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Jing Tong, Shan Mou, Lingyun Xiong, Zhenxing Wang, Rongrong Wang, Annika Weigand, Quan Yuan, Raymund E Horch, Jiaming Sun, Jie Yang
Lipotransfer has been applied in breast augmentation surgery for several years and the resident adipose-derived stem cells (ASCs) play an important role in enhancing fat graft survival. However, the interaction between ASCs and mammary epithelium is not fully understood. Many studies have shown that ASCs have a tumor-supportive effect in breast cancer. To the best of our knowledge, this is the first study on the effect of mammary epithelial cells on the human ASCs in 3D culture. ASCs were cultivated on matrigel in the conditioned medium (CM) prepared from a human breast epithelial cell line (HBL-100)...
2018: PloS One
Yeji An, Jessica R Adams, Daniel P Hollern, Anthony Zhao, Stephen G Chang, Miki S Gams, Philip E D Chung, Xiaping He, Rhea Jangra, Juhi S Shah, Joanna Yang, Lauren A Beck, Nandini Raghuram, Katelyn J Kozma, Amanda J Loch, Wei Wang, Cheng Fan, Susan J Done, Eldad Zacksenhaus, Cynthia J Guidos, Charles M Perou, Sean E Egan
CDH1 and PIK3CA are the two most frequently mutated genes in invasive lobular carcinoma (ILC) of the breast. Transcription profiling has identified molecular subtypes for ILC, one of which, immune-related (IR), is associated with gene expression linked to lymphocyte and macrophage infiltration. Here, we report that deletion of Cdh1, together with activation of Pik3ca in mammary epithelium of genetically modified mice, leads to formation of IR-ILC-like tumors with immune cell infiltration, as well as gene expression linked to T-regulatory (Treg) cell signaling and activation of targetable immune checkpoint pathways...
October 16, 2018: Cell Reports
Jason J Pitt, Markus Riester, Yonglan Zheng, Toshio F Yoshimatsu, Ayodele Sanni, Olayiwola Oluwasola, Artur Veloso, Emma Labrot, Shengfeng Wang, Abayomi Odetunde, Adeyinka Ademola, Babajide Okedere, Scott Mahan, Rebecca Leary, Maura Macomber, Mustapha Ajani, Ryan S Johnson, Dominic Fitzgerald, A Jason Grundstad, Jigyasa H Tuteja, Galina Khramtsova, Jing Zhang, Elisabeth Sveen, Bryce Hwang, Wendy Clayton, Chibuzor Nkwodimmah, Bisola Famooto, Esther Obasi, Victor Aderoju, Mobolaji Oludara, Folusho Omodele, Odunayo Akinyele, Adewunmi Adeoye, Temidayo Ogundiran, Chinedum Babalola, Kenzie MacIsaac, Abiodun Popoola, Michael P Morrissey, Lin S Chen, Jiebiao Wang, Christopher O Olopade, Adeyinka G Falusi, Wendy Winckler, Kerstin Haase, Peter Van Loo, John Obafunwa, Dimitris Papoutsakis, Oladosu Ojengbede, Barbara Weber, Nasiru Ibrahim, Kevin P White, Dezheng Huo, Olufunmilayo I Olopade, Jordi Barretina
Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 - tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation-indicating aggressive biology...
October 16, 2018: Nature Communications
Han-Wei Lin, Chi-Feng Fu, Ming-Cheng Chang, Tzu-Pin Lu, Hsiu-Ping Lin, Ying-Cheng Chiang, Chi-An Chen, Wen-Fang Cheng
AIM: To investigate the CDH1, DLEC1 and SFRP5 gene methylation panel for advanced epithelial ovarian carcinoma (EOC). MATERIALS & METHODS: One hundred and seventy-seven advanced EOC specimens were evaluated by methylation-specific PCR. We also used The Cancer Genome Atlas dataset to evaluate the panel. RESULTS: The presence of two or more methylated genes was significant in recurrence (hazard ratio [HR]: 1.91 [1.33-2.76]; p = 0.002) and death (HR: 1...
