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Xiaoming Ju, Xuanmao Jiao, Adam Ertel, Mathew C Casimiro, Gabriele Di Sante, Shengqiong Deng, Zhiping Li, Agnese Di Rocco, Tingting Zhan, Adam Hawkins, Tanya Stoyanova, Sebastiano Ando, Alessandro Fatatis, Michael P Lisanti, Leonard G Gomella, Lucia R Languino, Richard G Pestell
Proteomic analysis of castration-resistant prostate cancer demonstrated the enrichment of SRC tyrosine kinase activity in approximately ninety percent of patients. Src is known to induce cyclin D1, and a cyclin D1-regulated gene expression module predict poor outcome in human prostate cancer. The tumor-associated calcium signal transducer 2 [TACSTD2/Trop2/M1S1] is enriched in the prostate, promoting prostate stem cell self-renewal upon proteolytic activation via a γ-secretase cleavage complex (PS1, PS2) and TACE (ADAM17), which releases the Trop2 intracellular domain (Trop2 ICD)...
September 15, 2016: Cancer Research
Pavel Strop, Thomas-Toan Tran, Magdalena Dorywalska, Kathy Delaria, Russell Dushin, Oi Kwan Wong, Wei-Hsien Ho, Dahui Zhou, Aidong Wu, Eugenia Kraynov, Laura Aschenbrenner, Bora Han, Christopher J O'Donnell, Jaume Pons, Arvind Rajpal, Dave L Shelton, Shu-Hui Liu
Trop-2, also known as TACSTD2, EGP-1, GA733-1 and M1S1, is frequently expressed on a variety of human carcinomas and its expression is often associated with poor prognosis of the diseases. However, it is also present on the epithelium of several normal tissues. A comprehensively designed Trop-2-targeting ADC, balancing both efficacy and toxicity, is therefore necessary to achieve clinical utility. To this end, we developed a cleavable Trop-2-ADC (RN927C) using a site-specific transglutaminase-mediated conjugation method and a proprietary MTI (microtubule inhibitor) linker-payload, PF-06380101...
August 31, 2016: Molecular Cancer Therapeutics
Sara Morantes, Cerys J Evans, Ana V Valencia, Alice E Davidson, Alison J Hardcastle, Andrés Ruiz Linares, Stephen J Tuft, Miguel Cuevas
PURPOSE: To describe the clinical signs of gelatinous drop-like corneal dystrophy (GDLD) in a consanguineous Colombian family and determine the underlying genetic cause. METHODS: We performed ocular examination of available family members and bidirectionally Sanger sequenced the GDLD-associated gene, TACSTD2. In one individual, the presence of subepithelial amyloid was confirmed with biopsy. RESULTS: The parents were consanguineous and 5 of their 10 children had GDLD...
August 2016: Cornea
Jesus Cabral-Macias, Juan C Zenteno, Arturo Ramirez-Miranda, Alejandro Navas, Jose A Bermudez-Magner, Víctor M Boullosa-Graña, Enrique O Graue-Hernandez, Beatriz Buentello-Volante
PURPOSE: To describe the clinical findings and results of molecular analysis in a Mexican family diagnosed with gelatinous drop-like corneal dystrophy (GDLD). METHODS: Ophthalmological examination was performed in 1 unaffected and 4 affected relatives. Molecular analysis included polymerase chain reaction amplification and direct nucleotide sequencing of the entire TACSTD2 gene-coding region in genomic DNA. RESULTS: The corneal phenotype in adult patients was characterized by white-yellow nodular lesions on the corneal surface and stromal neovascularization...
July 2016: Cornea
Kanlayanee Sawanyawisuth, Nattawat Tantapotinan, Chaisiri Wongkham, Gregory J Riggins, Ratthaphol Kraiklang, Sopit Wongkham, Anucha Puapairoj
BACKGROUND AND AIM: Trophoblast cell surface antigen 2 (TROP2) or tumor-associated calcium signal transducer 2 (TACSTD2) is a 36-kDa type I transmembrane glycoprotein and exerts dual functions as an oncogene and tumor suppressor in cancer cells. In this study, we investigated the expression and functions of TROP2 in liver fluke-associated cholangiocarcinoma (CCA). MATERIAL AND METHODS: TROP2 expression in 85 CCA tissues was detected by using immunohistochemistry...
January 2016: Annals of Hepatology
Sum-Fu Chiang, Chih-Yen Kan, Yung-Chin Hsiao, Reiping Tang, Ling-Ling Hsieh, Jy-Ming Chiang, Wen-Sy Tsai, Chien-Yuh Yeh, Pao-Shiu Hsieh, Ying Liang, Jinn-Shiun Chen, Jau-Song Yu
BACKGROUND: The cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC). This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2), tetraspanin-6 (TSPAN6), bone marrow stromal antigen 2 (BST2), and tumor necrosis factor receptor superfamily member 16 (NGFR)) as potential plasma CRC biomarkers...
