The formation of osteolytic bone lesions is a key process for osteolytic cancer to metastasize to the bone and is under the control of a set of transcription factors. Recently, the inhibitor of differentiation 1 (Id1...The formation of osteolytic bone lesions is a key process for osteolytic cancer to metastasize to the bone and is under the control of a set of transcription factors. Recently, the inhibitor of differentiation 1 (Id1) has been linked with angiogenesis, tumorigenesis, metastasis and bone formation. However, the function of Id1 during the process of bone destruction caused by cancer in vivo has not yet been elucidated. We, therefore, examined whether and how Id1 affects the ability of cancer to form osteolytic lesion in vivo. The study used a lentiviral vector overexpressing short hairpin RNA (shRNA) targeting Id1 gene. PC3 cells, a prostate cancer cell line, were transduced with Id1 shRNA or negative control (NC) shRNA before implantation in BALB/c mice. Cells were implanted in a tibial injection model. Tumor formation in bone was monitored by X-ray. The relationship between parathyroid hormone-related protein (PTHrP), an osteolytic factor, and Id1 was analyzed by using immunohistochemistry in tissue sections from osteolytic lesion of the BALB/c mice. Our results showed that Id1 shRNA delivery to PC3 cells by lentivirus caused efficient and stable Id1 gene silencing. In the intratibial model, PC3 cells produced primarily osteolytic lesions in the bone. Eleven of 14 mice in Id1 shRNA group but only 4 of 14 mice in the NC shRNA group developed osteolytic lesions with cortical destruction at 4th week. Mice treated with Id1 shRNA had larger tumor volume in the bone and larger cortical destruction. The expression of PTHrP protein in PC3 cells was not affected by Id1 knockdown in vivo. These results indicate that Id1 may down-regulate the ability of PC3 cells to form osteolytic lesions in vivo and the signal pathway needs to be further investigated.展开更多
Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate bio...Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate biopsy,Gleason 4+4 score=8,70%,ISUP4 group,localized invasion of nerves.Progressed to metastatic castration-resistant prostate cancer after 8 months of novel endocrine therapy,persistent elevated PSA after endocrine therapy,chemotherapy,and radiation,abdominal metastasis,brain metastasis,gastric metastasis,and staging as neuroendocrine differentiation after second prostate biopsy,which is a highly malignant subtype and has been concerned as a mechanism of resistance to targeted therapies.We discuss how to choose a more optimal treatment plan and outline the patient's diagnostic and therapeutic course.We provide a reflection for the clinical study of metastatic castration-resistant prostate cancer with neuroendocrine type.展开更多
Objective: A method for separating mRNAs by means of the polymerase chain reaction (differential display mRNA), and identifying the genes related to radiation-induced lung cancer was introduced. Methods: The RNAs were...Objective: A method for separating mRNAs by means of the polymerase chain reaction (differential display mRNA), and identifying the genes related to radiation-induced lung cancer was introduced. Methods: The RNAs were isolated from two pairs of samples, SV40-immortalized human fetal tracheal fibroblast cell (SHTF) versus αSHTF cell (transformed SHTF cell induced by α particles) and lung cancer tissue versus normal lung tissue obtained from one miner, and amplified by RTPCR. The differential expressed gene fragments were displayed by autoradiograph or silver nitrate stain. Results: The differential display mRNA method was established using both cell and tissue samples. The bands stained by silver nitrate were clearer than those on X-ray film. The rate of reamplification of differentially expressed gene fragments stained by silver nitrate is 80%, higher than that by autoradiograph, 50%. Conclusion: Differential display mRNA method was established successfully on both cell and tissue samples. The modified method for staining band increased the rate of reamplification and established the basis for confirming relative genes.展开更多
