Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenocarcinoma of the pancreas generally remains an incurable disease by available treatment modalities, demanding the development of a suitable cell-culture/animal model and the discovery and evaluation of novel therapeutic agents. We report the clonal preservation of a human pancreatic cell line (KCI-MOH1) established from a 74-year-old African-American man diagnosed with pancreatic cancer. Initially the human primary tumor was grown as a xenograft in SCID mice and, subsequently, a cell line was established from tumors grown as a xenograft as reported in our earlier publication. The molecular characterization of the primary tumor, the tumors grown as xenograft, and the cell line all revealed similar genotypic properties. By using an automated DNA sequencer, a K-ras mutation (codon 12, GGT to CGT, Gly to Arg) was detected in the pancreatic tumor tissue taken from the patient, whereas no p53 mutation was detected. The same K-ras mutation and unaltered p53 was also found in the xenograft tumor and in the KCI-MOH1 cell line. Chromosome analysis of the cultured cells revealed: 42,XY,add(3)(p11.2),der(7)t(7;12) (p22;q12),-10,-12,add (14)(p11),-18,add (20)(q13),-22/84, idemx2, which is the same chromosome complement found in xenograft tumors. The KCI-MOH1 cell line grows well in tissue culture and forms tumors in the SCID mice when implanted subcutaneously, as well as in orthotopic sites. The KCI-MOH1 cell line-derived SCID mouse xenograft model was used for efficacy evaluation of bryostatin 1, auristatin-PE, spongistatin 1, and gemcitabine alone and in combination. Tumor growth inhibition (T/C expressed as percentage), tumor growth delay (T - C), and log 10 kill for these agents were 38%, 22 days, and 0.53; 15%, 30 days, and 0.80; 24%, 25 days, and 0.66; and 10%, 33 days, and 0.90, respectively. When given in combination, two of seven gemcitabine + auristatin-PE-treated animals were free of tumors for 150 days and were considered cured. Animals treated with a combination of bryostatin 1 and gemcitabine and a combination of spongistatin and gemcitabine produced remissions in only one of seven mice. From these results, we conclude that (a) this is the first study illustrating that clonal characteristics of primary pancreatic tumors remained unchanged when implanted in mice and as a permanent cell line grown in vitro; and (b) there is a synergistic effect between gemcitabine and selected marine products tested in this study, which is more apparent in the gemcitabine and auristatin-PE combination. The results of this preliminary study suggest that these agents should be explored clinically in the treatment of pancreatic cancer.
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PMID:Clonal preservation of human pancreatic cell line derived from primary pancreatic adenocarcinoma. 1054 95

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis in the process of tumor growth and metastasis in esophageal adenocarcinoma (EA). Polymorphisms in the VEGF gene have been associated with altered VEGF expression and plasma VEGF levels. We hypothesized that polymorphisms of VEGF may contribute to EA risk. Functional polymorphisms in the VEGF gene (-460C/T, +405C/G and +936C/T) were determined in 308 patients with EA and 546 healthy controls. Logistic regression analysis was employed to assess the associations between genotypes, haplotypes of VEGF and EA risk, adjusting for multiple confounding factors. Compared with the +936CC genotype, the combined +936CT+TT genotypes were significantly associated with increased risk of developing EA, with adjusted odds ratio (OR) = 1.49 [95% confidence interval (CI), 1.05-2.12; P = 0.027]. The -460CT+CC were associated with increased risk of EA in smokers (adjusted OR = 1.57; 95% CI, 1.07-2.30; P = 0.021), whereas the -460CT/CC were associated with decreased risk of EA (adjusted OR = 0.47; 95% CI, 0.25-0.91; P = 0.025) in non-smokers. Compared with non-smokers with the +460TT, smokers with the +460CT+CC had significantly higher risk of EA (adjusted OR = 3.32; 95% CI, 1.56-7.10; P = 0.002). No overall or interacting association with EA risk was found for the +405C/G polymorphism. Haplotype CGT (-460C/+405G/+936T) was significantly associated with higher risk of EA (adjusted OR = 1.70; 95% CI, 1.04-2.73; P = 0.034). These results suggested that cigarette smoking modifies the association between VEGF polymorphisms and EA risk among Caucasians.
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PMID:Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk. 1878 Aug 93