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https://www.readbyqxmd.com/read/28813705/the-lncrna-tug1-ezh2-axis-promotes-pancreatic-cancer-cell-proliferation-migration-and-emt-phenotype-formation-through-sponging-mir-382
#1
Liang Zhao, Hongwei Sun, Hongru Kong, Zongjing Chen, Bicheng Chen, Mengtao Zhou
BACKGROUND/AIMS: Pancreatic carcinoma (PC) is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1) was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of TUG1 in PC cell lines and tissues...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#2
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
#3
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
#4
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/28813665/lineage-restricted-mammary-stem-cells-sustain-the-development-homeostasis-and-regeneration-of-the-estrogen-receptor-positive-lineage
#5
Alexandra Van Keymeulen, Marco Fioramonti, Alessia Centonze, Gaëlle Bouvencourt, Younes Achouri, Cédric Blanpain
The mammary gland (MG) is composed of different cell lineages, including the basal and the luminal cells (LCs) that are maintained by distinct stem cell (SC) populations. LCs can be subdivided into estrogen receptor (ER)(+) and ER(-) cells. LCs act as the cancer cell of origin in different types of mammary tumors. It remains unclear whether the heterogeneity found in luminal-derived mammary tumors arises from a pre-existing heterogeneity within LCs. To investigate LC heterogeneity, we used lineage tracing to assess whether the ER(+) lineage is maintained by multipotent SCs or by lineage-restricted SCs...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813661/tissue-resident-macrophages-in-pancreatic-ductal-adenocarcinoma-originate-from-embryonic-hematopoiesis-and-promote-tumor-progression
#6
Yu Zhu, John M Herndon, Dorothy K Sojka, Ki-Wook Kim, Brett L Knolhoff, Chong Zuo, Darren R Cullinan, Jingqin Luo, Audrey R Bearden, Kory J Lavine, Wayne M Yokoyama, William G Hawkins, Ryan C Fields, Gwendalyn J Randolph, David G DeNardo
Tumor-associated macrophages (TAMs) are essential components of the cancer microenvironment and play critical roles in the regulation of tumor progression. Optimal therapeutic intervention requires in-depth understanding of the sources that sustain macrophages in malignant tissues. In this study, we investigated the ontogeny of TAMs in murine pancreatic ductal adenocarcinoma (PDAC) models. We identified both inflammatory monocytes and tissue-resident macrophages as sources of TAMs. Unexpectedly, significant portions of pancreas-resident macrophages originated from embryonic development and expanded through in situ proliferation during tumor progression...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813646/antihelminthic-drug-niclosamide-inhibits-cip2a-and-reactivates-tumor-suppressor-protein-phosphatase-2a-in-non-small-cell-lung-cancer-cells
#7
Myeong-Ok Kim, Min Ho Choe, Yi Na Yoon, Jiyeon Ahn, Minjin Yoo, Kwan-Young Jung, Sungkwan An, Sang-Gu Hwang, Jeong Su Oh, Jae-Sung Kim
Protein phosphatase 2A (PP2A) is a critical tumor suppressor complex responsible for the inactivation of various oncogenes. Recently, PP2A reactivation has emerged as an anticancer strategy. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous inhibitor of PP2A, is upregulated in many cancer cells, including non-small cell lung cancer (NSCLC) cells. We demonstrated that the antihelminthic drug niclosamide inhibited the expression of CIP2A and reactivated the tumor suppressor PP2A in NSCLC cells...
August 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28813596/molecular-imaging-of-p-glycoprotein-in-chemoresistant-tumors-using-a-dual-modality-pet-fluorescence-probe
#8
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
#9
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/28813488/role-of-post-chemotherapy-radiation-in-the-management-of-children-and-adolescents-with-primary-advanced-malignant-mediastinal-germ-cell-tumors
#10
Junting Huang, Yuting Tan, Zijun Zhen, Suying Lu, Feifei Sun, Jia Zhu, Juan Wang, Ru Liao, Xiaofei Sun
OBJECTIVE: Primary malignant mediastinal germ cell tumors (MMGCTs) are rare in children and adolescents and have a poorer prognosis than their gonadal counterparts. We report a single institutional experience of a 10-year period of primary advanced MMGCTs treated with chemotherapy, followed by radiotherapy in those who had residual mass. METHODS: Children and adolescents with primary advanced MMGCTs between 2005 and 2014 were identified from the Cancer Center, Sun Yat-Sen University...
2017: PloS One
https://www.readbyqxmd.com/read/28813196/hepatic-parenchymal-heterogeneity-as-a-marker-for-oxaliplatin-induced-sinusoidal-obstruction-syndrome-correlation-with-treatment-response-of-colorectal-cancer-liver-metastases
#11
Na Yeon Han, Beom Jin Park, Kyung Sook Yang, Min Ju Kim, Deuk Jae Sung, Ki Choon Sim, Sung Bum Cho
OBJECTIVE: The objective of our study was to evaluate the influence of oxaliplatin-based chemotherapy (OBC)-induced hepatic parenchymal heterogeneity detected on contrast-enhanced CT scans on response of liver metastasis. We chose to study hepatic parenchymal heterogeneity on the basis of the assumption that hepatic parenchymal heterogeneity may indicate the presence of chemotherapy-induced sinusoidal obstruction syndrome (SOS). MATERIALS AND METHODS: For this retrospective study, 104 patients with hepatic metastases from colorectal cancer (male-female ratio, 66:38; age range, 20-80 years) who had undergone OBC and serial CT studies were consecutively registered...
