AIM： Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma （EWDA）, is characterized by its benign microscopic appearance in contrast to its aggressive be...AIM： Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma （EWDA）, is characterized by its benign microscopic appearance in contrast to its aggressive behavior. In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA, we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products. METHODS： Clinicopathological features, including preoperative biopsy diagnosis, were reviewed. Using immunohitstochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected.RESULT： Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion, lymph node metastasis was not present and none of the patients died of the lesions （mean follow-up period, 56 too）. All 9 cases of EWDA could be classified into gastric phenotype （5 lesions） and intestinal phenotype （4 lesions）. The former resembled gastric foveolar epithelium, mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cellsand their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nulcear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein. CONCLUSION： Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c-erbB-2 protein over-expression. Because of its resemblance to normal gastric mucosa or mucosa with intestinal metaplasia, EWDA is often misdiagnosed. To prevent the misdiagnosis of such lesions, the clinical and pathologic characteristics should be taken into consideration.展开更多
Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologic...Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologically confirmed GA(low-grade:n=154;high-grade:n=438)from January 2008 to March 2018 who were divided into training(n=450)and validation(n=142)sets according to the time of computed tomography(CT)examination.Radiomic features were extracted from the portal venous phase CT images.The Mann-Whitney U test and the least absolute shrinkage and selection operator(LASSO)regression model were used for feature selection,data dimension reduction and radiomics signature construction.Multivariable logistic regression analysis was applied to develop the prediction model.The radiomics signature and independent clinicopathologic risk factors were incorporated and presented as a radiomics nomogram.The performance of the nomogram was assessed with respect to its calibration and discrimination.Results:A radiomics signature containing 12 selected features was significantly associated with the histologic grade of GA(P<0.001 for both training and validation sets).A nomogram including the radiomics signature and tumor location as predictors was developed.The model showed both good calibration and good discrimination,in which C-index in the training set,0.752[95%confidence interval(95%CI):0.701-0.803];C-index in the validation set,0.793(95%CI:0.711-0.874).Conclusions:This study developed a radiomics nomogram that incorporates tumor location and radiomics signatures,which can be useful in facilitating preoperative individualized prediction of histologic grade of GA.展开更多
AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture,...AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost completely inhibited by preventing the degradation of IkBalpha. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner. CONCLUSION: These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.展开更多
We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adeno-carcinoma. A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduo...We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adeno-carcinoma. A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduodenoscopy (EGD). Initial laboratory data showed the increased serum level of AFP and EGD revealed a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum. The patient underwent radical subtotal gastrectomywith D2 lymph node dissection and Billroth gastrojejunostomy. Histopathological evaluation confirmed double primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant chemotherapy were initiated. No recurrence or distant metastasis was observed at 4 years postoperatively.展开更多
AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell...AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/waf1) of SGC-7901 cells which were treated with various c9, t11-CLA concentrations (25, 50, 100 and 200 micromol.L(-1))of c 9, t 11-CLA for 24 and 48h, with a negative control (0.1% ethane). RESULTS: The cell growth and DNA synthesis of SGC-7901 cells were inhibited by c9, t11-CLA.SGC-7901 cells. Eight day after treatment with various concentrations of c9, t11-CLA mentioned above, the inhibition rates were 5.92%, 20.15%, 75.61% and 82.44%, respectively and inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 micromol.L, 24h) showed significantly less (3)H-TdR incorporation than that in the negative controls (P【0.05 and P【0.01). Immunocytochemical staining demonstrated that SGC-7901 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA (the expression rates were 7.2-3.0%, 24h and 9.1-0.9% at 48h, respectively), Cyclin A (11.0-2.3%, 24h and 8.5-0.5%,48h), B(1) (4.8-1.8% at 24h and 5.5-0.6% at 48h)and D(1) (3.6-1.4% at 24h and 3.7%-0 at 48h) as compared with those in the negative controls(the expressions of PCNA, Cyclin A, B(1) and D(1) were 6.5% at 24h and 9.0% at 48h, 4.2% at 24h and 5.1% at 48h, 9.5% at 24h and 6.0% at 48h,respectively)(P【0.01), whereas the expressions of P16(ink4a) and P21(cip/waf1), cyclin-dependent kinases inhibitors(CDKI), were increased. CONCLUSION: The cell growth and proliferation of SGC-7901 cell is inhibited by c9, t11-CLA via blocking the cell cycle, with reduced expressions of cyclin A,B(1) and D(1) and enhanced expressions of CDKI(P16(ink4a) and p21(cip/waf1)).展开更多