2015: Disease Markers
Annie Girard, Isabelle Dufort, Marc-André Sirard
Dairy cows expend great amounts of energy during the lactation peak to cope with milk production. A state of negative energy balance (NEB) was suggested as a cause for the suboptimal fertility observed during this period, via an interaction with ovarian function. The objective of this study was to identify the impact of NEB on gene expression in granulosa cells of dairy cows at 60 days postpartum and to suggest a potential treatment to improve ovarian function. Dairy cows at 60 days postpartum from 10 typical medium-sized farms were synchronized using a single injection of prostaglandin...
November 2015: Theriogenology
Jisun Kim, Sehwan Kim, Seyoon Ko, Yong-ho In, Hyeong-Gon Moon, Soo Kyung Ahn, Min Kyoon Kim, Minju Lee, Jin-Ha Hwang, Young Seok Ju, Jong-Il Kim, Dong-Young Noh, Sun Kim, Jung-Hoon Park, Hwanseok Rhee, Sunghoon Kim, Wonshik Han
Relatively few recurrent gene fusion events have been associated with breast cancer to date. In an effort to uncover novel fusion transcripts, we performed whole-transcriptome sequencing of 120 fresh-frozen primary breast cancer samples and five adjacent normal breast tissues using the Illumina HiSeq2000 platform. Three different fusion-detecting tools (deFuse, Chimerascan, and TopHatFusion) were used, and the results were compared. These tools detected 3,831, 6,630 and 516 fusion transcripts (FTs) overall...
November 2015: Genes, Chromosomes & Cancer
István Fűri, Alexandra Kalmár, Barnabás Wichmann, Sándor Spisák, Andrea Schöller, Barbara Barták, Zsolt Tulassay, Béla Molnár
BACKGROUND: Epithelial cells in malignant conditions release DNA into the extracellular compartment. Cell free DNA of tumor origin may act as a ligand of DNA sensing mechanisms and mediate changes in epithelial-stromal interactions. AIMS: To evaluate and compare the potential autocrine and paracrine regulatory effect of normal and malignant epithelial cell-related DNA on TLR9 and STING mediated pathways in HT-29 human colorectal adenocarcinoma cells and normal fibroblasts...
2015: PloS One
Anna Shvartsur, Benjamin Bonavida
Trop2 is a transmembrane glycoprotein encoded by the Tacstd2 gene. It is an intracellular calcium signal transducer that is differentially expressed in many cancers. It signals cells for self-renewal, proliferation, invasion, and survival. It has stem cell-like qualities. Trop2 is expressed in many normal tissues, though in contrast, it is overexpressed in many cancers and the overexpression of Trop2 is of prognostic significance. Several ligands have been proposed that interact with Trop2. Trop2 signals the cells via different pathways and it is transcriptionally regulated by a complex network of several transcription factors...
March 2015: Genes & Cancer
Bao Li, Yu-Bing Peng, Qi Chen, Juan Zhou, Ming Zhang, Hao Wang, Wen-Ji Li, Jun Da, Zhong Wang, Yan Gao
The human prostate contains two types of stromal cells, peripheral stromal cells (PSCs) and transitional stromal cells (TSCs). Here, we demonstrate the effects of PSCs and TSCs on tumorigenesis in prostate cancer (PCa) and identify the mechanisms underlying these effects. Using microarray analysis, we identified 3,643 differentially expressed genes in cocultures of TSCs, PSCs, and DU145 cells, a human prostate cancer cell line. Expression of cell division cycle 25 homolog A (CDC25A) was lower and that of tumor-associated calcium signal transducer 2 (TACSTD2) was higher in TSCs than in PSCs...
2015: Frontiers in Bioscience (Landmark Edition)
Tuantuan Gui, Xiao Dong, Rudong Li, Yixue Li, Zhen Wang
Liver cancer is one of the leading causes of cancer mortality worldwide. Hepatocellular carcinoma (HCC) is the main type of liver cancer. We applied a machine learning approach with maximum-relevance-minimum-redundancy (mRMR) algorithm followed by incremental feature selection (IFS) to a set of microarray data generated from 43 tumor and 52 nontumor samples. With the machine learning approach, we identified 117 gene probes that could optimally separate tumor and nontumor samples. These genes not only include known HCC-relevant genes such as MT1X, BMI1, and CAP2, but also include cancer genes that were not found previously to be closely related to HCC, such as TACSTD2...
January 2015: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
Yichao Xia, Bo Li, Ning Gao, Hui Xia, Yi Men, Ying Liu, Zhe Liu, Qianming Chen, Longjiang Li
Salivary adenoid cystic carcinoma (SACC) is a common salivary malignancy. The current treatment option for SACC is complete surgical excision with postoperative radiotherapy. The prognosis remains unsatisfactory, due to frequent local recurrence and distant metastases that directly reduce the overall survival time. Previous studies have shown that overexpression of tumor-associated calcium signal transducer 2 (TACSTD2) is associated with poor prognosis in various human epithelial cancers. The expression of TACSTD2 in SACC is currently unknown...
