Expressions and Prognostic Values of Notch3 and DLL4 in Human Breast Cancer.

Background: Notch signaling played a critical role in promoting breast tumorigenesis and progression. However, the role and prognostic value of Notch3 combined with DLL4 expression in breast carcinoma had not been explored. Methods: The retrospective study enrolled 90 breast cancer tissues and 60 noncancerous tissues from (conceal). The expression and prognostic value of Notch3 and DLL4 in patients with breast carcinoma were investigated using Oncomine and UALCAN database. Notch3 and DLL4 expression levels were detected by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. We analyzed the correlation between both proteins expression and clinicopathological parameters and survival data, respectively. Results: The expressions of Notch3 and DLL4 were increased, and Notch3 expression was significantly positively associated with DLL4 in breast carcinoma. The 2 proteins dramatically correlated with advanced stage, high grade and negative Her2 status. The overexpressing of single or both Notch3 and DLL4 resulted in shortened survival of breast cancer patients. And Notch3 overexpression was one of independent risk predictors to poor prognosis. Conclusion: The interaction of Notch3 receptor and DLL4 ligand accelerates oncogenesis, progression, and poor prognosis of breast cancer patients. Notch3 protein may serve as one of biomarker to independently predict prognosis of patients.

The value of S-Detect for the differential diagnosis of breast masses on ultrasound: a systematic review and pooled meta-analysis.

AIM: To evaluate the value of S-Detect (a computer aided diagnosis system using deep learning) in breast ultrasound (US) for discriminating benign and malignant breast masses. MATERIAL AND METHODS: A literature search was performed and relevant studies using S-Detect for the differential diagnosis of breast masses were selected. The quality of included studies was assessed using a Quality Assessment of Diagnostic Accuracy Studies (QUADAS) questionnaire. Two review authors independently searched the articles and assessed the eligibility of the reports. RESULTS: A total of ten studies were included in the meta-analysis. The pooled estimates of sensitivity and specificity were 0.82 (95%CI: 0.77-0.87) and 0.86 (95%CI: 0.76-0.92), respectively. In addition, the diagnostic odds ratios, positive likelihood ratio and negative likelihood ratio were 28 (95%CI: 16- 49), 5.7 (95%CI: 3.4-9.5), and 0.21 (95%CI: 0.16-0.27), respectively. Area under the curve was 0.89 (95%CI: 0.86-0.92). No significant publication bias was observed. CONCLUSIONS: S-Detect exhibited a favourable diagnostic value in assisting physicians discriminating benign and malignant breast masses and it can be considered as a useful complement for conventional US.

Low-Grade Chondrosarcoma In The Sellar Area: Case Report And Literature Review.

Low-grade chondrosarcoma (LGC) is a very rare intracranial tumor, particularly in the sellar area. Herein, we describe an unusual case of LGC occurring in the sellar area. A 52-year-old man presented with diminution of vision for more than 3 months, but did not exhibit headaches reported in previous cases. MRI showed that the maximum size of the tumor was 7 cm on the left side of the saddle. We characterized the specific pathological characteristics. Histologically, the tumor had polypoid areas and a lobulated growth pattern under low-power examination. At high magnification, the tumor consisted of small cells with hyperchromatic nuclei in the cartilage matrix, with an alternating loose hypocellular zone and rich myxoid area. In our case, LGC needed to be distinguished from chordoma. Immunohistochemically, the tumor cells showed diffuse positivity for S-100 and vimentin, IDH1 was weakly cytoplasm positive. The Ki-67 labeling index was less than 5%. Additionally, AE1/3, EMA, and CK19 were negative, which could be used to exclude chordoma. This case report expands the literature on LGC and will help clinicians and pathologists better understand this entity.

High infiltration of CD68-tumor associated macrophages, predict poor prognosis in Kazakh esophageal cancer patients.

Tumor-associated macrophages (TAMs), the most important immune cells in tumor microenvironment, were reported to play a key role in cancer progression, but the correlation of TAMs and Kazakh esophageal squamous cell carcinoma (ESCC) was still not clear, so we sought to identify the function of TAMs in Kazakh ESCC clinicopathological and prognostic evaluation. CD68 as the TAMs marker, and immunohistochemistry (IHC) was used to quantify the TAMs infiltrated in tumor nest and stroma, the IHC staining was also used to evaluate the expression of MMP-9 in Kazakh ESCCs. The density of CD68-TAMs in ESCCs tumor nest and stromal, were significantly higher than those of CANs (P<0.05). The increasing number of CD68-positive TAMs in tumor nest and stromal were positively associated with tumors lymph node metastasis and clinical stage (P<0.05). The expression of MMP-9 in Kazakh ESCCs was higher than that of CAN tissues (P<0.05). Increased MMP-9 expression in ESCCs was significantly associated with lymph node metastasis and tumor clinical stage (P<0.05). Importantly, the number of CD68-positive TAMs in ESCCs was significantly correlated with the expression of MMP-9 (P<0.05). Furthermore, the survival analyses demonstrated that high-density of CD68-TAMs in tumor nest was positively related to the shorter overall survival time of patients (P<0.05). Increasing numbers of CD68-TAMs promote higher expression of MMP-9 and may play an important role in the occurrence and progression of Kazakh ESCCs, and which could be used as important prognostic markers for Kazakh ESCCs.

Human papillomavirus infection correlates with inflammatory Stat3 signaling activity and IL-17 expression in patients with breast cancer.

OBJECTIVES: Microbiota has been suggested in promoting chronic inflammation in human tissues which, in turn, promotes tumor development. This study tests a hypothesis that high-risk human papillomavirus (HR-HPV) infection may correlate with proinflammatory Stat3 signaling activities and IL-17 levels in breast cancer (BC) patients. MATERIALS AND METHODS: This study examined HPV infection by GenChip technology, constitutively active Stat3 (p-Stat3) and IL-17 levels by immunohistochemistry (IHC) using specific antibodies in 379 BC patients, together with 245 paired adjacent breast adenosis (ABA) tissues and 100 unrelated breast adenosis (BA) tissues. RESULTS: We obtained four major findings: (1) HR-HPV16/18 infections existed in 10.5% (34/325) of BC issues, higher than control BA tissues (4%, 4/100, P = 0.047). (2) Using IHC methodology, BC tissues showed more overactive p-Stat3 (2+/3+, 38.5%, 146/379) than ABA tissues (27.3%, 67/245, P < 0.001); similarly, BC also had more tissues overexpressing IL-17 (2+/3+, 61.5%, 233/379) than ABA tissues (51.8%, 127/245, P < 0.001). (3) High levels (2+/3+) of both active p-Stat3 and IL-17 correlated with poor differentiation and lymph nodal metastasis in BC (both with P < 0.05), but not with patients' prognosis. (4) HR-HPV infections correlated with both active p-Stat3 (P = 0.018) and its downstream IL-17 levels (P = 0.021) in BC tissues. CONCLUSION: There may be a possible tri-lateral relationship among HPV infection, constitutive Stat3 activity and IL-17 level, whose collaborations could orchestrate a proinflammatory microenvironment in breast tissues by which promote carcinogenesis and/or facilitate progression of breast cancer.

Prognostic value of Sox2 expression in digestive tract cancers: A meta-analysis.

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.

Clinicopathological and prognostic role of SIRT1 in breast cancer patients: a meta-analysis.

