Gastric cancer(GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood ca...Gastric cancer(GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.展开更多
AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine...AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis.METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor Ⅷ-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.展开更多
Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and ...Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.展开更多
BACKGROUND:Community-acquired pneumonia(CAP)in autoimmune diseases(AID)-induced immunocompromised host(ICH)had a high incidence and poor prognosis.However,only a few studies had determined the clinical characteristics...BACKGROUND:Community-acquired pneumonia(CAP)in autoimmune diseases(AID)-induced immunocompromised host(ICH)had a high incidence and poor prognosis.However,only a few studies had determined the clinical characteristics of these patients.Our study was to explore the characteristics and predictors of mortality in CAP patients accompanied with AID-induced ICH.METHODS:From 2013 to 2018,a total of 94 CAP patients accompanied with AID-induced ICH,admitted to Emergency Department of Zhongshan Hospital,Fudan University,were enrolled in this study.Clinical data and the risk regression estimates of repeated predictors were evaluated by generalized estimating equations(GEEs)analysis.An open-cohort approach was used to classify patient's outcomes into the survival or non-survival group.RESULTS:The hospital mortality of patients with CAP occurring in AID-induced ICH was 60.64%.No significant differences were found with respect to clinical symptoms and lung images between survival and non-survival groups,while renal insufficiency and dysfunction of coagulation had higher proportions in non-survival patients(P<0.05).Both noninvasive ventilation(NIV)and invasive mechanical ventilation(IMV)were performed more frequently in non-survival group(P<0.05).By the multivariate GEEs analysis,the repeated measured longitudinal indices of neutrophilto-lymphocyte ratio(NLR)(odds ratio[OR]=1.055,95%confidence interval[95%CI]1.025–1.086),lactate dehydrogenase(LDH)(OR=1.004,95%CI 1.002–1.006)and serum creatinine(s Cr)(OR=1.018,95%CI 1.008–1.028),were associated with a higher risk of mortality.CONCLUSION:The CAP patients in AID-induced ICH had a high mortality.A significant relationship was demonstrated between the factors of NLR,LDH,s Cr and mortality risk in these patients.展开更多
Hepatocellular carcinoma(HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year,it has become the third most common cause of death from cancer worldwide. Hepatic ...Hepatocellular carcinoma(HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year,it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients,however,there is a high risk of recurrence in postoperativeHCC. In clinical practice,there exists an urgent need for valid prognostic markers to identify patients with prognosis,hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients.展开更多
AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy’s rule...AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy’s rule and the most important predictors for outcome. METHODS: The Adverse Drug Reaction Advisory Committee was set up in 1997 in our hospital to identify all suspicions of DILD following a structured prospective report form. Liver damage was divided into hepatocellular, cholestatic, and mixed types according to laboratory and histologic criteria when available. Further evaluation of causality assessment was performed. RESULTS: From January 1997 to December 2004, 265 patients were diagnosed with DILD,and 140 (52.8%) of them were female. hepatocellular damage was the most common (72.1%), the incidence of death was 9.9% in patients with hepatocellular damage and 9.5% in patients with cholestatic/mixed damage (P < 0.05). There was no difference in age of dead and recovered patients. The proportion of females and males was similar in recovered and dead patients, no difference was observed in duration of treatment between the two groups. The serum total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and aspartate transaminase (AST) (P = 0.013) values were higher in dead patients than in recovered patients. Chinese herbal medicine was the most frequently prescribed, accounting for 24.2% of the whole series. However, antitubercular drugs (3.4%) were found to be the primary etiological factor for fetal DILD. Factors associated with the development of fulminanthepatic failure were hepatic encephalopathy (OR = 43.66, 95% CI = 8.47-224.95, P < 0.0001), ascite (OR = 28.48, 95% CI = 9.26-87.58, P < 0.0001), jaundice (OR = 11.43, 95% CI = 1.52-85.96, P = 0.003), alcohol abuse (OR = 3.83, 95% CI = 1.26-11.67, P = 0.035) and direct bilirubin (OR = 1.93, 95% CI = 1.25-2.58, P = 0.012). CONCLUSION: Death occurs in 9.8% of patients with DILD. Chinese herbal medicine stands out as the most common drug for DILD. While an展开更多
