AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treat...AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.展开更多
AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis. METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we...AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis. METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we analyzed the expression of 47 296 transcripts in two batches of gastric cancer patients who underwent surgical resection. Thirty-nine samples in the first batch were used as the training set to discover candidate markers correlated to overall survival, and thirty-three samples in the second batch were used for validation. RESULTS: A panel of ten genes were identified as prognostic marker in the first batch samples and classified patients into a lowand a high-risk group with significantly different survival times (P = 0.000047). This prognostic marker was then verified in an independent validation sample batch (P = 0.0009). By comparing with the traditional Tumor-node-metastasis (TNM) staging system, this ten-gene prognostic marker showed consistent prognosis results. It was the only independent prognostic value by multivariate Cox regression analysis (P = 0.007). Interestingly, six of these ten genes are ribosomal proteins, suggesting a possible association between the deregulation of ribosome related gene expression and the poor prognosis. CONCLUSION: A ten-gene marker correlated with overall prognosis, including 6 ribosomal proteins, was identified and verified, which may complement the predictive value of TNM staging system.展开更多
OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38） and uPA and the correlation of their expression with breast cancer clinicopathological characteristics, and to investi...OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38） and uPA and the correlation of their expression with breast cancer clinicopathological characteristics, and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells.METHODS Immunohistochemistry （S-P） was used to test the expression of p-p38 and uPA in 60 specimens of breast cancer tissues. Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells, and uPA expression after treatment with SB203580, a specific inhibitor of p38 MAPK.RESULTS The positive rate of the p-p38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%,respectively. The expression of p-p38 was positively related to the expression of uPA （r = 0.316, P 〈 0.05）. The expression of p-p38 and uPA was related to lymph node metastasis and the TNM stage （P 〈 0.05）, but it was not related to the patient＇s age or tumor size （P 〉 0.05）. The expression of p-p38 and uPA in MDA- MB-231 cells was higher than that in MCF-7 cells. SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression.CONCLUSION The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up-regulating uPA expression ,and it may be an important process in breast cancer invasion and metastasis.展开更多
OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spheri...OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spherical self-organizing map （sSOM） analysis to characterize cells and tissues by the cell surface markers. In the microarray 1,797 probes for human genes coding membrane bound proteins were spotted. With this microarray the gene expression profiles of eight breast carcinoma cell lines were compared to identify the genes that were commonly expressed in breast carcinomas but not in normal cells. RESULTS The gene expression profiles of sSOM from the eight breast carcinoma cell lines were successfully distinguished from that of normal breast tissue derived cells suggesting the presence of genes of interest, sSOMon the data extensively filtered revealed several candidate genes, of which expression was significant in carcinoma cells but low in normal cells. Finally, TM9SF2 was nominated through validations of PCR procedures together with CD24 and ErbB3, which are known breast carcinoma markers. TMgSF2 expression was further confirmed by immunological staining. Interestingly, TMgSF2 was found to be expressed in all the cell lines evaluated while CD24 and ErbB3 were not in all of the carcinoma cells, supporting their relationship in sSOM. Although physiological significance of TMgSF2 is unknown yet, siRNA treatment significantly inhibited the growth of MDA- MB-231 cells. CONCLUSION We propose TM9SF2 as a novel and useful diagnostic marker as well as a potential molecular target specific to breast carcinoma cells covering wide range of breast cancer.展开更多