BACKGROUND: Silent mating type information regulation 2 homolog-1 (SIRT1) plays an important role in the progression and development of cancer, including breast cancer. However, the association between SIRT1 expression and clinicopathological parameters and prognosis in breast cancer remains inconclusive. To accurately evaluate the significance of SIRT1 expression in breast cancer, a meta-analysis based on published studies was performed. METHODS: The PubMed, Embase, ISI Web of Science, Science Direct, and Chinese National Knowledge Infrastructure databases were screened to retrieve relevant literature. The reported odds ratios (ORs) and hazard ratios (HRs) and their 95% corresponding confidence intervals (CIs) were pooled to estimate the strength of specific associations. RESULTS: Six studies involving 604 patients were included in the meta-analysis. The pooled analyses showed a significant correlation between SIRT1 expression and poor disease-free survival (DFS) (HR = 3.07, 95% CI: 1.92-4.91, Z = 4.69, P < 0.001) and overall survival (OS) (HR = 3.94, 95% CI: 2.19-7.10, Z = 4.57, P < 0.001). SIRT1 expression also significantly correlated with high TNM stage (pooled OR = 2.92, 95% CI: 1.84-4.63) and lymph node metastasis (pooled OR = 3.22, 95% CI: 0.98-10.57). CONCLUSIONS: Our meta-analysis shows that SIRT1 expression correlates with unfavorable clinical outcomes. We suggest that SIRT1 expression may have potential value in the pathological diagnosis and clinical treatment of patients with breast cancer. More studies are warranted to investigate the effect of SIRT1 on the survival of breast cancer patients.

Implications of the Notch1-Snail/Slug-epithelial to mesenchymal transition axis for lymph node metastasis in infiltrating ductal carcinoma.

Emerging evidence suggests that activation of the Notch1 signaling pathway inducing epithelial to mesenchymal transition (EMT) mediated by Snail/Slug promotes invasion and metastasis of breast cancer cells in vitro. However, the implication of the Notch1-Snail/Slug-EMT axis in breast cancer patients remains unclear. A total of 200 formalin-fixed paraffin-embedded samples of invasive ductal carcinoma (IDC), and 37 adjacent non-neoplastic tissue (ANNT) samples from patients who had not been treated with neoadjuvant therapy were examined. Expression of Notch1, Slug, Snail, E-cadherin, N-cadherin, and vimentin was determined by immunohistochemistry on tissue microarrays (TMAs). The correlation between protein expression and clinicopathological characteristics of breast cancer patients was also evaluated. Results showed that a significantly high percentage of cases with high expression of Notch1 (74%, 148/200), Slug (36%, 72/200), Snail (62%, 124/200), and N-cadherin (77%, 153/200) and a low percentage of cases with high expression of E-cadherin (27%, 54/200) were observed in IDC compared to those in ANNTs. High Notch1, Slug, Snail, and N-cadherin expression and low E-cadherin expression in patients with IDC were significantly correlated with lymph node metastasis. In addition, correlation analysis results revealed that high Notch1 expression was significantly associated with high Slug, Snail, and N-cadherin expression and low E-cadherin expression in IDC. Furthermore, a high Snail expression was significantly associated with low E-cadherin expression, and a high Slug expression was found to be significantly associated with increased N-cadherin expression in patients with IDC. Hence, our study suggested that the Notch1-Snail/Slug-EMT axis may be implicated in the lymph node metastasis affecting patients with IDC.

Correlation and prognostic value of SIRT1 and Notch1 signaling in breast cancer.

BACKGROUND: SIRT1 expression and Notch1 signaling have been implicated in tumorigenesis in many cancers, but their association with survival in breast cancer has not been determined. The purpose of this study was to assess the possible prognostic value of SIRT1, N1IC, and Snail expression in breast cancer patients. METHODS: Immunohistochemistry was performed to examine the expression of SIRT1, N1IC, and Snail, and the combined expression of SIRT1 and N1IC, using tissue microarrays containing breast cancer tissue and matched adjacent normal breast tissue from 150 breast cancer patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of SIRT1, N1IC, Snail and combined SIRT1/N1IC expression, in addition to other clinicopathological factors, including grade, lymph node status, disease stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 receptor status in breast carcinoma patients. RESULTS: SIRT1, N1IC, and Snail were all found to be highly expressed and an inverse correlation between SIRT1 and N1IC in breast cancer tissue. The three markers significantly correlated with lymph node status. Patients with low SIRT1 expression exhibited shorter overall survival (OS) and disease-free survival (DFS), and patients with combined low expression of SIRT1 and high expression of N1IC had the worse OS and DFS. Univariate and multivariate survival analysis revealed that low expression of SIRT1 and SIRT1-low/N1IC-high expression were independent prognostic factors for poor survival. CONCLUSIONS: These results suggest that low expression of SIRT1 or the combined low expression of SIRT1 and high expression of N1IC could be used as indicators of poor prognosis, and may represent novel therapeutic targets in breast cancer.

