Adenocarcinoma pancreatic

The less polar methyl ester 2 as prodrug showed better results in vivo and inhibits both farnesylation of the Ras protein and growth of Ras-transformed cells, whilst proliferation of Raf- or Mos-transformed cells was not influenced. Growth of human pancreatic adenocarcinoma cells with mutated K-Ras, c-Myc and p53 genes was inhibited by application of 2. If the compound is administered over a period of 5 days to mice with implanted Ras-dependent tumors, tumor growth can be reduced by up to 66% compared to untreated mice, whereas application of the antitumor antibiotic doxorubicin only resulted in 33% reduction under the same conditions. It is particularly noteworthy that treatment with the /1-turn mimetic - in contrast to treatment with doxorubicin - was without any visible side effects, such as weight loss. 

A cystic fibrosis pancreatic adenocarcinoma cell line. Proc Natl Acad Sci USA 87 4012-6. 

In a transgenic mouse model of ductal pancreatic adenocarcinoma, the development of ductal carcinoma is preceded by trans-differentiation of acinar cells to ductal-like cells.The anti-apoptotic protein Bc1-Xl is highly expressed... 

Hoffman JP, McGinn CJ, Szarka C, et al. A phase I study of preoperative gemcitabine with radiation therapy followed by postoperative gemcitabine for patients with localized resectable pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 1998 17 283a. 

Recent preoperative chemoradiation studies of resectable pancreatic cancer have demonstrated improved survival. One of the first of these evaluated preoperative therapy using 50.4 Gy standard fractionation irradiation with a concurrent continuous infusion of low-dose 5-FU in patients having resectable pancreatic adenocarcinoma (52). The recurrence rate and median survival duration were better than those historically reported for patients only undergoing pancreatoduodenectomy (53). These findings prompted further studies evaluating the role of preoperative chemoradiation in patients having resectable pancreatic cancer. Data on 132 consecutive patients who received preoperative 5-FU and... 

Shen J, Person MD, Zhu J et al. Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry. Cawcer Rex 2004 64 9018-9026. 

Kwak EL, Jankowski J, Thayer SP et al. Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res 2006 12 4283 287. 

Lev-Ari S, Vexler A, Starr A, Ashkenazy-Voghera M, Greif J, Aderka D, Ben-Yosef R. 2007. Curcumin augments gemcitabine cytotoxic effect on pancreatic adenocarcinoma cell lines. Cancer Invest 25 411-418. 

Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR, Chiao PJ. 1999. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res 5 119-127. 

In the studies of long-term exposure of rats to both triphenyltin hydroxide and bis(tributyltin)oxide, most of the tumors were found in endocrine glands. In addition to the pituitary adenomas associated with bis(tributyltin)oxide and triphenyltin hydroxide, there was also an increased incidence of pheochromocytomas of the adrenal gland, parathyroid carcinomas and pancreatic adenocarcinomas in animals from at least one sex. Triphenyltin hydroxide was associated with an increased incidence of testicular Leydig cell tumors in male rats at the highest dose. Hepatic tumors were found in male and female mice following 80 weeks of triphenyltin hydroxide administration. 

Jang JJ, Takahashi M, Furukawa F, et al. 1986. Inhibitory effect of dibutyltin dichloride on pancreatic adenocarcinoma development byn-nitrosobis(2-oxopropyl)amine in the Syrian hamster. Jpn J Cancer Res 77 1091-1094. 

Koopmann J, Zhang Z, White N, Rosenzweig J, Fedarko N, Jagannath S, et al. Serum diagnosis of pancreatic adenocarcinoma using surface-enhanced laser desorption and ionization mass spectrometry. Clin Cancer Res 2004 10(3) 860—868. 

Lithium gamolenate, a compound with in vitro antitumor activity, given intravenously or orally, was ineffective in treating advanced pancreatic adenocarcinoma (n = 278) (52). Adverse effects attributed to lithium (type unspecified) were reported in two of 93 in the oral group (mean serum lithium 0.15 mmol/1), five of 90 with low-dose intravenous administration (mean serum lithium 0.4 mmol/1), and seven of 95 with the high-dose intravenous administration (mean serum lithium 0.8 mmol/1). 

Chronic cocaine use, which is associated with immunosuppression, may be carcinogenic. The possible association between chronic cocaine exposure and pancreatic adenocarcinoma has been investigated (240,241). A study of hospital records in Brazil for the years 1986-1998 showed that of 198 patients with pancreatic adenocarcinoma, 13 (6.5%) were younger than 40 years of these, five had a history of chronic cocaine inhalation and one had abused marijuana. 

Duarte JG, do Nascimento AF, Pantoja JG, Chaves CP. Chronic inhaled cocaine abuse may predispose to the development of pancreatic adenocarcinoma. Am J Surg... 

Pancreatic adenocarcinoma is the fourth leading cause of cancer in the United States (Niederhuber et al, 1995). The main problem of combating pancreatic adenocarcinoma arises from a lack of specific symptoms and limitations in detection methods. The overwhelming majority of pancreatic carcinoma patients are discovered at a late clinical tumor stage. Only 10% of patients show a potentially curable resectable tumor. 

Lu, Z., Hu, L., Evers, S., Chen, J., Shen, Y. (2004). Differential expression profiling of human pancreatic adenocarcinoma and healthy pancreatic tissue. Proteomics 4, 3975-3988. 

Meyer, H. E., Hahn, S. A., Stuhler, K. (2005b). Application of DIGE saturation labeling for the analysis of micro-dissected precursor lesions of pancreatic adenocarcinoma. Proteomics 5, in press. 

Yanagihara, K.,Oka, M., Yamaguchi, K. (2002). Peptidomics-based approach reveals the secretion of the 29-residue COO H-terminal fragment of the putative tumor suppressor protein DMBTl from pancreatic adenocarcinoma cell lines. Cancer Res. 62, 4894-4898. 

Radiation recall consists of inflammatory reactions triggered by cytotoxic drugs in previously irradiated areas most are skin reactions. Gemcitabine has been implicated in several cases. The authors of a literature review discovered 12 cases of radiation recall caused by gemcitabine and reported a case of myositis in the rectus abdominis muscle of a patient with pancreatic adenocarcinoma as an effect of radiation recall (23). Most of the cases had inflammation of internal organs or tissues and 30% had dermatitis or mucositis. This is different from the effect of other agents that commonly cause radiation recall (anthracyclines and taxanes), with which 63% are skin reactions. Compared with anthracyclines and taxanes, the interval from the completion of radiation therapy to the start of chemotherapy is less with gemcitabine (median time 56 days, compared with 218 days for the taxanes and 646 days for doxorubicin). 

Lithium gamolenate, a compound with in vitro antitumor activity, given intravenously or orally, was ineffective in treating advanced pancreatic adenocarcinoma n — 278) (42). Adverse effects attributed to lithium... 

Johnson CD, Puntis M, Davidson N, Todd S, Bryce R. Randomized, dose-finding phase III study of lithium gamolenate in patients with advanced pancreatic adenocarcinoma. Br J Surg 2001 88(5) 662-8. 

Pipalamycin was discovered by Uchihata et al. in 2002 as an apoptosis inducer in apoptosis-resistant human pancreatic adenocarcinoma AsPC-1 cells from Streptomyces sp. (Fig. 15). In this apoptotic pathway, both caspase-3 and -9 are activated. Pipalamycin shows strong cytotoxicity against tumor cells and antibacterial activity against gram-positive bacteria ... 

---