OBJECTIVE To investigate the role of family aggregation and genetic factors of esophageal cancer （EC）, including carcinoma of gastric cardia （CGC）, in Cixian county, and to calculate the segregation ratio and heri...OBJECTIVE To investigate the role of family aggregation and genetic factors of esophageal cancer （EC）, including carcinoma of gastric cardia （CGC）, in Cixian county, and to calculate the segregation ratio and heritability of first-degree relatives （FDR） in EC cases.METHODS A case control study was conducted, and each of 285 esophageal cancer cases and FDR＇s case history and family medical history of EC in 1415 controls was carried by home visits to compare the incidence of EC in the crowds. The family aggregation of EC was found by X2 test for goodness of fit test according to binomial distribution. Li-Mantel-Gart method was used to calculate the segregation ratio and Falconer method was employed to compute the heritability （h2）.RESULTS The incidence rate of the FDR in the index case of EC （12.80%） was higher than that in the controls （7.52%）. There were significant differences between the 2 groups （X2= 44.34, P = 0.000）. The distribution of EC in the family did not agree with the binomial distribution, which presented a conspicuous familial aggregation （X2= 288.19, P 〈 0.0001）. The heritability of EC was （29.67 ±4.32）%, and segregation ratio was 0.1814 （95%CI = 0.1574-0.2054）, which is lower than 0.25, and can be regarded as a disease of multi-factorial inheritance.CONCLUSION The occurrence of EC in the Cixian County is the outcome of the mutual effect of genetic and environmental factors. The family history of upper gastrointestinal cancers increases the risk of EC in late generations.展开更多
Objectives:While programmed cell death 1(PD-1)inhibitors have improved cancer treatment,the function and mechanisms of programmed cell death ligand 1(PD-L1),particularly when expressed by cancer cells,remain unclear.T...Objectives:While programmed cell death 1(PD-1)inhibitors have improved cancer treatment,the function and mechanisms of programmed cell death ligand 1(PD-L1),particularly when expressed by cancer cells,remain unclear.This study aims to explore the role of PD-L1 within breast cancer cells and identify key targets for future immunotherapy.Methods:RNA-seq was performed on breast cancer cells with silenced PD-L1 to screen for differentially expressed genes,followed by bioinformatics analysis.Clinical specimens from breast cancer patients undergoing primary surgery without preoperative treatment were collected,along with in vitro analysis to validate the potential mechanism.Results:RNA-seq data revealed a significant positive correlation between Ecto-5′-nucleotidase(NT5E)expression and PD-L1.Bioinformatics analysis corroborated this positive correlation.Immunohistochemistry staining demonstrated higher NT5E expression associated with increased lymph node metastasis.High expression of the NT5E gene was associated with poor overall survival(OS)in breast cancer patients,as determined by KM plotter analysis.Following PD-L1 gene silencing by siRNA in breast cancer cells,NT5E mRNA and protein expression significantly decreased.Conversely,no significant changes were observed in PD-L1 expression after NT5E gene silencing.In vitro experiments confirmed that cancer cell proliferation and metastasis abilities were significantly reduced by either PD-L1 or NT5E gene down-regulation.Western blotting demonstrated that PD-L1 expressed by cancer cells regulates NT5E expression through the MAPK/ERK signaling pathway.Conclusion:This study proposes a potential mechanism wherein tumor-expressing PD-L1 regulates NT5E through the MAPK/ERK pathway.Downregulation of PD-L1 or NT5E can significantly inhibit the proliferation and metastatic ability of cancer cells,potentially providing practical therapeutic targets and prognostic markers for combined PD-L1 immunotherapy in breast cancer.展开更多