October 16, 2018: Epigenomics
Kristy Lee, Kate Krempely, Maegan E Roberts, Michael J Anderson, Fatima Carneiro, Elizabeth Chao, Katherine Dixon, Joana Figueiredo, Rajarshi Ghosh, David Huntsman, Pardeep Kaurah, Chimene Kesserwan, Tyler Landrith, Shuwei Li, Arjen R Mensenkamp, Carla Oliveira, Carolina Pardo, Tina Pesaran, Matthew Richardson, Thomas P Slavin, Amanda B Spurdle, Mackenzie Trapp, Leora Witkowski, Charles S Yi, Liying Zhang, Sharon E Plon, Kasmintan A Schrader, Rachid Karam
The variant curation guidelines published in 2015 by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) provided the genetics community with a framework to assess variant pathogenicity; however, these rules are not gene specific. Germline pathogenic variants in the CDH1 gene cause hereditary diffuse gastric cancer and lobular breast cancer, a clinically challenging cancer predisposition syndrome that often requires a multidisciplinary team of experts to be properly managed...
November 2018: Human Mutation
Florian Obermair, Melanie Rammer, Jonathan Burghofer, Theodora Malli, Anna Schossig, Katharina Wimmer, Wolfgang Kranewitter, Beate Mayrbaeurl, Hans-Christoph Duba, Gerald Webersinke
Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominantly inherited cancer syndrome associated with a high risk for diffuse gastric and lobular breast cancer, caused by heterozygous CDH1 germline mutations. Of note, also cleft lip/palate (CLP) has been described in few HDGC families. Here we report on an extensive pedigree presenting with HDGC, CLP and a CDH1 splice site mutation (c.687 + 1G > A) and review the literature for families with CDH1 mutations, HDGC and CLP. Transcript analysis showed that the c...
October 10, 2018: Familial Cancer
Xu Liang, Adrien Briaux, Véronique Becette, Camille Benoist, Anais Boulai, Walid Chemlali, Anne Schnitzler, Sylvain Baulande, Sofia Rivera, Marie-Ange Mouret-Reynier, Laurence Venat Bouvet, Thibaut De La Motte Rouge, Jérôme Lemonnier, Florence Lerebours, Céline Callens
BACKGROUND: Postmenopausal women with large, hormone receptor (HR)-positive/HER2-negative and low-proliferative breast cancer derived a benefit from neoadjuvant endocrine therapy (NET) in the CARMINA02 trial. This study was designed to correlate gene expression and mutation profiles with both response to NET and prognosis. METHODS: Gene expression profiling using RNA sequencing was performed in 86 pre-NET and post-NET tumor samples. Targeted next-generation sequencing of 91 candidate breast cancer-associated genes was performed on DNA samples from 89 patients...
October 11, 2018: Journal of Hematology & Oncology
Stephanie K Meyer, Michael Dunn, Daniel S Vidler, Andrew Porter, Peter G Blain, Paul A Jowsey
Microcephalin-1 (MCPH1) exists as 2 isoforms that regulate cyclin-dependent kinase-1 activation and chromosome condensation during mitosis, with MCPH1 mutations causing primary microcephaly. MCPH1 is also a tumor suppressor protein, with roles in DNA damage repair/checkpoints. Despite these important roles, there is little information on the cellular regulation of MCPH1. We show that both MCPH1 isoforms are phosphorylated in a cyclin-dependent kinase-1-dependent manner in mitosis and identify several novel phosphorylation sites...
October 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Natalia Ruiz-Lafuente, Manuel Muro, Alfredo Minguela, Antonio Parrado
The Th2 cytokine IL-4 triggers a signaling cascade which activates transcription by STAT6. The goals of the present study are to define the transcriptomic response of mouse spleen B cells (mSBC) to IL-4 used as single stimulus, its specificity compared to human peripheral blood B cells (hPBBC) and to mouse spleen T cells (mSTC), and the pathways affected. Oligonucleotide-based microarrays were performed using two references, the untreated sample and the cells cultured without IL-4, an experimental design which reduces the potential confounding effect of cellular stress during culture...
