Colorectal, other carcinomas

Importantly, other mucinous neoplasms with morphologic intestinal features, the colloid carcinoma of the lungi45 with goblet cells (100%), and a subset of ovarian mucinous carcinomas (64%) are CDX2 positive. The majority of the colloid lung tumors are TTF-1 positive, a feature that allows distinction from metastatic colorectal mucinous carcinoma. Ovarian mucinous carcinomas may be separated from gastrointestinal mucinous carcinomas by virtue of typical immunostaining for CK7 in the ovarian tumors. 

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)... 

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]. 

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. 

The other well-known member of this superfamily is CEA or carcinoem-bryonic antigen. CEA is a widely used tumor marker, especially for monitoring patients with diagnosed colorectal cancer (M5). It is a high-molecular-weight (Afr 200,000, approximately) glycoprotein containing about 60% carbohydrate. In normal colonic cells and in well-differentiated colon carcinomas, the distribution of CEA is apical. However, in undifferentiated colonic tumors, CEA is present on all of the cell membrane (J3). Whether this altered subcellular localization of CEA mediates cancer spread is presently unclear. 

It has been postulated that wood dust carcinoma results from a multistep process Exposure causes loss of cilia and hyperplasia of the goblet cells and initiation of cuboidal cell metaplasia, followed (after a quiescent period) by squamous cell metaplasia. Decades later, cellular aplasia leads to nasal adenocarcinoma. The time between first occupational exposure to wood dust and the development of nasal cavity adenocarcinoma averages 40 years. Other cancers, including lung cancer, Hodgkin disease, multiple myeloma, stomach cancer, and colorectal cancer and lymphosarcoma, have been mentioned in relation to wood... 

Investigative efforts are underway to further improve the results of multimodality therapy of colorectal carcinoma. In addition to previously discussed phase III trials, other studies are incorporating novel chemotherapeutic agents to improve systemic control and radiosensitization, optimizing physical delivery of radiation, and performing risk stratification with current molecular and genetic techniques. 

Irinotecan has demonstrated a broad spectrum of activity in vitro and in vivo, and synergistic effects have been observed when it is administered in combination with other antineoplastic agents. Clinically irinotecan is now an active agent in patients with colorectal carcinoma. Irinotecan is metabolized by carboxylesterase to an active metabolite. It is cleared by hepatic metabolism and biliary excretion with a terminal elimination half-life of approximately 15 hours. The principal toxicities associated with irinotecan are diarrhoea and leucopenia. 

Patients with other types of unresectable cancer also may benefit from chemotherapy, as evidenced by prolongation of life, shrinkage of tumor, and improvement in symptoms. Notable among these are ovarian epithelial and breast carcinomas, oat cell (small cell undifferentiated) carcinoma of the lung, and acute myelocytic leukemia. Cancers that are for the most part resistant to today s agents include melanoma, colorectal and renal carcinomas, and non-oat cell cancers of the lung. 

Carmustine and lomustine can produce remissions that last from 3 to 6 months in 40 to 50% of patients with primary brain tumors. Both drugs also are used as secondary treatment of Hodgkin s disease and in experimental combination chemotherapy for various types of lung cancer. Other tumors in which remission rates of 10 to 30% have been obtained are non-Hodgkin s lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and colorectal cancer. 

H. Other considerations Interferon alfa-2a has been designated an orphan drug product for the treatment of chronic myelogenous leukemia, AIDS-related Kaposi s sarcoma, renal cell carcinoma, metastatic malignant melanoma, and esophageal and colorectal cancer. 

Francis RJ, Sharma SK, Springer C, Green AJ, et al. 2002. A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours. Br J Cancer. 87 600-607. 

Bevacizumab [Avastin] Colorectal carcinoma Hemorrhage hypertension Gl distress [nausea, vomiting, diarrhea] blood disorders [leukopenia, neutropenia] others... 

The precise role of immunological surveillance in tumorigenesis is not well dehned for the majority of malignancies. The occurrence of a unique spectrum of malignancies in immunosuppressed individuals suggests either that immune surveillance is only important in certain tumors or that the duration needed to see an increased incidence of many more common tumors (e.g., colorectal, breast, lung, or prostate carcinomas) is not reached. Suppression of T cell mediated immunity has, however, been unequivocally associated with an increased incidence of certain mahgnancies. In patients with profound defects in T cell immunity the time to tumor detection is often shorter than for cancers induced by other mechanisms. 

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