Objective： To discuss the epidemic strength of cardia and distant stomach cancers in the high risk region of esophageal cancer along the south Taihang mountain such as in Shexian, Linxian, and Cixian Counties, and to...Objective： To discuss the epidemic strength of cardia and distant stomach cancers in the high risk region of esophageal cancer along the south Taihang mountain such as in Shexian, Linxian, and Cixian Counties, and to clarify the tasks for the control of upper gastrointestinal tract cancer as a whole in the region. Methods： Comparisons of incidence and mortality rates of esophageal, cardia and stomach cancers were made between Cixian, Linxian and Shexian Counties with reference to detection rates of cancer in situ and precancerous lesions of the three upper gastrointestinal cancers by endoscopic screening. The screening was performed from 1999 through 2004 in the three adjacent counties including a total of 6233 local residents aged 40 to 69 years old. Results： The incidence rates for cardia cancer for the male and female from 2000 through 2004 were 69.9 and 41.5, and the mortality rates were 54.3 and 33.2 respectively in Shexian County. Esophageal, cardia, and stomach cancers constitute about 70～80 percent of all malignant disease by incidence or mortality rates. Endoscopic survey with iodine staining can effectively detect squamous cell precancerous lesions in the esophagus, but the method is inadequate for the detection of adeno precancerous lesions of the cardia and stomach. Conclusion： The south Taihang mountain region is a high risk area not only for esophagus cancer, but also for cardia and stomach cancers. To control upper gastrointestinal tract cancers as a whole in the region, special attention should be paid to the control of cardia and stomach cancers. Presently, to find effective screening methods for detecting cardia and stomach precancerous lesions is especially important.展开更多
OBJECTIVE To demonstrate the effects of an inherited predisposition to familial esophageal squamous cell carcinoma （ESCC） through the comparison and analysis of the clinicopathologic differences between familial and...OBJECTIVE To demonstrate the effects of an inherited predisposition to familial esophageal squamous cell carcinoma （ESCC） through the comparison and analysis of the clinicopathologic differences between familial and sporadic ESCC cases. METHODS Differences in age of onset, prevalence rates of double primary ESCC, and survival rates between familial ESCC （n = 476） and sporadic ESCC cases （n = 1226） were analyzed. RESULTS Overall, familial ESCC cases showed a significantly younger age of onset （51.9±8.2 vs. 53.4 ±8.0, Pt.test = 0.00）, a significantly higher prevalence rate for double ESCC （2.73 % vs. 1.22%, adjusted with TNM：χMH2 = 4.029, P = 0.045）, and a lower survival rate than in sporadic cases （Pwald = 0.04）. The familial cases showed both a younger age of onset and poorer survival in most subgroups, and the differences were more marked in early-stage rather than in the .late-stage disease groups. CONCLUSION Theses findings confirm the existence of familial as opposed to sporadic ESCC. By the theory of the ＂two-hit＂ origin of cancer, these findings also suggest that the ＂first hit＂, a genetic predisposition, can affect the age of onset, number of primary carcinomas, and the prognosis for familial ESCC patients.展开更多
OBJECTIVE To investigate the natural history of fast developing esophageal and cardia precursors.METHODS Repetitive endoscopic screenings were performed among 40-69-year-olds in the high-incidence areas for esophageal...OBJECTIVE To investigate the natural history of fast developing esophageal and cardia precursors.METHODS Repetitive endoscopic screenings were performed among 40-69-year-olds in the high-incidence areas for esophageal cancer in Shexian. RESULTS The initial diagnosis and the lag-time for 7 subsequently identified severe dysplasia （SD） subjects were as follows： in one subject 13 months after a baseline diagnosis of normal epithelium, in another subject 7 months after a baseline diagnosis of base cell hyperplasia （BCH）, in four subjects 3, 4, 4, and 10.5 months after baseline diagnosis of mild dysplasia （mD）, and in one subject 12.5 months after a baseline diagnosis of moderate dysplasia （MD）. The initial diagnosis and the lag-time for 6 subsequently identified carcinomas in situ or intramucosal carcinoma cases were： in one case 48 months after a baseline diagnosis of mD, in 2 cases 4 and 13 