AIM To establish a tissue-specific gene therapy for colorectal carcinoma using bacterial ADP-ribosylating toxin genes.METHODS Pseudomonas exotoxin A domain Ⅱ+Ⅲ (PEA) was cloned from genomic DNA of Pseudomonas aerugi...AIM To establish a tissue-specific gene therapy for colorectal carcinoma using bacterial ADP-ribosylating toxin genes.METHODS Pseudomonas exotoxin A domain Ⅱ+Ⅲ (PEA) was cloned from genomic DNA of Pseudomonas aeruginosa. PEA and diphtheria toxin A chain gene (DTA) were modified to express eukaryotically. After sequencing, the toxin genes under the control of human carcinoembryonic antigen (CEA) promoter were cloned into retroviral vectors to construct CEAPEA and CEADTA respectively. In vitro cotransfection of the constructs with luciferase vectors and in vivo gene transfer in nude mice were subsequently carried out.RESULTS Both CEAPEA and CEADTA specifically inhibited the reporter gene expression in the CEA positive human colorectal carcinoma (CRC) cells in vitro. Direct injection of CEAPEA and CEADTA constructs into the established human tumors in BALB/c nude mice led to significant and selective reductions in CRC tumor size as compared with that in control groups.CONCLUSION The toxin genes, working as therapeutic genes, are suitable for the tissue-specific gene therapy for colorectal carcinoma.展开更多
Using targeted toxins is a promising approach for the therapy of cancer and autoimmune diseases, as well as other disorders/The high mobility group chromosomal protein N2 （HMGN2） is one of the most abundant and well...Using targeted toxins is a promising approach for the therapy of cancer and autoimmune diseases, as well as other disorders/The high mobility group chromosomal protein N2 （HMGN2） is one of the most abundant and well-characterized classes of nonhistone nuclear proteins, which seems to function as architectural elements in chromatin.2 Recently our group isolated an antimicrobial polypeptide from human LAK cells and cervical mucus,展开更多
In the past decade,an increased amount of clinicallyloriented research involving immunotoxins has been published. Immunotoxins are a group of artificially-made cytotoxic molecules targeting cancer cells.These molecule...In the past decade,an increased amount of clinicallyloriented research involving immunotoxins has been published. Immunotoxins are a group of artificially-made cytotoxic molecules targeting cancer cells.These molecules composed of a targeting moiety,such as a ligand or an antibody,linked to toxin moiety,which is a toxin with either truncated or deleted cell-binding domain that prevents it from binding to normal cells.Immunotoxins can be divided into two categories:chemically conjugated immunotoxins and recombinant ones.The immunotoxins of the first category have shown limited efficacy in clinical trials in patients with hematologic malignancies and solid tumors.Within the last few years,single-chain immunotoxins provide enhanced therapeutic efficacy over conjugated forms and result in improved antitumor activity.In this review,we briefly illustrate the design of the immunotoxins and their applications in clinical trials.Cellular & Molecular Immunology.2005;2(2):106-112.展开更多
To investigate inhibitory effect of recombinant transforming growth factora-pseudomonas exotoxin fusion protein (TGFInhibitory effect of TGF_α-PE40; TP40) on neointimal proliferation following arterial injury.Methods...To investigate inhibitory effect of recombinant transforming growth factora-pseudomonas exotoxin fusion protein (TGFInhibitory effect of TGF_α-PE40; TP40) on neointimal proliferation following arterial injury.Methods: Forty-eight male rabbits fed with rich cholesterol diet were randomized into the treatment group(n= 24)and the control group (n=24). The rabbits in the treatment group were treated by local adiministration of TP40 (30 μg) 24 h after arterial injury, and the control group were treated by saline. LM and computer image analysis were used to study the rabbit arterial segments 2, 4 and & weeks after treatment. Results: Irregular thickening of the arterial intima. large amounts of smooth muscle cells within the neointima, and stenosis of the arterial cavity in the control group, and significant inhibition of intimal proliferation and no stenosis of the arterial cavity in the treatment group were observed microscopically. Computer image analysis showed that the neointimal area and the ratio of neointimal/medial area of the treatment group at 2, 4 and 8weeks after treatment were signifantly smaller than those of the control groups (P<0. 01 ). COnclusion: The results suggest that TP40 can significantly inhibit neointimal proliferation following carotid arterial injury.展开更多
文摘AIM To establish a tissue-specific gene therapy for colorectal carcinoma using bacterial ADP-ribosylating toxin genes.METHODS Pseudomonas exotoxin A domain Ⅱ+Ⅲ (PEA) was cloned from genomic DNA of Pseudomonas aeruginosa. PEA and diphtheria toxin A chain gene (DTA) were modified to express eukaryotically. After sequencing, the toxin genes under the control of human carcinoembryonic antigen (CEA) promoter were cloned into retroviral vectors to construct CEAPEA and CEADTA respectively. In vitro cotransfection of the constructs with luciferase vectors and in vivo gene transfer in nude mice were subsequently carried out.RESULTS Both CEAPEA and CEADTA specifically inhibited the reporter gene expression in the CEA positive human colorectal carcinoma (CRC) cells in vitro. Direct injection of CEAPEA and CEADTA constructs into the established human tumors in BALB/c nude mice led to significant and selective reductions in CRC tumor size as compared with that in control groups.CONCLUSION The toxin genes, working as therapeutic genes, are suitable for the tissue-specific gene therapy for colorectal carcinoma.
基金This study was supported by grants from the China Methcal Board of New York Inc. （No. 98-681）, and the National Natural Science Foundation of China （No. 30470763 and No. 30671963）.
文摘Using targeted toxins is a promising approach for the therapy of cancer and autoimmune diseases, as well as other disorders/The high mobility group chromosomal protein N2 （HMGN2） is one of the most abundant and well-characterized classes of nonhistone nuclear proteins, which seems to function as architectural elements in chromatin.2 Recently our group isolated an antimicrobial polypeptide from human LAK cells and cervical mucus,
文摘In the past decade,an increased amount of clinicallyloriented research involving immunotoxins has been published. Immunotoxins are a group of artificially-made cytotoxic molecules targeting cancer cells.These molecules composed of a targeting moiety,such as a ligand or an antibody,linked to toxin moiety,which is a toxin with either truncated or deleted cell-binding domain that prevents it from binding to normal cells.Immunotoxins can be divided into two categories:chemically conjugated immunotoxins and recombinant ones.The immunotoxins of the first category have shown limited efficacy in clinical trials in patients with hematologic malignancies and solid tumors.Within the last few years,single-chain immunotoxins provide enhanced therapeutic efficacy over conjugated forms and result in improved antitumor activity.In this review,we briefly illustrate the design of the immunotoxins and their applications in clinical trials.Cellular & Molecular Immunology.2005;2(2):106-112.
文摘To investigate inhibitory effect of recombinant transforming growth factora-pseudomonas exotoxin fusion protein (TGFInhibitory effect of TGF_α-PE40; TP40) on neointimal proliferation following arterial injury.Methods: Forty-eight male rabbits fed with rich cholesterol diet were randomized into the treatment group(n= 24)and the control group (n=24). The rabbits in the treatment group were treated by local adiministration of TP40 (30 μg) 24 h after arterial injury, and the control group were treated by saline. LM and computer image analysis were used to study the rabbit arterial segments 2, 4 and & weeks after treatment. Results: Irregular thickening of the arterial intima. large amounts of smooth muscle cells within the neointima, and stenosis of the arterial cavity in the control group, and significant inhibition of intimal proliferation and no stenosis of the arterial cavity in the treatment group were observed microscopically. Computer image analysis showed that the neointimal area and the ratio of neointimal/medial area of the treatment group at 2, 4 and 8weeks after treatment were signifantly smaller than those of the control groups (P<0. 01 ). COnclusion: The results suggest that TP40 can significantly inhibit neointimal proliferation following carotid arterial injury.
