The propensity for tumorigenesis in human induced pluripotent stem cells is related with genomic instability / 癌症

The discovery of induced pluripotent stem cells(iPSCs) is a promising advancement in the field of regenerative medicine. Previous studies have indicated that the teratoma-forming propensity of iPSCs is variable; however, the relationship between tumorigenic potential and genomic instability in human iPSCs (HiPSCs) remains to be fully elucidated. Here, we evaluated the malignant potential of HiPSCs by using both colony formation assays and tumorigenicity tests. We demonstrated that HiPSCs formed tumorigenic colonies when grown in cancer cell culture medium and produced malignancies in immunodeficient mice. Furthermore, we analyzed genomic instability in HiPSCs using whole-genome copy number variation analysis and determined that the extent of genomic instability was related with both the cells' propensity to form colonies and their potential for tumorigenesis. These findings indicate a risk for potential malignancy of HiPSCs derived from genomic instability and suggest that quality control tests, including comprehensive tumorigenicity assays and genomic integrity validation, should be rigorously executed before the clinical application of HiPSCs. In addition, HiPSCs should be generated through the use of combined factors or other approaches that decrease the likelihood of genomic instability.

Prognostic significance of the 2004 WHO classification compared with the 1973 WHO classification for organ-confined invasive bladder cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the 2004 and 1973 WHO classifications for predicting tumor recurrence for organ-confined (T stage ≤ pT2b) invasive urothelial carcinoma of the bladder treated with radical cystectomy.</p><p><b>METHODS</b>From February 2000 to August 2011, the 173 consecutive cases of organ-confined invasive urothelial carcinoma of the bladder were treated with radical cystectomy. The data of clinical and follow-up information was collected. The Kaplan-Meier plots with Log-rank test were used to estimate recurrence-free survival (RFS). Univariate and multivariate analysis using the Cox proportional hazard regression model were performed to evaluate the impact of any clinicopathological prognostic factors (tumor grade, tumor stage, lymph node status, lymphovascular invasion, preoperative hydronephrosis, and non-pure urothelial carcinoma) on RFS.</p><p><b>RESULTS</b>The 5-year RFS was 84.7% for the entire cohort. Univariate and multivariate analysis demonstrated that when using the 2004 WHO classification, lymph node status (RR = 4.573, 95% CI: 1.469-14.237), tumor grade (RR = 9.993, 95% CI: 1.325-75.390) and preoperative hydronephrosis (RR = 3.207, 95% CI: 1.209-8.508) presented independent predictors for RFS; while using the 1973 WHO system, lymph node status (RR = 9.484, 95% CI: 3.450-26.074) and lymphovascular invasion (RR = 3.009, 95% CI: 1.062-8.526) were independent predictors.</p><p><b>CONCLUSIONS</b>The 2004 WHO classification, as an independent factor, is superior to the 1973 classification for predicting RFS in patients with organ-confined invasive bladder cancer treated with radical cystectomy. However, a further perspective study is needed to validate its role in prognosis.</p>

Reassessment of the predictive role of perivesical fat invasion in invasive bladder cancer prognosis in 151 Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Perivesical fat invasion is considered as an important prognostic factor for bladder cancer. However, the predictive role of perivesical fat invasion in invasive bladder cancer prognosis has never been reported in Chinese patients. The aim of the study was to assess the predictive value of perivesical fat invasion for prognoses of T2 and T3 bladder cancer in Chinese patients.</p><p><b>METHODS</b>One hundred and fifty-one patients who underwent radical cystectomy for pT2-3N0M0 invasive bladder cancer from 2001 to 2007 were studied. Cancer-specific survival rate (CSS) and recurrence-free survival rate (RFS) were compared between the pT2 and pT3 patient groups. Other clinicopathological parameters were also retrospectively analyzed by univariate and multivariate analyses to identify the independent predictor for the prognoses of this cohort.</p><p><b>RESULTS</b>Average patient age at surgery was 58 years. Ninety (60.3%) patients had grade I and II disease. During follow-up (median 66 months), 27 patients (17.9%) had tumor recurrence and 18 (11.9%) died of bladder cancer. In the univariate analysis, the CSS and RFS curves between T2 and T3 patients showed no significant difference (P = 0.756 and 0.354, respectively). Multivariate Cox regression showed that histological classification and grade were independent predictors for CSS, while grade was the sole independent predictor for RFS.</p><p><b>CONCLUSIONS</b>For this group of Chinese patients, perivesical fat invasion did not demonstrate a statistically significant difference in prognosis between T2 and T3 patients. Nontransitional cell carcinoma (non-TCC) and high-grade patients had short CSS, and patients with high-grade tumor had higher recurrent risk.</p>

Knockdown of nucleophosmin induces S-phase arrest in HepG2 cells / 癌症

Nucleophosmin/B23 (NPM) is a universally expressed nucleolar phosphoprotein that participates in proliferation, apoptosis, ribosome assembly, and centrosome duplication; however, the role of NPM in cell cycle regulation is not well characterized. We investigated the mechanism by which NPM is involved in cell cycle regulation. NPM was knocked down using siRNA in HepG2 hepatoblastoma cells. NPM translocation following actinomycin D (ActD) treatment was investigated using immunofluorescent staining. Expression of NPM and other factors involved in cell cycle regulation was examined by Western blotting. Cell cycle distribution was measured using flow cytometry to detect 5-ethynyl-2'-deoxyuridine (EdU) incorporation. Cell proliferation was quantified by the MTT assay. Knockdown of NPM increased the percentage of HepG2 cells in S phase and led to decreased expression of P53 and P21Cip1/WAF1. S-phase arrest in HepG2 cells was significantly enhanced by ActD treatment. Furthermore, knockdown of NPM abrogated ActD-induced G2/M phase cell cycle arrest. Taken together, these data demonstrate that inhibition of NPM has a significant effect on the cell cycle.

High expression of nucleophosmin/B23 in hepatocellular carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of nucleophosmin/B23 (B23) in tumor cells of hepatocellular carcinoma (HCC) and its clinicopathologic significance.</p><p><b>METHODS</b>Mouse monoclonal antibodies against B23 were raised by recombinant protein and hybridoma technology. Immunohistochemical study for B23 was performed on 103 cases of HCC, 12 cases of focal nodular hyperplasia and 17 cases of native liver tissue adjacent to hepatic hemangioma. Fresh specimens from 10 cases of HCC and the adjacent liver tissue were also collected for reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of B23 was analyzed and compared with that of proliferative cell nuclear antigen (PCNA) in these specimens.</p><p><b>RESULTS</b>RT-PCR and Western blot analysis showed that B23 expression in HCC was higher than that in adjacent liver tissue. Statistically significant difference in expressions of B23 and PCNA were also noted in the four groups studied (P < 0.01). B23 and PCNA expressions in HCC were higher than those in the other three groups (P < 0.01). There was also a statistically significant correlation between B23 and PCNA expressions amongst the four groups (r = 0.4769, P < 0.01). Besides, B23 expression in HCC correlated with pathologic tumor grading, serum alpha-fetal protein levels and cirrhotic status (P < 0.05).</p><p><b>CONCLUSIONS</b>B23 expression in HCC was significantly higher than that in liver tissues with non-malignant diseases. B23 may be used as a marker for neoplastic changes in liver cells and thus has potential clinicopathologic application.</p>