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

This study was conducted to assess the enhanced antitumor effects of natural human tumor necrosis factor alpha (nHuTNF-alpha) and natural human interferon alpha or gamma (nHuIFN-alpha or -gamma), in combination, on ten human cancer cell lines. The cell lines tested were colon cancer (RPMI4788), lung cancer (PC10), gastric cancer (MKN-1 and MKN-28), nasopharyngeal cancer (KB), leukemia (K562), lymphoma (Daudi), Liver cancer (H-7) and breast cancer (ZR-75-30 and ZR-75-1). A mixture of nHuTNF-alpha and nHuIFN-alpha (1:1, by unit) showed cytotoxic effects on nHuTNF-alpha resistant cell lines such as RPMI4788, KB and Daudi or nHuIFN-alpha resistant cell lines such as KB, and ZR-75-1, as well as on nHuTNF-alpha or nHuIFN-alpha sensitive cells. A synergistic antitumor effect occurred in four cell lines (RPMI4788, PC10, Daudi and ZR-75-1) treated with a combination of nHuTNF-alpha and nHuIFN-alpha. Also, a combined treatment with nHuTNF-alpha and nHuIFN-gamma (1:1/100, by unit) showed cytotoxic effects on nHuTNF-alpha or nHuIFN-gamma resistant cell lines such as MKN-1, MKN-28, Daudi, H-7 and ZR-75-1. A synergistic antitumor effect occurred in eight cell lines (RPMI4788, PC10, MKN-1, MKN-28, KB, Daudi, H-7 and ZR-75-1). Thus, the combined treatment with nHuTNF-alpha and nHuIFN-alpha or -gamma expanded the spectrum of sensitive cells. These results indicate that the combined use of nHuTNF and nHuIFN may provide a certain approach to cancer treatment.
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PMID:Synergistic antitumor effects of natural human tumor necrosis factor-alpha and natural human interferon-alpha or -gamma on human cancer cell lines. 250 39

Recombinant human interferon alpha inhibits growth of a human colon cancer cell line, Colo 205. To explore the mechanisms of IFN induced growth inhibition, quiescent Colo 205 cells were stimulated to proliferate in serum-free media by defined growth factors. Addition of insulin, transferrin and selenium (ITS) stimulated DNA synthesis, as measured by 3H-thymidine incorporation, in a dose-dependent manner. IFN-alpha (at concentrations greater than 100 U ml-1) inhibited ITS stimulated DNA synthesis by 63%. Inhibition of cell cycle traverse was confirmed by flow cytometric analysis. Although IFN inhibited growth of ITS-treated cells, steady state levels of c-myc mRNA remained above levels observed in unstimulated cells. IFN inhibited DNA synthesis only when added prior to mitogen stimulation. IFN, added 6 h after exposure of quiescent cells to ITS, failed to inhibit cell growth. Addition of increasing concentrations of ITS failed to overcome the IFN-induced growth inhibition. These results suggest IFN may inhibit cell growth in part by antagonizing the action of growth factors.
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PMID:Inhibition of mitogen stimulated growth of human colon cancer cells by interferon. 316 5

The antitumor effects of recombinant interferon alpha-2 (rIF) on clonogenic tumor cells were investigated in 29 cases of gastrointestinal cancer. An in vitro response (greater than or equal to 50% inhibition of tumor colony-forming units) was observed in 17% of the tumors, including 2 of 8 pancreatic, 2 of 6 gastric, and 1 of 10 colon cancer specimens. The relative efficacy of rIF in tissue cultures of pancreatic and gastric tumors was further substantiated by the resistance against simultaneously tested single conventional cytostatic drugs. Preliminary results of comparative studies of cloned interferon alpha-2 and human purified leukocyte interferon (hlIF) in 2 human colon cancer cell lines and 11 fresh tumor specimens suggest similar trends in terms of colony inhibition in individual assays. However, the interpatient differences indicate an overall superiority of the natural preparation (P less than 0.02).
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PMID:In vitro phase II trial of recombinant interferon alpha-2 in gastrointestinal cancer. 402 Jan 67

