[Overexpression of MKRN2 Inhibits the Growth of Ovarian Cancer Cells].

Ovarian cancer has a high mortality with low five-year survival rates. The role of the E3 ligase Makorin ring finger protein 2 (MKRN2) in ovarian cancer is unknown. This study investigated the impact of MKRN2 on the growth of ovarian cancer. MKRN2 expression in ovarian cancer tissue was analyzed by immunohistochemistry. Overexpression of MKRN2 was induced in two ovarian cancer cell lines (SKOV3 and CAOV3) by lentivirus transfection, and expression levels were verified by western blotting. Proliferation and growth were determined by CCK-8 and colony formation assays, while migration was examined using transwell assays and apoptosis by flow cytometry. Xenograft tumors of transfected SKOV3 cells were established in mice, and immunohistochemistry and TUNEL assays measured MKRN2 levels and apoptosis in tumor cells. Reduced levels of MKRN2 in cancerous tissue relative to non-cancerous ovarian tissues. Lentiviral-based MKRN2 overexpression in SKOV3 and CAOV3 cells reduced tumor-associated behavior while inducing apoptosis in vitro. In xenograft tumors, MKRN2 overexpression inhibited ovarian cancer growth and increased apoptosis in vivo. These findings imply the MKRN2 involvement in ovarian carcinogenesis and suggest its potential for treating the disease.

Proton pump inhibitor use and risk of spontaneous bacterial peritonitis in cirrhotic patients: a systematic review and meta-analysis.

We used a meta-analysis approach to investigate the association between proton pump inhibitor (PPI) use and risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. We searched Ovid Medline, Embase, and the Cochrane Library to identify eligible studies. We included studies that compared cirrhotic patients who did or did not use PPIs. The primary outcome was SBP, and the secondary outcome was overall bacterial infection. Results were pooled using random-effect models. This process led to identification of 12 journal articles and 5 conference abstracts. The pooled data showed that PPI use in patients with cirrhosis and ascites was significantly associated with an increased risk of SBP [odds ratio (OR) = 2.17; 95% confidence interval (CI) = 1.46-3.23; P < 0.05; I2 = 85.6%] and overall risk of bacterial infection (OR = 1.98; 95%CI = 1.36-2.87; P < 0.05; I2 = 0). Subgroup analysis revealed that journal articles and studies reporting adjusted effect estimates demonstrated that PPI users had a significantly increased risk of SBP (OR = 2.13; 95%CI = 1.61-2.82; P < 0.05; I2 = 29.4%; and OR = 1.98; 95%CI = 1.42-2.77; P < 0.05; I2 = 67%, respectively). In conclusion, PPI use increased the risk of SBP and overall bacterial infection in patients with cirrhosis and ascites. PPIs should be administered after careful assessment of the indications in cirrhotic patients. Future well-designed prospective studies are warranted to clarify the dose relationships and to compare infection risks associated with different classes of PPIs.

Expression of the apoptosis inhibitor livin in colorectal adenoma-carcinoma sequence: correlations with pathology and outcome.

The inhibitor of apoptosis family member livin is expressed in several types of cancer but not in most benign tissues, and it has been considered to be a poor prognostic mark in various malignancies. However, livin expression and its prognostic relevance have not been evaluated in colorectal adenoma-carcinoma sequence. In this study, we analyzed the difference of livin expression among normal mucosa, adenoma, and adenocarcinoma and investigated the relationship of livin expression in carcinomas with clinicopathological variables using immunohistochemistry and real-time reverse transcription-PCR. We observed that the expression of livin protein was mainly present on base of colorectal crypts in adenoma and throughout the epithelium in carcinoma, whereas did not present in accompanying normal mucosa, and the expression of livin messenger RNA (mRNA) in adenocarcinomas was significantly higher than in adenomas and in normal mucosa (P = 0.001, respectively), whereas, compared with normal mucosa, the expression level of livin mRNA was up-regulated in adenomas but no significant difference (P = 0.196). We also found that the expression levels of livin mRNA in rectal cancer was significantly higher than those in colonic cancer, and livin mRNA expression was strongly related to colorectal cancer invasive depth but not to clinical tumor stage, differentiation, lymph node metastasis, tumor morphological category and pathological type, and patient's age and gender. These findings support the possibility that the livin gene may play a role in colorectal tumorigenesis, and increased expression of livin mRNA may serve as a new target for colorectal cancer treatment.

A novel NF1 frame-shift mutation (c.702_703delGT) in a Chinese family with neurofibromatosis type 1.

