Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our expanding knowledge of the immune system has provided a basis of rationality for immunotherapy. Some non-specific immunotherapy has achieved the status of standard treatment: interferon in hairy cell leukemia and chronic myelogenous leukemia, BCG in bladder cancer, and levamisole in colon cancer adjuvant therapy. Tumor infiltrating lymphocytes, moreover, offer a level of specificity heretofore unknown. Combined with the newly available synthetic cytokines that regulate the normal immune system there is the potential for a major breakthrough in biotherapeutics. Problems remain. We have yet to identify tumor antigens with the precision necessary for effective immunotherapy. Indeed, we have no assurance that tumors will regularly synthesize new antigens. In the broad spectrum of immune deficiency syndromes, we have yet to see an increase in the common epithelial tumors that account for the great bulk of human cancer. This suggests that we still have a great deal more to learn.
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PMID:Immunotherapy of cancer with lymphokines and lymphokine-activated killer cells. 192 49

Antibody-dependent cell-mediated cytotoxicity (ADCC), medicated by peripheral blood Hypaque-Ficoll separated mononuclear cells, was studied in humans using chicken erythrocytes (CRBC) incubated in a 1:1200 dilution of rabbit anti-CRBC and human B erythrocytes (HRBC) incubation in a 1:20 dilution of isoantibody. At the optimal target effector ratio of 3:1, ADCC to both CRBC and HRBC was significantly higher than normal in 27 lung cancer, 18 malignant melanoma, and seven colon cancer patients, but not in 20 breast cancer patients. Chemotherapy (single-agent or combination) in 12 patients did not effect ADCC in vitro but significantly suppressed ADCC to both targets after only four or five days of therapy in vivo (ADCC to CRBC, 47.4 to 24.1% lysis: ADCC to HRBC, 48.1 to 16.3% lysis). Immunotherapy with intravenous (IV) corynebacterium parvum or IV methanol extraction residue of BCG (MER) boosted ADCC to both targets within four to seven days of the first dose. It was found that ADCC to HRBC but not to CRBC was completely absent in three cases of active hairy cell leukemia but was present in two cases in remission. The ADCC to HRBC showed an age-dependent increase in both the 51 normal subject and the cancer patients. This was not observed for ADCC to CRBC. The ADCC to CRBC was mediated mainly by an Fc-receptor-positive, nonadherent, small lymphocyte, and ADCC to HRBC was mediated entirely by an adherent monocyte. The ADCC did not correlate significantly with the H3 thymidine incorporation of peripheral blood mononuclear cells, cultured without stimulation for either one or seven days. It also did not correlate with the number of residual granulocytes in the mononuclear cell suspensions. Measurement of ADCC is a useful method of characterizing host defense in malignant disease and its modification by therapy.
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PMID:Antibody-dependent cell-mediated cytotoxicity in human cancer: characterization of patient leukocyte activity and treatment effects. 703 82

Meningitis due to Streptococcus bovis is rare. Only 14 cases having been reported in the English literature. All patients (including the patient described) had an underlying disease or were treated by pharmacological agents that predisposed the patient to the infection. Most were treated by monotherapy with penicillin G (or amoxicillin) and recovered. We describe a 74-year-old woman who had splenectomy as treatment for hairy cell leukemia 6 months before hospitalization for meningitis and sepsis by S. bovis type II. She was successfully treated with intravenous amoxicillin. There was neither evidence of endocarditis nor carcinoma of the colon. Although the association between S. bovis meningitis and endocarditis or carcinoma of the gastrointestinal tract is not well established, we recommend a full work-up for GI malignancy and endocarditis in every patient with S. bovis meningitis.
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PMID:[Meningitis due to Streptococcus bovis type II]. 1091 72

