Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported the production of a new monoclonal antibody (MAb) (SP-2) recognizing a 90-kDa tumor-associated antigen, termed 90K, which is increased in the serum of many cancer patients. Treatment of CG5 human breast cancer cells with recombinant interferon-alpha 2b (rIFN-alpha 2b) can increase the synthesis and release, in culture medium, of the 90K. The effect of rIFN-alpha 2b was dose-related and occurred at concentrations which did not affect cell proliferation. The increase of 90K expression was due to de novo protein synthesis since cycloheximide, added within 3 hr of the beginning of rIFN-alpha 2b stimulation treatment, completely abolished the effect of rIFN-alpha 2b. The stimulatory effect of rIFN-alpha 2b was already evident after 24 hr treatment. Finally, an increase in serum 90K levels was observed in 3 patients with advanced breast cancer receiving a short course of rIFN-alpha 2b (Intron A). No effect of rIFN-alpha 2b was seen in 3 normal women. The ability of rIFN-alpha 2b to increase the synthesis and release of 90K both in vitro and in vivo may be of clinical importance in the early detection of tumors.
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PMID:Recombinant human leukocyte interferon-alpha 2b stimulates the synthesis and release of a 90K tumor-associated antigen in human breast cancer cells. 340 63

Since interferon alfa-2b (Intron A) is useful as a single agent, it is important to determine if interferon can be combined with standard chemotherapy to improve both response and survival in patients with cancer. Using clonogenic assays, interferon was tested alone and in combination with cyclophosphamide (Cytoxan) or melphalan (Alkeran) using several dose and exposure schedules to evaluate cytotoxicity. In vitro, continuous-exposure interferon produced optimal cell kill. Maximum enhancement of cytotoxicity occurred with cyclophosphamide or melphalan pretreatment (1 hour) and/or simultaneous interferon treatment. Based upon these data, a phase I-II study was designed to determine the tolerance of cancer patients to a fixed dose of cyclophosphamide (150 mg/m2 p.o. daily X 4 days [days 2 to 5]) combined with increasing doses of interferon. Interferon was administered subcutaneously on treatment cycle days 1 to 5, plus days 8, 10, 12, 15, 17, and 19 of the 21-day regimen. Three patients had partial responses: one breast cancer, one angiosarcoma, and one myeloma (mixed). All patients reported mild flu-like symptoms, fatigue, and anorexia. Leukopenia occurred in all patients; three required treatment interruption to allow recovery. Eight patients had a fall in hemoglobin (mean decrease 1.4 g/dL). The combination of cyclophosphamide and interferon was safe and deserves further trial in cancer treatment. However, using this combination schedule, interferon doses greater than or equal to 5 X 10(6) IU were poorly tolerated and compromised administration of full-dose cyclophosphamide.
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PMID:Interferon alfa-2b-cyclophosphamide combination studies: in vitro and phase I-II clinical results. 376 44