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https://www.readbyqxmd.com/read/29775456/maternal-obesogenic-diet-induces-endometrial-hyperplasia-an-early-hallmark-of-endometrial-cancer-in-a-diethylstilbestrol-mouse-model
#1
Theresa O Owuor, Michaela Reid, Lauren Reschke, Ian Hagemann, Suellen Greco, Zeel Modi, Kelle H Moley
Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain...
2018: PloS One
https://www.readbyqxmd.com/read/29772439/long-noncoding-rna-meg3-inhibits-proliferation-of-chronic-myeloid-leukemia-cells-by-sponging-microrna21
#2
Ziye Li, Lin Yang, Xiaojun Liu, Ziyuan Nie, Jianmin Luo
The long noncoding RNA (lnc) maternally expressed 3 (MEG3) is downregulated in many types of cancers. However, the relationship between lncRNA MEG3, microRNA-21 (miR-21) and chronic myeloid leukemia (CML) blast crisis is unknown. This study examined bone marrow samples from 40 CML patients and 10 healthy donors. Proliferation and apoptosis assays, real-time polymerase chain reaction (PCR), bisulfite sequencing PCR, Western blotting, luciferase assay, RNA pull-down, RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP) and Chromatin immunoprecipitation (ChIP) were performed...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29772266/pten-pdz-binding-domain-suppresses-mammary-carcinogenesis-in-the-mmtv-pymt-breast-cancer-model
#3
Mingfei Yan, Yubing Wang, Chi Wai Wong, Penelope Mei-Yu Or, Kin Lok Wong, Lisha Li, Alexander M Many, Hong Guan, Ui Soon Khoo, Andrew M Chan
Phosphatase and tension homolog (PTEN) is a potent tumor suppressor that possesses a PDZ-binding domain (PDZ-BD) at the end of its carboxyl terminus, whose functions during tumorigenesis remains unclear. Here, we crossed a mouse strain with germline deletion of PTEN PDZ-BD with MMTV-PyMT breast cancer model, and found that knockout (KO) mice display normal development of mammary glands, but have both increased breast tumorigenicity and lung metastasis. Orthotopic allograft experiments suggest the loss of PTEN PDZ-BD in breast cancer cells rather than in tumor microenvironment plays a prominent role in increasing tumor burden...
May 14, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29771009/primary-tumor-sidedness-is-an-independent-prognostic-marker-for-survival-in-metastatic-colorectal-cancer-results-from-a-large-retrospective-cohort-with-mutational-analysis
#4
Sophia C Kamran, Jeffrey W Clark, Hui Zheng, Darrell R Borger, Lawrence S Blaszkowsky, Jill N Allen, Eunice L Kwak, Jennifer Y Wo, Aparna R Parikh, Ryan D Nipp, Janet E Murphy, Lipika Goyal, Andrew X Zhu, A John Iafrate, Ryan B Corcoran, David P Ryan, Theodore S Hong
Recent reports demonstrate inferior outcomes associated with primary right-sided vs left-sided colorectal tumors in patients with metastatic colorectal cancer (mCRC). We sought to describe our experience with mCRC patients on whom we have molecular data to determine whether primary tumor sidedness was an independent prognostic marker for overall survival (OS). mCRC patients with documented primary tumor sidedness who received mutational profiling between 2009 and 2014 were identified (n = 367, median follow-up 30...
May 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29770616/prevalence-of-germline-brca-mutations-among-women-with-carcinoma-of-the-peritoneum-or-fallopian-tube
#5
Min Chul Choi, Jin Sik Bae, Sang Geun Jung, Hyun Park, Won Duk Joo, Seung Hun Song, Chan Lee, Ji Ho Kim, Ki Chan Lee, Sunghoon Lee, Je Ho Lee
OBJECTIVE: The aim of the present study was to assess the frequency of germline mutations in patients with peritoneal carcinoma (PC) or the fallopian tube carcinoma (FTC), using a multi-gene panel. METHODS: Twenty-six patients diagnosed with either PC or FTC between January 2013 and December 2016 were recruited consecutively. Germline DNA was sequenced using a 6-gene next generation sequencing (NGS) panel following genetic counseling. Surgico-medical information was obtained from hospital records...