AIM:To characterize the differentially expressed gene profiles in livers from biliary atresia (BA) patients including,ascertain genes,functional categories and pathways that play a central role in the pathogenesis of ...AIM:To characterize the differentially expressed gene profiles in livers from biliary atresia (BA) patients including,ascertain genes,functional categories and pathways that play a central role in the pathogenesis of BA,and identify the novel prognostic markers for BA.METHODS:Liver tissue samples from control patients,neonatal cholestasis patients,and BA patients at the age of < 60 d,60-90 d,and > 90 d were pooled for DNA microarray analysis.Bioinformatics analysis was performed using,series test cluster of gene ontology,and Pathway-Finder software.Reverse-transcription polymerase chain reaction was performed to confirm changes in selected genes.Relation between RRAS gene expression and prognosis of 40 BA patients was analyzed in a 2-year follow-up study.RESULTS:The 4 identified significant gene expression profiles could confidently separate BA liver tissue from normal and other diseased liver tissues.The included genes were mainly involved in inflammation response and reconstruction of cellular matrix.The significant pathways associated with BA were primarily involved in autoimmune response,activation of T lymphocytes and its related cytokines.The RRAS,POMC,SLC26A6 and STX3 genes were important regulatory modules in pathogenesis of BA.The expression of RRAS was negatively correlated with the elimination rate of jaundice and positively correlated with the occurrence rate of cholangitis.CONCLUSION:Autoimmune response mediated by T lymphocytes may play a vital role in the pathogenesis of BA.The RRAS gene is an important regulatory module in the pathogenesis of BA,which may serve as a novel prognostic marker for BA.展开更多
AIM:To develop lymph node metastasis(LNM)-associated biomarkers for colorectal cancer(CRC) using quantitative proteome analysis.METHODS:Differences in protein expression between primary CRC with LNM(LNM CRC) and witho...AIM:To develop lymph node metastasis(LNM)-associated biomarkers for colorectal cancer(CRC) using quantitative proteome analysis.METHODS:Differences in protein expression between primary CRC with LNM(LNM CRC) and without LNM(non-LNM CRC) were assessed using methyl esterification stable isotope labeling coupled with 2D liquid chromatography followed by tandem mass spectrometry(2D-LC-MS/MS).The relationship to clinicopathological parameters and prognosis of candidate biomarkers was examined using an independent sample set.RESULTS:Forty-three proteins were found to be differentially expressed by at least 2.5-fold in two types of CRC.S100A4 was significantly upregulated in LNM CRC compared with non-LNM CRC,which was confirmed by Western blotting,immunohistochemistry and real-time quantitative polymerase chain reaction.Further immunohistochemistry on another 112 CRC cases showed that overexpression of S100A4 frequently existed in LNM CRC compared with non-LNM CRC(P < 0.001).Overexpression of S100A4 was significantly associated with LNM(P < 0.001),advanced TNM stage(P < 0.001),increased 5-year recurrence rate(P < 0.001) and decreased 5-year overall survival rate(P < 0.001).Univariate and multivariate analyses indicated that S100A4 expression was an independent prognostic factor for recurrence and survival of CRC patients(P < 0.05).CONCLUSION:S100A4 might serve as a powerful biomarker for LNM and a prognostic factor in CRC.展开更多
AIM:To verify that CD markers are available for detecting cancer stem cell populations and to evaluate their clinical significance in colon cancer.METHODS:Immunohistochemistry for CD133,CD24 and CD44 was performed on ...AIM:To verify that CD markers are available for detecting cancer stem cell populations and to evaluate their clinical significance in colon cancer.METHODS:Immunohistochemistry for CD133,CD24 and CD44 was performed on the tissue microarray of 523 colorectal adenocarcinomas.Medical records were reviewed and clinicopathological analysis was performed.RESULTS:In colorectal adenocarcinoma,128 of 523 cases(24.5%) were positive and 395 cases(75.5%) were negative for CD133 expression.Two hundred and sixty-four of 523 cases(50.5%) were positive and 259 cases(49.5%) were negative for CD24 expression.Five hundred and two of 523 cases(96%) were negative and 21 cases(4%) were positive for CD44 expression.Upon clinicopathological analysis,CD133 expression was present more in male patients(P = 0.002) and in advanced T stage cancer(P = 0.024).Correlation between CD24 expression and clinicopathological factors was seen in the degree of differentiation(P = 0.006).Correlation between CD44 expression and clinicopathological factors was seen in the tumor size(P = 0.001).Survival was not significantly related to CD133,CD24 and CD44 expression.CONCLUSION:CD markers were related to invasiveness and differentiation of colorectal adenocarcinoma.However,CD expression was not closely related to survival.展开更多
