Vitamin E and selenium partially prevent cytotoxicity, oxidative stress and DNA damage induced by T-2 toxin in bovine Leydig cells.

The objective of this study was to explore the protective mechanism of Vitamin E (VE) and selenium (Se) against T-2 toxin-induced oxidative damage of bovine Leydig cells. Leydig cells were isolated, cultured and divided into five treatment groups such as: control, T-2, Se + T-2, VE + T-2 and VE + Se + T-2. After treatment for 24 h, the cells and supernatants were harvested to examine the cell viability, the activities and mRNA expression of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), the content of malondialdehyde (MDA) and DNA damage. Results showed that T-2 toxin exposure significantly reduced the cell viability, increased the MDA level, reduced GSH-Px, SOD and CAT activities and increased DNA damage (P < 0.05). Meanwhile, T-2 toxin was attributed to the down-regulation of the mRNA expression of GSH-Px, SOD and CAT (P < 0.05). However, VE and Se reduced T-2 toxin-induced oxidative damage and tended to maintain normal levels (P < 0.05). Furthermore, VE and Se substantially up-regulated the activities and mRNA expressions of the GSH-Px, SOD and CAT. In conclusion, VE and Se, due to its anti-oxidative ability, could ameliorate T-2 toxin-induced cytotoxicities by regulating oxidative stress in bovine Leydig cells.

Down-regulated PLAC8 promotes hepatocellular carcinoma cell proliferation by enhancing PI3K/Akt/GSK3ß/Wnt/ß-catenin signaling.

Hepatocellular carcinoma (HCC) is a common, prevalent malignancy. Its poor prognosis is mainly related to high rate of diagnosis in non-curable stages, in which patients are suitable for palliative treatment. Placenta-specific 8 (PLAC8), also known as Onzin, is a small, highly conserved, cysteine-rich protein. In current study, we found that PLAC8 is prominently decreased in HCC tissues compared with adjacent tissues and patients with low level of PLAC8 suffered a poor prognosis. In addition, cellular function assays demonstrate that down-regulated PLAC8 promotes cell viability, proliferation and tumor formation both in vitro and in vivo. Furthermore, we validate that down-regulated PLAC8 enhances the activity of PI3K/Akt/GSK3ß and Wnt/ß-catenin signaling to promote cell proliferation. Moreover, we proved that highly expressed miR-185-5p targets PLAC8 in HCC tissues. In conclusion, our findings enlarged our knowledge about the roles of PLAC8 in HCC progression and miR-185-5p/PLAC8/ß-catenin axis might be a novel pathway for HCC treatment.

FokI Polymorphism of the Vitamin D Receptor Gene Is Associated with Susceptibility to Gastric Cancer: A Case-Control Study.

Vitamin D is a potential protective agent against cancer, and its activity is mediated mainly by vitamin D receptor (VDR). The FokI polymorphism (rs10735810) represents a T-to-C transition (ATG to ACG) in exon 2 of the VDR gene, and this ATG represents the translation-initiation codon, encoded by the f allele. The FokI polymorphism results in the generation of a protein shortened by three amino acids, translated from the downstream ATG codon (the F allele). We investigated the relationship between the FokI polymorphism and gastric cancer in a Chinese Han population. A total of 187 patients and 212 healthy controls were enrolled. The FokI polymorphism was detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. The f allele frequency was higher in patients than that in controls (51.6% and 43.6%, P < 0.05). Multivariate logistics regression analysis revealed patients with the f allele (Ff + ff) showed a higher risk of gastric cancer [odds ratio (95% confidence interval) 2.73 (1.13~4.32)]. Patients with the f allele (Ff + ff) also presented a poorly differentiated type of gastric cancer (P < 0.05) and higher levels of C-reactive protein on admission than the FF group (5.5 ± 2.4 mg/L vs. 3.4 ± 1.3 mg/L, P < 0.05). Here, we show an association between the VDR FokI polymorphism and the susceptibility to gastric cancer, which may be helpful for early detection of high-risk individuals with the f allele for gastric cancer. Conversely, the F allele may be a protective factor against gastric cancer.

