[Clinical characteristics and management of Petersen hernia after gastrectomy in patients with gastric cancer].

Objective: Petersen hernia is a rare but severe complication after gastrectomy, which has been reported by very few studies. This study is dedicated to summarize the clinical characteristics and management of Petersen hernia after gastrectomy in patients with gastric cancer in order to provide reference to clinical practice. Methods: A descriptive case-control study was carried out. All the qualified patients were screened from the database of digestive malignancies in Nanjing Drum Tower Hospital. The inclusion criteria were as follows: Petersen hernia confirmed during operation; previous gastrectomy history due to gastric cancer; complete clinical data. The clinical manifestation, perioperative data and follow-up outcome were summarized. Results: A total of 12 qualified patients were included. They were all male with a mean age of (65.3±8.5) years old, and whose clinical presentation had last for (6~143) hours (median: 21 hours). Common complaints included abdominal pain and bloating. All the patients were admitted to the emergency department. Preoperative CT showed dilatation and effusion of small intestine. Other imaging manifestations included whirlpool sign, target sign, mesenteric retraction or congestion and edema, abdominal and pelvic effusion, etc. Hematological examination showed white blood cell count, ratio of neutrophils, procalcitonin and C-reactive protein were higher than the normal range. The median interval to previous gastrectomy is 20.5 (0.5-55.0) months. The previous gastrectomy of 12 cases included 2 cases of laparoscopic surgery and 10 of laparotomies. Ten cases underwent emergency surgery immediately, and 2 cases underwent surgery after ineffective conservative treatment. Six cases received small bowel restoration without bowel resection, and the other 6 cases received small bowel resection with a mean length of 76 (11~300) cm. Six cases were transferred into ICU with a stay of (2.5±0.8) days. One case deceased at postoperative day 2, due to subtotal small bowel resection, and the other 11 cases survived without grade III or above complication according to Clavien-Dindo classification. The overall postoperative hospitalization was (9.2±3.6) days. During the postoperative follow-up, no acute gastrointestinal symptoms or acute abdomen recurred. Conclusions: Petersen hernia is more common in male, whose onset and progress are rapid and emergent, and prognosis is poor.

Genomic origin and EGFR-TKI treatments of pulmonary adenosquamous carcinoma.

BACKGROUND: Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. PATIENTS AND METHODS: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. RESULTS: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2). CONCLUSIONS: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.

Cloning and functional identification of moricins from the diamondback moth, Plutella xylostella (L.).

Antimicrobial peptides (AMPs) are small-molecule peptides that play crucial roles in insect innate immune responses. To better understand the function of AMPs in Plutella xylostella, one of the main pests of cruciferous vegetables, three full-length cDNAs encoding moricins were cloned from Pl. xylostella. Two variants of the moricin named PxMor2 and PxMor3 were heterologously expressed and purified. A secondary structure analysis using circular dichroism demonstrated that the two peptides adopted an α-helical structure in the membrane-like environment, but in aqueous solution, they were present in random coiled conformation. Antimicrobial activity assays demonstrated that PxMor2 exhibited high activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli; however, PxMor3 only demonstrated high activity against E. coli. Scanning electron microscopy and confocal laser-scanning microscopy analyses suggest that PxMors can lead to the disruption of bacterial membrane, which might be the mechanism by which PxMors inhibit bacterial growth. This study contributes to the understanding of Pl. xylostella AMPs and immune responses, and also enriches the knowledge of insect moricin.

[Effect of peroxisome proliferator-activated receptor-γ coactivator-1α on metastasis and anoikis resistance in colorectal cancer].

OBJECTIVE: To investigate the role of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in the metastasis of colorectal cancer and underlying mechanisms. METHODS: A colorectal cancer LoVo cell line transfected with a lentivirus vector stably expressinga shRNA targeting PGC-1αwas established. Cell proliferation was detected by CCK8 array. Migration and invasion were determined by Transwell assay. The expressions of epithelial-mesenchymal transition (EMT) markers were examined by western blot analysis. RESULTS: Down-regulation of PGC-1α significantly inhibited the migration (74.4±4.5 versus 31.4±3.8,P<0.05), invasion (55.0±7.7 versus 17.6±5.0,P<0.05) and anoikis resistance (32.3±4.3)% versus (54.3±4.8)%,P<0.05, of LoVo cells. However, knockdown of PGC-1α had little effect on cell proliferation. Moreover, knockdown of PGC-1α induced EMT of LoVo cells by up-regulating E-cadherin and down-regulating vimentin. Alternatively, the expression of PGC-1α was induced by cell detachment. PGC-1αexpression was also higher in the colorectal cancer tissues than that in para-cancerous tissues, and its expression in the invading front area was higher than that in the tumor center area. CONCLUSION: PGC-1α plays an important role in the metastasis of colorectal cancer, which may promote the invasion and anoikis resistance of colorectal cancer cells through EMT induction.