Long non-coding RNAs （lncRNAs） refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as...Long non-coding RNAs （lncRNAs） refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer ceils, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 （PRC2）. In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.展开更多
Small heat shock proteins encompass a widespread but diverse class of proteins, which play key roles in protecting organisms from various stressors. In the present study, the full-length cDNAs of two small heat shock ...Small heat shock proteins encompass a widespread but diverse class of proteins, which play key roles in protecting organisms from various stressors. In the present study, the full-length cDNAs of two small heat shock proteins （MgsHSP22 and MgsHSP24.1） were cloned from Mytilus galloprovincialis, which encoded peptides of 181 and 247 amino acids, respectively. Both MgsHSP22 and MgsHSP24.1 were detected in all tissues examined by real-time PCR, with the highest expression being observed in muscle and gonad tissues. The real-time PCR results revealed that Cd significantly inhibited MgsHSP22 expression at 24 h and MgsHSP24.1 at 24 and 48 h under 5 ug/L Cd2＋ exposure. MgsHSP24.1 expression was also significantly inhibited after 50 ug/L Cd2＋ exposure for 48 h. With regard to antioxidant enzymes, increased GPx and CAT activity were detected under Cd2＋ stress （5 and 50 ug/L）, while no significant difference in SOD activity was observed throughout the experiment. Overall, both MgsHsps and antioxidant enzymes revealed their potential as Cd stress biomarkers in M. galloprovincialis.展开更多
Interferon （IFN） is a cytokine with various biological functions, including antivirus, immunoregulation and anti- tumor. It has been wildly used in many anti-cancer therapies, including malignant melanoma, hepatocel...Interferon （IFN） is a cytokine with various biological functions, including antivirus, immunoregulation and anti- tumor. It has been wildly used in many anti-cancer therapies, including malignant melanoma, hepatocellular carcinoma, ad- vanced renal-cell carcinoma, non-Hodgkin＇s lymphoma, chronic myelogenous leukemia and AIDS-related Kaposi＇s sarcoma. However, its effective dose is always very high, which may bring some serious side effects, nevertheless, not all patients can benefit from the IFN therapy. So a problem we have faced is that how to improve the efficiency and sensitivity of IFN？ To solve this problem, many studies have been launched to find the effective prognostic factors and individual biomarkers for guiding the treatment better. In addition, further clarifying the anti-tumor mechanisms of IFN is benefit for explaining how the biomark- ers predict prognosis of patients. In recent studies, many IFN associated genes and proteins predicting sensitivity of IFN therapy have been found, which may associate with the progression of cancer, such as IFN regulatory factor （IRF）, IFNAR2 mRNA, microRNA, IFITM-I. Some factors in peripheral blood are easier to detect and have the potential to been popularized in clinical practice, such as CD8^high CD57^＋ lymphocyte levels in malignant melanoma, serum IFNAR2 mRNA in mCRC. This review briefly summarized the advances of antitumorally individual markers of IFN.展开更多
Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organ...Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include:fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed en- hancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.展开更多
Peptides in shrimp hemolymph play an important role in the innate immune response.Analysis of hemolymph will help to detect and identify potential novel biomarkers of microbial infection.We used magnetic bead-based pu...Peptides in shrimp hemolymph play an important role in the innate immune response.Analysis of hemolymph will help to detect and identify potential novel biomarkers of microbial infection.We used magnetic bead-based purification(ClinProt system) and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS) to characterize shrimp hemolymph peptides.Shrimp serum and plasma were used as the source of samples for comparative analysis,and it was found that serum was more suitable for shrimp hemolymph peptidomic analysis.To screen potential specific biomarkers in serum of immune-challenged shrimps,we applied magnetic bead-based MALDI-TOF MS to serum samples from 10 immune-challenged and 10 healthy shrimps.The spectra were analyzed using FlexAnalysis 3.0 and ClinProTools 2.1 software.Thirteen peptide peaks significantly different between the two groups were selected as candidate biomarkers of lipopolysaccharide(LPS)-infection.The diagnostic model established by genetic algorithm using five of these peaks was able to discriminate LPS-challenged shrimps from healthy control shrimps with a sensitivity of 90% and a specificity of 100%.Our approach in MALDITOF MS-based peptidomics is a powerful tool for screening bioactive peptides or biomarkers derived from hemolymph,and will help to enable a better understanding of the innate immune response of shrimps.展开更多
Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGF...Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGlaR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 （43%） advanced lung adenocarcinoma patients. Gender （P=0.003）, smoking status （P=0.001）, and abnormal serum status of carcinoembryonic antigen （CEA, P=0.028） were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation （P=0.046） with an odds ratio of 2.613 （95% Ch 1.018-6.710）. However, receiver operating characteristic （ROC） curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma （the area under the ROC curve was 0.608, P=0.069）. Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.展开更多
Microarray has become increasingly popular biotechnology in biological and medical researches, and has been widely applied in classification of treatment subtypes using expression patterns of biomarkers. We developed ...Microarray has become increasingly popular biotechnology in biological and medical researches, and has been widely applied in classification of treatment subtypes using expression patterns of biomarkers. We developed a statistical procedure to identify expression biomarkers for treatment subtype classification by constructing an F-statistic based on Henderson method Ⅲ. Monte Carlo simulations were conducted to examine the robustness and efficiency of the proposed method. Simulation results showed that our method could provide satisfying power of identifying differentially expressed genes （DEGs） with false discovery rate （FDR） lower than the given type I error rate. In addition, we analyzed a leukemia dataset collected from 38 leukemia patients with 27 samples diagnosed as acute lymphoblastic leukemia （ALL） and 11 samples as acute myeloid leukemia （AML）. We compared our results with those from the methods of significance analysis of microarray （SAM） and microarray analysis of variance （MAANOVA）. Among these three methods, only expression biomarkers identified by our method can precisely identify the three human acute leukemia subtypes.展开更多
MDM2 (the product of murine double minute 2 gene) is one of the most important negative regulators of p53,which can binds to p53 and initiates ubiquitin-mediated degradation.Besides,MDM2 also controls the activity of ...MDM2 (the product of murine double minute 2 gene) is one of the most important negative regulators of p53,which can binds to p53 and initiates ubiquitin-mediated degradation.Besides,MDM2 also controls the activity of several cell-cycle regulators,e.g.pRB,p21,E2F1,independently of p53.The important role of MDM2 in cell-cycle regulation indicates it to be a point of interest in cancer research.In recent years,studies revealed that MDM2 participated in the genesis and development of human tumors.The expression levels and activity of MDM2 was associated with the invasion,metastasis,prognosis and more practical,chemosensitivity.MDM2 is becoming a novel biomarker in cancer prognosis and chemosensitivity prediction.展开更多
Right ventricular failure(RVF)is a complicated syndrome with multiple etiologies.RVF relates to pulmonary hypertension,left ventricle failure,and congenital heart diseases.The origin of its pathway is based on patholo...Right ventricular failure(RVF)is a complicated syndrome with multiple etiologies.RVF relates to pulmonary hypertension,left ventricle failure,and congenital heart diseases.The origin of its pathway is based on pathological gene expression and concomitant diseases.Diagnosis of RVF is a serious problem for clinicians,but none of the criteria in current clinical practice provides uncontaminated information on either systolic or diastolic function.Perioperative assessment and bedside monitoring of right ventricle function have to be revised and widely used.Right ventricle function in transplant patients demands different evaluation using biomarkers or/and autopsy.Treatment of RVF has surgical and non-surgical approaches;both are still in development and need further clarification.展开更多
基金by Grant-in-Aid for Scientif ic Research (Category B, No. 18390168) for K Tsukamoto by the Ministry of Education, Culture, Sports, Science and Technology of Japan
文摘AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.