Discovered by Isaac and Lindemann as a substance able to induce a biological interference among viruses and host cells, interferon appeared to include three main antigenic classes: alpha, beta and gamma. There is a large variety of actions exhibited by different types of interferon and among them it is possible to distinguish an antiviral, antineoplastic, immunomodulatory or hormonal activity. Many years ago, the antiviral action seemed to be relative to some cellular membrane disorders, but later other mechanisms were stressed. Among them, it is worth describing the transcription and transduction of antiviral proteins like the oligoadenilsinthetase and proteinphosphokinase, able to cause the viral RNA breackage. The antineoplastic action is exerted by direct and indirect mechanisms. Direct mechanisms include an antiproliferative activity and the induction to cellular differentiation whereas the indirect ones involve the enhancement on tumor cell surfaces of some tumor associated antigens included in the I class of MHC system. The immunomodulatory action is exerted by the stimulation of macrophages, T cells and Killer cells cytotoxic activity. The list of viral diseases sensitive to interferon treatment includes condiloma acuminata, herpes zoster, chronic B and C hepatitis and Kaposi sarcoma AIDS-related. High proportions of overall response rate were observed among interferon treated patients with condiloma acuminata (80-100%). The use of interferon in the treatment of herpes zoster achieved good results regarding a shorter duration of the time spent to induce the chest pains and cutaneous symptoms disappearance when compared with that relative to other antiviral drugs. Results obtained in the treatment of chronic B and C hepatitis regard the disappearance of viral replication serological markers and the improvement of histological and enzymatic pattern. The effectiveness of interferon in the therapy of Kaposi sarcoma is demonstrated by the reduction of cutaneous symptoms and recurrent infectious diseases incidence. The use of interferon in treatment of solid tumors seems to play secondary role and, at any rate, to be adjuvant to chemotherapy. The administration of beta interferon as therapy of breast cancer seems to increase the estrogens and progesterone concentration in the neoplastic tissue and so it aims to improve the sensitivity to the tamoxifen treatment. The addition of interferon alpha both to 5-FU and cis-platinum seems to improve the proportion of overall response rate respectively in the treatment of colon cancer and head and neck cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Update on the use of interferons in clinical practice]. 758 95

In order to investigate the combined antitumor activity of 5-fluorouracil (5-FU), and recombinant human interferon alpha 2a (IFN alpha) or human fibroblastoid interferon beta (IFN beta), the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was carried out using a cultured human colon cancer cell line (C-1) and fresh surgical specimens of gastric and colon carcinomas. IFNs did not show positive antitumor activity against C-1 cells, whereas 5-FU showed time- and concentration-dependent antitumor activity against C-1 cells. Furthermore, the antitumor activity of 5-FU on C-1 cells was augmented by IFN alpha or beta. When 5-FU (50 micrograms/ml) with IFN alpha (50 IU/ml). or IFN beta (50 IU/ml) was applied for the MTT assay with 48 hours incubation of fresh surgical specimens of gastric and colon carcinomas, the inhibition rates increased by 10% in 9 of 21 gastric specimens and in 18 of 36 colon carcinomas for IFN alpha (47.4% or 27/57), and in 8 of 15 gastric specimens and in 15 of 28 colon carcinomas for IFN beta (53.5% or 23/43). These results suggest that the chemosensitivity to 5-FU of human gastric and colon carcinomas is increased in the presence of IFNs, without involvement of the host-mediated immune system, and that this combined effect can be predicted by the MTT assay in vitro.
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PMID:Interferons alpha-2a and beta increase the antitumor activity, detected by MTT assay, of 5-fluorouracil against experimental and clinical human gastrointestinal carcinomas. 906 9

