Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus (T2DM) and arteriosclerosis obliteran (ASO) when treated with Probucol plus Cilostazol in combination and indi...Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus (T2DM) and arteriosclerosis obliteran (ASO) when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety (QTc intervals) were set, respectively. Probucol significantly reduced total cholesterol (P 〈 0.001), low-density lipoprotein cholesterol (LDL-C), (P = 0.01), and high-density lipoprotein cholesterol (HDL-C) (P 〈 0.001) compared with conventional therapy. Cilostazol was effective in increasing HDL-C (P = 0.002) and reducing triglycerides levels (P 〈 0.01) compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein (Ox-LDL, P = 0.065). No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.展开更多
Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significa...Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed.Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Followup ranged from 32 months up to 6 years.Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative(TN),respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than15%(P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15%(P = 0.000).Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients.展开更多
In this study,the fatty acids(FAs) of the organs and tissues of sea cucumber(Apostichopus japonicus) were profiled in order to compare the FA composition of sea cucumber collected from natural habitat(wild) and cages(...In this study,the fatty acids(FAs) of the organs and tissues of sea cucumber(Apostichopus japonicus) were profiled in order to compare the FA composition of sea cucumber collected from natural habitat(wild) and cages(cultured).The differences in FA contents in dermomuscular tube,peripharyngeal annulus,gonad and intestine(with or without content) between the wild and the cultured were determined.The main fatty acids in all organs and tissues were 20:5n-3,16:1n-7,20:4n-6,22:6n-3,18:0,and 18:1n-7.The basically different FAs of body wall and digestive tube were 16:1n-7,18:1n-9 and 20:1n-11.The ratio of saturated to mono-and polyunsaturated FAs in digestive tube was independent on inside content while there was a redistribution of the total amount of n-3 and n-6 fatty acids.The comparison of FA composition of the wild and the cultured sea cucumber showed that 20:5n-3,16:1n-7 and 18:1n-7 predominated the wild while 20:4n-6 predominated the cultured.The content of branched-chain fatty acids in the wild was 3%–4% and about 9% in the cultured.The possible FAs for identifying the wild and the cultured sea cucumbers were selected.It was suggested that the indexes such as the ratio of either(n-3:n-6) to(n-7:n-6) or(n-3) +(n-7) to(n-6) may serve as the biomarkers distinguishing the wild and the cultured sea cucumber.展开更多
AIM: TO determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection (“anti-HBc alone”) among human immunodeficiency virus (HIV) type-1 infe...AIM: TO determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection (“anti-HBc alone”) among human immunodeficiency virus (HIV) type-1 infected patients. Occult hepatitis B infection frequency was also evaluated. METHODS: Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus (HBV) infection were classified into three groups: past hepatitis, "anti-HBc alone" and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus (HCV) were performed on "anti-HBc alone" patients. RESULTS: One hundred and eighty seven (53.7%) HIV-positive patients had markers of HBV infection: 118 past infection (63.1%), 14 chronic hepatitis (7.5%) and 55 "anti-HBc alone" (29.4%). Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals (Cl) 1.33-4.00] and antibodies to HCV infection [odds ratio (OR) 2.87; 95% CI 1.10-7.48] were factors independently associated with the "anti-HBc alone" pattern. No differences in liver disease frequency were detected between both groups. Serum levels of anti-HBs were not associated with HCV infection (nor viral replication or HCV genotype), or with HIV replication or CD4 level. No "anti-HBc alone" patient tested positive for HBV DNA. CONCLUSION: "Anti-HBc alone" prevalence in HIM- positive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury,展开更多
In this work, we analyzed only the patients of the NSTEMI (non ST-segment elevation myocardial infarction) who arrived at the hospital within 12 h after symptoms started. Using NSTEMI follow-up data within, the charac...In this work, we analyzed only the patients of the NSTEMI (non ST-segment elevation myocardial infarction) who arrived at the hospital within 12 h after symptoms started. Using NSTEMI follow-up data within, the characteristics of the clinical data, the risk factor, and the blood tested in the hospital visit were analyzed for MACE (major adverse cardiac events) patients. MACE includes cardiac death, MI (myocardial infarction), Re-PCI, and CABG (coronary artery bypass graft). As a result, from the NSTEMI patients which can be followed up for over 12 m, NT-ProBNP (p=0.014) and age (p=0.045) are found to be the independent risk factors related to MACE. Accordingly, they can be useful for the diagnosis and prognosis for NSTEMI patients as a biomarker.展开更多
