Search Results
Search for other papers by James Yao in
Google Scholar
PubMed
Search for other papers by Abhishek Garg in
Google Scholar
PubMed
Search for other papers by David Chen in
Google Scholar
PubMed
Search for other papers by Jaume Capdevila in
Google Scholar
PubMed
Search for other papers by Paul Engstrom in
Google Scholar
PubMed
Search for other papers by Rodney Pommier in
Google Scholar
PubMed
Search for other papers by Eric Van Cutsem in
Google Scholar
PubMed
Search for other papers by Simron Singh in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Search for other papers by Wei He in
Google Scholar
PubMed
Search for other papers by Markus Riester in
Google Scholar
PubMed
Search for other papers by Parul Patel in
Google Scholar
PubMed
Search for other papers by Maurizio Voi in
Google Scholar
PubMed
Search for other papers by Michael Morrissey in
Google Scholar
PubMed
Search for other papers by Marianne Pavel in
Google Scholar
PubMed
Search for other papers by Matthew Helmut Kulke in
Google Scholar
PubMed
Neuroendocrine tumors (NETs) have historically been subcategorized according to histologic features and the site of anatomic origin. Here, we characterize the genomic alterations in patients enrolled in three phase 3 clinical trials of NET of different anatomic origins and assess the potential correlation with clinical outcomes. Whole-exome and targeted panel sequencing was used to characterize 225 NET samples collected in the RADIANT series of clinical trials. Genomic profiling of NET was analyzed along with nongenomic biomarker data on the tumor grade and circulating chromogranin A (CgA) and neuron-specific enolase (NSE) levels from these patients enrolled in clinical trials. Our results highlight recurrent large-scale chromosomal alterations as a common theme among NET. Although the specific pattern of chromosomal alterations differed between tumor subtypes, the evidence for generalized chromosomal instability (CIN) was observed across all primary sites of NET. In pancreatic NET, although the P value was not significant, higher CIN suggests a trend toward longer survival (HR, 0.55, P = 0.077), whereas in the gastrointestinal NET, lower CIN was associated with longer survival (HR, 0.44, P = 0.0006). Our multivariate analyses demonstrated that when combined with other clinical data among patients with progressive advanced NETs, chromosomal level alteration adds important prognostic information. Large-scale CIN is a common feature of NET, and specific patterns of chromosomal gain and loss appeared to have independent prognostic value in NET subtypes. However, whether CIN in general has clinical significance in NET requires validation in larger patient cohort and warrants further mechanistic studies.
Deeley Research Centre, Department of Biochemistry and Microbiology, Department of Biochemistry and Medical Genetics, Department of Pathology and Laboratory Medicine, BC Cancer Agency, 2410 Lee Avenue, 3rd Floor Research, Victoria, British Columbia, Canada V8R 6V5
Search for other papers by Nathan R West in
Google Scholar
PubMed
Search for other papers by Leigh C Murphy in
Google Scholar
PubMed
Deeley Research Centre, Department of Biochemistry and Microbiology, Department of Biochemistry and Medical Genetics, Department of Pathology and Laboratory Medicine, BC Cancer Agency, 2410 Lee Avenue, 3rd Floor Research, Victoria, British Columbia, Canada V8R 6V5
Deeley Research Centre, Department of Biochemistry and Microbiology, Department of Biochemistry and Medical Genetics, Department of Pathology and Laboratory Medicine, BC Cancer Agency, 2410 Lee Avenue, 3rd Floor Research, Victoria, British Columbia, Canada V8R 6V5
Search for other papers by Peter H Watson in
Google Scholar
PubMed
The most important clinical biomarker for breast cancer management is oestrogen receptor alpha (ERα). Tumours that express ER are candidates for endocrine therapy and are biologically less aggressive, while ER-negative tumours are largely treated with conventional chemotherapy and have a poor prognosis. Despite its significance, the mechanisms regulating ER expression are poorly understood. We hypothesised that the inflammatory cytokine oncostatin M (OSM) can downregulate ER expression in breast cancer. Recombinant OSM potently suppressed ER protein and mRNA expression in vitro in a dose- and time-dependent manner in two human ER+ breast cancer cell lines, MCF7 and T47D. This was dependent on the expression of OSM receptor beta (OSMRβ) and could be blocked by inhibition of the MEKK1/2 mitogen-activated protein kinases. ER loss was also necessary for maximal OSM-induced signal transduction and migratory activity. In vivo, high expression of OSM and OSMR mRNA (determined by RT-PCR) was associated with reduced ER (P<0.01) and progesterone receptor (P<0.05) protein levels in a cohort of 70 invasive breast cancers. High OSM and OSMR mRNA expression was also associated with low expression of ESR1 (ER, P<0.0001) and ER-regulated genes in a previously published breast cancer gene expression dataset (n=321 cases). In the latter cohort, high OSMR expression was associated with shorter recurrence-free and overall survival in univariate (P<0.0001) and multivariate (P=0.022) analyses. OSM signalling may be a novel factor causing suppression of ER and disease progression in breast cancer.
