[High expression of the stemness-associated molecule Nanog in esophageal squamous cell carcinoma tissues promotes tumor invasion and metastasis by activating the TGF-ß signaling pathway].

OBJECTIVE: To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma (ESCC). METHODS: We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients. GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog, and TIMER online tool was used to analyze the correlations among TßR1, MMP-2, and MMP-9 in esophageal cancer. RESULTS: Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated. Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age, gender, or tumor differentiation. The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time. Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-ß signaling pathway, and the expressions of MMP-2/MMP-9 and TßR1 were positively correlated. In cultured ESCC cells, Nanog knockdown significantly decreased the expression of TßR1, p-Smad2/3, MMP-2, and MMP-9 and strongly inhibited cell migration. CONCLUSION: The high expressions of Nanog, MMP-2, and MMP-9, which are positively correlated, are closely related with invasion depth, lymph node metastasis, and prognosis of ESCC. Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-ß signaling pathway, and its high expression promotes migration of ESCC cells.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma

Objectives High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. Methods HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. Results The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). Conclusions HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration (AU)

The expression and potential mechanism of EGFR and EZH2 in breast cancer.

BACKGROUND: The purpose of our research was to investigate the expression of epidermal growth factor receptor (EGFR) and zeste gene enhancer homolog 2 (EZH2) in breast cancer, and to explore their potential common pathways. METHODS: Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the protein and corresponding mRNA expression of EGFR and EZH2 in breast cancer tissues and benign tissues. Then, the relationship between EGFR and EZH2 along with the corresponding clinicopathological parameters were also analyzed. Bioinformatics tools were applied to explore the possible common pathways. RESULTS: The results showed that both EGFR and EZH2 protein and mRNA were highly expressed in breast cancer tissues, and there was a positive correlation between EGFR and EZH2. Moreover, we found that increased mRNA expression was correlated with lymph node metastasis and clinical stage (P<0.05). Furthermore, the enrichment results of co-expressed genes indicated that EGFR and EZH2 may work together in the FOXO signaling pathway, affecting the growth and metastasis of breast cancer cells. CONCLUSIONS: The high expression of both EGFR and EZH2 mRNA in breast cancer was related to lymph node metastasis and clinical staging. The FOXO signaling pathway may be their common signaling pathway that affects tumor cell invasion and metastasis.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma.

OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.

Clinical Observation of Trantuzumab Combined with Preoperative Adjuvant Chemotherapy in the Treatment of Her-2 Positive Breast Cancer / 中国药房

OBJECTIVE:To observe the effect of trantuzumab combined with preoperative adjuvant chemotherapy in the treat-ment of human epidermal growth factor receptors 2 (Her-2) positive breast cancer,and to investigate its clinical value. METH-ODS:80 patients with Her-2 positive breast cancer were selected and randomly divided into observation group and control group, with 40 cases in each group. The control group received routine preoperative adjuvant chemotherapy+modified radical mastectomy for Her-2 positive breast cancer;observation group was additionally treated with trastuzumab intravenously before operation,initial dose of 4 mg/kg,followed by 2 mg/kg,once a week,for consecutive 3 weeks,on the basis of control group. The effects of two regimen on the expression of HER-2,CD-34,MGA,E-cadherin and GCDFE-15 in Her 2 positive breast cancer focus were com-pared between 2 groups. ADR and follow-up survey were recorded. RESULTS:Compared with before chemotherapy,the expres-sion of HER-2(+)in observation group increased significantly,while that of HER-2(+ + +)decreased significantly;MGA posi-tive rate and GCDFP-15 positive rate decreased significantly while E-cadherin positive rate increased significantly;MDV of CD34 expression decreased significantly,with statistical significance(P0.05). CONCLUSIONS:Trastuzumab combined with preoperative adjuvant chemotherapy have good clinical efficacy and safety,and it can effectively reduce related indicator of Her-2 positive breast cancer focus. So it has positive significance in reducing recurrence and metastasis of breast cancer.

