Cancer, pancreatic

After using C A19-9 as the only accepted diagnostic marker for pancreatic cancer for two decades [92], a bewildering number of potential biomarkers are currently under evaluation [93]. Apeak (3334.7 Da) found by SELDI-TOF-MS in 5/15 pancreatic adenocarcinoma cell lines was identified by Qq-TOF-MS/MS as the COOH-terminal fragment of DMBTl, a putative tumor suppression protein intracellularly generated by Umited prior proteolysis. Analyses of other cell lines suggested that the marker may be unique to pancreatic adenocarcinoma [94]. In another study, a differentially expressed peak (—16,570 Da) was detected in 10/15 samples from pancreatic adenocarcinoma in contrast to only 1/7 with other pancreatic diseases. The peak was identified as hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein I (HIP-PAP I) by SELDI immunoassay [95]. 

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The usual dose consists of 1000 mg/m2 i.v. It is the most active single agent for treating pancreatic cancer, and it is used as a fust-line treatment for both pancreatic and small cell lung cancers. The dose-limiting toxicity is bone marrow suppression. 

CCI-779 - renal carcinoma, lymphoma AP23573 - sarcomas RAD-001 - pancreatic cancer Again, several preclinical studies suggest that rapalogs will have synergistic affects when used in combination with other chemotherapeutics. 

Erlotinib (Tarceva) TKI EGFR Inhibition of kinase activity - ATP-competitive NSCLC Pancreatic cancer... 

These drug are prescribed as replacement therapy for those with pancreatic enzyme insufficiency. Conditions or diseases that may cause a decrease in or absence of pancreatic digestive enzymes include cystic fibrosis, chronic pancreatitis, cancer of the pancreas,... 

Figure 24.3 Strategic pathway of Bayesian Markov model showing decision points for diagnosis of pancreatic cancer [14]. Bx = biopsy Dx = diagnosis.

In all analyses, there is uncertainty about the accuracy of the results that may be dealt with via sensitivity analyses [1, 2]. In these analyses, one essentially asks the question What if These allow one to vary key values over clinically feasible ranges to determine whether the decision remains the same, that is, if the strategy initially found to be cost-effective remains the dominant strategy. By performing sensitivity analyses, one can increase the level of confidence in the conclusions. Sensitivity analyses also allow one to determine threshold values for these key parameters at which the decision would change. For example, in the previous example of a Bayesian evaluation embedded in a decision-analytic model of pancreatic cancer, a sensitivity analysis (Fig. 24.6) was conducted to evaluate the relationship... 

In pancreatic cancer, receptor and ligand expression were localized to the cytoplasm of malignant cells but still correlated positively with advanced stage, proliferation, and angiogenesis (47). 

Kuwada Y, Sasaki T, Morinaka K, Kitadai Y, Mukaida N, Chayama K. Potential involvement of IL-8 and its receptors in the invasiveness of pancreatic cancer cells. Int J Oncol 2003 22 765-771. 

Kimsey TF, Campbell AS, Albo D, Wang TN. Co-localization of macrophage inflammatory protein-3a (Mip-3a) and its receptor, CCR6, promotes pancreatic cancer cell invasion. Cancer J 2004 10 374-380. 

Although earlier work had showed a positive association between coffee consumption and pancreatic cancer rates across countries,2 it was the much-publicized case-control study of MacMahon et al.3 in 1981 that attracted widespread attention to the question of a possible link. In that study, which was designed primarily to investigate the role of smoking and alcohol in pancreatic cancer, 369 pancreatic cancer patients prior to diagnosis and 644 hospital controls reported their typical daily coffee and tea consumption. Unexpectedly, the authors found a significantly increased risk of pancreatic cancer associated with coffee consumption (overall rela-... 

A few years later in 1983, Whittemore and colleagues11 analyzed data on 50,000 former male students who had attended Harvard University between 1916 and 1950. In a 16 to 50 year follow-up, they compared coffee and tea drinking practices of 126 men in the college cohort, who had subsequently died of pancreatic cancer, with those of 504 surviving class-... 

Feinstein, A.R., Horwitz, R. I., Spitzer, W. O., Battista, R. N., Coffee and pancreatic cancer The problems of etiologic science and epidemiologic case-control research, JAMA, 246, 957, 1981. 

Hirayama, T., Epidemiology of pancreatic cancer in Japan, Jpn J Clin Oncol, 19, 208, 1989. 

Gold, E. B., Epidemiology of and risk factors for pancreatic cancer, Surg Clin North Am, 75, 819, 1995. 

Hardell L, Carlberg M, Hardell K, Bjomfoth H, Wickbom G, Ionescu M, van-Bavel B, Lindstrom G (2007) Decreased survival in pancreatic cancer patients with high concentrations of organochlorines in adipose tissue. Biomed Pharmacother 61 (10) 659-664. doi 10.1016/j.biopha.2007.04.006... 

Gress TM et al. Identification of genes with specific expression in pancreatic cancer by cDNA representational difference analysis. Genes Chromosom Cancer 1997 17 1-7. 

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