OBJECTIVE To establish a serum protein pattern model for screening pancreatic cancer. METHODS Twenty-nine serum samples from patients with pancreatic cancer were collected before surgery, and an additional 57 serum sa...OBJECTIVE To establish a serum protein pattern model for screening pancreatic cancer. METHODS Twenty-nine serum samples from patients with pancreatic cancer were collected before surgery, and an additional 57 serum samples from age and sex-matched individuals without cancer were used as controls. WCX magnetic beans and a PBS II-C protein chip reader (Ciphergen Biosystems Inc) were employed to detect the protein fingerprint expression of all serum samples. The resulting profiles comparing serum from cancer and normal patients were analyzed with the Biomarker Wizard system, to establish a model using the Biomarker Pattern system software. A double-blind test was used to determine the sensitivity and specificity of the model.RESULTS A group of 4 biomarkers (relative molecular weights were 5,705 Da, 4,935 Da, 5,318 Da, 3,243 Da) were selected to set up a decision tree to produce the classification model to effectively screen pancreatic cancer patients. The results yielded a sensitivity of 100% (20/20), specificity of 97.4% (37/38). The ROC curve was 99.7%. A double-blind test used to challenge the model resulted in a sensitivity of 88.9% and a specificity of 89.5%. CONCLUSION New serum biomarkers of pancreatic cancer have been identified. The pattern of combined markers provides a powerful and reliable diagnostic method for pancreatic cancer with high sensitivity and specificity.展开更多
AIM: TO characterize a culture model of rat CCA cells, which were derived from a transplantable TTA-induced CCA and designated as Chang Gung CCA (CGCCA). METHODS: The CGCCA cells were cultured at in vitro passage ...AIM: TO characterize a culture model of rat CCA cells, which were derived from a transplantable TTA-induced CCA and designated as Chang Gung CCA (CGCCA). METHODS: The CGCCA cells were cultured at in vitro passage 12 times on a culture dish in DMEM medium. To measure the doubling time, 103 cells were plated in a 96-well plate containing the growth medium. The cells were harvested 4 to 10 d after seeding, and a standard MTT assay was used to measure the growth. The phenotype of CACCA cell and xenograft was determined by immunohistochemical study. We also determine the chromosomal alterations of CGCCA, G-banding and spectral karyotyping studies were performed. The CGCCA cell line was transplanted into the nude mice for examining its tumorigenicity. 2-Deoxy-2-(18F)fluoro-D- glucose (FDG) autoradiography was also performed to evaluate the FDG uptake of the tumor xenograft. RESULTS: The doubling time for the CGCCA cell line was 32 h. After transplantation into nude mice, FDG autoradiography showed that the tumors formed at the cell transplantation site had a latency period of 4-6 wk with high FDG uptake excluding necrosis tissue. Moreover, immunohistochemical staining revealed prominent cytoplasmic expression of c-erb-B2, CK19, c-Met, COX-n, EGFR, MUC4, and a negative expression of K-ras. All data confirmed the phenotypic features of the CGCCA cell line coincide with the xenograft mice tumors, indicating cells containing the tumorigenicity of CCA originated from CCA. In addition, karyotypic band- ing analysis showed that the diploid (2n) cell status combines with ring and giant rod marker chromosomes in these clones; either both types simultaneously appeared or only one type of marker chromosome in a pair appeared in a cell. The major materials contained in the marker chromosome were primarily identified from chromosome 4. CONCLUSION: The current CGCCA cell line may be used as a non-K-ras effect CCA model and to obtain information and reveal novel pathways for CCA. Further applications regarding tumor markers or therapeutic targeting of CCA should be addressed accordingly.展开更多
Researchers in bioinformatics, biostatistics and other related fields seek biomarkers for many purposes, including risk assessment, disease diagnosis and prognosis, which can be formulated as a patient classification....Researchers in bioinformatics, biostatistics and other related fields seek biomarkers for many purposes, including risk assessment, disease diagnosis and prognosis, which can be formulated as a patient classification. In this paper, a new method of using a tree regression to improve logistic classification model is introduced in biomarker data analysis. The numerical results show that the linear logistic model can be significantly improved by a tree regression on the residuals. Although the classification problem of binary responses is discussed in this research, the idea is easy to extend to the classification of multinomial responses.展开更多