基金Supported by the National 863 Program (SQ2009AA02-XK1482570 and 2006AA02A402)Beijing Municipal Committeeof Science and Technology (D0905001040631) Beijing Capi-tal Development Foundation of Health Bureau (2007-2051)
文摘AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis. METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we analyzed the expression of 47 296 transcripts in two batches of gastric cancer patients who underwent surgical resection. Thirty-nine samples in the first batch were used as the training set to discover candidate markers correlated to overall survival, and thirty-three samples in the second batch were used for validation. RESULTS: A panel of ten genes were identified as prognostic marker in the first batch samples and classified patients into a lowand a high-risk group with significantly different survival times (P = 0.000047). This prognostic marker was then verified in an independent validation sample batch (P = 0.0009). By comparing with the traditional Tumor-node-metastasis (TNM) staging system, this ten-gene prognostic marker showed consistent prognosis results. It was the only independent prognostic value by multivariate Cox regression analysis (P = 0.007). Interestingly, six of these ten genes are ribosomal proteins, suggesting a possible association between the deregulation of ribosome related gene expression and the poor prognosis. CONCLUSION: A ten-gene marker correlated with overall prognosis, including 6 ribosomal proteins, was identified and verified, which may complement the predictive value of TNM staging system.
文摘OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38） and uPA and the correlation of their expression with breast cancer clinicopathological characteristics, and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells.METHODS Immunohistochemistry （S-P） was used to test the expression of p-p38 and uPA in 60 specimens of breast cancer tissues. Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells, and uPA expression after treatment with SB203580, a specific inhibitor of p38 MAPK.RESULTS The positive rate of the p-p38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%,respectively. The expression of p-p38 was positively related to the expression of uPA （r = 0.316, P 〈 0.05）. The expression of p-p38 and uPA was related to lymph node metastasis and the TNM stage （P 〈 0.05）, but it was not related to the patient＇s age or tumor size （P 〉 0.05）. The expression of p-p38 and uPA in MDA- MB-231 cells was higher than that in MCF-7 cells. SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression.CONCLUSION The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up-regulating uPA expression ,and it may be an important process in breast cancer invasion and metastasis.
基金supported by the Grantin-Aid for scientific research(B)No.18300164"Screening of carcinoma cell surface markers and its application in molecular targeting with bionanocapsules"Japan Society for the Promotion of Science(JSPS).
文摘OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spherical self-organizing map （sSOM） analysis to characterize cells and tissues by the cell surface markers. In the microarray 1,797 probes for human genes coding membrane bound proteins were spotted. With this microarray the gene expression profiles of eight breast carcinoma cell lines were compared to identify the genes that were commonly expressed in breast carcinomas but not in normal cells. RESULTS The gene expression profiles of sSOM from the eight breast carcinoma cell lines were successfully distinguished from that of normal breast tissue derived cells suggesting the presence of genes of interest, sSOMon the data extensively filtered revealed several candidate genes, of which expression was significant in carcinoma cells but low in normal cells. Finally, TM9SF2 was nominated through validations of PCR procedures together with CD24 and ErbB3, which are known breast carcinoma markers. TMgSF2 expression was further confirmed by immunological staining. Interestingly, TMgSF2 was found to be expressed in all the cell lines evaluated while CD24 and ErbB3 were not in all of the carcinoma cells, supporting their relationship in sSOM. Although physiological significance of TMgSF2 is unknown yet, siRNA treatment significantly inhibited the growth of MDA- MB-231 cells. CONCLUSION We propose TM9SF2 as a novel and useful diagnostic marker as well as a potential molecular target specific to breast carcinoma cells covering wide range of breast cancer.