months after baseline diagnoses of MD, and in the other 3 cases 3.5, 9, and 17.5 months after baseline diagnoses of SD. The initial diagnosis and lag-time for 3 subsequently identified invasive cancer cases, were： in one case 50 months after a baseline diagnosis of MD, in 2 cases 14 and 19 months after baseline diagnoses of SD. In addition, during a 4-year-follow-up of 18 subjects after endoscopic mucosa resection, 9 of them were found to have developed precursors again at other sites, and also additional findings were obtained for 11 of the 16 dysplasia cases by repetitive biopsy in less than 2 months after the initial endoscopy. CONCLUSION A 5-year screening interval for BCH and mD, and a 3-year interval for MD may be too long for the fast developing precursors. Periodic screenings with shorter intervals should be considered to control the number of interval cases due to fast development, multifocal carcinogenesis, and false negative results inherent in one-time endoscopic biopsy sampling.展开更多
In this report,the PMA-induced chromosomeaberration rates (CAR) of cultured peripheralblood cells of 10 untreated esophageal cancer and14 normal subjects were studied.At the same time,the levels of SOD of midium ultra...In this report,the PMA-induced chromosomeaberration rates (CAR) of cultured peripheralblood cells of 10 untreated esophageal cancer and14 normal subjects were studied.At the same time,the levels of SOD of midium ultrafiltrates fromPMA-treated cultures after 1 ed 48 h were deter-minated.展开更多
In this study,the chromosome aberrations ofcultured peripheral blood cells of 28 untreatedesophageal cancer and 25 normal individuals weretaken.PMA-induced CA was compared with spontane-ous one.The peripheral blood wh...In this study,the chromosome aberrations ofcultured peripheral blood cells of 28 untreatedesophageal cancer and 25 normal individuals weretaken.PMA-induced CA was compared with spontane-ous one.The peripheral blood white ce1ls展开更多
Background We investigated the possible association of the functional polymorphisms in the tumor necrosis factor （TNF） genes with susceptibility to esophageal squamous cell carcinoma （ESCC） and gastric cardiac ade...Background We investigated the possible association of the functional polymorphisms in the tumor necrosis factor （TNF） genes with susceptibility to esophageal squamous cell carcinoma （ESCC） and gastric cardiac adenocarcinoma （GCA）.Methods The TNF-α-308G/A and TNF-β ＋ 252G/A single nucleotide polymorphisms （SNPs） were genotyped using polymerase-chain reaction-restriction fragment length polymorphism （PCR-RFLP） analysis, in 555 cancer patients （291 ESCC and 264 GCA） and 437 healthy controls in a high incidence region of North China. Results Among healthy controls, frequencies of the TNF-α 1/1, 1/2 and 2/2 genotypes were 89.4% ,9.2% and 1.4% respectively, while frequencies of the TNF-β B1/B1, B1/B2 and B2/B2 genotypes were 12.6% , 32.3% and 55.1%, respectively. No significant difference was found in the overall genotype and allelotype distribution of the TNF-α-308G/A and TNF-β ＋ 252G/A SNPs among cancer patients and controls. However, both the B1/B1 genotype and B1/B2 genotype significantly increased the risk of developing ESCC [ the age and gender adjusted odds ratio （OR） =2.04 and 1.91, 95% confidence interval （CI） = 1.04 -4.43 and 1.14 - 2.60, respectively] and GCA （the age and gender adjusted OR =2. 68 and 2. 64, 95% CI = 1.14 -6.29 and 1.47 -4.72, respectively） in individuals with negative family history of UGIC, in comparison with the B2/B2 genotype. When the two TNF polymorphisms were combined and analyzed, individuals with the TNF-β B1/B2 and TNF-α1/2 or 2/2 genotypes significantly reduced the risk of developing ESCC and GCA, in comparison with those harboring the TNF-β B2/B2 and TNF-α 1/1 genotypes （ the age and gender adjusted OR = 0.37 and 0. 34, 95% CI =0. 15 -0.92 and 0. 13 -0.90, respectively）. Conclusions Therefore, the TNF-α -308G/A and TNF-β ＋ 252G/A genotyping may be used as a stratification markers to predicate the risk of ESCC and GCA development in North China.展开更多