In vivo electroporation of plasmid DNA (DNA-EP) is an efficient and safe method for vaccines resulting in increased DNA uptake, enhanced protein expression and increased immune responses to the target antigen in a variety of species. To further enhance the efficacy of DNA-EP, we have evaluated the toll-like receptor7 (TLR7) agonist-2, 9, substituted 8-hydroxyadenosine derivative or SM360320--as an adjuvant to vaccines against HER2/neu and CEA in BALB-neuT and CEA transgenic mice (CEA.Tg), respectively. SM360320 induced in vivo secretion of interferon alpha (IFNalpha) and exerted a significant antitumor effect in CEA.Tg mice challenged with a syngenic tumor cell line expressing CEA and an additive effect with a CEA vaccine. Additionally, combination of SM360320 with plasmid encoding the extracellular and transmembrane domain of ratHER2/neu affected the spontaneous tumor progression in BALB-neuT mice treated in an advanced disease setting. The antitumor effect in mice treated with DNA-EP and SM360320 was associated with an anti-CEA and anti-p185(neu) antibody isotype switch from IgG1 to IgG2a. These data demonstrate that SM360320 exerts significant antitumor effects and can act in association with DNA-EP for CEA-positive colon cancer and HER2-positive mammary carcinoma. These observations therefore emphasize the potential of SM360320 as immunological adjuvant for therapeutic DNA vaccines.
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PMID:An oral TLR7 agonist is a potent adjuvant of DNA vaccination in transgenic mouse tumor models. 1898 54

Pancreatic neuroendocrine tumors constitute about 2% of all gastrointestinal neoplasms. Approximately half of the pancreatic euroendocrine tumors are nonfunctional. Due to lack of specific symptoms, most patients with nonfunctional pancreatic neuroendocrine tumors present with locally advanced or metastatic disease. Second primary malignancies are seen very rarely in these patients. Colon carcinoma ranks third in frequency among primary sites of cancer in both men and women in western countries. Presence of a metachronous colon adenocarcinoma in a patient with nonfunctional pancreatic neuroendocrine tumor has not been reported before. We present a patient who had an asymptomatic mass in the head of the pancreas, detected by ultrasonography in 1996. The patient did not consent to operation. In 2002, after the diagnosis of an unresectable, nonfunctional pancreatic neuroendocrine tumor, interferon alpha- 2b and octreotide were started. A year after biological treatment, he refused further treatment. In 2004, during the evaluation of dissemination of the asymptomatic disease, positron emission tomography revealed a high uptake by the descending colon despite the failure of other imaging methods. After surgery for operable colon carcinoma, the patient received chemotherapy and biological therapy for both tumors. Since 2005, he has been doing well without any further treatment thus far. In conclusion, computerized tomography/magnetic resonance imaging and octreotide scintigraphy may be insufficient to show disseminated disease and asymptomatic second primary malignancies. Therefore, positron emission tomography is a valuable promising option for the evaluation of gastroenteropancreatic neuroendocrine tumors and concomitant or metachronous malignancies. Lifelong follow-up by a multidisciplinary oncology team is needed so that a long-term survival can be achieved with integrated multimodal systemic treatment approaches.
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PMID:A patient with nonfunctional pancreatic neuroendocrine tumor and incidental metachronous colon carcinoma detected by positron emission tomography: case report. 1982 Dec 5

Sarcoidosis is an inflammatory disease involving multiple-organs with an unknown cause. The new onset of sarcoidosis associated with therapeutic agents has been observed in 3 clinical settings; tumor necrosis factor antagonists in autoimmune rheumatologic diseases, interferon alpha with or without ribavirin in patients with chronic hepatitis C or melanoma, and antineoplastic agent-associated sarcoidosis in patients with hematologic malignancies. Here, we report a female patient who developed sarcoidosis after capecitabine treatment as an adjuvant chemotherapy for sigmoid colon cancer. To our knowledge, this is the first report of a capecitabine-induced sarcoidosis.
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PMID:A case of capecitabine-induced sarcoidosis. 2322 72