Metastatic pattern and prognosis of gastrointestinal stromal tumor (GIST): a SEER-based analysis.

PURPOSE: This SEER-based study aimed to explore and analyze the relationship of metastasis of liver, lung and bone of GIST patients and their prognosis. METHODS: The data of GIST patients were from Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 and all the statistical analyses were conducted by statistical software package SPSS (Version 22.0). RESULTS: A total of 4224 GIST patients were identified, of which 388 (9.19%) patients with liver metastasis, 20 (0.47%) patients with bone metastasis and 32 (0.76%) patients with lung metastasis. There was no significant difference of risk of bone or lung metastasis between patients with and without liver metastasis (P = 0.935). The median overall survival of patients with liver, bone, or lung metastasis was, respectively, 49 months, 18 months, and 20 months, which were all shorter than that of patients without metastasis. The overall survival of patients with both liver and bone metastasis and those with metastasis of all three sites was not significantly different from that of patients with only liver metastasis. The multivariate analysis showed age of less than 65 years, female patients, married status and receiving surgery were all the beneficial factors for prognosis of GIST patients with liver metastasis. CONCLUSIONS: Patients with metastasis had a poorer prognosis than those without. Liver metastasis might have no relationship with bone or lung metastasis and liver might play a more dominant role than the other two sites in the prognosis of GIST patients with metastasis. So, more attention should be paid to liver status in diagnosis and treatment of GIST patients.

Association between GSTM1, GSTT1, and GSTP1 polymorphisms and gastric cancer risk, and their interactions with environmental factors.

Glutathione S-transferase (GST) is an important member of phase II metabolic enzymes; GSTM1, GSTT1, and GSTP1 belong to three subfamilies of the GST enzyme. Polymorphisms in GSTM1, GSTT1, and GSTP1 could affect detoxification processes, and increase individuals' susceptibility to cancers. We aimed to investigate the association between GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of gastric cancer in a Chinese population. In addition, we also examined the effect of gene-environmental interactions, and their effect on risk of this cancer. Between July 2013 and June 2015, we recruited 242 gastric cancer patients and 396 healthy controls for our study. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to characterize genetic polymorphisms in GSTM1, GSTT1, and GSTP1. We observed that the Val/Val genotype of GSTP1 was associated with increased risk of gastric cancer when compared with the Ile/Ile genotype (OR = 3.19, 95%CI = 1.84-5.56). Moreover, the Val allele of GSTP1 was associated with higher susceptibility to gastric cancer as compared with the Ile allele (OR = 1.52, 95%CI = 1.19-1.93). However, GSTM1 and GSTT1 polymorphisms did not affect the development of gastric cancer. In conclusion, our study indicated that GSTP1 Ile105Val, but not GSTM1 and GSTT1 polymorphisms, was associated with risk of gastric cancer.

Osteoblast differentiation of rabbit adipose-derived stem cells by polyethylenimine-mediated BMP-2 gene transfection in vitro.

The aim of this study was to examine the efficiency of polyethylenimine-mediated transfection of the human bone morphogenetic protein-2 (BMP-2) gene into rabbit adipose-derived stem cells (ADSCs), and its effect on osteoblast differentiation. Adipose tissue was isolated from the necks of adult Japanese white rabbits and cultured in vitro to obtain ADSCs. Gene delivery of BMP-2 was mediated by polyethylenimine and stable transformants were selected by G-418. The expression of BMP-2 mRNA was confirmed by reverse transcription-polymerase chain reaction, and of the BMP-2 protein by ELISA. Osteocalcin and collagen type I were detected by western blot and by an alkaline phosphatase kit. Alizarin red S stain was also utilized to examine osteogenesis. The non-transfected group was considered as a control. In this study, we successfully derived ADSCs from rabbit adipose tissue. Through passages 3-6, the expression of CD29 and CD44 gradually increased, whereas the expression of CD34 and CD45 gradually decreased. Both mRNA and protein expression of BMP-2 were confirmed following polyethylenimine-mediated BMP-2 gene delivery. In addition, the expression of alkaline phosphatase, osteocalcin, and collagen type I was found to be upregulated and alizarin red S staining was positive in transfected ADSCs, indicating BMP-2-induced osteogenesis. Therefore, this study determined that polyethylenimine was able to mediate BMP-2 gene delivery and induce osteogenic differentiation of ADSCs.

Analysis of ADH1B Arg47His, ALDH2 Glu487Lys, and CYP4502E1 polymorphisms in gastric cancer risk and interaction with environmental factors.

Gastric cancer is the fourth commonly diagnosed cancer and the second most frequent cause of cancer death worldwide. Genetic variations in ADH1B and ALDH2 may alter the function and activity of the corresponding enzymes, leading to differences in acetaldehyde exposure between drinkers. Cytochrome P4502E1 (CYP4502E1) is a phase I enzyme that plays an important role in metabolizing nitrosamine compounds and the bioactivation of procarcinogens. During the period of July 2013 to July 2015, 246 patients and 274 controls were enrolled from the First Affiliated Hospital of Jinan University. In the codominant model, the AA genotype of ALDH2 Glu487Lys significantly elevated the risk of gastric cancer in comparison with the GG genotype of ALDH2 Glu487Lys. In the recessive model, the AA genotype of ALDH2 Glu487Lys significantly increased the risk of gastric cancer compared to the GG+GA genotype (OR = 2.34 95%CI = 1.02-5.70). We found in the codominant model that individuals harboring the C2/C2 genotype of CYP4502E1 had a higher risk of developing gastric cancer than those with the C1/C1 genotype. In addition, in the recessive model, we found that the C2/C2 genotype correlated with an elevated risk of gastric cancer in comparison with the C1/C1+C1/C2 genotype (OR = 4.90, 95%CI = 2.04-13.51). However, no significant relationship was measured between ADH1B Arg47His and gastric cancer risk. In summary, the results of our study indicate that ALDH2 Glu487Lys and CYP4502E1 polymorphisms could be risk factors for the development of gastric cancer in the Chinese population.

