Sarcomatoid carcinoma of the prostate with bladder invasion shortly after androgen deprivation: Two case reports.

BACKGROUND: To summarize the imaging, morphological and biological characteristics of sarcomatoid carcinoma (SC) of the prostate with bladder invasion not long after castration. CASE SUMMARY: Our two cases were initially diagnosed with adenocarcinoma of the prostate due to dysuria. However, prostate SC was diagnosed after transurethral resection of the prostate (TURP) and castration after only 5 and 10 mo, respectively. Distinctive liver-like tissues appeared in the second TURP procedure in case 1, while a white, fish flesh-like, narrow pedicled soft globe protruded from the prostate to the bladder in case 2. CONCLUSION: The sarcomatoid component of SC may arise from one of the specific groups of cancer cells that are resistant to hormonal therapy. Morphological characteristics of SCs can present as "red hepatization" and "fish flesh". SCs grow rapidly and have a poor prognosis, and thus, extensive TURP plus radiation may be the treatment of choice.

Y772 phosphorylation of EphA2 is responsible for EphA2-dependent NPC nasopharyngeal carcinoma growth by Shp2/Erk-1/2 signaling pathway.

EphA2 is an important oncogenic protein and emerging drug target, but the oncogenic role and mechanism of ligand-independent phosphorylation of EphA2 at tyrosine 772 (pY772-EphA2) is unclear. In this study, we established nasopharyngeal carcinoma (NPC) cell lines with stable expression of exogenous EphA2 and EphA2-Y772A (phosphorylation inactivation) using endogenous EphA2-knockdown cells, and observed that pY772A EphA2 was responsible for EphA2-promoting NPC cell proliferation and anchorage-independent and in vivo growth in mice. Mechanistically, EphA2-Y772A mediated EphA2-activating Shp2/Erk-1/2 signaling pathway in the NPC cells, and Gab1 (Grb2-associated binder 1) and Grb2 (growth factor receptor-bound protein 2) were involved in pY772-EphA2 activating this signaling pathway. Our results further showed that Shp2/Erk-1/2 signaling mediated pY772-EphA2-promoting NPC cell proliferation and anchorage-independent growth. Moreover, we observed that EphA2 tyrosine kinase inhibitor ALW-II-41-27 inhibited pY772-EphA2 and EphA2-Y772A decreased the inhibitory effect of ALW-II-41-27 on NPC cell proliferation. Collectively, our results demonstrate that pY772-EphA2 is responsible for EphA2-dependent NPC cell growth in vitro and in vivo by activating Shp2/Erk-1/2 signaling pathway, and is a pharmacologic target of ALW-II-41-27, suggesting that pY772-EphA2 can serve as a therapeutic target in NPC and perhaps in other cancers.

HDAC7 promotes the oncogenicity of nasopharyngeal carcinoma cells by miR-4465-EphA2 signaling axis.

HDAC7 plays a crucial role in cancers, and is the main drug target of several HDAC inhibitors. However, the role and mechanism of HDAC7 in nasopharyngeal carcinoma (NPC) are still unclear. In this study, we observed that HDAC7 was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa (NNM) tissues, HDAC7 expression levels were positively correlated with NPC progression and negatively correlated with patient prognosis, and HDAC7 knockdown dramatically inhibited the in vitro proliferation, migration, and invasion of NPC cells, and the growth of NPC xenografts in mice, indicating the HDAC7 promotes the oncogenicity of NPC. Mechanistically, HDAC7 promoted the in vitro proliferation, migration, and invasion of NPC cells by upregulating EphA2, in which miR-4465 mediated HDAC7-regulating EphA2, a direct target gene of miR-4465. We further showed that miR-4465 was significantly downregulated in the NPC tissues relative to NNM tissues, and inhibited the in vitro proliferation, migration, and invasion of NPC cells by targeting EphA2 expression. Moreover, we observed that the expressions of HDAC7, miR-4465, and EphA2 in NPC tissues were correlated. The results suggest that HDAC7 promotes the oncogenicity of NPC by downregulating miR-4465 and subsequently upregulating EphA2, highlighting HDAC7 as a potential therapeutic target for NPC.

Heterozygous p53-R280T Mutation Enhances the Oncogenicity of NPC Cells Through Activating PI3K-Akt Signaling Pathway.

A heterozygous point mutation of p53 gene at codon 280 from AGA to ACA (R280T) frequently occurs in nasopharyngeal carcinoma (NPC) cell lines, and about 10% NPC tissues. However, the role of this mutation in the pathogenesis of NPC remains unclear. In this study, we generated p53 knockout (KO) NPC cell lines from CNE2 cells carrying heterozygous p53 R280T (p53-R280T) mutation and C666-1 cells carrying wild-type p53 by CRISPR-Cas9 gene editing system, and found that KO of heterozygous p53-R280T significantly decreased NPC cell proliferation and increased NPC cell apoptosis, whereas KO of wild-type p53 had opposite effects on NPC cell proliferation and apoptosis. Moreover, KO of heterozygous p53-R280T inhibited the anchorage-independent growth and in vivo tumorigenicity of NPC cells. mRNA sequencing of heterozygous p53-R280T KO and control CNE2 cells revealed that heterozygous p53-R280T mutation activated PI3K-Akt signaling pathway. Moreover, blocking of PI3K-Akt signaling pathway abolished heterozygous p53-R280T mutation-promoting NPC cell proliferation and survival. Our data indicate that p53 with heterozygous R280T mutation functions as an oncogene, and promotes the oncogenicity of NPC cells by activating PI3K-Akt signaling pathway.

Gender differences among homicide offenders with schizophrenia in Hunan Province, China.

This study aimed to understand the demographic, clinical and criminological characteristics of Chinese homicide offenders with schizophrenia from a gender-based perspective. Information on all homicide offenders with schizophrenia who received forensic psychiatric assessment between 2010 and 2016 in Hunan Province, China, was systematically retrieved (n = 669). Gender differences in the above characteristics were analyzed, and independent correlates of homicide were explored. The male to female ratio of homicide offenders was about 4:1. Proportionally more males were single, unemployed and younger when committing their first crime than was apparent in females. Male perpetrators were more often influenced by delusions. Females were more likely to target their close family members. For males, living in rural areas and having a family history of mental disorder were positively associated with homicide, while having a criminal history and being unemployed were negatively associated. For females, younger age was positively, while being unmarried and unemployment were negatively associated with homicide. Our results indicate significant gender differences among Chinese homicide offenders with schizophrenia in demographic, clinical and criminological characteristics and in independent correlates of homicide. Further research in this field, especially aims at determining risk factors for crime in this population, should take the gender differences into account.

Association between schizophrenia and violence among Chinese female offenders.

Little is known about the association between schizophrenia and violence in women in China. This study aimed to examine the association between schizophrenia and violence in Chinese female offenders. Fifty-two schizophrenia patients were identified from the female offenders who received forensic psychiatric assessments in 2011 in Hunan province, China. Using a propensity score matching method, 104 matched controls without psychiatric disorders were selected from female criminals in Hunan province. Violent offences and homicides were verified and recorded. The percentages of violent offences and homicides were significantly higher in female offenders with schizophrenia than in controls (78.8% vs. 30.8%, P < 0.001; 44.2% vs. 18.3%, P = 0.001, respectively). Multivariate logistic regression analyses revealed that diagnosis of schizophrenia, younger age at first offence, living in rural area and a lower education level were independently and positively associated with violent offences, while having a diagnosis of schizophrenia and lower education level were associated with homicides. There appears to be an independent and positive association between schizophrenia and violent offence in Chinese female offenders. Effective preventive approaches on violence in female schizophrenia patients are warranted.