Associations between TLR9 polymorphisms and cancer risk: evidence from an updated meta-analysis of 25,685 subjects.

A meta-analysis incorporating 34 case-control studies from 19 articles involving 12,197 cases and 13,488 controls was conducted to assess the effects of three genetic variants of Toll-like receptor 9 (TLR9): rs187084, rs352140, and rs5743836. Studies on associations between TLR9 polymorphisms and cancer risk were systematically searched in electronic databases. The reported odds ratios (OR) and 95% confidence intervals (CI) were pooled to assess the strength of any associations. The results showed that the rs187084 polymorphism was significantly associated with an increased risk of cancer (CC vs TC+TT: OR=1.14, 95% CI=1.02-1.28), specifically cervical cancer (C vs T: OR=1.19, 95% CI=1.05-1.34; TC vs TT: OR=1.32, 95% CI=1.10-1.58; CC vs TT: OR=1.31, 95% CI= 1.03-1.68; CC+TC vs TT: OR=1.32, 95% CI=1.11-1.56), and that this association was significantly positive in Caucasians (CC vs. TC+TT: OR=1.18, 95% CI=1.01-1.38). The rs352140 polymorphism had a protective effect on breast cancer (GA vs GG: OR=0.77, 95% CI=0.66-0.89), whereas the rs5743836 polymorphism was likely protective for digestive system cancers (CC+TC vs TT: OR=0.81, 95% CI=0.66-0.98). In conclusion, our results suggest that the rs187084 polymorphism may be associated with an elevated cancer risk, whereas polymorphisms of rs352140 and rs5743836 may play protective roles in the development of breast and digestive system cancers, respectively. From the results of this meta-analysis further large-scale case-control studies are warranted to verify associations between TLR9 polymorphisms and cancer.

Human leukocyte antigen-DRB1*1501 and DQB1*0602 alleles are cervical cancer protective factors among Uighur and Han people in Xinjiang, China.

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer. However, only some high risk human papillomavirus (HR-HPV)-infected women progress to cervical cancer, host immunogenetic factors human leukocyte antigen (HLA) may account for viral antigens presenting individually or together in the progression to cervical cancer. This study examined the association between the development of invasive cervical cancer (ICC) and the determinant factors including HLA-DRB1*1501 and DQB1*0602, HR-HPV infection among Chinese Uighur and Han populations. Blood samples, cervical swabs and biopsies were obtained from 287 patients with ICC (192 Uighurs and 95 Hans) and 312 healthy controls (218 Uighurs and 94 Hans). HPV DNA was detected by PCR and HLA-DRB1*1501 and DQB1*0602 alleles were performed using PCR-SSP method. HPV16 infection rates was significantly higher among Uighur and Han with ICC as compared to healthy controls (OR = 58.317; 95% CI: 39.663-85.744; OR = 33.778; 95% CI: 12.581-90.691; P < 0.05 for all). HLA-DRB1*1501 (OR = 0.305; 95% CI: 0.115-0.813; P < 0.05) and HLA-DRB1*1501-DQB1*0602 haplotype frequencies (OR = 0.274; 95% CI: 0.086-0.874; P < 0.05) were significantly reduced in Han ICC. The HLA-DQB1*0602 frequency significantly decreased among Uighur women with ICC (OR = 0.482; 95% CI: 0.325-0.716; P < 0.05). Similar tendencies were observed for DQB1*0602 with HPV16-positive ICC (OR = 0.550; 95% CI: 0.362-0.837; P < 0.05). This study suggests that HLA-DRB1*1501 and DQB1*0602 alleles may influence the immune response to HPV16 infection and decrease the risk of ICC among Uighurs and Hans in Xinjiang, China.