March 26, 2018: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29770434/tumor-yap1-and-pten-expression-correlates-with-tumor-associated-myeloid-suppressor-cell-expansion-and-reduced-survival-in-colorectal-cancer
#6
Rong Yang, Ting-Ting Cai, Xiao-Jun Wu, Yi-Na Liu, Jia He, Xiao-Shi Zhang, Gang Ma, Jiang Li
The expansion of myeloid-derived suppressor cells (MDSCs) correlates with tumorigenesis in colorectal cancer (CRC). Here, we found a significant association between CD33+ MDSC number and YAP1 and PTEN levels in CRC patients (P < 0.05). Moreover, the CD33+ MDSCs, YAP1 and PTEN were identified as predictors for the prognosis of CRC patients (P < 0.05). Notably, CD33+ MDSCs were an independent survival predictor for CRC patients through a Cox model analysis. In vitro data determined that the expression levels of YAP1 and PTEN in CRC-derived cell lines were associated with CRC-derived MDSC induction, and the blockade of YAP1 and PTEN decreased CRC-derived MDSC induction...
May 16, 2018: Immunology
https://www.readbyqxmd.com/read/29770149/diffuse-gastric-ganglioneuromatosis-novel-presentation-of-pten-hamartoma-syndrome-case-report-and-review-of-gastric-ganglioneuromatous-proliferations-and-a-novel-pten-gene-mutation
#7
Alexander J Williams, Emily S Doherty, Michael H Hart, Douglas J Grider
Gastrointestinal ganglioneuromatous proliferations are rare, most often found in the colon, and are three types: polypoid ganglioneuromas, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. We present a case of diffuse ganglioneuromatosis in the posterior gastric wall in a nine-year-old female. To our knowledge, this is the first reported case of diffuse ganglioneuromatosis located in the stomach. Only six cases of gastric ganglioneuromatous proliferations have previously been reported, two in English and none were diffuse ganglioneuromatosis...
2018: Case Reports in Medicine
https://www.readbyqxmd.com/read/29769567/genomic-alterations-of-ground-glass-nodular-lung-adenocarcinoma
#8
Hyun Lee, Je-Gun Joung, Hyun-Tae Shin, Duk-Hwan Kim, Yujin Kim, Hojoong Kim, O Jung Kwon, Young Mog Shim, Ho Yun Lee, Kyung Soo Lee, Yoon-La Choi, Woong-Yang Park, D Neil Hayes, Sang-Won Um
In-depth molecular pathogenesis of ground-glass nodular lung adenocarcinoma has not been well understood. The objectives of this study were to identify genomic alterations in ground-glass nodular lung adenocarcinomas and to investigate whether viral transcripts were detected in these tumors. Nine patients with pure (n = 4) and part-solid (n = 5) ground-glass nodular adenocarcinomas were included. Six were females with a median age of 58 years. We performed targeted exon sequencing and RNA sequencing...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29767245/mir-142-5p-regulates-cd4-t-cells-in-human-non-small-cell-lung-cancer-through-pd-l1-expression-via-the-pten-pathway
#9
Jun Wan, Xiean Ling, Bin Peng, Guanggui Ding
The present study aimed to evaluate the function of microRNA (miR)-142-5p on cancer immunity to induce apoptosis in human non-small cell lung cancer (NSCLC) and its mechanism. miR-142-5p expression was upregulated, and CD4+ T cell levels were reduced in patients with NSCLC. Overexpression of miR-142-5p expression inhibited the cancer effects of CD4+ T cells on NSCLC cell lines, and downregulation of miR-142-5p increased the cancer effects of CD4+ T cells on NSCLC cell lines, compared with the control group...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29767231/bidirectional-modulation-of-insulin-action-by-reactive-oxygen-species-in-3t3%C3%A2-l1-adipocytes
#10
Mingfeng Ma, Yingyao Quan, Yong Li, Xu He, Jing Xiao, Meixiao Zhan, Wei Zhao, Yongjie Xin, Ligong Lu, Liangping Luo
Reactive oxygen species (ROS) serve an important role in glucose‑lipid metabolic regulation. In the present study, the results demonstrated that there was bidirectional regulation of insulin action in 3T3‑L1 adipocytes treated with ROS. Transient and acute ROS exposure improved insulin‑induced metabolic effects in 3T3‑L1 adipocytes. Hydrogen peroxide (H2O2), as a stable and diffusible ROS, diffused into adipocytes and altered intracellular redox homeostasis, resulting in oxidation and inactivation of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)...