AIM To evaluate the role of albumin at the time of ulcerative colitis(UC) diagnosis in predicting the clinical course of disease.METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs he...AIM To evaluate the role of albumin at the time of ulcerative colitis(UC) diagnosis in predicting the clinical course of disease.METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia(i.e.,≤ 3.5 gm/dl) or normal albumin levels(i.e.,> 3.5 gm/dl) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined asalbumin level ≤ 3.5 g/dl at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids(CS),thiopurines,anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients,but 92(11.4%) patients did not have their albumin levels checked at the time of UC diagnosis,and they were excluded. A total of 710 patients,who had albumin levels checked at time of UC diagnosis,were included in our study. Amongst them,536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use(adjusted HR = 1.7,95%CI: 1.3-2.3),higher likelihood of thiopurine or anti-TNF use(adjusted HR = 1.72,95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients,but it was not statistically significant(Adjusted HR = 1.7,95%CI: 0.90-3.25).CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis.展开更多
Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers fo...Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.展开更多
Colorectal cancer(CRC) is the third leading cause of cancer death worldwide, which is consequence of multistep tumorigenesis of several genetic and epigenetic events. Since CRC is mostly asymptomatic until it progress...Colorectal cancer(CRC) is the third leading cause of cancer death worldwide, which is consequence of multistep tumorigenesis of several genetic and epigenetic events. Since CRC is mostly asymptomatic until it progresses to advanced stages, the early detection using effective screening approaches, selection of appropriate therapeutic strategies and efficient follow-up programs are essential to reduce CRC mortalities. Biomarker discovery for CRC based on the personalized genotype and clinical information could facilitate the classification of patients with certain types and stages of cancer to tailor preventive and therapeutic approaches. These cancer-related biomarkers should be highly sensitive and specific in a wide range of specimen(s)(including tumor tissues, patients' fluids or stool). Reliable biomarkers which enable the early detection of CRC, can improve early diagnosis, prognosis, treatment response prediction, and recurrence risk. Advances in our understanding of the natural history of CRC have led to the development of different CRC associated molecular and cellular biomarkers. This review highlights the new trends and approaches in CRC biomarker discovery, which could be potentially used for early diagnosis, development of new therapeutic approaches and follow-up of patients.展开更多
Colorectal cancer remains one of the most common and lethal malignancies worldwide despite the use of various therapeutic strategies. A better understanding of the mechanisms responsible for tumor initiation and progr...Colorectal cancer remains one of the most common and lethal malignancies worldwide despite the use of various therapeutic strategies. A better understanding of the mechanisms responsible for tumor initiation and progression is essential for the development of novel, more powerful therapies. The traditional, so-called “stochastic model” of tumor development, which assumes that each cancer cell is tumorigenic, has been deeply challenged during the past decade by the identification of cancer stem cells (CSCs), a biologically distinct subset of cells within the bulk of tumor mass. This discovery led to the development of the hierarchical model of tumorigenesis which assumes that only CSCs have the ability to initiate tumor growth, both at primary and metastatic sites. This model implies that the elimination of all CSCs is fundamental to eradicate tumors and that failure to do so might be responsible for the occurrence of relapses and/or metastases frequently observed in the clinical management of colorectal cancer patients. Identification and isolation of CSCs is essential for a better understanding of their role in the tumorigenetic process and for the development of CSC-specific therapies. Several methods have been used for this purpose and many efforts have been focused on the identification of specific CSC-surface markers. This review provides an overview of the proposed roles of CSC in human colorectal tumorigenesis focusing on the most important molecules identified as CSC-specific markers in colorectal cancer and on the potential strategies for the development of CSC-targeted therapy.展开更多
