment and thus minimizing the formation of new metastatic sites. RECENT FINDINGS: Retrospective and population-based studies have suggested that the addition of local treatment to systemic therapy may improve survival in this patient group...
August 14, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28816643/pharmacometabolomics-informs-quantitative-radiomics-for-glioblastoma-diagnostic-innovation
#6
Theodora Katsila, Minos-Timotheos Matsoukas, George P Patrinos, Dimitrios Kardamakis
Applications of omics systems biology technologies have enormous promise for radiology and diagnostics in surgical fields. In this context, the emerging fields of radiomics (a systems scale approach to radiology using a host of technologies, including omics) and pharmacometabolomics (use of metabolomics for patient and disease stratification and guiding precision medicine) offer much synergy for diagnostic innovation in surgery, particularly in neurosurgery. This synthesis of omics fields and applications is timely because diagnostic accuracy in central nervous system tumors still challenges decision-making...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28816149/a-multi-institution-retrospective-analysis-of-cervix-intracavitary-brachytherapy-treatments-part-1-is-eqd2-good-enough-for-reporting-radiobiological-effects
#7
Emma C Fields, Rakhi Melvani, George Hajdok, David D'Souza, Bernard Jones, Kelly Stuhr, Quentin Diot, Christine M Fisher, Nitai Mukhopadhyay, Dorin Todor
PURPOSE: When brachytherapy doses are reported or added, biologically effective dose (BED) minimum dose covering 90% of the volume (D90) is used as if dose is delivered uniformly to the target. Unlike BED(D90), equivalent uniform BED (EUBED) and generalized biologically equivalent uniform dose (gBEUD) are quantities that integrate dose inhomogeneity. Here we compared BED(D90) and equivalent uniform BED (EUBED)/gBEUD in 3 settings: (1) 2 sites using tandem and ovoid (T&O) but different styles of implants; (2) 2 sites using different devices-T&O and tandem and ring (T&R)-and different styles; and (3) the same site using T&O and T&R with the same style...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28815349/tumor-volume-doubling-time-as-a-dynamic-prognostic-marker-for-patients-with-hepatocellular-carcinoma
#8
Jong Kwan Kim, Hyung-Don Kim, Mi-Jung Jun, Sung-Cheol Yun, Ju Hyun Shim, Han Chu Lee, Danbi Lee, Jihyun An, Young-Suk Lim, Young-Hwa Chung, Yung Sang Lee, Kang Mo Kim
BACKGROUND AND AIMS: To evaluate the clinical value of tumor growth rate in hepatocellular carcinoma (HCC) patients, we investigated the growth rate of HCC by calculating the tumor volume doubling time (TVDT) and its impact on survival and recurrence. METHODS: A retrospective cohort study of 269 HCC patients who underwent two or more pretreatment imaging studies of computed tomography or magnetic resonance imaging was performed. Tumor growth rate and TVDT were calculated by comparing tumor volumes between imaging studies...
August 16, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28815347/the-tumor-stromal-ratio-as-a-strong-prognosticator-for-advanced-gastric-cancer-patients-proposal-of-a-new-tsnm-staging-system
#9
Chunwei Peng, Jiuyang Liu, Guifang Yang, Yan Li
BACKGROUND: Insufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance. METHODS: Tissue samples from the most invasive part of the primary gastric cancer (GC) of 494 patients were analyzed for their TSR, and a new TSNM (tumor-stromal node metastasis) staging system based on patho-biological behaviors was established and assessed...
August 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28815334/clinical-characteristics-of-patient-selection-and-imaging-predictors-of-outcome-in-solid-tumors-treated-with-checkpoint-inhibitors
#10
REVIEW
Sabrina Rossi, Luca Toschi, Angelo Castello, Fabio Grizzi, Luigi Mansi, Egesta Lopci
The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types...
August 16, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28815294/diallyl-trisulfide-inhibits-proliferation-invasion-and-angiogenesis-of-glioma-cells-by-inactivating-wnt-%C3%AE-catenin-signaling
#11
Qingxia Tao, Cuiying Wu, Ruxiang Xu, Lijun Niu, Jiazhen Qin, Ning Liu, Peng Zhang, Chong Wang
Aberrant activation of Wnt/β-catenin signaling leads to increased cell proliferation and survival and promotes the development of various human tumors, including glioma, one of the most common primary brain tumors. The treatment efficacy of many anticancer drugs remains limited or unsatisfactory and it is urgently necessary to develop effective and low-toxicity anticancer drugs or strategies, especially for glioma. Here, we report that diallyl trisulfide suppresses survival, migration, invasion and angiogenesis in glioma cells...
August 17, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28815223/hepatocellular-carcinoma-when-is-liver-transplantation-oncologically-futile
#12
REVIEW
André Viveiros, Heinz Zoller, Armin Finkenstedt
Selection criteria of patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) have been progressively expanded since the introduction of the Milan criteria. Transplanting patients with unfavourable tumor characteristics increases the risk of tumor recurrence and impacts post-transplant survival. Although tumor number and size are the basis of widely accepted selection criteria and correlate with tumor grading and microvascular invasion, stronger predictors of tumor recurrence have been recently identified...
2017: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28815037/elevated-serum-dand5-is-associated-with-metastasis-and-predicts-poor-prognosis-in-colorectal-cancer
#13
Xiaofei Miao, Ye Zhang, Jialin Sun, Songkui Cui, Qingyang Meng, Kuiyu Zhu, Xingqian Hu, Tong Wang
BACKGROUND: The biologic and clinical significance of DAND5 remains unknown in colorectal cancer (CRC). OBJECTIVE: Herein, we investigated the function of DAND5 and evaluated its clinical significance in both serum and matched primary tumors in patients with CRC. METHODS: The role of DAND5 was explored in CRC cells and clinical significance of DAND5 was investigated in CRC patients (n = 217) and healthy controls (n = 63). RESULTS: Knockdown of DAND5 significantly decreased CRC cell proliferation, migration and invasion partly associated with epithelial-mesenchymal transition phenotype...
