Prognostic value of Sox2 expression in digestive tract cancers: A meta-analysis / 华中科技大学学报（医学）（英德文版）

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.

Evaluation of triage strategies for high-risk human papilloma virus testing as primary screening for cervical cancer / 肿瘤

Objective: To evaluate the performance and application value of several triage strategies for high-risk human papillomavirus (HR-HPV) DNA testing as primary screening of human cervical cancer. Methods: The data from cross-sectional population-based studies for screening human cervical cancer carried out in Xiangyuan county of Shanxi province, China, 2003 were reanalyzed. Totally 1788 women were included in this study. All women were screened by liquid-based cytology (LBC), HR-HPV DNA testing-hybrid capture 2 (HPV-HC2) (for primary screening and analysis of high- and low-level viral loads), and visual inspection with acetic acid (VIA), then all positive women in any test were referred for colposcopy. If the colposcopy result was positive, the woman was referred for biopsy for the final pathological result. This study simulated the strategy in which HPV-HC2 testing was used as primary screening of cervical cancer, then LBC, VIA, HPV-HC2 high- and low-level viral load tests were used as the triage for HPV-positive women. The above strategies were compared by sensitivity, specificity, colposcopy referral rate and other indexes for high-grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer. Moreover, the application value of the above strategies was analyzed by receiver operator characteristic (ROC) curve and the area under curve (AUC) (αcorrection = 0.0125). Results: The colposcopy referral rate, sensitivity, specificity and positive predictive value (PPV) of HPV primary screening with HPV-HC2 for detecting HSIL and invasive cervical cancer were 18.1%, 95.7%, 85.0% and 20.4%, respectively. After HPV primary screening, the referral rates of three strategies of triage with LBC, VIA and HR-HPV-HC2 low viral load were decreased to 8.7%, 4.5% and 9.8%, respectively; the specificity values were increased to 94.3%, 97.5% and 93.1%, respectively; the positive predictive values were increased to 37.2%, 46.9% and 32.0%, respectively; the sensitivity values were decreased to 84.1%, 55.1% and 81.2%, respectively. The difference of AUC between HPV primary screening and its combination with the triage of LBC or HPV-HC2 low viral load was not statistically significant (both P > 0.012 5), but the difference of AUC between HPV primary screening and its combination with the triage of VIA or HPV-HC2 high viral load was statistically significant (both P < 0.001). Conclusion: Considering the economy and adaptability, increasing the cut-off of HPV DNA testing (cut-off ≥10 pg/mL) to improve the screening efficiency of human cervical cancer is feasible and effective in low-resource and less-developed areas. HR-HPV primary screening with the triage of LBC can be introduced widespreadly in high-developed areas. HR-HPV primary screening with the triage of VIA is feasible in rural areas, but the skills of the health care providers responsible for testing should be trained and improved.

The Catechol-O-Methyltransferase Val158Met Polymorphism Contributes to the Risk of Breast Cancer in the Chinese Population: An Updated Meta-Analysis / 한국유방암학회지

PURPOSE: Catechol-O-methyltransferase (COMT) enzyme plays a central role in estrogen-induced carcinogenesis. Emerging evidence from association studies has revealed that the functional Val158Met polymorphism (rs4680 G>A) of the Catechol-O-methyltransferase gene (COMT) has been implicated in susceptibility to breast cancer in the Chinese population, while results of individual published studies remain inconclusive and inconsistent. To assess this association in the Chinese population, a meta-analysis was performed. METHODS: Eligible studies were searched on MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, and the Chinese Biomedicine Database. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the association between COMT polymorphisms and the risk of breast cancer using RevMan 5.2 and Stata 12.0 software. RESULTS: The meta-analysis included 14 eligible studies, with a total of 4,626 breast cancer cases and 5,637 controls. Overall, the COMT Val158Met polymorphism (rs4680 G>A) was significantly associated with an increased risk of breast cancer in several genetic models (A/A vs. G/G: OR, 1.59, 95% CI, 1.12-2.27; A/A vs. G/A+G/G: OR, 1.62, 95% CI, 1.14-2.29; A vs. G: OR, 1.15, 95% CI, 1.00-1.32), and a subgroup analysis according to menopausal status showed that this association was especially evident among premenopausal Chinese women (A/A vs. G/G: OR, 1.87, 95% CI, 0.99-3.54; A/A vs. G/A+G/G: OR, 1.94, 95% CI, 1.03-3.63). CONCLUSION: The results of this meta-analysis indicated that COMT Val158Met variants contribute to breast cancer susceptibility in the Chinese population, particularly among premenopausal women.

