Synchronous colorectal carcinoma refers to more than one primary colorectal carcinoma detected in a single patient at initial presentation.A literature review has shown that the prevalence of the disease is approximat...Synchronous colorectal carcinoma refers to more than one primary colorectal carcinoma detected in a single patient at initial presentation.A literature review has shown that the prevalence of the disease is approximately 3.5%of all colorectal carcinomas.This disease has a male to female ratio of 1.8:1.The mean age at presentation of patients with synchronous colorectal cancer is in the early half of the seventh decade.Patients with inflammatory bowel diseases(ulcerative colitis and Crohn’s disease),hereditary non-polyposis colorectal cancer,familial adenomatous polyposis and serrated polyps/hyperplastic polyposis are known to have a higher risk of synchronous colorectal carcinoma.These predisposing factors account for slightly more than 10%of synchronous colorectal carcinomas.Synchronous colorectal carcinoma is more common in the right colon when compared to solitary colorectal cancer.On pathological examination,some synchronous colorectal carcinomas are mucinous adenocarcinomas.They are usually associated with adenomas and metachronous colorectal carcinomas.Most of the patients with synchronous colorectal cancer have two carcinomas but up to six have been reported in one patient.Patients with synchronous colorectal carcinoma havea higher proportion of microsatellite instability cancer than patients with a solitary colorectal carcinoma.Also,limited data have revealed that in many synchronous colorectal carcinomas,carcinomas in the same patient have different patterns of microsatellite instability status,p53 mutation and K-ras mutation.Overall,the prognosis of patients with synchronous colorectal carcinoma is not significantly different from that in patients with solitary colorectal carcinoma,although a marginally better prognosis has been reported in patients with synchronous colorectal carcinoma in some series.A different management approach and long-term clinical follow-up are recommended for some patients with synchronous colorectal cancer.展开更多
Irinotecan is the second line chemotherapy for advanced stage colorectal cancer (CRC) after failure of first line chemotherapy with oxaliplatin and 5-fluorouracil. The aim of this review is to analyse the data on irin...Irinotecan is the second line chemotherapy for advanced stage colorectal cancer (CRC) after failure of first line chemotherapy with oxaliplatin and 5-fluorouracil. The aim of this review is to analyse the data on irinotecan as second line chemotherapy for advanced CRC and the potential roles of the molecular markers, p53 and vascular endothelial growth factor (VEGF) in the management of advanced CRC. Thus, the English literature from 1980 to 2008 concerning irinotecan, p53, VEGF and CRC was reviewed. On review, Phase and clinical trials showed thatirinotecan improves pain-free survival, quality of life, 1-year survival, progression-free survival and overall survival in advanced CRC. p53 and VEGF were expressed in CRC and had a predictive power of aggressive clinical behaviour in CRC. Irinotecan sensitizes p53 wild type, mutant and null cells to Fasmediated cell apoptosis in CRC cells. Wild type p53 cells were more sensitive to irinotecan than mutated p53. Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is onlylimited by irinotecan toxicity levels. To conclude, irinotecan improves the patient's quality of life and the survival rates of patients with advanced CRC. p53 and VEGF status of the patients' tumour is likely to affect the responsiveness of CRC to irinotecan. It is recommended that studies of the expression of these molecular markers in relation to chemoresponsiveness ofirinotecan should be carried out for better management of patients with advanced CRC.展开更多
With the understanding of the complex interaction between the tumour microenvironment and immunotherapy,there is increasing interest in the role of immune regulators in the treatment of head and neck squamous cell car...With the understanding of the complex interaction between the tumour microenvironment and immunotherapy,there is increasing interest in the role of immune regulators in the treatment of head and neck squamous cell carcinoma(HNSCC).Activation of T cells and immune checkpoint molecules is important for the immune response to cancers.Immune checkpoint molecules include cytotoxic T lymphocyte antigen 4(CTLA-4),programmed death 1(PD-1),T-cell immunoglobulin mucin protein 3(TIM-3),lymphocyte activation gene 3(LAG-3),T cell immunoglobin and immunoreceptor tyrosine-based inhibitory motif(TIGIT),glucocorticoid-induced tumour necrosis factor receptor(GITR)and V-domain Ig suppressor of T cell activation(VISTA).Many clinical trials using checkpoint inhibitors,as both monotherapies and combination therapies,have been initiated targeting these immune checkpoint molecules.This review summarizes the functional mechanism and use of various immune checkpoint molecules in HNSCC,including monotherapies and combination therapies,and provides better treatment options for patients with HNSCC.展开更多
AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expressio...AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was stud-ied by using the RNA interference (RNAi) approach through transfecting the GAEC1 -overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1 -targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1 -targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10 ) and upregulation of trinucleotide repeat containing 6C (TNRC6C ) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 ± 16.33 vs 12.62 ± 12.44, P = 0.032). No significant correction was observed among the TNRC6C protein expression level and the clinocopathologcial features of esophageal squamous cell carcinoma. CONCLUSION: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma.展开更多
