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Background: Metabolic syndrome (MetS) is a group of clinicopathological manifestations. The outcome of liver surgery in metabolic syndrome-related hepatocellular carcinoma (MetS-HCC) still needs to be evaluated. We aim to clarify the outcomes following liver resection in patients with MetS-HCC compared those with hepatitis B virus-related HCC (HBV-HCC).Methods: All the consecutive patients undergoing hepatectomy for HCC between January 2009 and December 2012 were retrospectively considered. Patients were divided into three groups: MetS-HCC, MetS-HBV-HCC, and HBV-HCC. Data on clinical characteristics, postoperative complications, and long-term outcome were collected and analyzed.Results: A total of 1352 patients were included in this study. In MetS-HCC group, the severe morbidity rate was 33.33%, which was higher than that of HBV-HCC group (15.68%). In subgroup analysis, patients with MetS-HCC in American Joint Committee on Cancer (AJCC) stage I had superior DFS and OS when compared with those of the other two groups.Conclusions: We should pay more attention to patients with MetS-HCC perioperatively due to the high rate of surgical complications. Nevertheless, curative treatment should be provided to patients with MetS. [ABSTRACT FROM AUTHOR]

Incarcerated femoral hernia is a common surgical acute abdominal disease. Laparoscopic surgery is considered a safe and effective method for treating incarcerated femoral hernias, which have different surgical approaches to releasing the contents of the hernia. We report the case of a 65-year-old female with a right incarcerated femoral hernia with an irreducible mass in the right femoral region for 2 days diagnosed by physical examination and abdominal ultrasonography. We used a catheter to inject normal saline into the hernia sac during surgery. Injury and rupture of the small intestine were avoided, and the polypropylene mesh was successfully repaired. Incarcerated femoral hernias is a common surgical emergency that can lead to intestinal obstruction, strangulation, or infarction. Laparoscopy is advantageous for treating incarcerated femoral hernias. In our case, spatial replacement theory was used to release the incarcerated small intestine. The principle is that changing the internal and external pressures of the hernial sac returns the hernia contents. The non-necrotic small intestine did not lead to intraperitoneal infection, and the standard transabdominal preperitoneal repair was simultaneously performed with a polypropylene mesh. Laparoscopic incarcerated femoral hernia repair is a common emergency surgery that is safe and feasible for treating incarcerated femoral hernia using the spatial replacement method, the most beneficial to patients. • Laparoscopic exploration to determine bowel activity in incarcerated femoral hernias • Using the space replacement method to successfully release the incarcerated small intestine can avoid iatrogenic intestinal damage • The non-necrotic small intestine will not cause intra-abdominal infection, and at the same time use polypropylene mesh for standard TAPP repair to avoid secondary hernia repair [ABSTRACT FROM AUTHOR]

[Display omitted] Autophagy has become a promising target for cancer therapy. Fangchinoline (Fan) has been shown to exert anticancer effects in some types of cancers. However, the anticancer effects on colorectal cancer (CRC) and the underlying mechanisms have never been elucidated. More specifically, regulation of autophagy in CRC by Fan has never been reported before. In the present study, Fan was found to induce apoptosis and autophagic flux in the CRC cell lines HT29 and HCT116, which was reflected by the enhanced levels of LC3-II protein and p62 degradation, and the increased formation of autophagosomes and puncta formation by LC3-II. Meanwhile, combination with the early-stage autophagy inhibitor 3-methyladenine (3-MA) but not the late-stage autophagy inhibitor chloroquine (CQ) further increased Fan-induced cell death, which suggested the cytoprotective function of autophagy induced by Fan in both HT29 and HCT116 cells. Moreover, Fan treatment demonstrated a dose- and time-dependently increase in the phosphorylation of AMPK and decrease in the phosphorylation of mammalian target of rapamycin (mTOR) and ULK1, leading to the activation of the AMPK/mTOR/ULK1 signaling pathway. Furthermore, in the HT29 xenograft model, Fan inhibited tumor growth in vivo. These results indicate that Fan inhibited CRC cell growth both in vitro and in vivo and revealed a new molecular mechanism involved in the anticancer effect of Fan on CRC, suggesting that Fan is a potent autophagy inducer and might be a promising anticancer agent. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) are an integral part of the tumor microenvironment (TME), which is involved in therapy resistance. This study aimed to investigate the role of CAFs in radiosensitivity of breast cancer cells. The CAFs were isolated from the breast cancer tissues, and the conditioned medium was collected to culture breast cancer cells. Radiation-induced DNA damage was evaluated by immunofluorescence and western blotting. Cytokine array and enzyme-linked immunosorbent assay were performed to analyze the secretion of cytokines and growth factors. An in vitro clonogenic survival assay and in vivo xenograft mouse model were performed to determine the radiosensitivity of breast cancer cells. Finally, the expression of hepatocyte growth factor (HGF) and c-Met in the breast cancer tissues were detected by immunohistochemistry. The CAFs were found to secrete HGF to activate the c-Met signaling pathway, which induced epithelial-to-mesenchymal transition, growth, and radioresistance of breast cancer cells. Furthermore, radiation was observed to enhance HGF secretion by CAFs and increase c-Met expression in breast cancer cells, which led to HGF/c-Met signaling pathway activation. Moreover, radiation-induced tumor necrosis factor α (TNFα) secretion by breast cancer cells promoted CAF proliferation and HGF secretion. Additionally, HGF and c-Met high expression were associated with worse recurrence-free survival in patients with breast cancer who had received radiation therapy. The findings revealed that HGF and TNFα are critical for the crosstalk between breast cancer cells and CAFs in the TME and that the HGF/c-Met signaling pathway is a promising therapeutic target for radiosensitizing breast cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] Ovarian cancer (OC) is the most common gynecological malignancy. Chemotherapy failure is a major challenge in OC treatment. Targeting autophagy is a promising strategy to enhance the cytotoxicity of chemotherapeutic agents. In this study, we found that costunolide (CTD) inhibits autophagic flux and exhibits high therapeutic efficacy for OC treatment in an in vitro model. Mechanistically, CTD inactivates AMPK/mTOR signaling to inhibit autophagy initiation at the early stage and blocks mTORC1-dependent autophagosome–lysosome fusion at the late stage during autophagy by disrupting SNARE complex (STX17–SNAP29–VAMP8) formation, resulting in lethal autophagy arrest in OC cells. Furthermore, CTD sensitizes OC cells to cisplatin (CDDP) by blocking CDDP-induced autophagy both in vitro and in vivo. Together, our data provide novel mechanistic insights into CTD-induced autophagy arrest and suggest a new autophagy inhibitor for effective treatment of OC. [ABSTRACT FROM AUTHOR]

