MAP7 Promotes Breast Cancer Cell Migration and Invasion by Regulating the NF-B Pathway.

OBJECTIVE: To investigate and explore the molecular mechanisms of MAP7 on breast cancer cell migration and invasion. METHODS: The MAP7 transcript data in TCGA database was firstly statistically analyzed. Then, immunohistochemistry and western blot assays were applied to check MAP7 expression levels in breast cancer tissues or cell lines. EdU immunofluorescent staining assay was applied to reveal the cell proliferation of breast cancer cells after knockdown or overexpression of MAP7. Scratch and Transwell assays were applied to observe cell invasion and migration after knockdown or overexpression of MAP7. The western blot assays were employed to prove the expression levels of NF-B p65 and IBα after knockdown or overexpression of MAP7. Finally, breast xenograft model was established to verify the tumor volume and weight in mice. RESULTS: The results indicated the mRNA and protein expression of MAP7 was higher in breast cancer tissues or cell lines than that in normal tissue or normal breast epithelial cells, respectively. MAP7 promoted proliferation, migration, and invasion of breast cancer cells. Knockdown or overexpression of MAP7 in breast cancer cells would inhibit or promote phosphorylation of NF-B p65 and IBα protein. Finally, MAP7 can also promote tumor growth in mice. CONCLUSIONS: MAP7 facilitated breast cancer cell migration and invasion by regulating the NF-B pathway.

The Role of Adjuvant Chemotherapy in Metaplastic Breast Carcinoma: A Competing Risk Analysis of the SEER Database.

Purpose: Chemotherapy is the clinically recommended treatment for patients with operable metaplastic breast carcinoma (MBC); however, its impact remains controversial. This study investigated the possible role of chemotherapy in the treatment of MBC. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify the operable MBC patients. The competing risk analysis along with the propensity score matching (PSM) method was performed to evaluate the effect of chemotherapy. Moreover, a competing risk nomogram was built to identify prognosis in patients with MBC. Results: Of the 1137 patients with MBC, 775 received chemotherapy and 362 did not receive chemotherapy. The 5-year cumulative incidence of breast cancer-specific death (BCSD) showed similar outcomes in both the Chemo and No-Chemo groups (21.1 vs. 24.3%, p = 0.57). Chemotherapy showed no apparent association with BCSD (HR, 1.07; 95% CI, 0.72-1.60; p = 0.72), even after subgroup analysis or PSM. Race, tumor size, lymph node status, and radiation were identified as the significant factors for MBC after a penalized variable selection process. In addition, a competing risk nomogram showed relatively good accuracy of prediction with a C-index of 0.766 (95% CI, 0.700-0.824). Conclusion: Our findings demonstrated that chemotherapy did not improve BCSD for operable MBC patients. Thus, it may indicate the need to reduce exposure to the current chemotherapy strategies for patients with resectable MBC. Additionally, some novel treatment strategies are required urgently to identify and target the potential biomarkers.

Role of marital status on the prognosis in esophagus adenocarcinoma: a real-world competing risk analysis.

Aim: The purpose of this study was to assess the role of marital status in esophageal adenocarcinoma (EAC). Methods: We identified 8341 EAC patients based on the Surveillance, Epidemiology and End Results database during 2007-2015, of whom 7275 were male and 1066 were female. Temporal trends, competing risk analysis and propensity score matching were performed. Results: There was an upward trend for the rate of unmarried patients in both male and female populations (p < 0.05). Unmarried status represented an independent risk factor for higher cancer-specific death (CSD) in males (hazard ratio: 1.11; 95% CI: 1.04-1.18; p = 0.001) but not in females (hazard ratio: 0.96; 95% CI: 0.81-1.13; p = 0.610). Married EAC patients experienced lower CSD compared with their unmarried counterparts in the male cohort.

Intraperitoneal perfusion chemotherapy and whole abdominal hyperthermia using external radiofrequency following radical D2 resection for treatment of advanced gastric cancer.

BACKGROUND: The peritoneum is the most frequent site of disease recurrence in gastric cancer, and the prognosis remains poor. This study assessed the role of adjuvant intraperitoneal (IP) chemotherapy with whole abdominal hyperthermia using external radiofrequency in gastric cancer patients after D2 dissection. METHODS: Patients with gastric cancer who underwent gastrectomy with D2 regional lymph node dissection were enrolled in the study. Patients received IP chemotherapy with whole abdominal hyperthermia. Preheated normal saline containing 75 mg/m2 of cisplatin was delivered into the abdominal cavity through a Tenckhoff catheter at McBurney's point. Regional hyperthermia was performed using two sets of orthogonal radiofrequency waves immediately after all saline was irrigated into the abdominal cavity. For each patient, recurrent or metastatic sites and adverse events were evaluated. RESULTS: A total of 22 patients were finally included. All patients tolerated hyperthermia well. Only two patients experienced grade 1 superficial thermal injury. The most frequent grade 3/4 adverse events were myelosuppression, nausea/vomiting, trichomadesis and liver dysfunction. We also found IP chemotherapy with whole abdominal hyperthermia could reduce the total recurrent/metastatic rate, especially peritoneal metastasis (4.5%). CONCLUSIONS: This hypothesis-generating study indicated that IP chemotherapy with whole abdominal hyperthermia might be feasible for gastric cancer patients after D2 resection.

miRNA-200c enhances radiosensitivity of esophageal cancer by cell cycle arrest and targeting P21.