Stomach cancer is one of the common malignancies with dramatic geographical varia-tion in its incidence. Zanhuang County in Hebei Province is a high-incidence area ofstomach cancer with an average mortality rate as hi...Stomach cancer is one of the common malignancies with dramatic geographical varia-tion in its incidence. Zanhuang County in Hebei Province is a high-incidence area ofstomach cancer with an average mortality rate as high as 59/10~5/a, even up to 126.59/10~5/ain some townships. Our previous studies indicated that the high incidence of stomachcancer was closely associated with Aspergillus versicolor and its toxin sterigmatocystin(ST).展开更多
文摘OBJECTIVE To investigate the role of family aggregation and genetic factors of esophageal cancer （EC）, including carcinoma of gastric cardia （CGC）, in Cixian county, and to calculate the segregation ratio and heritability of first-degree relatives （FDR） in EC cases.METHODS A case control study was conducted, and each of 285 esophageal cancer cases and FDR＇s case history and family medical history of EC in 1415 controls was carried by home visits to compare the incidence of EC in the crowds. The family aggregation of EC was found by X2 test for goodness of fit test according to binomial distribution. Li-Mantel-Gart method was used to calculate the segregation ratio and Falconer method was employed to compute the heritability （h2）.RESULTS The incidence rate of the FDR in the index case of EC （12.80%） was higher than that in the controls （7.52%）. There were significant differences between the 2 groups （X2= 44.34, P = 0.000）. The distribution of EC in the family did not agree with the binomial distribution, which presented a conspicuous familial aggregation （X2= 288.19, P 〈 0.0001）. The heritability of EC was （29.67 ±4.32）%, and segregation ratio was 0.1814 （95%CI = 0.1574-0.2054）, which is lower than 0.25, and can be regarded as a disease of multi-factorial inheritance.CONCLUSION The occurrence of EC in the Cixian County is the outcome of the mutual effect of genetic and environmental factors. The family history of upper gastrointestinal cancers increases the risk of EC in late generations.
基金Provincial Natural Science Foundation J230016Provincial Natural Science Foundation H2023206441Hebei Province Major Science and Technology Support Program Project S&T Program of Hebei 242W7701Z.
文摘Objectives:While programmed cell death 1(PD-1)inhibitors have improved cancer treatment,the function and mechanisms of programmed cell death ligand 1(PD-L1),particularly when expressed by cancer cells,remain unclear.This study aims to explore the role of PD-L1 within breast cancer cells and identify key targets for future immunotherapy.Methods:RNA-seq was performed on breast cancer cells with silenced PD-L1 to screen for differentially expressed genes,followed by bioinformatics analysis.Clinical specimens from breast cancer patients undergoing primary surgery without preoperative treatment were collected,along with in vitro analysis to validate the potential mechanism.Results:RNA-seq data revealed a significant positive correlation between Ecto-5′-nucleotidase(NT5E)expression and PD-L1.Bioinformatics analysis corroborated this positive correlation.Immunohistochemistry staining demonstrated higher NT5E expression associated with increased lymph node metastasis.High expression of the NT5E gene was associated with poor overall survival(OS)in breast cancer patients,as determined by KM plotter analysis.Following PD-L1 gene silencing by siRNA in breast cancer cells,NT5E mRNA and protein expression significantly decreased.Conversely,no significant changes were observed in PD-L1 expression after NT5E gene silencing.In vitro experiments confirmed that cancer cell proliferation and metastasis abilities were significantly reduced by either PD-L1 or NT5E gene down-regulation.Western blotting demonstrated that PD-L1 expressed by cancer cells regulates NT5E expression through the MAPK/ERK signaling pathway.Conclusion:This study proposes a potential mechanism wherein tumor-expressing PD-L1 regulates NT5E through the MAPK/ERK pathway.Downregulation of PD-L1 or NT5E can significantly inhibit the proliferation and metastatic ability of cancer cells,potentially providing practical therapeutic targets and prognostic markers for combined PD-L1 immunotherapy in breast cancer.
