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The performance of combining fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) in colorectal cancer (CRC) screening in economically and medically underserved populations is uncertain. This study investigated the performance of a CRC screening protocol of combining FITs and an HRFQ as primary screening methods in a rural Chinese population. A CRC mass screening was conducted using FITs and an HRFQ as the first and colonoscopy as the second stage of screening in Jiashan, 2007–2009. The target population was 31,963 residents in three communities. The compliance was 84.7% for HRFQ, 76.4% for FITs, and 78.7% for colonoscopy. The detected rates of cancer, adenoma, nonadenomatous polyps, and advanced neoplasm were 2.7%, 14.8%, 5.9%, and 8.9% by FITs, which were higher than those by HRFQ (0.5%, 9.2%, 4.8%, and 3.8%, respectively). There was no significant difference in detected rate for nonadenomatous polyps between FITs and HRFQ. A total of 41.2% adenomas, 53.2% nonadenomatous polyps, and 29.8% advanced neoplasms were detected by HRFQ but missed by FITs. Positive predictive value of the screening protocol of combining FITs and HRFQ for advanced neoplasm was 5.7%, which was higher than FITs alone. Men had a higher prevalence of advanced neoplasm than women. Results indicate that combining FITs and HRFQ as primary screening methods is an efficient CRC screening strategy in economically and medically underserved populations. Cancer Prev Res; 4(10); 1572–9. ©2011 AACR.

Perspective on This Article from Performance of a Colorectal Cancer Screening Protocol in an Economically and Medically Underserved Population

Background. This study is aimed at identifying the important biomarkers associated with bone metastasis (BM) in breast cancer (BRCA). Methods. The GSE175692 dataset was used to detect significant differential expressed genes (DEGs) between BRCA samples with or without BM, and DEG-related pathways were then explored. Further, we constructed the protein-protein interaction (PPI) network on GEGs and filtered 5 vital nodes. We then performed the Cox regression, Kaplan-Meier analysis, nomogram, and ROC curve to filter the most significant prognosis genes. The GSE14020 and GSE124647 datasets were used to verify the expression and prognostic value of hub genes, respectively. Finally, the gene set enrichment analysis (GSEA) was performed to reveal the potential mechanism. Results. Totally, 74 DEGs were detected, which mainly correlated with infectious disease, signaling molecules, and interaction. The 5 important DEGs were then filtered, and the Cox regression further showed that 2 genes, including prominin 1 (PROM1) and C-C motif chemokine ligand 2 (CCL2), were related to the prognosis of BRCA metastasis patients. Especially, PROM1 presented a better prognostic performance on the survival probability of patients than CCL2. Verification analysis further confirmed the abnormal expression and significant prognostic influence of PROM1. Finally, GSEA revealed that PROM1 was negatively related to IGF1 and mTOR pathways in BRCA metastasis. Conclusion. PROM1 was an important biomarker associated with BRCA bone metastasis and affected the prognosis of metastatic BRCA patients. It may play a vital role in metastatic BRCA by negatively regulating IGF1 and mTOR pathways.

BackgroundThis study aimed to explore the important biomarker associated with bone metastasis (BM) in breast cancer (BRCA).MethodsThe GSE175692 dataset was used to detect significant differential expressed genes (DEGs) between BRCA samples with or without BM, and important pathways were then explored. Further, we constructed protein-protein interaction (PPI) network on GEGs and filtered 5 vital nodes. Through performing cox regression, Kaplan-Meier analysis, nomogram, ROC curve, and risk score model, significant prognostic factor was gradually identified. Finally, gene set enrichment analysis (GSEA) analysis was performed to reveal the potential mechanism.ResultsTotally, 74 DEGs were detected, which mainly correlated with infectious disease, signaling molecules and interaction. The 5 important DEGs were filtered, and cox regression further showed that prominin-1 (PROM1) and C-C Motif Chemokine Ligand 2 (CCL2) were prognosis-related factors. A negative correlation was observed between the expression of these 2 genes and the overall survival of metastatic BRCA patients. Especially, PROM1 presented a better prognostic performance on the survival probability of patients. Prognosis verification analysis also confirmed the significant influence of PROM1 on patient’s survival. In addition, we found that PROM1 expression was related to the distant metastasis-free survival in BRCA. Finally, GSEA analysis revealed that PROM1 was negatively related to IGF1 and mTOR pathways involved in BRCA metastasis. Conclusion PROM1 was identified as an important DEGs associated with BRCA bone metastasis. It acted as a vital prognostic biomarker involved in BRCA metastasis, which may be due to the negative regulation of IGF1 and mTOR pathways.

Background To date, no single colorectal cancer (CRC) screening strategy has been determined to be applicable worldwide. In China, a CRC screening protocol that combines double fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) as the first stage of screening and colonoscopy as the second stage of screening (scenario A) was adapted by the Chinese Ministry of Health in 2006. However, applying this CRC screening protocol nationally remains difficult because its effectiveness and convenience are controversial. This study evaluated the effects of subitems of the CRC screening protocol in China. Methods CRC screening results (scenario A) from Jiashan County, China, (2007–2009) were used to analyze the detection rates of CRC and advanced neoplasms as well as the cost-effectiveness of the protocol. Scenario A was divided into scenarios B–G (by selecting some items at the first stage of screening) for analysis. Results Compared with scenario A, removing the whole HRFQ (scenario F) reduced advanced neoplasm and adenoma detections by 29.8 and 41.2%, respectively, whereas the whole HRFQ accounted for 10.1% of the total screening cost. Removing FITs (scenario G) reduced CRC, advanced neoplasm and adenoma detections by 71.8, 56.9 and 47.7%, respectively, and the costs per case of CRC and advanced neoplasm were 82.0 and 19.1% higher, respectively, than those in scenario A. In scenarios B–E (deleting some high-risk factor questions on the HRFQ), the odds ratios (ORs) of the detection rates and costs per CRC, advanced neoplasm, adenoma, and neoplasm case were near 1.00. Scenarios C and D reduced the high-risk population and total screening costs by less than 6.0 and 4.1%, respectively. Scenarios E and B (FITs and a personal history of cancer or colorectal adenoma were reserved) reduced the high-risk population by 17.6 and 24.2% and the total screening costs by 11.2 and 15.4%, respectively, while the numbers of CRC cases were not missed, and advanced neoplasms detected decreased by only 5 and 11%, respectively. Conclusion The results of this study demonstrate that FITs and a personal history of colorectal adenoma are the most effective items in the Chinese CRC screening protocol.