AIM:To investigate the possible correlation of the expression of gonadotropin releasing hormone(GnRH) and its receptor with of proliferating cell nuclear antigen(PCNA) in human gastric adenocarcinoma cell proliferatio...AIM:To investigate the possible correlation of the expression of gonadotropin releasing hormone(GnRH) and its receptor with of proliferating cell nuclear antigen(PCNA) in human gastric adenocarcinoma cell proliferation and differentiation.METHODS:GnRH and its receptor and PCNA were detected in 30 gastric adenocarcinoma by immunohistochemical ABC technique. RESULTS:GnRH and its receptor had the same distribution pattern in gastric adenocarcinoma cells.The positive signal was found mainly in cytoplasm.The content of GnRH and its receptor immunoreative product in high differentiatied adenocarcinoma was significantly higher than those of the other two groups and the low differentiatied adenocarcinoma was the lowest(P< 0.05).PCNA positive signal which was found mainly in nucleus was gradually abated along with the raising of the extent of the differentiation.The differences were significant among the three groups(P< 0.05). In human gastric adenocarcinoma,the expression of GnRH and its receptor was negative correlation with the expression of PCNA(r=0.9).CONCLUSION:GnRH might be involved in the regulation of human gastric adenocarcinoma cell proliferation and differentiation.展开更多
BACKGROUND Albumin-bilirubin(ALBI)score is an indicator of liver dysfunction and is useful for predicting prognosis of hepatocellular carcinomas.Currently,this liver function index has been used to predict prognosis i...BACKGROUND Albumin-bilirubin(ALBI)score is an indicator of liver dysfunction and is useful for predicting prognosis of hepatocellular carcinomas.Currently,this liver function index has been used to predict prognosis in other neoplasms.However,the significance of ALBI score in gastric cancer(GC)after radical resection has not been elucidated.AIM To evaluate the prognostic value of the preoperative ALBI status in patients with GC who received curative treatment.METHODS Patients with GC who underwent curative intended gastrectomy were retrospectively evaluated from our prospective database.ALBI score was calculated as follows:(log10 bilirubin×0.660)+(albumin×-0.085).The receiver operating characteristic curve with area under the curve(AUC)was plotted to evaluate the ability of ALBI score in predicting recurrence or death.The optimal cutoff value was determined by maximizing Youden’s index,and patients were divided into low and high-ALBI groups.The Kaplan-Meier curve was used to analyze the survival,and the log-rank test was used for comparison between groups.RESULTS A total of 361 patients(235 males)were enrolled.The median ALBI value for the entire cohort was-2.89(IQR-3.13;-2.59).The AUC for ALBI score was 0.617(95%CI:0.556-0.673,P<0.001),and the cutoff value was-2.82.Accordingly,211(58.4%)patients were classified as low-ALBI group and 150(41.6%)as high-ALBI group.Older age(P=0.005),lower hemoglobin level(P<0.001),American Society of Anesthesiologists classification III/IV(P=0.001),and D1 lymphadenectomy P=0.003)were more frequent in the high-ALBI group.There was no difference between both groups in terms of Lauren histological type,depth of tumor invasion(pT),presence of lymph node metastasis(pN),and pathologic(pTNM)stage.Major postoperative complication,and mortality at 30 and 90 days were higher in the high-ALBI patients.In the survival analysis,the high-ALBI group had worse disease-free survival(DFS)and overall survival(OS)compared to those with low-ALBI(P<0.001).When stratified by pTNM,the difference between ALBI groups was maintained in stage I/II and stage III CG for DFS(P<0.001 and P=0.021,respectively);and for OS(P<0.001 and P=0.063,respectively).In multivariate analysis,total gastrectomy,advanced pT stage,presence of lymph node metastasis and high-ALBI were independent factors associated with worse survival.CONCLUSION The preoperative ALBI score is able to predict the outcomes of patients with GC,where high-ALBI patients have worse prognosis.Also,ALBI score allows risk stratification of patients within the same pTNM stages,and represents an independent risk factor associated with survival.展开更多
基金Supported by Grants-in-aid for Cancer Research from the Ministry of Education, Science and Culture, Japan and the Fukuoka Cancer Society, Fukuoka, Japan
文摘AIM： Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma （EWDA）, is characterized by its benign microscopic appearance in contrast to its aggressive behavior. In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA, we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products. METHODS： Clinicopathological features, including preoperative biopsy diagnosis, were reviewed. Using immunohitstochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected.RESULT： Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion, lymph node metastasis was not present and none of the patients died of the lesions （mean follow-up period, 56 too）. All 9 cases of EWDA could be classified into gastric phenotype （5 lesions） and intestinal phenotype （4 lesions）. The former resembled gastric foveolar epithelium, mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cellsand their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nulcear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein. CONCLUSION： Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c-erbB-2 protein over-expression. Because of its resemblance to normal gastric mucosa or mucosa with intestinal metaplasia, EWDA is often misdiagnosed. To prevent the misdiagnosis of such lesions, the clinical and pathologic characteristics should be taken into consideration.
