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https://www.readbyqxmd.com/read/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#1
Caterina Marchiò, Felipe C Geyer, Charlotte Ky Ng, Salvatore Piscuoglio, Maria R De Filippo, Marco Cupo, Anne M Schultheis, Raymond S Lim, Kathleen A Burke, Elena Guerini-Rocco, Mauro Papotti, Larry Norton, Anna Sapino, Britta Weigelt, Jorge S Reis-Filho
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair...
December 7, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27924948/foxa1-gata3-and-ppar%C3%A9-cooperate-to-drive-luminal-subtype-in-bladder-cancer-a-molecular-analysis-of-established-human-cell-lines
#2
Joshua I Warrick, Vonn Walter, Hironobu Yamashita, Eunah Chung, Lauren Shuman, Vasty Osei Amponsa, Zongyu Zheng, Wilson Chan, Tiffany L Whitcomb, Feng Yue, Tejaswi Iyyanki, Yuka I Kawasawa, Matthew Kaag, Wansong Guo, Jay D Raman, Joo-Seop Park, David J DeGraff
Discrete bladder cancer molecular subtypes exhibit differential clinical aggressiveness and therapeutic response, which may have significant implications for identifying novel treatments for this common malignancy. However, research is hindered by the lack of suitable models to study each subtype. To address this limitation, we classified bladder cancer cell lines into molecular subtypes using publically available data in the Cancer Cell Line Encyclopedia (CCLE), guided by genomic characterization of bladder cancer by The Cancer Genome Atlas (TCGA)...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917009/induced-expression-of-cancer-stem-cell-markers-aldh1a3-and-sox-2-in-hierarchical-reconstitution-of-apoptosis-resistant-human-breast-cancer-cells
#3
Karin Kashii-Magaribuchi, Rie Takeuchi, Yuko Haisa, Akemi Sakamoto, Aimi Itoh, Yuki Izawa, Miyuki Isa, Mayu Fukuzawa, Motonobu Murakami, Rei Takahashi
We established an experimental system that can induce p53-dependent apoptosis by doxycycline treatment to analyze characteristics of the apoptosis-resistant cancer cell subpopulation in the human breast cancer cell line HCC1937. Expression patterns of the stem cell markers, ALDH1A3 and Sox-2, the luminal differentiation marker, GATA3 and the proliferation index marker, Ki-67 were analyzed using immunostaining and fluorescence-activated cell sorting (FACS). After doxycycline treatment, the number of viable cells was gradually decreased over seven days in a time-dependent manner due to p53-induced apoptosis; however, the number of smaller-sized ALDH1A3(+) cells assessed by immunostaining increased sharply after 1 day of doxycycline treatment, suggesting their apoptosis-resistant nature...
November 1, 2016: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/27912316/th2-cells-in-health-and-disease
#4
Toshinori Nakayama, Kiyoshi Hirahara, Atsushi Onodera, Yusuke Endo, Hiroyuki Hosokawa, Kenta Shinoda, Damon J Tumes, Yoshitaka Okamoto
Helper T (Th) cell subsets direct immune responses by producing signature cytokines. Th2 cells produce IL-4, IL-5, and IL-13, which are important in humoral immunity and protection from helminth infection and are central to the pathogenesis of many allergic inflammatory diseases. Molecular analysis of Th2 cell differentiation and maintenance of function has led to recent discoveries that have refined our understanding of Th2 cell biology. Epigenetic regulation of Gata3 expression by chromatin remodeling complexes such as Polycomb and Trithorax is crucial for maintaining Th2 cell identity...
