Multiple neoplasias

Cole AR et al. Proteomic analysis of colonic crypts from normal, multiple intestinal neoplasia and p53-null mice a comparison with colonic polyps. Electrophoresis 2000 21 1772-1781. 

Davis P, Iwahashi CK and Yokoyama W. 2003. Whole almonds activate gastrointestinal (GI) tract antiproliferative signaling in APCmin (multiple intestinal neoplasia) mice. FACEB J 17(5) AQ1153. 

Podsypanina, K., EUenson, L.H., Nemes, A., Gu, J., Tamura, M., Yamada, K.M., Cordon-Cardo, C., Catoretti, G., Fisher, P.E., and Parsons, R., 1999, Mutation of PTEN/MMACl in mice causes neoplasia in multiple organ sytems. Proc. Natl. Acad. Sci. USA 96 1563-1568. 

Several inherited cancer syndromes are also known to result from mutations in proto-oncogenes. An example is given by the RET proto-oncogene. Depending on the type of mutation and on which part of the gene is affected, RET mutations can lead to multiple endocrine neoplasia 2A or 2B or familial medullary thyroid carcinoma. These familial cancers are inherited in autosomal dominant fashion. A second example is the CDK4 proto-oncogene, which when mutated can cause familial melanoma. 

Dasgupta P. Somatostatin analogues multiple roles in cellular proliferation, neoplasia, and angiogenesis. Pharmacol Ther 2004 102 61-85. 

Selective COX-2 inhibitors have also been shown to prevent early and late forms of colorectal neoplasia in rat models. Reddy et al. showed that administration of celecoxib inhibited aberrant colonic crypt foci (ACF) induction and multiplicity by about 40-49% in an azoxymethane-induced ACF rat model (81). Later the same investigators also showed that dietary administration of celecoxib can inhibit both the incidence and multiplicity of colon tumors by about 93 % and 97 %, respectively in the same rat model (82). Other researchers reported similar results with the Min mouse model (52). There is little data on human clinical trials with selective COX-2 inhibitors for colorectal tumor prevention. Recently Steinbach et al. conducted a double-blind, placebo-controlled study with 77 patients with FAP, and reported that treatment with celecoxib, a selective COX-2 inhibitor, for 6 mo led to a significant reduction (28%) in the number of colorectal polyps in these patients (50). Collectively, COX-2 nonspecific or specific NSAIDs appear to have chemopreventive activity against colorectal cancer development. Selective... 

A. Although all of the conditions can present as an asymptomatic nodule in the thyroid, the marked hypercalcemia in this patient makes hyperparathyroidism the probable diagnosis. Carcinomas of the thyroid are common, and outcomes are improved with early diagnosis. Medullary carcinoma and hyperparathyroidism caused by hyperplasia may be inherited and are associated with the multiple endocrine neoplasia syndromes. 

Melnick, R.L., Sills. R.C., Roycroft. J.H., Chou, B.J., Ragan, H.A. Miller, R.A. (1994) Isoprene, an endogenous hydrocarbon and industrial chemical, induces multiple organ neoplasia in rodents after 26 weeks of inhalation exposure. Cancer Res., 54, 5333-5339... 

Oikarinen, S, Pajari, A., Salminen, I., Heinonen, S.M., Adlercreutz, H., and Mutanen, M. 2005. Effects of a flaxseed mixture and plant oils rich in alpha-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice. Br. J. Nutr. 94, 510-518. 

Products that may have the potential to stimulate growth or induce proliferation or clonal expansion of cell types, in particular, transformed cells, all processes that may eventually lead to neoplasia should be evaluated with respect to receptor expression in various malignant and normal human cells that are relevant to the patient population under study [27], In such cases normal human cell lines and multiple human cancer cell lines expressing the relevant receptor, as well as primary cells derived from human tumor explants, should be used for in vitro assessment. When in vitro data demonstrate enhanced growth, further studies in relevant in vivo xenograft animal models with receptor expressing tumor cell lines may be needed. In addition incorporation of sensitive indexes of cellular proliferation in long-term repeat-dose toxicity studies may provide useful information. 