基金This work was supported by the grants from The Natural Scientific Foundation of Hebei Province (No. C 2005000797 Hebei Significant Topic of Tackle Key Programs (No. 03276198D) Hebei Technology Program Item (No. 032761100D-1)
文摘Objective： To discuss the epidemic strength of cardia and distant stomach cancers in the high risk region of esophageal cancer along the south Taihang mountain such as in Shexian, Linxian, and Cixian Counties, and to clarify the tasks for the control of upper gastrointestinal tract cancer as a whole in the region. Methods： Comparisons of incidence and mortality rates of esophageal, cardia and stomach cancers were made between Cixian, Linxian and Shexian Counties with reference to detection rates of cancer in situ and precancerous lesions of the three upper gastrointestinal cancers by endoscopic screening. The screening was performed from 1999 through 2004 in the three adjacent counties including a total of 6233 local residents aged 40 to 69 years old. Results： The incidence rates for cardia cancer for the male and female from 2000 through 2004 were 69.9 and 41.5, and the mortality rates were 54.3 and 33.2 respectively in Shexian County. Esophageal, cardia, and stomach cancers constitute about 70～80 percent of all malignant disease by incidence or mortality rates. Endoscopic survey with iodine staining can effectively detect squamous cell precancerous lesions in the esophagus, but the method is inadequate for the detection of adeno precancerous lesions of the cardia and stomach. Conclusion： The south Taihang mountain region is a high risk area not only for esophagus cancer, but also for cardia and stomach cancers. To control upper gastrointestinal tract cancers as a whole in the region, special attention should be paid to the control of cardia and stomach cancers. Presently, to find effective screening methods for detecting cardia and stomach precancerous lesions is especially important.
基金supported by grants from the National Scientific Support Program during the Eleventh Five-year Period (No.2006BAI02A0)the Hebei Provincial Program for the Subjects with High Scholarship and Creative Research Potential in Ordinary Colleges and Universities+1 种基金the Natural Scientific Foundation of Hebei Province (No.C2005000797)the International Science and Technology Cooperation Item of Hebei Province (No.09396105D).
文摘OBJECTIVE To demonstrate the effects of an inherited predisposition to familial esophageal squamous cell carcinoma （ESCC） through the comparison and analysis of the clinicopathologic differences between familial and sporadic ESCC cases. METHODS Differences in age of onset, prevalence rates of double primary ESCC, and survival rates between familial ESCC （n = 476） and sporadic ESCC cases （n = 1226） were analyzed. RESULTS Overall, familial ESCC cases showed a significantly younger age of onset （51.9±8.2 vs. 53.4 ±8.0, Pt.test = 0.00）, a significantly higher prevalence rate for double ESCC （2.73 % vs. 1.22%, adjusted with TNM：χMH2 = 4.029, P = 0.045）, and a lower survival rate than in sporadic cases （Pwald = 0.04）. The familial cases showed both a younger age of onset and poorer survival in most subgroups, and the differences were more marked in early-stage rather than in the .late-stage disease groups. CONCLUSION Theses findings confirm the existence of familial as opposed to sporadic ESCC. By the theory of the ＂two-hit＂ origin of cancer, these findings also suggest that the ＂first hit＂, a genetic predisposition, can affect the age of onset, number of primary carcinomas, and the prognosis for familial ESCC patients.
基金This work was partially supported by Grantsfrom the Hebei Provincial Natural ScientificFoundation(No.C2005000797)fromFunds for the Potential y Distinguished Sci-entific Project Construction in Hebei Universi-ties.
文摘OBJECTIVE To investigate the natural history of fast developing esophageal and cardia precursors.METHODS Repetitive endoscopic screenings were performed among 40-69-year-olds in the high-incidence areas for esophageal cancer in Shexian. RESULTS The initial diagnosis and the lag-time for 7 subsequently identified severe dysplasia （SD） subjects were as follows： in one subject 13 months after a baseline diagnosis of normal epithelium, in another subject 7 months after a baseline diagnosis of base cell hyperplasia （BCH）, in four subjects 3, 4, 4, and 10.5 months after baseline diagnosis of mild dysplasia （mD）, and in one subject 12.5 months after a baseline diagnosis of moderate dysplasia （MD）. The initial diagnosis and the lag-time for 6 subsequently identified carcinomas in situ or intramucosal carcinoma cases were： in one case 48 months after a baseline diagnosis of mD, in 2 cases 4 and 13 months after baseline diagnoses of MD, and in the other 3 cases 3.5, 9, and 17.5 months after baseline diagnoses of SD. The initial diagnosis and lag-time for 3 subsequently identified invasive cancer cases, were： in one case 50 months after a baseline diagnosis of MD, in 2 cases 14 and 19 months after baseline diagnoses of SD. In addition, during a 4-year-follow-up of 18 subjects after endoscopic mucosa resection, 9 of them were found to have developed precursors again at other sites, and also additional findings were obtained for 11 of the 16 dysplasia cases by repetitive biopsy in less than 2 months after the initial endoscopy. CONCLUSION A 5-year screening interval for BCH and mD, and a 3-year interval for MD may be too long for the fast developing precursors. Periodic screenings with shorter intervals should be considered to control the number of interval cases due to fast development, multifocal carcinogenesis, and false negative results inherent in one-time endoscopic biopsy sampling.
