Colorectal cancer(CRC) is the second leading cause of cancer worldwide. CRC is still associated with a poor prognosis among patients with advanced disease. On the contrary, due to its slow progression from detectable ...Colorectal cancer(CRC) is the second leading cause of cancer worldwide. CRC is still associated with a poor prognosis among patients with advanced disease. On the contrary, due to its slow progression from detectable precancerous lesions, the prognosis for patients with early stages of CRC is encouraging. While most robust methods are invasive and costly, actual patient-friendly screening methods for CRC suffer of lack of sensitivity and specificity. Therefore, the development of sensitive, non-invasive and cost-effective methods for CRC detection and prognosis are necessary for increasing the chances of a cure. Beyond its beneficial functions for the host, increasing evidence suggests that the intestinal microbiota is a key factor associated with carcinogenesis. Many clinical studies have reported a disruption in the gut microbiota balance and an alteration in the faecal metabolome of CRC patients, suggesting the potential use of a microbialbased test as a non-invasive diagnostic and/or prognostic tool for CRC screening. This review aims to discuss the microbial signatures associated with CRC known to date, including dysbiosis and faecal metabolome alterations, andthe potential use of microbial variation markers for noninvasive early diagnosis and/or prognostic assessment of CRC and advanced adenomas. We will finally discuss the possible use of these markers as predicators for treatment response and their limitations.展开更多
Background The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their releva...Background The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis.Methods We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed.Results Minichromosome maintenance complex component 2 （MCM2） and cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis （HR=0.63, 95%CI： 0.46-0.86）.Cyclin A expression above the median predicted an improved patient prognosis （HR=0.71, 95%CI： 0.53-0.95）. For mismatch repair deficiency and transforming growth factor β receptor type Ⅱ （TGFBRII） overexpression there was a borderline association with a poorer prognosis （HR=0.69, 95%C/： 0.46-1.04 and HR=2.11, 95%CI： 1.02-4.40,respectively）. No apparent associations were found for other markers.Conclusion This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.展开更多
Objective The objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension （IPAH）.Date sources We searched literature from PubMed and CNKI databases both ...Objective The objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension （IPAH）.Date sources We searched literature from PubMed and CNKI databases both in English and Chinese up to 2013.Study selection Data about mortality and cut-off value are from clinical trials and identified by analysis.Results IPAH is an unexplained,progressive,and rare disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance.The diagnosis is difficult,mortality of IPAH is high,and the survival periods are only 2-3 years after diagnosis.Investigations in recent years have identified a range of prognostic markers for IPAH,including the 6-minute walking test,red blood cell distribution width,and platelet levels,as well as imaging findings.Changes in these markers are important sources of information to predict the prognosis of patients with IPAH,which carries significant benefits for treatment planning.Conclusion Even though the prognosis of IPAH has been investigated,the mortality is also high.More accurate and meaningful assessment for the prognosis of IPAH is required.展开更多
Epigenetic is the study of those alterations regulating gene expression without altering DNA sequence and inherited by transmission through cell division. Mutational and epimutational events that alterate cellular gro...Epigenetic is the study of those alterations regulating gene expression without altering DNA sequence and inherited by transmission through cell division. Mutational and epimutational events that alterate cellular growth and division are combined in carcinogenesis. Advances in genome and epigenome-wide analysis identify DNA hypomethylation,hypermethylation of tumor suppressor genes,aberrant histone modifications and/or specific mi RNA expression profiles to contribute to tumor initiation and progression. The major challenge for cancer researchers is to enlighten the complex relationship between the epigenetic and genetic machinery in order tooptimize combined therapies,reducing chemoresistance and minimizing adverse effects in cancer patients. In this review we will cover many distinct aspects of epigenetic phenomenon. Firstly,we will globally explain the most common epigenetic events and their effects on gene expression regulation. Secondly,we will review the evidence of the correlation between epigenetics and cancer progression,focusing in particular on the effect of aberrant hypo- and hyper-methylation. We will also consider the main methods currently used for methylation analysis,covering both locus-specific technologies and genome-wide analysis. Finally,we will discuss the introduction of novel epigenetic drugs in combination with conventional treatments in order to develop more effective cancer therapies. Such information could help in understanding the important role of epigenetics in cancer.展开更多
