AIM： TO determine the influence of excision repair cross complementing group 1 （ERCC1） codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvan...AIM： TO determine the influence of excision repair cross complementing group 1 （ERCC1） codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. METHODS： Eighty-nine gastric cancer patients treated with oxalipatin-based adjuvant chemotherapy were included in this study. ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction （PCR-LDR） method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available. RESULTS： No significant relationship was found between ERCC1 codon 118 polymorphism and ERCC1 mRNA level. The median relapse-free and overall survival period was 20.1 mo and 28.4 too, respectively. The relapse-free and overall survivals in patients with lOW levels of ERCC1 mRNA were significantly longer than those in patients with high levels （P 〈 0.05）, while there was no significant association found between ERCC1 118 genotypes and the disease prognosis. Multivariate analysis also showed that ERCC1 mRNA level was a potential predictor for relapse and survival in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy （P 〈 0.05）. CONCLUSION： ERCC1 codon 118 polymorphisrn has no significant impact on ERCC1 rnRNA expression, and the intraturnoral ERCC1 rnRNA level but not codon 118 polymorphisrn may be a useful predictive parameter for the relapse and survival of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy.展开更多
A subgroup H of a finite group G is said to be complemented in G if there exists a subgroup K of G such that G = HK and H n X = 1. In this easel K is called a complement of H in G. In this note some results on complem...A subgroup H of a finite group G is said to be complemented in G if there exists a subgroup K of G such that G = HK and H n X = 1. In this easel K is called a complement of H in G. In this note some results on complemented subgroups of finite groups are obtained.展开更多
Objective: The aim of the study was to explore the effect of demethylating agent 5-Aza-2'-deoxycytidine (5-ADC) on expression of Fanconi anemia complementation group F (FANCF) gene and the proliferation of cervica...Objective: The aim of the study was to explore the effect of demethylating agent 5-Aza-2'-deoxycytidine (5-ADC) on expression of Fanconi anemia complementation group F (FANCF) gene and the proliferation of cervical cancer cells, to observe cell's sensitivity to chemotherapeutic drug taxol, and to explore the antitumor effect of 5-ADC as well as the new treatment of cervical cancer. Methods: Cervical cancer cell lines SiHa (FANCF gene full-methylated) and Hela (unmethylated) were treated with 5-ADC. We used the methylation-specific PCR (MSP), reverse transcription-polymerase chain reaction (RT-PCR) and Western blot to detect the FANCF methylation, mRNA and protein respectively. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the proliferation of cells. The cytotoxicity of taxol was measured by flow cytometer. The nude mice bearing SiHa was used to observe the effect of 5-ADC in vivo. Results: Inhibition of DNA promoter methylation by 5-ADC reactivated the expression of FANCF mRNA and protein in SiHa cells, consistent with decreased growth speed and increased taxol resistance. These results were proven in experiments in vivo. Conclusion: The 5-ADC probably become a potential treatment drug through inhibiting the proliferation of cervical cancer cells in taxol-resistant patients.展开更多
Background Several studies have evaluated the association between polymorphisms of encoding excision repair cross complementation group 1 （ERCC1） enzyme and lung cancer risk in diverse populations but with conflicti...Background Several studies have evaluated the association between polymorphisms of encoding excision repair cross complementation group 1 （ERCC1） enzyme and lung cancer risk in diverse populations but with conflicting results.By pooling the relatively small samples in each study, it is possible to perform a meta-analysis of the evidence by rigorous methods.Methods Embase, Ovid, Medline and Chinese National Knowledge Infrastructure were searched. Additional studies were identified from references in original studies or review articles. Articles meeting the inclusion criteria were reviewed systematically, and the reported data were aggregated using the statistical techniques of meta-analysis.Results We found 3810 cases with lung cancer and 4332 controls from seven eligible studies. T19007C polymorphism showed