Predictive and Prognostic Biomarkers for Patients Treated with Anti-EGFR Agents in Lung Cancer: A Systemic Review and Meta-Analysis.

BACKGROUND: Several studies have investigated predictive and prognostic biomarkers for patients treated with anti-epidermal growth factor receptor (EGFR) agents in lung cancer. However, the conclusion is controversial. MATERIALS AND METHODS: A meta-analysis was conducted to evaluate the associations of mutant K-ras, PIK3CA and PTEN deficiency with the efficacy of anti-EGFR agents in lung cancer. The primary endpoint was objective response rate (ORR). The secondary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 61 studies were included in the final meta-analysis. The result showed that K-ras mutation was a good predictor for ORR (RR=0.42, 95%CI, 0.33-0.55, p=0.000) and an effective prognostic marker for OS (HR=1.37, 95%CI, 1.15-1.65, p=0.001) and PFS (HR=1.33, 95%CI, 1.05-1.69, p=0.019). However, PTEN deficiency or PIK3CA mutation did not show any significance predictive value for ORR (PTEN, RR=0.82, 95%CI, 0.56-1.19, p=0.286; PIK3CA, RR=1.08, 95%CI, 0.17-6.66, P=0.938). And PTEN deficiency or expression of PIK3CA did not show significance prognostic value for OS (PTEN, HR=0.88, 95%CI, 0.31-2.46,P=0.805; PIK3CA, HR=0.79, 95%CI: 0.23-2.68, P=0.706). CONCLUSIONS: Our meta-analysis showed that K-ras mutation may be an effective predictor in lung cancer patients treated with anti-EGFR agents. Whereas, the predictive and prognostic value of PTEN deficiency and PIK3CA mutation need to be further investigated.

Prognostic impact of elevation of vascular endothelial growth factor family expression in patients with non-small cell lung cancer: an updated meta-analysis.

BACKGROUND: The vascular endothelial growth factor family has been implicated in tumorigenesis and metastasis. The prognostic value of each vascular endothelial growth factor family member, particular VEGF/ VEGFR co-expression, in patients with non-small lung cancer remains controversial. MATERIALS AND METHODS: Relevant literature was identified by searching PubMed, EMBASE and Web of Science. Studies evaluating expression of VEGFs and/or VEGFRs by immunohistochemistry or ELISA in lung cancer tissue were eligible for inclusion. Hazard ratios (HRs) and 95% confidence intervals (CIs) from individual study were pooled by using a fixed- or random-effect model, heterogeneity and publication bias analyses were also performed. RESULTS: 74 studies covering 7,631 patients were included in the meta-analysis. Regarding pro-angiogenesis factors, the expression of VEGFA (HR=1.633, 95%CI: 1.490-1.791) and VEGFR1 (HR=1.924, 95%CI: 1.220-3.034) was associated separately with poor survival. Especially, VEGFA over-expression was an independent prognostic factor in adenocarcinoma (ADC) (HR=1.775, 95%CI: 1.384-2.275) and SCC (HR=2.919, 95%CI: 2.060-4.137). Co-expression of VEGFA/VEGFR2 (HR=2.011, 95%CI: 1.405-2.876) was also significantly associated with worse survival. For lymphangiogenesis factors, the expression of VEGFC (HR=1.611, 95%CI: 1.407-1.844) predicted a poor prognosis. Co-expression of VEGFC/VEGFR3 (HR=2.436, 95%CI: 1.468-4.043) emerged as a preferable prognostic marker. CONCLUSIONS: The expression of VEGFA (particularly in SCC and early stage NSCLC), VEGFC, VEGFR1 indicates separately an unfavorable prognosis in patients with NSCLC. Co-expression VEGFA/ VEGFR2 is comparable with VEGFC/VEGFR3, both featuring sufficient discrimination value as preferable as prognostic biologic markers.