Chemotherapy with improved effect in patients with metastatic pancreatic cancer has recently been established, launching a new era for patients with this very aggressive disease. FOLFIRINOX and gemcitabine plus nab-pa...Chemotherapy with improved effect in patients with metastatic pancreatic cancer has recently been established, launching a new era for patients with this very aggressive disease. FOLFIRINOX and gemcitabine plus nab-paclitaxel are different regimens, both capable of stabilizing the disease, thus increasing the number of patients who can reach second line and even third line of treatment. Concurrently, new windows of opportunity open for nutritional support and other therapeutic interventions, improving quality of life. Also pancreatic surgery has changed significantly during the latest years. Extended operations, including vascular/multivisceral resections are frequently performed in specialized centers, pushing borders of resectability. Potentially curative treatment including neoadjuvant and adjuvant chemotherapy is offered new patient groups. Translational research is the basis for the essential understanding of the ongoing development. Even thou biomarkers for clinical management of patients with periampullary tumors have almost been lacking, biomarker driven trials are now in progress. New insight is constantly made available for clinicians; one recent example is selection of patients for gemcitabine treatment based on the expression level of the human equilibrium nucleoside transporter 1. An example of new diagnostic tools is identification of early pancreatic cancer patients by a three-biomarker panel in urine: The proteins lymphatic vessel endothelial hyaluronan receptor 1, regenerating gene 1 alpha and translation elongation factor 1 alpha. Requirement of treatment guideline revisions is intensifying, as combined chemotherapy regimens result in unexpected advantages. The European Study Group for Pancreatic Cancer 4 trial outcome is an illustration: Addition of capecitabine in the adjuvant setting improved overall survival more than expected from the effect in advanced disease. Rapid implementation of new treatment options is mandatory when progress finally extends to patients with this serious disease.展开更多
Sepsis is one of the leading worldwide causes of morbidity and mortality in critically-ill patients. Prediction of outcome in patients with sepsis requires repeated clinical interpretation of the patients' conditi...Sepsis is one of the leading worldwide causes of morbidity and mortality in critically-ill patients. Prediction of outcome in patients with sepsis requires repeated clinical interpretation of the patients' conditions, clinical assessment of tissue hypoxia and the use of severity scoring systems, because the prognostic categorization accuracy of severity scoring indices alone, is relatively poor. Generally, such categorization depends on the severity of the septic state, ranging from systemic inflammatory response to septic shock. Now, there is no gold standard for the clinical assessment of tissue hypoxia which can be achieved by both global and regional oxygen extractabilities, added to prognostic pro-inflammatory mediators. Because the technology used to identify the genetic make-up of the human being is rapidly advancing, the structure of 30 000 genes which make-up the human DNA bank is now known. This would allow easy prognostic categorization of critically-ill patients including those suffering from sepsis. The present review spots lights on the main severity scoring systems used for outcome prediction in septic patients. For morbidity prediction, it discusses the Multiple Organ Dysfunction score, the sequential organ failure assessment score, and the logistic organdysfunction score. For mortality/survival prediction, it discusses the Acute Physiology and Chronic Health Evaluation scores, the Therapeutic Intervention Scoring System, the Simplified acute physiology score and the Mortality Probability Models. An ideal severity scoring system for prognostic categorization of patients with systemic sepsis is far from being reached. Scoring systems should be used with repeated clinical interpretation of the patients' conditions, and the assessment of tissue hypoxia in order to attain satisfactory discriminative performance and calibration power.展开更多
棘皮动物微管相关类蛋白4-间变性淋巴瘤激酶(echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase,EML4-ALK)融合占非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的3%-5%。随着对该驱动基因的深入研究...棘皮动物微管相关类蛋白4-间变性淋巴瘤激酶(echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase,EML4-ALK)融合占非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的3%-5%。随着对该驱动基因的深入研究,以Crizotinib为代表的ALK抑制剂逐渐被开发并应用于临床。然而,不同患者对ALK靶向治疗的反应存在差异,且多数ALK靶向治疗患者最终会不可避免地出现耐药,导致肿瘤进展。利用预后标志物监测患者疗效及时改变治疗方案,以及根据耐药机制选择个体化的后续治疗,可以有效地改善患者的预后。本文将对ALK抑制剂的耐药机制以及相关的预后标志物展开综述,探讨ALK靶向治疗疗效预测以及耐药患者后续治疗方案的选择。展开更多