Why does it seem that, repeatedly, when a new treatment with a striking effect is discovered in the cancer field, it is effective for a very rare cancer type? For example, groundbreaking therapeutic discoveries have been made for extremely uncommon malignancies such as hairy cell leukemia, chronic myelogenous leukemia, seminoma, gastrointestinal stromal tumor, (del)5q myelodysplastic syndrome, and acute promyelocytic leukemia. In contrast, progress in the most common and most intensively studied tumors - lung, breast, prostate, and colon cancer - has been slow and incremental. We hypothesize that the reason for this phenomenon is that the pathophysiologic basis for a tumor being rare is one and the same as the reason that it may ultimately be so treatable. That is, if a cancer can be derived only via a single aberrant molecular genetic aberration, then it should be both rare and easily targeted by a molecular cancer therapeutic approach. If, on the other hand, many distinct pathways can lead to the development of a specific tumor type, it should occur much more commonly and be significantly more difficult to treat. The corollary to our hypothesis is the prediction that new therapies will continue to show their most salutary effects in rare cancers. Furthermore, only by stratifying the common tumors, especially when using targeted agents, into the molecular subsets of diseases that compose them are we likely to achieve a substantial effect in these disorders.
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PMID:Uncommon tumors and exceptional therapies: paradox or paradigm? 1743 Nov

Pseudomonas exotoxin (PE)-based immunotoxins (antibody-toxin fusion proteins) have achieved frequent complete remissions in patients with hairy cell leukemia but far fewer objective responses in other cancers. To address possible mechanisms of resistance, we investigated immunotoxin activity in a model system using the colon cancer cell line, DLD1. Despite causing complete inhibition of protein synthesis, there was no evidence that an immunotoxin targeted to the transferrin receptor caused apoptosis in these cells. To address a possible protective role of prosurvival Bcl-2 proteins, the BH3-only mimetic, ABT-737, was tested alone or in combination with immunotoxins. Neither the immunotoxin nor ABT-737 alone activated caspase 3, whereas the combination exhibited substantial activation. In other epithelial cell lines, ABT-737 enhanced the cytotoxicity of PE-related immunotoxins by as much as 20-fold, but did not enhance diphtheria toxin or cycloheximide. Because PE translocates to the cytosol via the endoplasmic reticulum (ER) and the other toxins do not, ABT-737-mediated effects on the ER were investigated. ABT-737 treatment stimulated increased levels of ER stress response factor, ATF4. Because of its activity in the ER, ABT-737 might be particularly well suited for enhancing the activity of immunotoxins that translocate from the ER to the cell cytosol.
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PMID:ABT-737 overcomes resistance to immunotoxin-mediated apoptosis and enhances the delivery of pseudomonas exotoxin-based proteins to the cell cytosol. 2058 62

Mutations in the RAS/RAF/MEK/ERK pathway leading to constitutive activation and uncontrolled cellular growth have been identified in various human malignancies, making this pathway a target for potential therapeutics. The activating BRAFV600E mutation is one well-characterized oncogenic mutation that has been described and targeted with clinical success in various malignancies, including melanoma and hairy cell leukemia. Although BRAF-directed treatments have yielded clinical benefit in a subset of tumor types, such as melanoma, thyroid cancer, and lung cancer, BRAF inhibition fails to confer a clinical benefit in colon cancer. Identification of patients for whom BRAF inhibition may produce clinically meaningful outcomes is imperative. The incidence of BRAF mutations in neuroendocrine carcinoma (NEC) is estimated to be 5% to 10%. A recent case series demonstrated benefit in targeting the BRAFV600E mutation in metastatic high-grade rectal NECs. Combination BRAF and MEK inhibition is known to yield improved outcomes compared with BRAF inhibition alone in melanoma. This report presents 2 patients with high-grade colorectal NECs who had different responses to treatment with combined BRAF/MEK inhibition after experiencing disease progression through first-line platinum-based chemotherapy. One patient experienced an excellent initial response to therapy before ultimately experiencing progression, and in the other patient initially had stable disease before eventually experiencing progression. These cases highlight the complicated role BRAF mutations play in gastrointestinal NECs, and the need for further research to identify not only patients who may benefit from BRAF-directed therapies but also strategies to avoid development of resistance.
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PMID:Targeting BRAF Mutations in High-Grade Neuroendocrine Carcinoma of the Colon. 3018 15