May 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29765551/functional-significance-of-co-occurring-mutations-in-pik3ca-and-map3k1-in-breast-cancer
#11
Alvaro Avivar-Valderas, Robert McEwen, Amir Taheri-Ghahfarokhi, Larissa S Carnevalli, Elizabeth L Hardaker, Marcello Maresca, Kevin Hudson, Elizabeth A Harrington, Francisco Cruzalegui
The PI3Kα signaling pathway is frequently hyper-activated in breast cancer (BrCa), as a result of mutations/amplifications in oncogenes (e.g. HER2 ), decreased function in tumor suppressors (e.g. PTEN ) or activating mutations in key components of the pathway. In particular, activating mutations of PIK3CA (~45%) are frequently found in luminal A BrCa samples. Genomic studies have uncovered inactivating mutations in MAP3K1 (13-20%) and MAP2K4 (~8%), two upstream kinases of the JNK apoptotic pathway in luminal A BrCa samples...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765547/signature-program-a-platform-of-basket-trials
#12
Eric D Slosberg, Barinder P Kang, Julio Peguero, Matthew Taylor, Todd M Bauer, Donald A Berry, Fadi Braiteh, Alexander Spira, Funda Meric-Bernstam, Steven Stein, Sarina A Piha-Paul, August Salvado
Investigating targeted therapies can be challenging due to diverse tumor mutations and slow patient accrual for clinical studies. The Signature Program is a series of 8 phase 2, agent-specific basket protocols using a rapid study start-up approach involving no predetermined study sites. Each protocol evaluated 1 agent (buparlisib, dovitinib, binimetinib, encorafenib, sonidegib, BGJ398, ceritinib, or ribociclib) in patients with solid or hematologic malignancies and an actionable mutation. The primary endpoint of each study was the clinical benefit rate (ie, complete or partial response, or stable disease) at 16 weeks...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765535/effects-of-cb2-and-trpv1-receptors-stimulation-in-pediatric-acute-t-lymphoblastic-leukemia
#13
Francesca Punzo, Iolanda Manzo, Chiara Tortora, Elvira Pota, Velia D' Angelo, Giulia Bellini, Alessandra Di Paola, Federica Verace, Fiorina Casale, Francesca Rossi
T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy. The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells, therefore we chose to selectively stimulate CB2 and TRPV1...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765523/overexpressing-tpte2-tpip-a-homolog-of-the-human-tumor-suppressor-gene-pten-rescues-the-abnormal-phenotype-of-the-pten-mutant
#14
Daniel F Lusche, Emma C Buchele, Kanoe B Russell, Benjamin A Soll, Michele I Vitolo, Michael R Klemme, Deborah J Wessels, David R Soll
One possible approach to normalize mutant cells that are metastatic and tumorigenic, is to upregulate a functionally similar homolog of the mutated gene. Here we have explored this hypothesis by generating an overexpressor of TPTE2 ( TPIP ), a homolog of PTEN , in PTEN-/- mutants, the latter generated by targeted mutagenesis of a human epithelial cell line. Overexpression of TPTE2 normalized phenotypic changes associated with the PTEN mutation. The PTEN-/- -associated changes rescued by overexpressing TPTE2 included 1) accelerated wound healing in the presence or absence of added growth factors (GFs), 2) increased division rates on a 2D substrate in the presence of GFs, 3) adhesion and viability on a 2D substrate in the absence of GFs, 4) viability in a 3D Matrigel model in the absence of GFs and substrate adhesion 5) loss of apoptosis-associated annexin V cell surface binding sites...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765153/cox-2-mediates-pro-tumorigenic-effects-of-pkc%C3%AE%C2%B5-in-prostate-cancer
#15
Rachana Garg, Jorge M Blando, Carlos J Perez, Priti Lal, Michael D Feldman, Emer M Smyth, Emanuela Ricciotti, Tilo Grosser, Fernando Benavides, Marcelo G Kazanietz
The pro-oncogenic kinase PKCε is overexpressed in human prostate cancer and cooperates with loss of the tumor suppressor Pten for the development of prostatic adenocarcinoma. However, the effectors driving PKCε-mediated phenotypes remain poorly defined. Here, using cellular and mouse models, we showed that PKCε overexpression acts synergistically with Pten loss to promote NF-κB activation and induce cyclooxygenase-2 (COX-2) expression, phenotypic traits which are also observed in human prostate tumors. Targeted disruption of PKCε from prostate cancer cells impaired COX-2 induction and PGE2 production...
