Totally laparoscopic gallbladder-preserving surgery: A minimally invasive and favorable approach for cholelithiasis.

The aim of the present study was to investigate the effectiveness of laparoscopic gallbladder-preserving surgery (L-GPS) for cholelithiasis and the feasibility and value of totally laparoscopic GPS (TL-GPS). A total of 517 patients underwent L-GPS, including 365 cases of laparoscopy-assisted GPS (LA-GPS), 143 cases of TL-GPS (preservation rate, 98.3%) and nine conversions to laparoscopic cholecystectomy. The surgeries were all performed by one medical team and the mean operating time was 72 min. All macroscopic calculi were removed through endoscopy. The number of calculi observed in the patients was between one and several dozen; diameters ranged between 0.1 and 2.5 cm. Only three cases of incisional infection were noted in the LA-GPS group and long-term follow-up showed a low recurrence rate of 1.2%. L-GPS is, therefore, an excellent approach to cure cholelithiasis and TL-GPS is a feasible and effective option that could avoid incisional complications.

Disturbance of autophagy-lysosome signaling molecule expression in human gastric adenocarcinoma.

Autophagy is classified as type II programmed cell death and may participate in tumorigenesis. However, changes in autophagy-lysosome signaling and the relationship between the apoptotic cascade and gastric cancer cells have not been fully elucidated. The present study investigated the induction of autophagy in poorly differentiated human gastric adenocarcinoma. Immunoblotting revealed markedly induced autophagy in low grade differentiated gastric adenocarcinoma, indicated by elevation of microtubule-associated protein 1 light chain 3-I/II conversion and Beclin 1 in human gastric carcinomas. In addition, the diffuse (poorly differentiated) subtype showed significantly elevated Lamp2 and cathepsin B protein levels. Concomitantly, significant induction of anti-apoptotic events were indicated by changes in B-cell lymphoma 2 (Bcl-2) and X-linked inhibitor of apoptosis protein levels. Notably, confocal laser microscope data indicated co-expression of Bcl-2 and Beclin 1 in poorly differentiated human gastric adenocarcinoma. Results of this study indicate that the autophagy-lysosome signaling participates in poorly differentiated human gastric adenocarcinoma and there are intracellular links between autophagic signaling and the apoptotic cascade.

Blocking Bcl-2 leads to autophagy activation and cell death of the HEPG2 liver cancer cell line.

BACKGROUND: Apoptosis may be induced after Bcl-2 expression is inhibited in proliferative cancer cells. This study focused on the effect of autophagy activation by ABT737 on anti-tumor effects of epirubicin. METHODS: Cytotoxic effects of ABT737 on the HepG2 liver cancer cell line were assessed by MTT assay and cell apoptosis through flow cytometry. Mitochondrial membrane potential was measured by fluorescence microscopy. Monodansylcadaverin (MDC) staining was used to detect activation of autophagy. Expression of p53, p62, LC3, and Beclin1, apoptotic or autophagy related proteins, was detected by Western blotting. RESULTS: ABT737 and epirubicin induced growth inhibition in HepG2 cells in a dose- and time-dependent manner. Both ABT737 and epirubicin alone could induce cell apoptosis with a reduction in mitochondrial membrane potential as well as increased apoptotic protein expression. Further increase of apoptosis was detected when HepG2 cells were co- treated with ABT373 and epirubicin. Furthermore, our results demonstrated that ABT373 or epirubicin ccould activate cell autophagy with elevated autophagosome formation, increased expression of autophagy related proteins and LC3 fluorescent puncta. CONCLUSIONS: ABT737 influences cancer cells through both apoptotic and autophagic mechanisms, and ABT737 may enhance the effects of epirubicin on HepG2 cells by activating autophagy and inducing apoptosis.

Inhibition of proliferation of estrogen receptor­positive MCF­7 human breast cancer cells by tamoxifen through c­Jun transcription factors.

Activator of protein 1 (AP-1) is a heterodimeric transcription factor composed of various members of the Jun and Fos families and binds to DNA at specific AP-1 binding sites. AP-1 transcriptional activity is increased by phosphorylation at serine residues in the c­Jun component of AP-1. In the present study, the proliferation of MCF-7 breast cancer cells was found to be suppressed by tamoxifen (TAM)-activated c-Jun through the protein kinase C (PKC) pathway. The molecular mechanism by which c­Jun activation induces antiproliferative signals in estrogen receptor (ER)-positive MCF-7 human breast cancer cells remains unknown. TAM inhibited the proliferation of ER-positive MCF-7 human breast cancer cells and ER-negative MDA-MB-435 human breast cancer cells and 48 h incubation with 10 µM TAM led to inhibition of 80% of proliferation. In addition, no significant difference in c-Jun mRNA and protein levels was detected in MCF-7 and MDA-MB-435 cells stimulated by TAM for 48 h. TAM treatment of MCF-7 cells activated the transcriptional activity of AP-1, which responds specifically to phorbol ester. To determine the role of c-Jun in the antiproliferation of MCF-7 cells stimulated by TAM, the inhibition rates of MCF­7 cells were correlated with c­Jun expression and stimulation of TAM. Results showed that the inhibition rate of TAM-stimulated MCF-7 cells was positively regulated by overexpression of c-Jun and negatively regulated by underexpression of c-Jun. Overall, these results indicate that the TAM-stimulated antiproliferation of MCF-7 cells is positively regulated by c-Jun through activation of the PKC pathway.