Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of the tyrosine kinase (TK) inhibitors, genistein, and tyrphostin (RG-50864) on the contractile action of epidermal growth factor - urogastrone (EGF-URO), transforming growth factor-alpha (TGF-alpha), and other agonists in two smooth muscle bioassay systems (guinea pig gastric longitudinal muscle, LM, and circular muscle, CM). We also studied the inhibition by tyrphostin of EGF-URO stimulated protein phosphorylation in identical smooth muscle strips. The selective inhibition by genistein and tyrphostin of EGF-URO and TGF-alpha induced contraction, but not of carbachol- and bradykinin-mediated contraction, occurred at much lower concentrations (genistein, less than 7.4 microM (2 micrograms/mL); tyrphostin, less than 20 microM (4 micrograms/mL)) than those used in previously published studies with these TK inhibitors. In LM tissue, the IC50 values were for genistein 1.1 +/- 0.1 microM (0.30 micrograms/mL; mean +/- SEM) and 3.6 +/- 0.5 microM (0.74 micrograms/mL) for tyrphostin, yielding a molar potency ratio (GS: TP) of 1:3 in the longitudinal preparation. In CM tissue, the IC50 values were 3.0 +/- 0.3 microM (0.81 micrograms/mL) for genistein and 2.4 +/- 0.2 microM (0.49 micrograms/mL) for tyrphostin, yielding a molar potency ratio (GS:TP) of 1.0:0.8 in the circular strips. The inhibition by genistein and tyrphostin of EGF-URO and TGF-alpha mediated contraction was rapid (beginning within minutes) and was reversible upon washing the preparations free from the enzyme inhibitors. In intact tissue strips studied under bioassay conditions, tyrphostin (40 microM) also blocked EGF-URO triggered phosphorylation of substrates detected on Western blots using monoclonal antiphosphotyrosine antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyrosine kinase inhibitors and the contractile action of epidermal growth factor-urogastrone and other agonists in gastric smooth muscle. 131 19

Impaired liver regeneration in cirrhosis complicates the surgical treatment of liver tumors which arise in this setting. We developed a rat model to investigate the regenerative response of cirrhotic liver after hepatectomy and studied the effect of exogenous transforming growth factor-alpha (TGF-alpha), a potent liver mitogen. Micronodular cirrhosis was established by the simultaneous administration of CCl4 and phenobarbital. Hepatic DNA synthesis ([3H]thymidine incorporation into DNA) 24 hr after partial hepatectomy in cirrhotic rats was 15.6 +/- 3.4 cpm/micrograms DNA (means +/- SEM), which was significantly lower than in normal rats (37.3 +/- 3.4 cpm/micrograms DNA, P less than 0.05). Exogenous TGF-alpha (30 nmol/kg, sc every 12 hr) significantly improved [3H]thymidine incorporation (35.6 +/- 8.2 cpm/micrograms DNA, P less than 0.05). An autoradiographic nuclear labeling index also confirmed increased DNA synthesis (6.7% vs 13.4%). TGF-alpha had no effect on normal regenerating liver (42.5 +/- 8.8 cpm/micrograms DNA, NS). Although the significance of TGF-alpha-enhanced liver regeneration in cirrhosis has yet to be assessed, this model may be useful for the study of mechanisms which control hepatic proliferation.
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PMID:Transforming growth factor-alpha (TGF-alpha) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats. 152 43