基金supported by the National Key Research and Development Program of China(No.2017YFC 1309100)the National Science Fund for Distinguished Young Scholars(No.81925023)the National Natural Science Foundation of China(No.82071892,81771912,81901910)。
文摘Objectives:To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma(GA).Methods:This retrospective study enrolled 592 patients with clinicopathologically confirmed GA(low-grade:n=154;high-grade:n=438)from January 2008 to March 2018 who were divided into training(n=450)and validation(n=142)sets according to the time of computed tomography(CT)examination.Radiomic features were extracted from the portal venous phase CT images.The Mann-Whitney U test and the least absolute shrinkage and selection operator(LASSO)regression model were used for feature selection,data dimension reduction and radiomics signature construction.Multivariable logistic regression analysis was applied to develop the prediction model.The radiomics signature and independent clinicopathologic risk factors were incorporated and presented as a radiomics nomogram.The performance of the nomogram was assessed with respect to its calibration and discrimination.Results:A radiomics signature containing 12 selected features was significantly associated with the histologic grade of GA(P<0.001 for both training and validation sets).A nomogram including the radiomics signature and tumor location as predictors was developed.The model showed both good calibration and good discrimination,in which C-index in the training set,0.752[95%confidence interval(95%CI):0.701-0.803];C-index in the validation set,0.793(95%CI:0.711-0.874).Conclusions:This study developed a radiomics nomogram that incorporates tumor location and radiomics signatures,which can be useful in facilitating preoperative individualized prediction of histologic grade of GA.
基金National Natural Science Foundation of China,No.39770300,30070873the Overseas Chinese Affairs Office of the State Council Foundation,No.98-33
文摘AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost completely inhibited by preventing the degradation of IkBalpha. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner. CONCLUSION: These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.
文摘We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adeno-carcinoma. A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduodenoscopy (EGD). Initial laboratory data showed the increased serum level of AFP and EGD revealed a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum. The patient underwent radical subtotal gastrectomywith D2 lymph node dissection and Billroth gastrojejunostomy. Histopathological evaluation confirmed double primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant chemotherapy were initiated. No recurrence or distant metastasis was observed at 4 years postoperatively.
基金the National Natural Science Foundation of China,No.39870661
文摘AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/waf1) of SGC-7901 cells which were treated with various c9, t11-CLA concentrations (25, 50, 100 and 200 micromol.L(-1))of c 9, t 11-CLA for 24 and 48h, with a negative control (0.1% ethane). RESULTS: The cell growth and DNA synthesis of SGC-7901 cells were inhibited by c9, t11-CLA.SGC-7901 cells. Eight day after treatment with various concentrations of c9, t11-CLA mentioned above, the inhibition rates were 5.92%, 20.15%, 75.61% and 82.44%, respectively and inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 micromol.L, 24h) showed significantly less (3)H-TdR incorporation than that in the negative controls (P【0.05 and P【0.01). Immunocytochemical staining demonstrated that SGC-7901 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA (the expression rates were 7.2-3.0%, 24h and 9.1-0.9% at 48h, respectively), Cyclin A (11.0-2.3%, 24h and 8.5-0.5%,48h), B(1) (4.8-1.8% at 24h and 5.5-0.6% at 48h)and D(1) (3.6-1.4% at 24h and 3.7%-0 at 48h) as compared with those in the negative controls(the expressions of PCNA, Cyclin A, B(1) and D(1) were 6.5% at 24h and 9.0% at 48h, 4.2% at 24h and 5.1% at 48h, 9.5% at 24h and 6.0% at 48h,respectively)(P【0.01), whereas the expressions of P16(ink4a) and P21(cip/waf1), cyclin-dependent kinases inhibitors(CDKI), were increased. CONCLUSION: The cell growth and proliferation of SGC-7901 cell is inhibited by c9, t11-CLA via blocking the cell cycle, with reduced expressions of cyclin A,B(1) and D(1) and enhanced expressions of CDKI(P16(ink4a) and p21(cip/waf1)).