Background AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of the mammary SWI/SNF chromatin remodeling complex and a tumor suppressor protein. The loss of ARID1A been observed in several types of human cancers and associated with poor patient prognosis. Previously, we have reported that ARID1A protein was rapidly ubiquitinated and destructed in gastric cancer cells during DNA damage response. However, the ubiquitin e3 ligase that mediated this process remains unclear. Materials and methods The interaction between ARID1A and β-TRCP was verified by co-immunoprecipitation (Co-IP) assay. The degron site of ARID1A protein was analyzed by bioinformatics assay. Short hairpin RNAs (shRNAs) were used to knockdown (KD) gene expression. Results Here we show that DNA damage promotes ARID1A ubiquitination and subsequent destruction via the ubiquitin E3 ligase complex SCFβ-TRCP. β-TRCP recognizes ARID1A through a canonical degron site (DSGXXS) after its phosphorylation in response to DNA damage. Notably, genetic inactivation of the Ataxia Telangiectasia Mutated (ATM) kinase impaired DNA damage-induced ARID1A destruction. Conclusions Our studies provide a novel molecular mechanism for the negative regulation of ARID1A by β-TRCP and ATM in DNA damaged gastric cancer cells.

Colorectal cancer (CRC) has complex pathological features that defy the linear-additive reasoning prevailing in current biomedicine studies. In pursuing a mechanistic understanding behind such complexity, we constructed a core molecular–cellular interaction network underlying CRC and investigated its nonlinear dynamical properties. The hypothesis and modelling method has been developed previously and tested in various cancer studies. The network dynamics reveal a landscape of several attractive basins corresponding to both normal intestinal phenotype and robust tumour subtypes, identified by their different molecular signatures. Comparison between the modelling results and gene expression profiles from patients collected at the second affiliated hospital of Zhejiang University is presented as validation. The numerical ‘driving’ experiment suggests that CRC pathogenesis may depend on pathways involved in gastrointestinal track development and molecules associated with mesenchymal lineage differentiation, such as Stat5, BMP, retinoic acid signalling pathways, Runx and Hox transcription families. We show that the multi-faceted response to immune stimulation and therapies, as well as different carcinogenesis and metastasis routes, can be straightforwardly understood and analysed under such a framework.

Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13- 1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.

To investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX). Mice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot. In response to PDS-C therapy, the peripheral WBC, NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner. Similarly, bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells (P

This study investigated the cost-effectiveness between double and single Fecal Immunochemical Test(s) (FIT) in a mass CRC screening. A two-stage sequential screening was conducted. FIT was used as a primary screening test and recommended twice by an interval of one week at the first screening stage. We defined the first-time FIT as FIT1 and the second-time FIT as FIT2. If either FIT1 or FIT2 was positive (+), then a colonoscopy was recommended at the second stage. Costs were recorded and analyzed. A total of 24,419 participants completed either FIT1 or FIT2. The detection rate of advanced neoplasm was 19.2% among both FIT1+ and FIT2+, especially high among men with age ≥55 (27.4%). About 15.4% CRC, 18.9% advanced neoplasm, and 29.9% adenoma missed by FIT1 were detected by FIT2 alone. Average cost was $2,935 for double FITs and $2,121 for FIT1 to detect each CRC and $901 for double FITs and $680 for FIT1 to detect each advanced neoplasm. Double FITs are overall more cost-effective, having significantly higher positive and detection rates with an acceptable higher cost, than single FIT. Double FITs should be encouraged for the first screening in a mass CRC screening, especially in economically and medically underserved populations/areas/countries.

A new series of tubulin polymerization inhibitors based on the 2-aryl/heteroaryl-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole scaffold was synthesized and evaluated for growth inhibition activity on a panel of cancer cell lines, cell cycle effects, and in vivo potency. Structure-activity relationships were elucidated with various substitutions at the 2-position of the thiazole skeleton. Hydrophobic moieties, such as phenyl and 3-thienyl, were well tolerated at this position, and variation of the phenyl substituents had remarkable effects on potency. The most active compound (3b) induced apoptosis through the mitochondrial pathway with activation of caspase-3. We also showed that it has potential antivascular activity since it reduced in vitro endothelial cell migration and disrupted capillary-like tube formation at noncytotoxic concentrations. Furthermore, compound 3b significantly reduced the growth of the HT-29 xenograft in a nude mouse model, suggesting that 3b is a promising new antimitotic agent with clinical potential.