November 28, 2016: Annual Review of Immunology
https://www.readbyqxmd.com/read/27904775/disease-evolution-and-heterogeneity-in-bilateral-breast-cancer
#5
Elena Fountzilas, Vassiliki Kotoula, Flora Zagouri, Eleni Giannoulatou, George Kouvatseas, George Pentheroudakis, Triantafyllia Koletsa, Mattheos Bobos, Kyriaki Papadopoulou, Epaminontas Samantas, Efterpi Demiri, Spyros Miliaras, Christos Christodoulou, Sofia Chrisafi, Evangelia Razis, Florentia Fostira, Dimitrios Pectasides, George Zografos, George Fountzilas
Bilateral breast cancers (BBC) are currently treated as independent tumors arising in the same patient. Herein, we investigated whether BBC indeed evolve independently at the genomic level. We examined paired targeted next generation sequencing genotypes from 155 paraffin tumors corresponding to 76 BBC patients (75 women and one man; 52 concurrent and 24 metachronous), for coding mutations (amino acid changing, minor allele frequency <0.1%) and single nucleotide polymorphism (SNP) zygosity. Germline genotypes were available for 29 patients...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#6
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27893417/genetic-and-epigenetic-silencing-of-mircorna-506-3p-enhances-cotl1-oncogene-expression-to-foster-non-small-lung-cancer-progression
#7
Shanqi Guo, Peiying Yang, Xingkang Jiang, Xiaojiang Li, Yuanyuan Wang, Xin Zhang, Binxu Sun, Yao Zhang, Yingjie Jia
Although previous studies suggested that microRNA-506-3p (miR-506-3p) was frequently downregulated, and functioned as a tumor suppressor in several cancers, the biological role and intrinsic regulatory mechanisms of miR-506-3p in non-small cell lung cancer (NSCLC) remain elusive. The present study found miR-506-3p expression was downregulated in advanced NSCLC tissues and cell lines. The expression of miR-506-3p in NSCLC was inversely correlated with larger tumor size, advanced TNM stage and lymph node metastasis...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27878828/rhs6-coordinately-regulates-the-th2-cytokine-genes-by-recruiting-gata3-satb1-and-irf4
#8
S S Hwang, S W Jang, K O Lee, H S Kim, G R Lee
BACKGROUND: Asthma is a Th2 cell-driven inflammatory disease and a major public health concern. The cis-acting element Rad50 hypersensitive site 6 (RHS6) in the Th2 locus control region is essential for regulation of the Th2 cytokine genes; however, its role in allergic airway inflammation and underlying molecular mechanisms of the regulation by RHS6 are poorly understood. OBJECTIVE: We sought to understand the role of RHS6 in the development of allergic airway inflammation and its molecular mechanism for Th2 cytokine expression...
November 5, 2016: Allergy
https://www.readbyqxmd.com/read/27870920/picroside-ii-attenuates-airway-inflammation-by-downregulating-the-transcription-factor-gata3-and-th2-related-cytokines-in-a-mouse-model-of-hdm-induced-allergic-asthma
#9
Jin Choi, Bo Kyong Choi, Jin Seok Kim, Jae-Won Lee, Hyun Ah Park, Hyung Won Ryu, Su Ui Lee, Kwang Woo Hwang, Won-Kee Yun, Hyoung-Chin Kim, Kyung-Seop Ahn, Sei-Ryang Oh, Hyun-Jun Lee
Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM)-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), the levels of total immunoglobulin (Ig) E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues...
2016: PloS One
https://www.readbyqxmd.com/read/27867016/vasohibin-2-promotes-epithelial-mesenchymal-transition-in-human-breast-cancer-via-activation-of-transforming-growth-factor-%C3%AE-1-and-hypoxia-dependent-repression-of-gata-binding-factor-3
#10
Min Tu, Zhanjun Li, Xian Liu, Nan Lv, Chunhua Xi, Zipeng Lu, Jishu Wei, Guoxin Song, Jianmin Chen, Feng Guo, Kuirong Jiang, Shui Wang, Wentao Gao, Yi Miao
Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2, and expression of a dominant negative TGFβ type II receptor could block VASH2-mediated EMT...
