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https://www.readbyqxmd.com/read/28921987/a-novel-aryl-urea-fatty-acid-that-targets-the-mitochondrion-and-depletes-cardiolipin-to-promote-killing-of-breast-cancer-cells
#1
Tristan Rawling, Hassan Choucair, Nooshin Koolaji, Kirsi Bourget, Sarah E Allison, Yong-Juan Chen, Colin R Dunstan, Michael Murray
Cancer cell mitochondria are promising anticancer drug targets because they control cell death and are structurally and functionally different from normal cell mitochondria. We synthesized aryl-urea fatty acids and found that the analogue 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid (13b) decreased proliferation and activated apoptosis in MDA-MB-231 breast cancer cells in vitro and in vivo. In mechanistic studies 13b emerged as the prototype of a novel class of mitochondrion-targeted agents that deplete cardiolipin and promote cancer cell death...
September 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28921573/contralateral-breast-cancers-independent-cancers-or-metastases
#2
Colin B Begg, Irina Ostrovnaya, Felipe C Geyer, Anastasios D Papanastasiou, Charlotte Ky Ng, Rita Sakr, Jonine L Bernstein, Kathleen A Burke, Tari A King, Salvatore Piscuoglio, Audrey Mauguen, Irene Orlow, Britta Weigelt, Venkatraman E Seshan, Monica Morrow, Jorge S Reis-Filho
A cancer in the contralateral breast in a woman with a previous or synchronous breast cancer is typically considered to be an independent primary tumor. Emerging evidence suggests that in a small subset of these cases the second tumor represents a metastasis. We sought to investigate the issue using massively parallel sequencing targeting 254 genes recurrently mutated in breast cancer. We examined the tumor archives at Memorial Sloan Kettering Cancer Center for the period 1995-2006 to identify cases of contralateral breast cancer where surgery for both tumors was performed at the Center...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28919776/safety-pharmacokinetics-and-pharmacodynamics-of-oral-omaveloxolone-rta-408-a-synthetic-triterpenoid-in-a-first-in-human-trial-of-patients-with-advanced-solid-tumors
#3
Ben C Creelan, Dmitry I Gabrilovich, Jhanelle E Gray, Charles C Williams, Tawee Tanvetyanon, Eric B Haura, Jeffrey S Weber, Geoffrey T Gibney, Joseph Markowitz, Joel W Proksch, Scott A Reisman, Mark D McKee, Melanie P Chin, Colin J Meyer, Scott J Antonia
BACKGROUND: Omaveloxolone is a semisynthetic oleanane triterpenoid that potently activates Nrf2 with subsequent antioxidant function. We conducted a first-in-human Phase I clinical trial (NCT02029729) with the primary objectives to determine the appropriate dose for Phase II studies, characterize pharmacokinetic and pharmacodynamic parameters, and assess antitumor activity. METHODS: Omaveloxolone was administered orally once daily continuously in a 28-day cycle for patients with stage 4 relapsed/refractory melanoma or non-small cell lung cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28916400/assessing-changes-in-the-activity-levels-of-breast-cancer-patients-during-radiation-therapy
#4
Colin E Champ, Nitin Ohri, Rainer J Klement, Matthew Cantor, Sushil Beriwal, Scott M Glaser, Ryan P Smith
BACKGROUND: Radiation therapy (RT) is often delivered after lumpectomy for women with breast cancer. A common perceived side effect of RT is fatigue, yet its exact effect on activity levels and sleep is unknown. In this study we analyzed the change in activity levels and sleep using an activity tracking device before, during, and after RT for women with early stage breast cancer and ductal carcinoma in situ who underwent adjuvant RT. PATIENTS AND METHODS: After institutional review board approval, activity levels were quantified before, during, and after RT with measurements of steps, miles walked, calories burned, and sleep metrics in 10 women fitted with activity trackers...