The performance of combining fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) in colorectal cancer (CRC) screening in economically and medically underserved populations is uncertain. This study investigated the performance of a CRC screening protocol of combining FITs and an HRFQ as primary screening methods in a rural Chinese population. A CRC mass screening was conducted using FITs and an HRFQ as the first and colonoscopy as the second stage of screening in Jiashan, 2007–2009. The target population was 31,963 residents in three communities. The compliance was 84.7% for HRFQ, 76.4% for FITs, and 78.7% for colonoscopy. The detected rates of cancer, adenoma, nonadenomatous polyps, and advanced neoplasm were 2.7%, 14.8%, 5.9%, and 8.9% by FITs, which were higher than those by HRFQ (0.5%, 9.2%, 4.8%, and 3.8%, respectively). There was no significant difference in detected rate for nonadenomatous polyps between FITs and HRFQ. A total of 41.2% adenomas, 53.2% nonadenomatous polyps, and 29.8% advanced neoplasms were detected by HRFQ but missed by FITs. Positive predictive value of the screening protocol of combining FITs and HRFQ for advanced neoplasm was 5.7%, which was higher than FITs alone. Men had a higher prevalence of advanced neoplasm than women. Results indicate that combining FITs and HRFQ as primary screening methods is an efficient CRC screening strategy in economically and medically underserved populations. Cancer Prev Res; 4(10); 1572–9. ©2011 AACR.

To determine serum adiponectin, C-reactive protein (CRP), TNF-α and IL-6 levels in impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) patients with periodontitis before and after periodontal intervention, and to investigate the relationship between T2DM and periodontitis.A total of 50 IGT and 106 T2DM patients with periodontitis were enrolled. The T2DM patients were divided into two groups: T2DM without macrovascular disease (DM1) group and T2DM with macrovascular disease (DM2) group. Each group was randomly divided into two subgroups according to whether they performed periodontal intervention. The normal control group (NC group) consisted of 30 healthy adults. The serum adiponectin, CRP, TNF-α and IL-6 levels were measured at baseline and 3 months after periodontal intervention.The serum adiponectin levels at baseline had decreased tendency with significant difference between each two groups, while CRP, TNF-α, and IL-6 levels had increased tendency with significant difference between each two groups among NC, IGT, DM1 and DM2 groups (all P0.01). At 3 months after periodontal intervention, the serum adiponectin levels were increased than those without periodontal intervention (all P0.01), while CRP, IL-6 and TNF-α significantly decreased (all P0.05) in both IGT and DM1 groups. In DM2 group, only CRP levels at 3 months after periodontal intervention were significantly decreased (P0.05). Moreover, the HbAlc levels in T2DM patients were improved at 3 months after periodontal invention (P0.01).Periodontal intervention is helpful for glucose control, which may be associated with increased serum adiponectin levels and decreased inflammatory cytokine levels.

Objectives: To use surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) protein chip array technology to detect proteomic patterns in the serum of women with endometriosis; build diagnostic models; and evaluate their clinical significance. Methods: Serum samples from women with endometriosis and healthy women were studied using SELDI-TOF-MS protein chip technology. For every matched pair, two-thirds of the samples were used to look for different patterns and one-third was used for cross-validation. Results: Five potential biomarkers were found and the diagnostic system distinguished endometriosis from validation samples with a sensitivity of 91.7% and a specificity of 90.0%. Conclusion: This method shows great potential in identifying biomarkers to be used for endometriosis screening.

Objective: By using lingual artery chemoembolization on the basis of detailed basic studies to search an additional way for treatment of certain tongue carcinoma. Methods: Study of lingual artery cast specimens in post-mortem human was processed. Patients with tongue carcinoma were chemoembolized with Carboplatinum microcapsules. Results: Microcapsule embolism located approximately at the fifth to the sixth branches level of deep lingual artery. Effective clinical outcomes complied with the anatomy. Conclusion: Lingual artery chemoembolization with microcapsuled Carboplatinum of 214.0 ± 48.0 μm showed nice efficacy in therapy of mid-tongue carcinoma.

Objective: Microcapsule chemoembolism is a promising treatment of tumors. We describe a deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum. Methods: Lingual artery cast specimens from cadavers were microscopically examined, and 78 patients with tongue cancer were recruited and treated with the deep lingual arterial embolization therapy. Results: Microcapsule embolism occurred approximately at the fifth or sixth level of the deep lingual artery branches. The five-year survival rate was 88.5% (69 out of 78), and the ten-year survival rate 52.6% (41 out of 78). Conclusion: The deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum is an effective therapy to treat carcinoma in mid-margin or mid-body of the tongue.

Objective The aim of this study was to develop an alternative treatment approach using lingual artery chemoembolization for certain tongue carcinomas. Study design Fifty-three lingual artery, postmortem, cast human specimens were studied. Seventy-eight patients with tongue carcinoma were chemoembolized with Car-platinum microcapsules. Results The deposition of the microcapsule embolism was approximately at the fifth- to the sixth-branch level of the deep lingual artery. The results complied with the anatomy, and the clinical outcomes were effective. Conclusions Lingual artery chemoembolization showed efficacy for curing carcinoma in the midmargin and midbody areas of the tongue, within the limitations of this study.