August 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28814897/discordance-of-the-estrogen-receptor-and-her-2-neu-in-breast-cancer-from-primary-lesion-to-first-and-second-metastatic-site
#14
Elyse E Lower, Shagufta Khan, Diane Kennedy, Robert P Baughman
BACKGROUND: Hormone receptor and HER-2/neu discordance between the primary lesion and first metastasis has been reported. This study was performed to determine further biomarker discordance rates between the first and subsequent metastatic breast cancer lesions. METHODS: We performed a retrospective review of paired biomarkers from primary breast cancers compared to first reported and subsequent metastases from 103 patients with breast cancer. The estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu status were reported at all three time points...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28814834/intracellular-trafficking-of-new-anticancer-therapeutics-antibody-drug-conjugates
#15
REVIEW
Muhammad Kalim, Jie Chen, Shenghao Wang, Caiyao Lin, Saif Ullah, Keying Liang, Qian Ding, Shuqing Chen, Jinbiao Zhan
Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28814802/relationship-between-necrotic-patterns-in-glioblastoma-and-patient-survival-fractal-dimension-and-lacunarity-analyses-using-magnetic-resonance-imaging
#16
Shuai Liu, Yinyan Wang, Kaibin Xu, Zheng Wang, Xing Fan, Chuanbao Zhang, Shaowu Li, Xiaoguang Qiu, Tao Jiang
Necrosis is a hallmark feature of glioblastoma (GBM). This study investigated the prognostic role of necrotic patterns in GBM using fractal dimension (FD) and lacunarity analyses of magnetic resonance imaging (MRI) data and evaluated the role of lacunarity in the biological processes leading to necrosis. We retrospectively reviewed clinical and MRI data of 95 patients with GBM. FD and lacunarity of the necrosis on MRI were calculated by fractal analysis and subjected to survival analysis. We also performed gene ontology analysis in 32 patients with available RNA-seq data...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814670/mtg16-is-a-tumor-suppressor-in-colitis-associated-carcinoma
#17
Elizabeth M McDonough, Caitlyn W Barrett, Bobak Parang, Mukul K Mittal, J Joshua Smith, Amber M Bradley, Yash A Choksi, Lori A Coburn, Sarah P Short, Joshua J Thompson, Baolin Zhang, Shenika V Poindexter, Melissa A Fischer, Xi Chen, Jiang Li, Frank L Revetta, Rishi Naik, M Kay Washington, Michael J Rosen, Scott W Hiebert, Keith T Wilson, Christopher S Williams
MTG16 is a member of the myeloid translocation gene (MTG) family of transcriptional corepressors. While MTGs were originally identified in chromosomal translocations in acute myeloid leukemia, recent studies have uncovered a role in intestinal biology. For example, Mtg16-/- mice have increased intestinal proliferation and are more sensitive to intestinal injury in colitis models. MTG16 is also underexpressed in patients with moderate/severe ulcerative colitis. Based on these findings, we postulated that MTG16 might protect against colitis-associated carcinogenesis...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814433/personalized-medicine-based-approach-to-model-patterns-of-chemoresistance-and-tumor-recurrence-using-ovarian-cancer-stem-cell-spheroids
#18
Shreya Raghavan, Pooja Mehta, Maria W Ward, Michael E Bregenzer, Elyse M A Fleck, Lijun Tan, Karen McLean, Ronald Buckanovich, Geeta Mehta
PURPOSE: Chemoresistant ovarian cancers grow in suspension within the ascites fluid. In order to screen the effect of chemotherapeutics and biologics on resistant ovarian cancers with a personalized basis, we developed a 3D hanging drop spheroid platform. EXPERIMENTAL DESIGN: We initiated spheroids with primary ALDH+ CD133+ ovarian cancer stem cells (OvCSCs) from different patient samples, and demonstrated that stem cell progeny from harvested spheroids was similar to the primary tumor...
August 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28814331/circulating-levels-of-soluble-fas-scd95-are-associated-with-risk-for-development-of-a-nonresolving-acute-kidney-injury-subphenotype
#19
Pavan K Bhatraju, Cassianne Robinson-Cohen, Carmen Mikacenic, Susanna Harju-Baker, Victoria Dmyterko, Natalie S J Slivinski, W Conrad Liles, Jonathan Himmelfarb, Susan R Heckbert, Mark M Wurfel
BACKGROUND: Critically ill patients with acute kidney injury (AKI) can be divided into two subphenotypes, resolving or nonresolving, on the basis of the trajectory of serum creatinine. It is unknown if the biology underlying these two AKI recovery patterns is different. METHODS: We measured eight circulating biomarkers in plasma obtained from a cohort of patients admitted to an intensive care unit (ICU) (n = 1241) with systemic inflammatory response syndrome...
August 17, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28814085/differentially-regulated-adamts1-8-and-18-in-gastric-adenocarcinoma
#20
M O Kilic, B Aynekin, A Kara, D Icen, K Demircan
OBJECTIVE: The aim is to investigate the expression status of ADAMTS1,8, and 18 proteases in gastric cancer (GC) and lymphatic metastasis. BACKGROUND: A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) is a new protease family, and has important biological functions such as hemostasis, extracellular matrix remodeling and regulation of angiogenesis. METHODS: The immunostaining status of ADAMTS1,8, and 18 were investigated in formalin-fixed paraffin-embedded samples of 25 patients who underwent curative resection for GC...
2017: Bratislavské Lekárske Listy
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