Hypofractionated Radiotherapy in Combination With Chemotherapy Improves Outcome of Patients With Esophageal Carcinoma Tracheoesophageal Groove Lymph Node Metastasis.

This study investigated the efficiency and safety of hypofractionated radiotherapy (HFR) combined with paclitaxel chemotherapy for the treatment of postsurgery tracheoesophageal groove lymph node (TGLN) metastasis in patients with esophageal cancer (EC). Fifty-three EC patients with TGLN metastasis after surgery admitted to the Yancheng Third People's Hospital from January 2013 to June 2015 were included in this study. They were randomly divided into the HFR group (n = 25) and conventional fractioned radiotherapy (CFR) group (n = 28) based on the random grouping method. Patients in the HFR group received treatment with radiation of 60 Gy (5 fractions per week, total 20 fractions) combined with paclitaxel chemotherapy at a dose of 50 mg once per week for 4 weeks. Patients in the CFR group received radiation of 60 Gy (5 fractions per week, total 30 fractions) combined with paclitaxel chemotherapy at a dose of 50 mg once per week for 6 weeks. The adverse events and treatment outcomes in these two groups were analyzed. It was found that there was no significant difference in the incidence of radiation esophagitis in the HFR group compared with that of the CFR group (grades 3-4, 44.0 vs. 25.0%; P = 0.149). There was no statistical difference in the incidence of radiation pneumonitis between these two groups (grades 3-4, 16.0 vs. 7.1%; P = 0.314). No statistical difference was noticed in complete response (CR), partial response (PR), and no response (NR) between these two groups. The median overall survival (OS) in the HRF group was significantly longer compared with that of the CRF group (24.2 months (95% CI, 16.2-32.1 months) vs. 11.8 months (95% CI, 9.2-14.4 months); P = 0.024). Our results indicated that the combination of HFR and chemotherapy improved the prognosis of EC patients with TGLN metastasis with no increased adverse events.

Nomogram Based on Systemic Immune-Inflammation Index to Predict Overall Survival in Gastric Cancer Patients.

BACKGROUND: The systemic immune-inflammation index (SII), based on peripheral lymphocytes, neutrophils, and platelet count, has been used as a prognostic marker for several tumors. However, use of the SII has not been reported for gastric cancer. METHODS: We evaluated the prognostic value of the SII in primary and validation cohorts. We also established an effective prognostic nomogram for gastric cancer based on R language. The predictive accuracy and discriminative ability of the nomogram were determined using the concordance index (C index) and a calibration curve and were compared with TNM classifications. RESULTS: The Kaplan-Meier survival analysis results showed that the high SII was associated with poor prognosis of gastric cancer patients in the primary and validation cohorts. SII proved to be related to tumor location, histological grade, tumor size, TNM stage, and perineural infiltration in patients with gastric cancer and was an independent prognostic factor for patients with gastric cancer. SII has a better predictive ability than other existing prognostic indexes based on inflammation, such as NLR, PLR, and MLR. The nomogram established can accurately predict the 3- and 5-year survival rates of patients with gastric cancer after operation, and its accuracy is significantly higher than that of the 8th edition of the AJCC staging system. CONCLUSION: SII can independently predict the overall survival of patients with gastric cancer after operation, which is superior to the existing systemic inflammatory indexes. The prognostic nomogram based on SII is a reliable model for predicting the postoperative survival of patients with gastric cancer.

Development and validation of nomogram based on lncRNA ZFAS1 for predicting survival in lymph node-negative esophageal squamous cell carcinoma patients.

BACKGROUND: There is increasing evidence of a relationship between long non-coding RNA (lncRNA) and cancer. This study aimed to examine the prognostic value of the lncRNA ZFAS1 in esophageal squamous cell carcinoma (ESCC). RESULTS: The results showed that ZFAS1 expression was significantly higher in ESCC tissues compared with the corresponding adjacent normal tissues (P < 0.001). ESCC patients with high ZFAS1 expression had a poor overall survival (OS). Histological grade, T stage and ZFAS1 expression were integrated to develop the nomogram. The nomogram showed a significantly better prediction of OS for patients with lymph node-negative ESCC. The ROC curve also showed higher specificity and sensitivity for predicting 3- and 5-year ESCC patient survival compared with the AJCC staging system. The decision curve analysis also indicated a greater potential for the nomogram in clinical application compared with the AJCC staging system. Importantly, our findings were supported by a validation cohort. MATERIALS AND METHODS: We retrospectively investigated 398 lymph node-negative ESCC patients. Data from the primary cohort (n = 246) were used to develop a multivariate nomogram. The nomogram was internally validated for discrimination and calibration with bootstrap samples and was externally validated with an independent patient cohort (n = 152). CONCLUSIONS: Our proposed nomogram, which integrates clinicopathological factors and ZFAS1 expression, can accurately predict the prognosis of lymph node-negative ESCC patients without preoperative chemoradiotherapy.

Identification of key genes and molecular mechanisms associated with dedifferentiated liposarcoma based on bioinformatic methods.

BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is one of the most deadly types of soft tissue sarcoma. To date, there have been few studies dedicated to elucidating the molecular mechanisms behind the disease; therefore, the molecular mechanisms behind this malignancy remain largely unknown. MATERIALS AND METHODS: Microarray profiles of 46 DDLPS samples and nine normal fat controls were extracted from Gene Expression Omnibus (GEO). Quality control for these microarray profiles was performed before analysis. Hierarchical clustering and principal component analysis were used to distinguish the general differences in gene expression between DDLPS samples and the normal fat controls. Differentially expressed genes (DEGs) were identified using the Limma package in R. Next, the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained using the online tool DAVID (http://david.abcc.ncifcrf.gov/). A protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Furthermore, the hub genes within the PPI network were identified. RESULTS: All 55 microarray profiles were confirmed to be of high quality. The gene expression pattern of DDLPS samples was significantly different from that of normal fat controls. In total, 700 DEGs were identified, and 83 enriched GO terms and three KEGG pathways were obtained. Specifically, within the DEGs of DDLPS samples, several pathways were identified as being significantly enriched, including the PPAR signaling pathway, cell cycle pathway, and pyruvate metabolism pathway. Furthermore, the dysregulated PPI network of DDLPS was constructed, and 14 hub genes were identified. Characteristic of DDLPS, the genes CDK4 and MDM2 were universally found to be up-regulated and amplified in gene copy number. CONCLUSION: This study used bioinformatics to comprehensively mine DDLPS microarray data in order to obtain a deeper understanding of the molecular mechanism of DDLPS.

Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression in Non-Small Cell Lung Cancer.

Previous studies reported that elevated expression of long noncoding RNA (lncRNA) GAS5 led to the arrest of non-small cell lung cancer (NSCLC) cell growth and a promotion of apoptosis both in vitro and in vivo. However, its underlying molecular mechanism in NSCLC is still unclear. In the present study, we noted that GAS5 was downregulated in NSCLC tissues and cells and was negatively correlated with miR-23a expression. Luciferase reporter assay and qRT-PCR analysis demonstrated that GAS5 directly interacted with miR-23a and reversely regulated its expression. miR-23a overexpression markedly promoted NSCLC cell proliferation and invasion, while GAS5 overexpression dramatically inhibited NSCLC cell proliferation and invasion and promoted apoptosis. Functional analysis indicated that miR-23a overexpression significantly abolished GAS5 overexpression-induced inhibition of proliferation and invasion, as well as promotion of apoptosis in NSCLC cells. Moreover, xenograft experiments further revealed that upregulation of GAS5 notably impaired the growth of transplanted tumors by suppressing miR-23a in nude mice. These results suggested that overexpression of lncRNA GAS5 inhibits tumorigenesis of NSCLC by inhibiting miR-23a in vitro and in vivo, providing a potential therapeutic strategy for patients with NSCLC.

In vitro evaluation of dual agonists for PPARγ/ß from the flower of Edgeworthia gardneri (wall.) Meisn.

ETHNOPHARMACOLOGICAL RELEVANCE: In Tibet, the flower of Edgeworthia gardneri (Wall.) Meisn., locally named "Lvluohua, [symbols: see text]", has been traditionally used to treat diabetes mellitus for many years. AIM OF THIS STUDY: To evaluate the activity of dual agonists for PPARγ/ß from the flower of E.gardneri in vitro. MATERIALS AND METHODS: HeLa cells were transiently co-transfected with the re-constructed plasmids of pBIND-PPARγ-LBD or pBIND-PPARß-LBD and rL4.35. The activities of crude extracts, secondary fractions and compounds from the flower of E.gardneri were evaluated with the transfected cells. Rosiglitazone (at 0.5 µg/mL) and L-165041 (at 0.5 µg/mL) were used as the positive controls for PPARγ and PPARß respectively. RESULTS: The results demonstrated that n-hexane, ethyl acetate and n-butanol extracts from the flower of E.gardneri were able to significantly activate PPARγ and PPARß respectively, and the activity of ethyl acetate extract was much better. We further observed that, among the 11 secondary fractions of ethyl acetate extract, the fr. 9 could activate PPARγ and PPARß significantly. Moreover, umbelliferone (from fr.9) and pentadecanoic acid could activate PPARγ and PPARß at the same time. CONCLUSIONS: The extracts from the flower of E.gardneri could significantly activate PPARγ and PPARß. Besides, umbelliferone and pentadecanoic acid isolated from the flower of E.gardneri were the new agonists for PPARγ and PPARß.

Clinical experience with radio-, chemo- and hyperthermotherapy combined trimodality on locally advanced esophageal cancer.

Esophageal cancer is a highly malignant and lethal disease with a low 5-year survival rate. Therefore, an effective treatment modality is required. To investigate the treatment efficacy and toxicity of radio-, chemo- and hyper-thermotherapy combined trimodality on locally advanced esophageal cancer, the medical records of 78 patients with pathologically confirmed esophageal cancer treated with chemoradiotherapy plus hyperthemia at our institution were retrospectively investigated and the 3-year outcome was carefully assessed. All 78 patients received intensity-modulated radiation therapy at a total dose of 60-66 Gy, in a conventional schedule of 1.8-2.1 Gy/fraction, 5 fractions/week. They also received 4-6 courses of chemotherapy, consisting of 450 mg/m2 5-fluorouracil for 1-5 days and 25 mg/m2 cisplatin for 1-5 days, in addition to 6-12 sessions of hyperthermia, performed twice a week. Out of the 78 cases, complete remission of the primary tumor was observed in 31 (39.7%), partial remission in 44 (56.4%) and no change in 3 (3.9%) cases. The treatment response rate was 96.1%. The overall survival (OS) rate at 1, 2 and 3 years was 67.9, 41.0 and 33.3%, respectively. No significant difference in adverse effects was observed between this treatment regimen and other similar studies. Our preliminary results demonstrated that the chemo-, radio- and hyperthermotherapy combined trimodality exhibited excellent short-term clinical outcomes as regards tumor response rate and a sound long-term OS, with endurable adverse events. This trimodal treatment requires further investigation to establish its beneficial role in the treatment of patients with locally advanced esophageal cancer.