Prostate cancer is a complex, heterogeneous disease that mainly affects the older male population with a high-mortality rate. The mechanisms underlying prostate cancer progression are still incompletely understood. Be...Prostate cancer is a complex, heterogeneous disease that mainly affects the older male population with a high-mortality rate. The mechanisms underlying prostate cancer progression are still incompletely understood. Beta-adrenergic signaling has been shown to regulate multiple cellular processes as a mediator of chronic stress. Recently, beta-adrenergic signaling has been reported to affect the development of aggressive prostate cancer by regulating neuroendocrine differentiation, angiogenesis, and metastasis. Here, we briefly summarize and discuss recent advances in these areas and their implications in prostate cancer therapeutics. We aim to provide a better understanding of the contribution of beta-adrenergic signaling to the progression of aggressive prostate cancer.展开更多
To investigate genes involved in cancer metastasis, mRNA differential display was used to compare the levels of gene expression of two cancer sublines derived from prostate carcinoma cell PC-3M that had different meta...To investigate genes involved in cancer metastasis, mRNA differential display was used to compare the levels of gene expression of two cancer sublines derived from prostate carcinoma cell PC-3M that had different metastatic potentials. The differentially expressed genes were confirmed by Northern blot, and sequenced. The full-length cDNA of a tumor metastasis suppressor gene (TMSG-1) was obtained by using EST assembling and verified by RT-PCR and sequencing. The results showed that expression levels of TMSG-1 were lower in the highly metastatic cell line 1E8, compared with the non-metastatic cell line 2B4. The difference was significant. Full-length cDNA of TMSG-1 was about 2 kb, containing an open reading frame that encoded a protein of 230 amino acids. GenBank Blastn showed no marked homology with known genes. The functional prediction of amino acids sequence encoded by TMSG-1 gene indicated TMSG-1 protein was transmembrane protein, with 3 transmembrane domains, 3 putative protein kinase phosphorylation sites, 2 casein kinase II phosphorylation sites and 1 N-myristoylation site. The pattern of TMSG-1 expression in 6 types of human tumor tissues indicated levels of transcripts were the highest in prostate carcinoma. TMSG-1 had lower expression in metastases of lung carcinoma compared to primary lung carcinoma. Similarly the expression levels were higher in well-differentiated colon carcinoma than that in poorly differentiated colon carcinoma. TMSG-1 could also be detected in breast, ovarian, and pancreatic carcinoma. In 9 samples of primary gastric carcinoma tissues, RT-PCR and densitometric analysis demonstrated TMSG-1 expression levels in samples with lymph node metastases had a decreased tendency, compared to those without lymph node metastases. The difference was significant by student's t test (p<0.05). These results indicated TMSG-1 expression levels were inversely correlated with tumor metastatic potential.展开更多
目的探讨SPECT/CT骨定量分析获得最大标准摄取值(SUV_(max))对老年前列腺癌骨转移的鉴别诊断价值。方法回顾性分析2019年1~12月我院158例确诊前列腺癌患者的99mTc-MDPSPECT/CT骨显像资料。对异常放射性浓聚灶及182个正常椎体行SPECT/CT...目的探讨SPECT/CT骨定量分析获得最大标准摄取值(SUV_(max))对老年前列腺癌骨转移的鉴别诊断价值。方法回顾性分析2019年1~12月我院158例确诊前列腺癌患者的99mTc-MDPSPECT/CT骨显像资料。对异常放射性浓聚灶及182个正常椎体行SPECT/CT检查及骨定量分析,比较良恶性病灶与正常椎体之间SUV_(max)的差异性。选取2019年1~4月46例患者的144个异常浓聚灶,通过绘制ROC曲线得到SUV_(max)的最佳临界值;选取2019年5~12月293个异常浓聚灶,使用SUV_(max)的最佳临界值比较SPECT/CT骨定量分析与常规SPECT/CT的诊断效能。结果以病理或随访作为判断标准,所有老年前列腺癌患者共437个异常浓聚灶(恶性254个,良性183个),恶性病灶的SUV_(max)明显高于良性病灶(43.93±19.09 vs 15.26±6.81,P<0.01)和正常椎体(6.54±1.19,P<0.01)。通过ROC曲线得到SUV_(max)≥19.2为诊断恶性病灶的最佳临界值,常规SPECT/CT与SPECT/CT骨定量诊断的准确度、敏感度、特异性、阳性预测率、阴性预测率分别为81.6%和94.5%、93.0%和96.5%、65.2%和91.7%、79.2%和94.3%、86.8%和94.9%,SPECT/CT骨定量诊断的准确度、特异性、阳性预测率和阴性预测率均明显高于常规SPECT/CT。结论SPECT/CT骨定量分析在老年前列腺癌骨转移的鉴别诊断中具有重要临床应用价值,具有临床应用的潜力。展开更多
基金supported by a grant from the National Natural Science Foundation of China(No.30772206)
