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Biomedical subjects

T R Wilson

Publications and source records attributed to T R Wilson.

18 recordsLinked to original sources
PubMed2006

c-FLIP inhibits chemotherapy-induced colorectal cancer cell death.

c-FLIP inhibits caspase 8 activation and apoptosis mediated by death receptors such as Fas and DR5. We studied the effect of c-FLIP on the apoptotic response to chemotherapies used in colorectal cancer (CRC) (5-fluorouracil, oxaliplatin and irinotecan). Simultaneous downregulation of both c-FLIP splice forms c-FLIP(L) and c-FLIP(S) with siRNA synergistically enhanced chemotherapy-induced apoptosis in p53 wild-type (HCT116p53(+/+), RKO), null (HCT116p53(-/-)) and mutant (H630) CRC cell lines. Furthermore, overexpression of c-FLIP(L), but not c-FLIP(S), potently inhibited apoptosis induced by chemotherapy in HCT116p53(+/+) cells, suggesting that c-FLIP(L) was the more important splice form in mediating chemoresistance. In support of this, siRNA specifically targeted against c-FLIP(L) synergistically enhanced chemotherapy-induced apoptosis in a manner similar to the siRNA targeted against both splice forms. Inhibition of caspase 8 blocked the enhanced apoptosis induced by c-FLIP-targeted (FT) siRNA and chemotherapy. Furthermore, we found that downregulating cell surface DR5, but not Fas, also inhibited apoptosis induced by FT siRNA and chemotherapy. Interestingly, these effects were not dependent on activation of DR5 by its ligand TRAIL. These results indicate that c-FLIP inhibits TRAIL-independent, DR5- and caspase 8-dependent apoptosis in response to chemotherapy in CRC cells. Moreover, targeting c-FLIP in combination with existing chemotherapies may have therapeutic potential for the treatment of CRC.

Antineoplastic Agents↗
PubMed1994

Distribution and reactivity of inhaled 14C-labeled toluene diisocyanate (TDI) in rats.

Inhalation exposure to toluene diisocyanate (TDI) can result in a variety of airway diseases. Concern has been expressed that a putative carcinogenic potential of TDI exists as a result of the formation of toluenediamine (TDA) by hydrolysis of the isocyanate in the body. Results from long-term bioassays (TDI inhalation versus gavage in rats and mice) are contradictory and discrepancies do exist concerning the interpretation of adverse effects. This study was performed to analyze the distribution and reactivity of radioactively-labeled TDI using vapor exposure in a rat model system. Rats were exposed to 14C-TDI vapors at concentrations ranging from 0.026 to 0.821 ppm for 4 h. All tissues examined showed detectable quantities of radioactivity, with the airways, gastrointestinal system and blood having the highest levels which increased with exposure concentration. The concentration of radioactivity in the bloodstream after exposure was linear with respect to dose. The majority (74-87%) of the label associated with the blood was recovered in the plasma, and of this, 97-100% of the 14C existed in the form of biomolecular conjugates. Analysis of stomach contents shows that the majority of the label is also associated with high (> 10 kDa) molecular weight species. While a larger percentage (28%) of the label is found in the low molecular weight fraction relative to blood, this low molecular weight labeled material represents at least eight different components. Thus, over the vapor exposure concentrations and time tested, it appears that conjugation is the predominant reaction and that free TDA is not a primary in vivo reaction product under the conditions tested.

Administration, Inhalation↗
PubMed1988

The impact of hypothyroidism and thyroxine replacement on the expression of hepatic alpha 1-, alpha 2- and beta-adrenergic receptors in rat liver plasma membranes.

1. Liver plasma membranes were isolated from control, propylthiouracil-induced hypothyroid and thyroxine-replaced rats; relative specific activities of 5'-nucleotidase were found to be similar, 5.6-6.1, demonstrating that comparable purity levels were achieved. 2. Radioligand binding studies indicated that hepatic alpha 1-, alpha 2- and beta-adrenergic receptor binding to control liver membranes was 1963.23 +/- 59.34, 77.64 +/- 2.20 and 111.18 +/- 11.04 fmol.mg-1, respectively. 3. Hypothyroidism induced a 67% and 54% decrease, respectively, in hepatic alpha 1- and alpha 2-adrenergic receptor binding with no change in beta-adrenergic receptor binding. 4. Thyroxine replacement achieved an 85% and 100% restoration, respectively, in hepatic alpha 1- and alpha 2-adrenergic receptor expression with no effect on the beta-adrenergic receptor.

Animals↗
PubMed1979

Growth of body protein, fat, and skeleton in steers fed on three planes of nutrition.

The growth of body protein, fat, and skeleton of growing steers was determined from published experimental data of steers fed three planes of nutrition. Each animal was partitioned into: 1) metabolically slow tissue which included hide, hooves, horns, skeleton, and fat, and 2) metabolically active tissue (MAT) which were the remaining tissues. MAT grew exponentially in time and approached the same final value for all planes of nutrition; however, growth rates depended on energy intake. The mass of active tissues was described by MATkg = 27 + 393 (1 - e-t/tau) where t and tau are in months; tau was 25.8, 46.7, and 57.4 months for the high, medium, and low planes of nutrition, respectively. The finding that MAT retained the same mathematical form but grew more slowly on the lower nutritional planes suggests that changes in energy set the scale of physiological age. Fat deposition was linear with time for all groups, although the rates depended on energy intake. The rates were 8.21, 2.08, and 1.29 kg/month for the high, mediu, and low planes of nutrition, respectively. The results suggest that steers are not programmed to synthesize protein first and then fat only with the remaining energy; rather the level of energy intake and the age determine how the ingested energy is partitioned into protein and fat synthesis.

Adipose Tissue↗