S-adenosylmethionine induces apoptosis and cycle arrest of gallbladder carcinoma cells by suppression of JAK2/STAT3 pathways.

S-adenosylmethionine (SAM) is a naturally occurring physiologic molecule found ubiquitously in all mammalian cells and an essential compound in many metabolic pathways. It has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, the precise molecular mechanism involved in its anticancer effect is not yet clear. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of SAM on human gallbladder cancer cells (GBC-SD and SGC-996) in vitro and in vivo. Cells were dealt with SAM and subjected to cell viability, colony formation, Hoechst staining, apoptosis, cycle arrest, western blot, and xenograft tumorigenicity assay. Experimental results showed that SAM could significantly inhibit the growth and proliferation and induce the apoptosis as well as cell cycle arrest in G0/G1 phase of GBC-SD and SGC-996 cells in a dose-dependent manner in vitro. The expression levels of p-JAK2, p-STAT3, Mcl-1, and Bcl-XL were significantly downregulated. In addition, inhibition of the JAK2/STAT3 pathway significantly enhanced the anti-apoptotic effect of SAM, suggesting the key roles of JAK2/STAT3 in the process. More importantly, our in vivo studies demonstrated that administration of SAM could significantly decrease the tumor weight and volume and immunohistochemistry analysis proved the downregulation of p-JAK2 and p-STAT3 in tumor tissues following SAM treatment, consistent with our in vitro results. In summary, our findings indicated that SAM can inhibit cell proliferation and induce apoptosis as well as cycle arrest of GBC cells by suppression of JAK2/STAT3 pathways and the dramatic effects of SAM hinting that SAM might be a useful therapeutic option for patients suffering from gallbladder cancer.

Study on the effect of integrin ανß6 on the proliferation and apoptosis of thyroid carcinoma cells.

PURPOSE: To study the effect of integrin αvß6 on the proliferation and apoptosis of thyroid carcinoma cells. METHODS: The experiment was conducted on 3 groups : the control group, the positive observation group (in which the ανß6 on the surface of the thyroid carcinoma cell line SW579 was blocked by monoclonal antibody 10D5) and the negative observation group (in which the ανß6 was dealt with the negative placebo of 10D5-the IgG2a). Cell proliferation was detected by MTT assay, apoptosis by flow cytometry and the protein levels in Caspase-3, CyclinB1 and Bcl-xl as well as the protein levels in ERK, p-ERK, JNK, p-JNK, p38 and p-p38 were detected by Western blot. RESULTS: The cell survival rates of the control group and the negative observation group were prominently higher than those of the positive observation group, following decrease in the apoptosis rates, and the differences were statistically significant (p<0.05). The protein levels in CyclinB1 and Bcl-x1 of the control group and the negative observation group were prominently higher than those of the positive observation group, whereas the levels in Caspase-3 were decreased; the differences were statistically significant (p<0.05). The protein levels in p-ERK, p-JNK and p-p38 of the control group and the negative observation group were prominently higher than those of the positive observation group, while the protein levels of ERK, JNK and p38 showed no difference. CONCLUSION: Integrin ανß6 can mediate the MAPK signal pathway of the cells and regulate the expression of CyclinB1 and the apoptosis-related proteins like Bcl-x1 and Caspase-2, thus affecting the process of the proliferation and apoptosis of thyroid carcinoma cells.

Elevated expression of KLK8 predicts poor prognosis in colorectal cancer.

KLK8, also known as neuropsin, is one of fifteen members of the human kallikrein-related peptidase (KLK) gene family, which consists of enzymes with serine protease enzymatic activity. Aberrant KLK8 expression has been reported in several malignancies. However, the clinicopathological significance and prognostic value of KLK8 expression in colorectal cancer (CRC) are unknown. Therefore, analysis of public datasets, quantitative real-time PCR and western blot analysis were performed to assess KLK8 expression in CRC at both the mRNA and protein level. KLK8 expression was also assessed by immunohistochemistry in a tissue microarray containing 124 CRC specimens. We observed that KLK8 was overexpressed in CRC tissues and was significantly associated with TNM stage, vascular invasion, differentiation and AJCC stage. Univariate and multivariate Cox analyses confirmed that KLK8 is a significant independent prognostic factor for both DFS and OS. Cell function assays also indicated that KLK8 could facilitate CRC cell proliferation, migration and invasion in vitro. In conclusion, elevated KLK8 expression was correlated with the progression of CRC and is a potential independent prognostic indicator for CRC.