Esophageal squamous cancer is one of the most fatal malignancies and often suffer recurrence after radiotherapy. Downregulation of miRNA-200c is associated with radiotolerance. We aim to investigate the role of miRNA-200c in radiosensitivity and develop a systemic treatment strategy for esophageal squamous cancer. Overexpression of miRNA-200c by transfection was determined by RT-PCR. Radiosensitizing effect of miRNA-200c on esophageal squamous cancer cells was determined by clonogenic assay and xenograft model. Cell cycle was analyzed by flow cytometry. The levels of Cyclin B1, cyclin D1, cyclin E1, CDK2, CDK4, Cdc2 and P21 protein expressions were detected by western blotting. The results of our study revealed that miRNA-200c enhanced the radiosensitivity significantly in esophageal squamous cancer cell line in vitro and in vivo. miRNA-200c induced G2/M and sub-G1 phase arrest and reduced S phase rate of the irradiated Eca-109 cells and downregulated expression levels of Cyclin B1, cdc2 and upregulated P21 expression level. Present results demonstrate that downregulation of miRNA-200c is associated with radiotolerance. miRNA-200c increases radiosensitivity by G2/M and sub-G1 phase arrest through modulating Cyclin B1, cdc2 and P21 expression levels.

Curcumin Inhibits Gastric Carcinoma Cell Growth and Induces Apoptosis by Suppressing the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND Curcumin has well-known, explicit biological anti-tumor properties. The Wnt/ß-catenin signaling pathway plays a central role in tumor cell proliferation and curcumin can regulate the Wnt/b-catenin signaling pathway of several carcinomas. The aim of this study was to investigate the impact of curcumin on the Wnt/ß-catenin signaling pathway in human gastric cancer cells. MATERIAL AND METHODS We used 3 gastric cancer cell lines: SNU-1, SNU-5, and AGS. Research methods used were MTT assay, flow cytometry, clonogenic assay, annexin V/PI method, Western blotting analysis, tumor formation assay, and in vivo in the TUNEL assay. RESULTS Curcumin markedly impaired tumor cell viability and induced apoptosis in vitro. Curcumin significantly suppressed the levels of Wnt3a, LRP6, phospho-LRP6, ß-catenin, phospho-ß-catenin, C-myc, and survivin. Xenograft growth in vivo was inhibited and the target genes of Wnt/ß-catenin signaling were also reduced by curcumin treatment. CONCLUSIONS Curcumin exerts anti-proliferative and pro-apoptotic effect in gastric cancer cells and in a xenograft model. Inhibition of the Wnt/ß-catenin signaling pathway and the subsequently reduced expression of Wnt target genes show potential as a newly-identified molecular mechanism of curcumin treatment.

Polyphyllin II Restores Sensitization of the Resistance of PC-9/ZD Cells to Gefitinib by a Negative Regulation of the PI3K/Akt/mTOR Signaling Pathway.

BACKGROUND: EGFR tyrosine kinase inhibitors (TKIs) are widely used for advanced nonsmall cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation and provide a promising treatment strategy. However, acquired resistance to EGFR-TKIs restricts their application. The mechanisms underlying acquired resistance to TKIs have been explored and Phosphoinositide 3- kinase (PI3K)/Akt/mTOR pathway plays a very important role in NSCLC development as well as EGFR-TKI resistance. Polyphyllin II(PP II) is the main steroidal saponin constituent which derives from the root of Paris polychylia. OBJECTIVE: We examined the sensitizing effect of PP II to gefitinib on proliferation, apoptosis, PI3K/Akt/mTOR signaling pathway and tumor growth on gefitinib-resistant NSCLC in vitro and in vivo. METHODS: Gefitinib-resistant PC-9/ZD cells and gefitinib-sensitive PC-9 cells were used. In the absence of PI3K siRNA, MTT assay, Annexin V/PI analyses, Western blot, and Immunohistochemistry analysis by TUNEL assays for xenograft model were carried out. RESULTS: PP II promoted the anti-proliferative effects of gefitinib and gefitinib-induced apoptosis via activation of caspases and cleavage of PARP. PP II elevated sensitization of gefitinib through targeting the PI3K/Akt/mTOR. PP II with gefitinib treatment was more effective in inhibiting tumor growth and PI3K inactivation on gefitinib-resistant xenograft. CONCLUSION: The results indicated that PP II elevated sensitization of drug-resistant PC-9/ZD cells to gefitinib through the inhibition of PI3K/Akt/mTOR signaling pathway. It provides a potential new strategy to overcome gefitinib resistance for EGFR-TKI resistant NSCLC.

Dietary fibre intake and risk of breast cancer: A systematic review and meta-analysis of epidemiological studies.

Current evidence from randomised controlled trials on the effects of dietary fibre intake on breast cancer risk is inconsistent. We conducted a meta-analysis to determine the effectiveness of dietary fibre intake in reducing breast cancer risk. We searched for prospective and case-control studies on dietary fibre intake and breast cancer risk in the English language through March 2016. Twenty-four epidemiologic studies obtained through the PubMed, Embase, Web of Science, and Cochrane Library databases were systematically reviewed. A random-effects model was used to compute the pooled risk estimates by extracting the risk estimate of the highest and lowest reported categories of intake from each study. The meta-analyses showed a 12% decrease in breast cancer risk with dietary fibre intake. The association between dietary fibre intake and breast cancer risk was significant when stratified according to Jadad scores, study types, and menopause status. Dose-response analysis showed that every 10 g/d increment in dietary fibre intake was associated with a 4% reduction in breast cancer risk, and little evidence of publication bias was found. Thus, dietary fibre consumption is significantly associated with a reduced risk of breast cancer, particularly in postmenopausal women.