Notch1 single nucleotide polymorphism rs3124591 is associated with the risk of development of invasive ductal breast carcinoma in a Chinese population.

Accumulated evidence has revealed the presence of Notch receptor polymorphisms in non-tumorous diseases; however, few studies have investigated the association of Notch polymorphisms with breast cancer risk. A total of 100 invasive ductal carcinoma (IDC) and 50 ductal carcinoma in situ (DCIS) patients and 100 usual ductal hyperplasia (UDH) controls were genotyped for the following Notch receptor single nucleotide polymorphisms (SNPs) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: Notch1, rs3124591; Notch2, rs11249433; Notch3, rs3815188, and rs1043994; and Notch4, rs367398, and rs520692. Immunohistochemistry was used to determine the effect of Notch polymorphisms on corresponding Notch protein expression in successfully genotyped patients. The frequency of rs3124591 TC genotype was significantly higher in IDC (24.7%, 20/81) and DCIS (30%, 12/40) patients than in UDH controls (8%, 8/97) (P = 0.002 and P = 0.011, respectively). However, the distribution of other SNP genotypes was not significantly different between IDC and DCIS patients and UDH controls. The frequency of TC genotype was significantly higher in poorly differentiated tumors than in well-differentiated and moderately differentiated tumors (P = 0.022). Importantly, a positive correlation between the rs3124591 TC genotype and high Notch1 protein expression was observed in DCIS patients (P = 0.043) but not in IDC patients. This is the first study to suggest an increased risk of IDC and DCIS of the breast for the Notch1 rs3124591 variant. Furthermore, given the inconsistent associations between the rs3124591 variant and Notch1 expression in IDC and DCIS, this variant may affect breast cancer risk through mechanisms in the latter stage other than alterations in Notch1 protein expression.

The Catechol-O-Methyltransferase Val158Met Polymorphism Contributes to the Risk of Breast Cancer in the Chinese Population: An Updated Meta-Analysis.

PURPOSE: Catechol-O-methyltransferase (COMT) enzyme plays a central role in estrogen-induced carcinogenesis. Emerging evidence from association studies has revealed that the functional Val158Met polymorphism (rs4680 G>A) of the Catechol-O-methyltransferase gene (COMT) has been implicated in susceptibility to breast cancer in the Chinese population, while results of individual published studies remain inconclusive and inconsistent. To assess this association in the Chinese population, a meta-analysis was performed. METHODS: Eligible studies were searched on MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, and the Chinese Biomedicine Database. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the association between COMT polymorphisms and the risk of breast cancer using RevMan 5.2 and Stata 12.0 software. RESULTS: The meta-analysis included 14 eligible studies, with a total of 4,626 breast cancer cases and 5,637 controls. Overall, the COMT Val158Met polymorphism (rs4680 G>A) was significantly associated with an increased risk of breast cancer in several genetic models (A/A vs. G/G: OR, 1.59, 95% CI, 1.12-2.27; A/A vs. G/A+G/G: OR, 1.62, 95% CI, 1.14-2.29; A vs. G: OR, 1.15, 95% CI, 1.00-1.32), and a subgroup analysis according to menopausal status showed that this association was especially evident among premenopausal Chinese women (A/A vs. G/G: OR, 1.87, 95% CI, 0.99-3.54; A/A vs. G/A+G/G: OR, 1.94, 95% CI, 1.03-3.63). CONCLUSION: The results of this meta-analysis indicated that COMT Val158Met variants contribute to breast cancer susceptibility in the Chinese population, particularly among premenopausal women.

BRCA1 gene exon 11 mutations in Uighur and Han women with early-onset sporadic breast cancer in the northwest region of China.

The prevalence of BRCA1 gene mutations in breast cancer differs between diverse ethnic groups. Relatively little information is known about patterns of BRCA1 mutations in early-onset breast cancer in women of Uighur or Han descent, the major ethnic populations of the Xinjiang region in China. The aim of this study was to identify BRCA1 mutations in Uighur and Han patients with early-onset (age <35 years), and sporadic breast cancer for genetic predisposition to breast cancer. For detection of BRCA1 mutations, we used a polymerase chain reaction single-stranded conformation polymorphism approach, followed by direct DNA sequencing in 22 Uighur and 13 Han women with early-onset sporadic breast cancer, and 32 women with benign breast diseases. The prevalence of BRCA1 mutations in this population was 22.9% (8/35) among early-onset sporadic breast cancer cases. Of these, 31.8% (7/22) of Uighur patients and 7.69% (1/13) of Han patients were found to have BRCA1 mutations. In 7 Uighur patients with BRCA1 mutations, there were 11 unique sequence alterations in the BRCA1 gene, including 4 clearly disease-associated mutations on exon 11 and 3 variants of uncertain clinical significance on exon 11, meanwhile 4 neutral variants on intron 20 or 2. None of the 11 BRCA1 mutations identified have been previously reported in the Breast Cancer Information Core database. These findings reflect the prevalence of BRCA1 mutations in Uighur women with early-onset and sporadic breast cancer, which will allow for provision of appropriate genetic counseling and treatment for Uighur patients in the Xinjiang region.

Multiple polymorphisms within the PLCE1 are associated with esophageal cancer via promoting the gene expression in a Chinese Kazakh population.

Although recent genome-wide association studies of esophageal squamous cell carcinoma (ESCC) identified a susceptibility locus in phospholipase C epsilon 1 (PLCE1) in Chinese Han populations, few studies further confirmed these findings in pure Kazakh population in which there are higher incidence and mortality of ESCC. Here, we investigated the potential associations between 19 SNPs of PLCE1 and susceptibility to ESCC in 222 cases and 326 controls from a pure ethnic population of Kazakh. Real-time PCR and immunohistochemistry were performed to detect the PLCE1 expression levels and evaluate their association with PLCE1 polymorphism. We found that only 4 SNPs (rs753724, rs11187842, rs2274223, and rs12263737) with moderate linkage disequilibrium (LD) confer significantly increased risk of ESCC, with the ORs ranging from 1.43 to 2.04, and there was a risk allele dose-dependent increase in ESCC risk (P-trend=0.043). Especially, the risk effects of rs2274223 were more evident in poor differentiation and advanced clinical stages of Kazakh ESCC. Additionally, the significantly lowest PLCE1 mRNA expression was found in the KYSE-150 cell line having no risk alleles compared with other three cell lines having risk alleles, and the normal tissues of both homozygous mutant type of PLCE1 rs12263737 and rs2274223 had a higher PLCE1 staining score than that of homozygous wild type. Our findings suggested that genetic variants in PLCE1 might serve as candidate markers for Kazakh ESCC susceptibility, and these LD variants might influence ESCC risk individually and jointly by promoting the messenger RNA and protein expression of the gene.

Synuclein-γ suppression mediated by RNA interference inhibits the clonogenicity and invasiveness of MCF-7 cells.

The aim of the present study was to investigate the effects of synuclein-γ (SNCG) downregulation by RNA interference (RNAi) on the clonogenicity and invasiveness of MCF-7 breast cancer cells. This study used four pairs of SNCG-specific siRNAs which were designed and cloned into the pGPU6 plasmid for introduction into an MCF-7 cell line. The SNCG knockdown efficacies of the four siRNAs were compared using the reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. The cells' clonogenic and invasive phenotypes were examined with clonogenic and Boyden chamber assays. In comparison with the non-specific siRNA and empty vector controls, all four SNCG siRNAs were observed to significantly inhibit SNCG expression at the mRNA and protein levels (F=481.06, P<0.001; F=147.42, P<0.0001). SNCG suppression mediated by RNAi successfully inhibited the clonogenicity (P=0.002) and invasiveness (P<0.001) of transfected MCF-7 cells. According to the results of the present study, we concluded that SNCG suppression mediated by RNAi significantly suppressed SNCG expression at the mRNA and protein levels, suggesting that SNCG suppression mediated by an RNAi strategy may become a novel approach for treating advanced breast cancer.