December 2018: Biochemistry and Biophysics Reports
Ashley Rg Libby, David A Joy, Po-Lin So, Mohammad A Mandegar, Jonathon M Muncie, Federico N Mendoza-Camacho, Valerie M Weaver, Bruce R Conklin, Todd C McDevitt
Morphogenesis involves interactions of asymmetric cell populations to form complex multicellular patterns and structures comprised of distinct cell types. However, current methods to model morphogenic events lack control over cell-type co-emergence and offer little capability to selectively perturb specific cell subpopulations. Our in vitro system interrogates cell-cell interactions and multicellular organization within human induced pluripotent stem cell (hiPSC) colonies. We examined effects of induced mosaic knockdown of molecular regulators of cortical tension (ROCK1) and cell-cell adhesion (CDH1) with CRISPR interference...
October 9, 2018: ELife
Yohei Sekino, Naoya Sakamoto, Keisuke Goto, Ririno Honma, Yoshinori Shigematsu, Thang Pham Quoc, Kazuhiro Sentani, Naohide Oue, Jun Teishima, Fumi Kawakami, Jose A Karam, Kanishka Sircar, Akio Matsubara, Wataru Yasui
BACKGROUND: The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis in some cancers. However, the expression and biological role of T-UCRs in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of Uc.416 + A and analyze the association between Uc.416 + A and epithelial-to-mesenchymal transition in RCC. METHODS: Expression of Uc...
October 4, 2018: BMC Cancer
Chaping Cheng, Zhongzhong Ji, Yaru Sheng, Jinming Wang, Yujiao Sun, Huifang Zhao, Xiaoxia Li, Xue Wang, Yuman He, Jufang Yao, Li Wang, Chenlu Zhang, Yanjing Guo, Jianming Zhang, Wei-Qiang Gao, Helen He Zhu
Tumor metastasis is the major cause of death for prostate cancer (PCa) patients. However, the treatment options for metastatic PCa are very limited. Epithelial-mesenchymal transition (EMT) has been reported to be an indispensable step for tumor metastasis and is suggested to associate with acquisition of cancer stem cell (CSC) attributes. We propose that small-molecule compounds that can reverse EMT or induce mesenchymal-epithelial transition (MET) of PCa cells may serve as drug candidates for anti-metastasis therapy...
2018: Theranostics
Qiuyang Zhang, Agoston T Agoston, Thai H Pham, Wei Zhang, Xi Zhang, Xiaofang Huo, Sui Peng, Manisha Bajpai, Kiron Das, Robert D Odze, Stuart J Spechler, Rhonda F Souza
BACKGROUND & AIMS: Metaplastic glands buried under squamous epithelium are frequently detected in patients with Barrett's esophagus (BE). This sub-squamous intestinal metaplasia (SSIM) might be responsible for cancers that develop despite endoscopic surveillance, and for metaplasia recurrences after endoscopic ablation. To determine whether reflux induces BE cells to undergo epithelial to mesenchymal transition (EMT) that produces SSIM, we assessed EMT in BE cells exposed to acidic bile salts, and in rat and human esophageal tissues...
September 27, 2018: Gastroenterology
Jessica Moretta, Pascaline Berthet, Valérie Bonadona, Olivier Caron, Odile Cohen-Haguenauer, Chrystelle Colas, Carole Corsini, Véronica Cusin, Antoine De Pauw, Capucine Delnatte, Sophie Dussart, Christophe Jamain, Michel Longy, Elisabeth Luporsi, Christine Maugard, Tan Dat Nguyen, Pascal Pujol, Dominique Vaur, Nadine Andrieu, Christine Lasset, Catherine Noguès
INTRODUCTION: Next generation sequencing allows the simultaneous analysis of large panel of genes for families or individuals with a strong suspicion of hereditary breast and/or ovarian cancer (HBOC). Because of lack of guidelines, several panels of genes potentially involved in HBOC were designed, with large disparities not only in their composition but also in medical care offered to mutation carriers. Then, homogenization in practices is needed. METHODS: The French Genetic and Cancer Group (GGC) - Unicancer conducted an exhaustive bibliographic work on 18 genes of interest...
September 27, 2018: Bulletin du Cancer
Andrés F Cardona, Zyanya Lucia Zatarain-Barrón, Cladelis Rubio, Stella Martínez, Alejandro Ruiz-Patiño, Luisa Ricaurte, Adriana Serna, Rodolfo Barrios, Juan Carlos Garzón, Constanza Navarrete, Alberto Balaguera, Luis Corrales, Leonardo Rojas, Oscar Arrieta
Here we report a case of a young, never-smoker Hispanic woman with a hereditary familial overlap syndrome (Li-Fraumeni plus CDH1). The patient developed multiple synchronous primary lung adenocarcinomas related to Intra-Alveolar Tumor Spread (STAS) several years after the diagnosis of a locally advanced lower limb osteosarcoma. Comprehensive genomic profiling by next generation sequencing (NGS) was performed on 90 cancer-related genes over each lung lesion (including two nodules of acinar adenocarcinoma, one lepidic spread tumor and in the STAS area)...