no significant effect on lung cancer risk （C allele vs. T allele： odds ratio （OR）=0.91, 95% confidence interval （CI）=0.80-1.04; CC vs. TT： OR=0.76, 95% CI=0.56-1.02; CC vs. （CT＋TT）： OR=0.96, 95% CI=-0.84-1.10）. Similarly,there was no significant main effects for T19007C polymorphism on lung cancer risk when stratified analyses by ethnicity （Chinese or Caucasian）. No significant association was found between C8092A polymorphism （3060 patients and 2729 controls） and the risk of lung cancer （A allele vs. C allele： OR=1.03, 95% CI=0.95-1.11; AA vs. CC： OR=1.08, 95% CI=-0.88-1.33; AA vs. （AC＋CC）： OR=1.08, 95% CI=-0.88-1.31）.Conclusion We found little evidence of an association between the T1900C or C8092A polymorphisms of ERCC 1 and the risk of lung cancer in Caucasian or Han Chinese people.展开更多
Aim:Excision repair cross complementation group 1(ERCC1)has a key role in enhanced DNA damage repair caused by oxaliplatin-based therapy and may lead to resistance of these platinum drugs in colorectal cancer(CRC)pati...Aim:Excision repair cross complementation group 1(ERCC1)has a key role in enhanced DNA damage repair caused by oxaliplatin-based therapy and may lead to resistance of these platinum drugs in colorectal cancer(CRC)patients.Hence,the present preliminary study aimed to explore the role of ERCC1 C/T polymorphism at codon 118 as well as its immunoreactivity in patients with primary CRC.Methods:ERCC1 polymorphism was studied using PCR-RFLP and ERCC1 protein expression was examined by immunohistochemistry in 50 CRC patients.Results:ERCC1 codon 118 C/T polymorphism analysis reported the predominance of C/T(52%)genotype as compared to C/C(38%)and T/T(10%)genotypes.Furthermore,72%of patients showed positive ERCC1 protein expression.Significant correlation was not observed between clinicopathological parameters and ERCC1 polymorphism,while ERCC1 protein expression significantly correlated only with tumor site(colon vs.rectum)(P=0.046).Further,the present study failed to demonstrate the role of ERCC1 C118T polymorphism or protein expression as useful prognostic markers in CRC patients.Conclusion:ERCC1-positive protein expression may be a useful marker for rectal cancer patients.However,further evaluation in a larger set of CRC patients is required to better understand the role of ERCC1.展开更多
Cisplatin resistance in tumors is closely linked to the upregulation of the nucleotide excision repair(NER)pathway,particularly the excision repair cross-complementing-1–xeroderma pigmentosum complementation group F(...Cisplatin resistance in tumors is closely linked to the upregulation of the nucleotide excision repair(NER)pathway,particularly the excision repair cross-complementing-1–xeroderma pigmentosum complementation group F(ERCC1–XPF)complex.Here,we present a tumor-responsive microneedle(MN)patch platform for localized co-delivery of a NER-targeting proteolysis-targeting chimera(PROTAC)degrader(NERiP)and a Pt(Ⅳ)prodrug to overcome this resistance.This platform integrates pH-responsive PEG-PAE micelles,which co-encapsulate NERiP and Pt(Ⅳ),into dissolvable methacrylated hyaluronic acid microneedles for transdermal administration.Upon insertion into tumor-bearing skin,the MNs enable sustained and localized release of the micelles.In the mildly acidic tumor microenvironment,the micelles undergo surface charge reversal and rapid disassembly,resulting in synchronized release of both agents.This spatiotemporally coordinated delivery effectively downregulates ERCC1–XPF proteins and promotes platinum-induced DNA crosslinking,thereby enhancing apoptosis in cisplatin-resistant A375/CDDP melanoma cells.In vivo studies demonstrate that MN-mediated delivery significantly improves intratumoral drug accumulation and deep tissue penetration,achieving a tumor growth inhibition rate of 79.9%with minimal systemic toxicity.By combining tumor microenvironment-responsive release with minimally invasive localized delivery,this strategy enables synergistic NER pathway suppression and platinum-mediated genotoxicity.Furthermore,the MN platform ensures deep intratumoral distribution and prolonged retention,offering a promising therapeutic approach to address platinum resistance in solid tumors.展开更多
基金Supported by A Grant From Scientif ic and Technologic Bureau of Wuxi, CLZ00612
