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C Chiao

Publications and source records attributed to C Chiao.

10 recordsLinked to original sources
PubMed2001

HIV type 1 Tat inhibits tumor necrosis factor alpha-induced repression of tumor necrosis factor receptor p55 and amplifies tumor necrosis factor alpha activity in stably tat-transfected HeLa Cells.

The human immunodeficiency virus type 1 (HIV-1) Tat protein is a key regulatory protein in the HIV-1 replication cycle. Tat interacts with cellular transcriptional factors and cytokines, such as tumor necrosis factor (TNF-alpha), and alters the expression of a variety of genes in HIV-1-infected and noninfected cells. To further elucidate the mechanisms by which HIV-1 Tat amplifies the activity of TNF-alpha, we transfected the HIV-1 tat gene into an epithelial (HeLa) cell line. We observed that Tat-expressing cells had increased NF-kappa B-dependent trans-activational activity due to enhanced NF-kappa B--DNA binding in response to TNF-alpha treatment. Tumor necrosis factor receptor (TNFR) p55 was the prominent receptor, as neutralizing antibodies to TNFR p55, but not to TNFR p75, blocked TNF-alpha-mediated NF-kappa B activation. Furthermore, tat-transfected cells were more sensitive to TNF-alpha-induced cytotoxicity and only the neutralizing antibodies to TNFR p55 completely protected the cells. To determine whether TNFR p55 was involved in amplification of cellular response to TNF-alpha by HIV-1 Tat, we investigated the effect of TNF-alpha on TNFR p55 expression in the tat-transfected cells. TNF-alpha treatment resulted in a reduction in both TNFR p55 mRNA and protein levels in the control cells but not in the tat-transfected cells as determined with Northern blot and Western blot analyses, respectively. Our results indicate that HIV-1 Tat may inhibit TNF-alpha-induced repression of TNFR p55 and thereby amplify TNF-alpha activity in these stably transfected cells.

Antigens, CD↗
PubMed2000

Identification of c-myc responsive genes using rat cDNA microarray.

c-Myc functions through direct activation or repression of transcription. Using cDNA microarray analysis, we have identified c-Myc-responsive genes by comparing gene expression profiles between c-myc null and c-myc wild-type rat fibroblast cells and between c-myc null and c-myc null cells reconstituted with c-myc. From a panel of 4400 cDNA elements, we found 198 genes responsive to c-myc when comparing wild-type or reconstituted cells with the null cells. The plurality of the named c-Myc-responsive genes that were up-regulated, including 30 ribosomal protein genes, are involved in macromolecular synthesis and metabolism, suggesting a major role of c-Myc in the regulation of protein synthetic and metabolic pathways. When ectopically overexpressed, c-Myc induced a different and smaller set of c-Myc-responsive genes as compared with the physiologically expressed c-Myc condition. Thus, these results from expression profiling suggest a new primary function for c-Myc and raise the possibility that the physiological and transforming functions of c-myc may be separable.

Animals↗
PubMed1999

Loss of KAI1 expression in the progression of colorectal cancer.

The transmembrane 4 superfamily member KAI1 (CD82) has been shown to inhibit pulmonary metastases in experimental metastasis models of prostate cancer and melanoma. KAI1 expression is decreased in the progression of common solid epithelial tumors of adulthood, including lung, prostate, breast, esophageal, gastric, pancreatic, and bladder cancers. The purpose of our study was to investigate KAI1 expression in the progression of human colorectal cancer. We first analyzed 20 colorectal cancer cell lines by immunoblot techniques. KAI1 was expressed heterogeneously, with the tumor cell lines having a more complex degree of glycosylation compared with that of the normal colonic tissue. KAI1 was highly expressed in the primary SW480 colon cancer cell line but was down-regulated 15-fold in the matched metastatic SW620 cell line. We also investigated KAI1 protein expression by immunohistochemistry in tissues from 84 patients with colorectal cancer. Each tissue section was assigned a KAI1 mean score (KMS) from 0 to 300 based on the product of the percentage of cells that stained for KAI1 and the intensity of the stain (1, 2, or 3). In 84 patients with colorectal cancer, KAI1 was expressed at high levels in normal colonic mucosa (KMS 226) but was expressed at lower levels in the primary tumors (KMS 65; P < 0.0001). In a subset of 12 patients with stage IV metastatic disease, we observed a progressive down-regulation of KAI1, from the normal adjacent colonic mucosa (KMS 193) to the primary tumor (KMS 72; P = 0.0001) to the liver metastasis (KMS 25; tumor compared with metastasis, P = 0.0135). We found no correlation between loss of KAI1 expression and stage of disease. In 10 patients, we also noted loss of KAI1 expression in the transition from normal colonic mucosa (KMS 237) to adenoma (KMS 174) to carcinoma (KMS 62; P < 0.0167 for all three comparisons). We conclude that the down-regulation of KAI1 occurs early in the progression of colorectal cancer.