Effects of microporous porcine acellular dermal matrix combined with bone marrow mesenchymal cells of rats on the regeneration of cutaneous appendages cells in nude mice / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe the effects of microporous porcine acellular dermal matrix (ADM) combined with bone marrow mesenchymal cells (BMMCs) population containing bone mesenchymal stem cells (BMSCs) of rats on the regeneration of cutaneous appendages cells in nude mice.</p><p><b>METHODS</b>Split-thickness dermal grafts, 20 cm×10 cm in size and 0.3 mm in thickness, were prepared from a healthy pig which was sacrificed under sanitary condition. Laser microporous porcine ADM (LPADM) was produced by laser punching, hypertonic saline solution acellular method, and crosslinking treatment, and nonporous porcine ADM (NPADM) was produced by the latter two procedures. Then the appearance observation, histological examination and scanning electron microscope observation were conducted. BMMCs were isolated and cultured from tibia and femur after sacrifice of an SD rat. Osteogenic and adipogenic differentiation experiments were conducted among the adherent cells in the third passage. Then they were inoculated to LPADM and NPADM to construct BMMCs-LPADM and BMMCs-NPADM materials. Twenty-one healthy nude mice were divided into BMMCs-LPADM+NPADM group (A, n = 6), LPADM+split-thickness skin graft group (B, n = 6), BMMCs-LPADM+split-thickness skin graft group (C, n = 6), BMMCs-NPADM+split-thickness skin graft group (D, n= 3) according to randomized block. After anesthesia, a 2 cm×2 cm full-thickness skin defect reaching deep fascia was reproduced in the middle of the back of each nude mouse, and a split-thickness skin graft of the same size was obtained, and then prepared skin grafts were transplanted to cover the wounds respectively. On post transplantation day (PTD) 5, 7, and 14, local condition and adverse effects observation was conducted; one nude mouse was sacrificed each time to harvest all the transplant for tissue structure observation with HE staining. On PTD 7 and 14, neonatal skin appendages in corresponding composite materials were observed with transmission electron microscope.</p><p><b>RESULTS</b>(1) LPADM and NPADM appeared to be porcelain white, soft, and flexible. No cellular component was observed in acellular dermal matrix. Scanning electron microscope showed that the collagen fibers were orderly arranged. LPADM had microporous structure. (2) Cells in the third passage were orderly arranged with the shape similar to fibroblasts with high growth speed. (3) Induced differentiation experiments showed that cells could differentiate into osteoblasts and adipocytes. (4) On PTD 5, the NPADM in group A was dry in part; skin grafts in group D were dry and necrotic, and there was no infection and inflammation in groups A and D; skin grafts in groups B and C survived. On PTD 7 and 14, the overlaying material in group A was black, dry, and hard in part; the skin grafts in group D turned to be completely black, dry, and necrotic, and pale yellow clear exudate was found in subcutaneous area; there was no obvious purulent discharge in groups A and D; the appearance of skin grafts in groups B and C was close to the surrounding skin. (5) On PTD 5 and 7, in groups A, B, and C, vascularization was apparent in the pores of dermal matrix, and red blood cells could be found. In group D, skin grafts were dry and necrotic. On PTD 14, in groups A, B, and C, the pore structure of dermal matrix was fully vascularized in which a large number of red blood cells were visible. In group A, the microporous dermal matrix survived, but the overlaying NPADM was not attached closely. In groups B and C, the skin grafts were closely connected to the dermal matrix, and no cutaneous appendages were observed. In group C, special monolayer cells were found at the junction between skin graft and dermal matrix. (6) Skin grafts in group D failed to survive; they were not observed with the electron microscope. On PTD 7, there were no significant differences among groups A, B, and C. On PTD 14, no sebaceous gland-like cell or sweat gland-like cell and no newborn nerve ending were observed in skin grafts in groups A and B, in spite of the immigration of fibroblasts. In group C, a large number of new capillaries were observed at the junction between the skin graft and dermal matrix; rough endoplasmic reticulum of fibroblasts proliferated exuberantly; newborn unmyelinated nerve endings were observed; single free sweat gland-like cells and sebaceous gland-like cells were observed in superficial dermal matrix.</p><p><b>CONCLUSIONS</b>LPADM, which provides a "cell niche-like" micro-environment for the migration and differentiation of the BMMCs population, when combining with the split-thickness skin graft, can induce exogenous differentiation of BMSCs in vivo, thus achieving the reconstruction of skin appendages.</p>