Inhibition of mTOR suppresses human gallbladder carcinoma cell proliferation and enhances the cytotoxicity of 5-fluorouracil by downregulating MDR1 expression.

OBJECTIVE: Although 5-fluorouracil (5-FU) is widely used in the treatment of various cancers, drug resistance remains a limitation for its anti-cancer activity. Mammalian target of rapamycin (mTOR) is deregulated in diverse human cancers, including gallbladder carcinoma and mTOR inhibitors show promising anti-cancer activities with proliferation inhibitory effects. This study aims to clarify the benefit of the combination of 5-FU and the mTOR inhibitor, OSI-027, on gallbladder carcinoma cell proliferation. MATERIALS AND METHODS: Two gallbladder carcinoma cell lines and two agents (5-FU and OSI-027) were used in the present study. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. The expression of MDR1 protein was determined by western blot analysis. RESULTS: The combination of OSI-027 with 5-FU showed a synergistic anti-proliferative effect on the gallbladder cancer cells, RBE and GBC-SD cells. Upon 5-FU treatment, MDR1 expression was upregulated and OSI-027 could reverse 5-FU-induced MDR1 upregulation. Moreover, MDR1 depletion sensitized gallbladder carcinoma cells to 5-FU stimulation and attenuated the synergistic effect of OSI-027 and 5-FU. Finally, we determined that OSI-027 downregulated MDR1 expression by suppressing its synthesis rather than by promoting its degradation. CONCLUSIONS: Dual mTORC1/mTORC2 inhibitors such as OSI-027 are promising therapeutic agents in combination with 5-FU for the treatment of human gallbladder cancer.

Effect of phospholipid on trichosanthin adsorption at the air-water interface.

Trichosanthin (TCS) is a toxic protein with multiple pharmacological properties. It belongs to the type I ribosome inactivating protein (RIP) family and can inactivate the eukaryotic ribosome through its RNA N-glycosidase activity. The interaction between TCS and phospholipid membrane was thought to be essential for its physiological effect, for it must get across the cell membrane before it can enter the cytoplasm and exert its RIP function. In order to study the TCS-phospholipid interaction, the difference between spontaneous and phospholipid induced adsorption of TCS at the air-water interface was investigated, and the results were analyzed according to the diffusion-penetration-rearrangement adsorption model. The results showed that both negatively charged 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and neutral 1,2-dipalmitoyl-sn-glycero-3-phosphocholine can accelerate the adsorption rate, while there exists a possible membrane induced conformational change of TCS which is specific for the negatively charged DPPG. We also proposed a revised model for the diffusion controlled initial adsorption period.

The membrane insertion of trichosanthin is membrane-surface-pH dependent.

Trichosanthin (TCS) is the active component extracted from Tianhuafen, a traditional herbal medicine that has been used for abortion in China for centuries. It belongs to the type-I ribosome-inactivating protein (RIP) family and can inactivate the eukaryotic ribosome through its RNA N-glycosidase activity. Recent studies have shown TCS to be multifunctional, its pharmacological properties including immunomodulatory, anti-tumour and anti-HIV activities. The membrane-insertion property of TCS is thought to be essential for its physiological effect, for it must get across the membrane before it can enter the cytoplasm and exert its RIP function. In this paper, the membrane-insertion mechanism of TCS was studied. The monolayer experiment revealed that TCS's membrane-insertion ability was dependent on low pH. Fluorescence spectroscopy using 1-anilinonaphthalene-8-sulphonic acid as a probe showed that low pH may induce the conformational change of TCS that leads to the hydrophobic-site exposure, and the CD result showed that this conformational change did not alter its secondary structure. Such conformational change leads to an intermediate state, called the 'molten globular state' by previous investigators. The pH-dependent membrane insertion and conformational change were related by the fact that the optimal membrane-surface pH needed was the same for the two events. From these and other results, a membrane-insertion model was proposed.