October 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Minoru Terashima, Akihiko Ishimura, Sasithorn Wanna-Udom, Takeshi Suzuki
Long noncoding RNAs (lncRNAs) are important regulatory molecules in various biological and pathological processes, including cancer development. We have previously shown that the MEG3 lncRNA plays an essential role in transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) of human lung cancer cells. In this study, we investigated the function of another lncRNA, MEG8, which shares the DLK1-DIO3 locus with MEG3, in the regulation of EMT. MEG8 lncRNA expression was immediately induced during TGF-β-mediated EMT of A549 and LC2/ad lung cancer and Panc1 pancreatic cancer cell lines...
September 27, 2018: Journal of Biological Chemistry
Juliane Hoyer, Georgia Vasileiou, Steffen Uebe, Marius Wunderle, Cornelia Kraus, Peter A Fasching, Christian T Thiel, Arndt Hartmann, Matthias W Beckmann, Michael P Lux, André Reis
BACKGROUND: Breast cancer is the most common cancer in women. 12-15% of all tumors are triple-negative breast cancers (TNBC). So far, TNBC has been mainly associated with mutations in BRCA1. The presence of other predisposing genes seems likely since DNA damage repair is a complex process that involves several genes. Therefore we investigated if mutations in other genes are involved in cancer development and whether TNBC is an additional indicator of mutational status besides family history and age of onset...
September 26, 2018: BMC Cancer
Jie Xie, Yan Yang, Jiali Sun, Zhi Jiao, Haozheng Zhang, Jie Chen
PURPOSE: Six-transmembrane epithelial antigen of prostate 1 (STEAP1) is a cell surface antigen overexpressed in multiple cancers and is associated with malignancy and disease prognosis. The aims of this study were to evaluate STEAP1 expression in breast cancer and to determine the mechanisms involved. METHODS: STEAP1 expression was compared in normal breast tissue (n = 40), benign fibroadenoma (n = 52), and primary breast cancer (n = 211) using immunohistochemistry...
August 30, 2018: Clinical Breast Cancer
Cheng Chen, Maimaiti Aihemaiti, Xin Zhang, Hui Qu, Jie Jiao, Qilong Sun, Wenbin Yu
Colorectal cancer (CRC) is ranked third as the most common malignancy, and it develops into metastasis at a high rate. Importantly, distant metastasis is considered to be a key factor for colorectal therapy. In the present study, we identified FOXD4, a transcription factor belonging to the forkhead/winged helix-box (FOX) family, as a novel biomarker for diagnosis and treatment of patients with CRC. We revealed that FOXD4 was up-regulated in CRC tissues and increased the metastatic ability of CRC cells. Additionally, FOXD4 affected the metastasis of CRC by inducing the epithelial-mesenchymal transition (EMT) process...
September 25, 2018: Cancer Biology & Therapy
S Warrier, J Taelman, L Tilleman, M Van der Jeught, G Duggal, S Lierman, M Popovic, A Van Soom, L Peelman, F Van Nieuwerburgh, D Deforce, S M Chuva de Sousa Lopes, P De Sutter, B Heindryckx
STUDY QUESTION: What are the transcriptional changes occurring during the human embryonic stem cell (hESC) derivation process, from the inner cell mass (ICM) to post-ICM intermediate stage (PICMI) to hESC stage, that have downstream effects on pluripotency states and differentiation? SUMMARY ANSWER: We reveal that although the PICMI is transcriptionally similar to the hESC profile and distinct from ICM, it exhibits upregulation of primordial germ cell (PGC) markers, dependence on leukemia inhibitory factor (LIF) signaling, upregulation of naïve pluripotency-specific signaling networks and appears to be an intermediate switching point from naïve to primed pluripotency...
September 17, 2018: Molecular Human Reproduction
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