Objective To conduct a case-control study on the association of the nucleotide polymorphisms in the promoter region of the matrix metalloproteinase-9 (MMP-9) gene with phenotype of esophageal cancer. Methods All subjects were unrelated residents in northern regions of China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to determine the MMP-9 genotypes. Results The overall distribution of genotypes in the patients was not different from that in the controls (OR=0.77, 95% CI=0.45-1.34; P=0.36). There were no significant differences between the patients and the control subjects in terms of the distributions of sex and age, smoking status, alcohol dependence, pickled diet status, or history of environmental exposure. The patients were further examined with stratifications by age, sex, grade, depth of tumor invasion, lymphatic invasion, venous invasion and TNM staging. The results showed no pronounced association among the stratifications. Conclusion There is no significant association between the MMP-9 single nucleotide polymorphism genotypes and phenotype of esophageal cancer.

Objective Systemic chemotherapy for metastatic pancreatic cancer is still a difficult problem in clinical practice. The standard chemotherapy of pancreatic cancer has been gemcitabine, but the response rate is low. Therefore, it is in urgent need to explore an effective clinical therapy for this cancer. This paper, a case report, is aimed at discussing the effectiveness of vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer. Methods A 52-year-old female patient was diagnosed with pancreas cancer with liver metastasis at the time of the first visit to our hospital. Systemic chemotherapy with vinorelbine and cisplatin combined with endostatin was conducted. Results Liver metastases almost disappeared after the first cycle of chemotherapy. The primary tumor decreased by one third in size after four cycles and disappeared after the sixth cycle according to the CT scan evaluation. Conclusion Vinorelbine and cisplatin combined with endostatin can be a promising regimen for metastatic pancreatic cancer.

Objective To study the identification rate of sentinel lymph node (SLN) in patients with breast cancer (BC) and the accuracy in predicting axillary lymph node(ALN) metastasis using methylene blue (MB) and patent blue violet (PBV) injection. Methods From October, 1999 to April, 2001, 94 patients with BC were selected for this study. Of them, 32 patients were injected with 1% MB and 62 patients with 1% PBV to identify SLN. All 94 patients underwent the axillary lymph node dissection. Results In MB group and PBV group , the SLN identification rate were 65.6% (21/32), 88.7% (55/62); the accuracy rate to predict axillary lymph node status were 90.5% (19/21), 98.2% (54/55) respectively. Conclusion Compared with MB ,PVB is the more ideal vital blue dye in identification of SNB.

Objective:To inhibit the Itch gene expression of T-lymphocytes and investigate the immune activity of T lymphocytes using ultrasound-targeted microbubble destruction (UTMD).Methods:T lymphocytes were separated by magnetic bead, and to establish an Itch gene targeted short hairpin RNA (shRNA) plasmid. There were three groups in this study: ①experimental group, Itch-shRNA plasmid-SonoVue microbubbles combined with ultrasound irradiation; ②control group, negative control shRNA plasmid-SonoVue microbubbles combined with ultrasound irradiation; ③blank group, untreated. Forty-eight hours after UTMD transfection, transfection efficiency was detected and analyzed by fluorescence microscopy and flow cytometry, the expression of Itch protein was measured with Western blotting.Seventy-two hours after UTMD transfection, the secretion of interleukin 2 (IL-2) and interferon γ (IFN-γ) in the cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA was used to compare the differences between groups, and LSD- t test was used to compare the differences between groups. Results:The UTMD mediated shRNA transfection rate was 52.3%, and the relative expression levels of Itch protein in the experimental group, control group and blank group were 0.301±0.080, 0.773±0.101 and 0.719±0.090, respectively, and the difference was statistically significant( F=24.441, P<0.01). The Itch gene expression can be effectively suppressed in the experimental group. Seventy-two hours after transfection, the concentrations of IL-2 in the experimental group, control group and blank group were (417.3±37.1)ng/L, (158.7±17.3)ng/L and (147.0±10.2)ng/L, respectively, and the difference was statistically significant( F=118.701, P<0.001) and the concentrations of IFN-γ were (168.3±12.1)ng/L, (74.3±3.7)ng/L and (74.6±7.1)ng/L, respectively, and the difference was statistically significant ( F=126.833, P<0.001). The expression levels of IL-2 and IFN-γ in the experimental group were significantly higher than those in the control group and the blank group. Conclusions:UTMD mediated shRNA transfection can significantly decrease the expression of Itch and promote immune activity of T lymphocyte.

【Objective】 To select and identify miRNA signatures to predict TMB level in gastric cancer based on The Cancer Genome Atlas (TCGA) database and machine learning methods. 【Methods】 MiRNA expression and somatic mutation profiles of gastric cancer (GC) were downloaded from TCGA database. R "limma" package was performed to select differentially expressed miRNAs between high-TMB and low-TMB groups. Two machine learning algorisms, random forest (RF), and Support Vector Machine-Recursive Feature Elimination were utilized to identify miRNAs with the highest discriminative ability. ROC was used to test the predictive ability of these signatures in multiple datasets. Besides, immune cells of different TMB levels were compared by the CIBERSORT method. 【Results】 A total of 56 differentially expressed miRNAs (DE-miRNAs) were filtered. Functional enrichment analysis showed that these DE miRNAs are mainly enriched in signaling pathways related to tumor occurrence and development as well as immunity-related biological processes. The RF and SVM-RFE algorithms jointly identified 10 diagnostic features of miRNAs, among which only hsa-miR-210-3p is considered the most relevant predictive biomarker for TMB classification. The AUC value of hsa-miR-210-3p in the training, testing, and total sets is 0.822, 0.721, and 0.793, respectively, and has been validated in other cancer types. Besides, CIBERSORT analysis suggests differences in immune cell infiltration between high- and low-TMB groups. Meanwhile, there is a significant positive correlation between the expression of immune checkpoint related genes and mismatch repair related genes and hsa-miR-210-3p. 【Conclusion】 This study successfully identified hsa-miR-210-3p as a predictive biomarker for TMB classification, which can effectively predict TMB values in gastric cancer and other cancer patients and may provide some guidance for immunotherapy.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic