OBJECTIVE To explore the relationship between CAR and the development of human lung cancer, as well as to provide the basis for the clinical treatment of lung cancer using an adenovirus vector-based gene therapy. METH...OBJECTIVE To explore the relationship between CAR and the development of human lung cancer, as well as to provide the basis for the clinical treatment of lung cancer using an adenovirus vector-based gene therapy. METHODS CAR expression was assessed immunohisto- chemically in tumoral, paraneoplastic and normal samples from 112 lung cancer patients. At the same time, the mRNA and protein expression of CAR in 32 cases were determined by RT-PCR and Western blot. The relationship between CAR expression and clinicopathologic parameters was statistically analyzed. RESULTS There was no expression of CAR in normal lung tissue but a little in paraneoplastic tissue. The positive rate was 43% in squamous cell carcinoma, and 70% in adenocarcinoma. Both were much significantly higher than that in paraneoplastic tissue. The CAR expression level in adenocarcinoma was higher than that in squamous cell cancer, mRNA expression by RT-PCR and protein expression by Western blot were consistent with immunohistochemistry results. CONCLUSION CAR is overexpressed in human lung cancer, especially in adenocarcinoma. This data offer the reliable basis for adenovirus-mediated gene therapy of lung cancer; more important, CAR may take part in the formation or development of lung cancer; this may be exploitable for the development of antibody-directed therapy in human lung cancer.展开更多
OBJECTIVE To observe the effects of sense and antisense oligodeoxynucleotides of tankyrase 1 （TANK1-SODN and TANK1-ASODN） on murine tumor growth following intratumoral injection, investigate the actual suppressing r...OBJECTIVE To observe the effects of sense and antisense oligodeoxynucleotides of tankyrase 1 （TANK1-SODN and TANK1-ASODN） on murine tumor growth following intratumoral injection, investigate the actual suppressing result and mechanism of TANK1-ASODN on cancer cell proliferation, and discuss the possibility of using it in gene therapy on human lung cancer cells. METHODS After BALB/c nude mice had been subcutaneously inoculated with human lung cancer cell line CALU and it had grown into tumor nodules, we distributed these mice randomly into 3 groups： 4 in saline treatment group, and 5 each in TANK1-SODN group, and TANK1-ASODN groups. Then multiple direct intratumoral injections of synthesized TANK1-ASODN given continuously into tumor nodules for 16 days, this was compared with TANK1-SODN and saline control groups. During the experiment we measured the tumor volume every 5 days with vernier calipers; observed the histopathological characteristics of tumor tissues under microscope; went further to detect the minute changing of ultrastructure of cancer cells by electron microscope; tested the expression levels of ki67 and hTERT protein by means of SABC immunohistochemical method; and detected the lung cancer cells＇ hTERT mRNA expression level by hybridization in situ （ISH） in each group. RESULTS After 16 days of continuous injection, the tumor volume in TANK1-ASODN group was significantly smaller than the other 2 groups （both P 〈 0.01）; quite a lot of tumor cell degeneration and necrosis were observed in mice given TANK1-ASODN. The results of electron microscope also showed that TANK1-ASODN has the power to kill cancer cells in various ways. Moreover, statistically signi.cant decreases in the positive expression ratio of Ki67 Labeling Index （P 〈 0.01）, hTERT protein （P 〈 0.01）, and hTERT mRNA （P 〈 0.01） were consistently observed in the TANK1-ASODN group. CONCLUSION Human lung cancer cell line CALU expressed high telomerase activity. TANK1-ASODN had the ability to decline the high expression level of hTERT; inhibit the activity of telomerase, accelerate tumor cell degeneration and necrosis; and then suppress the proliferation of cancer cells.展开更多
文摘OBJECTIVE To explore the relationship between CAR and the development of human lung cancer, as well as to provide the basis for the clinical treatment of lung cancer using an adenovirus vector-based gene therapy. METHODS CAR expression was assessed immunohisto- chemically in tumoral, paraneoplastic and normal samples from 112 lung cancer patients. At the same time, the mRNA and protein expression of CAR in 32 cases were determined by RT-PCR and Western blot. The relationship between CAR expression and clinicopathologic parameters was statistically analyzed. RESULTS There was no expression of CAR in normal lung tissue but a little in paraneoplastic tissue. The positive rate was 43% in squamous cell carcinoma, and 70% in adenocarcinoma. Both were much significantly higher than that in paraneoplastic tissue. The CAR expression level in adenocarcinoma was higher than that in squamous cell cancer, mRNA expression by RT-PCR and protein expression by Western blot were consistent with immunohistochemistry results. CONCLUSION CAR is overexpressed in human lung cancer, especially in adenocarcinoma. This data offer the reliable basis for adenovirus-mediated gene therapy of lung cancer; more important, CAR may take part in the formation or development of lung cancer; this may be exploitable for the development of antibody-directed therapy in human lung cancer.
文摘OBJECTIVE To observe the effects of sense and antisense oligodeoxynucleotides of tankyrase 1 （TANK1-SODN and TANK1-ASODN） on murine tumor growth following intratumoral injection, investigate the actual suppressing result and mechanism of TANK1-ASODN on cancer cell proliferation, and discuss the possibility of using it in gene therapy on human lung cancer cells. METHODS After BALB/c nude mice had been subcutaneously inoculated with human lung cancer cell line CALU and it had grown into tumor nodules, we distributed these mice randomly into 3 groups： 4 in saline treatment group, and 5 each in TANK1-SODN group, and TANK1-ASODN groups. Then multiple direct intratumoral injections of synthesized TANK1-ASODN given continuously into tumor nodules for 16 days, this was compared with TANK1-SODN and saline control groups. During the experiment we measured the tumor volume every 5 days with vernier calipers; observed the histopathological characteristics of tumor tissues under microscope; went further to detect the minute changing of ultrastructure of cancer cells by electron microscope; tested the expression levels of ki67 and hTERT protein by means of SABC immunohistochemical method; and detected the lung cancer cells＇ hTERT mRNA expression level by hybridization in situ （ISH） in each group. RESULTS After 16 days of continuous injection, the tumor volume in TANK1-ASODN group was significantly smaller than the other 2 groups （both P 〈 0.01）; quite a lot of tumor cell degeneration and necrosis were observed in mice given TANK1-ASODN. The results of electron microscope also showed that TANK1-ASODN has the power to kill cancer cells in various ways. Moreover, statistically signi.cant decreases in the positive expression ratio of Ki67 Labeling Index （P 〈 0.01）, hTERT protein （P 〈 0.01）, and hTERT mRNA （P 〈 0.01） were consistently observed in the TANK1-ASODN group. CONCLUSION Human lung cancer cell line CALU expressed high telomerase activity. TANK1-ASODN had the ability to decline the high expression level of hTERT; inhibit the activity of telomerase, accelerate tumor cell degeneration and necrosis; and then suppress the proliferation of cancer cells.