November 17, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27866814/predictors-of-tissue-healing-in-ulcerative-colitis-patients-treated-with-anti-tnf
#11
Nikos Viazis, Marios Giakoumis, Giorgos Bamias, Dimitris Goukos, Theodoros Koukouratos, Konstantina Katopodi, Pantelis Karatzas, Christos Triantos, Chrisostomos Tsolias, Georgios Theocharis, George L Daikos, Spyros D Ladas, Dimitrios G Karamanolis, Gerasimos J Mantzaris
AIM: To identify factors predicting mucosal healing in ulcerative colitis patients treated with anti-TNFα agents with or without azathioprine. METHODS: In a prospective, multicenter, one-year study biologic naïve patients aged 25-65 years, with corticosteroid-dependent or refractory colitis received combination treatment with anti-TNFα and azathioprine for 6 months followed by anti-TNFα monotherapy. Patients who denied combination therapy or were outside this age range received anti-TNFα monotherapy (controls)...
October 20, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/27858144/th9-and-other-il-9-producing-cells-in-allergic-asthma
#12
REVIEW
Sonja Koch, Nina Sopel, Susetta Finotto
Allergic asthma is a worldwide increasing chronic disease of the airways which affects more than 300 million people. It is associated with increased IgE, mast cell activation, airway hyperresponsiveness (AHR), mucus overproduction and remodeling of the airways. Previously, this pathological trait has been associated with T helper type 2 (Th2) cells. Recently, different CD4(+) T cell subsets (Th17, Th9) as well as cells of innate immunity, like mast cells and innate lymphoid cells type 2 (ILC2s), which are all capable of producing the rediscovered cytokine IL-9, are known to contribute to this disease...
November 17, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27857060/identification-of-transcription-factors-tfs-and-targets-involved-in-the-cholangiocarcinoma-cca-by-integrated-analysis
#13
L Yang, S Feng, Y Yang
The present study was designed to investigate the upstream transcription factors (TFs) and the signature genes in cholangiocarcinoma (CCA), providing better clues on the regulatory mechanisms and therapeutic applications. Gene expression data sets of CCA were searched in the Gene Expression Omnibus database for integrated analysis. Functional annotation of differently expressed genes (DEGs) was then conducted and the TFs were identified. Moreover, a global transcriptional regulatory network of TFs-targets was constructed...
November 18, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27844410/the-great-mimicker-metastatic-breast-carcinoma-to-the-head-and-neck-with-emphasis-on-unusual-clinical-and-pathologic-features
#14
Dikson Dibe Gondim, Rebecca Chernock, Samir El-Mofty, James S Lewis
Distant metastases are relatively common in breast cancer, but spread to the head and neck region is uncommon and can be diagnostically challenging. Pathology databases of two academic hospitals were searched for patients. The diagnoses were by morphologic comparison with the primary breast specimen (when available) or through the use of immunohistochemical stains characteristic of breast carcinoma (cytokeratin 7, mammaglobin, GCDFP15, and/or GATA3 positive-excluding new primary tumors at the respective head and neck sites)...
