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C Kao

Publications and source records attributed to C Kao.

87 records · Page 5Linked to original sources
PubMed1988

The lit gene product which blocks bacteriophage T4 late gene expression is a membrane protein encoded by a cryptic DNA element, e14.

Escherichia coli lit(Con) mutations cause a severe inhibition of gene expression late in infection by bacteriophage T4 owing to the overproduction of one, and possibly two, proteins (C. Kao, E. Gumbs, and L. Snyder, J. Bacteriol. 169:1232-1238, 1987). One or both of these proteins interact, either directly or indirectly, with a short sequence about one-quarter of the way into the major capsid protein gene of T4, and the inhibition occurs when this late gene of the virus is expressed. In this report we show that lit(Con) mutations are up-promoter mutations in the cryptic DNA element e14 and that only one of the proteins, gplit, of about 34 kilodaltons, is required for the inhibition. We have sequenced the lit gene and the surrounding regions. From the sequence, and from cell fractionation studies, we conclude that gplit is an inner membrane protein. Since the assembly of T4 heads is thought to occur on the inner face of the inner membrane, we propose that gplit interferes with a normal regulation which coordinates the synthesis of proteins and the assembly of T4 heads.

Amino Acid Sequence↗
PubMed1987

Cloning and characterization of the Escherichia coli lit gene, which blocks bacteriophage T4 late gene expression.

Escherichia coli lit mutations inhibit gene expression late in infection by bacteriophage T4. We cloned the lit gene from wild-type E. coli and three independent lit mutants. We present evidence that lit mutations [renamed lit(Con) mutations] cause overproduction of the lit gene product and that overproduction of this product causes the inhibition of gene expression. We also present evidence that the lit gene product is nonessential for E. coli growth, although the gene is common to most E. coli K-12 strains.

Cloning, Molecular↗
PubMedDate not supplied

p53 adenoviral vector (Ad-CMV-p53) induced prostatic growth inhibition of primary cultures of human prostate and an experimental rat model.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common proliferative disease affecting men. Numerous minimally invasive technologies are being developed or are currently in use to obviate the need for transurethral surgery. The goal of the present study was to develop a novel molecular based approach for the treatment of BPH using recombinant p53 adenoviral vector. The over-expression of wt-p53 can cause cell apoptosis or cell growth arrest, thus preventing the uncontrolled cell proliferation underlying BPH pathophysiology. METHODS: Ad-CMV-p53, a replication-deficient recombinant adenovirus containing cytomegalovirus promoter driving p53 gene, was used. Human prostate stromal (PS) cells were evaluated for apoptosis (TUNEL assay), mRNA levels of key cell cycle regulators influencing apoptosis (p-53, Bax and Bcl-2) using quantitative RT-PCR and cytotoxicity after Ad-CMV-p53. Ad-CMV-p53 was unilaterally injected into rat ventral prostates and growth inhibition was measured by prostate weight 3 weeks after injection. RESULTS: In vitro exposure to Ad-CMV-p53 significantly inhibited the proliferation of PS cells, induced mRNA over-expression of both wt-p53 and Bax, and increased the proportion of apoptotic cells. A 30% decrease in average prostate weight was demonstrated in rodents after Ad-CMV-p53 injection. CONCLUSIONS: The results suggest that further investigation of molecular gene therapy with recombinant wt-p53 adenovirus for the treatment of BPH is warranted.

Adenoviridae↗
PubMedDate not supplied

Death rates in 71 men with antisocial personality disorder. A comparison with general population mortality.

Mortality data are presented from a 16- to 45-year follow-up study of 71 men with antisocial personality disorder. Death ascertainment was made through both a personal follow-up and use of the National Death Index. Comparisons were made with the mortality experience of the general population of the state of Iowa by using gender and age standardized mortality ratios. Seventeen men died (24%) died during the follow-up. Antisocial men younger than 40 years were at excessive risk for premature death (standardized mortality ratio [SMR] = 33, P < 0.25): men between ages 40 and 60 years also appeared to be at risk for premature death, although the excess was not statistically significant. Three subjects (18% of all deaths) died of complications from diabetes mellitus (SMR = 14, P < 0.05). Deaths were spread out among the four decades of follow-up. The findings and their implications are discussed.

Adult↗
PubMedDate not supplied

Chemogene therapy: osteocalcin promoter-based suicide gene therapy in combination with methotrexate in a murine osteosarcoma model.

We previously reported that the recombinant adenovirus (Ad) vector containing the thymidine kinase (TK) gene driven by the osteocalcin (OC) promoter (Ad-OC-TK), when delivered concurrently with acyclovir (ACV), is highly selective in blocking the growth of osteosarcoma in experimental models (Cancer Res. 1996;56:4614-4619). To investigate the possible additive effects of the combined treatment of gene therapy and conventional chemotherapy (chemogene therapy), we compared the effect of low dose (IC10) methotrexate (MTX) and OC promoter-based toxic gene therapy with either of these single modalities alone. We choose low dose MTX with the intent of determining whether chemosensitization of the osteosarcoma may be possible in combination with gene therapy with an overall reduced toxicity profile and enhanced therapeutic efficacy when compared to a single agent alone. In vitro, the combined treatments of MTX (3 ng/mL) and Ad-OC-TK (20 multiplicity of infection (MOI)/target cell) plus ACV (10 mg/mL) had an additive therapeutic effect over that of either MTX (P < 0.05) or Ad-OC-TK plus ACV treatment alone (P < 0.05). In vivo, nude mice with subcutaneous tumors of either human osteosarcoma (MG-63) or rat osteosarcoma (ROS) received three intratumoral injections of Ad-OC-TK (5 x 10(8) PFU) plus daily intraperitoneal ACV (40 mg/kg body weight) for 2 weeks in combination with five weekly bolus intraperitoneal MTX (87.5 mg/kg). Osteosarcoma tumor growth was inhibited more efficiently than by either Ad-OC-TK plus ACV (P < 0.05) or MTX treatment (P < 0.005) alone. At day 45 in the ROS group, 100% of the animals survived when treated with chemogene therapy, whereas 80% survived with gene therapy and no animals survived in the MTX-treated or untreated controls. In summary, we developed a novel therapeutic strategy for the treatment of osteosarcoma employing both chemotherapy and gene therapy. Chemogene therapy could potentially achieve better antitumor effects with reduced toxicity than the conventional chemotherapy or gene therapy protocols alone.

Acyclovir↗
PubMedDate not supplied

In vivo suppression of osteosarcoma pulmonary metastasis with intravenous osteocalcin promoter-based toxic gene therapy.

Pulmonary metastases are the main cause of death of patients with several types of cancer, including osteosarcoma, renal cell carcinoma, malignant melanoma, and breast cancer. Previously, we demonstrated that intralesional injection of the recombinant adenovirus (Ad) vector containing the herpes simplex virus thymidine kinase (TK) gene driven by an osteocalcin (OC) promoter (Ad-OC-TK) effectively suppressed the growth of osteosarcoma cells in vitro and tumors in vivo in a tumor-specific manner when supplemented with the prodrug acyclovir (ACV). In this communication, we studied the potential efficacy of the treatment of osteosarcoma pulmonary metastases with a systemic delivery route of Ad-OC-TK supplemented with ACV. We established osteosarcoma lung metastases in nude mice by the intravenous injection of rat osteosarcoma cells, ROS 17/2.8. These cells colonized and formed tumor nodules within 1 week in the lungs of nude mice. Whereas systemic delivery of a recombinant Ad vector containing the Escherichia coli beta-galactosidase (beta-gal) gene driven by a Rous sarcoma virus universal promoter (Ad-RSV-beta-gal) resulted in the nonspecific expression of beta-gal activity in the lung parenchyma, Ad-OC-beta-gal administration resulted in specific beta-gal expression in tumor cells deposited in the lung. When nude mice bearing ROS 17/2.8 lung tumors were treated with systemic Ad-OC-TK through tail vein administration, subsequent intraperitoneal ACV treatment significantly decreased the number of tumor nodules (P < .0001) and the net lung wet weight (P = .0005) while significantly increasing (.005 < P < .01) the survival of animals, when compared with untreated and Ad-OC-TK- or ACV-treated control groups. These results suggest that Ad-OC-TK/ACV may be used as a systemic therapy for the treatment of osteosarcoma lung metastasis.

Acyclovir↗