目的联合检测肺腺癌患者外周血中细胞角蛋白(cytokeratin,CK,肺腺癌循环肿瘤细胞阳性)和CD133基因(肺癌干细胞标志物)的表达,探讨二者在评估肺腺癌预后的临床价值。方法选取2014年6月至2016年6月昆明总医院心胸外科和宣威市第一人民医...目的联合检测肺腺癌患者外周血中细胞角蛋白(cytokeratin,CK,肺腺癌循环肿瘤细胞阳性)和CD133基因(肺癌干细胞标志物)的表达,探讨二者在评估肺腺癌预后的临床价值。方法选取2014年6月至2016年6月昆明总医院心胸外科和宣威市第一人民医院心胸外科的178例未化疗的肺腺癌手术患者,中位年龄59岁,其中男性78例,女性100例。收集患者术前外周血标本10 m L,细胞块法和CK(免疫细胞化学法)用于检测CTC,PCR法用于检测CD133表达。免疫组化法检测肺腺癌组织中CK、Vimentin(Vim)、TTF-1、Ki-67、CD133的表达,并分析与外周血CK和CD133表达的关系。根据外周血CK和CD133的检测结果,将病例分为CK/CD133双阳性组和非双阳性组,统计学分析两组间临床病理因素的差异。结果 178例肺腺癌患者外周血CTC(CK阳性)的检出率为48.3%(86/178),与癌组织中Ki-67、Vim表达显著正相关(P<0.05);外周血的CD133阳性表达率为66.9%(119/178),与癌组织Vim、CD133表达显著正相关(P<0.05);外周血CK/CD133双阳组53例(29.8%),双阳组淋巴结转移率显著增高,肺腺癌组织学分化级别显著降低,临床分期显著提高,转移率显著增高(P<0.05)。结论肺腺癌患者外周血中CK与CD133双阳性表达提示外周血存在干性特征的循环肿瘤细胞,表明预后不良,联合检测CK与CD133可用于肺腺癌患者预后监测和指导治疗。展开更多
BACKGROUND： Previous researches in pancreatic cancer demonstrated a negative correlation between secreted protein acidic and rich in cysteine （SPARC） expression in primary tumor and survival, but not for SPARC expr...BACKGROUND： Previous researches in pancreatic cancer demonstrated a negative correlation between secreted protein acidic and rich in cysteine （SPARC） expression in primary tumor and survival, but not for SPARC expression in lymph node. In the present study, we aimed to evaluate the SPARC expression in various types of tissues and its impact on patients＇ prognosis. METHODS： The expression of SPARC was examined by immunohistochemistry in resected pancreatic cancer specimens. Kaplan-Meier analyses and Cox proportional hazards regres- sion were applied to assess the mortality risk. RESULTS： A total of 222 tissue samples from 73 patients were collected to evaluate the SPARC expression, which included 73 paired primary tumor and adjacent normal tissues, 38 paired metastatic and normal lymph nodes. The proportion of posi tive SPARC expression in metastatic lymph node was high （32/38）, whereas in normal lymph node it was negative （0/38）. Positive SPARC expression in primary tumor cells was associ- ated with a significantly decreased overall survival （P=0.007） and disease-free survival （P=0.003）, whereas in other types of tissues it did not show a predictive role for prognosis. Univariate and multivariate analyses both confirmed this significance. CONCLUSION： SPARC can serve a dual function role as both predictor for prognosis and potentially biomarker for lymph node metastasis in resected pancreatic cancer patients.展开更多
文摘Gastric cancer(GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.
基金Supported by the Major State Basic Research Development Program (973 Program) of China (No. 2003CB515507) and Science and Technology Fund by Department of Education of Anhui Province
文摘AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis.METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor Ⅷ-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.
基金Supported by the National Research,Development and Innovation Office,No.NVKP_16-1-2016-0004
文摘Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.
基金the Shanghai Traditional Medicine Development Project (ZY3-CCCX3-3018, ZHYY- ZXYJH-201615)the National Natural Science Foundation of China (81471840, 81171837)+1 种基金the Zhongshan Hospital Distinguished Young Scholars and the Shanghai Municipal Planning Commission of science and Research Fund (20134Y023)Key Project of Shanghai Municipal Health Bureau (2016ZB0202).
文摘BACKGROUND:Community-acquired pneumonia(CAP)in autoimmune diseases(AID)-induced immunocompromised host(ICH)had a high incidence and poor prognosis.However,only a few studies had determined the clinical characteristics of these patients.Our study was to explore the characteristics and predictors of mortality in CAP patients accompanied with AID-induced ICH.METHODS:From 2013 to 2018,a total of 94 CAP patients accompanied with AID-induced ICH,admitted to Emergency Department of Zhongshan Hospital,Fudan University,were enrolled in this study.Clinical data and the risk regression estimates of repeated predictors were evaluated by generalized estimating equations(GEEs)analysis.An open-cohort approach was used to classify patient's outcomes into the survival or non-survival group.RESULTS:The hospital mortality of patients with CAP occurring in AID-induced ICH was 60.64%.No significant differences were found with respect to clinical symptoms and lung images between survival and non-survival groups,while renal insufficiency and dysfunction of coagulation had higher proportions in non-survival patients(P<0.05).Both noninvasive ventilation(NIV)and invasive mechanical ventilation(IMV)were performed more frequently in non-survival group(P<0.05).By the multivariate GEEs analysis,the repeated measured longitudinal indices of neutrophilto-lymphocyte ratio(NLR)(odds ratio[OR]=1.055,95%confidence interval[95%CI]1.025–1.086),lactate dehydrogenase(LDH)(OR=1.004,95%CI 1.002–1.006)and serum creatinine(s Cr)(OR=1.018,95%CI 1.008–1.028),were associated with a higher risk of mortality.CONCLUSION:The CAP patients in AID-induced ICH had a high mortality.A significant relationship was demonstrated between the factors of NLR,LDH,s Cr and mortality risk in these patients.