文摘The formation of osteolytic bone lesions is a key process for osteolytic cancer to metastasize to the bone and is under the control of a set of transcription factors. Recently, the inhibitor of differentiation 1 (Id1) has been linked with angiogenesis, tumorigenesis, metastasis and bone formation. However, the function of Id1 during the process of bone destruction caused by cancer in vivo has not yet been elucidated. We, therefore, examined whether and how Id1 affects the ability of cancer to form osteolytic lesion in vivo. The study used a lentiviral vector overexpressing short hairpin RNA (shRNA) targeting Id1 gene. PC3 cells, a prostate cancer cell line, were transduced with Id1 shRNA or negative control (NC) shRNA before implantation in BALB/c mice. Cells were implanted in a tibial injection model. Tumor formation in bone was monitored by X-ray. The relationship between parathyroid hormone-related protein (PTHrP), an osteolytic factor, and Id1 was analyzed by using immunohistochemistry in tissue sections from osteolytic lesion of the BALB/c mice. Our results showed that Id1 shRNA delivery to PC3 cells by lentivirus caused efficient and stable Id1 gene silencing. In the intratibial model, PC3 cells produced primarily osteolytic lesions in the bone. Eleven of 14 mice in Id1 shRNA group but only 4 of 14 mice in the NC shRNA group developed osteolytic lesions with cortical destruction at 4th week. Mice treated with Id1 shRNA had larger tumor volume in the bone and larger cortical destruction. The expression of PTHrP protein in PC3 cells was not affected by Id1 knockdown in vivo. These results indicate that Id1 may down-regulate the ability of PC3 cells to form osteolytic lesions in vivo and the signal pathway needs to be further investigated.
基金co-first authors:Zeng-Feng Hanco-first authors/Corresponding to:Bin-Xu Sun,Department of Oncology,The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion.No.88 Changling Road,Xiqing District,Tianjin 300381,China.E-mail:sunbinxu@126.comCorresponding to:Shan-Qi Guo,Department of Oncology,The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion.No.88 Changling Road,Xiqing District,Tianjin 300381,China.E-mail:15022476737@163.com.
文摘Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate biopsy,Gleason 4+4 score=8,70%,ISUP4 group,localized invasion of nerves.Progressed to metastatic castration-resistant prostate cancer after 8 months of novel endocrine therapy,persistent elevated PSA after endocrine therapy,chemotherapy,and radiation,abdominal metastasis,brain metastasis,gastric metastasis,and staging as neuroendocrine differentiation after second prostate biopsy,which is a highly malignant subtype and has been concerned as a mechanism of resistance to targeted therapies.We discuss how to choose a more optimal treatment plan and outline the patient's diagnostic and therapeutic course.We provide a reflection for the clinical study of metastatic castration-resistant prostate cancer with neuroendocrine type.
文摘Objective: A method for separating mRNAs by means of the polymerase chain reaction (differential display mRNA), and identifying the genes related to radiation-induced lung cancer was introduced. Methods: The RNAs were isolated from two pairs of samples, SV40-immortalized human fetal tracheal fibroblast cell (SHTF) versus αSHTF cell (transformed SHTF cell induced by α particles) and lung cancer tissue versus normal lung tissue obtained from one miner, and amplified by RTPCR. The differential expressed gene fragments were displayed by autoradiograph or silver nitrate stain. Results: The differential display mRNA method was established using both cell and tissue samples. The bands stained by silver nitrate were clearer than those on X-ray film. The rate of reamplification of differentially expressed gene fragments stained by silver nitrate is 80%, higher than that by autoradiograph, 50%. Conclusion: Differential display mRNA method was established successfully on both cell and tissue samples. The modified method for staining band increased the rate of reamplification and established the basis for confirming relative genes.
