The objective of this study is to evaluate retrospectively the effectiveness of multiple-drug chemotherapeutics regimen that included high-dose methotrexate (HD-MTX) for treating primary osteosarcoma. 148 newly diagnosed patients with Stage I and II osteosarcoma who received HD-MTX/HD-MTX/DDP(cisplatin)/ADM(doxorubicin) and/or HD-MTX/IFO(Ifosfamide)/DDP/ADM before and after the surgery were retrospectively analyzed to measure the efficacy of this regimen. The significance of various variables as predictive prognostic factors of the patient survival rate was also evaluated. The overall 3-year survival rate of the patients was 79.73 %. The survival rate was improved to 85.71 % in the patients who received surgery and a complete 4-cycle chemotherapy. In addition, the rates of disease-free survival (DFS), local recurrence, and distant metastasis were 68.13, 3.30, and 10.81 %, respectively. Our analysis showed that completing 4-cycle chemotherapy produced a significant impact on the overall 3-year survival and DFS rates (P < 0.05). The overall 3-year survival was correlated with pathological fracture, chemotherapy completion, histological response, local recurrence, and distance metastasis (single-factor P < 0.05). Multivariate analysis further evidenced that these predictive factors were independently correlated to the survival rate (multi-factor P < 0.05). The complete 4-cycle multiple-drug chemotherapy consisting of HD-MTX, doxorubicin, cisplatin, and ifosfamide combined with surgical resection was found to be effective in improving the survival rate of osteosarcoma patients. Furthermore, the presence of pathological fracture, poor histological response, local recurrence, and distant metastasis was negatively correlated with the survival rate. Patient age, gender, location of primary tumor, and serum alkaline phosphatase level were not found to show the prognostic significance.

Gastric cancer (GC) refers to malignancy that occurs in the stomach. It is the most common malignant tumour in the digestive tract, and the leading cause of cancer-related mortality worldwide. 1 Despite rapid advances in early diagnosis and surgical treatments in the past few decades, the 5-year relative survival rate of GC is still below 30%. 2 So far, the pathogenic mechanism of GC is still largely unknown. Nevertheless, there is accumulating evidence to support that genetic factors play an important role in its pathogenesis. Firstly, numerous genetic loci have been found to be associated with an increased risk of GC. 3-5 Secondly, family clustering of GC is not uncommon, and positive family history in first-degree relatives has also been proved to be a strong independent risk factor of GC. 6Overall, these findings jointly indicate that genetic predisposition to GC is crucial for its occurrence and development.It has been well established that immune dysfunction is implicated in the pathogenesis of GC. Firstly, it was found that suppressor T cells were increased while cytotoxic T cells were decreased in GC patients. 7 Secondly, several pilot studies have demonstrated that immune-stimulatory therapy could result in disease regression and prolonged survival in GC patients. 8,9 As a result, certain gene polymorphism in regulators of anti-tumour immune responses were thought to be implicated in the development of GC. Recently, many genetic association studies have been carried out to investigate the potential roles of interleukin-2 (IL-2), IL-4, IL-6 and IL-8 gene polymorphisms in GC, however, the results of these studies Summary Recently, the roles of interleukin-2 (IL-2), IL-4, IL-6 and IL-8 gene polymorphisms in gastric cancer (GC) have been studied extensively, with conflicting results. Therefore, we conducted the present meta-analyses to better elucidate the roles of interleukin gene polymorphisms in GC. Eligible articles were searched in PubMed, MEDLINE,Embase, Web of Science and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential association between interleukin gene polymorphisms and the risk of GC. A total of 63 case-control studies was finally included in our analyses. Significant associations with the risk of GC were detected for the IL-6 rs1800796 and IL-8 rs4073 polymorphisms in overall analyses. Further subgroup analyses based on ethnicities of participants revealed that the IL-4 rs2243250, IL-6 rs1800796 and IL-8 rs4073 polymorphisms were significantly associated with the risk of GC in Asians. Moreover, IL-8 rs4073 polymorphism was also significantly associated with the risk of GC in Africans. In conclusion, our findings suggested that IL-4 rs2243250, IL-6 rs1800796 and IL-8 rs4073 polymorphisms may serve as genetic biomarkers of GC. K E Y W O R D Sgastric cancer, gene polymorphisms, interleukin, meta-analysis

Gastric cancer (GC) is the most common malignancy of the stomach. This study was aimed at elucidating the regulatory network of circRNA-miRNA-mRNA and identifying the precise inflammation-related targets in GC. The expression profiles of GSE83521, GSE78091, and GSE33651 were obtained from the GEO database. Interactions between miRNAs and circRNAs were investigated by the Circular RNA Interactome, and targets of miRNAs were predicted with miRTarBase. Then, a circRNA/miRNA/mRNA regulatory network was constructed. Also, functional enrichment analysis of selected differentially expressed genes (DEGs) was performed. The inflammation-/GC-related targets were collected in the GeneCards and GenLiP3 database, respectively. And a protein-protein interaction (PPI) network of DE mRNAs was constructed with STRING and Cytoscape to identify hub genes. The genetic alterations, neighboring gene networks, expression levels, and the poor prognosis of hub genes were investigated in cBioPortal, Oncomine, and Human Protein Atlas databases and Kaplan-Meier plotter, respectively. A total of 10 DE miRNAs and 33 DEGs were identified. The regulatory network contained 26 circRNAs, 10 miRNAs, and 1459 mRNAs. Functional enrichment analysis revealed that the selected 33 DEGs were involved in negative regulation of fat cell differentiation, response to wounding, extracellular matrix- (ECM-) receptor interaction, and regulation of cell growth pathways. THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were selected as inflammation-related hub genes of GC in the PPI network. The genetic alterations in these hub genes were related to amplification and missense mutations. Furthermore, the genes RYR2, ERBB2, PI3KCA, and HELZ2 were connected to hub genes in this study. The hub gene levels in clinical specimens were markedly upregulated in GC tissues and correlated with poor overall survival (OS). Our results suggest that THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were associated with the pathogenesis of gastric carcinogenesis and may serve as biomarkers and inflammation-related targets for GC.