Abstract: Mammosphere culture of cancer cell lines is an important approach used for enrichment of stem-like cancer cells (SLCs), but over-subcultured cell lines have been experimentally shown to change properties over time. It remains unclear if mammosphere cells (MSs) derived from high-passage cancer cell lines retain the tumorigenicity and radioresistance seen in MSs from primary or low-passage cell lines. In this study, we report that mammospheres derived from MCF-7 sublines after different passage numbers were consistently enriched for CD44+/CD24−/low cells but were not consistently enriched for tumorigenic and radioresistant cells. The tumorigenicity and radioresistance of MSs were associated with their sphere-forming ability, proliferation ability in vitro, and intracellular reactive oxygen species (ROS) levels. The radioresistant MSs showed significant cell cycle arrest in G2/M phase after X-ray irradiation and expressed higher ataxia telangiectasia mutated (ATM) mRNA levels. These results suggest that MSs from high-passage cancer cell lines were not consistently enriched for stem-like cancer cells with higher tumorigenicity and enhanced radioresistance. [Copyright &y& Elsevier]

Purpose: Polo-like kinase 1 (PLK1) is a protein kinase that is overexpressed in breast cancer and may represent an attractive target for breast cancer treatment. However, few studies have investigated the relationship between PLK1 and radiosensitivity in breast cancer. Here, we attempted to explore whether PLK1 inhibition could sensitize breast cancer cells to radiation.Methods and Materials: Breast cancer cells were treated with PLK1 small interference RNA or the PLK1-inhibitor, GSK461364. Cell proliferation was assessed using a colony formation assay. Cell cycle analyses were performed by flow cytometry. DNA damage, autophagy, and reactive oxygen species induced by ionizing radiation were detected by immunofluorescence, Western blot, and flow cytometry, respectively. Microtubule-associated protein 1 light chain 3 alpha (LC3) puncta were detected using an immunofluorescence assay. A clonogenic survival assay was used to determine the effect of PLK1 inhibition on cell radiosensitivity. A xenograft mouse model of breast cancer cells was used to investigate the potential synergistic effects of PLK1 inhibition and irradiation in vivo. Finally, the expression of PLK1 and LC3 in the breast cancer tissues was evaluated by immunohistochemistry.Results: PLK1 inhibition significantly suppressed the proliferation and increased the radiosensitivity of breast cancer cells. Pharmacologic inhibition of PLK1 by the selective inhibitor, GSK461364, enhanced the radiosensitivity of breast cancer cells in vivo (n = 4, P = .002). Mechanistically, PLK1 inhibition led to the downregulation of radiation-induced reactive oxygen species and autophagy, thereby increasing the radiosensitivity of breast cancer cells. Additionally, we detected a positive correlation between the expression of PLK1 and LC3 in human breast cancer samples (n = 102, R = 0.486, P = .005).Conclusions: Our findings indicate that PLK1 inhibition enhances the radiosensitivity of breast cancer cells in a manner associated with the suppression of radiation-induced autophagy. The inhibition of PLK1 represents a promising strategy for radiosensitizing breast cancer. [ABSTRACT FROM AUTHOR]