AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this dru...AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.展开更多
Cells usually undergo a long journey of evolution during the progression from normal to precancerous cells and finally to full-fledged cancer cells. Multiple genomic aberrations are acquired during this journey that c...Cells usually undergo a long journey of evolution during the progression from normal to precancerous cells and finally to full-fledged cancer cells. Multiple genomic aberrations are acquired during this journey that could either act as drivers to confer significant growth advantages or act as passengers with little effect on the tumor growth. Recent advances in sequencing technology have made it feasible to decipher the evolutionary course of a cancer cell on a genome-wide level by evaluating the relative number of mutated alleles. Novel terms such as chromothripsis and chromoplexy have been introduced to describe the newly identified patterns of cancer genome evolution. These new insights have greatly expanded our understanding of the initiation and progression of cancers,which should aid in improving the efficiency of cancer management and treatment.展开更多
Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bear-ing UGT1A1*28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of i...Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bear-ing UGT1A1*28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1*28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UG-T1A1*28 (TA 7/7), while UGT1A1*6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1*28 polymorphism (TA 6/7) as well as the UG-T1A1*6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinote-can dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1*28 and UGT1A1*6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinote-can. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1*28 and UGT1A1*6 polymorphisms.展开更多
BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incid...BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.展开更多
In clinical practice, patients undergoing chemotherapy display prominent individual differences, adverse reactions and sensitivity to antineoplastic therapy. Those differences are caused by individual genetic polymorp...In clinical practice, patients undergoing chemotherapy display prominent individual differences, adverse reactions and sensitivity to antineoplastic therapy. Those differences are caused by individual genetic polymorphism of related genes. Genetic variation can induce distinct alterations of drug-metabolizing enzymes, drug transporters, drug targets and DNA repair enzymes and thereby influence the ability of the drugs to reach their target sites. This article reviews in detail the potential interactions mentioned above.展开更多
Inflammation has been considered as one of the hallmarks of cancer,and chronic hepatitis is a major cause of liver cancer.This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will ...Inflammation has been considered as one of the hallmarks of cancer,and chronic hepatitis is a major cause of liver cancer.This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research,including cellular interaction,cytokines,microRNA and stem cells.All of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma.展开更多
文摘AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.
文摘Cells usually undergo a long journey of evolution during the progression from normal to precancerous cells and finally to full-fledged cancer cells. Multiple genomic aberrations are acquired during this journey that could either act as drivers to confer significant growth advantages or act as passengers with little effect on the tumor growth. Recent advances in sequencing technology have made it feasible to decipher the evolutionary course of a cancer cell on a genome-wide level by evaluating the relative number of mutated alleles. Novel terms such as chromothripsis and chromoplexy have been introduced to describe the newly identified patterns of cancer genome evolution. These new insights have greatly expanded our understanding of the initiation and progression of cancers,which should aid in improving the efficiency of cancer management and treatment.
基金Supported by National Natural Science Foundation Project,Grants No.30971579Capital Development Foundation,No.2007-2029
文摘Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bear-ing UGT1A1*28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1*28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UG-T1A1*28 (TA 7/7), while UGT1A1*6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1*28 polymorphism (TA 6/7) as well as the UG-T1A1*6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinote-can dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1*28 and UGT1A1*6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinote-can. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1*28 and UGT1A1*6 polymorphisms.
基金National Key R&D Program of China,No.2019YFB1309704。
文摘BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.
文摘In clinical practice, patients undergoing chemotherapy display prominent individual differences, adverse reactions and sensitivity to antineoplastic therapy. Those differences are caused by individual genetic polymorphism of related genes. Genetic variation can induce distinct alterations of drug-metabolizing enzymes, drug transporters, drug targets and DNA repair enzymes and thereby influence the ability of the drugs to reach their target sites. This article reviews in detail the potential interactions mentioned above.
文摘Inflammation has been considered as one of the hallmarks of cancer,and chronic hepatitis is a major cause of liver cancer.This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research,including cellular interaction,cytokines,microRNA and stem cells.All of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma.