文摘In this report,the PMA-induced chromosomeaberration rates (CAR) of cultured peripheralblood cells of 10 untreated esophageal cancer and14 normal subjects were studied.At the same time,the levels of SOD of midium ultrafiltrates fromPMA-treated cultures after 1 ed 48 h were deter-minated.
文摘In this study,the chromosome aberrations ofcultured peripheral blood cells of 28 untreatedesophageal cancer and 25 normal individuals weretaken.PMA-induced CA was compared with spontane-ous one.The peripheral blood white ce1ls
基金This study was supported by a grant from the National NaturalScience Foundation China (No.30371591)
文摘Background We investigated the possible association of the functional polymorphisms in the tumor necrosis factor （TNF） genes with susceptibility to esophageal squamous cell carcinoma （ESCC） and gastric cardiac adenocarcinoma （GCA）.Methods The TNF-α-308G/A and TNF-β ＋ 252G/A single nucleotide polymorphisms （SNPs） were genotyped using polymerase-chain reaction-restriction fragment length polymorphism （PCR-RFLP） analysis, in 555 cancer patients （291 ESCC and 264 GCA） and 437 healthy controls in a high incidence region of North China. Results Among healthy controls, frequencies of the TNF-α 1/1, 1/2 and 2/2 genotypes were 89.4% ,9.2% and 1.4% respectively, while frequencies of the TNF-β B1/B1, B1/B2 and B2/B2 genotypes were 12.6% , 32.3% and 55.1%, respectively. No significant difference was found in the overall genotype and allelotype distribution of the TNF-α-308G/A and TNF-β ＋ 252G/A SNPs among cancer patients and controls. However, both the B1/B1 genotype and B1/B2 genotype significantly increased the risk of developing ESCC [ the age and gender adjusted odds ratio （OR） =2.04 and 1.91, 95% confidence interval （CI） = 1.04 -4.43 and 1.14 - 2.60, respectively] and GCA （the age and gender adjusted OR =2. 68 and 2. 64, 95% CI = 1.14 -6.29 and 1.47 -4.72, respectively） in individuals with negative family history of UGIC, in comparison with the B2/B2 genotype. When the two TNF polymorphisms were combined and analyzed, individuals with the TNF-β B1/B2 and TNF-α1/2 or 2/2 genotypes significantly reduced the risk of developing ESCC and GCA, in comparison with those harboring the TNF-β B2/B2 and TNF-α 1/1 genotypes （ the age and gender adjusted OR = 0.37 and 0. 34, 95% CI =0. 15 -0.92 and 0. 13 -0.90, respectively）. Conclusions Therefore, the TNF-α -308G/A and TNF-β ＋ 252G/A genotyping may be used as a stratification markers to predicate the risk of ESCC and GCA development in North China.
基金Project supported by the National Natural Science Foundation of China.
文摘Stomach cancer is one of the common malignancies with dramatic geographical varia-tion in its incidence. Zanhuang County in Hebei Province is a high-incidence area ofstomach cancer with an average mortality rate as high as 59/10~5/a, even up to 126.59/10~5/ain some townships. Our previous studies indicated that the high incidence of stomachcancer was closely associated with Aspergillus versicolor and its toxin sterigmatocystin(ST).