Search for other papers by Josefine Bostner in
Google Scholar
PubMed
Search for other papers by Elin Karlsson in
Google Scholar
PubMed
Search for other papers by Cecilia Bivik Eding in
Google Scholar
PubMed
Search for other papers by Gizeh Perez-Tenorio in
Google Scholar
PubMed
Search for other papers by Hanna Franzén in
Google Scholar
PubMed
Search for other papers by Aelita Konstantinell in
Google Scholar
PubMed
Search for other papers by Tommy Fornander in
Google Scholar
PubMed
Search for other papers by Bo Nordenskjöld in
Google Scholar
PubMed
Search for other papers by Olle Stål in
Google Scholar
PubMed
expression and RPS6KB1 gene amplification and expression ( van der Hage et al . 2004 , Perez-Tenorio et al . 2011 ). The S6K1 antibody demonstrated high specificity and could serve as a clinical biomarker. Overactivated S6K has been suggested an upcoming
Search for other papers by Kjell Oberg in
Google Scholar
PubMed
applied in most NETs but should be complemented with specific markers related to localisation of the primary tumour as well as clinical symptoms. Although CgA serve as a good clinical biomarker, we are in deep need of new biomarkers for detection of early
Search for other papers by T L Veveris-Lowe in
Google Scholar
PubMed
Search for other papers by M G Lawrence in
Google Scholar
PubMed
Search for other papers by R L Collard in
Google Scholar
PubMed
Search for other papers by L Bui in
Google Scholar
PubMed
Search for other papers by A C Herington in
Google Scholar
PubMed
Search for other papers by D L Nicol in
Google Scholar
PubMed
Search for other papers by J A Clements in
Google Scholar
PubMed
, Willemsen NM, Myers SA & Dong Y 2004 The tissue kallikrein family of serine proteases: functional roles in human disease and potential as clinical biomarkers. Critical Reviews in Clinical Laboratory Sciences 41 265 –312
Search for other papers by Bo Chen in
Google Scholar
PubMed
Search for other papers by Guochun Zhang in
Google Scholar
PubMed
Search for other papers by Guangnan Wei in
Google Scholar
PubMed
School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
Search for other papers by Yulei Wang in
Google Scholar
PubMed
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
Search for other papers by Liping Guo in
Google Scholar
PubMed
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
Search for other papers by Jiali Lin in
Google Scholar
PubMed
Search for other papers by Kai Li in
Google Scholar
PubMed
Search for other papers by Hsiaopei Mok in
Google Scholar
PubMed
Search for other papers by Li Cao in
Google Scholar
PubMed
Search for other papers by Chongyang Ren in
Google Scholar
PubMed
Search for other papers by Lingzhu Wen in
Google Scholar
PubMed
Search for other papers by Minghan Jia in
Google Scholar
PubMed
Search for other papers by Cheukfai Li in
Google Scholar
PubMed
Search for other papers by Ting Hou in
Google Scholar
PubMed
Search for other papers by Han Han-Zhang in
Google Scholar
PubMed
Search for other papers by Jing Liu in
Google Scholar
PubMed
Search for other papers by Charles M Balch in
Google Scholar
PubMed
Search for other papers by Ning Liao in
Google Scholar
PubMed
has been explored as an effective strategy to repress tumor growth, and synthetic lethal interactions have been described with PARP inhibition and CDK12 as a clinical biomarker for response in cancer treatment ( Bajrami et al. 2014 , Johnson et
Search for other papers by Masaki Shiota in
Google Scholar
PubMed
Search for other papers by Momoe Itsumi in
Google Scholar
PubMed
Search for other papers by Ario Takeuchi in
Google Scholar
PubMed
Departments of Urology, Anatomic Pathology, Department of Urology, Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3‐1‐1 Maidashi, Higashi‐ku, Fukuoka 812‐8582, Japan
Search for other papers by Kenjiro Imada in