The fecal immunochemical test (FIT) that quantifies hemoglobin concentration is reported to be better than qualitative FIT and the reason for its superiority has not been interpreted. To evaluate and understand the superiority of quantitative FIT, a representative randomly selected population (n=2355) in Jiashan County, China, aged 40-74 years was invited for colorectal cancer screening in 2012. Three fecal samples were collected from each participant by one optimized and two common sampling devices, and then tested by both quantitative and qualitative FITs. Colonoscopy was provided independently to all participants. The performances of five featured screening strategies were compared. A total of 1020 participants were eligible. For screening advanced neoplasia, the positive predictive value (PPV) and the specificity of the strategy that tested one sample dissolved in an optimized device by quantitative FIT [PPV=40.8%, 95% confidence interval (CI): 27.1-54.6; specificity=96.8%, 95% CI: 95.7-98.0] were significantly improved over the strategy that tested one sample dissolved in the common device by qualitative FIT (PPV=14.1%, 95% CI: 8.2-19.9; specificity=87.9%, 95% CI: 85.8-89.9), whereas the sensitivity did not differ (39.2 and 37.3%, P=0.89). Similar disparity in performance was observed between the strategies using qualitative FIT to test one sample dissolved in optimized (PPV=29.5%, 95% CI: 18.1-41.0; specificity=95.3%, 95% CI: 94.0-96.7) versus common sampling devices. High sensitivity for advanced neoplasia was observed in the strategy that tested two samples by qualitative FIT (52.9%, 95% CI: 39.2-66.6). Quantitative FIT is better than qualitative FIT for screening advanced colorectal neoplasia. However, the fecal sampling device might contribute most significantly toward the superiority of quantitative FIT.

Objective: To prepare microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2 (TIMP-2), and investigate their biological characteristics in vitro. Methods: Chinese hamster ovary (CHO) cells were stably transfected with a human TIMP-2 expression vector, encapsulated in barium alginate microcapsules and cultured in vitro. Morphological appearance of the microcapsules was observed under a light microscope. Cell viability was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Enzyme linked immunosorbent assay (ELISA) and reverse zymography were used to confirm the release of biologically active TIMP-2 from the microcapsules. Cryopreservation study of the microencapsulated cells was carried out using dimethyl sulfoxide (DMSO) as preservative agent. Results: The microcapsules appeared like a sphere with diameter of 300~600 μm. The surface of the capsule wall was clearly smooth. The microencapsulated cells survived well and kept proliferating over the 6 weeks observed. No significant difference in TIMP-2 secretion was found between encapsulated and unencapsulated cells. Reverse zymography confirmed the bioactivity of MMP (matrix metalloproteinase) inhibition of TIMP-2. The cryopreservation process did not damage the microcapsule morphology nor the viability of the cells inside. Conclusion: Microencapsulated engineered CHO cells survive at least 6 weeks after preparation in vitro, and secrete bioactive TIMP-2 freely from the microcapsules.

Removing relatively large adrenal myelolipomas using retroperitoneal laparoscopy is difficult and carries risk of intraoperative injury to adjacent organs and vessels. We aimed to introduce a new method of retroperitoneal laparoscopic liposuction with suction units for resection of large adrenal myelolipomas.From June 2005 to October 2011, 8 patients (nine lesions, including bilateral lesions in 1 patient) with adrenal myelolipoma more than 8 cm in maximum diameter underwent retroperitoneal laparoscopic liposuction with suction units. Patients included 3 males and 5 females with a mean age of 47 years (range, 35-62 years). Tumor resection was performed after deflation and shrinkage of tumor. The mean maximum diameter was 10.5 cm, ranging from 8 to 14 cm. Five tumors were located on the right side, two were on the left side, and one was bilateral. Adrenal computed tomography was done in each patient preoperatively. Round or oval masses were found in dense fat in the adrenal area, and all cases were diagnosed as adrenal myelolipoma. Five patients had backache or abdominal discomfort; three patients had no symptoms.The mean operation time was 75 minutes, and the mean intraoperative blood loss was 30 mL. The mean postoperative length of stay was 3 days. No significant intraoperative or postoperative complications occurred. The follow-up length ranged from 8 to 77 months. No tumor recurrence was observed.Retroperitoneal laparoscopic liposuction with suction units is safe and effective for resection of relatively large adrenal myelolipomas. Deflation and shrinkage of the tumor make the operation safer and easier without affecting its pathological diagnosis.

Objective: Cancer stromal fibroblasts are important members of the cancer microenvironment. In this study, we determined the effect of sunitinib, a small molecule tyrosine kinase inhibitor, on the primary human colonic fibroblasts. Methods: Cell cycle analysis and cell proliferation assays were performed to evaluate the inhibitory effect of sunitinib in vitro. Western-blot analysis was performed to evaluate variations in the levels of phosphorylated platelet-derived growth factor receptor β (PDGFR-β), Akt, and ERK proteins. Co-injection of SW620 cells and colonic fibroblasts in nude mice was employed to test anti-growth efficacy in vivo. Results: Sunitinib was found to effectively inhibit the growth of primary colonic fibroblasts. Low-dose sunitinib blocked the PDGF-BB-induced cell proliferation and PDGFR-β signaling. Co-injection of SW620 cells and colonic fibroblasts in nude mice generated greater tumor volumes than single injection of SW620 cells. Sunitinib treatment inhibited the SW620 cell+colonic fibroblast tumor growth more effectively than treatment of 5-fluorouracil. Conclusions: Sunitinib mesylate inhibited the proliferation of primary human colonic fibroblasts through target-inhibited PDGFR signaling in vitro and in vivo.