Expression of HGF and Met in human tissues of colorectal cancers: biological and clinical implications for synchronous liver metastasis.

BACKGROUND AND AIMS: Synchronous liver metastasis (SLM) remains a significant problem in newly diagnosed colorectal cancer (CRC). The system of hepatocyte growth factor (HGF) and Met plays an important role in cancer invasion and metastasis and is being developed to be targeted drugs. We aimed to investigate the role of HGF/Met in SLM based on a case-matched study and comparison between primary tumors and matched metastases. METHODS: A group of 30 patients with SLM and other two groups of patients without SLM in a hospital database were collected. They were matched into according to clinicopathological factors. 81 patients were included in the study. Their tissues of primary colorectal cancers, lymph nodes and liver metastases were collected to detect HGF and Met expression by immunohistochemistry and RT-PCR. RESULTS: Expression of HGF and Met at the protein level and the RNA level in primary CRCs with SLM were significantly higher than that in primary colorectal carcinomas without liver metastases (all P value<0.05). Their expression was only related to SLM when concurrent with regional lymph node metastasis (all P value<0.05) but had little influence on SLM without involvement of lymph node metastasis (all P value>0.05). Comparison their expression between primary tumors and matched metastases, major concordance and minor difference existed. CONCLUSIONS: HGF and Met may exert functions in the development of SLM when concurrent with lymph node metastases but had little influence on SLM without lymph node metastasis, further indicating their roles and potential values for a subtype of colorectal cancer metastasis. Major concordance and minor difference exist between primary tumors and matched metastases, which further provides evidence for evaluating the response to their inhibitors based on primary tumors or metastases.

MicroRNA-34b functions as a tumor suppressor and acts as a nodal point in the feedback loop with Met.

MicroRNAs (miRNAs), as a class of naturally occurring small non-coding RNAs, play profound and pervasive roles in cancer initiation and progression. Extensive decrease in miRNA levels are frequently observed in human cancers, indicating that miRNAs may function intrinsically in tumor suppression. However, the underlying mechanisms of miRNA interactions with cellular pathways are still unclear. The expression of miR-34b in non-small cell lung cancer (NSCLC) tissues was detected using quantitative real-time PCR. The relations between miR-34b expression levels and pathological stage or lymph node metastasis were assessed using the Spearman correlation test. For in vitro studies, lung cancer cells were transfected with double stranded synthetic miRNA mimics (syn-hsa-miR-34b miScript miRNA) and scrambled controls. Immunohistochemistry was used to validate the related downstream proteins of miR-34b. The expression of miR-34b was lower in NSCLC tissues compared to that in pericarcinous tissues of lung cancer. Additionally, the Spearman correlation test showed that lower miR-34b expression was correlated with higher lymph node metastasis. In vitro gain-of-function experiments indicated that miR-34b suppressed cell proliferation by inducing cell apoptosis. IHC results showed association between lower miR-34b and overexpression of phospho-Met, p53 (phospho S392) and Mdm2. Consistent with the opposing correlation between the expression of miR-34b and lymph node metastasis in NSCLC, miR-34b may play an important role in NSCLC progression. Furthermore, miR-34b downregulates Met, with subsequent changes of downstream p53 (phospho S392) and Mdm2, and inversely p53 upregulates miR-34b in a feedback loop, which provides new insights into the roles of miR-34 family members in the regulation of signaling pathways of NSCLC.

Loss of DBC2 expression is an early and progressive event in the development of lung adenocarcinoma.

PURPOSE: DBC2 (Deleted in Breast Cancer 2) has been indicated to be a tumor suppressor gene in many cancers including lung adenocarcinoma recently. In this study, we aimed to explore the expression status of DBC2 in different subtypes of lung adenocarcinoma (from pre-invasive to invasive lesions), and to determine if downregulation becomes more marked with pathological progression. METHODS: We collected 172 tissue samples from different subtypes of lung adenocarcinoma and investigated the frequency of DBC2 loss by immunohistochemistry. RESULTS: Our results indicated that DBC2 downregulation is a relatively frequent event in lung adenocarcinoma. Moreover, as the adenocarcinoma subtype turns to be more invasive, more downregulation occurred. CONCLUSION: We conclude that loss of DBC2 expression is an early and progressive event in the pathogenesis of lung adenocarcinoma. Positive DBC2 immunohistochemistry may become an indicator for early stage disease and better prognosis of lung adenocarcinomas.