文摘AIM： TO determine the influence of excision repair cross complementing group 1 （ERCC1） codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. METHODS： Eighty-nine gastric cancer patients treated with oxalipatin-based adjuvant chemotherapy were included in this study. ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction （PCR-LDR） method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available. RESULTS： No significant relationship was found between ERCC1 codon 118 polymorphism and ERCC1 mRNA level. The median relapse-free and overall survival period was 20.1 mo and 28.4 too, respectively. The relapse-free and overall survivals in patients with lOW levels of ERCC1 mRNA were significantly longer than those in patients with high levels （P 〈 0.05）, while there was no significant association found between ERCC1 118 genotypes and the disease prognosis. Multivariate analysis also showed that ERCC1 mRNA level was a potential predictor for relapse and survival in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy （P 〈 0.05）. CONCLUSION： ERCC1 codon 118 polymorphisrn has no significant impact on ERCC1 rnRNA expression, and the intraturnoral ERCC1 rnRNA level but not codon 118 polymorphisrn may be a useful predictive parameter for the relapse and survival of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy.
基金Project supported by the National Natural Science Foundation of China (No.19671073) and theYouth Science Foundation of Shanxi
文摘A subgroup H of a finite group G is said to be complemented in G if there exists a subgroup K of G such that G = HK and H n X = 1. In this easel K is called a complement of H in G. In this note some results on complemented subgroups of finite groups are obtained.
基金Supported by the grant from the National Science Foundation of Chongqing (No. cstc2011jjA10081)
文摘Objective: The aim of the study was to explore the effect of demethylating agent 5-Aza-2'-deoxycytidine (5-ADC) on expression of Fanconi anemia complementation group F (FANCF) gene and the proliferation of cervical cancer cells, to observe cell's sensitivity to chemotherapeutic drug taxol, and to explore the antitumor effect of 5-ADC as well as the new treatment of cervical cancer. Methods: Cervical cancer cell lines SiHa (FANCF gene full-methylated) and Hela (unmethylated) were treated with 5-ADC. We used the methylation-specific PCR (MSP), reverse transcription-polymerase chain reaction (RT-PCR) and Western blot to detect the FANCF methylation, mRNA and protein respectively. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the proliferation of cells. The cytotoxicity of taxol was measured by flow cytometer. The nude mice bearing SiHa was used to observe the effect of 5-ADC in vivo. Results: Inhibition of DNA promoter methylation by 5-ADC reactivated the expression of FANCF mRNA and protein in SiHa cells, consistent with decreased growth speed and increased taxol resistance. These results were proven in experiments in vivo. Conclusion: The 5-ADC probably become a potential treatment drug through inhibiting the proliferation of cervical cancer cells in taxol-resistant patients.
文摘Background Several studies have evaluated the association between polymorphisms of encoding excision repair cross complementation group 1 （ERCC1） enzyme and lung cancer risk in diverse populations but with conflicting results.By pooling the relatively small samples in each study, it is possible to perform a meta-analysis of the evidence by rigorous methods.Methods Embase, Ovid, Medline and Chinese National Knowledge Infrastructure were searched. Additional studies were identified from references in original studies or review articles. Articles meeting the inclusion criteria were reviewed systematically, and the reported data were aggregated using the statistical techniques of meta-analysis.Results We found 3810 cases with lung cancer and 4332 controls from seven eligible studies. T19007C polymorphism showed no significant effect on lung cancer risk （C allele vs. T allele： odds ratio （OR）=0.91, 95% confidence interval （CI）=0.80-1.04; CC vs. TT： OR=0.76, 95% CI=0.56-1.02; CC vs. （CT＋TT）： OR=0.96, 95% CI=-0.84-1.10）. Similarly,there was no significant main effects for T19007C polymorphism on lung cancer risk when stratified analyses by ethnicity （Chinese or Caucasian）. No significant association was found between C8092A polymorphism （3060 patients and 2729 controls） and the risk of lung cancer （A allele vs. C allele： OR=1.03, 95% CI=0.95-1.11; AA vs. CC： OR=1.08, 95% CI=-0.88-1.33; AA vs. （AC＋CC）： OR=1.08, 95% CI=-0.88-1.31）.Conclusion We found little evidence of an association between the T1900C or C8092A polymorphisms of ERCC 1 and the risk of lung cancer in Caucasian or Han Chinese people.
