Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-two normal LEW/Sea rats were transplanted a piece of syngeneic pancreas between the peritoneum and abdominal muscle. Among them, 17 (68%) of the 25 rats that received pancreatic transplantation at 41-50 days of age had a surviving beta-cell mass at 5.5-7.1 months after transplantation. Among the 25 rats, 12 rats injected with interleukin-1 receptor (IL-1R) and IL-2Rbeta peptides at post-transplantation showed better surviving grafts at 5.5 months' observation. Only 2 (25%) of the other 7 young rats that received a pancreatic graft at 20 days of age had a small mass at 21 days post-transplantation. Flow cytometer (FCM) analyses showed that thymus OX40(+) (CD134(+)) T-cells were increased up to 37+/-4% at the graft rejection in the 13 old rats without the IL-R peptide injections. The 7 young rats had 99% of thymus OX40(+) T-cells. However, the 12 old rats injected with the IL-R peptides showed suppressed numbers of thymus OX40(+) T-cells (8-13+/-3%). The long-term surviving, but apoptotic, grafted beta-cells were stained positively both with anti-insulin monoclonal antibody (mAb) and with anti-c-erbB-2/human epidermal growth factor receptor (HER)-2/neu mAb. Expression of a c-erb family oncogene was shown on the pancreatic graft surviving for 7.1 months. Electron microscopic analysis of the grafted beta-cells showed abnormally large beta granules and loss of functioning mitochondria in the cytoplasm. In 18 (56%) of the 32 rats, the 220-bp and 380-bp specific products of insulin-degrading enzyme (IDE) gene were amplified using the polymerase chain reaction (PCR) of the liver DNA. Among the 18 rats, 6 rats expressed 2 extra hands of 280-bp and 700-bp in a correlation with the high levels of the transforming growth factor-alpha (TGF-alpha) cDNA of 120-bp which was amplified in the quantitative reverse-transcriptase (RT)-PCR of the liver cDNA. Among the selected 11 rats, 5 rats showed large amounts of the 120-bp TGF-alpha cDNA. Host pancreatic RT-PCR showed 235-bp or 250-bp bcl-2 and 181-bp bcl-xS gene products. The bcl-2 cDNA of the host pancreas was amplified actively when the pancreatic graft was being rejected. Exceptionally, the one female injected with the IL-R peptides showed a low level of the liver TGF-alpha cDNA together with the pancreatic expressions of Bax (140-bp), bcl-2 and like interleukin converting enzyme (LICE) (318-bp) cDNA. Insulin secretion from the grafted beta-cells and IL-1beta-induced Fas-mediated apoptosis of the beta-cells were suspected to be present at the same time in the female with the best graft survival.
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PMID:Oncogene expression on the syngeneic beta-cells of long-term surviving pancreatic grafts and better effects of interleukin-1 receptor (IL-1R) and IL-2Rbeta on the grafted beta-cells in LEW/Sea strain rats. 1272 75

The aims of this study were to determine the effects of (a) combining the epidermal growth factor receptor (EGFR) blocker (erlotinib) and the cyclooxygenase-2 inhibitor (celecoxib) on cell growth and apoptosis in human pancreatic cancer cell lines, (b) baseline EGFR expression on the potentiation of erlotinib-induced apoptosis by celecoxib, and (c) the effects of the combination on the expression of the COX-2, EGFR, HER-2/neu, and nuclear factor-kappaB (NF-kappaB). Baseline expression of EGFR was determined by Western blot analysis in five human pancreatic cancer cell lines. BxPC-3, PANC-1, and HPAC had high EGFR and MIAPaCa had low EGFR. Cells were grown in culture and treated with erlotinib (1 and 10 micromol/L), celecoxib (1 and 10 micromol/L), and the combination. Growth inhibition was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and apoptosis was assayed by ELISA. Reverse transcriptase-PCR was used to evaluate COX-2 and EGFR mRNA. EGFR, COX-2, and HER-2/neu expression was determined by Western immunoblotting. Electrophoretic mobility shift assay was used to evaluate NF-kappaB activation. Growth inhibition and apoptosis were significantly (P < 0.05) higher in BxPC-3, HPAC, and PANC-1 cells treated with celecoxib and erlotinib than cells treated with either celecoxib or erlotinib. However, no potentiation in growth inhibition or apoptosis was observed in the MIAPaCa cell line with low expression of the EGFR. Significant down-regulation of COX-2 and EGFR expression was observed in the BxPC-3 and HPAC cells treated with the combination of erlotinib (1 micromol/L) and celecoxib (10 micromol/L) compared with celecoxib- or erlotinib-treated cells. Celecoxib significantly down-regulated HER-2/neu expression in BxPC-3 and HPAC cell lines. Significant inhibition of NF-kappaB activation was observed in BxPC-3 and HPAC cell lines treated with erlotinib and celecoxib. (a) Celecoxib can potentiate erlotinib-induced growth inhibition and apoptosis in pancreatic cell lines, (b) high baseline EGFR expression is a predictor of this potentiation, and (c) the down-regulation of EGFR, COX-2, and HER-2/neu expression and NF-kappaB inactivation contributes to the potentiation of erlotinib by celecoxib.
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PMID:Simultaneous targeting of the epidermal growth factor receptor and cyclooxygenase-2 pathways for pancreatic cancer therapy. 1637 9