Importance To date, no consistency exists across studies that have evaluated the relationship between hepatic lipase gene ( LIPC ) rs10468017 variant and advanced age-related macular degeneration (AMD). Objective To summarize all relevant evidence for a relationship between LIPC variant and advanced AMD. Data Sources The PubMed and Embase databases were searched for studies potentially eligible in any language published up to September 15, 2013. Study Selection Case-control studies of 2 or more comparison groups that included patients with advanced AMD (choroidal neovascularization or geographic atrophy). Data Extraction and Synthesis Allele frequencies and genotype distributions of rs10468017 variant. Main Outcomes and Measures Summary odds ratios (ORs) and 95% CIs were estimated under different genetic models using meta-analytic methods. A stratified analysis by advanced AMD subtypes and race/ethnicity was performed, as well as a sensitivity analysis. Results Data from 10 case-control studies were included in the meta-analysis. The rs10468017 variant ( C → T ) showed significant summary ORs of 0.81 (95% CI, 0.75-0.88), 0.83 (95% CI, 0.70-0.98), and 0.60 (95% CI, 0.44-0.81) under the allelic ( T vs C ), heterozygous ( TC vs CC ), and homozygous ( TT vs CC ) models, respectively. Carrying at least 1 copy of the T allele decreased the risk of choroidal neovascularization and geographic atrophy by 20% (OR, 0.80; 95% CI, 0.74-0.87) and 29% (OR, 0.71; 95% CI, 0.59-0.86), respectively. The pooled OR for white race/ethnicity under an allelic model was 0.80 (95% CI, 0.74-0.87). The sensitivity analysis indicated the robustness of our findings, and no evidence of publication bias was observed in our meta-analysis. Conclusions and Relevance Our meta-analysis indicates that LIPC rs10468017 variant is associated with a reduced risk of advanced AMD. This finding may lead to insights regarding the pathogenesis, prevention, and treatment of AMD.

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein chip array technology was used to detect the serum proteomic patterns in patients with endometriosis. Four potential biomarkers (8,141 m/z, 6,096 m/z, 5,894 m/z, and 3,269 m/z) were found. This method showed great potential in screening better biomarkers for endometriosis.

Objective: To investigate the gene regulation of taxolinduced apoptosis. Methods: Northern blot hybridization, enzyme activity assay of S-AdoMet synthetase and flow cytometry were performed in the investigation of expression in the mRNA level and biological action of SAdoMet synthetase in taxoMnduced apoptosis in human breast cancer cell line (BCap 37). Results: Up-regulation of S-AdoMet synthetase expression was resulted by taxol treatment and the expression peaked at 48 hours.Moreover,the up-regulation of S-AdoMet synthetase was associated with cytotoxicity of antimicrotubule agents including taxol and colchicine. Inhibition rate of S-AdoMet synthetase activity by 1% DMSO was 34% in taxol-treated cells and 14% in taxoiuntreated cells compared to control groups, respectively. Posttreatment with 1% DMSO following pretreatment with individual antitumor agent for 3 hrs promoted apoptotic cell death of taxol-,colchicine-,and adriamycintreated Bcap37 cells. Conclusion: The induction of apoptosis enhanced by post-treatment with DMSO in taxol-treated cells is probably linked to its inhibition on enzyme activity of S-AdoMet synthetase ,suggesting that the increased expression of S-AdoMet synthetase possibly plays an important role in protecting cells from DNA fragmentation in taxoMnduced apoptosis.

To compare the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method in colorectal cancer screening.A representative random population of 9000 subjects aging between 40 and 74 years old were selected from Xuxiang, Haining city, Zhejiang province, by random cluster sampling method in year 2011. The fecal samples from each subject were separately detected by the two methods, namely fecal occult blood quantitive testing instrument and colloidal gold strip method. The positive result was standardized by hemoglobin concentration (HGB) ≥ 100 ng/ml under the application of quantitive testing instrument, or color-developing by colloidal gold strip method. The positive subjects from either method would be provided a further colonoscopy examination for pathological diagnosis. The positive rate and consistency of the two methods were compared, as well as the positive predictive value and population detecting rate of the colorectal cancer and adenoma.A total of 6475 (71.9%) subjects submitted their two fecal samples according to our requirement in 9000 subjects. There were separately 319 positive cases (4.9%) and 146 positive cases (2.3%) by the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method, including 45 positive in both tests (Kappa = 0.168, 95%CI:0.119-0.217).184 out of the 319 positive cases (57.7%) in the test by quantitive testing instrument and 89 out of 146 positive cases (61.0%) in the test by colloidal gold strip method received the colonoscopy examination. There were no significant statistical differences between the two methods in the positive predictive value of colorectal cancer (P0.05) , developing adenoma and non-developing adenoma.However, the population detecting rate of the colorectal cancer and developing adenoma were higher in the test by quantitive testing instrument (26 cases, 0.402%) than it in the test by colloidal gold strip method (10 cases, 0.154%). The difference showed statistical significance (χ(2) = 7.131, P0.01).The performances of fecal occult blood quantitive testing instrument might be better than colloidal gold strip method in colorectal cancer screening. However, the results need to be further verified.

The aim of this study was to evaluate the performance of qualitative and quantitative fecal immunochemical tests (FITs) in population screening for colorectal neoplasm. A total of 9000 participants aged between 40 and 74 years were enrolled in this study. Each participant received two stool sampling tubes and was asked to simultaneously submit two stool samples from the same bowel movement. The stool samples of each participant were tested using an immunogold labeling FIT dipstick (qualitative FIT) and an automated fecal blood analyzer (quantitative FIT). Colonoscopy was performed for those who test positive in either FIT. The positive predictive values and population detection rates of the FITs for predicting colorectal neoplasm were compared. A total of 6494 (72.16%) participants simultaneously submitted two stool samples. The diagnostic consistency for a positive result between quantitative and qualitative FITs was poor (κ=0.278, 95% confidence interval=0.223-0.333). The positive predictive values of the quantitative FIT were significantly higher than those of the qualitative FIT for predicting large (≥1 cm) adenomas (23 cases, 14.29% and 16 cases, 6.72%, P=0.013) and colorectal cancer (10 cases, 6.21% and 5 cases, 2.10%, P=0.034); however, the population detection rate for advanced neoplasm of the quantitative FIT was not significantly different from that of the qualitative FIT. Quantitative FIT is superior to qualitative FIT in predicting advanced colorectal neoplasm during colorectal cancer screening. Further studies are needed to elucidate the causes of the predictive superiority.

