Purpose: Gastrointestinal stromal tumors (GIST) are a distinctive group of mesenchymal neoplasms of the gastrointestinal tract. The oncogene KIT has a central role in the pathogenesis of GIST, with c-kit receptor tyrosine kinase (KIT) protein expression being the gold standard in its diagnosis. The identification of GIST patients has become crucial, because the tyrosine kinase inhibitor Imatinib is effective in the treatment of this malignancy. However, a small set of GISTs remain unrecognized, because KIT protein expression is not always evident. The aim of this study was the identification of new markers for the differential diagnosis of GIST.Experimental Design: By analyzing publicly available data from transcriptional profiling of sarcomas, we found that protein kinase C (PKC-), a novel PKC isotype involved in T-cell activation, is highly and specifically expressed in GIST. PKC-expression in GIST was confirmed by reverse transcription-PCR and Western blot. PKC-was analyzed by immunohistochemistry in a panel of 26 GIST, 12 non-GIST soft-tissue sarcomas, and 35 tumors from other histologies.Results: We found that all of the GISTs expressed PKC-, whereas this protein was undetectable in other mesenchymal or epithelial tumors, including non-GIST KITpositive tumors. PKC-immunoreactivity was also observed in interstitial cells of Cajal.Conclusions: Our results show that PKC-is easily detected by immunohistochemistry in GIST specimens and that it could be a sensitive and specific marker for the diagnosis of this malignancy.
BackgroundThe collagen11A1 (COL11A1) gene is overexpressed in pancreatic cancer. The expression of COL11A1 protein could be involved in desmoplastic events in pancreatic cancer, but an antibody that specifically stains the COL11A1 protein is not currently available.Methods and findingsA total of 54 pancreatic ductal adenocarcinomas (PDAC), 23 chronic pancreatitis (CP) samples, and cultured peritumoral stromal cells of PDAC (passages 3-6) were studied. Normal human pancreas tissue samples were obtained through a cadaveric organ donation program.1) Validation of COL11A1 gene overexpression by q-RT-PCR. Findings: the expression of COL11A1 gene is significantly increased in PDAC samples vs. normal and CP samples.2) Analysis of COL11A1 by immunohistochemistry using highly specific anti-proCOL11A1 antibodies. Findings: anti-proCOL11A1 stains stromal cells/cancer-associated fibroblasts (CAFs) of PDAC but it does not stain chronic benign condition (chronic pancreatitis) stromal cells, epithelial cells, or normal fibroblasts.3) Evaluation of the discrimination ability of the antibody. Findings: anti-proCOL11A1 immunostaining accurately discriminates between PDAC and CP (AUC 0.936, 95% CI 0.851, 0.981).4) Phenotypic characterization of proCOL11A1+ stromal cells co-staining with mesenchymal, epithelial and stellate cell markers on pancreatic tissue samples and cultured peritumoral pancreatic cancer stromal cells. Findings: ProCOL11A1+ cells present co-staining with mesenchymal, stellate and epithelial markers (EMT phenotype) in different proportions.Conclusions/SignificanceDetection of proCOL11A1 through immunostaining with this newly-developed antibody allows for a highly accurate distinction between PDAC and CP. Unlike other available antibodies commonly used to detect CAFs, anti-proCOL11A1 is negative in stromal cells of the normal pancreas and almost absent in benign inflammation. These results strongly suggest that proCOL11A1 is a specific marker for CAFs, and thus, anti-proCOL11A1 is a powerful new tool for cancer research and clinical diagnostics.
Research on juvenile justice aims to identify profiles of risk and protective factors in juvenile offenders. This paper presents a study of profiles of risk factors that influence young offenders toward committing sanctionable antisocial behavior (S-ASB). Decision tree analysis is used as a multivariate approach to the phenomenon of repeated sanctionable antisocial behavior in juvenile offenders in Spain. The study sample was made up of the set of juveniles who were charged in a court case in the Juvenile Court of Almeria (Spain). The period of study of recidivism was two years from the baseline. The object of study is presented, through the implementation of a decision tree. Two profiles of risk and protective factors are found. Risk factors associated with higher rates of recidivism are antisocial peers, age at baseline S-ASB, problems in school and criminality in family members.
Research on adolescent-to-parent violence (APV) associates specific psychosocial characteristics with adolescents who assault their parents, whether they are within or outside the juvenile justice system, or whether these characteristics are shared by other adolescents convicted of other crimes. The aim of this paper is to compare three groups of adolescents. Those who have been sentenced for APV are compared with adolescents who have committed other crimes, and with a group who have not been involved in the justice system. The sample used consists of 148 male participants between the ages of 14 and 21. A comparison is made regarding type of self-reported behavior, frequency of drug use, academic performance, exposure to violence, self-concept, and parents’ conflict resolution tactics. The results obtained indicate that adolescents with judicial measures, regardless of the crime committed, differ from those who have not been in trouble with the justice system in terms of them having suffered violence in the street, the frequency with which they use drugs and in their academic achievement. Likewise, adolescents convicted of APV differ from the other two groups in the frequency with which they are victims of violence at home, in that their mothers use the tactic of asking somebody else for help as a way of solving marital conflicts, and in having a more negative family self-concept. The results are discussed highlighting the importance of taking into account whether a sample is judicial, clinical, or community, and the specific APV behaviors which are measured.
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