Expression of ß-arrestin 1 in gastric cardiac adenocarcinoma and its relation with progression.

OBJECTIVE: Arrestins act as mediators of G protein-coupled receptor (GPCR) desensitization and trafficking, also actin as a scaffold for many intracellular signaling network. The role that ß-arrestin 1 plays in gastric cardiac adenocarcinoma (GCA) and its clinicopathologic significance are untouched. METHODS: Fifty patients with gastric cardiac adenocarcinoma were retrospectively enrolled and ß-arrestin 1 was detected using immunohistochemistry in tissue samples. RESULTS: Nuclear expression of ß-arrestin 1 was observed in 78% of GCA samples (39/50) and cytoplasmic expression in 70% (35/50). ß-arrestin 1 could be found in both nucleus and cytoplasm of 54% GCA (27/50) or in either of them in 94% (47/50). ß-arrestin 1 protein positivity in well/ moderately differentiated carcinomas was significantly higher than that in poorly differentiated carcinomas (P=0.005). We found increased expression of ß-arrestin 1 in cytoplasm was correlated with lymph nodal metastasis (P=0.002) and pathological lymph nodal staging (P=0.030). We also found ß-arrestin 1 to be over-expressed in glandular epithelia cells of mucinous adenocarcinoma, a tumour type associated with an adverse outcome of gastric cardiac adenocarcinoma (P=0.022). CONCLUSION: ß-arrestin 1 is over-expressed in the nucleus and/or cytoplasm of gastric cardiac adenocarcinoma. However, ß-arrestin 1 has no relationship with the prognosis of gastric cardiac adenocarcinoma (P>0.05). Our data imply that ß-arrestin 1 in cytoplasm may be involved in differentiation and metastasis of gastric cardiac adenocarcinoma.

[Based on EMR for design of telemedical regional healthcare platform].

According to international medical information standard and Chinese healthcare management criterion,this paper study EMR features which focus on standard documents exchange and sharing.Tele Regional Healthcare Platform is established by EMR in order to realize medical resource sharing between big hospital in the situation of China, one solution is offered to stave difficulty and high expense of medical service in countryside.

[Clinical therapeutic effect of esophageal carcinoma with hand video assisted surgery].

OBJECTIVE: To explore the clinical therapeutic effect of esophageal carcinoma with hand video assisted surgery. METHODS: Forty cases which C TNM stage was T3N1M0 received hand video assisted surgery (HVATS group), 40 cases received routine operation (control group). Recurrence survival analysis of each group was analyzed with SPSS10.0 software according to the date of the stage and survival rate. RESULTS: All group have satisfied surgical result. All patients have good quality of life. The 3 year survival rate was 52.7% in HVATS group and 51.3% in control group. The difference of survival rate was no significance. CONCLUSION: Hand video assisted surgery for esophageal carcinoma had same result as routine thoracic operation. Short operation time, less trauma and fast recovery are the advantages of hand video assisted surgery.

[A prospective longitudinal study examining the impact on short term quality of life of hand video-assisted thoracoscopic surgical esophagectomy in patients with esophageal cancer].

