BACKGROUND Mutational activation of Ras genes is established as a prognostic factor for the genesis of a constitutively active RAS-mitogen activated protein kinase pathway that leads to cancer.Heterogeneity among the ...BACKGROUND Mutational activation of Ras genes is established as a prognostic factor for the genesis of a constitutively active RAS-mitogen activated protein kinase pathway that leads to cancer.Heterogeneity among the distribution of the most frequent mutations in Ras isoforms is reported in different patient populations with urothelial carcinoma of the bladder(UCB).AIM To determine the presence/absence of mutations in Ras isoforms in patients with UCB in order to predict disease outcome.METHODS This study was performed to determine the mutational spectrum at the hotspot regions of H-Ras,K-Ras and N-Ras genes by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and DNA sequencing followed by their clinical impact(if any)by examining the relationship of mutational spectrum with clinical histopathological variables in 87 UCB patients.RESULTS None of the 87 UCB patients showed point mutations in codon 12 of H-Ras gene;codon 61 of N-Ras gene and codons 12,13 of K-Ras gene by PCR-RFLP.Direct DNA sequencing of tumor and normal control bladder mucosal specimens followed by Blastn alignment with the reference wild-type sequences failed to identify even one nucleotide difference in the coding exons 1 and 2 of H-Ras,NRas and K-Ras genes in the tumor and control bladder mucosal specimens.CONCLUSION Our findings on the lack of mutations in H-Ras,K-Ras and N-Ras genes could be explained on the basis of different etiological mechanisms involved in tumor development/progression,inherent genetic susceptibility,tissue specificity or alternative Ras dysfunction such as gene amplification and/or overexpression in a given cohort of patients.展开更多
Background Superficial urothelial carcinoma （SUC） of the bladder is a common urinary tract tumor in China. There is a high recurrence rate of this tumor even after surgery and intravesical instillation. Previous rep...Background Superficial urothelial carcinoma （SUC） of the bladder is a common urinary tract tumor in China. There is a high recurrence rate of this tumor even after surgery and intravesical instillation. Previous reports have described a suppression of the immune system in cancer patients. Dendritic cells （DCs） play a pivotal role in the induction of an effective antitumor immune response. The aim of this study was to investigate the effects of surgery and epirubicin intravesical chemotherapy （IC） on peripheral blood DCs in subsets of patients with bladder SUC. Methods A total of 66 SUC patients and 38 healthy controls were enrolled in this study. All the patients had undergone transurethral resection （TUR） of their cancer and adjunctive IC after tumor removal. The patients were divided into a non-recurrence group （n=40） and a recurrence group （n=26） based on the presence or absence of tumor recurrence. Blood samples were taken preoperatively （PreOP）, on postoperative days （POD） 1 and 7, and at postoperative month （POM） 3. Flow cytometric analysis was used for the determination and quantitation of the surface markers CD80 and CD86 in circulating DC subsets. Results The preoperative percentages of myeloid dendritic cells （mDCs） and expression of CD80 and CD86 were impaired in SUC patients compared to healthy controls （P 〈0.05）. The percentages of mDCs and these surface markers decreased significantly on POD 1 and increased on POD 7, remaining higher than the preoperative values in POM 3 （P 〈0.05）. The percentages of mDCs, and CD80 and CD86 in the non-recurrence group on PreOP, POD 7, and POM 3 were higher than those in recurrence group. Conclusions Surgical removal of SUC and adjunctive IC were associated with improved circulating mDC counts and function. Persistent depression of mDC counts and function after treatment in recurrence patients indicated lower antitumor immunity that may lead to tumor recurrence.展开更多
文摘BACKGROUND Mutational activation of Ras genes is established as a prognostic factor for the genesis of a constitutively active RAS-mitogen activated protein kinase pathway that leads to cancer.Heterogeneity among the distribution of the most frequent mutations in Ras isoforms is reported in different patient populations with urothelial carcinoma of the bladder(UCB).AIM To determine the presence/absence of mutations in Ras isoforms in patients with UCB in order to predict disease outcome.METHODS This study was performed to determine the mutational spectrum at the hotspot regions of H-Ras,K-Ras and N-Ras genes by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and DNA sequencing followed by their clinical impact(if any)by examining the relationship of mutational spectrum with clinical histopathological variables in 87 UCB patients.RESULTS None of the 87 UCB patients showed point mutations in codon 12 of H-Ras gene;codon 61 of N-Ras gene and codons 12,13 of K-Ras gene by PCR-RFLP.Direct DNA sequencing of tumor and normal control bladder mucosal specimens followed by Blastn alignment with the reference wild-type sequences failed to identify even one nucleotide difference in the coding exons 1 and 2 of H-Ras,NRas and K-Ras genes in the tumor and control bladder mucosal specimens.CONCLUSION Our findings on the lack of mutations in H-Ras,K-Ras and N-Ras genes could be explained on the basis of different etiological mechanisms involved in tumor development/progression,inherent genetic susceptibility,tissue specificity or alternative Ras dysfunction such as gene amplification and/or overexpression in a given cohort of patients.
文摘Background Superficial urothelial carcinoma （SUC） of the bladder is a common urinary tract tumor in China. There is a high recurrence rate of this tumor even after surgery and intravesical instillation. Previous reports have described a suppression of the immune system in cancer patients. Dendritic cells （DCs） play a pivotal role in the induction of an effective antitumor immune response. The aim of this study was to investigate the effects of surgery and epirubicin intravesical chemotherapy （IC） on peripheral blood DCs in subsets of patients with bladder SUC. Methods A total of 66 SUC patients and 38 healthy controls were enrolled in this study. All the patients had undergone transurethral resection （TUR） of their cancer and adjunctive IC after tumor removal. The patients were divided into a non-recurrence group （n=40） and a recurrence group （n=26） based on the presence or absence of tumor recurrence. Blood samples were taken preoperatively （PreOP）, on postoperative days （POD） 1 and 7, and at postoperative month （POM） 3. Flow cytometric analysis was used for the determination and quantitation of the surface markers CD80 and CD86 in circulating DC subsets. Results The preoperative percentages of myeloid dendritic cells （mDCs） and expression of CD80 and CD86 were impaired in SUC patients compared to healthy controls （P 〈0.05）. The percentages of mDCs and these surface markers decreased significantly on POD 1 and increased on POD 7, remaining higher than the preoperative values in POM 3 （P 〈0.05）. The percentages of mDCs, and CD80 and CD86 in the non-recurrence group on PreOP, POD 7, and POM 3 were higher than those in recurrence group. Conclusions Surgical removal of SUC and adjunctive IC were associated with improved circulating mDC counts and function. Persistent depression of mDC counts and function after treatment in recurrence patients indicated lower antitumor immunity that may lead to tumor recurrence.