Google Scholar
PubMed
Search for other papers by Akira Yokomizo in
Google Scholar
PubMed
Search for other papers by Hidetoshi Kuruma in
Google Scholar
PubMed
Search for other papers by Junichi Inokuchi in
Google Scholar
PubMed
Search for other papers by Katsunori Tatsugami in
Google Scholar
PubMed
Search for other papers by Takeshi Uchiumi in
Google Scholar
PubMed
Search for other papers by Yoshinao Oda in
Google Scholar
PubMed
Search for other papers by Seiji Naito in
Google Scholar
PubMed
2 995 – 1003 . ( doi:10.1158/2159-8290.CD-12-0222 ). Perry KT Anthony CT Case T Steiner MS 1997 Transforming growth factor β as a clinical biomarker for prostate cancer . Urology 49 151 – 155 . ( doi:10.1016/S0090
Search for other papers by Y Dong in
Google Scholar
PubMed
Search for other papers by L T Bui in
Google Scholar
PubMed
Search for other papers by D M Odorico in
Google Scholar
PubMed
Search for other papers by O L Tan in
Google Scholar
PubMed
Search for other papers by S A Myers in
Google Scholar
PubMed
Search for other papers by H Samaratunga in
Google Scholar
PubMed
Search for other papers by R A Gardiner in
Google Scholar
PubMed
Search for other papers by J A Clements in
Google Scholar
PubMed
clinical biomarkers. Critical Reviews in Clinical Laboratory Sciences 41 265 –312. Day CH , Fanger GR, Retter MW, Hylander BL, Penetrante RB, Houghton RL, Zhang X, McNeill PD, Filho AM, Nolasco M, Badaro R, Cheever MA, Reed
Search for other papers by Brendan M Finnerty in
Google Scholar
PubMed
Search for other papers by Maureen D Moore in
Google Scholar
PubMed
Search for other papers by Akanksha Verma in
Google Scholar
PubMed
Search for other papers by Anna Aronova in
Google Scholar
PubMed
Search for other papers by Shixia Huang in
Google Scholar
PubMed
Search for other papers by Dean P Edwards in
Google Scholar
PubMed
Search for other papers by Zhengming Chen in
Google Scholar
PubMed
Search for other papers by Marco Seandel in
Google Scholar
PubMed
Search for other papers by Theresa Scognamiglio in
Google Scholar
PubMed
Search for other papers by Yi-Chieh Nancy Du in
Google Scholar
PubMed
Search for other papers by Olivier Elemento in
Google Scholar
PubMed
Search for other papers by Rasa Zarnegar in
Google Scholar
PubMed
Search for other papers by Irene M Min in
Google Scholar
PubMed
Search for other papers by Thomas J Fahey III in
Google Scholar
PubMed
as both a clinical biomarker and potential therapeutic target in metastatic PNETs should be further investigated in prospective cohorts. Supplementary data This is linked to the online version of the paper at https://doi.org/10.1530/ERC-18
Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA
Search for other papers by Lingfan Xu in
Google Scholar
PubMed
Search for other papers by Enze Ma in
Google Scholar
PubMed
Department of Urology, Jiangxi Province People’s Hospital, Nanchang, China
Search for other papers by Tao Zeng in
Google Scholar
PubMed
Search for other papers by Ruya Zhao in
Google Scholar
PubMed
Search for other papers by Yulei Tao in
Google Scholar
PubMed
Search for other papers by Xufeng Chen in
Google Scholar
PubMed
Search for other papers by Jeff Groth in
Google Scholar
PubMed
Search for other papers by Chaozhao Liang in
Google Scholar
PubMed
Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina, USA
Search for other papers by Hailiang Hu in
Google Scholar
PubMed
Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina, USA
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA
Search for other papers by Jiaoti Huang in
Google Scholar
PubMed
significant clinical biomarker since its genomic abnormalities would link to high pretreatment LDH level and poor response to docetaxel in mCRPC ( Hiew et al . 2018 ). Furthermore, 64.3% of the patients with high LDH level were determined to have DNA repair