Study on quality standards for Chimonanthus nitens.

Chimonanthus nitens Oliv. is a commonly used traditional Chinese medicine. Terpenoids, flavonoids, and coumarins are usually considered its main bioactive ingredients. Thus, qualitative and quantitative analyses of these compounds are crucial in quality control studies of Chimonanthus nitens. In this study, five compounds were identified by double-development thin layer chromatography (TLC) and the content of four compounds was determined by high performance liquid chromatography; the detection wavelength was set to 344 nm and the column temperature was 40°C. All calibration curves showed good linear regression (R2 > 0.9995). The average recoveries ranged from 97.06 to 104.44%. The RSD was below 4.2%. Four compounds remained stable over 24 h and the relative standard deviation (RSD) of the precision of their measurement was less than 1.5%. The developed method was reproducible, sensitive, and simple, and could be used for quality control of Chimonanthus nitens.

MicroRNAs in avian influenza virus H9N2-infected and non-infected chicken embryo fibroblasts.

There is limited information about microRNAs (miR-NAs) in H9N2 subtype influenza virus-infected chicken cells or tissues. In this study, 10,487,469 and 13,119,795 reads were obtained from in-fected and non-infected chicken embryo fibroblasts, respectively. Seven hundred and thirty-six and 1004 miRNAs, including mature miRNAs and precursors, were obtained from the infected and non-infected fibro-blasts, respectively. Of those miRNAs, 48 were expressed differently between the groups: 37 had a low expression level in the infected chick-en embryo fibroblast, and the remaining 11 had a higher expression level. Every miRNA was predicted to target immune response-related genes. It has been found that some of the miRNAs, such as gga-miR-146c, gga-miR-181a, gga-miR-181b, gga-miR-30b, gga-miR-30c, gga-miR-30e, and gga-miR-455, are expressed differently in other types of influenza-infected chicken cells or tissues.

Germline mutations of DICER1 in Chinese women with BRCA1/BRCA2-negative familial breast cancer.

Germline mutations in identified breast cancer susceptibility genes account for less than 20% of Chinese familial breast cancers. Dicer is an essential component of the microRNA-producing machinery; germline mutations of DICER1 have been confirmed in familial pleuropulmonary blastoma, ovarian sex cord-stromal tumors, and other cancers. Low expression of DICER1 is frequently detected in breast cancer. However, whether germline mutations of DICER1 occur in familial breast cancers remain unknown. Sixty-five breast cancer probands from BRCA1/BRCA2-negative Chinese breast cancer families were screened for germline mutations in DICER1. In addition, 100 unrelated healthy females were enrolled as controls. A polymerase chain reaction sequencing assay was used to screen for mutations in coding regions and at the exon-intron boundaries of DICER1. All variants in introns were evaluated using the NNSplice software to determine the potential splicing effect. A total of 12 germline variants were found, including 11 variants in introns and 1 variant in the 3'-non-coding region. Four variants (IVS8-205 C>T, IVS11+131 delGAAA, IVS16+42 delTA, and IVS19+160 T>C) were novel. Three variants (IVS11+105 C>T, IVS16+42 delTA, and 6095 T>A) may affect splice sites. None of the observed variants appeared to be disease-related, suggesting that germline mutations in DICER1 are rare or absent in familial breast cancer patients.

Genetic diversity and relationships in cultivars of Lolium multiflorum Lam. using sequence-related amplified polymorphism markers.

Sequence-related amplified polymorphism (SRAP) markers were used to analyze and estimate the genetic variability, level of diversity, and relationships among 20 cultivars and strains of annual ryegrass (Lolium multiflorum Lam.). Eighteen SRAP primer combinations generated 334 amplification bands, of which 298 were polymorphic. The polymorphism information content ranged from 0.4715 (me10 + em1) to 0.5000 (me5 + em7), with an average of 0.4921. The genetic similarity coefficient ranged from 0.4304 to 0.8529, and coefficients between 0.65 and 0.90 accounted for 90.00%. The cluster analysis separated the accessions into five groups partly according to their germplasm resource origins.

Association of DNA repair gene polymorphisms with response to chemotherapy and prognosis of gastric cancer.

We investigated the correlation between the response to chemotherapy in patients and excision repair cross-complimenta-ry group 1 gene (ERCC1) and xeroderma pigmentosum complemen-tation group F gene (XPF) polymorphisms and the effect of these polymorphisms on the clinical outcome of gastric cancer. Samples from a total of 255 patients with newly diagnosed and histopatho-logically confirmed primary gastric cancer were collected in our study. The ERCC1 rs11615, ERCC1 rs2298881, XPF rs2276465, and XPF rs6498486 polymorphisms were genotyped. Among the 255 patients, the median follow-up time was 29.7 months. A total of 103 patients (40.4%) died from gastric cancer during the follow-up period. We observed that the XPF rs6498486 CC genotype and the XPF rs2276465 GG genotype were associated with response to che-motherapy, with odds ratios and 95% confidence intervals of 3.88 (1.23-16.07) and 2.66 (1.17-6.45), respectively. In the Cox propor-tional hazards model, patients carrying the ERCC1 rs11615 AA gen-otype and the XPF rs2276465 GG genotype showed only a 0.22- and 0.30-fold increased risk of death from gastric cancer. We found that the XPF rs6498486 and XPF rs2276465 polymorphisms are mark-ers of response to oxaliplatin/5-fluorouracil-based chemotherapy in gastric cancer patients.