基金Supported by Inserm and UniversitéClermont Auvergne(UMR 1071)INRA(USC-2018)grants from"Conseil regional Auvergne-Rhones-Alpes"and FDER/CPER
文摘Colorectal cancer(CRC) is the second leading cause of cancer worldwide. CRC is still associated with a poor prognosis among patients with advanced disease. On the contrary, due to its slow progression from detectable precancerous lesions, the prognosis for patients with early stages of CRC is encouraging. While most robust methods are invasive and costly, actual patient-friendly screening methods for CRC suffer of lack of sensitivity and specificity. Therefore, the development of sensitive, non-invasive and cost-effective methods for CRC detection and prognosis are necessary for increasing the chances of a cure. Beyond its beneficial functions for the host, increasing evidence suggests that the intestinal microbiota is a key factor associated with carcinogenesis. Many clinical studies have reported a disruption in the gut microbiota balance and an alteration in the faecal metabolome of CRC patients, suggesting the potential use of a microbialbased test as a non-invasive diagnostic and/or prognostic tool for CRC screening. This review aims to discuss the microbial signatures associated with CRC known to date, including dysbiosis and faecal metabolome alterations, andthe potential use of microbial variation markers for noninvasive early diagnosis and/or prognostic assessment of CRC and advanced adenomas. We will finally discuss the possible use of these markers as predicators for treatment response and their limitations.
文摘Background The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis.Methods We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed.Results Minichromosome maintenance complex component 2 （MCM2） and cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis （HR=0.63, 95%CI： 0.46-0.86）.Cyclin A expression above the median predicted an improved patient prognosis （HR=0.71, 95%CI： 0.53-0.95）. For mismatch repair deficiency and transforming growth factor β receptor type Ⅱ （TGFBRII） overexpression there was a borderline association with a poorer prognosis （HR=0.69, 95%C/： 0.46-1.04 and HR=2.11, 95%CI： 1.02-4.40,respectively）. No apparent associations were found for other markers.Conclusion This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.
基金This work was supported by a grant from the Beijing Natural Science Foundation （No. 7121014）.
文摘Objective The objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension （IPAH）.Date sources We searched literature from PubMed and CNKI databases both in English and Chinese up to 2013.Study selection Data about mortality and cut-off value are from clinical trials and identified by analysis.Results IPAH is an unexplained,progressive,and rare disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance.The diagnosis is difficult,mortality of IPAH is high,and the survival periods are only 2-3 years after diagnosis.Investigations in recent years have identified a range of prognostic markers for IPAH,including the 6-minute walking test,red blood cell distribution width,and platelet levels,as well as imaging findings.Changes in these markers are important sources of information to predict the prognosis of patients with IPAH,which carries significant benefits for treatment planning.Conclusion Even though the prognosis of IPAH has been investigated,the mortality is also high.More accurate and meaningful assessment for the prognosis of IPAH is required.
文摘Epigenetic is the study of those alterations regulating gene expression without altering DNA sequence and inherited by transmission through cell division. Mutational and epimutational events that alterate cellular growth and division are combined in carcinogenesis. Advances in genome and epigenome-wide analysis identify DNA hypomethylation,hypermethylation of tumor suppressor genes,aberrant histone modifications and/or specific mi RNA expression profiles to contribute to tumor initiation and progression. The major challenge for cancer researchers is to enlighten the complex relationship between the epigenetic and genetic machinery in order tooptimize combined therapies,reducing chemoresistance and minimizing adverse effects in cancer patients. In this review we will cover many distinct aspects of epigenetic phenomenon. Firstly,we will globally explain the most common epigenetic events and their effects on gene expression regulation. Secondly,we will review the evidence of the correlation between epigenetics and cancer progression,focusing in particular on the effect of aberrant hypo- and hyper-methylation. We will also consider the main methods currently used for methylation analysis,covering both locus-specific technologies and genome-wide analysis. Finally,we will discuss the introduction of novel epigenetic drugs in combination with conventional treatments in order to develop more effective cancer therapies. Such information could help in understanding the important role of epigenetics in cancer.