November 14, 2016: Head and Neck Pathology
https://www.readbyqxmd.com/read/27833659/identification-of-activated-enhancers-and-linked-transcription-factors-in-breast-prostate-and-kidney-tumors-by-tracing-enhancer-networks-using-epigenetic-traits
#15
Suhn Kyong Rhie, Yu Guo, Yu Gyoung Tak, Lijing Yao, Hui Shen, Gerhard A Coetzee, Peter W Laird, Peggy J Farnham
BACKGROUND: Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27829216/ern1-and-alpk1-inhibit-differentiation-of-bi-potential-tumor-initiating-cells-in-human-breast-cancer
#16
Juliane Strietz, Stella S Stepputtis, Bogdan-Tiberius Preca, Corinne Vannier, Mihee M Kim, David J Castro, Qingyan Au, Melanie Boerries, Hauke Busch, Pedro Aza-Blanc, Susanne Heynen-Genel, Peter Bronsert, Bernhard Kuster, Elmar Stickeler, Thomas Brabletz, Robert G Oshima, Jochen Maurer
Cancers are heterogeneous by nature. While traditional oncology screens commonly use a single endpoint of cell viability, altering the phenotype of tumor-initiating cells may reveal alternative targets that regulate cellular growth by processes other than apoptosis or cell division. We evaluated the impact of knocking down expression of 420 kinases in bi-lineage triple-negative breast cancer (TNBC) cells that express characteristics of both myoepithelial and luminal cells. Knockdown of ERN1 or ALPK1 induces bi-lineage MDA-MB-468 cells to lose the myoepithelial marker keratin 5 but not the luminal markers keratin 8 and GATA3...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27828906/a-case-of-metastatic-urothelial-carcinoma-of-the-retina-and-vitreous
#17
Katherine E Whalen, Ralph C Eagle, Tamara R Vrabec
PURPOSE: To report a rare case of vitreoretinal metastasis from urothelial carcinoma of the bladder. METHODS: Case report. RESULTS: A 55-year-old male with a history of bladder cancer developed atypical vitritis and a white fundus mass. IV fluorescein angiography demonstrated connection between the retinal and tumor vasculature consistent with a retinal malignancy. Cytologic analysis of the vitreous sample revealed large atypical cells with pleomorphic nuclei, mucin vacuoles, and rare mitotic figures...
November 8, 2016: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/27822317/narrowing-the-foxf1-distant-enhancer-region-on-16q24-1-critical-for-acdmpv
#18
Przemyslaw Szafranski, Carmen Herrera, Lori A Proe, Brittany Coffman, Debra L Kearney, Edwina Popek, Paweł Stankiewicz
BACKGROUND: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder caused by heterozygous point mutations or genomic deletions involving FOXF1 or its 60-kb tissue-specific enhancer region mapping 270 kb upstream of FOXF1 and involving fetal lung-expressed long non-coding RNA genes and CpG-enriched sites. Recently, we have proposed that the FOXF1 locus at 16q24.1 may be a subject of genomic imprinting. FINDINGS: Using custom-designed aCGH and Sanger sequencing, we have identified a novel de novo 104 kb genomic deletion upstream of FOXF1 in a patient with histopathologically verified full phenotype of ACDMPV...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27816291/atrophying-pityriasis-versicolor-as-an-idiosyncratic-t%C3%A2-cell-mediated-response-to-malassezia-a-case-series
#19
Jonathan Michael Stephen Levy, Cynthia Magro
BACKGROUND: Atrophying pityriasis versicolor (PV), first described in 1971, is a rare variant in which lesions appear atrophic. OBJECTIVE: We sought to determine the pathophysiology of atrophying PV. METHODS: A retrospective chart review identified 6 cases of atrophying PV. In all cases, routine light microscopy, an elastic tissue stain, and immunohistochemical assessment for the expression of CD3, CD4, CD8, GATA3 and CXCR3 was performed. RESULTS: All cases demonstrated hyperkeratosis with intracorneal infiltration by pathogenic hyphal forms as well as epidermal attenuation and papillary dermal elastolysis...
November 2, 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27814345/pro-inflammatory-immune-responses-in-leukocytes-of-premature-infants-exposed-to-maternal-chorioamnionitis-or-funisitis
#20
Courtney M Jackson, Casey B Wells, Meredith E Tabangin, Jareen Meinzen-Derr, Alan H Jobe, Claire A Chougnet
BACKGROUND: Acute chorioamnionitis contributes to premature birth, and is associated with post-birth complications. How chorioamnionitis impacts neonate's developing immune system has not been well defined. METHODS: Blood from extremely preterm infants (=28 weeks gestation) was drawn at the 1(st), 2(nd), and 4(th) week of life. Blood was either left unstimulated or stimulated for 4 hours with PMA/ionomycin. mRNA expression of transcription factors in unstimulated cells (RORC, TBET, GATA3, FOXP3) and inflammatory cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-5, and IL-6) in unstimulated and stimulated cells were analyzed...
November 4, 2016: Pediatric Research
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