Interferons (IFN) are glycoproteins that, among other products, are released from virus-infected cells. In neighboring cells, interferon stimulates the production of antiviral proteins. These inhibit the synthesis of viral proteins by (preferential) destruction of viral DNA or by suppressing its translation. Interferons are not directed against a specific virus, but have a broad spectrum of antiviral action that is, however, species-specific. Thus, interferon for use in humans must be obtained from cells of human origin, such as leukocytes (IFN-a), fibroblasts (IFN-p), or lymphocytes (IFN-y). Interferons are used in the treatment of certain viral diseases, as well as malignant neoplasias and autoimmune diseases e.g., IFN-a for the treatment of chronic hepatitis C and hairy cell leukemia and IFN-p in severe herpes virus infections and multiple sclerosis. 

C. Eng. The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung s disease. Seminars in medicine of the Beth Israel Hospital, Boston. NEn J Med, 335 (13), 943-951, 1996. 

MEN, multiple endocrine neoplasias, including thyroid carcinomas and tumours of the adrenal medulla, (phaeochromocytoma). 

Muscle weakness and diffuse myalgia were reported in a 17-year-old man with multiple endocrine neoplasia syndrome type 1 taking ketoconazole for oral candidiasis. The electromyogram showed a distinct myopathic pattern. Withdrawal of the ketoconazole was followed by rapid improvement (SEDA-17, 323). 

Cancer, or neoplasia, which occurs in one of every four individuals and results in the death of one of every five individuals in the United States, is a complex disease with multiple causes. Many intrinsic and extrinsic factors influence the development of cancer. Intrinsic or host factors include age, sex, genetic constitution, immune system function, metabolism, hormone levels, and nutritional status. Extrinsic factors include substances eaten, drunk, or smoked workplace and environmental (air, water, and soil) exposures natural and medical radiation exposure ... 

A classical example is alcoholic cirrhosis, which in the case of chronic alcohol abuse, leads to multiple, polyclonal areas of liver cell hyperplasia and an increased risk for development of hepatocellular neoplasia. In both preneoplasia and certain forms of hyperplasia, the antecedent lesions typically have a higher rate of cell proliferation than the surrounding normal cells and, thus, these cells are at increased risk to sustain additional genetic damage and progress to the next stage in the carcinogenic process. 

Initiators/initiation Effect is irreversible Only one exposure may suffice Multiple exposures may be additive Cannot identify initiated cells Agents are considered carcinogens Agents are usually mutagenic No measurable threshold dose Must be administered before the promoter Does not result in neoplasia unless promoter is subsequently applied... 

Eisenhofer G, Lenders JW, Linehan WM, Walther MM, Goldstein DS, Reiser HR. Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. N Engl J Med 1999 340 1872-9. 

Eisenhofer G, Walther MM, Huynh TT, Li ST, Bornstein SR, Vortmeyer A, et al. Pheochromocy-tomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes. J CUn Endocrinol Metab 2001 86 1999-2008. 

Multiple endocrine neoplasia type I with pituitary and pancreatic tumors... 

Multiple endocrine neoplasia type II with medullary thyroid carcinoma and pheochroniocytoma Malignancy... 

Calcitonin is secreted by the parafollicular or C cells, which arise from the neural crest and are distributed throughout the thyroid gland. These cells are included in the APUD (cmine precursor uptake and decarboxylation) family, which explains the association of medullary thyroid carcinoma (a tumor of the C cells) and other tumors of the APUD family in multiple endocrine neoplasia type 2A and -2B (MEN-2A and MEN-2B). Release of calcitonin is stimulated by calcium, and it has been used pharmacologically as an inhibitor of bone resorption. 

Decker RA, Peacock ML, Borst MJ, Sweet JD, Thompson NW. Progress in genetic screening of multiple endocrine neoplasia type 2A is calcitonin testing obsolete Surgery 1995 118 257-64. 

Gagel RE. Multiple endocrine neoplasia type II and familial medullary thyroid carcinoma impact of genetic screening on management. Cancer Treat Res 1997 89 421-41. 

Kaplan MM, Stall GM, Cmnmings T, MacAulay A, MacAulay A, Motte P, Wolfe HJ, et al. High-sensitivity serum calcitonin assays applied to screening for thyroid C-celi disease in multiple endocrine neoplasia type 2A. Henry Ford Hosp Med J 1992 40 227-31. 

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