Adenoma↗
PubMed1999

Two posttranscriptional pathways that regulate p21(Cip1/Waf1/Sdi1) are identified by HPV16-E6 interaction and correlate with life span and cellular senescence.

The p21((Cip1/Waf1/Sdi1)) protein is a cyclin-dependent kinase inhibitor that is induced in normal human fibroblasts (NHF) following DNA damage, following serum stimulation, and at cellular senescence. Expression of the human papilloma virus 16 E6 oncoprotein in NHF cells results in the loss of the p21 protein, independent of mRNA level under most conditions. The p21 protein levels in NHF-E6 cells remained low following DNA damage or serum stimulation even though mRNA levels increased. In contrast, the p21 protein was transiently induced in NHF-E6 cells at the onset of cellular senescence. Expression of the E6 oncoprotein in transformed cells had no effect on p21 protein levels. This demonstrates that two posttranscriptional pathways regulate expression of p21 protein in NHF cells under different conditions. Disruption of posttranscriptional regulation is correlated with extension of life span, altered cell fate, and transformation.

Cell Transformation, Viral↗
PubMed1997

p53-dependent p21 induction following gamma-irradiation without concomitant p53 induction in a human peripheral neuroepithelioma cell line.

We previously generated cell hybrids between a derivative of the E6-containing HeLa cell line and a p53 null peripheral neuroepithelioma (PNET) cell line. Although p53 protein from the hybrids was genotypically wild type, it did not demonstrate wild-type behavior. Therefore, in the present study, we introduced wild-type p53 into the PNET parent to investigate whether p53 retained wild-type function within this cell line. Although the p53 null PNET parent lacked detectable p21 protein, introduction of wild-type p53 resulted in a detectable expression of p21 protein in all clones tested, suggestive of wild-type p53 function. In addition, p53 expression was necessary for induction of p21 in response to irradiation, and, furthermore, we show this induction to occur at the transcriptional level. Although introduction of wild-type p53 seems to be responsible for p21 induction, the overall protein levels of p53 were not induced. The involvement of p53 in up-regulating p21 is further substantiated by the observation that p21 up-regulation was dependent on the introduction of the wild-type protein. Our results suggest that wild-type p53 is capable of up-regulating p21 in response to DNA damage in the absence of p53 induction.

Biological Transport↗
PubMed1995

Apoptosis and altered redox state induced by caffeic acid phenethyl ester (CAPE) in transformed rat fibroblast cells.

Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of bee hives, was shown previously to block tumor promoter- and carcinogen-generated oxidative processes in several assays and to engender differential toxicity to some transformed cells. To study the mechanisms of CAPE-induced differential cytotoxicity, nontumorigenic rat embryo fibroblasts (CREF) and adenovirus (type 5)-transformed CREF cells (Wt3A) were used. As shown by nucleosomal-length DNA degradation, morphological alterations by electron microscopy, in situ labeling of 3'-OH ends, and the appearance of a hypodiploid cell population by bivariant flow cytometry, cell death induced by CAPE in the transformed Wt3A cells was apoptosis. Under the same CAPE treatment conditions, CREF cells transiently growth arrested. Both CREF and Wt3A cells were radioresistant, suggesting deficiencies in the proteins controlling the G1 checkpoint. To explore possible mechanisms of CAPE-induced apoptosis, it was determined whether CAPE-induced toxicity was influenced by the redox state of the cells. Depletion of cellular glutathione (GSH) with buthionine sulfoximine before CAPE treatment caused CREF sensitive to CAPE-induced cell death. GSH levels were also determined in CAPE-treated CREF and Wt3A cells. The GSH level in the CREF cells was unaffected by CAPE, whereas the Wt3A cells showed a significant reduction. When the GSH levels were increased in Wt3A cells by treatment with the reducing agent, N-acetyl-cysteine before CAPE treatment, the Wt3A cells were partially rescued. Furthermore, Bcl2, which protects cells from oxidative stress, had a protective effect against CAPE-induced apoptosis in Wt3A cells. Finally, the sensitivity of Wt3A cells to a known oxidant, hydrogen peroxide (H2O2), was examined. Wt3A cells were killed by H2O2-induced apoptosis, whereas CREF cells remained resistant. When Wt3A cells were treated with catalase, a cellular enzyme that inactivates H2O2, CAPE-induced apoptosis in Wt3A cells was reduced, further proving that Wt3A cells were more sensitive than CREF cells to oxidative stress. These results suggest that CAPE can modulate the redox state of cells. Sensitivity of cells to CAPE-induced cell death may be determined by the loss of normal redox state regulation in transformed cells.