Humoral hypercalcemia of malignancy is a multifactorial syndrome caused by the action of tumor-produced factors on target organs of bone, kidney, and intestine to disrupt normal calcium homeostasis. Although parathyroid hormone-related protein (PTHrP) plays an integral role in the syndrome, tumors also produce other hypercalcemic factors, such as transforming growth factor-alpha (TGF-alpha), which may modulate the effects of PTHrP. In order to determine if the effects of PTHrP on calcium homeostasis can be modulated by TGF-alpha, we have used a human squamous cell carcinoma cell line (RWGT2) which produces PTHrP alone and Chinese hamster ovarian (CHO) cells expressing only transfected human TGF-alpha complementary DNA (CHO/TGF-alpha). We studied the effects of these tumors on calcium homeostasis in nude mice bearing both tumors or each tumor alone. Whole blood ionized calcium concentrations (mean +/- SEM in mmol/L) were significantly higher in mice bearing both RWGT2 and CHO/TGF-alpha tumors (3.11 +/- 0.06, P < 0.05) when compared with mice bearing either RWGT2 alone (2.02 +/- 0.06), CHO/TGF-alpha alone (1.42 +/- 0.01), or RWGT2 and nontransfected CHO tumors (1.86 +/- 0.01). This enhanced effect was also observed using continuous PTHrP-(1-34) infusion (2 micrograms/day) in mice bearing CHO/TGF-alpha tumors. In addition, tumor cell conditioned media was tested for bone resorbing activity in organ cultures of fetal rat long bones previously incorporated with 45calcium (45Ca++). Conditioned medium at 0.1% (vol/vol) from either RWGT2 or CHO/TGF-alpha had no bone resorbing activity over control (%45Ca++ release, mean +/- SEM; control 23 +/- 1, RWGT2 19 +/- 1, CHO/TGF-alpha 23 +/- 1). However, the combination of 0.1% conditioned medium from RWGT2 and CHO/TGF-alpha significantly increased bone resorption (53 +/- 2, P < 0.05). These data demonstrate that the hypercalcemic effects of tumor-produced PTHrP are enhanced by TGF-alpha and that this effect may be due to increased bone resorption.
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PMID:The combined effect of tumor-produced parathyroid hormone-related protein and transforming growth factor-alpha enhance hypercalcemia in vivo and bone resorption in vitro. 832 57

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) promote the differentiation and proliferation of epithelia as well as the proliferation and chemotaxis of fibroblasts. Additionally, EGF promotes wound healing in tissues composed largely of epithelial cells and fibroblasts. We hypothesized that EGF and TGF-alpha regulate the differentiation and proliferation of the epithelial lining and the migration and proliferation of fibroblasts in the subepithelial space of the middle ear mucosa in children with otitis media. As an initial test of this hypothesis, EGF and TGF-alpha concentrations were measured in 82 middle ear effusions of children undergoing tympanostomy tube placement. EGF was present in 45% of these effusions, and TGF-alpha was present in 6%. The mean concentration +/- SEM values for EGF and TGF-alpha were 19+/-7.6 and 3.7+/-7.9 pg/mL, respectively. In addition, neutrophils, macrophages, and lymphocytes in middle ear effusions stained for EGF by immunocytochemistry. We conclude that growth factors are frequently present in middle ear effusions of children with otitis media.
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PMID:Epidermal growth factor and transforming growth factor-alpha in middle ear effusion. 985 26

The objective was to ascertain fibroblast growth factor-2 (FGF2), epidermal growth factor (EGF), and transforming growth factor-alpha (TGFalpha) mRNA expression and testis morphology during accelerated testicular growth after hemicastration in the neonatal boar. On Day 10 after birth (Day 0), boars were assigned to control (n = 28), no treatment; hemicastrated (n = 28), left testis removed. The right testis in both groups (n = 7) was removed on Days 5, 10, 15, and 20. Expression of mRNA for FGF2, EGF, and TGFalpha was determined by qRT-PCR using TaqMan. Testicular morphology was determined on Day 15. On Day 10, hemicastrated boars had a greater (P = 0.01) testis weight (6.2 +/- 0.8 g; mean +/- SEM) than controls (4.3 +/- 0.4 g) and on Day 15 testis weight in hemicastrated boars (8.8 +/- 0.8 g) was twice (P < 0.01) that of control boars (4.2 +/- 0.3 g). Seminiferous tubule volume was approximately doubled in hemicastrated boars (P < 0.01) and was associated with an increase (P < 0.01) in Sertoli cell number. Interstitial compartment volume was greater (P < 0.01) in hemicastrated boars. Leydig cell numbers were similar (P = 0.14) but volume was greater (P < 0.01) for hemicastrates. There were no differences (P > 0.05) between control and hemicastrated boars in TGFalpha or FGF2 expression on Day 5 or Day 10, and EGF was not detected. It was concluded that upregulation of TGFalpha or FGF2 expression is not a pre-requisite for enhanced testicular growth and increased Sertoli cell proliferation that occurs subsequent to hemicastration in the neonatal boar.
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PMID:Expression of FGF2 and TGFalpha and testis morphology during testicular hypertrophy subsequent to hemicastration in the neonatal boar. 1827 82