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https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#1
Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#2
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813674/an-integrated-systems-biology-approach-identifies-trim25-as-a-key-determinant-of-breast-cancer-metastasis
#3
Logan A Walsh, Mariano J Alvarez, Erich Y Sabio, Marsha Reyngold, Vladimir Makarov, Suranjit Mukherjee, Ken-Wing Lee, Alexis Desrichard, Şevin Turcan, Martin G Dalin, Vinagolu K Rajasekhar, Shuibing Chen, Linda T Vahdat, Andrea Califano, Timothy A Chan
At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813596/molecular-imaging-of-p-glycoprotein-in-chemoresistant-tumors-using-a-dual-modality-pet-fluorescence-probe
#4
Mengzhe Wang, Chengqiong Mao, Hui Wang, Xueying Ling, Zhanhong Wu, Zi-Bo Li, Xin Ming
Overexpression of P-glycoprotein (Pgp) has been considered a primary cause for multidrug resistance in a variety of cancers for three decades. However, clinical translation of Pgp targeted therapeutics has been hindered by lack of patient preselection based on the Pgp presence in tumors. We aim to develop a molecularly targeted probe for imaging tumoral Pgp in vivo with positron emission tomography (PET) and fluorescence, and to provide a tool for preselecting the patients with tumoral Pgp expression. Thus, a Pgp monoclonal antibody 15D3 was chemically modified with IRDye800 (IR800) and DOTA chelator...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28813586/breast-cancer-and-exposure-to-aircraft-road-and-railway-noise-a-case-control-study-based-on-health-insurance-records
#5
Janice Hegewald, Melanie Schubert, Mandy Wagner, Patrik Dröge, Ursel Prote, Enno Swart, Ulrich Möhler, Hajo Zeeb, Andreas Seidler
Objectives Aircraft, road, and rail traffic noise can cause sleep disturbances. Since night work and shorter sleep durations have been linked to increased risks of breast cancer, we examined if 24-hour, or day- or night-time traffic noise exposure may also increase the risk of breast cancer. Methods To investigate the noise-related risks of breast cancer, the pseudonymized insurance records of three large statutory health companies (2005-2010) for women aged ≥40 years living in the region surrounding the Frankfurt international airport were analyzed with address-specific acoustic data representing aircraft, road, and rail-traffic noise...
August 16, 2017: Scandinavian Journal of Work, Environment & Health
https://www.readbyqxmd.com/read/28813438/heritability-estimation-using-a-regularized-regression-approach-herra-applicable-to-continuous-dichotomous-or-age-at-onset-outcome
#6
Malka Gorfine, Sonja I Berndt, Jenny Chang-Claude, Michael Hoffmeister, Loic Le Marchand, John Potter, Martha L Slattery, Nir Keret, Ulrike Peters, Li Hsu
The popular Genome-wide Complex Trait Analysis (GCTA) software uses the random-effects models for estimating the narrow-sense heritability based on GWAS data of unrelated individuals without knowing and identifying the causal loci. Many methods have since extended this approach to various situations. However, since the proportion of causal loci among the variants is typically very small and GCTA uses all variants to calculate the similarities among individuals, the estimation of heritability may be unstable, resulting in a large variance of the estimates...
2017: PloS One
https://www.readbyqxmd.com/read/28813191/effect-and-efficiency-of-an-embedded-palliative-care-nurse-practitioner-in-an-oncology-clinic
#7
Anne M Walling, Sarah F D'Ambruoso, Jennifer L Malin, Sara Hurvitz, Ann Zisser, Anne Coscarelli, Robin Clarke, Andrew Hackbarth, Christopher Pietras, Frances Watts, Bruce Ferrell, Samuel Skootsky, Neil S Wenger
PURPOSE: To test a simultaneous care model for palliative care for patients with advanced cancer by embedding a palliative care nurse practitioner (NP) in an oncology clinic. METHODS: We evaluated the effect of the intervention in two oncologists' clinics beginning March 2014 by using implementation strategies, including use of a structured referral mechanism, routine symptom screening, integration of a psychology-based cancer supportive care center, implementation team meetings, team training, and a metrics dashboard for continuous quality improvement...
