Colorectal carcinomas

IL-2 has been approved for the heatment of renal cell carcinoma and also has shown good activity in malignant melanoma. Both of these tumors are refractory to chemotherapy. IL-2 has also been used invesdgationally, both alone and in combinadon with LAK cells, with chemotherapy and with other biological response modifier s (BRM s) to d eat a variety of different cancers (e.g., head and neck carcinoma, colorectal cancer, cend al nervous system cancer etc). In addidon to cancer therapy, IL-2 has been used to d eat padents infected with human immunodeficiency virus and it has been used ex vivo to generate antiviral T cells which were reinfused into padents (Lewko and Oldham, 2003 Dorr, 1993). 

Coffin CM, Swanson PE, Wick MR, et al. An immunohistochemical comparison of chordoma with renal cell carcinoma, colorectal adenocarcinoma, and myxopapillary ependymoma A potential diagnostic dilemma in the diminutive biopsy. Mod Pathol. 1993 6 531-538. 

This mitochondrial peroxisome enzyme, alpha-meth-ylacyl-CoA racemase (AMACR) (encoded by the gene P504S) catalyzes the racemization of alpha-methyl branched carboxylic coenzyme A thioesters and is present in prostate tissue and a wide variety of carcinomas (colorectal, ovarian, breast, bladder, lung, renal cell), melanoma, and lymphoma.AMACR is useful in prostate needle biopsies when the differential diagnosis... 

It has been traditionally used for the treatment of inflammatory process by several oriental systems of herbal medicine. In the traditional Chinese medicine, this species is among 50 fundamental herbs used, belonging to the Pharmacopoeia of the People s Republic of China [67], Tetrandrine showed potent antiproliferative activity against a broad panel of human cell lines, including those derived from hepatocellular carcinoma, colorectal, and esophageal cancers [68, 69],... 

Indication for use Hepatocellular carcinoma Hepatocellular carcinoma, colorectal metastases... 

Cancer treatment is a multimodality treatment, i.e., surgery is combined with radiotherapy and antineoplastic chemotherapy. The latter treatment mode is used mainly for cancers which have disseminated. Different forms of cancer differ in their sensitivity to chemotherapy with antineoplastic agents. The most responsive include lymphomas, leukemias, choriocarcinoma and testicular carcinoma, while solid tumors such as colorectal, pancreatic and squamous cell bronchial carcinomas generally show a poor response. The clinical use of antineoplastic agents is characterized by the following principles. 

Cancer Elevated levels of AEA in glioblastomas, increased levels of 2-AG in meningiomas, elevated levels of both AEA and 2-AG in colorectal carcinoma, with possible anti-tumour action Inhibitors of degradation (both FAAH and cellular re-uptake)... 

Growth inhibition by TGF- 3, associated with inhibition of c-myc, cdks, reduction in cyclin D1 levels, and inhibition of cdk-4-associated Rb kinase activity, as well as induction of cdk inhibitors pi5 and p27, has been noted in intestinal epithelial cells. Loss of responsiveness to growth inhibition from TGF- 3 occurs in many cell types including breast, colorectal carcinoma, and pancreatic carcinoma cells. Mutational inactivation of T 3RH represents one mechanism of this process, which in many cases, leads to the development of gastrointestinal cancer. Thirteen percent of colorectal carcinomas are thought to be associated with a replication error (RER) or microsatellite instability phenotype. Subsequent inactivation of T 3RII and... 

ADCC. Cetuximab is approved for treatment of metastatic colorectal cancer (CRC) and squamous cell carcinoma of the head and neck (SCCHN). Interestingly, an adverse event, acneiform rash seems to correlate with a better response to cetuximab, while there is no such correlation with expression levels of EGFR assessed by immunohistochemistry. Further side effects are rare infusion reactions and hypomagnesia. Two other anti-EGFR antibodies approved for clinical use are the fully human antibody panitumumab (Vectibix)... 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

Adenomatous polyposis coli (APC) gene A tumor suppressor gene, acting as a gatekeeper to prevent development of tumors. A familial cancer syndrome called FAP, or familial adenomatous polyposis, is caused by mutations in APC. Mutation of APC also occurs commonly in sporadic cases of colorectal carcinoma. 