基金Supported by National Natural Science Foundation of China,No.30973139
文摘AIM:To characterize the differentially expressed gene profiles in livers from biliary atresia (BA) patients including,ascertain genes,functional categories and pathways that play a central role in the pathogenesis of BA,and identify the novel prognostic markers for BA.METHODS:Liver tissue samples from control patients,neonatal cholestasis patients,and BA patients at the age of < 60 d,60-90 d,and > 90 d were pooled for DNA microarray analysis.Bioinformatics analysis was performed using,series test cluster of gene ontology,and Pathway-Finder software.Reverse-transcription polymerase chain reaction was performed to confirm changes in selected genes.Relation between RRAS gene expression and prognosis of 40 BA patients was analyzed in a 2-year follow-up study.RESULTS:The 4 identified significant gene expression profiles could confidently separate BA liver tissue from normal and other diseased liver tissues.The included genes were mainly involved in inflammation response and reconstruction of cellular matrix.The significant pathways associated with BA were primarily involved in autoimmune response,activation of T lymphocytes and its related cytokines.The RRAS,POMC,SLC26A6 and STX3 genes were important regulatory modules in pathogenesis of BA.The expression of RRAS was negatively correlated with the elimination rate of jaundice and positively correlated with the occurrence rate of cholangitis.CONCLUSION:Autoimmune response mediated by T lymphocytes may play a vital role in the pathogenesis of BA.The RRAS gene is an important regulatory module in the pathogenesis of BA,which may serve as a novel prognostic marker for BA.
基金Supported by Shanghai Momentous Program,Grant No.07dz19505Shanghai Rising-star Program from the Science and Technology Commission of Shanghai Municipality,No.10QA1401400,China
文摘AIM:To develop lymph node metastasis(LNM)-associated biomarkers for colorectal cancer(CRC) using quantitative proteome analysis.METHODS:Differences in protein expression between primary CRC with LNM(LNM CRC) and without LNM(non-LNM CRC) were assessed using methyl esterification stable isotope labeling coupled with 2D liquid chromatography followed by tandem mass spectrometry(2D-LC-MS/MS).The relationship to clinicopathological parameters and prognosis of candidate biomarkers was examined using an independent sample set.RESULTS:Forty-three proteins were found to be differentially expressed by at least 2.5-fold in two types of CRC.S100A4 was significantly upregulated in LNM CRC compared with non-LNM CRC,which was confirmed by Western blotting,immunohistochemistry and real-time quantitative polymerase chain reaction.Further immunohistochemistry on another 112 CRC cases showed that overexpression of S100A4 frequently existed in LNM CRC compared with non-LNM CRC(P < 0.001).Overexpression of S100A4 was significantly associated with LNM(P < 0.001),advanced TNM stage(P < 0.001),increased 5-year recurrence rate(P < 0.001) and decreased 5-year overall survival rate(P < 0.001).Univariate and multivariate analyses indicated that S100A4 expression was an independent prognostic factor for recurrence and survival of CRC patients(P < 0.05).CONCLUSION:S100A4 might serve as a powerful biomarker for LNM and a prognostic factor in CRC.
基金Supported by The Research fund of Hanyang University (HY-2007-C) to Paik SS
文摘AIM:To verify that CD markers are available for detecting cancer stem cell populations and to evaluate their clinical significance in colon cancer.METHODS:Immunohistochemistry for CD133,CD24 and CD44 was performed on the tissue microarray of 523 colorectal adenocarcinomas.Medical records were reviewed and clinicopathological analysis was performed.RESULTS:In colorectal adenocarcinoma,128 of 523 cases(24.5%) were positive and 395 cases(75.5%) were negative for CD133 expression.Two hundred and sixty-four of 523 cases(50.5%) were positive and 259 cases(49.5%) were negative for CD24 expression.Five hundred and two of 523 cases(96%) were negative and 21 cases(4%) were positive for CD44 expression.Upon clinicopathological analysis,CD133 expression was present more in male patients(P = 0.002) and in advanced T stage cancer(P = 0.024).Correlation between CD24 expression and clinicopathological factors was seen in the degree of differentiation(P = 0.006).Correlation between CD44 expression and clinicopathological factors was seen in the tumor size(P = 0.001).Survival was not significantly related to CD133,CD24 and CD44 expression.CONCLUSION:CD markers were related to invasiveness and differentiation of colorectal adenocarcinoma.However,CD expression was not closely related to survival.