August 16, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28812991/the-retinoblastoma-rb-tumor-suppressor-pushing-back-against-genome-instability-on-multiple-fronts
#8
REVIEW
Renier Vélez-Cruz, David G Johnson
The retinoblastoma (RB) tumor suppressor is known as a master regulator of the cell cycle. RB is mutated or functionally inactivated in the majority of human cancers. This transcriptional regulator exerts its function in cell cycle control through its interaction with the E2F family of transcription factors and with chromatin remodelers and modifiers that contribute to the repression of genes important for cell cycle progression. Over the years, studies have shown that RB participates in multiple processes in addition to cell cycle control...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28812972/barbershop-prostate-cancer-education-factors-associated-with-client-knowledge
#9
Barry C Hill, David R Black, Cleveland G Shields
The purpose of this paper is to identify characteristics of Black barbershop clients and barbers in an urban Midwestern city participating in a health promotion program called Affecting Cancer Together (ACT) that are associated with client knowledge about prostate cancer. Statistical analyses examined client and barber characteristics for their potential association with client prostate cancer knowledge, while controlling for ACT variables. Study findings suggested clients who are married (β = 0.99; CI [0...
September 2017: American Journal of Men's Health
https://www.readbyqxmd.com/read/28812918/tyrosine-kinase-inhibitors-for-advanced-or-metastatic-thyroid-cancer-a-meta-analysis-of-randomized-controlled-trials
#10
Jen-Wei Liu, Chiehfeng Chen, El-Wui Loh, Chun-Cheng Chu, Mu-Yi Wang, Hsin-Ju Ouyang, Ya-Ting Chang, Wei-Zhan Zhuang, Ching-Wen Chou, Der-Jr Huang, Chia-Hwa Lee, Yun Yen, Ka-Wai Tam
BACKGROUND AND AIMS: Radioiodine-refractory advanced or metastatic thyroid cancer has poor prognosis. We conducted a meta-analysis of randomized controlled trials to evaluate the effectiveness and safety of tyrosine kinase inhibitors (TKIs) for advanced or metastatic thyroid cancer treatment. METHODS: Studies published until April 2017 were selected. The pooled effect size was calculated through meta-analysis by using random effects models. Outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (RR), and adverse events (AEs)...
August 16, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28812721/predicting-evolution
#11
Michael Lässig, Ville Mustonen, Aleksandra M Walczak
The face of evolutionary biology is changing: from reconstructing and analysing the past to predicting future evolutionary processes. Recent developments include prediction of reproducible patterns in parallel evolution experiments, forecasting the future of individual populations using data from their past, and controlled manipulation of evolutionary dynamics. Here we undertake a synthesis of central concepts for evolutionary predictions, based on examples of microbial and viral systems, cancer cell populations, and immune receptor repertoires...
February 21, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812582/control-of-intestinal-stem-cell-function-and-proliferation-by-mitochondrial-pyruvate-metabolism
#12
John C Schell, Dona R Wisidagama, Claire Bensard, Helong Zhao, Peng Wei, Jason Tanner, Aimee Flores, Jeffrey Mohlman, Lise K Sorensen, Christian S Earl, Kristofor A Olson, Ren Miao, T Cameron Waller, Don Delker, Priyanka Kanth, Lei Jiang, Ralph J DeBerardinis, Mary P Bronner, Dean Y Li, James E Cox, Heather R Christofk, William E Lowry, Carl S Thummel, Jared Rutter
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation...
August 14, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28812429/metastatic-colon-adenocarcinoma-has-a-significantly-elevated-expression-of-il-10-compared-to-primary-colon-adenocarcinoma-tumors
#13
Michelle H Townsend, Abigail M Felsted, Stephen R Piccolo, Richard A Robison, Kim L O'Neill
Classical anti-inflammatory cytokines are known to play a role in both cancer progression as well as cancer elimination. We evaluated the anti-inflammatory cytokines IL-10 and TGF-β in patients with colon adenocarcinoma and metastatic colon adenocarcinoma utilizing immunohistochemical assays to determine the expression of the cytokines between various malignant tissues. We found tissues stained with TGF-β showed no significant upregulation within malignant tumors when compared to normal tissue controls. We observed high levels of TGF-β presence in most tissues similar to GAPDH expression...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28812391/ph-sensitive-polymersomes-controlling-swelling-via-copolymer-structure-and-chemical-composition
#14
Simone Villani, Renata Adami, Ernesto Reverchon, Anna Maria Ferretti, Alessandro Ponti, Marilena Lepretti, Ivana Caputo, Lorella Izzo
pH-sensitive vesicles used as drug delivery systems (DDSs) are generally composed of protonable copolymers. The disaggregation of these nanoparticles (NPs) during drug release implies the dispersion of positively charged cytotoxic polyelectrolytes in the human body. To alleviate such issue, we synthesised A(BC)n amphiphilic block copolymers with linear (n = 1) and branched (n = 2) architectures to obtain pH-sensitive vesicles capable of releasing drugs in acidic conditions via controlled swelling instead of disaggregation...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28812388/silk-nanoparticles-proof-of-lysosomotropic-anticancer-drug-delivery-at-single-cell-resolution
#15
John D Totten, Thidarat Wongpinyochit, F Philipp Seib
Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release is currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28812325/ambiguity-in-a-masculine-world-being-a-brca1-2-mutation-carrier-and-a-man-with-prostate-cancer
#16
C Moynihan, E K Bancroft, A Mitra, A Ardern-Jones, E Castro, E C Page, R A Eeles
BACKGROUND: Increased risk of prostate cancer(PCa) is observed in men with BRCA1/BRCA2 mutations. Sex and gender are key determinants of health and disease although unequal care exists between the sexes. Stereotypical male attitudes are shown to lead to poor health outcomes. METHODS: Men with BRCA1/2 mutations and diagnosed with PCa were identified and invited to participate in a qualitative interview study. Data were analysed using a Framework approach. 'Masculinity theory' was used to report the impact of having both a BRCA1/2 mutation and PCa...
August 15, 2017: Psycho-oncology
https://www.readbyqxmd.com/read/28812301/changing-treatment-paradigms-for-brain-metastases-from-melanoma-part-1-diagnosis-prognosis-symptom-control-and-local-treatment
#17
REVIEW
Vyshak Alva Venur, Pauline Funchain, Rupesh Kotecha, Samuel T Chao, Manmeet S Ahluwalia
Melanoma is the third most common cause of brain metastases, after lung and breast cancer. The management of melanoma brain metastases can be broadly divided into symptom control and therapeutic strategies. Supportive treatments include corticosteroids to reduce peritumoral edema, antiepileptics for seizure control, and medications to preserve cognitive function. Until recently, therapeutic strategies consisted primarily of local treatments, including surgery, whole-brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS)...
August 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28812120/risk-adapted-robotic-stereotactic-body-radiation-therapy-for-inoperable-early-stage-non-small-cell-lung-cancer
#18
Susanne Temming, Martin Kocher, Erich Stoelben, Lars Hagmeyer, De-Hua Chang, Konrad Frank, Khosro Hekmat, Juergen Wolf, Wolfgang W Baus, Robert Semrau, Christian Baues, S Marnitz
PURPOSE: To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients. METHODS: From 2012 to 2016, 106 patients (median age 74 years, range 50-94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent (18)F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy...
August 15, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28811977/epigenetic-regulation-of-the-extrinsic-oncosuppressor-ptx3-gene-in-inflammation-and-cancer
#19
Marcello Rubino, Paolo Kunderfranco, Gianluca Basso, Carolina Magdalen Greco, Fabio Pasqualini, Simone Serio, Massimo Roncalli, Luigi Laghi, Alberto Mantovani, Roberto Papait, Cecilia Garlanda
PTX3 is a component of the humoral arm of innate immunity and an extrinsic oncosuppressor gene taming tumor-promoting inflammation. Here, we show that two enhancers differently regulate PTX3 expression: enhancer 1, located 230 kb upstream of PTX3 promoter, mediated the action of inflammatory transcription factors; and enhancer 2, encompassing PTX3 second exon, was implicated in pre-initiation complex assembly. Polycomb repressive complex 2 silenced these regulatory elements and the promoter in basal condition...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811964/pd-l2-expression-in-colorectal-cancer-independent-prognostic-effect-and-targetability-by-deglycosylation
#20
Huanbin Wang, Han Yao, Chushu Li, Lunxi Liang, Yao Zhang, Hubing Shi, Chongzhi Zhou, Yingxuan Chen, Jing-Yuan Fang, Jie Xu
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46...
2017: Oncoimmunology
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