基金supported by Gujarat Cancer Society(GCS)/Gujarat Cancer and Research Institute(GCRI)and Directorate of Medical Education and Research(DMER).
文摘Aim:Excision repair cross complementation group 1(ERCC1)has a key role in enhanced DNA damage repair caused by oxaliplatin-based therapy and may lead to resistance of these platinum drugs in colorectal cancer(CRC)patients.Hence,the present preliminary study aimed to explore the role of ERCC1 C/T polymorphism at codon 118 as well as its immunoreactivity in patients with primary CRC.Methods:ERCC1 polymorphism was studied using PCR-RFLP and ERCC1 protein expression was examined by immunohistochemistry in 50 CRC patients.Results:ERCC1 codon 118 C/T polymorphism analysis reported the predominance of C/T(52%)genotype as compared to C/C(38%)and T/T(10%)genotypes.Furthermore,72%of patients showed positive ERCC1 protein expression.Significant correlation was not observed between clinicopathological parameters and ERCC1 polymorphism,while ERCC1 protein expression significantly correlated only with tumor site(colon vs.rectum)(P=0.046).Further,the present study failed to demonstrate the role of ERCC1 C118T polymorphism or protein expression as useful prognostic markers in CRC patients.Conclusion:ERCC1-positive protein expression may be a useful marker for rectal cancer patients.However,further evaluation in a larger set of CRC patients is required to better understand the role of ERCC1.
基金financially supported by the National Natural Science Foundation of China(No.32000996)the Key Program of Nanozyme Laboratory in Zhongyuan(No.NLZ-KP2024NIC02)the Grant for International Joint Research Project of the Institute of Medical Science,the University of Tokyo(No.Extension-2019-K3005).
文摘Cisplatin resistance in tumors is closely linked to the upregulation of the nucleotide excision repair(NER)pathway,particularly the excision repair cross-complementing-1–xeroderma pigmentosum complementation group F(ERCC1–XPF)complex.Here,we present a tumor-responsive microneedle(MN)patch platform for localized co-delivery of a NER-targeting proteolysis-targeting chimera(PROTAC)degrader(NERiP)and a Pt(Ⅳ)prodrug to overcome this resistance.This platform integrates pH-responsive PEG-PAE micelles,which co-encapsulate NERiP and Pt(Ⅳ),into dissolvable methacrylated hyaluronic acid microneedles for transdermal administration.Upon insertion into tumor-bearing skin,the MNs enable sustained and localized release of the micelles.In the mildly acidic tumor microenvironment,the micelles undergo surface charge reversal and rapid disassembly,resulting in synchronized release of both agents.This spatiotemporally coordinated delivery effectively downregulates ERCC1–XPF proteins and promotes platinum-induced DNA crosslinking,thereby enhancing apoptosis in cisplatin-resistant A375/CDDP melanoma cells.In vivo studies demonstrate that MN-mediated delivery significantly improves intratumoral drug accumulation and deep tissue penetration,achieving a tumor growth inhibition rate of 79.9%with minimal systemic toxicity.By combining tumor microenvironment-responsive release with minimally invasive localized delivery,this strategy enables synergistic NER pathway suppression and platinum-mediated genotoxicity.Furthermore,the MN platform ensures deep intratumoral distribution and prolonged retention,offering a promising therapeutic approach to address platinum resistance in solid tumors.