文摘Long non-coding RNAs （lncRNAs） refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer ceils, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 （PRC2）. In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.
基金Supported by the 100 Talents Program of the Chinese Academy of Sciencesthe National Natural Science Foundation of China(No.41206105)the Key Deployment Program of Chinese Academy of Sciences(No.KZZD-EW-14-03)
文摘Small heat shock proteins encompass a widespread but diverse class of proteins, which play key roles in protecting organisms from various stressors. In the present study, the full-length cDNAs of two small heat shock proteins （MgsHSP22 and MgsHSP24.1） were cloned from Mytilus galloprovincialis, which encoded peptides of 181 and 247 amino acids, respectively. Both MgsHSP22 and MgsHSP24.1 were detected in all tissues examined by real-time PCR, with the highest expression being observed in muscle and gonad tissues. The real-time PCR results revealed that Cd significantly inhibited MgsHSP22 expression at 24 h and MgsHSP24.1 at 24 and 48 h under 5 ug/L Cd2＋ exposure. MgsHSP24.1 expression was also significantly inhibited after 50 ug/L Cd2＋ exposure for 48 h. With regard to antioxidant enzymes, increased GPx and CAT activity were detected under Cd2＋ stress （5 and 50 ug/L）, while no significant difference in SOD activity was observed throughout the experiment. Overall, both MgsHsps and antioxidant enzymes revealed their potential as Cd stress biomarkers in M. galloprovincialis.
文摘Interferon （IFN） is a cytokine with various biological functions, including antivirus, immunoregulation and anti- tumor. It has been wildly used in many anti-cancer therapies, including malignant melanoma, hepatocellular carcinoma, ad- vanced renal-cell carcinoma, non-Hodgkin＇s lymphoma, chronic myelogenous leukemia and AIDS-related Kaposi＇s sarcoma. However, its effective dose is always very high, which may bring some serious side effects, nevertheless, not all patients can benefit from the IFN therapy. So a problem we have faced is that how to improve the efficiency and sensitivity of IFN？ To solve this problem, many studies have been launched to find the effective prognostic factors and individual biomarkers for guiding the treatment better. In addition, further clarifying the anti-tumor mechanisms of IFN is benefit for explaining how the biomark- ers predict prognosis of patients. In recent studies, many IFN associated genes and proteins predicting sensitivity of IFN therapy have been found, which may associate with the progression of cancer, such as IFN regulatory factor （IRF）, IFNAR2 mRNA, microRNA, IFITM-I. Some factors in peripheral blood are easier to detect and have the potential to been popularized in clinical practice, such as CD8^high CD57^＋ lymphocyte levels in malignant melanoma, serum IFNAR2 mRNA in mCRC. This review briefly summarized the advances of antitumorally individual markers of IFN.
文摘Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include:fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed en- hancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.