Gunther K, Leier J, Henning G, et al. Prediction of lymph node metastasis in colorectal carcinoma by expression of chemokine receptor CCR7. Int J Oncol 2005 116 726-733. 

CA 125 is a mucin-like glycoprotein antigenic determinant expressed on the surface of coelomic epithelium and human ovarian carcinoma cells however, it does not appear to be specific for ovarian cancer because elevated levels have been reported in breast and colorectal cancers. Studies have shown increased CA 125 levels in patients with ovarian cancer, whereas decreased CA 125 levels in chemotherapy are associated with improved possibility for survival. Some studies have shown failure of CA 125 levels to return to normal after chemotherapy, indicating... 

CEA is a prototypic tumor marker. It is neither organ specific nor tumor specific. CEA concentrations are elevated (greater than 3.0 ng/ml) in the sera of patients with colorectal, gastric, pancreatic, hepatocellular, and biliary carcinoma. The... 

CEA levels are elevated in benign diseases such as inflammatory bowel disease, chronic gastritis and peptic ulcer, cirrhosis, and hepatitis. CEA testing is recommended primarily to monitor patients after surgery for recurrent colorectal carcinoma. Twenty percent of colorectal carcinomas do not express CEA therefore, immunohistochemical methods are recommended to identify the negative cases. If a 5.0 ng/ml cutoff is used as the detection criterion, approximately 60 to 90 percent of the clinical cases will be detected for recurrences 2 to 10 months prior to clinical symptoms (37, 38). 

The enthusiasm for using Caco-2 cells and other epithelial cell cultures in studies of drug transport processes has been explained by the ease with which new information can be derived from these fairly simple in vitro models [7]. For instance, drug transport studies in Caco-2 cells grown on permeable supports are easy to perform under controlled conditions. This makes it possible to extract information about specific transport processes that would be difficult to obtain in more complex models such as those based on whole tissues from experimental animals. Much of our knowledge about active and passive transport mechanisms in epithelia has therefore been obtained from Caco-2 cells and other epithelial cell cultures [10-15]. This has been possible since Caco-2 cells are unusually well differentiated. In many respects they are therefore functionally similar to the human small intestinal enterocyte, despite the fact that they originate from a human colorectal carcinoma [16, 17]. 

Normal colon mucosa versus colorectal carcinoma 226... 

Stulik J et al. Protein abundance alterations in matched sets of macroscopically normal colon mucosa and colorectal carcinoma. Electrophoresis 1999 20 3638-3646. 

Thus, oxygen radical production by leukocytes can be responsible for cancer development. However, the levels of leukocyte oxygen radical generation depend on the type of cancer. For example, PMNs and monocytes from peripheral blood of patients with lung cancer produced a diminished amount of superoxide [169], Timoshenko et al. [170] observed the reduction of superoxide production in bronchial carcinoma patients after the incubation of neutrophils with concanavalin A or human lectin, while neutrophils from breast cancer patients exhibited no change in their activity. Chemotherapy of lung and colorectal carcinoma patients also reduced neutrophil superoxide production. Human ALL and AML cells produced, as a rule, the diminished amounts of superoxide in response to PMA or FMLP [171], On the other hand total SOD activity was enhanced in AML cells but diminished in ALL cells, while MnSOD in AML cells was very low. It has been proposed that decreased superoxide production may be responsible for susceptibility to infections in cancer patients. 

Ch. 25). This means that mutations in these proteins that result in alterations in their regulatory properties can lead to oncogenesis. Ras in particular has been implicated in several human cancers [32]. It has been estimated that as many as 30% of all human cancers contain mutations in one of the three Ras genes. While the frequency of Ras mutations in some types of human cancer is very low, its frequency in certain cancers, such as squamous cell carcinoma, lymphatic cancers and colorectal adenocarcinoma, is very high. 

When colorectal carcinoma is suspected, a careful personal and family history and physical examination should be performed. 

---