The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predic...The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predicting hepatitis B e antigen (HBeAg) seroconversion in these patients during IFN therapy. Two groups of patients were enrolled: training and validation. In the training group, 2-DE experiments and subsequent identification of altered levels of proteins showed that α-2-HS-glycoprotein, leucine-rich α-2-glycoprotein, and haptoglobin were significantly upregulated as compared with baseline levels in the HBeAg seroconversion group, whereas apolipoprotein C-III precursor, leucine-rich α-2-glycoprotein, and α-albumin were downregulated in the non-seroconversion group. For patients with HBeAg seroconversion in the training group, Western blot analyses showed that α-2-HS-glycoprotein levels in 75% of patients were significantly upregulated at the end of the treatment as compared with baseline levels. Subsequent experiments in the validation group showed that α-2-HS-glycoprotein levels were significantly increased at week 4 in 83.33% of patients in the HBeAg seroconversion group. Dynamic changes in the serum level of α-2-HS-glycoprotein may be a potential early marker for predicting HBeAg seroconversion during IFN treatment for CHB.展开更多
MicroRNAs(miRNAs) are small noncoding RNAs that are emerging as pivotal modulators in virtually all aspects of cardiac biology,from cardiac development to cardiomyocyte survival and hypertrophy.The miRNA profiling,fol...MicroRNAs(miRNAs) are small noncoding RNAs that are emerging as pivotal modulators in virtually all aspects of cardiac biology,from cardiac development to cardiomyocyte survival and hypertrophy.The miRNA profiling,following gain-and loss-of-function studies using in vitro and in vivo models,has identified wide-ranging functions for miRNAs in the heart,providing new perspectives on their contributions to cardiac pathogenesis,and revealing potential therapeutic targets and diagnostic biomarkers.This review summarizes current progress in regulation of miRNAs in heart development and disease.展开更多
Surveillance to detect cancer recurrence is an important part of care for cancer survivors.In this paper we discuss the design of optimal strategies for early detection of disease recurrence based on each patient'...Surveillance to detect cancer recurrence is an important part of care for cancer survivors.In this paper we discuss the design of optimal strategies for early detection of disease recurrence based on each patient's distinct biomarker trajectory and periodically updated risk estimated in the setting of a prospective cohort study.We adopt a latent class joint model which considers a longitudinal biomarker process and an event process jointly,to address heterogeneity of patients and disease,to discover distinct biomarker trajectory patterns,to classify patients into different risk groups,and to predict the risk of disease recurrence.The model is used to develop a monitoring strategy that dynamically modifies the monitoring intervals according to patients' current risk derived from periodically updated biomarker measurements and other indicators of disease spread.The optimal biomarker assessment time is derived using a utility function.We develop an algorithm to apply the proposed strategy to monitoring of new patients after initial treatment.We illustrate the models and the derivation of the optimal strategy using simulated data from monitoring prostate cancer recurrence over a 5-year period.展开更多
Informative proteins are the proteins that play critical functional roles inside cells.They are the fundamental knowledge of translating bioinformatics into clinical practices.Many methods of identifying informative b...Informative proteins are the proteins that play critical functional roles inside cells.They are the fundamental knowledge of translating bioinformatics into clinical practices.Many methods of identifying informative biomarkers have been developed which are heuristic and arbitrary,without considering the dynamics characteristics of biological processes.In this paper,we present a generative model of identifying the informative proteins by systematically analyzing the topological variety of dynamic protein-protein interaction networks(PPINs).In this model,the common representation of multiple PPINs is learned using a deep feature generation model,based on which the original PPINs are rebuilt and the reconstruction errors are analyzed to locate the informative proteins.Experiments were implemented on data of yeast cell cycles and different prostate cancer stages.We analyze the effectiveness of reconstruction by comparing different methods,and the ranking results of informative proteins were also compared with the results from the baseline methods.Our method is able to reveal the critical members in the dynamic progresses which can be further studied to testify the possibilities for biomarker research.展开更多
文摘Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus (T2DM) and arteriosclerosis obliteran (ASO) when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety (QTc intervals) were set, respectively. Probucol significantly reduced total cholesterol (P 〈 0.001), low-density lipoprotein cholesterol (LDL-C), (P = 0.01), and high-density lipoprotein cholesterol (HDL-C) (P 〈 0.001) compared with conventional therapy. Cilostazol was effective in increasing HDL-C (P = 0.002) and reducing triglycerides levels (P 〈 0.01) compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein (Ox-LDL, P = 0.065). No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.