基金Supported by the National Natural Science Foundation of China(No.30600458)
文摘Peptides in shrimp hemolymph play an important role in the innate immune response.Analysis of hemolymph will help to detect and identify potential novel biomarkers of microbial infection.We used magnetic bead-based purification(ClinProt system) and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS) to characterize shrimp hemolymph peptides.Shrimp serum and plasma were used as the source of samples for comparative analysis,and it was found that serum was more suitable for shrimp hemolymph peptidomic analysis.To screen potential specific biomarkers in serum of immune-challenged shrimps,we applied magnetic bead-based MALDI-TOF MS to serum samples from 10 immune-challenged and 10 healthy shrimps.The spectra were analyzed using FlexAnalysis 3.0 and ClinProTools 2.1 software.Thirteen peptide peaks significantly different between the two groups were selected as candidate biomarkers of lipopolysaccharide(LPS)-infection.The diagnostic model established by genetic algorithm using five of these peaks was able to discriminate LPS-challenged shrimps from healthy control shrimps with a sensitivity of 90% and a specificity of 100%.Our approach in MALDITOF MS-based peptidomics is a powerful tool for screening bioactive peptides or biomarkers derived from hemolymph,and will help to enable a better understanding of the innate immune response of shrimps.
基金Supported by National Natural Science Fund of China(31370920)Public Technology Research Program of Zhejiang Province(2014C33157)Medical and Health Research Project of Zhejiang Province(2014KYA225)
文摘Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGlaR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 （43%） advanced lung adenocarcinoma patients. Gender （P=0.003）, smoking status （P=0.001）, and abnormal serum status of carcinoembryonic antigen （CEA, P=0.028） were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation （P=0.046） with an odds ratio of 2.613 （95% Ch 1.018-6.710）. However, receiver operating characteristic （ROC） curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma （the area under the ROC curve was 0.608, P=0.069）. Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.
基金Project partly supported by the National Basic Research Program(973) of China (No. 2004CB117306) and the National Natural Sci-ence Foundation of China (No. 2002AA234031)
文摘Microarray has become increasingly popular biotechnology in biological and medical researches, and has been widely applied in classification of treatment subtypes using expression patterns of biomarkers. We developed a statistical procedure to identify expression biomarkers for treatment subtype classification by constructing an F-statistic based on Henderson method Ⅲ. Monte Carlo simulations were conducted to examine the robustness and efficiency of the proposed method. Simulation results showed that our method could provide satisfying power of identifying differentially expressed genes （DEGs） with false discovery rate （FDR） lower than the given type I error rate. In addition, we analyzed a leukemia dataset collected from 38 leukemia patients with 27 samples diagnosed as acute lymphoblastic leukemia （ALL） and 11 samples as acute myeloid leukemia （AML）. We compared our results with those from the methods of significance analysis of microarray （SAM） and microarray analysis of variance （MAANOVA）. Among these three methods, only expression biomarkers identified by our method can precisely identify the three human acute leukemia subtypes.
基金Supported by a grant from the National Natural Sciences Foundation of China (No.200803150007)
文摘MDM2 (the product of murine double minute 2 gene) is one of the most important negative regulators of p53,which can binds to p53 and initiates ubiquitin-mediated degradation.Besides,MDM2 also controls the activity of several cell-cycle regulators,e.g.pRB,p21,E2F1,independently of p53.The important role of MDM2 in cell-cycle regulation indicates it to be a point of interest in cancer research.In recent years,studies revealed that MDM2 participated in the genesis and development of human tumors.The expression levels and activity of MDM2 was associated with the invasion,metastasis,prognosis and more practical,chemosensitivity.MDM2 is becoming a novel biomarker in cancer prognosis and chemosensitivity prediction.
文摘Right ventricular failure(RVF)is a complicated syndrome with multiple etiologies.RVF relates to pulmonary hypertension,left ventricle failure,and congenital heart diseases.The origin of its pathway is based on pathological gene expression and concomitant diseases.Diagnosis of RVF is a serious problem for clinicians,but none of the criteria in current clinical practice provides uncontaminated information on either systolic or diastolic function.Perioperative assessment and bedside monitoring of right ventricle function have to be revised and widely used.Right ventricle function in transplant patients demands different evaluation using biomarkers or/and autopsy.Treatment of RVF has surgical and non-surgical approaches;both are still in development and need further clarification.
