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

Based on recent preclinical data suggesting synergism between 5-fluorouracil (5-FU) and interferon alpha (IFN-alpha) and clinical activity of the combination therapy in colon cancer, 14 patients with advanced gastric cancer were treated with combination therapy of 5-FU and recombinant interferon alpha-2b (rIFN alpha-2b) (Intron A, Schering, Kenilworth, NJ, U.S.A.). The maximum tolerated dose was 5-FU 750 mg/m2/day given as a continuous infusion daily for 5 days followed by weekly bolus injection of the same initial daily dose, plus rIFN alpha-2b 5 X 10(6) U given subcutaneously 3 times weekly starting day 1 of 5-FU infusion. The dose-limiting toxicities were fatigue/weakness, diarrhea, and neurologic toxicities such as somnolence and confusion. The other common side effects were nausea, fever, leukocytopenia, thrombocytopenia, and the darkening of the skin. Of 13 evaluable patients, 4 had a partial response (duration 6, 14, 24, and 28 weeks). These data suggest that combination therapy of 5-FU plus rIFN alpha-2b is tolerable and has manageable side effects in patients with advanced gastric cancer. Further Phase II study will be needed to define the antitumor activity of this combination.
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PMID:Combination of 5-fluorouracil and recombinant interferon alpha-2B in advanced gastric cancer. A phase I study. 155 2

Interferon alfa-2b has recently been approved by the FDA as the first effective adjuvant therapy for the treatment of the "high risk for recurrence" melanoma patient. In a landmark study (ECOG 1684), the use of high dose Interferon alfa-2b for one year in melanoma patients with either deep primary melanomas or resected nodal metastases resulted in significant increases in overall survival (p = 0.04) and disease-free survival (p < 0.01) compared to the control, observation arm. If one considers only those patients with nodal metastases (89% of the study population) the survival benefit associated with adjuvant Interferon alfa-2b had a p value of 0.008. This survival benefit is on par with the survival benefit experienced with the adjuvant therapy of either breast or colon cancer. Because of the survival benefit associated with the adjuvant therapy, one could argue that any melanoma patient with a significant risk of nodal metastases (tumor thickness greater than 1.0 mm) should have a nodal staging procedure. Lymphatic mapping and sentinel node biopsy techniques are the least morbid and costly method to obtain this information. By performing nodal staging on patients with melanomas greater than 1.0 mm in thickness, effective adjuvant therapy can be applied in a selective fashion, exposing only those patients who have the most to benefit to the toxicities of the therapy.
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PMID:The adjuvant treatment of malignant melanoma. 914 64

The regulation of urokinase plasminogen activator receptor (uPAR) gene expression by interferon-alpha (IFN-alpha, or Intron A) and interferon-gamma (IFN-gamma) was studied in a HCT116 colon cancer cell line. uPAR mRNA levels were increased in a dose- and time-dependent manner in cells stimulated with IFN-alpha or IFN-gamma. uPAR protein levels reflected IFN-alpha and IFN-gamma induction of uPAR mRNA production. Cycloheximide, a protein synthesis inhibitor, also induced uPAR mRNA accumulation either alone or in combination with IFN-alpha or IFN-gamma, suggesting that the effect on uPAR mRNA levels activated by IFN-alpha or IFN-gamma does not require de novo protein synthesis. Both sodium butyrate and amiloride inhibited the uPAR mRNA levels induced by IFN-alpha or IFN-gamma. These results may provide useful information for the treatment of patients receiving IFN-alpha or IFN-gamma.
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PMID:Interferon-alpha (Intron A) upregulates urokinase-type plasminogen activator receptor gene expression. 1207 Jul 11