Acetylcysteine↗
PubMed1995

Phenobarbital modulates the type of cell death by rat hepatocytes during deprivation of serum in vitro.

An immortal line of chemically altered rat hepatocytes was used to study the effects of the liver tumor promoter, phenobarbital (PB), on hepatocyte growth and viability in vitro. When the serum concentration in medium was changed from 10% to 0.5%, cell proliferation decreased and hepatocytes died. Death of the hepatocytes occurred after 2 days in low-serum medium. PB appeared to control the type of cell death that occurred. In the absence of PB in low-serum medium, most dead cells had morphological changes that are characteristic of necrosis as determined by both light and electron microscopy. In the presence of PB, the dead cells had alterations typical of apoptosis. Biochemical features of cell death in low-serum medium were also analyzed. DNA isolated from cells in low serum with PB showed nucleosome-length fragments after gel electrophoresis, whereas DNA from cells in low serum without PB appeared as randomly degraded fragments. Although proliferation of hepatocytes in low-serum decreased by 75%, the appearance of apoptosis in the presence of PB was associated with increased expression of the c-myc gene. Based on these observations, we conclude that PB can modulate the type of cell death that occurs after serum deprivation in this line of immortal rat hepatocytes. PB seemed to prevent necrotic cell death in low serum, and cells died through a gene-directed pathway of apoptosis.

Animals↗
PubMed1995

Derivation of phenobarbital-responsive immortal rat hepatocytes.

Two lines of rat hepatocytes, designated 6/15 and 6/27, were obtained from carcinogen-treated livers by cultivation in medium containing the liver tumor promoter, phenobarbital (PB). Both lines appeared to be PB-responsive and to have an unlimited in vitro proliferative lifespan, i.e., immortality. The ability of pure 6/27 hepatocytes to form colonies from single cells was strictly dependent upon PB; it was reduced by 97 to 99% in the absence of PB. These hepatocytes were not tumorigenic. For 6/27 hepatocytes in early passages where cultures contained fibroblast contaminants and later when they were a pure culture, PB was able to enhance colony growth from single cells and facilitated population expansion by sustaining DNA synthesis and by inhibiting cell lysis. The 6/15 line displayed PB-dependent colony formation and was not tumorigenic at early passages. At later passages 6/15 hepatocytes were less dependent on PB for colony formation, and they formed hepatocellular carcinoma when transplanted into livers of syngeneic rats. The demonstration that PB sustained the proliferation and viability of hepatocytes with enhanced growth capacity and indefinite proliferative lifespan suggests that PB may be necessary for progression of these chemically initiated hepatocytes to immortal and tumorigenic lines in vitro.

Animals↗
PubMed1994

Hyperbaric oxygen therapy in hemorrhagic radiation cystitis: a report of 20 cases.

Radiation cystitis with macroscopic hematuria has been a frustrating clinical problem for urologists. Since 1985 hyperbaric oxygen (HBO) has been used to treat this disease, showing favorable results. Between November 1989 and October 1992, 20 female patients with hemorrhagic radiation cystitis were treated with HBO at a pressure of 2.5 atm abs, breathing 100% O2 for 100 min in our multiplace hyperbaric chamber. After an average of 44 HBO sessions, macroscopic hematuria was completely halted in 16 patients (80%) and markedly decreased in 2 patients (10%). Comparison of the cystoscopic findings before and after HBO showed a significant decrease in hemorrhagic sites and telangiectasis of the bladder mucosa. One patient had urinary frequency and urgency without hematuria during her hospital stay. After 30 sessions of HBO therapy, her symptoms subsided, and the cystoscopic findings were much improved. Only one patient failed to respond to HBO and underwent ileal conduit diversion. The mean follow-up period was 14 mo. (5-41 mo.). From our clinical results and cystoscopic findings, we suggest that HBO is an effective and safe treatment for hemorrhagic radiation cystitis.

Adult↗