文摘AIM:To investigate the possible correlation of the expression of gonadotropin releasing hormone(GnRH) and its receptor with of proliferating cell nuclear antigen(PCNA) in human gastric adenocarcinoma cell proliferation and differentiation.METHODS:GnRH and its receptor and PCNA were detected in 30 gastric adenocarcinoma by immunohistochemical ABC technique. RESULTS:GnRH and its receptor had the same distribution pattern in gastric adenocarcinoma cells.The positive signal was found mainly in cytoplasm.The content of GnRH and its receptor immunoreative product in high differentiatied adenocarcinoma was significantly higher than those of the other two groups and the low differentiatied adenocarcinoma was the lowest(P< 0.05).PCNA positive signal which was found mainly in nucleus was gradually abated along with the raising of the extent of the differentiation.The differences were significant among the three groups(P< 0.05). In human gastric adenocarcinoma,the expression of GnRH and its receptor was negative correlation with the expression of PCNA(r=0.9).CONCLUSION:GnRH might be involved in the regulation of human gastric adenocarcinoma cell proliferation and differentiation.
文摘BACKGROUND Albumin-bilirubin(ALBI)score is an indicator of liver dysfunction and is useful for predicting prognosis of hepatocellular carcinomas.Currently,this liver function index has been used to predict prognosis in other neoplasms.However,the significance of ALBI score in gastric cancer(GC)after radical resection has not been elucidated.AIM To evaluate the prognostic value of the preoperative ALBI status in patients with GC who received curative treatment.METHODS Patients with GC who underwent curative intended gastrectomy were retrospectively evaluated from our prospective database.ALBI score was calculated as follows:(log10 bilirubin×0.660)+(albumin×-0.085).The receiver operating characteristic curve with area under the curve(AUC)was plotted to evaluate the ability of ALBI score in predicting recurrence or death.The optimal cutoff value was determined by maximizing Youden’s index,and patients were divided into low and high-ALBI groups.The Kaplan-Meier curve was used to analyze the survival,and the log-rank test was used for comparison between groups.RESULTS A total of 361 patients(235 males)were enrolled.The median ALBI value for the entire cohort was-2.89(IQR-3.13;-2.59).The AUC for ALBI score was 0.617(95%CI:0.556-0.673,P<0.001),and the cutoff value was-2.82.Accordingly,211(58.4%)patients were classified as low-ALBI group and 150(41.6%)as high-ALBI group.Older age(P=0.005),lower hemoglobin level(P<0.001),American Society of Anesthesiologists classification III/IV(P=0.001),and D1 lymphadenectomy P=0.003)were more frequent in the high-ALBI group.There was no difference between both groups in terms of Lauren histological type,depth of tumor invasion(pT),presence of lymph node metastasis(pN),and pathologic(pTNM)stage.Major postoperative complication,and mortality at 30 and 90 days were higher in the high-ALBI patients.In the survival analysis,the high-ALBI group had worse disease-free survival(DFS)and overall survival(OS)compared to those with low-ALBI(P<0.001).When stratified by pTNM,the difference between ALBI groups was maintained in stage I/II and stage III CG for DFS(P<0.001 and P=0.021,respectively);and for OS(P<0.001 and P=0.063,respectively).In multivariate analysis,total gastrectomy,advanced pT stage,presence of lymph node metastasis and high-ALBI were independent factors associated with worse survival.CONCLUSION The preoperative ALBI score is able to predict the outcomes of patients with GC,where high-ALBI patients have worse prognosis.Also,ALBI score allows risk stratification of patients within the same pTNM stages,and represents an independent risk factor associated with survival.