August 24, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28912487/cscape-a-tool-for-predicting-oncogenic-single-point-mutations-in-the-cancer-genome
#5
Mark F Rogers, Hashem A Shihab, Tom R Gaunt, Colin Campbell
For somatic point mutations in coding and non-coding regions of the genome, we propose CScape, an integrative classifier for predicting the likelihood that mutations are cancer drivers. Tested on somatic mutations, CScape tends to outperform alternative methods, reaching 91% balanced accuracy in coding regions and 70% in non-coding regions, while even higher accuracy may be achieved using thresholds to isolate high-confidence predictions. Positive predictions tend to cluster in genomic regions, so we apply a statistical approach to isolate coding and non-coding regions of the cancer genome that appear enriched for high-confidence predicted disease-drivers...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904067/whole-genome-sequencing-reveals-breast-cancers-with-mismatch-repair-deficiency
#6
Helen Davies, Sandro Morganella, Colin A Purdie, Se Jin Jang, Elin Borgen, Hege Russnes, Dominik Glodzik, Xueqing Zou, Alain Viari, Andrea L Richardson, Anne-Lise Børresen-Dale, Alastair Thompson, Jorunn E Eyfjord, Gu Kong, Michael R Stratton, Serena Nik-Zainal
Mismatch repair (MMR)-deficient cancers have been discovered to be highly responsive to immune therapies such as PD-1 checkpoint blockade, making their definition in patients, where they may be relatively rare, paramount for treatment decisions. In this study, we utilized patterns of mutagenesis known as mutational signatures, which are imprints of the mutagenic processes associated with MMR deficiency, to identify MMR-deficient breast tumors from a whole-genome sequencing dataset comprising a cohort of 640 patients...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28899863/a-unified-approach-to-targeting-the-lysosome-s-degradative-and-growth-signaling-roles
#7
Vito W Rebecca, Michael C Nicastri, Noel McLaughlin, Colin Fennelly, Quentin McAfee, Amruta Ronghe, Michel Nofal, Chun-Yan Lim, Eric Witze, Cynthia I Chude, Gao Zhang, Gretchen M Alicea, Shengfu Piao, Sengottuvelan Murugan, Rani Ojha, Samuel M Levi, Zhi Wei, Julie S Barber-Rotenberg, Maureen E Murphy, Gordon B Mills, Yiling Lu, Joshua Rabinowitz, Ronen Marmorstein, Qin Liu, Shujing Liu, Xiaowei Xu, Meenhard Herlyn, Roberto Zoncu, Donita C Brady, David W Speicher, Jeffrey D Winkler, Ravi K Amaravadi
Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e. autophagy and macropinocytosis), while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQs) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy...
September 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28898700/muc1-and-hif-1alpha-signaling-crosstalk-induces-anabolic-glucose-metabolism-to-impart-gemcitabine-resistance-to-pancreatic-cancer
#8
Surendra K Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V Chaika, Enza Vernucci, Ryan J King, Jaime Abrego, Gennifer D Goode, Aneesha Dasgupta, Alysha L Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J Augustine, Divya Murthy, Kuldeep S Attri, Oksana Mashadova, Paul M Grandgenett, Robert Powers, Quan P Ly, Audrey J Lazenby, Jean L Grem, Fang Yu, José M Matés, John M Asara, Jung-Whan Kim, Jordan H Hankins, Colin Weekes, Michael A Hollingsworth, Natalie J Serkova, Aaron R Sasson, Jason B Fleming, Jennifer M Oliveto, Costas A Lyssiotis, Lewis C Cantley, Lyudmyla Berim, Pankaj K Singh
No abstract text is available yet for this article.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28890819/the-role-of-induction-chemotherapy-chemoradiotherapy-in-localised-pancreatic-cancer-initial-experience-in-scotland
#9
Derek Grose, David McIntosh, Nigel Jamieson, Ross Carter, Euan Dickson, David Chang, Husam Marashi, Christina Wilson, Mohammed Alfayez, Ashleigh Kerr, Roisin O'Donoghue, Lea Haskins, Fraser Duthie, Colin J McKay, Janet Graham
BACKGROUND: Despite being relatively rare pancreatic cancer is one of the highest causes of death. Even within the potentially resectable group outcomes are poor. We present our initial experiences utilising a neoadjuvant approach to localised pancreatic cancer, evaluating survival, response rates and tolerability. METHODS: This was a retrospective analysis of a prospectively maintained database. Patients from 2012 to 2015 referred to a busy regional Hepato-Pancreatic Biliary (HPB) MDT were included...
August 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28887438/-silencing-of-retrotransposons-by-setdb1-inhibits-the-interferon-response-in-acute-myeloid-leukemia
#10
Trinna L Cuellar, Anna-Maria Herzner, Xiaotian Zhang, Yogesh Goyal, Colin Watanabe, Brad A Friedman, Vasantharajan Janakiraman, Steffen Durinck, Jeremy Stinson, David Arnott, Tommy K Cheung, Subhra Chaudhuri, Zora Modrusan, Jonas Martin Doerr, Marie Classon, Benjamin Haley
A propensity for rewiring genetic and epigenetic regulatory networks, thus enabling sustained cell proliferation, suppression of apoptosis, and the ability to evade the immune system, is vital to cancer cell propagation. An increased understanding of how this is achieved is critical for identifying or improving therapeutic interventions. In this study, using acute myeloid leukemia (AML) human cell lines and a custom CRISPR/Cas9 screening platform, we identify the H3K9 methyltransferase SETDB1 as a novel, negative regulator of innate immunity...
September 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28882662/the-hyperlipidemia-effect-pseudohyponatremia-in-pancreatic-cancer
#11
Michael L Adashek, Bennett W Clark, John C Sperati, Colin J Massey
No abstract text is available yet for this article.
September 4, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28872778/effects-of-thiazolidinedione-in-patients-with-active-bladder-cancer
#12
Roger Li, Michael J Metcalfe, J E Ferguson Rd, Sharada Mokkapati, Graciela M Nogueras González, Colin P Dinney, Neema Navai, David J McConkey, Sunil K Sahai, Ashish M Kamat
OBJECTIVE: To examine the influence of perioperative thiazolidinedione (TZD) on cancer-specific outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma (UC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort of 173 diabetic patients undergoing RC from 2005 to 2010 was identified. Of those, 53 were on TZD treatment at the time of surgery, with 33 patients taking pioglitazone. Baseline clincopathologic characteristics, as well as cancer specific survival (CSS), recurrence free survival (RFS), and overall survival (OS) were compared between the patients on and off of TZD at the time of RC...
September 5, 2017: BJU International
https://www.readbyqxmd.com/read/28868260/tpoab-and-thyroid-function-are-not-associated-with-breast-cancer-outcome-evidence-from-a-large-scale-study-using-data-from-the-taxotere-as-adjuvant-chemotherapy-trial-tact-cruk01-001
#13
Ilaria Muller, Lucy S Kilburn, Peter N Taylor, Peter J Barrett-Lee, Judith M Bliss, Paul Ellis, Marian E Ludgate, Colin M Dayan
BACKGROUND: Small-scale studies correlated the presence of thyroid autoimmunity with both improved or worsened breast cancer outcome. OBJECTIVES: We aimed to clarify this association in a large cohort using the phase III, randomized, controlled Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001). METHODS: TACT women >18 years old with node-positive or high-risk node-negative early breast cancer (pT1-3a, pN0-1, M0), with stored plasma (n = 1,974), taken 15...
July 2017: European Thyroid Journal
https://www.readbyqxmd.com/read/28864460/a-germline-fanca-alteration-that-is-associated-with-increased-sensitivity-to-dna-damaging-agents
#14
David C Wilkes, Verena Sailer, Hui Xue, Hongwei Cheng, Colin C Collins, Martin Gleave, Yuzhuo Wang, Francesca Demichelis, Himisha Beltran, Mark A Rubin, David S Rickman
Defects in genes involved in DNA damage repair (DDR) pathway are emerging as novel biomarkers and targets for new prostate cancer drug therapies. A previous report revealed an association between an exceptional response to cisplatin treatment and a somatic loss of heterozygosity (LOH) of FANCA in a patient with metastatic prostate cancer who also harbored a germline FANCA variant (S1088F). Although germline FANCA mutations are the most frequent alterations in patients with Fanconi anemia, germline alterations are less common in prostate cancer...
September 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28860112/risk-factors-for-falls-in-older-patients-with-cancer
#15
Xiaotao Zhang, Ming Sun, Suyu Liu, Cheuk Hong Leung, Linda Pang, Uday R Popat, Richard Champlin, Holly M Holmes, Vicente Valero, Colin P Dinney, Debu Tripathy, Beatrice J Edwards
OBJECTIVES: A rising number of patients with cancer are older adults (65 years of age and older), and this proportion will increase to 70% by the year 2020. Falls are a common condition in older adults. We sought to assess the prevalence and risk factors for falls in older patients with cancer. METHODS: This is a single-site, retrospective cohort study. Patients who were receiving cancer care underwent a comprehensive geriatric assessments, including cognitive, functional, nutritional, physical, falls in the prior 6 months and comorbidity assessment...