Expression of CCR4 in gallbladder carcinoma tissues and its clinical significance / 中华肝胆外科杂志

Objective To study the expression of CCR4 in gallbladder carcinoma tissues,and to determine its relationship with clinical pathological factors and its influence on prognosis of gallbladder cancer.Methods The expressions of CCR4 in gallbladder carcinoma tissues,and chronic cholecystitis gallbladder mucosal tissues were detected using immune histochemical methods and they were analyzed together with the clinical records.Survival analysis was used to compare the expressions of CCR4 between the positive group and the negative group.Multiple factors analysis was carried out using the Cox regression model.Correlation between the expressions of CCR4 in gallbladder tissues and the clinical pathologic factors was done using the Chi-square test.Results CCR4 is expressed tan-yellow in gallbladder cell cytoplasm and/or cell membrane.The expression of CCR4 protein in the gallbladder carcinoma was obviously higher than in the chronic cholecystitis gallbladder epithelial tissues (P ＜ 0.05).A high expression of CCR4 was not correlated with patients' age,gender,pathological classification,distant metastasis and nerve/lymphatic invasion factors.It was,however correlated with tumor lymph node metastasis (P ＜ 0.05) and histological grading (P ＜ 0.05).Kaplan Meier survival analysis showed the postoperative survival between the CCR4 positive group and the negative group were significant different (P ＜0.05).On multiple factors analysis,CCR4 expression level was an independent risk factor of survival of patients after gallbladder surgery.Conclusions The chemokine receptor CCR4 expressed in gallbladder carcinoma.Its level of expression correlated with lymph node metastasis and histological grading.It was an independent risk factor of survival in patients with gallbladder carcinoma after surgery.As it was associated with invasion and metastasis of gallbladder carcinoma,antitumor treatment targeting CCR4 is expected to become a novel treatment of gallbladder carcinoma.

Expression and clinical biological significance of fibroblast specific protein-1 in human lung cancer tissue / 中国医师进修杂志

Objective To observe the expression of fibroblast specific protein-1 (S100A4) in human lung cancer,and investigate roles of S100A4 in the infiltration and metastasis of lung cancer. Methods Immunohistochemical S-P method was used to detect the expression of S100A4 in 50 lung cancer tissues and 6 normal lung tissues. Results The expression of S100A4 was up-regulated in lung cancer tissues.Significant differences of the expression rates of S100A4 was found between lung cancer and normal groups (P

Effects of Danshen Injection on the Malignant Obstructive Jaundice in the SD Rat Model / 华中科技大学学报（医学）（英德文版）

To observe the effects of Danshen on the growth of hepatocellular carcinoma in the SD rats, a model of malignant obstructive jaundice was established by inoculation of transplanted tumor into the hepatic portal with the walker-256 hepatocarcine line, which resulted in the obstruction by the infiltration and metastasis of hepatocellular carcinoma. SD rats were divided into 4 groups: the rats were treated by 0.9 % NS (n=24, control group), inosine+vitamin C (n=40, InV group), Danshen (n=40, DS group) and 5-FU (n=40, 5-FU group), respectively. The liver function, morphological changes and the expressions of PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues,adjacent lobe (left-internal lobe) and lung tissues were observed after the treatment with the 4 agents.Our results showed that the protective effect of Danshen on liver function was significantly better than that of NS and 5-FU (P＜0.01). No significant difference in protective effect was observed between DS group and InV group (P＞0.05). Danshen also provided protective effect on the morphological damage of liver caused by obstructive jaundice. The rates of carcinoma-inhibition and metastasis inhibition were significantly higher than those of NS and inosine+vitamin C (P＜0.01). No significant difference in this regard existed between DS group and 5-FU group (P＞0.05). The expressions of PCNA,VEGF and ICAM-1 PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe (left-internal lobe) and lung tissues were lower than those in control group and InV group, with the differences being significant (P＜0.01). No significant differences were found between DS group and 5-FU group in the expression levels of PCNA and VEGF (P＞0.05) but ICAM-1 (P＜0.05). It is concluded that Danshen injection not only has protective effects on liver injury caused by obstructive jaundice, but can inhibit the proliferation and growth of hepatocarcinoma,interfere with the vascularization of tumors, prevent recurrence and metastasis of hepatocarcineoma.