文摘Hepatocellular carcinoma(HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year,it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients,however,there is a high risk of recurrence in postoperativeHCC. In clinical practice,there exists an urgent need for valid prognostic markers to identify patients with prognosis,hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients.
文摘AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy’s rule and the most important predictors for outcome. METHODS: The Adverse Drug Reaction Advisory Committee was set up in 1997 in our hospital to identify all suspicions of DILD following a structured prospective report form. Liver damage was divided into hepatocellular, cholestatic, and mixed types according to laboratory and histologic criteria when available. Further evaluation of causality assessment was performed. RESULTS: From January 1997 to December 2004, 265 patients were diagnosed with DILD,and 140 (52.8%) of them were female. hepatocellular damage was the most common (72.1%), the incidence of death was 9.9% in patients with hepatocellular damage and 9.5% in patients with cholestatic/mixed damage (P < 0.05). There was no difference in age of dead and recovered patients. The proportion of females and males was similar in recovered and dead patients, no difference was observed in duration of treatment between the two groups. The serum total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and aspartate transaminase (AST) (P = 0.013) values were higher in dead patients than in recovered patients. Chinese herbal medicine was the most frequently prescribed, accounting for 24.2% of the whole series. However, antitubercular drugs (3.4%) were found to be the primary etiological factor for fetal DILD. Factors associated with the development of fulminanthepatic failure were hepatic encephalopathy (OR = 43.66, 95% CI = 8.47-224.95, P < 0.0001), ascite (OR = 28.48, 95% CI = 9.26-87.58, P < 0.0001), jaundice (OR = 11.43, 95% CI = 1.52-85.96, P = 0.003), alcohol abuse (OR = 3.83, 95% CI = 1.26-11.67, P = 0.035) and direct bilirubin (OR = 1.93, 95% CI = 1.25-2.58, P = 0.012). CONCLUSION: Death occurs in 9.8% of patients with DILD. Chinese herbal medicine stands out as the most common drug for DILD. While an
文摘AIM To evaluate the role of albumin at the time of ulcerative colitis(UC) diagnosis in predicting the clinical course of disease.METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia(i.e.,≤ 3.5 gm/dl) or normal albumin levels(i.e.,> 3.5 gm/dl) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined asalbumin level ≤ 3.5 g/dl at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids(CS),thiopurines,anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients,but 92(11.4%) patients did not have their albumin levels checked at the time of UC diagnosis,and they were excluded. A total of 710 patients,who had albumin levels checked at time of UC diagnosis,were included in our study. Amongst them,536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use(adjusted HR = 1.7,95%CI: 1.3-2.3),higher likelihood of thiopurine or anti-TNF use(adjusted HR = 1.72,95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients,but it was not statistically significant(Adjusted HR = 1.7,95%CI: 0.90-3.25).CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis.
基金supported by grants from the Ministry of Science and Technology of China(2011CB504304 and 2012CB967003)the National Natural Science Foundation of China(81271902 and 81230045)
文摘Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.
文摘Colorectal cancer(CRC) is the third leading cause of cancer death worldwide, which is consequence of multistep tumorigenesis of several genetic and epigenetic events. Since CRC is mostly asymptomatic until it progresses to advanced stages, the early detection using effective screening approaches, selection of appropriate therapeutic strategies and efficient follow-up programs are essential to reduce CRC mortalities. Biomarker discovery for CRC based on the personalized genotype and clinical information could facilitate the classification of patients with certain types and stages of cancer to tailor preventive and therapeutic approaches. These cancer-related biomarkers should be highly sensitive and specific in a wide range of specimen(s)(including tumor tissues, patients' fluids or stool). Reliable biomarkers which enable the early detection of CRC, can improve early diagnosis, prognosis, treatment response prediction, and recurrence risk. Advances in our understanding of the natural history of CRC have led to the development of different CRC associated molecular and cellular biomarkers. This review highlights the new trends and approaches in CRC biomarker discovery, which could be potentially used for early diagnosis, development of new therapeutic approaches and follow-up of patients.
文摘Colorectal cancer remains one of the most common and lethal malignancies worldwide despite the use of various therapeutic strategies. A better understanding of the mechanisms responsible for tumor initiation and progression is essential for the development of novel, more powerful therapies. The traditional, so-called “stochastic model” of tumor development, which assumes that each cancer cell is tumorigenic, has been deeply challenged during the past decade by the identification of cancer stem cells (CSCs), a biologically distinct subset of cells within the bulk of tumor mass. This discovery led to the development of the hierarchical model of tumorigenesis which assumes that only CSCs have the ability to initiate tumor growth, both at primary and metastatic sites. This model implies that the elimination of all CSCs is fundamental to eradicate tumors and that failure to do so might be responsible for the occurrence of relapses and/or metastases frequently observed in the clinical management of colorectal cancer patients. Identification and isolation of CSCs is essential for a better understanding of their role in the tumorigenetic process and for the development of CSC-specific therapies. Several methods have been used for this purpose and many efforts have been focused on the identification of specific CSC-surface markers. This review provides an overview of the proposed roles of CSC in human colorectal tumorigenesis focusing on the most important molecules identified as CSC-specific markers in colorectal cancer and on the potential strategies for the development of CSC-targeted therapy.
文摘目的联合检测肺腺癌患者外周血中细胞角蛋白(cytokeratin,CK,肺腺癌循环肿瘤细胞阳性)和CD133基因(肺癌干细胞标志物)的表达,探讨二者在评估肺腺癌预后的临床价值。方法选取2014年6月至2016年6月昆明总医院心胸外科和宣威市第一人民医院心胸外科的178例未化疗的肺腺癌手术患者,中位年龄59岁,其中男性78例,女性100例。收集患者术前外周血标本10 m L,细胞块法和CK(免疫细胞化学法)用于检测CTC,PCR法用于检测CD133表达。免疫组化法检测肺腺癌组织中CK、Vimentin(Vim)、TTF-1、Ki-67、CD133的表达,并分析与外周血CK和CD133表达的关系。根据外周血CK和CD133的检测结果,将病例分为CK/CD133双阳性组和非双阳性组,统计学分析两组间临床病理因素的差异。结果 178例肺腺癌患者外周血CTC(CK阳性)的检出率为48.3%(86/178),与癌组织中Ki-67、Vim表达显著正相关(P<0.05);外周血的CD133阳性表达率为66.9%(119/178),与癌组织Vim、CD133表达显著正相关(P<0.05);外周血CK/CD133双阳组53例(29.8%),双阳组淋巴结转移率显著增高,肺腺癌组织学分化级别显著降低,临床分期显著提高,转移率显著增高(P<0.05)。结论肺腺癌患者外周血中CK与CD133双阳性表达提示外周血存在干性特征的循环肿瘤细胞,表明预后不良,联合检测CK与CD133可用于肺腺癌患者预后监测和指导治疗。
基金supported by grants from the National Natural Science Foundation of China(81201896 and 81071884)the Research Fund for the Doctoral Program of Higher Education of China(20130071110052)
文摘BACKGROUND： Previous researches in pancreatic cancer demonstrated a negative correlation between secreted protein acidic and rich in cysteine （SPARC） expression in primary tumor and survival, but not for SPARC expression in lymph node. In the present study, we aimed to evaluate the SPARC expression in various types of tissues and its impact on patients＇ prognosis. METHODS： The expression of SPARC was examined by immunohistochemistry in resected pancreatic cancer specimens. Kaplan-Meier analyses and Cox proportional hazards regres- sion were applied to assess the mortality risk. RESULTS： A total of 222 tissue samples from 73 patients were collected to evaluate the SPARC expression, which included 73 paired primary tumor and adjacent normal tissues, 38 paired metastatic and normal lymph nodes. The proportion of posi tive SPARC expression in metastatic lymph node was high （32/38）, whereas in normal lymph node it was negative （0/38）. Positive SPARC expression in primary tumor cells was associ- ated with a significantly decreased overall survival （P=0.007） and disease-free survival （P=0.003）, whereas in other types of tissues it did not show a predictive role for prognosis. Univariate and multivariate analyses both confirmed this significance. CONCLUSION： SPARC can serve a dual function role as both predictor for prognosis and potentially biomarker for lymph node metastasis in resected pancreatic cancer patients.