August 31, 2017: BMJ Supportive & Palliative Care
https://www.readbyqxmd.com/read/28856078/participating-in-an-international-stereotactic-radiotherapy-patient-registry-the-establishment-of-data-collection-pathways
#16
Aylin Yahya, Eva Arneric, Elizabeth Kernutt, Fiona Baldacchino, Claire Haworth, Mary-Anne Kedda, Colin Tang, Sean Bydder, Tammy Corica
Aim To describe data collection pathways and practical challenges experienced by an academic comprehensive cancer centre aiming to record clinical data for patients being treated with a novel radiotherapy treatment modality. Methods Various options to capture data from all patients treated with the CyberKnife Robotic Radiosurgery System at Sir Charles Gairdner Hospital (SCGH) in Western Australia were explored. An international multicenter web-based secure database established and maintained by the Radiosurgery Society the RSSearch® Patient Registry was selected...
June 29, 2017: Curēus
https://www.readbyqxmd.com/read/28842510/impact-of-therapy-on-genomics-and-transcriptomics-in-high-risk-prostate-cancer-treated-with-neoadjuvant-docetaxel-and-androgen-deprivation-therapy
#17
Himisha Beltran, Alexander W Wyatt, Edmund Chedgy, Adam Donoghue, Matti Annala, Evan Warner, Kevin Beja, Michael Sigouros, Fan Mo, Ladan Fazli, Colin C Collins, James A Eastham, Michael J Morris, Mary-Ellen Taplin, Andrea Sboner, Susan Halabi, Martin E Gleave
BACKGROUND: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued Phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify predictive biomarkers. METHODS: We evaluated baseline clinical data, needle biopsies and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center...
August 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28835501/inherited-chromosomally-integrated-human-herpesvirus-6-genomes-are-ancient-intact-and-potentially-able-to-reactivate-from-telomeres
#18
Enjie Zhang, Adam J Bell, Gavin S Wilkie, Nicolás M Suárez, Chiara Batini, Colin D Veal, Isaac Armendáriz-Castillo, Rita Neumann, Victoria E Cotton, Yan Huang, David J Porteous, Ruth F Jarrett, Andrew J Davison, Nicola J Royle
The genomes of human herpesviruses 6A and 6B (HHV-6A and HHV-6B) have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. About 1% of people worldwide are carriers of chromosomally integrated HHV-6 (ciHHV-6), which is inherited as a genetic trait. Understanding the consequences of integration for the evolution of the viral genome, for the telomere and for the risk of disease associated with carrier status is hampered by a lack of knowledge about ciHHV-6 genomes...
August 23, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28834453/intravesical-rad-ifn%C3%AE-syn3-for-patients-with-high-grade-bacillus-calmette-guerin-refractory-or-relapsed-non-muscle-invasive-bladder-cancer-a-phase-ii-randomized-study
#19
Neal D Shore, Stephen A Boorjian, Daniel J Canter, Kenneth Ogan, Lawrence I Karsh, Tracy M Downs, Leonard G Gomella, Ashish M Kamat, Yair Lotan, Robert S Svatek, Trinity J Bivalacqua, Robert L Grubb, Tracey L Krupski, Seth P Lerner, Michael E Woods, Brant A Inman, Matthew I Milowsky, Alan Boyd, F Peter Treasure, Gillian Gregory, David G Sawutz, Seppo Yla-Herttuala, Nigel R Parker, Colin P N Dinney
Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials...
August 23, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28811957/mapping-the-human-t-cell-repertoire-to-recurrent-driver-mutations-in-myd88-and-ezh2-in-lymphoma
#20
Julie S Nielsen, Andrew R Chang, Darin A Wick, Colin G Sedgwick, Zusheng Zong, Andrew J Mungall, Spencer D Martin, Natalie N Kinloch, Susann Ott-Langer, Zabrina L Brumme, Steven P Treon, Joseph M Connors, Randy D Gascoyne, John R Webb, Brian R Berry, Ryan D Morin, Nicol Macpherson, Brad H Nelson
Oncogenic "driver" mutations are theoretically attractive targets for the immunotherapy of lymphoid cancers, yet the proportion that can be recognized by T cells remains poorly defined. To address this issue without any confounding effects of the patient's immune system, we assessed T cells from 19 healthy donors for recognition of three common driver mutations in lymphoma: MYD88(L265P), EZH2(Y641F) , and EZH2(Y641N) . Donors collectively expressed the 10 most prevalent HLA class I alleles, including HLA-A*02:01...
2017: Oncoimmunology
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