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Jimmy Brown

Publications and source records attributed to Jimmy Brown.

7 recordsLinked to original sources
PubMed2005

Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1alpha and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells.

Hypoxia-inducible factor-1alpha (HIF-1alpha) is overexpressed in many human tumors and their metastases, and is closely associated with a more aggressive tumor phenotype. In this study, we investigated the effect of resveratrol, a natural product commonly found in grapes and various other fruits, on hypoxia-induced HIF-1alpha protein accumulation and vascular endothelial growth factor (VEGF) expression in human tongue squamous cell carcinomas and hepatoma cells. Our results showed that resveratrol significantly inhibited both basal level and hypoxia-induced HIF-1alpha protein accumulation in cancer cells, but did not affect HIF-1alpha mRNA levels. Pretreatment of cells with resveratrol significantly reduced hypoxia-induced VEGF promoter activities and VEGF expression at both mRNA and protein levels. The mechanism of resveratrol inhibition of hypoxia-induced HIF-1alpha accumulation seems to involve a gradually shortened half-life of HIF-1alpha protein caused by an enhanced protein degradation through the 26S proteasome system. In addition, resveratrol remarkably inhibited hypoxia-mediated activation of extracellular signal-regulated kinase 1/2 and Akt, leading to a marked decrease in hypoxia-induced HIF-1alpha protein accumulation and VEGF transcriptional activation. Functionally, we observed that resveratrol also significantly inhibited the hypoxia-stimulated invasiveness of cancer cells. These data suggested that HIF-1alpha/VEGF could be a promising drug target for resveratrol in the development of an effective chemopreventive and anticancer therapy in human cancers.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Treatment with siRNA and antisense oligonucleotides targeted to HIF-1alpha induced apoptosis in human tongue squamous cell carcinomas.

Overexpression of hypoxia inducible factor-1alpha (HIF-1alpha) in cancers has been correlated to a more aggressive tumor phenotype. We investigated the effect of HIF-1alpha knockout on the in vitro survival and death of human tongue squamous cell carcinomas (SCC-4 and SCC-9). Under normoxic condition, a basal level of HIF-1alpha protein was constitutively expressed in SCC-9 cells, albeit an undetectable level of HIF-1alpha messages. Exposure to hypoxia induced only a transient increase in mRNA transcript but a prolonged elevation of HIF-1alpha protein and its immediate downstream target gene product, VEGF. Under normoxic or hypoxic conditions, treatment of SCC-9 cells with AS-HIF-1alpha ODN suppressed both constitutive and hypoxia-induced HIF-1alpha expression at both mRNA and protein levels. Knockout of HIF-1alpha gene expression via either AS-HIF-1alpha ODN or siRNA (siRNAHIF-1alpha) treatment resulted in inhibition of cell proliferation and induced apoptosis in SCC-4 and SCC-9 cells. We also demonstrated that exposure of SCC-9 cells to hypoxia led to a time-dependent increase in the expression of bcl-2 and IAP-2, but not p53. The attenuated levels of bcl-2 and IAP-2, and the enhanced activity of caspase-3 after treatment with AS-HIF-1alpha ODN may contribute partly to the effects of HIF-1alpha blockade on SCC-9 cell death. Collectively, our data suggest that a constitutive or hypoxia-induced expression of HIF-1alpha in SCC-9 and SCC-4 cells is sufficient to confer target genes expression essential for tumor proliferation and survival. As a result, interfering with HIF-1alpha pathways by antisense or siRNA strategy may provide a therapeutic target for human tongue squamous cell carcinomas.

Apoptosis↗
PubMed2004

Actinobacillus actinomycetemcomitans suppresses rat natural killer cell activity in vivo.

