Differences in phenotype and gene expression of prostate stromal cells from patients of varying ages and their influence on tumour formation by prostate epithelial cells

Prostate cancer （PCa） is an age-related disease, and the stromal microenvironment plays an important role in prostatic malignant progression. However, the differences in prostate stromal cells present in young and old tissue are still obscure. We established primary cultured stromal cells from normal prostatic peripheral zone （PZ） of donors of varying ages and found that cultured stromal cells from old donors （PZ-old） were more enlarged and polygonal than those from young donors （PZ-young）. Furthermore, based on immunocytochemical and ultrastructural analysis, the components of stromal cells changed from a majority of fibroblasts to a mixture of fibroblasts and myofibroblasts with increasing donor age. Using a three-dimensional in vitro culture system, we found that PZ-old stromal cells could enhance the proliferation, migration and invasion of cocultured benign BPH-1 and PC-3 cells. Using an in vivo tissue recombination system, we also found that PZ-old stromal cells are more effective than PZ-young cells in promoting tumour formation by BPH-1 cells of high passage（〉100） and PC-3 cells. To probe the possible mechanism of these effects, we performed cDNA microarray analysis and profiled 509 upregulated genes and 188 downregulated genes in PZ-old cells. Among the changed genes, we found genes coding for a subset of paracrine factors that are capable of influencing adjacent epithelial cells; these include hepatocyte growth factor （HGF）, fibroblast growth factor 5 （FGF5）, insulin-like growth factor 2 （IGF2）, insulin-like growth factor-binding protein 4 （IGFBP4）, IGFBP5 and matrix metallopeptidase 1 （MMP1）. Changes in the expression of these genes were further confirmed by quantitative real-time polymerase chain reaction （PCR）, Western blotting and enzyme-linked immunosorbent assays. Overall, our findings indicate that stromal cells from prostate PZ of old donors are more active than similar cells from young donors in promoting the malignant process of adjacent epithelial cells. This finding hints at a new potential strategy for the prevention of PCa.

Diagnostic efficacy of the Japan Narrow-band-imaging Expert Team and Pit pattern classifications for colorectal lesions: A meta-analysis

BACKGROUND Pit pattern classification using magnifying chromoendoscopy is the established method for diagnosing colorectal lesions. The Japan Narrow-band-imaging(NBI) Expert Team(JNET) classification is a novel NBI magnifying endoscopic classification that focuses on the vessel, and surface patterns.AIM To determine the diagnostic efficacy of each category of the JNET and Pit pattern classifications for colorectal lesions.METHODS A systematic literature search was performed using PubMed, Embase, the Cochrane Library, and Web of Science databases. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic curve of each category of the JNET and Pit pattern classifications were calculated.RESULTS A total of 19227 colorectal lesions in 31 studies were included. The diagnostic performance of the JNET classification was equivalent to the Pit pattern classification in each corresponding category. The pooled sensitivity, specificity,and area under the curve(AUC) for each category of the JNET classification were as follows: 0.73(95%CI: 0.55-0.85), 0.99(95%CI: 0.97-1.00), and 0.97(95%CI: 0.95-0.98), respectively, for Type 1;0.88(95%CI: 0.78-0.94), 0.72(95%CI: 0.64-0.79), and 0.84(95%CI: 0.81-0.87), respectively, for Type 2 A;0.56(95%CI: 0.47-0.64), 0.91(95%CI: 0.79-0.96), and 0.72(95%CI: 0.68-0.76), respectively, for Type 2 B;0.51(95%CI: 0.42-0.61), 1.00(95%CI: 1.00-1.00), and 0.90(95%CI: 0.87-0.93), respectively, for Type 3.CONCLUSION This meta-analysis suggests that the diagnostic efficacy of the JNET classification may be equivalent to that of the Pit pattern classification. However, due to its simpler and clearer clinical application, the JNET classification should be promoted for the classification of colorectal lesions, and to guide the treatment strategy.

Clinicopathological features and survival analysis of gastroenteropancreatic neuroendocrine neoplasms: a retrospective study in a single center of China

Objective： To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms（GEP-NENs） in a Chinese population.Methods： We investigated 154 consecutive patients（88 males, 66 females; median age 56 years, age range 9-86 years） diagnosed with GEP-NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved.Results： The pancreas was the most common site of involvement（63/154, 40.9%）. Tumor size varied from 0.3 to 16.0 cm（median, 1.2 cm）. The patients were followed up for a median period of 22 months（range, 1-157 months）. The estimated 3- and 5-year overall survival（OS） rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome.Conclusions： Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.

c-Jun N-terminal kinase 3 deficiency protects axotomized retinal ganglion cells via affecting mitochondria involved apoptosis pathway

AIM: To illustrate the isoform-specific role and mechanism of c-Jun N-terminal kinases(JNKs) in mouse optic nerve axotomy induced neurotrauma. METHODS: We firstly investigated the expression of JNK1, JNK2, and JNK3 in the retinal ganglion cells(RGCs) by double-immunofluorescent staining. Then we created optic nerve axotomy model in wild type as well as JNK1, JNK2, JNK3, isoform specific gene deficiency mice. With that, we checked the protein expression profile of JNKs and its active form, and quantified the survival RGCs number by immunofluorescence staining. We further explored the molecules underlying isoform specific protective effect by real-time polymerase chain reaction(PCR) and Western blotting assay. RESULTS: We found that all the three isoforms of JNKs were expressed in the RGCs. Deficiency of JNK3, but not JNK1 or JNK2, significantly alleviated optic nerve axotomyinduced RGCs apoptosis. We further established that expression of Noxa, a pro-apoptotic member of BH3 family, was significantly suppressed only in JNK3 gene deficiency mice. But tumor necrosis factor receptor 1(TNFR1) and Fas, two key modulators of death receptor mediated apoptosis pathway, did not display obvious change in the expression. CONCLUSION: It is suggested that mitochondria mediated apoptosis, but not death receptor mediated apoptosis got involved in the JNK3 gene deficiency induced RGCs protection. Our study provides a novel insight into the isoform-specific role of JNKs in neurotrauma and indicates some cues for its therapeutics.

Primary urachal adenocarcinoma: a rare case report

Primary urachal carcinoma is a very rare cancer with a poor prognosis.It generally presents as a highgrade,high-stage tumor,and in most cases the patient has developed regional or distant metastasis at the time of presentation.Here,we report a very interesting case of primary urachal adenocarcinoma with signet ring cell carcinoma in a 58-year-old male who presented with a lower abdominal mass and discomfort.In this case,urachal carcinoma was successfully treated with surgery using an extended partial bladder cystectomy approach with excision of the urachal mass and umbilicus.The patient also underwent systematic chemotherapy with 5-fluorourical and cisplatin.During the 12-month follow-up period,the patient did not experience recurrence or metastasis.Overall,we found that an organ preserving extended partial cystectomy along with chemotherapy was an optimal treatment method that helped improve the patient's quality of the life with no recurrence of cancer so far.