The biological importance of microtubules make them an interesting target for the synthesis of antitumor agents. The 2-(3',4',5'-trimethoxybenzoyl)-5-aminobenzo[b]thiophene moiety was identified as a novel scaffold for the preparation of potent inhibitors of microtubule polymerization acting through the colchicine site of tubulin. The position of the methoxy group on the benzo[b]thiophene was important for maximal antiproliferative activity. Structure-activity relationship analysis established that the best activities were obtained with amino and methoxy groups placed at the C-5 and C-7 positions, respectively. Compounds 3c-e showed more potent inhibition of tubulin polymerization than combretastatin A-4 and strong binding to the colchicine site. These compounds also demonstrated substantial antiproliferative activity, with IC50 values ranging from 2.6 to 18 nM in a variety of cancer cell lines. Importantly, compound 3c (50 mg/kg), significantly inhibited the growth of the human osteosarcoma MNNG/HOS xenograft in nude mice.

In search of new compounds with strong antiproliferative activity and simple molecular structure, we designed a novel series of agents based on the 2-amino-3-alkoxycarbonyl/cyano-5-arylethylthiophene scaffold. The presence of the ethyl spacer between the 2′,5′-dimethoxyphenyl and the 5-position of the thiophene ring, as well as the number and location of methoxy substitutents on the phenyl ring, played a profound role in affecting the antiproliferative activity. Among the synthesized compounds, we identified the 2-amino-3-cyano-[2-(2,5-dimethoxyphenyl)ethyl] thiophene 2c as the most promising derivative against a wide panel of cancer cell lines (IC50 = 17–130 nM). The antiproliferative activity of this compound appears to correlate well with its ability to inhibit tubulin assembly and the binding of colchicine to tubulin. Moreover 2c, as determined by flow cytometry, strongly induced arrest in the G2/M phase of the cell cycle, and annexin-V and propidium iodide staining indicate that cell death proceeds through an apoptotic mechanism that follows the intrinsic mitochondrial pathway.

Supplemental Digital Content is available in the text, The gradient monotonicity of existing tumor, node, metastases staging systems for colorectal cancer is unsatisfactory. Our proposed T-plus staging system strengthens weighting of the T stage. In this study, applicability of the T-plus staging system was verified with data of a Chinese colorectal cancer center. Records of 2080 nonmetastatic, advanced cancer patients undergoing colorectal cancer surgery from 1985 to 2011 were reviewed for T, N stage pathology and follow-up information. Using overall and disease-specific survival data, the 7th edition tumor, node, metastases staging system and the T-plus staging system were compared for stage homogeneity and discrimination and gradient monotonicity. For gradient monotonicity, the T-plus staging system was superior for both colon and rectal cancer. With Kaplan–Meier survival curves, the T-plus staging system discriminated among different stages, and the corresponding survival was inversely associated with the stage. However, for the 7th edition tumor, node, metastases staging system, stage IIIa had a better prognosis than stage II for rectal cancer and stage I for colon cancer. For homogeneity within the same stage and discrimination between different stages, the 2 staging systems were similar for colorectal cancer, but the T-plus system was clearly better for colon cancer. The T-plus staging system provides good gradient monotonicity. For future colorectal cancer staging systems, we propose replacement of lymph node status as the criterion to discriminate colorectal cancer stage II and stage III with greater weighting of the T stage.

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The optimal disease staging system and treatment approaches have not yet been defined. This study aimed to evaluate the prediction of different staging systems for prognosis and treatment options of SCCE. We retrospectively accessed the clinicopathologic characteristics, treatment strategy, and prognosis of 76 patients diagnosed with primary SCCE between 2001 and 2011. The 1-, 2-, 3-, and 5-year overall survival rates were 58%, 31%, 19%, and 13%, respectively. Univariate analysis showed that the 2002 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification (P = 0.002), Veterans Administration Lung Study Group (VALSG) stage (P = 0.001), predisposing factors (P < 0.001), T category (P = 0.023), and M category (P < 0.001) were prognostic factors for overall survival. Multivariate analysis showed that the 2002 AJCC TNM stage (P < 0.001) was the only independent prognostic factor for survival. The value of the area under the receiver operator characteristic (ROC) curve (AUC) of the 2002 AJCC TNM staging system was larger than that of VALSG staging system with regard to predicting overall survival (0.774 vs. 0.620). None of the single treatment regimens showed any benefit for survival by Cox regression analysis. Thus, the 2002 AJCC TMN staging system improved the prediction of SCCE prognosis; however, the optimal treatment regimen for SCCE remains unclear.

Recently, the number of patients with prostate cancer who needed to be treated with radical prostatectomy increased rapidly in China. There is still a difference between clinical staging and the post-operative final pathologic staging; hence, an excellent tool for accurately predicting the pathologic stages of prostate cancer is needed urgently in clinical practice. The Partin tables are the most popular and widely used tool for predicting the pathologic stages of prostate cancer because of its high accuracy and ease of implementation. The aim of this study was to externally validate the accuracy of the three versions of the Partin tables in predicting the post-operative pathologic stages in Chinese patients with prostate cancer.We retrospectively analyzed the data from 203 patients with prostate cancer who underwent radical prostatectomies between June 2000 and May 2012. The accuracies of the three versions of the Partin tables in predicting the post-operative pathologic stages in Chinese patients with prostate cancer were evaluated using the area under the receiver operating characteristic curve (AUC).Using the 1997, 2001, and 2007 Partin tables for predicting the current cases, the AUC of organ confinement (OC) was 0.877, 0.788, and 0.726; the AUC of extracapsular extension (ECE) was 0.525, 0.615, and 0.608; the AUC of seminal vesicle invasion (SVI) was 0.875, 0.649, and 0.820; and the AUC of pelvic lymph node invasion (LNI) was 0.808, 0.758, and 0.735 respectively.The accuracies of the three versions of Partin tables in predicting OC, SVI, and LNI were good, especially the 2001 Partin table for SVI. In contrast, the accuracy of the three versions of the Partin tables in predicting ECE was fair. The 1997 Partin table was much better than the 2007 table in predicting OC, and the 2001 table in predicting SVI. The 2007 Partin table did not show any advantages.

