Construction of iron metabolism-related prognostic features of gastric cancer based on RNA sequencing and TCGA database.

BACKGROUND: Researches have manifested that the disorder of iron metabolism is participated in Gastric cancer (GC), but whether iron metabolism-relevant genes (IMRGs) is related to the survival outcome of GC remain unknown. METHODS: Eleven tumor as well as nine adjacent normal tissues from GC patients were underwent mRNA sequencing, and the The Cancer Genome Atlas Stomach Cancer (TCGA-STAD) datasets were acquired from the TCGA database. Cox analyses and least absolute shrinkage and selection operator (LASSO) regression were applied to build a IMRGs signature. The relationship between signature genes and the infiltration profiling of 24 immune cells were investigated using single-sample GSEA (ssGSEA). Meanwhile, the potential biological significance, genes that act synergistically with signature genes, and the upstream regulatory targets were predicted. Finally, the abundance of the signature genes were measured via the quantitative real-time PCR (qRT-PCR). RESULTS: A IMRGs signature was constructed according to the expression and corresponding coefficient of DOHH, P4HA3 and MMP1 (The Schoenfeld individual test showed risk score was not significant with P values = 0.83). The prognostic outcome of patients in the high-risk group was terrible (p < 0.05). Receiver operating characteristic (ROC) curves confirmed that the IMRGs signature presented good efficiency for predicting GC prognosis (AUC > 0.6). The nomogram was performed well for clinical utilize (C-index = 0.60), and the MMP1 expression significantly increased in the cohorts at age > 60 and Stage II-IV (p < 0.05). The positive correlation of P4HA3 and MMP1 expression as well as the negative correlation of DOHH expression with risk score (p < 0.0001) and worse prognosis (p < 0.05) were detected as well. Furthermore, 11 differential immune cells were associated with these signature genes (most p < 0.01). Finally, qRT-PCR revealed that the abundance of DOHH, P4HA3 and MMP1 were high in tumor cases, indicating the complex mechanism between the high expression of DOHH as a protective factor and the high expression of P4HA3 and MMP1 as the risk factors in the development of GC. CONCLUSION: An iron metabolism-related signature was constructed and has significant values for foretelling the OS of GC.

Talin2 regulates invasion of human breast cancer MDA-MB-231 cells via alteration of the tumor microenvironment.

The talin proteins are a key component of the extracellular matrix-integrin-cytoskeleton system, and our previous study suggested that talin2 contributes to the tumor invasion and metastasis processes regulated by the tumor microenvironment. In the present study, the specific effects of talin2 on the invasive ability of breast cancer cells, as well as the underlying mechanism, were investigated by creating two MDA-MB-231 cell lines with stable talin2 knockdown by specific RNA interference. Initially, it was confirmed that the expression levels of talin2 in human breast cancer tissues were upregulated compared with in normal adjacent tissues. Subsequently, invasion and wound healing assays revealed that depletion of talin2 in MDA-MB-231 cells decreased their migratory and invasive abilities. Western blot analysis demonstrated that knockdown of talin2 in MDA-MB-231 cells caused marked downregulation of the tumor microenvironment markers hypoxia-inducible factor 1α, phosphorylated ribosomal protein S6 kinase, phosphorylated protein kinase B and phosphorylated mechanistic target of rapamycin. Furthermore, knockdown of talin2 decreased the basal contents of glucose and lactic acid in the breast cancer cell line. In conclusion, the findings of the present study demonstrated that talin2 knockdown may inhibit the invasive ability of human breast cancer MDA-MB-23l cells via alterations in the tumor microenvironment.

Prophylactic air-extraction strategy after thoracoscopic wedge resection.

BACKGROUND: Since the conception of enhanced recovery after surgery protocols, tubeless strategies have become popular. Herein, we introduce a previously unreported alternative air-extraction strategy for patients who have undergone thoracoscopic wedge resection and explore its feasibility and safety. METHODS: Between January 2015 and June 2017, 264 consecutive patients underwent thoracoscopic wedge resection with different drainage strategies. Patients were divided according to the postoperative drainage strategies used: routine chest tube drainage (RT group), complete omission of chest tube drainage (OT group), and prophylactic air-extraction catheter insertion procedure (PC group). Using the propensity score matching method, clinical parameters and objective operative qualities were compared among the three groups. RESULTS: Optimal 1:1 matching was used to form pairs of RT (n =36) and PC (n =36) groups and balance baseline characteristics among the three groups. The incidence rates of pneumothorax were 5.6% (2/36), 9.8% (5/51), and 19.4% (7/36) in the RT, OT, and PC groups, respectively (P = 0.07). Chest tube reinsertion incidence for postoperative pneumothorax was 19.4% (1/7) in the PC group and 60% (3/5) in the OT group. Other postoperative complications were comparable among these groups. CONCLUSIONS: The prophylactic air-extraction strategy may be an alternative procedure for selected patients. Remedial air extraction may reduce the occurrence of chest tube reinsertion for pneumothorax patients, but further investigation is required.