文摘Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed.Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Followup ranged from 32 months up to 6 years.Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative(TN),respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than15%(P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15%(P = 0.000).Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients.
文摘In this study,the fatty acids(FAs) of the organs and tissues of sea cucumber(Apostichopus japonicus) were profiled in order to compare the FA composition of sea cucumber collected from natural habitat(wild) and cages(cultured).The differences in FA contents in dermomuscular tube,peripharyngeal annulus,gonad and intestine(with or without content) between the wild and the cultured were determined.The main fatty acids in all organs and tissues were 20:5n-3,16:1n-7,20:4n-6,22:6n-3,18:0,and 18:1n-7.The basically different FAs of body wall and digestive tube were 16:1n-7,18:1n-9 and 20:1n-11.The ratio of saturated to mono-and polyunsaturated FAs in digestive tube was independent on inside content while there was a redistribution of the total amount of n-3 and n-6 fatty acids.The comparison of FA composition of the wild and the cultured sea cucumber showed that 20:5n-3,16:1n-7 and 18:1n-7 predominated the wild while 20:4n-6 predominated the cultured.The content of branched-chain fatty acids in the wild was 3%–4% and about 9% in the cultured.The possible FAs for identifying the wild and the cultured sea cucumbers were selected.It was suggested that the indexes such as the ratio of either(n-3:n-6) to(n-7:n-6) or(n-3) +(n-7) to(n-6) may serve as the biomarkers distinguishing the wild and the cultured sea cucumber.
文摘AIM: TO determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection (“anti-HBc alone”) among human immunodeficiency virus (HIV) type-1 infected patients. Occult hepatitis B infection frequency was also evaluated. METHODS: Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus (HBV) infection were classified into three groups: past hepatitis, "anti-HBc alone" and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus (HCV) were performed on "anti-HBc alone" patients. RESULTS: One hundred and eighty seven (53.7%) HIV-positive patients had markers of HBV infection: 118 past infection (63.1%), 14 chronic hepatitis (7.5%) and 55 "anti-HBc alone" (29.4%). Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals (Cl) 1.33-4.00] and antibodies to HCV infection [odds ratio (OR) 2.87; 95% CI 1.10-7.48] were factors independently associated with the "anti-HBc alone" pattern. No differences in liver disease frequency were detected between both groups. Serum levels of anti-HBs were not associated with HCV infection (nor viral replication or HCV genotype), or with HIV replication or CD4 level. No "anti-HBc alone" patient tested positive for HBV DNA. CONCLUSION: "Anti-HBc alone" prevalence in HIM- positive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury,
基金Project(2012-0000478) supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST)
文摘In this work, we analyzed only the patients of the NSTEMI (non ST-segment elevation myocardial infarction) who arrived at the hospital within 12 h after symptoms started. Using NSTEMI follow-up data within, the characteristics of the clinical data, the risk factor, and the blood tested in the hospital visit were analyzed for MACE (major adverse cardiac events) patients. MACE includes cardiac death, MI (myocardial infarction), Re-PCI, and CABG (coronary artery bypass graft). As a result, from the NSTEMI patients which can be followed up for over 12 m, NT-ProBNP (p=0.014) and age (p=0.045) are found to be the independent risk factors related to MACE. Accordingly, they can be useful for the diagnosis and prognosis for NSTEMI patients as a biomarker.
基金a grant from the Key Project of Science and Technology Commission of Liaoning Province,China (No. 2005225003-3)
文摘OBJECTIVE To establish a serum protein pattern model for screening pancreatic cancer. METHODS Twenty-nine serum samples from patients with pancreatic cancer were collected before surgery, and an additional 57 serum samples from age and sex-matched individuals without cancer were used as controls. WCX magnetic beans and a PBS II-C protein chip reader (Ciphergen Biosystems Inc) were employed to detect the protein fingerprint expression of all serum samples. The resulting profiles comparing serum from cancer and normal patients were analyzed with the Biomarker Wizard system, to establish a model using the Biomarker Pattern system software. A double-blind test was used to determine the sensitivity and specificity of the model.RESULTS A group of 4 biomarkers (relative molecular weights were 5,705 Da, 4,935 Da, 5,318 Da, 3,243 Da) were selected to set up a decision tree to produce the classification model to effectively screen pancreatic cancer patients. The results yielded a sensitivity of 100% (20/20), specificity of 97.4% (37/38). The ROC curve was 99.7%. A double-blind test used to challenge the model resulted in a sensitivity of 88.9% and a specificity of 89.5%. CONCLUSION New serum biomarkers of pancreatic cancer have been identified. The pattern of combined markers provides a powerful and reliable diagnostic method for pancreatic cancer with high sensitivity and specificity.
文摘AIM: TO characterize a culture model of rat CCA cells, which were derived from a transplantable TTA-induced CCA and designated as Chang Gung CCA (CGCCA). METHODS: The CGCCA cells were cultured at in vitro passage 12 times on a culture dish in DMEM medium. To measure the doubling time, 103 cells were plated in a 96-well plate containing the growth medium. The cells were harvested 4 to 10 d after seeding, and a standard MTT assay was used to measure the growth. The phenotype of CACCA cell and xenograft was determined by immunohistochemical study. We also determine the chromosomal alterations of CGCCA, G-banding and spectral karyotyping studies were performed. The CGCCA cell line was transplanted into the nude mice for examining its tumorigenicity. 2-Deoxy-2-(18F)fluoro-D- glucose (FDG) autoradiography was also performed to evaluate the FDG uptake of the tumor xenograft. RESULTS: The doubling time for the CGCCA cell line was 32 h. After transplantation into nude mice, FDG autoradiography showed that the tumors formed at the cell transplantation site had a latency period of 4-6 wk with high FDG uptake excluding necrosis tissue. Moreover, immunohistochemical staining revealed prominent cytoplasmic expression of c-erb-B2, CK19, c-Met, COX-n, EGFR, MUC4, and a negative expression of K-ras. All data confirmed the phenotypic features of the CGCCA cell line coincide with the xenograft mice tumors, indicating cells containing the tumorigenicity of CCA originated from CCA. In addition, karyotypic band- ing analysis showed that the diploid (2n) cell status combines with ring and giant rod marker chromosomes in these clones; either both types simultaneously appeared or only one type of marker chromosome in a pair appeared in a cell. The major materials contained in the marker chromosome were primarily identified from chromosome 4. CONCLUSION: The current CGCCA cell line may be used as a non-K-ras effect CCA model and to obtain information and reveal novel pathways for CCA. Further applications regarding tumor markers or therapeutic targeting of CCA should be addressed accordingly.
文摘Researchers in bioinformatics, biostatistics and other related fields seek biomarkers for many purposes, including risk assessment, disease diagnosis and prognosis, which can be formulated as a patient classification. In this paper, a new method of using a tree regression to improve logistic classification model is introduced in biomarker data analysis. The numerical results show that the linear logistic model can be significantly improved by a tree regression on the residuals. Although the classification problem of binary responses is discussed in this research, the idea is easy to extend to the classification of multinomial responses.