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The optimal disease staging system and treatment approaches have not yet been defined. This study aimed to evaluate the prediction of different staging systems for prognosis and treatment options of SCCE. We retrospectively accessed the clinicopathologic characteristics, treatment strategy, and prognosis of 76 patients diagnosed with primary SCCE between 2001 and 2011. The 1-, 2-, 3-, and 5-year overall survival rates were 58%, 31%, 19%, and 13%, respectively. Univariate analysis showed that the 2002 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification (P = 0.002), Veterans Administration Lung Study Group (VALSG) stage (P = 0.001), predisposing factors (P < 0.001), T category (P = 0.023), and M category (P < 0.001) were prognostic factors for overall survival. Multivariate analysis showed that the 2002 AJCC TNM stage (P < 0.001) was the only independent prognostic factor for survival. The value of the area under the receiver operator characteristic (ROC) curve (AUC) of the 2002 AJCC TNM staging system was larger than that of VALSG staging system with regard to predicting overall survival (0.774 vs. 0.620). None of the single treatment regimens showed any benefit for survival by Cox regression analysis. Thus, the 2002 AJCC TMN staging system improved the prediction of SCCE prognosis; however, the optimal treatment regimen for SCCE remains unclear.

The cooperation and communication between different cell signaling transduction pathways are considered critical in the development of various types of cancer as well as drug resistance. There is evidence of crosstalk between the G protein-coupled receptor 30 (GPR30), the newly discovered estrogen receptor (ER), and the ErbB family. Heregulin (HRG)-β1, the ligand for ErbB3 and ErbB4, upregulates GPR30 expression in MCF-7, T-47D and BT-474 breast cancer cell lines that express ERα. In the present study, recombinant human HRG-β1 was used to investigate the upregulation of GPR30 expression by HRGs in MCF-7 breast cancer cells which were ERα-positive. In MCF-7 cells, the ErbB2 inhibitor, AG825, the MAPK inhibitor, PD98059, and the MEK1/2 inhibitor, U0126, blocked the HRG-β1-induced GPR30 expression. 17-β-estradiol (E2) boosted the HRG-β1-induced proliferation, migration and invasion of MCF-7 cells. Similar to E2, the specific GPR30 agonist, G-1, promoted HRG-β1-induced migration and invasion, but inhibited growth. Using the specific GPR30 antagonist, G-15, or the small interfering RNA for GPR30, the functions of GPR30 after treatment with HRG-β1 were further investegated. The results from our study indicate that the interruption between GPR30 signaling and the ErbB family system may serve as a promising therapeutic strategy for breast cancer.

Estrogen receptor (ER)-negative breast cancer cells are probably more aggressive with larger metastatic potential than ER-positive cells. Loss of ER in recurrent breast cancer is associated with poor response to endocrine therapy. G protein-coupled receptor 30 (GPR30) is expressed in half of ER-negative breast cancers. Tumor cell-derived heregulin-β1 (HRG-β1) is also found mainly in ER-negative cancer. In SkBr3 breast cancer cells that lack ER but express GPR30, HRG-β1 upregulates mRNA and protein levels of GPR30 by promoting ErbB2–ErbB3 heterodimerization and activating the downstream MAPK–ERK signaling pathway. Moreover, GPR30 boosts HRG-β1-induced migration and invasion of SkBr3 cells after combinative treatment with E2, 4-hydroxy-tamoxifen or the specific GPR30 agonist G-1, which are blocked by the specific GPR30 antagonist G-15 or the transfection with the small interfering RNA for GPR30. The ErbB2 inhibitor AG825 and the MEK1/2 inhibitor U0126 also partly inhibit the enhanced migration and invasion. Therefore, HRG-β1-induced migration and invasion partly depend on the upregulation of GPR30 expression through activation of the ErbB2–ERK pathway in SkBr3 cells. The results of this study indicate that the crosstalk between GPR30 and HRGs signaling is important for endocrine therapy resistance and may provide a new therapeutic way to treat breast cancer.

Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. Two series of 1,5-diaryl substituted 1,2,3,4-tetrazoles were concisely synthesized, using a palladium-catalyzed cross-coupling reaction, and identified as potent antiproliferative agents and novel tubulin polymerization inhibitors that act at the colchicine site. SAR analysis indicated that compounds with a 4-ethoxyphenyl group at the N-1 or C-5 position of the 1,2,3,4-tetrazole ring exhibited maximal activity. Several of these compounds also had potent activity in inhibiting the growth of multidrug resistant cells overexpressing P-glycoprotein. Active compounds induced apoptosis through the mitochondrial pathway with activation of caspase-9 and caspase-3. Furthermore, compound 4l significantly reduced in vivo the growth of the HT-29 xenograft in a nude mouse model, suggesting that 4l is a promising new antimitotic agent with clinical potential.