August 16, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28813180/inflammatory-signaling-cascades-and-autophagy-in-cancer
#12
Teresa Monkkonen, Jayanta Debnath
Tumor-associated inflammation is predictive of poor prognosis and drives a variety of tumorigenic phenotypes, including tumor proliferation and survival, angiogenesis, invasiveness, and metastasis. Here, we review mammalian data addressing the interaction of macroautophagy/autophagy with key signaling cascades associated with tumor inflammation. Although our understanding of this area remains incomplete, certain inflammatory pathways have emerged as important mediators of the crosstalk between autophagy and inflammation in tumors...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28813164/pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-results-from-the-phase-ib-keynote-028-study
#13
Patrick A Ott, Elena Elez, Sandrine Hiret, Dong-Wan Kim, Anne Morosky, Sanatan Saraf, Bilal Piperdi, Janice M Mehnert
Purpose The safety and efficacy of pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), were assessed in patients with programmed death ligand 1 (PD-L1)-expressing extensive-stage small-cell lung cancer (SCLC) in the multicohort, phase Ib open-label KEYNOTE-028 study ( ClinicalTrials.gov identifier: NCT02054806). Methods Patients with SCLC received pembrolizumab 10 mg/kg every 2 weeks for 24 months or until disease progression or intolerable toxicity occurred. PD-L1 expression was assessed by immunohistochemistry...
August 16, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28813020/nine-new-triterpene-glycosides-magnumosides-a%C3%A2-a%C3%A2-b%C3%A2-b%C3%A2-c%C3%A2-c%C3%A2-and-c%C3%A2-from-the-vietnamese-sea-cucumber-neothyonidium-massinium-magnum-structures-and-activities-against-tumor-cells-independently-and-in-synergy-with-radioactive-irradiation
#14
Alexandra S Silchenko, Anatoly I Kalinovsky, Sergey A Avilov, Vladimir I Kalinin, Pelageya V Andrijaschenko, Pavel S Dmitrenok, Ekaterina A Chingizova, Svetlana P Ermakova, Olesya S Malyarenko, Tatyana N Dautova
Nine new sulfated triterpene glycosides, magnumosides A₁ (1), A₂ (2), A₃ (3), A₄ (4), B₁ (5), B₂ (6), C₁ (7), C₂ (8) and C₄ (9) as well as a known colochiroside B₂ (10) have been isolated from the tropical Indo-West Pacific sea cucumber Neothynidium (=Massinium) magnum (Phyllophoridae, Dendrochirotida) collected in the Vietnamese shallow waters. The structures of new glycosides were elucidated by 2D NMR spectroscopy and mass-spectrometry. All the isolated new glycosides were characterized by the non-holostane type lanostane aglycones having 18(16)-lactone and 7(8)-double bond and differed from each other by the side chains and carbohydrate moieties structures...
August 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28813011/insights-into-the-effect-of-the-g245s-single-point-mutation-on-the-structure-of-p53-and-the-binding-of-the-protein-to-dna
#15
Marco Gaetano Lepre, Sara Ibrahim Omar, Gianvito Grasso, Umberto Morbiducci, Marco Agostino Deriu, Jack A Tuszynski
The transcription factor p53 is a potent tumor suppressor dubbed as the "guardian of the genome" because of its ability to orchestrate protective biological outputs in response to a variety of oncogenic stresses. Mutation and thus inactivation of p53 can be found in 50% of human tumors. The majority are missense mutations located in the DNA binding region. Among them, G245S is known to be a structural hotspot mutation. To understand the behaviors and differences between the wild-type and mutant, both a dimer of the wild type p53 (wt-p53) and its G245S mutant (G245S-mp53), complexed with DNA, were simulated using molecular dynamics for more than 1 μs...
August 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28812991/the-retinoblastoma-rb-tumor-suppressor-pushing-back-against-genome-instability-on-multiple-fronts
#16
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/28812986/epigenome-aberrations-emerging-driving-factors-of-the-clear-cell-renal-cell-carcinoma
#17
REVIEW
Ali Mehdi, Yasser Riazalhosseini
Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau (VHL) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28812983/a-microfluidic-platform-for-modeling-metastatic-cancer-cell-matrix-invasion
#18
Laura Blaha, Chentian Zhang, Mario Cabodi, Joyce Y Wong
Invasion of the extracellular matrix is a critical step in the colonization of metastatic tumors. The invasion process is thought to be driven by both chemokine signaling and interactions between invading cancer cells and physical components of the metastatic niche, including endothelial cells that line capillary walls and serve as a barrier to both diffusion and invasion of the underlying tissue. Transwell chambers, a tool for generating artificial chemokine gradients to induce cell migration, have facilitated recent work to investigate the chemokine contributions to matrix invasion...
August 16, 2017: Biofabrication
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#19
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28812429/metastatic-colon-adenocarcinoma-has-a-significantly-elevated-expression-of-il-10-compared-to-primary-colon-adenocarcinoma-tumors
#20
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
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