October 2014: Oncology Letters
Rob Noorlag, Petra van der Groep, Frank K J Leusink, Sander R van Hooff, Michaël H Frank, Stefan M Willems, Robert J J van Es
BACKGROUND: Gene expression profiling revealed a strong signature predicting lymph node metastases in oral squamous cell carcinoma (OSCC). Four of the most predictive genes are secretory leukocyte protease inhibitor (SLPI), lipocalin-2 (LCN2), thrombospondin-2 (THBS2), and tumor-associated calcium signal transducer 2 (TACSTD2). This study correlates their protein expression with lymph node metastases, overall survival (OS), and disease-specific survival (DSS). METHODS: Two hundred twelve patients with OSCC were included for protein expression analysis by immunohistochemistry...
August 2015: Head & Neck
F Wang, X Liu, P Yang, L Guo, C Liu, H Li, S Long, Y Shen, H Wan
Tumor-associated calcium signal transducer 2 (TACSTD2), a calcium signal transducer, is universally expressed in stratified squamous epithelia of many organs, including skin, esophagus and cervix. Although TACSTD2, was reported to be overexpressed in many epithelial tumors, which has increased interest in using it as a molecular target for cancer therapy, the role of TACSTD2 in carcinogenesis of squamous cell carcinoma (SCC) is largely unclear and controversial. To explore the role of TACSTD2, temporal-spatial expression of TACSTD2 was analyzed in both normal and SCC tissues...
2014: Cell Death & Disease
Roxana C Mustata, Gabriela Vasile, Valeria Fernandez-Vallone, Sandra Strollo, Anne Lefort, Frédérick Libert, Daniel Monteyne, David Pérez-Morga, Gilbert Vassart, Marie-Isabelle Garcia
Immortal spheroids were generated from fetal mouse intestine using the culture system initially developed to culture organoids from adult intestinal epithelium. Spheroid proportion progressively decreases from fetal to postnatal period, with a corresponding increase in production of organoids. Like organoids, spheroids show Wnt-dependent indefinite self-renewing properties but display a poorly differentiated phenotype reminiscent of incompletely caudalized progenitors. The spheroid transcriptome is strikingly different from that of adult intestinal stem cells, with minimal overlap of Wnt target gene expression...
October 31, 2013: Cell Reports
Olivier Govaere, Mina Komuta, Johannes Berkers, Bart Spee, Carl Janssen, Francesca de Luca, Aezam Katoonizadeh, Jasper Wouters, Léon C van Kempen, Anne Durnez, Chris Verslype, Joery De Kock, Vera Rogiers, Leo A van Grunsven, Baki Topal, Jacques Pirenne, Hugo Vankelecom, Frederik Nevens, Joost van den Oord, Massimo Pinzani, Tania Roskams
OBJECTIVE: Keratin (K)19, a biliary/hepatic progenitor cell (HPC) marker, is expressed in a subset of hepatocellular carcinomas (HCC) with poor prognosis. The underlying mechanisms driving this phenotype of K19-positive HCC remain elusive. DESIGN: Clinicopathological value of K19 was compared with EpCAM, and α-fetoprotein, in a Caucasian cohort of 242 consecutive patients (167 surgical specimens, 75 needle biopsies) with different underlying aetiologies. Using microarrays and microRNA profiling the molecular phenotype of K19-positive HCCs was identified...
April 2014: Gut
Koji Kitazawa, Satoshi Kawasaki, Katsuhiko Shinomiya, Keita Aoi, Akira Matsuda, Toshinari Funaki, Kenta Yamasaki, Mina Nakatsukasa, Nobuyuki Ebihara, Akira Murakami, Junji Hamuro, Shigeru Kinoshita
PURPOSE: Gelatinous drop-like corneal dystrophy (GDLD) is characterized by subepithelial amyloid deposition that engenders severe vision loss. The exact mechanism of this disease has yet to be elucidated. No fundamental treatment exists. This study was conducted to establish an immortalized corneal epithelial cell line to be used as a GDLD disease model. METHODS: A corneal tissue specimen was obtained from a GDLD patient during surgery. Corneal epithelial cells were enzymatically separated from the cornea and were dissociated further into single cells...
August 2013: Investigative Ophthalmology & Visual Science
Shigeru Kinoshita, Satoshi Kawasaki, Koji Kitazawa, Katsuhiko Shinomiya
PURPOSE: To report the establishment of a human conjunctival epithelial cell line lacking the functional tumor-associated calcium signal transducer 2 (TACSTD2) gene to be used as an in vitro model of gelatinous drop-like corneal dystrophy (GDLD), a rare disease in which the corneal epithelial barrier function is significantly compromized by the loss of function mutation of the TACSTD2 gene. METHODS: A small piece of conjunctival tissue was obtained from a GDLD patient...
December 2012: Transactions of the American Ophthalmological Society
B P Telugu, K Adachi, J M Schlitt, T Ezashi, D J Schust, R M Roberts, L C Schulz
INTRODUCTION: Preeclampsia and other placental pathologies are characterized by a lack of spiral artery remodeling associated with insufficient invasion by extravillous trophoblast cells (EVT). Because trophoblast invasion occurs in early pregnancy when access to human placental tissue is limited, there is a need for model systems for the study of trophoblast differentiation and invasion. Human embryonic stem cells (hESC) treated with BMP4- differentiate to trophoblast, and express HLA-G, a marker of EVT...
July 2013: Placenta
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