Biological characteristics of MMP and VEGF and their roles in theinfiltration and metastasis of nasopharynx carcinoma / 医学研究生学报

Researches have indicated that matrix metalloproteinases (MMP) and vascular endothelial growth factors (VEGF) play a key role in the metastasis of nasopharynx carcinoma (NPC). They promote tumor cell infiltration and metastasis by proteolysis of extracellular matrix proteolysis of tumor cells and induction of angiogenesis and lymphangioenesis. Researches on the mechanism of MMPs and VEGFs on NPC may help to further understand the metastasis of NPC and develop new methods for the diagnosis and treatment of NPC and other tumors as well.

Effects of DanShen injection in treating the malignant obstractive jaundice in the SD rat model / 西安交通大学学报(医学版)

Objective To observe the effects of DanShen on the growth of hepatocellular carcinoma in malignant obstructive jaundice in the SD rat model. Methods The model was established by vaccination of transplanting tumour in the porta hepatis with the walker-256 hepatocarcine line, and then obstruction was caused by the infiltration and metastasis of hepatocellular carcinoma. ② The SD rats were divided into four groups: the rats treated by 0.9% NS (n=12), the rats treated by Inosine + Vitamin C (n=20), the rats treated by DanShen (n=20) and the rats treated by 5-FU(n=20). ③ The liver function, morphological changes and the expression of PCNA VEGF and ICAM-1 in carcinoma and peri-carcinoma tissues, adjacent lobe (left-internal lobe) as well as lung tissues were observed after four experimental groups were successively treated by four medicines. ④ Statistical analysis was done to the experimental results. Results ① The growth of rats treated by DanShen injection showed that liver injury caused by malignant obstructive jaundice was significantly relieved compared with liver function and pathological morphological changes in other groups(P0.05); ③ The expression of PCNA VEGF and ICAM-1 in carcinoma, peri-carcinoma adjacent lobe (left-internal lobe) tissues as well as lung tissues were significantly downgraded in groups treated by DanShen injection compared with those in groups treated with 0.9%NS and Inosine combined with Vitamine C (P0.05). Conclusion DanShen injection not only has protective effects on liver injury caused by obstructive jaundice, but the medicine can inhibit the proliferation and growth of hepatocarcinoma, interfere with the vascularization of tumors, and prevent recurrence and metastasis of hepatocarcinoma.

The effect of Danshen on the expression of PCNA during malignant biliary obstruction / 西安交通大学学报(医学版)

Objective To establish malignant biliary obstruction model on SD rats and to study the effects of Danshen injection on the growth of hepatocellular carcinoma, morphological change and the expression of proliferating cell nuclear antigen (PCNA) in carcinoma and peri-carcinoma tissues. Methods Malignant biliary obstruction model on SD rats was made by vaccination of transplanted tumor in the liver nearby the portal hepatis with Walker-256 hepatocarcinoma cell line which infiltrating and metastasizing to proximal common bile duct causing an obstruction. The SD rats were divided into four groups: those treated with 0.9% N S (n=12), with Inosine+VC (n=20), with Danshen (n=20) and with 5-FU (n=20), respectively. Results The growth and expression of PCNA in carcinoma, peri-carcinoma adjacent lobe tissues were significantly downgraded after treatment by Danshen injection compared with the rats treated by 0.9% N S and Inosine combined with Vitamine C and the infiltration was increased. The expression of PCNA in carcinoma, peri-carcinoma adjacent lobe tissues were downgraded compared with that of the rats treated by 5-FU while growth of hepatocarcinoma was slightly downgraded after treatment with Danshen injection. Conclusion Danshen shows protective effects on morphological change in SD rat model of malignant biliary obstruction. It can also inhibit the growth of hepatocarcinoma through inhibiting the proliferation of hepatocarcinoma cells and increasing reversion of hepatocarcinoma cells.