文摘Chemotherapy with improved effect in patients with metastatic pancreatic cancer has recently been established, launching a new era for patients with this very aggressive disease. FOLFIRINOX and gemcitabine plus nab-paclitaxel are different regimens, both capable of stabilizing the disease, thus increasing the number of patients who can reach second line and even third line of treatment. Concurrently, new windows of opportunity open for nutritional support and other therapeutic interventions, improving quality of life. Also pancreatic surgery has changed significantly during the latest years. Extended operations, including vascular/multivisceral resections are frequently performed in specialized centers, pushing borders of resectability. Potentially curative treatment including neoadjuvant and adjuvant chemotherapy is offered new patient groups. Translational research is the basis for the essential understanding of the ongoing development. Even thou biomarkers for clinical management of patients with periampullary tumors have almost been lacking, biomarker driven trials are now in progress. New insight is constantly made available for clinicians; one recent example is selection of patients for gemcitabine treatment based on the expression level of the human equilibrium nucleoside transporter 1. An example of new diagnostic tools is identification of early pancreatic cancer patients by a three-biomarker panel in urine: The proteins lymphatic vessel endothelial hyaluronan receptor 1, regenerating gene 1 alpha and translation elongation factor 1 alpha. Requirement of treatment guideline revisions is intensifying, as combined chemotherapy regimens result in unexpected advantages. The European Study Group for Pancreatic Cancer 4 trial outcome is an illustration: Addition of capecitabine in the adjuvant setting improved overall survival more than expected from the effect in advanced disease. Rapid implementation of new treatment options is mandatory when progress finally extends to patients with this serious disease.
文摘Sepsis is one of the leading worldwide causes of morbidity and mortality in critically-ill patients. Prediction of outcome in patients with sepsis requires repeated clinical interpretation of the patients' conditions, clinical assessment of tissue hypoxia and the use of severity scoring systems, because the prognostic categorization accuracy of severity scoring indices alone, is relatively poor. Generally, such categorization depends on the severity of the septic state, ranging from systemic inflammatory response to septic shock. Now, there is no gold standard for the clinical assessment of tissue hypoxia which can be achieved by both global and regional oxygen extractabilities, added to prognostic pro-inflammatory mediators. Because the technology used to identify the genetic make-up of the human being is rapidly advancing, the structure of 30 000 genes which make-up the human DNA bank is now known. This would allow easy prognostic categorization of critically-ill patients including those suffering from sepsis. The present review spots lights on the main severity scoring systems used for outcome prediction in septic patients. For morbidity prediction, it discusses the Multiple Organ Dysfunction score, the sequential organ failure assessment score, and the logistic organdysfunction score. For mortality/survival prediction, it discusses the Acute Physiology and Chronic Health Evaluation scores, the Therapeutic Intervention Scoring System, the Simplified acute physiology score and the Mortality Probability Models. An ideal severity scoring system for prognostic categorization of patients with systemic sepsis is far from being reached. Scoring systems should be used with repeated clinical interpretation of the patients' conditions, and the assessment of tissue hypoxia in order to attain satisfactory discriminative performance and calibration power.
文摘棘皮动物微管相关类蛋白4-间变性淋巴瘤激酶(echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase,EML4-ALK)融合占非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的3%-5%。随着对该驱动基因的深入研究,以Crizotinib为代表的ALK抑制剂逐渐被开发并应用于临床。然而,不同患者对ALK靶向治疗的反应存在差异,且多数ALK靶向治疗患者最终会不可避免地出现耐药,导致肿瘤进展。利用预后标志物监测患者疗效及时改变治疗方案,以及根据耐药机制选择个体化的后续治疗,可以有效地改善患者的预后。本文将对ALK抑制剂的耐药机制以及相关的预后标志物展开综述,探讨ALK靶向治疗疗效预测以及耐药患者后续治疗方案的选择。