OBJECTIVE: To examine the immune suppressive effect of Actinobacillus actinomycetemcomitans (Aa) on rat natural killer (NK) cell activity in vivo. MATERIAL AND METHODS: Sprague Dawley rats were given Aa in 2 different manners: (i) by mixing Aa with food at a dose of 10(8) cells/rat/day for 3 months; or (ii) by a single i.m. injection of live Aa at doses of 10(6) and 10(7) cells/rat/day. NK cell activity was measured by means of a 51Cr-release assay using YAC-1 tumor cells as targets. RESULTS: Rats that had been infected by Aa mixed with food experienced significant suppression of their NK cell activity; this reached approximately =50% of control values at 2 and 3 months post-Aa infection. The suppression in NK cell activity was related to decreases in the extent of conjugate formation between effectors and YAC-1 target tumor cells (51.7%) and the extent of lysis of target cells (75.7%). The results also showed that addition of an admixture of Aa-treated NK cells to the control NK cells caused 75% and 53% decreases in activity at effector:target ratios of 25:1 and 50:1, respectively. In addition, a significant increase in the extent of T-suppressor cells (154.8% of control) was detected at 3 months post-Aa infection. In contrast, the single injection of live bacteria resulted in a remarkable, dose-dependent inhibition of NK cell activity (55% and 71% at doses of 10(6) and 10(7) cells/rat/day, respectively) as early as 2 days post-treatment. This also reflected significant suppression in the effector:target conjugate formation ratio (52% of control). The data also revealed a 150-188% increase in the number of splenic lymphocytes post-Aa injection. These effects were transient and normal levels were re-established by the fifth day CONCLUSION: Aa treatment causes suppression of NK cell activity and the mode of action may be due to induction of T-suppressor cells or dilution of NK cells with other lymphoid cell populations. The degree of suppression is affected by the way in which Aa is introduced to the host. These results may contribute to the understanding of how Aa evades host defense.

Aggregatibacter actinomycetemcomitans↗
PubMed2003

Phagocytosis of candida albicans by lymphatic tumour cells in vitro.

Experiments were carried out to investigate whether different lymphatic tumour cell lines have similar kinetic characteristics of phagocytosis of microorganisms. Six tumour cell lines were used. These were a human T-cell line (CEM), a mouse T-cell line (YAC-1), a human B-cell line (LAZ), and a human erythroleukemic tumour cells (K562), whereas 2 cell lines of professional phagocytosis were used as controls, a human macrophage cell line (THP1) and a mouse macrophage cell line (P388D1). Tumour cells were mixed with candida albicans at a ratio of 10:1 of candida to tumour cells and the percentage of tumour cells that had attached/phagocytosed candida was determined. After 4 h coculture with candida, tumour cells not of T-cell origin (LAZ and K562) showed moderate level of phagocytosis (28%), whereas tumour cells of T-cell origin (CEM and YAC-1) demonstrated low levels of phagocytosis (15%) as compared to macrophage cell lines (THP1 and P388D1) that showed maximum phagocytosis (64-78%). Acid phosphatase (AcPase) activity was increased by 33% during coculture of YAC-1 cells and yeast cells. In conclusion, the results suggest that lymphatic tumour cells of nonphagocytic origin acquire phagocytic properties during the course of malignancy, and digestion of phagocytosed yeast cells maybe related with AcPase activity, as well as that of other lysosomal enzymes. This phenomenon may represent one mechanism by which tumour cells downregulate immune surveillance.

Acid Phosphatase↗
PubMed2003

Adult supraglottitis subsequent to smoking crack cocaine.

Supraglottitis is one possible complication of smoking crack cocaine. From 1992 through 2001, our institution treated nine patients for thermal supraglottitis secondary to crack cocaine inhalation. In this article, we describe two of these cases, and we briefly review what is known about this entity and the mechanism of injury. We also provide our recommendations for management.

Adult↗
PubMedDate not supplied

Human squamous cell carcinoma of the tongue and colon undergoes apoptosis upon phagocytosis of Saccharomyces cerevisiae, the baker's yeast, in vitro.

The present study was carried out to evaluate the effect of phagocytosis of killed yeast on the induction of apoptosis in two human solid tumors of the gastrointestinal (GI): the squamous cell carcinomas of the tongue (SCCA) are (SCC-4 and SCC-9) and the adenocarcinomas of the colon (ADENOCA) are (Caco-2 and DLD-1). Cancer cells were cultured with heat killed Saccharomyces cerevisiae, baker's and brewer's yeast, at ratio of yeast to cancer cells = 10:1. The percentage of tumor cells that had attached/phagocytosed yeast and oxidative burst was determined by using oxidative sensitive dye (DCFH-DA) and flow cytometry. SCC-4 and colon Caco-2 cells demonstrated initial high levels of phagocytosis that peaked (35.8-52.8%) at 2 hr. The oral SCC-9 and colon DLD-1 cells demonstrated low phagocytic activity (7-12%). Phagocytosis was not associated with oxidative burst. Upon phagocytosis of yeast, cancer cells underwent apoptosis that was maximized at 4 hr. Yeast-induced apoptosis was significant in SCC-4 (45%), as compared with SCC-9 cells (17%), and Caco-2 (76%), as compared with DLD cells (12%). Apoptosis in cancer cells was inhibited by caspase inhibitor, Z-VAD-FMK; this suggests that caspases may be involved in apoptosis of the GI cancers. This data may have clinical implications for the treatment of solid tumors.

Adenocarcinoma↗