文摘Prostate cancer is a complex, heterogeneous disease that mainly affects the older male population with a high-mortality rate. The mechanisms underlying prostate cancer progression are still incompletely understood. Beta-adrenergic signaling has been shown to regulate multiple cellular processes as a mediator of chronic stress. Recently, beta-adrenergic signaling has been reported to affect the development of aggressive prostate cancer by regulating neuroendocrine differentiation, angiogenesis, and metastasis. Here, we briefly summarize and discuss recent advances in these areas and their implications in prostate cancer therapeutics. We aim to provide a better understanding of the contribution of beta-adrenergic signaling to the progression of aggressive prostate cancer.
基金This work was supported by the National Natural Science Foundation of China (Grant No.30170363) Key Project on Science and Technology of Chinese Ministry of Education (Grant No. 01003), Doctoral Training Foundation of Chinese Ministry of Education (
文摘To investigate genes involved in cancer metastasis, mRNA differential display was used to compare the levels of gene expression of two cancer sublines derived from prostate carcinoma cell PC-3M that had different metastatic potentials. The differentially expressed genes were confirmed by Northern blot, and sequenced. The full-length cDNA of a tumor metastasis suppressor gene (TMSG-1) was obtained by using EST assembling and verified by RT-PCR and sequencing. The results showed that expression levels of TMSG-1 were lower in the highly metastatic cell line 1E8, compared with the non-metastatic cell line 2B4. The difference was significant. Full-length cDNA of TMSG-1 was about 2 kb, containing an open reading frame that encoded a protein of 230 amino acids. GenBank Blastn showed no marked homology with known genes. The functional prediction of amino acids sequence encoded by TMSG-1 gene indicated TMSG-1 protein was transmembrane protein, with 3 transmembrane domains, 3 putative protein kinase phosphorylation sites, 2 casein kinase II phosphorylation sites and 1 N-myristoylation site. The pattern of TMSG-1 expression in 6 types of human tumor tissues indicated levels of transcripts were the highest in prostate carcinoma. TMSG-1 had lower expression in metastases of lung carcinoma compared to primary lung carcinoma. Similarly the expression levels were higher in well-differentiated colon carcinoma than that in poorly differentiated colon carcinoma. TMSG-1 could also be detected in breast, ovarian, and pancreatic carcinoma. In 9 samples of primary gastric carcinoma tissues, RT-PCR and densitometric analysis demonstrated TMSG-1 expression levels in samples with lymph node metastases had a decreased tendency, compared to those without lymph node metastases. The difference was significant by student's t test (p<0.05). These results indicated TMSG-1 expression levels were inversely correlated with tumor metastatic potential.
文摘目的探讨SPECT/CT骨定量分析获得最大标准摄取值(SUV_(max))对老年前列腺癌骨转移的鉴别诊断价值。方法回顾性分析2019年1~12月我院158例确诊前列腺癌患者的99mTc-MDPSPECT/CT骨显像资料。对异常放射性浓聚灶及182个正常椎体行SPECT/CT检查及骨定量分析,比较良恶性病灶与正常椎体之间SUV_(max)的差异性。选取2019年1~4月46例患者的144个异常浓聚灶,通过绘制ROC曲线得到SUV_(max)的最佳临界值;选取2019年5~12月293个异常浓聚灶,使用SUV_(max)的最佳临界值比较SPECT/CT骨定量分析与常规SPECT/CT的诊断效能。结果以病理或随访作为判断标准,所有老年前列腺癌患者共437个异常浓聚灶(恶性254个,良性183个),恶性病灶的SUV_(max)明显高于良性病灶(43.93±19.09 vs 15.26±6.81,P<0.01)和正常椎体(6.54±1.19,P<0.01)。通过ROC曲线得到SUV_(max)≥19.2为诊断恶性病灶的最佳临界值,常规SPECT/CT与SPECT/CT骨定量诊断的准确度、敏感度、特异性、阳性预测率、阴性预测率分别为81.6%和94.5%、93.0%和96.5%、65.2%和91.7%、79.2%和94.3%、86.8%和94.9%,SPECT/CT骨定量诊断的准确度、特异性、阳性预测率和阴性预测率均明显高于常规SPECT/CT。结论SPECT/CT骨定量分析在老年前列腺癌骨转移的鉴别诊断中具有重要临床应用价值,具有临床应用的潜力。