Antitumor activity of recombinant RGD-IFN-α2a-core fusion protein in vitro.

Interferon (IFN) regulates immune responses and antitumor activity. Arginine-glycine-aspartic acid (RGD) peptides can specifically bind to integrin αvß3, a transmembrane receptor that is highly expressed on the surface of various cancer cells. In this study, we expressed recombinant RGD-IFN-α2a-core fusion proteins and assessed their antitumor activity in vitro. Two RGD-IFN-α2a-core fusion proteins and a negative control protein were expressed in vitro. These two RGD-IFN-α2a-core fusion proteins could bind the tumor cell surface specifically and did not bind to normal cells. RGD-IFN-α2a-core fusion protein treatment of tumor cells significantly reduced cell viability and induced apoptosis in a dose-dependent manner. At the 'mRNA' level, both proteins could upregulate CASP3 expression. These data indicate that both laboratory-engineered RGD-IFN-α2a-core fusion proteins could bind the surface of tumor cells and induce apoptosis in vitro. Further studies will investigate the in-vivo antitumor activities of the RGD-IFN-α2a-core fusion proteins.

Predictive factors associated with gefitinib response in patients with advanced non-small-cell lung cancer (NSCLC).

PURPOSE: A number of different clinical characteristics have been reported to singly correlate with therapeutic activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced non-small-cell lung cancer (NSCLC). This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. PATIENTS AND METHODS: EGFR gene typing in 33 advanced NSCLC patients received gefitinib (250 mg/day) were analyzed with mutant-enriched PCR assay. Gefitinib response was evaluated with potential predictive factors retrospectively. RESULTS: The overall objective response rate (ORR) and median progression-free survival (PFS) in the 33 patients treated by gefitinib were 45.5% and 3.0 (2.0-4.0) months. The ORR and median PFS in EGFR gene mutation patients were significantly higher/longer than those in EGFR gene wild-type patients (P<0.01). Similarly, the ORR and median PFS in non-smoker patients were significantly higher/longer than those in smoker patients (P<0.05, P<0.01, respectively). However, no difference for ORR and median PFS occurred between male and female patients. Logistic multivariate analysis showed that only EGFR mutated gene was significantly associated with the ORR (P<0.01). Both EGFR mutated gene and non-smoker were the major factors that contributed to PFS (P<0.05). CONCLUSIONS: EGFR mutated gene and non-smoker status are potential predictors for gefitinib response in NSCLC patients.

Health related quality of life in patients with chronic gastritis and peptic ulcer and factors with impact: a longitudinal study.

BACKGROUND: The assessment of Health Related Quality of Life (HRQOL) has been applied as a significant outcome indicator for patients with chronic diseases. No HRQOL study, however, has looked at HRQOL in patients with chronic gastritis and peptic ulcers. This paper focuses on comparing HRQOL in patients with chronic gastritis and peptic ulcers and examining the factors that influence the HRQOL of such patients. Results can be used for making decisions in clinical trials as well as aiding individual management and preventive care of these diseases. METHODS: The Chinese version of the SF-36 (CSF-36) was administered twice to 244 patients with chronic gastritis and peptic ulcers. Mean scores across the two disease groups were compared using t-tests, change over time was analyzed with paired samples t-tests, and factors predicting HRQOL were investigated using the univariate general linear model. RESULTS: The mean domain scores of patients with chronic gastritis were lower than those for patients with peptic ulcers, with the exception of physical functioning. Both groups had lower HRQOL compared with population norms. Mean domain scores increased after treatment in both groups. HRQOL in patients with these two chronic diseases differed by age, education level, marriage, income, and gender, but their explanatory power was relatively low. CONCLUSION: Quality of life of patients with chronic gastritis was lower than that of patients with peptic ulcers, which was lower than population norms. Quality of life in both patients groups was associated with socio-demographic risk factors.

Somatostatin receptor-based molecular imaging and therapy for neuroendocrine tumors.

Neuroendocrine tumors (NETs) are tumors originated from neuroendocrine cells in the body. The localization and the detection of the extent of NETs are important for diagnosis and treatment, which should be individualized according to the tumor type, burden, and symptoms. Molecular imaging of NETs with high sensitivity and specificity is achieved by nuclear medicine method using single photon-emitting and positron-emitting radiopharmaceuticals. Somatostatin receptor imaging (SRI) using SPECT or PET as a whole-body imaging technique has become a crucial part of the management of NETs. The radiotherapy with somatostatin analogues labeled with therapeutic beta emitters, such as lutetium-177 or yttrium-90, has been proved to be an option of therapy for patients with unresectable and metastasized NETs. Molecular imaging can deliver an important message to improve the outcome for patients with NETs by earlier diagnosis, better choice of the therapeutic method, and evaluation of the therapeutic response.