Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incidental prostate cancer (PCa) has been demonstrated at autopsy in about 80% of men aged 80 years and above and also in 10%-15% of younger men aged 30-50 years in the United States. These data imply a wide variation in aggressiveness of prostate cancer, from indolent tumors to aggressive cancers that kill the patients. The use of prostate specific antigen (PSA) in screening for PCa may detect even indolent disease for which radical prostatectomy may not be necessary. Currently available criteria such as histological grade, PSA level, stage of the disease do not always predict outcome. Furthermore, only about 80% of men with metastatic PCa will respond to first line hormone manipulation and once the patient develops hormone resistant prostate cancer (HRPCa), survival remains poor. Recent genomic and proteomic studies have provided many novel molecular markers that may help to redefine prognostic parameters. This paper is a review of studies using these novel markers in order to determine whether prostate cancer patients with the following characteristics have more aggressive cancer than those without: a) high serum levels of cathepsin B, survivin, Her - 2 / neu, IGFBP-2; b) low serum stefin A, IGFBP-3, c) positive immuno-staining of primary tumors for Her-2/neu, survivin and cathepsin B / stefin A ratio > 1 and d) gene expression of AMACR, HER-2/neu, high Bcl-2: Bax ratio and EZH2 in cancer cells. These markers have been chosen for review because they are among the most promising markers emerging currently.
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PMID:The importance of determining the aggressiveness of prostate cancer using serum and tissue molecular markers. 1840 43

Mouse models of gastroesophageal junction (GEJ) cancer strive to recapitulate the intratumoral heterogeneity and cellular crosstalk within patient tumors to improve clinical translation. GEJ cancers remain a therapeutic challenge due to the lack of a reliable mouse model for preclinical drug testing. In this study, a novel patient-derived orthotopic xenograft (PDOX) was established from GEJ cancer via transabdominal surgical implantation. Patient tumor was compared to subcutaneously implanted patient-derived tumor xenograft (PDX) and PDOX by Hematoxylin and Eosin staining, immunohistochemistry and next-generation sequencing. Treatment efficacy studies of radiotherapy were performed. We observed that mechanical abrasion of mouse GEJ prior to surgical implantation of a patient-derived tumor in situ promotes tumor engraftment (100%, n=6). Complete PDOX engraftment was observed with rapid intra- and extraluminal tumor growth, as evidenced by magnetic resonance imaging. PDOXs contain fibroblasts, tumor-associated macrophages, immune and inflammatory cells, vascular and lymphatic vessels. Stromal hallmarks of aggressive GEJ cancers are recapitulated in a GEJ PDOX mouse model. PDOXs demonstrate tumor invasion into vasculature and perineural space. Next-generation sequencing revealed loss of heterozygosity with very high allelic frequency in NOTCH3, TGFB1, EZH2 and KMT2C in the patient tumor, the subcutaneous PDX and the PDOX. Immunohistochemical analysis of Her2/neu (also known as ERBB2), p53 (also known as TP53) and p16 (also known as CDKN2A) in PDX and PDOX revealed maintenance of expression of proteins found in patient tumors, but membranous EGFR overexpression in patient tumor cells was absent in both xenografts. Targeted radiotherapy in this model suggested a decrease in size by 61% according to Response Evaluation Criteria in Solid Tumors (RECIST), indicating a partial response to radiation therapy. Our GEJ PDOX model exhibits remarkable fidelity to human disease and captures the precise tissue microenvironment present within the local GEJ architecture, providing a novel tool for translating findings from studies on human GEJ cancer. This model can be applied to study metastatic progression and to develop novel therapeutic approaches for the treatment of GEJ cancer.This article has an associated First Person interview with the first author of the paper.
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PMID:A novel patient-derived orthotopic xenograft model of esophageal adenocarcinoma provides a platform for translational discoveries. 3173 9