[Relationship between rs2274223 and rs3765524 polymorphisms of PLCE1 and risk of esophageal squamous cell carcinoma in a Kazakh Chinese population].

OBJECTIVE: To investigate the association between the rs2274223 and rs3765524 polymorphism of phospholipase C epsilon 1 (PLCE1) gene and the susceptibility to develop esophageal squamous cell carcinoma (ESCC) in a pure Kazakh Chinese population. METHODS: Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was utilized to genotype the potentially functional single nucleotide polymorphism rs2274223 A>G and rs3765524 C>T of PLCE1 in an ongoing hospital-based and case-control study of 200 ESCC cases with 300 cancer-free age ( ± 5 years) and sex matched controls. Statistical analyses were performed with Statistical Products and Services Solutions software (version 13.0). Adjusted odds ratios (OR) and 95% confidence evaluation intervals (95%CI) measured by multivariate logistic regression analysis were adopted to study the correlation of the gene polymorphism with the susceptibility to ESCC. RESULTS: The genotype frequencies observed for rs2274223 was consistent with Hardy-Weinberg equilibrium in controls. Univariate analysis revealed significant differences between cases and controls with respect to genotype distribution for rs2274223 (P = 0.006). The variants of rs2274223 were found to confer significantly increased risk of ESCC (GG vs AA: OR = 3.17, 95%CI = 1.45-6.93; AG/GG vs AA: OR = 1.55, 95%CI = 1.08-2.22) in the Kazakh Chinese population. Moreover, AG/GG genotype of rs2274223 was found to be significantly associated with poorly-differentiated ESCC (OR = 2.48, 95%CI = 1.10-5.60). When the ESCC patients were divided into two subgroups, stage I/II and stage III/IV according to the AJCC TNM classification, the GT/GG genotype of rs2274223 was significantly associated with stage III/IV ESCC (OR = 1.85, 95%CI = 1.05-3.25). No significant association was found between rs3765524 and Kazakh ESCC. CONCLUSIONS: These results indicate that rs2274223 site polymorphism of the PLCE1 gene is strongly associated with risk of ESCC in a Kazakh Chinese population, especially the poorly-differentiated and stage III/IV ESCC.

[Effect of anti-osteopontin antibody on expression of IL-2 and IL-5 in hepatic alveolar hydatid tissue of gerbil].

OBJECTIVE: To observe the effect of anti-osteopontin antibody on the level of IL-2 and IL-5 in the liver of gerbil infected with Echinococcus multilocularis (Em). METHODS: 180 gerbils were infected with echinococcus protoscoleces (approximately 400 for each gerbil) by abdominal opening inoculation in liver. The gerbils were randomly divided into three groups with 60 each: experiment group (group A, with anti-osteopontin antibody interference), control group (group B, with normal rabbit serum injection) and model group (group C, with no interference). Ten gerbils from each group were sacrificed at 20, 60, 100, 140, 180, and 220 days post-infection respectively. The liver tissue with hydatid cysts was collected and the expression of IL-2 and IL-5 was observed after immunohistochemistry staining (SP method). RESULTS: E. multilocularis hydatid tissue spreaded over the liver and abdominal cavity. The positive expression rate of IL-2 in the tissue showed no statistical difference among the three groups (P > 0.05). On the days 140 and 180, however, the positive expression rate of IL-5 in group A was 40% and 20% respectively, considerably lower than that in group B (100% and 90%) and group C (90% and 80% respectively). CONCLUSION: The anti-osteopontin antibody can reduce Th2 type cytokine response in the Em-infected gerbils, which may strengthen the immunity of the host.

[The correlation between osteopontin and metastasis of hepatic Echinococcus multilocularis infection].