This study aimed to characterize the clinical features of a Chinese pedigree with neurofibromatosis type 1 (NF1) and to identify mutations in the NF1 gene. In this three-generation family containing 8 members, 5 had been diagnosed with NF1 and the others were asymptomatic. All members of the family underwent complete medical examinations. Molecular genetic analyses were performed on all subjects included in the study. All exons of NF1 were amplified by polymerase chain reaction, sequenced, and compared with a reference database. Possible changes in function of the protein induced by amino acid variants were predicted by bioinformatic analysis. In this family, the 5 patients presented different clinical phenotypes, but all manifested typical café-au-lait macules. One novel frame-shift mutation, c.702_703delGT, in exon 7 of NF1 was identified in all affected family members, but not in the unaffected family members or in 102 normal controls. This mutation generates a premature stop codon at amino acid position 720. Additionally, a synonymous mutation c.702 G>A was found in 3 family members, including 2 affected and 1 normal individuals. In conclusion, our study suggests that a novel c.702_703delGT frame-shift mutation in NF1 is likely to be responsible for the pathogenesis of NF1 in this family. To the best of our knowledge, it is the first time that a c.702_703delGT mutation has been identified in a family with neurofibromatosis type 1.

Efficacy of osimertinib for the treatment of previously EGFR TKI treated NSCLC patients: a meta-analysis.

BACKGROUND: This study evaluates the efficacy of osimertinib for the treatment of previously epidermal growth factor receptor tyrosine kinase inhibitors (EFGR-TKI) treated non-small cell lung cancer (NSCLC) patients. METHOD: Research articles reporting the efficacy of osimertinib for NSCLC patients were identified from literature databases (Embase, Ovid, PubMed and Scopus) by following pre-determined eligibility criteria. Response and survival data were extracted from study reports and were pooled under random-effects model to obtain overall/subgroup effect sizes of selected efficacy outcomes. RESULTS: Nine studies (950 patients; age 60.1 years [95% confidence interval: 57.2, 63.1]; 65% [95% CI: 62, 69] females; 69% [35, 100] with T790M; 61% [53, 68] with ex19del; and 35% [29, 41] with L858R mutations). Osimertinib treatment was associated with a PFS of 11.17 months [7.80, 14.55] which was longer in treatment-naïve (20.30 [15.37, 25.23]) than in prior EGFR-TKI-treated (10.20 [9.60, 10.80]) patients. 1-year survival was 81.29% [73.25, 89.32]. Complete response rate was 1.48% [1.19, 1.76]. PR was achieved in 53.18% [24.18, 82.18] patients which differed between treatment-naïve and prior EGFR-TKI-treated patients (74.48 [65.59, 83.37] and 67.99% [62.68, 73.30], respectively. Objective response rate and disease control rates were 69.80% [64.84, 74.77] and 92.43% [89.42, 95.43], respectively, which did not differ between treatment-naïve and prior EGFR-TKI-treated patients. CONCLUSION: Osimertinib treatment yields approximately 10 months PFS in prior EGFR-TKI-treated and 20 months in treatment-naïve NSCLC patients. Partial response rate is also higher in treatment-naïve patients. However, objective response rate (ORR) and disease control rate (DCR) did not differ between groups of patients.

Effects of mycophenolate mofetil on chronic allograft nephropathy by affecting RHO/ROCK signal pathways.

AIM: We sought to investigate the effects of mycophenolate mofetil (MMF) on chronic allograft nephropathy (CAN) by affecting Rho and ROCK signal pathways. METHODS: Male inbred F344 rat renal grafts orthotopically transplanted into Lewis rats were first treated with CsA (10 mg/kg(-1).d(-1) x 10 d) and then divided into 3 groups (each n = 9): (1) orally vehicle, (2) cyclosporine (CsA, 6 mg/kg(-1).d(-1)) and (3) MMF (20 mg/kg(-1).d(-1)). In addition we performed autografts of F344 (n = 10) at 4, 8, and 12 weeks, serum creatinine (SCr) was measured and pathologic changes assessed. Expression of RhoA and ROCK-1 was determined by real-time reverse transcriptase polymerase chain reaction. Expressions of alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were observed by immunohistochemistry. RESULTS: SCr and Banff score began to increase at 4 weeks in all 3 allografted groups with obvious deterioration in both the vehicle and CsA groups at 8 and 12 weeks. The differences between vehicle/CsA and autografts were significant (P = .000). SCr and Banff score among the MMF group increased mildly and moderately at 8 and 12 weeks, respectively, but were significantly lower than those in the vehicle/CsA cohort (P < .05). Expressions of RhoA and ROCK-1 mRNAs and proteins were observed in mesangial and tubular cells, increasing gradually along with the progression of chronic allograft nephropathy (CAN). There was a negative correlation between RhoA/ROCK-1 mRNA and Banff score (r = -.637, p = .000; r = -.676, P = .000) or SCr (r = -.705, P = .000; r = -.756, P = .000). MMF downregulated gene and protein expressions of RhoA and ROCK-1. CsA had little effect on these expressions. Expressions of alpha-SMA and CTGF were observed in renal epithelial and tubular cells. CONCLUSION: Herein we have demonstrated abnormal expression of RhoA and ROCK-1 signal pathways, which may play roles in CAN. MMF may attenuate CAN by downregulating the expression of RhoA/ROCK-1, alpha-SMA, and CTGF.

Quantitative analysis of PPARdelta mRNA by real-time RT-PCR in 86 rectal cancer tissues.

AIM: The purpose of this study is to clarify the expression change of PPARdelta gene in human colorectal cancer tissues. METHODS: Applying real-time RT-PCR, we quantified PPARdelta mRNA in a series of 86 tissues from excised primary rectal cancers. In each case, accompanying normal mucosa was collected for comparison. RESULTS: Among the 86 rectal cancer tissues, 48 cases showed PPARdelta overexpression: 39 tumours gave an expression level 1.5-5 times, five tumours 10-20 times, and four tumours more than 20 times relative to normal mucosa. However, the general level of PPARdelta mRNA in rectal cancer tissues is not statistically different from normal mucosa. CONCLUSIONS: The expression of PPARdelta gene in rectal cancers is not statistically different from normal mucosa.

[Cultured human peripheral lymphocyte chromosome aberration induced by fusarium T-2 toxin].

In Linxian County, a high incidence area of esophageal cancer, staple food is heavily contaminated by fungi of Fusarium genus. In this paper, it is demonstrated for the first time that T-2 toxin produced by Fusarium can induce various structural aberrations in chromosomes of cultured human peripheral lymphocytes. Peripheral blood cells from 10 normal subjects were cultured for 48 hours. 8732 metaphase plates were analysed, including T-2 toxin-treated group and the control group. The average rate of chromosome aberration was 6.88% in the toxin group, while only 0.2% in the control group. There was a significant difference between these two groups (P less than 0.001). It was observed that T-2 toxin had both mitogenic and direct cytotoxic effects on human lymphocytes. At a lower dose of T-2 toxin (0.1-5 ng/ml for 24 hours), the number of mitosis was increased and chromosome aberration was induced but at a higher dose (10-100 ng/ml), T-2 toxin inhibited mitosis and killed the cells. These results suggest that T-2 toxin possess a carcinogenic potential.

[Trichothecenes in staple food from a high-incidence area of carcinoma of the esophagus and gastric cardia and their carcinogenic potential].

This is the first report to demonstrate the presence of a group of mycotoxins in corn-staple food of Linxian residents, including Nivalenoal (NIV), Deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl-deoxynivalenol (15-ADON), T-2 toxin (these 5 toxins belong to trichothecenes) and zearalenone (ZEN). These 6 toxins were produced by Fusarium species. Using TLC, HPLC, GC, monoclonal antibody affinity column chromatography combined with RIA, respectively, 107 corn samples from Linxian and 2 rice samples from USA were analyzed. It was demonstrated that the average level of NIV was 757 +/- 707(54-2,760)ng/g, DON was 5,376 +/- 4,460 (360-12,670) ng/g with 100% positivity in corn samples consumed as staple food by esophageal cancer patients and their families. Corn samples collected from 5 villages in Linxian at different seasons in 1984-1986 all showed high levels of NIV and DON with 100% positivity which suggested that NIV and DON were consistently and widely existed in Linxian corn samples. Levels of 3-ADON and 15-ADON in Linxian corn were 113 +/- 57 and 495 +/- 538 ng/g. This paper also first demonstrates that the extracts of corn from esophageal cancer patients' families and their NIV and DON fractions purified by HPLC could induce significant chromosome aberrations in V79 cells, indicating that they had carcinogenic potential. Pure toxins of NIV, DON, T-2 and 3-ADON could induce chromosome aberrations in V79 cells starting from 1 ng/ml-a very low concentration. When concentrations increased to certain range they all showed toxic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Diffusion tensor imaging for predicting hand motor outcome in chronic stroke patients.

OBJECTIVE: Previous studies have indicated that diffusion tensor imaging (DTI) values are related to clinical outcome in stroke patients. This prospective study explored whether DTI values were predictive for hand function outcome in chronic stroke patients. METHODS: The DTI parameters (rλ1, rλ23, fractional anisotropy [rFA] and mean diffusivity [rMD]) were investigated in patients with completely paralysed hands (CPH; n=10) or partially paralysed hands (PPH; n=10), by two methods of analysis: segment of the corticospinal tract [sCST] analysis; pure region of interest [ROI] analysis. Spearman's correlation coefficient was used to assess the correlation between the DTI parameters and the following clinical measures: Fugl-Meyer Assessment [FMA]; National Institutes of Health Stroke Scale [NIHSS]. RESULTS: Significant differences were found between CPH and PPH for rFA and rλ23 (sCST analysis) and for rMD and rλ23 (ROI analysis). The rλ23 (sCST analysis) correlated with the NIHSS; the rMD (sCST analysis) correlated with the FMA (hand). CONCLUSION: The three parameters, rFA, rλ23 and rMD may have predictive value for evaluating hand function outcome in chronic stroke patients.