To evaluate a colorectal cancer screening program by tumor detection rate and discussing its application values.In total, 43 713 subjects were recruited in the screening program who were the registered people aged 40 - 74 in Xiacheng and Jiashan during year 2007 - 2009. The first screening involved questionnaire survey of colorectal cancer related risk factors and fecal occult blood test (FOBT), colonoscopy was performed when a positive result was observed in the first screening. If polyps were found during colonoscopy, biopsy and pathological diagnosis were carried out. The screening data were analyzed and the tumor detection rate was calculated according to age or sex.6489 subjects (14.85%) belonged to the high risk group of colorectal cancer in the first screening, in which 4701 subjects finished complete colonoscopy. Finally, 569 colorectal neoplasm were diagnosed, the detection rate was 12.10% (95%CI: 11.17% - 13.04%). It included 52 colorectal cancer (1.11%, 95%CI: 0.81% - 1.41%), 183 advanced adenoma (3.89%, 95%CI: 3.34% - 4.45%), 334 non-advanced adenoma (7.10%, 95%CI: 6.37% - 7.84%). The highest detective rate was observed in male group that aged 70 - 74 (22.81%, 95%CI: 16.98% - 28.70%), the lowest detective rate was observed in female group aged 40 - 44 (2.49%, 95%CI: 0.79% - 4.20%).The current colorectal cancer screening program in China works well, but the revision of the program is necessary.

Objective To evaluate the effects of periodontal intervention on inflammatory cytokines, adiponectin, insulin resistance (IR), and metabolic control and to investigate the relationship between type 2 diabetes mellitus (T2DM) and moderately poor glycemic control and chronic periodontitis. Methods and Patients A total of 190 moderately poorly controlled (HbA1c between 7.5% and 9.5%) T2DM patients with periodontitis were randomly divided into two groups according to whether they underwent periodontal intervention: T2DM-NT and T2DM-T group. The levels of serum adiponectin, C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), lipid profile, glucose, insulin, homeostasis model of assessment - insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were measured at baseline and after 3 months. Results The levels of clinical periodontal variables, the probing depth, attachment loss, bleeding index, and plaque index were improved significantly in T2DM-T group after 3 months compared to T2DM-NT group (all p

Incidence and mortality of colorectal cancer has increased significantly in recent years. Screening for colorectal cancer is the most effective method to decrease mortality. Colorectal adenoma is the precancerous lesion of colorectal cancer and can be detected through colonoscopy, which is the crucial in the early diagnosis and early treatment for colorectal cancer. The first step of screening is the selection of target population and the second step is colorectal examination. The selection of candidate for screening has direct effect on the efficacy of screening. The methods in common use include fecal occult blood test, questionnaire for high risk factors of colorectal cancer, colonoscopy, sigmoidoscopy, and CT virtual colonoscopy. Among those, colonoscopy is the most reliable method and widely used in the screening for colorectal cancer.

Gastric duplication cyst (GDC) lined by pseudostratified columnar ciliated epithelium (PCCE) is an uncommon lesion stemming from a foregut developmental malformation. Its clinical and radiological presentation is usually nonspecific. In this study, we reported a 76-year-old man who presented with an incidentally found perigastric mass. An exploratory laparotomy revealed a non-communicating cyst below the gastroesophageal junction, measuring 4 cm×4 cm in size. Microscopically, the gastric cyst was lined merely by PCCE. Although rare, GDC lined by PCCE should be included in the differential diagnosis of gastric wall masses. Surgical intervention is warranted in patients who have clinical symptoms, or who are aged more than 50 years.

A wide variety of small molecules with diverse molecular scaffolds inhibit microtubule formation. In this article we report a one-pot procedure for the preparation of a novel 2-(N-pyrrolidinyl)-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole in which the size of the substituent at the C-2 position of the thiazole ring plays an essential role in compound activity. The most active agent (3f) inhibited at submicromolar concentrations the growth of tumor cell lines. It also inhibited tubulin polymerization with an activity quantitatively similar to that of CA-4, and treatment of HeLa cells resulted in their arrest at the G2-M phase of the cell cycle. Furthermore, 3f was effective against multidrug resistant cancer cells and inhibited the growth of the HT-29 xenograft in a nude mouse model. This indicated that 3f is a promising new antimitotic agent with encouraging preclinical potential. ispartof: European Journal of Medicinal Chemistry vol:46 issue:12 pages:6015-6024 ispartof: location:France status: published

To screen out specifically-expressed serum protein markers in familial adenomatous polyposis (FAP) and to establish a serum protein fingerprint diagnostic model for distinguishing FAP from sporadic colorectal adenomas.Serum samples were collected from 19 FAP cases and 16 sporadic colorectal adenomas with informed consent. Serum protein fingerprint profiles were detected by SELDI-TOF-MS with CM 10 protein chip to screen out FAP adenoma-related serum protein markers, and support vector machine (SVG) technique was used to establish the diagnostic model to distinguish FAP from sporadic colorectal adenomas.Six differently-expressed protein peaks (P0.01) were detected. Among them proteins of 5640, 3160, 4180 and 4290 m/z were highly expressed in FAP adenomas, and proteins of 3940 and 3400 m/z were highly expressed in sporadic colorectal adenomas. The accuracy of diagnostic model established with SVG to distinguish FAP adenomas and sporadic colorectal adenomas was 94.7% and 93.7%, respectively.SELDI-TOF-MS can be effectively used to screen out the differentially expressed serum protein markers in FAP adenomas and sporadic colorectal adenomas, and a diagnostic model build by SVG to distinguish them has been successfully established. Therefore, a useful breakthrough point for research on molecular mechanisms of FAP pathogenesis is provided.