OBJECTIVE: To evaluate the impact of hand video-assisted thoracoscopic surgery (HVATS) and Ivor-Lewis surgery on short term quality of life (QL) of patients with esophageal cancer. METHODS: Thirty-nine consecutive patients with esophageal cancer were classified into HVATS group (n = 21) and Ivor-Lewis group (n = 18) randomly, all patients completed the Chinese versions of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and QLQ-OES18 before treatment and at regular intervals until 6 months after operation. MEAN scores were calculated for every patient. RESULTS: Baseline functional and symptom QL MEAN scores were similar in both groups. All patients reported worse functional, symptom and global QL scores (QOL) within 6 months after operation than before. HVATS group gained higher functional, global QL scores and lower symptom scores than Ivor-Lewis group, moreover, patients' QL scores of HVATS group returned to preoperative levels more quickly than those patients in Ivor-Lewis group. Significant differences were found in global health (QOL), physical functioning, fatigue and pain scales between groups. In both groups, QLQ-OES18 dysphagia scales were improved after surgery,but no significant differences were found at scales respect to esophageal cancer. CONCLUSIONS: HVATS esophagectomy is a safe procedure which has a low disturbance to patients' short term Quality of Life compared with Ivor-Lewis esophagectomy. It might seem reasonable to choose HVATS esophagectomy for patients with early stage esophageal cancer.

18F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer.

BACKGROUND: The outcome of surgical treatment of non-small-cell lung cancer (NSCLC) remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. (18)F-fluoro-2-deoxy-glucose ((18)F-FDG) uptake on positron-emission tomography (PET) is associated with the aggressiveness of NSCLC. The present study focused on the role of (18)F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC. METHODS: A retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value (SUV(max)), in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients' recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUV(max) and other factors was also analyzed. RESULTS: Patients with SUV(max) more than 11 had a disease-free survival and overall survival shorter than patients with SUV(max) less than 11 in univariate analyses (P < 0.001, P = 0.002). In the multivariate analysis, SUV(max) (dichotomized by 11) was the only significant predictor for tumor recurrence. TNM stage and SUV(max) (dichotomized by 11) were independent predictors for the overall survival. Associations of SUV(max) with p53 overexpression, proliferating cell nuclear antigen (PCNA) labeling index and microvascular density of the tumor were significant in the entire group. CONCLUSIONS: (18)F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.

[Clinical value of videomediastinoscopy in diagnosis of mediastinal disease].

OBJECTIVE: To evaluate the role of videomediastinoscopy in the diagnosis of disease of the mediastinum. METHODS: We retrospectively reviewed the clinical records of the 115 patients who underwent videomediastinoscopy. Local anesthesia or general anesthesia was employed. This operation consisted of cervical videomediastinoscopy in 102 patients, parasternal videomediastinoscopy in 13 patients, ninety-one patients had videomediastinoscopy for diagnosis of isolated mediastinal mass or lymphadenopathy, 25 patients with non small cell lung cancer or suspected lung cancer showed enlarged mediastinal lymph nodes radiographically in the chest. RESULTS: Among the patients with mediastinal disease, sarcoidosis was diagnosed in 37 patients, tuberculosis in 14 patients, lymphoma in 15 patients, nodal metastasis in 18 patients, noncaseating granulomata without classical "sarcoid" in 6 patients, with the accuracy of 93.3% (84/90); and staging of lung cancer in 25 patients, with the accuracy of 100% (25/25). The total accuracy of videomediastinoscoy and CT was 94.8% (109/115), 56.5% (65/115), respectively. Mean operative time was 26 min. There was neither complication nor mortality. CONCLUSION: videomediastinoscopy is a safe and effective procedure for the diagnosis of mediastinal disease and the staging of lung cancer.

[Resection for lung cancer invading the superior vena cava].

OBJECTIVE: To analyze the feasibility and the value of resection for lung cancer invading the superior vena cava (SVC). METHODS: Between 1988 and 2005 the data of 31 patients who underwent resection were analyzed retrospectively. The reconstruction was done using simple suture, pericardial patch or prosthetic replacement. Postoperative morbidity, long-term survival were examined using the Kaplan-Meier method (Log rank test) and the COX model for survival. RESULTS: Seventeen squamous cell carcinomas, 8 adenocarcinomas, and 6 undifferentiated small cell carcinomas were resected. There were 13 partial SVC resection, the reconstruction was done using a simple running in 5 patients, and a pericardial patch in 8 patients. Eighteen patients underwent complete resection of SVC with prosthetic replacement. The time of clamping the SVC system was from 8 to 35 minutes for complete resection patients, while the time was from 3 to 15 minutes for partial resection patients. One patient didn't clamp the SVC. Postoperative morbidity and mortality were 48% and 0%, respectively. One, 3 and 5-year survival rates were 61%, 33% and 21%, respectively, with median survival at 31 months. Survival rate of patients with N2 disease was obviously lower than those with localized (N0/N1) nodal disease (chi2 = 14.3, P = 0.000), the median survival was 42 and 13 months respectively. There were no significant effects on overall survival with pathologic features and surgery methods. Survival rate of patients with induction chemotherapy before operation or intraoperative chemotherapy was higher than those received direct surgery (chi2 = 5.0, P = 0.025), the median survival was 39 and 14 months respectively. CONCLUSIONS: The resection of the SVC for involvement by lung cancer can be performed in selected patients, especially for those with localized (N0/N1) nodal disease. Induction chemotherapy should be performed.

[Hand-assisted video-thoracoscopy for resection of esophageal cancer].

OBJECTIVE: To explore the feasibility and advantages of hand-assisted video-thoracoscopy for resection of esophageal cancer. METHODS: Forty-five patients with esophageal cancer received hand-assisted video-thoracoscopic esophagectomy (group I). 45 patients underwent esophagectomy through routine open thoracotomy during the same period as control (group II). The data of lymph node resection, operating time and blood loss were compared. RESULTS: There were no operative mortality in 2 groups. In group I, the number of dissected paraesophageal lymph nodes, cardiac lymph nodes and left gastric nodes were (3.6 +/- 1.0), (1.3 +/- 1.1) and (4.3 +/- 1.4), respectively. While for group II the dissected lymph nodes were (3.3 +/- 1.5), (1.6 +/- 1.1) and (4.7 +/- 2.1), respectively. There was no significant difference between two groups (P > 0.05). However, the number of dissected mediastinal nodes was (6.6 +/- 3.7) for group I and (3.8 +/- 2.5) for group II (chi(2) = 2.95, P < 0.05). The mean operating time was (29 +/- 5) minutes for group I and (60 +/- 6) minutes for group II. The mean blood loss was (93 +/- 19) ml for group I and (145 +/- 35) ml for group II. The mean chest tube drainage was (201 +/- 45) ml for group I and (295 +/- 57) ml for group II in the first postoperative day. The difference in above parameters between 2 groups was significant (chi(2) = 18.69, 6.13, 6.08, P < 0.001). CONCLUSIONS: It is suggested that hand-assisted video-thoracoscopic esophagectomy is a safer, minimal invasive procedure in the resection of esophagus carcinoma.

[The clinical significance of vascular endothelial growth factor and intercellular adhesion molecule-1 expression in non-small cell lung cancer].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1), and their relationship to behaviors of the non-small-cell lung cancer. METHODS: The study included 86 patients with non-small-cell lung cancer. A rapid immunohistochemical method (streptoavidin-peroxidase, SP) was used to detect VEGF and ICAM-1 expression. All patients were treated surgically and without preoperative radio- or chemotherapy. RESULTS: The positive expression of VEGF was significantly correlated with the lymph node metastasis, TNM stage, prognosis and hematogenous tumor metastasis positively, but ICAM-1 was negatively. For patients with positive expression of VEGF and negative expression of ICAM-1, the 5-year survival rate was the lowest in all patients. CONCLUSIONS: The expression of VEGF and ICAM-1 correlates with the malignant behavior of non-small-cell lung cancer. Examination of VEGF and ICAM-1 in non-small-cell lung cancer may help to evaluate its intensity of lymph node metastasis, TNM stage and prognosis. VEGF and ICAM-1 may play an important role in the development and metastasis of non-small-cell lung cancer.