Comparison of the breast and areola approaches for endoscopic thyroidectomy in patients with microcarcinoma.

The safety, advantages and disadvantages of thyroidectomy for microcarcinoma through the areola approach and breast approach were compared. Fifty patients diagnosed with thyroid microcarcinoma in our department from January 2014 to June 2015 were selected. The areola approach was carried out for 21 patients whereas the breast approach for 29 patients. Endoscopic thyroid lobectomy, isthmus resection and dissection of central group lymph nodes was performed. The clinical outcomes of the two surgical approaches were compared. Comparing operating time, blood loss during surgery, number of lymph node dissections, postoperative hospitalization time and surgical complications between the surgical approaches, there were no significant differences (P>0.05). Comparing patient satisfaction of cosmetic results from the incisions, the difference was statistically significant (P<0.05). Endoscopic thyroidectomy via areola approach and breast approach have equal curative effects for the treatment of thyroid microcarcinoma. However, the areola approach can achieve better cosmetic results and is a safe and ideal surgical method, that we recommend be widely used.

A Controlled Study of Alprostadil Liposomal Preparation in the Treatment of Blue Toe Syndrome.

The aim of this study is to examine the efficacy of alprostadil liposomal preparation in the treatment of blue toe syndrome. As many as 32 patients with blue toe syndrome were randomized into the test group and a control group. Patients out of the test group were treated with alprostadil liposomal preparation, while those out of the control group received placebo administration. Inter-group comparisons were conducted for the post-therapeutic changes of microcirculation and improvements of clinical symptoms. In the test group, there were eight subjects with marked response (50.0 %), six subjects with partial response (37.5 %), and two subjects with no response (12.5 %), with the overall response rate of 87.5 %. In the control group, there were three cases (18.8 %), one case (6.4 %), and 12 cases (75 %), respectively, with the overall response rate of 25.0 %. The inter-group difference of response was statistically significant (Χ (2) = 12.987, P = 0.002 < 0.05). In the test group, there was one case of administration site redness which could be resolved spontaneously. No other adverse drug reactions were reported. No any complaints were reported for the control group. The inter-group difference of nail-fold microcirculation was not statistically significant (P > 0.05). The post-therapeutic points of nail-fold microcirculation in the test group decreased significantly (P < 0.05), but no significant changes were observed for the control group (P > 0.05). The post-therapeutic waveform changes of photoelectric plethysmography were significant for the test group in comparison to the control. The safety and efficacy of alprostadil liposomal preparation have been demonstrated in the treatment of blue toe syndrome.

Investigation on etiology of hepatic venous obstruction Budd-Chiari syndrome.

Budd-Chiari syndrome (BCS) is an uncommon clinical condition with a complex etiology. Pathogenesis of BCS is still poorly understood. We included hepatic veno-occlusive lesion tissues of 20 patients (patients group) with hepatic venous obstruction BCS and compared with 20 similar tissues with other etiologies (control group). Morphological changes in hepatic veno-occlusive lesion tissues and the positive expression of proliferating cell nuclear antigen (PCNA), C-myc, and P-53 were observed by the pathological examination (H&E staining) and immunohistochemistry assay. Our results showed that PCNA and C-myc positive cell densities were significantly higher in patient group than control group. P-53 positive cell density showed increasing trends in patients than control group. Moreover, we observed irregular hyperplasia in intimal tissue, fibrous connective tissue, and smooth muscle cell, accompanied by tissue degeneration (hyaloid degeneration and fibrinoid degeneration) and a large quantity of inflammatory cell infiltration. In conclusion, an overexpression of PCNA, C-myc, and a weak positive expression of P53 might launch the extremely irregular hepatic venous intimal hyperplasia, which is probably one of the etiologies of hepatic venous obstruction BCS.