基金supported by the National Basic Research Program of China (Grant Nos. 2005CB522902 and 2007CB512900)the National High Technology Research and Development Program of China (Grant No. 2006AA02A410)+4 种基金the National Natural Science Foundation of China (Grant No. 30901256)the Beijing Natural Science Foundation (Grant No. 7102153)National Science and Technology Major Project for Infectious Diseases Control During the 11th Five-Year Plan Period (Grant Nos. 2008ZX10002-012 and 2008ZX10002-013)Peking University People’s Hospital Research Development Funds (Grant No. RDC 2009-13)Key Clinical Research Program of Ministry of Health of China
文摘The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predicting hepatitis B e antigen (HBeAg) seroconversion in these patients during IFN therapy. Two groups of patients were enrolled: training and validation. In the training group, 2-DE experiments and subsequent identification of altered levels of proteins showed that α-2-HS-glycoprotein, leucine-rich α-2-glycoprotein, and haptoglobin were significantly upregulated as compared with baseline levels in the HBeAg seroconversion group, whereas apolipoprotein C-III precursor, leucine-rich α-2-glycoprotein, and α-albumin were downregulated in the non-seroconversion group. For patients with HBeAg seroconversion in the training group, Western blot analyses showed that α-2-HS-glycoprotein levels in 75% of patients were significantly upregulated at the end of the treatment as compared with baseline levels. Subsequent experiments in the validation group showed that α-2-HS-glycoprotein levels were significantly increased at week 4 in 83.33% of patients in the HBeAg seroconversion group. Dynamic changes in the serum level of α-2-HS-glycoprotein may be a potential early marker for predicting HBeAg seroconversion during IFN treatment for CHB.
基金supported by the National Natural Science Foundation of China (Grant No. 81070103)National Natural Science Foundation of Major International Cooperation Projects in China (Grant No. 81120108003) to Yu XiYong
文摘MicroRNAs(miRNAs) are small noncoding RNAs that are emerging as pivotal modulators in virtually all aspects of cardiac biology,from cardiac development to cardiomyocyte survival and hypertrophy.The miRNA profiling,following gain-and loss-of-function studies using in vitro and in vivo models,has identified wide-ranging functions for miRNAs in the heart,providing new perspectives on their contributions to cardiac pathogenesis,and revealing potential therapeutic targets and diagnostic biomarkers.This review summarizes current progress in regulation of miRNAs in heart development and disease.
基金supported by National Cancer Institute(Grant No.U01CA079778)
文摘Surveillance to detect cancer recurrence is an important part of care for cancer survivors.In this paper we discuss the design of optimal strategies for early detection of disease recurrence based on each patient's distinct biomarker trajectory and periodically updated risk estimated in the setting of a prospective cohort study.We adopt a latent class joint model which considers a longitudinal biomarker process and an event process jointly,to address heterogeneity of patients and disease,to discover distinct biomarker trajectory patterns,to classify patients into different risk groups,and to predict the risk of disease recurrence.The model is used to develop a monitoring strategy that dynamically modifies the monitoring intervals according to patients' current risk derived from periodically updated biomarker measurements and other indicators of disease spread.The optimal biomarker assessment time is derived using a utility function.We develop an algorithm to apply the proposed strategy to monitoring of new patients after initial treatment.We illustrate the models and the derivation of the optimal strategy using simulated data from monitoring prostate cancer recurrence over a 5-year period.
基金supported by National Natural Science Foundation of China(30970780)Ph.D.Programs Foundation of Ministry of Education of China(20091103110005)+4 种基金the Project for the Innovation Team of Beijing,National Natural Science Foundation of China(81370038)the Beijing Natural Science Foundation(7142012)the Science and Technology Project of Beijing Municipal Education Commission(km201410005003)the Rixin Fund of Beijing University of Technology(2013-RX-L04)the Basic Research Fund of Beijing University of Technology
文摘Informative proteins are the proteins that play critical functional roles inside cells.They are the fundamental knowledge of translating bioinformatics into clinical practices.Many methods of identifying informative biomarkers have been developed which are heuristic and arbitrary,without considering the dynamics characteristics of biological processes.In this paper,we present a generative model of identifying the informative proteins by systematically analyzing the topological variety of dynamic protein-protein interaction networks(PPINs).In this model,the common representation of multiple PPINs is learned using a deep feature generation model,based on which the original PPINs are rebuilt and the reconstruction errors are analyzed to locate the informative proteins.Experiments were implemented on data of yeast cell cycles and different prostate cancer stages.We analyze the effectiveness of reconstruction by comparing different methods,and the ranking results of informative proteins were also compared with the results from the baseline methods.Our method is able to reveal the critical members in the dynamic progresses which can be further studied to testify the possibilities for biomarker research.