OBJECTIVE: To investigate the expression and distribution of osteopontin (OPN) in Echinococcus multilocularis cyst, and explore the role of OPN in the metastasis of hepatic E. multilocularis infection. METHODS: Forty gerbils were infected with 20% E. multilocularis suspension (0.1 ml per gerbil) through abdominal opening injection in liver. Gerbils were sacrificed at 100 days postinfection for observing the growth and metastasis of hepatic echinococcus cyst. The liver, hepatic echinococcus cyst and metastasis tissue were observed on HE stain; the expression of OPN were measured by immunohistochemistry staining (SP method). RESULTS: E. multilocularis were spread over the liver and abdominal cavity. Expression of OPN was found at different degree in echinococcus cysts. The positive expression rate of OPN in echinococcus cysts was 70% (28/40). OPN was mainly distributed in the germinal layer, inflammatory cells and some liver cells. 60% (24/40) occurred thoracic lymph node metastases. The OPN expression rate in hepatic echinococcus cysts with thoracic lymph node metastases (83%, 20/24) was significantly higher than that of hepatic echinococcus cysts without thoracic lymph node metastases (50%, 8/16) (P < 0.05). The positive expression of OPN in lymph node metastases (92%, 22/24) was higher than that of hepatic echinococcus cyst (70%, 28/40) (P < 0.05). CONCLUSION: Osteopontin mainly distributes in the germinal layer of hepatic echinococcus cyst and inflammatory cells, which might be involved in metastasis of hepatic E. multilocularis infection.

[Detection and clinical significance of Notch1 methylation in breast cancer and intraductal proliferative breast lesions].

OBJECTIVE: To explore the relevance between the promoter methylation status of Notch1 gene and the invasive ductal carcinoma and ductal hyperplastic lesions of the breast. METHODS: Methylation status of Notch1 gene in human breast invasive ductal carcinoma (IDC, n = 89), ductal carcinoma in situ (DCIS, n = 20), atypical ductal hyperplasia (ADH, n = 11) and usual ductal hyperplasia (UDH, n = 20) were quantitatively evaluated by MALDI-TOF MS. The expression of Notch1 protein was detected by immunohistochemical stain (SP method). RESULTS: Positive expression rates of Notch1 protein in IDC and DCIS were 91.0% (81/89) and 75.0% (15/20), respectively, which were significantly higher than those of ADH (4/11) and UDH (30.0%, 6/20;P < 0.05). Notch1 protein expression was correlated significantly with lymph node metastasis, pathological grades and TNM stages of IDC. The mean methylation levels of Notch1 gene at CpG_3, CpG_4.5 and CpG_8 significantly decreased in IDC group compared with those of DCIS, ADH and UDH groups (P < 0.0083). In breast carcinomas, the mean methylation rates of Notch1 gene at CpG_4.5, CpG_10.11, and CpG_14.15.16 loci in cases with axillary node metastasis were significantly lower than those without axillary node metastasis (P < 0.05); and the methylation rates at CpG_14.15.16 and CpG_18 loci in stage Iwere lower than that in stage II, further lower than that in stage III (P < 0.05); and that in CpG_1.2, CpG_12.13 loci in grade I (highly-differentiated group) were higher than that in grade II (moderate-differentiated group) and grade III (poorly-differentiated group) (P < 0.05); and the methylation rates at CpG_3, CpG_8 and CpG_14.15.16 loci in ER(+) PR(+) HER2(-) group were lower than that in ER(-) PR(-) HER2(+) group (P < 0.05). CONCLUSIONS: There is an overall hypomethylation of Notch1 gene in breast invasive ductal carcinomas with corresponding over-expression of Notch1 protein. This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notch1, and this change may have important significance in breast tumorigenesis and the development. Specific hypomethylation at CpG_3, CpG_ 4.5 and CpG_8 loci of Notch1 gene may play a role in the pathogenesis of breast carcinoma, suggesting the progression and/or malignant transformation from benign glandular lesions of the breast.