文摘Synchronous colorectal carcinoma refers to more than one primary colorectal carcinoma detected in a single patient at initial presentation.A literature review has shown that the prevalence of the disease is approximately 3.5%of all colorectal carcinomas.This disease has a male to female ratio of 1.8:1.The mean age at presentation of patients with synchronous colorectal cancer is in the early half of the seventh decade.Patients with inflammatory bowel diseases(ulcerative colitis and Crohn’s disease),hereditary non-polyposis colorectal cancer,familial adenomatous polyposis and serrated polyps/hyperplastic polyposis are known to have a higher risk of synchronous colorectal carcinoma.These predisposing factors account for slightly more than 10%of synchronous colorectal carcinomas.Synchronous colorectal carcinoma is more common in the right colon when compared to solitary colorectal cancer.On pathological examination,some synchronous colorectal carcinomas are mucinous adenocarcinomas.They are usually associated with adenomas and metachronous colorectal carcinomas.Most of the patients with synchronous colorectal cancer have two carcinomas but up to six have been reported in one patient.Patients with synchronous colorectal carcinoma havea higher proportion of microsatellite instability cancer than patients with a solitary colorectal carcinoma.Also,limited data have revealed that in many synchronous colorectal carcinomas,carcinomas in the same patient have different patterns of microsatellite instability status,p53 mutation and K-ras mutation.Overall,the prognosis of patients with synchronous colorectal carcinoma is not significantly different from that in patients with solitary colorectal carcinoma,although a marginally better prognosis has been reported in patients with synchronous colorectal carcinoma in some series.A different management approach and long-term clinical follow-up are recommended for some patients with synchronous colorectal cancer.
基金Supported by A research fund of Queensland Cancer Council and Pathology Scholarship from Royal College of Pathologists of Australasia
文摘Irinotecan is the second line chemotherapy for advanced stage colorectal cancer (CRC) after failure of first line chemotherapy with oxaliplatin and 5-fluorouracil. The aim of this review is to analyse the data on irinotecan as second line chemotherapy for advanced CRC and the potential roles of the molecular markers, p53 and vascular endothelial growth factor (VEGF) in the management of advanced CRC. Thus, the English literature from 1980 to 2008 concerning irinotecan, p53, VEGF and CRC was reviewed. On review, Phase and clinical trials showed thatirinotecan improves pain-free survival, quality of life, 1-year survival, progression-free survival and overall survival in advanced CRC. p53 and VEGF were expressed in CRC and had a predictive power of aggressive clinical behaviour in CRC. Irinotecan sensitizes p53 wild type, mutant and null cells to Fasmediated cell apoptosis in CRC cells. Wild type p53 cells were more sensitive to irinotecan than mutated p53. Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is onlylimited by irinotecan toxicity levels. To conclude, irinotecan improves the patient's quality of life and the survival rates of patients with advanced CRC. p53 and VEGF status of the patients' tumour is likely to affect the responsiveness of CRC to irinotecan. It is recommended that studies of the expression of these molecular markers in relation to chemoresponsiveness ofirinotecan should be carried out for better management of patients with advanced CRC.
文摘With the understanding of the complex interaction between the tumour microenvironment and immunotherapy,there is increasing interest in the role of immune regulators in the treatment of head and neck squamous cell carcinoma(HNSCC).Activation of T cells and immune checkpoint molecules is important for the immune response to cancers.Immune checkpoint molecules include cytotoxic T lymphocyte antigen 4(CTLA-4),programmed death 1(PD-1),T-cell immunoglobulin mucin protein 3(TIM-3),lymphocyte activation gene 3(LAG-3),T cell immunoglobin and immunoreceptor tyrosine-based inhibitory motif(TIGIT),glucocorticoid-induced tumour necrosis factor receptor(GITR)and V-domain Ig suppressor of T cell activation(VISTA).Many clinical trials using checkpoint inhibitors,as both monotherapies and combination therapies,have been initiated targeting these immune checkpoint molecules.This review summarizes the functional mechanism and use of various immune checkpoint molecules in HNSCC,including monotherapies and combination therapies,and provides better treatment options for patients with HNSCC.
基金Supported by The General Research Fund, offered by Research Grant Council of Hong Kong to Tang JCO and Lam AKY, PolyU5627/08MGriffith Health Institute Project Grant
文摘AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was stud-ied by using the RNA interference (RNAi) approach through transfecting the GAEC1 -overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1 -targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1 -targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10 ) and upregulation of trinucleotide repeat containing 6C (TNRC6C ) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 ± 16.33 vs 12.62 ± 12.44, P = 0.032). No significant correction was observed among the TNRC6C protein expression level and the clinocopathologcial features of esophageal squamous cell carcinoma. CONCLUSION: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma.