AIM To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC). METHODS EnVision immunohistochemistry was us...AIM To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC). METHODS EnVision immunohistochemistry was used to stain for ROR2 and WNT5a in 46 SC/ASC patients and 80 AC patients. RESULTS Poorly differentiated AC among AC patients aged >45 years were significantly more frequent compared with SC/ASC patients, while tumors with a maximal diameter >3 cm in the SC/ASC group were significantly more frequent compared with the AC group. Positive ROR2 and WNT5a expression was significantly lower in SC/ASC or AC with a maximal mass diameter = 3 cm, a TNM stage of I + II, no lymph node metastasis, no surrounding invasion, and radical resection than in patients with a maximal mass diameter >3 cm, TNM stage., lymph node metastasis, surrounding invasion, and no resection. Positive ROR2 expression in patients with highly differentiated SC/ASC was significantly lower than in patients with poorly differentiated SC/ASC. Positive ROR2 and WNT5a expression levels in highly differentiated AC were significantly lower than in poorly differentiated AC. Kaplan-Meier survival analysis showed that differentiation degree, maximal mass diameter, TNM stage, lymph node metastasis, surrounding invasion, surgical procedure and the ROR2 and WNT5a expression levels were closely related to average survival of SC/ASC or AC. The survival of SC/ASC or AC patients with positive expression of ROR2 and WNT5a was significantly shorter than that of patients with negative expression results. Cox multivariate analysis revealed that poor differentiation, a maximal diameter of the mass >= 3 cm, TNM stage. or., lymph node metastasis, surrounding invasion, unresected surgery and positive ROR2 or WNT5a expression in the SC/ASC or AC patients were negatively correlated with the postoperative survival rate and positively correlated with mortality, which are risk factors and independent prognostic predictors. CONCLUSION SC/ASC or AC patients with positive R展开更多
In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as ty...In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as type A1 (BDA1). Over 100 cases from different ethnic groups have so far been reported. However, the real breakthrough in identifying the cause of BDA1 has only taken place in the last few years with the progress of the mapping and identification of one of the genes responsible for this disorder, thus providing an answer for a century old riddle. In this article, we attempt to review the current state of knowledge on the genetic features of BDA1 with its century-old history and signalling pathway of IHH, and also discuss genotype-phenotype correlation not only of BDA1, but also of all types of brachydactyly.展开更多
Aim:Lung metastasis is a leading cause of death in patients with osteosarcoma(OS).No effective therapy exists that improves the five-year overall survival rate of OS patients with metastasis.Therefore,finding novel th...Aim:Lung metastasis is a leading cause of death in patients with osteosarcoma(OS).No effective therapy exists that improves the five-year overall survival rate of OS patients with metastasis.Therefore,finding novel therapeutic targets will help develop new treatment strategies for OS patients with lung metastasis.Methods:Based on analysis of gene expression profiles between sublines of the Dunn OS LM8 cell line with high(LM8-H)and low(LM8-L)metastatic ability,we have identified Wnt signal-related genes that play an important role in lung metastasis of OS.Function of the genes was investigated by establishing sublines of gene knockout and assessing their metastatic ability using a mouse lung metastasis model.The molecular mechanism underlying the function of the genes was further investigated by in vitro experiments.Results:We have identified that receptor tyrosine kinase-like orphan receptor 2(ROR2),a receptor of the non-canonical Wnt signaling pathway,was involved in OS cell survival in lung capillaries during metastasis.LM8-H knocked out of Ror2(H/Ror2-KO)significantly reduced lung metastasis by decreasing the viability in lung capillaries 48 h after intravenous injection.In vitro study revealed that ROR2 increased anoikis resistance through AKT activation.Reconstitution of ROR2 expression in H/Ror2-KO cells restored their metastatic ability and viability in lung capillaries.Conclusion:The results demonstrate a novel ROR2 function in OS lung metastasis and may inform new treatment strategies for OS patients.展开更多
基金Supported by the National Natural Science Foundation of China,No.81372628 and No.81402536the Changsha Science and Technology Plan,No.K1205018-31
文摘AIM To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC). METHODS EnVision immunohistochemistry was used to stain for ROR2 and WNT5a in 46 SC/ASC patients and 80 AC patients. RESULTS Poorly differentiated AC among AC patients aged >45 years were significantly more frequent compared with SC/ASC patients, while tumors with a maximal diameter >3 cm in the SC/ASC group were significantly more frequent compared with the AC group. Positive ROR2 and WNT5a expression was significantly lower in SC/ASC or AC with a maximal mass diameter = 3 cm, a TNM stage of I + II, no lymph node metastasis, no surrounding invasion, and radical resection than in patients with a maximal mass diameter >3 cm, TNM stage., lymph node metastasis, surrounding invasion, and no resection. Positive ROR2 expression in patients with highly differentiated SC/ASC was significantly lower than in patients with poorly differentiated SC/ASC. Positive ROR2 and WNT5a expression levels in highly differentiated AC were significantly lower than in poorly differentiated AC. Kaplan-Meier survival analysis showed that differentiation degree, maximal mass diameter, TNM stage, lymph node metastasis, surrounding invasion, surgical procedure and the ROR2 and WNT5a expression levels were closely related to average survival of SC/ASC or AC. The survival of SC/ASC or AC patients with positive expression of ROR2 and WNT5a was significantly shorter than that of patients with negative expression results. Cox multivariate analysis revealed that poor differentiation, a maximal diameter of the mass >= 3 cm, TNM stage. or., lymph node metastasis, surrounding invasion, unresected surgery and positive ROR2 or WNT5a expression in the SC/ASC or AC patients were negatively correlated with the postoperative survival rate and positively correlated with mortality, which are risk factors and independent prognostic predictors. CONCLUSION SC/ASC or AC patients with positive R
基金This project was supported by NSFC/RGC joint Research Grant(No.N-HKU705/02)the Major State Basic Research Development Program of China(No.2001CB5 10301).
文摘In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as type A1 (BDA1). Over 100 cases from different ethnic groups have so far been reported. However, the real breakthrough in identifying the cause of BDA1 has only taken place in the last few years with the progress of the mapping and identification of one of the genes responsible for this disorder, thus providing an answer for a century old riddle. In this article, we attempt to review the current state of knowledge on the genetic features of BDA1 with its century-old history and signalling pathway of IHH, and also discuss genotype-phenotype correlation not only of BDA1, but also of all types of brachydactyly.
基金a Grant-in-Aid for Scientific Research on Innovative Areas“Integrative Research on Cancer Microenvironment Networks from the Ministry of Education”,Culture,Sports,Science and Technology of Japan”(Kizaka-Kondoh S)Grant-in-Aid for Young Scientist(B)(Kuchimaru T)。
文摘Aim:Lung metastasis is a leading cause of death in patients with osteosarcoma(OS).No effective therapy exists that improves the five-year overall survival rate of OS patients with metastasis.Therefore,finding novel therapeutic targets will help develop new treatment strategies for OS patients with lung metastasis.Methods:Based on analysis of gene expression profiles between sublines of the Dunn OS LM8 cell line with high(LM8-H)and low(LM8-L)metastatic ability,we have identified Wnt signal-related genes that play an important role in lung metastasis of OS.Function of the genes was investigated by establishing sublines of gene knockout and assessing their metastatic ability using a mouse lung metastasis model.The molecular mechanism underlying the function of the genes was further investigated by in vitro experiments.Results:We have identified that receptor tyrosine kinase-like orphan receptor 2(ROR2),a receptor of the non-canonical Wnt signaling pathway,was involved in OS cell survival in lung capillaries during metastasis.LM8-H knocked out of Ror2(H/Ror2-KO)significantly reduced lung metastasis by decreasing the viability in lung capillaries 48 h after intravenous injection.In vitro study revealed that ROR2 increased anoikis resistance through AKT activation.Reconstitution of ROR2 expression in H/Ror2-KO cells restored their metastatic ability and viability in lung capillaries.Conclusion:The results demonstrate a novel ROR2 function in OS lung metastasis and may inform new treatment strategies for OS patients.
