Small intestinal adenocarcinomas

Cell monolayers grown on permeable culture inserts form confluent mono-layers with barrier properties and can be used for drug absorption experiments. The most well-known cell line for the in vitro determination of intestinal drug permeability is the human colon adenocarcinoma Caco-2 [20, 21], The utility of the Caco-2 cell line is due to its spontaneous differentiation to enterocytes under conventional cell culture conditions upon reaching confluency on a porous membrane to resemble the intestinal epithelium. This cell model displays small intestinal carriers, brush borders, villous cell model, tight junctions, and high resistance [22], Caco-2 cells express active transport systems, brush border enzymes, and phase I and II enzymes [22-24], Permeability models... 

Caco-2 cells and isolated small intestine are models of basic nutrition that contributed to the understanding of resveratrol absorption and bioavailability. While the Caco-2 absorption model is a well-defined cellular in vitro system based on a human colonic adenocarcinoma cell line, the isolated small intestine model is nearer to in vivo conditions and is also simpler to handle. It also avoids the methodological problems of in vivo perfusion models [Barthe et al., 1998, 1999]. 

The tumors in the colon and small intestine were principally polypoid adenocarcinomas with histological and other characteristics of tumors induced by alkylhydrazines and their derivatives (18). Although the percentage of rats with small intestinal or colon tumors was not influenced by diet, the number of tumors per rat in the small intestine and colon was significantly greater with 15.0 or 22.5% protein compared to 7.5% protein (Table II). Ear tumors, observed first during the 21st week of the experiment... 

With one important exception, dioxoles and oxathioles do not appear to be a particularly toxic class of compounds. The exception is 1,2-oxathiolane 2,2-dioxide (propane sultone) which produces brain tumors, leukaemias and adenocarcinomas of the small intestine in rats treated with 28 mg kg-1 orally twice a week for 60 weeks. If the toxicity is associated with its ability to act as an alkylating agent, then higher homologs should have similar, but reduced, carcinogenic potential. 

Nicklin P, Irwin B, Hassan I et al. (1992) Permeable support type influences the transport of compounds across CACO-2 cells. Int J Pharm 93 197-209 Pappenheimer JR, Reiss KZ (1987) Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat. J Membr Biol 100 123-136 Peters WHM, Reolofs HMJ (1992) Biochemical characterization of resistance to mitoxantrone and adriamycin in CACO-2 human colon adenocarcinoma cells a possible role for glutathione-S-transferase. Cancer Res 52 1886-1890... 

Svrcek M, Jourdan F, Sebbagh N, et al. Immunohistochemical analysis of adenocarcinoma of the small intestine a tissue mi-ctoarray study. J Clin Pathol. 2003 56 898-903. 

Intestinal-type adenocarcinomas (ITACs) are rare tumors of the sinonasal tract that bear a remarkable histologic resemblance to tumors arising in the intestines. Rare cases can even resemble normal small intestinal mucosa. There is an epidemiologic linkage to occupational exposure to wood dust, particularly the hard woods, as found in furniture making. ITAC is more common in males by a ratio of 4 1 and occurs over a broad age range, with an average of 58 years. 

Small intestinal adenocarcinomas stain diffusely and strongly with CKs 18 and 19. ° In contrast to normal small intestinal epithelium, nonampullary small intestinal adenocarcinomas tend to develop CK7 expression and lose CK20 expression. > 85 Approximately two thirds of small intestinal adenocarcinomas coexpress both CK7 and CK20, and the remaining 33% are... 

Fewer small intestinal adenocarcinomas (60% to 70%) express CDX2 and villin, compared with colorectal adenocarcinomas. 

CK7 and AMACR can help differentiate small intestinal adenocarcinomas (CK7-I-/AMACR-) from colorectal adenocarcinomas (CK7-/AMACR-I-). 

FIGURE 14.14 Small intestinal adenocarcinoma (A, H E stain). This is an example of a small intestinal adenocarcinoma that strongly expresses CK7 (B), CK20 (C), and CDX2 (D). 

Chen ZM, Wang HL. Alteration of cytokeratin 7 and cytokeratin 20 expression profile is uniquely associated with tumorigene-sis of primary adenocarcinoma of the small intestine. Am J Surg Pathol. 2004 28 1352-1359. 

Zhang MQ, Lin F, Hui P, et al. Expression of mucins, SIMA, villin, and CDX2 in small-intestinal adenocarcinoma. Am J Clin Pathol. 2007 128 808-816. 

Cytokeratin 20 (CK20) is a type I acidic low molecular weight cytokeratin that was initially described in 1992. 1 It is found in normal tissues of the stomach, intestine, urothelium, and in Merkel cells. It is found in most adenocarcinomas of the large and small intestines, in mucinous tumors of the ovary, and in Merkel cell carcinomas, and it is frequently present in urothelial carcinoma and in adenocarcinomas of the stomach, pancreas, and bile ducts. It is a useful marker for primary mucinous tumors of the ovary and for various types of metastases that are found in the ovaries. 

Blaker H, Helmchen B, Bonisch A, Aulmann S, Penzel R, Otto HF, Riekta- RJ. Mutational activation of the RAS-RAF-MAPK and Wnt pathway in small intestinal adenocarcinomas. Scand J Gastroenterol. 2004 39 748-53. 

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