May 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29763381/the-mfge8-%C3%AE-8%C3%AE-1-pten-pathway-regulates-airway-smooth-muscle-contraction-in-allergic-inflammation
#16
Amin Khalifeh-Soltani, Deepti Gupta, Arnold Ha, Michael J Podolsky, Ritwik Datta, Kamran Atabai
Asthma affects ∼300 million people worldwide. Despite multiple treatment options, asthma treatment remains unsatisfactory in a subset of patients. Airway obstruction is a hallmark of allergic asthma and is largely due to airway smooth muscle hypercontractility induced by airway inflammation. Identification of molecular pathways that regulate airway smooth muscle hypercontractility is of considerable therapeutic interest. We previously identified roles for milk fat globule epidermal growth factor-like 8 (Mfge8) in opposing the effects of allergic inflammation on increasing airway smooth muscle contractile force...
May 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29762822/linc-ror-promotes-endometrial-cell-proliferation-by-activating-the-pi3k-akt-pathway
#17
X-Y Xu, J Zhang, Y-H Qi, M Kong, S-A Liu, J-J Hu
OBJECTIVE: To observe the expressions of Linc-ROR and proteins in the PI3K-Akt pathway in an ectopic lesion of adenomyosis. PATIENTS AND METHODS: The expression of Linc-ROR in the ectopic endometrium, eutopic endometrium, and normal endometrium of adenomyosis was detected by qRT-PCR. Western blot was used to detect the protein expressions of PI3K-Akt in endometriosis and lesion endometriosis. Cell counting kit-8 (CCK-8) assay was utilized to detect cell proliferative activity...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29762619/isolation-and-genome-sequencing-of-individual-circulating-tumor-cells-using-hydrogel-encapsulation-and-laser-capture-microdissection
#18
Emily S Park, Justin P Yan, Richard A Ang, Jeong Hyun Lee, Xiaoyan Deng, Simon P Duffy, Kevin Beja, Matti Annala, Peter C Black, Kim N Chi, Alexander W Wyatt, Hongshen Ma
Circulating tumor cells (CTCs) are malignant cells released into the bloodstream with the potential to form metastases in secondary sites. These cells, acquired non-invasively, represent a sample of highly relevant tumor tissue that is an alternative to difficult and low-yield tumor biopsies. In recent years, there has been growing interest in genomic profiling of CTCs to enable longitudinal monitoring of the tumor's adaptive response to therapy. However, due to their extreme rarity, genotyping CTCs has proved challenging...
May 15, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29757152/dynamic-seesaw-model-for-rapid-signaling-responses-in-eukaryotic-chemotaxis
#19
Shiliang Feng, Lvwen Zhou, ShouQin Lü, Yan Zhang
Directed movement of eukaryotic cells toward spatiotemporally varied chemotactic stimuli enables rapid intracellular signaling responses. While macroscopic cellular manifestation is shaped by balancing external stimuli strength with finite internal delays, the organizing principles of the underlying molecular mechanisms remain to be clarified. Here, we developed a novel modeling framework based on a simple seesaw mechanism to elucidate how cells repeatedly reverse polarity. As a key feature of the modeling, the bottom module of bidirectional molecular transport is successively controlled by three upstream modules of signal reception, initial signal processing, and Rho GTPase regulation...
May 14, 2018: Physical Biology
https://www.readbyqxmd.com/read/29754406/targeting-twist1-through-loss-of-function-inhibits-tumorigenicity-of-human-glioblastoma
#20
Andrei M Mikheev, Svetlana A Mikheeva, Liza J Severs, Cory C Funk, Lei Huang, José L McFaline-Figueroa, Jeanette Schwensen, Cole Trapnell, Nathan D Price, Stephen Wong, Robert C Rostomily
Twist1 (TW) is a bHLH transcription factor (TF) and master regulator of the epithelial to mesenchymal transition (EMT). In vitro, TW promotes mesenchymal change, invasion and self-renewal in glioblastoma (GBM) cells. However the potential therapeutic relevance of TW has not been established through loss of function studies in human GBM cell xenograft models. The effects of TW loss of function (gene editing and knock down) on inhibition of tumorigenicity of U87MG and GBM4 glioma stem cells were tested in orthotopic xenograft models and conditional knockdown in established flank xenograft tumors...
May 13, 2018: Molecular Oncology
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