Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The low-molecular-weight imidazoquinolinamine derivative, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (imiquimod, previously described as R-837), induced alpha-interferon (IFN-alpha) in mice. IFN induction was identified at oral doses as low as 3 mg/kg. The 10% lethal dose for daily treatment with imiquimod was 200 mg/kg. Oral treatment with 30 mg/kg imiquimod once every three days significantly inhibited MC-26 colon carcinoma. Delay of treatment from day 1 to day 5, when tumors were easily palpable, did not reduce benefits. Ten daily treatments were slightly more effective than five. However, delivery of the same total dose of imiquimod either once every day for 20 days, once every 4 days, once every 7 days, or once every 10 days inhibited tumor growth to the same level. The antitumor effects of imiquimod were significantly abrogated by an antiserum to murine IFN-alpha, suggesting that the antitumor effect was to a substantial extent mediated by IFN induction. Imiquimod also significantly reduced the number of lung colonies in mice inoculated i.v. with MC-26 tumor cells. Combination of treatment with imiquimod and cyclophosphamide was significantly (P less than 0.01) better than treatment with either drug alone. Combination treatment with cyclophosphamide led to cures in some of the mice inoculated either s.c. or i.v. with MC-26 cells. Treatment with imiquimod also inhibited the growth of RIF-1 sarcoma and Lewis lung carcinoma but was ineffective for P388 leukemia. Imiquimod is an oral IFN-alpha inducer with antitumor effectiveness for transplantable murine tumors.
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PMID:Inhibition of murine tumor growth by an interferon-inducing imidazoquinolinamine. 137 95

ALDARA (imiquimod cream 5%) recently became available for the treatment of genital and perianal warts; however, the topical mechanism of action of imiquimod is not fully understood. Imiquimod, and its analogs R-842, S-27609, and S-28463, are potent anti-viral and anti-tumor agents in animal models. Much of the biologic activity of these compounds can be attributed to the induction of cytokines, including interferon-alpha, tumor necrosis factor-alpha, interleukins-1, -6, -8, and others. This study was performed to characterize the response of mice and rats to topical application of imiquimod and S-28463 and also to evaluate these agents in cultures of murine and human skin cells. Topical administration of imiquimod or S-28463 to the flanks of hairless mice and rats leads to increases in local concentrations of interferon and tumor necrosis factor in the skin. The concentrations of interferon and tumor necrosis factor were higher at the site of drug application than in skin from the contralateral flank or skin from untreated animals. Interferon-alpha mRNA levels were also elevated in the skin of mice after topical application of either imiquimod or S-28463. In vitro, both imiquimod and S-28463 induced increases in interferon and tumor necrosis factor in cultures of cells isolated from hairless mouse skin. Imiquimod also increased interleukin-8 concentrations in human keratinocyte and fibroblast cultures, whereas S-28463 induced increases in tumor necrosis factor in fibroblast cultures. These results demonstrate that imiquimod and S-28463 stimulate production of cytokines in the skin after topical application, which may play a major role in its activity in genital wart patients.
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PMID:Cytokine induction in hairless mouse and rat skin after topical application of the immune response modifiers imiquimod and S-28463. 957 37

Among HIV-seropositive women there is a high prevalence of anogenital human papillomavirus (HPV) infection. HPV-DNA is more frequent detected in cervicovaginal-lavage specimens from HIV-seropositive women as in those from HIV-seronegative women. We and others suggest that HIV-infection increases the risk to have HPV-associated lesions of the lower female genital tract, especially the risk for developing a squamous intraepithelial lesion of the cervix. In this report we describe the current diagnostic and therapeutic strategies in HIV-seropositive women with HPV-infection. The gynecological examination should be performed at six to twelve month intervals, including the colposcopy and the Pap smear test. We hope to improve the quality of our screening program by doing an additional HPV-test. At last we investigate the CD4+ T-lymphocyte counts because it is observed that women with low CD4+ cell counts (< 200/microliter) were more likely to have persistent HPV-infection as those with higher counts (> 500/microliter). The treatment method is dependent on the development of the HPV-associated lesion and the clinical status of the HIV infected women. In cases with external warts local application of Condylox should be the first line treatment. Probably in about few months we could use other drugs like Wartec or Aldara in Germany. But the effectiveness of these drugs in HIV-positive women has to be proven yet. In the cause of persistence of external warts or recurrence of the disease the systemical application of Intron A or Roferon A is possible. The CO2-lasertreatment is performed under colposcopic guidance, especially in cases with multicentric condylomatous lesions. The treatment of cervical intraepithelial neoplasia (CIN) by CO2-laservaporisation or Loop Electrosurgical Excision Procedure (LEEP) is based on the clear colposcopic visualisation of the upper limit of the lesion. If CIN reaches the endocervix, being out of colposcopic view, and the squamocolumnar junction is localised in the endocervical canal conisation by laser or cold knife has to be performed. Before performing the treatment of CIN one should exclude multicentric cervical, vaginal and vulval intraepithelial neoplasia by colposcopy, because multicentric intraepithelial neoplasia of the lower female genital tract is more frequently than in HIV-seronegative women. Multicentric disease seems to be one cause of the high recurrence of HIV-seropositive women. However, higher levels of immunosuppression (CD4+ T-lymphocyte counts < 200/microliter) are also important determinants of recurrence of the disease. Therefore, an accurate short-term follow-up with colposcopy, Pap test and HPV test should be carried out after the treatment of HIV-seropositive women with low CD4+ counts.
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PMID:[Diagnostic and therapeutic concepts of HPV infection in HIV-positive women]. 1009 10

The mechanism of action of imiquimod 5% cream applied topically to patients with genital warts was evaluated in a double-blind, placebo-controlled study. Imiquimod (16 patients) or placebo (three patients) was applied three times per week for up to 16 weeks. All imiquimod-treated patients had a > or =75% reduction in total wart area while only one of three placebo-treated patients had a similar reduction. Wart biopsies were taken at prestudy, week 6, and end of treatment. Polymerase chain reaction (PCR) for human papillomavirus (HPV) DNA and reverse transcriptase (RT)-PCR for messenger (m)RNAs were used to identify cytokines, cellular markers, viral gene products, and cell cycle markers in these biopsies. Treatment with imiquimod, an immune response modifier, stimulated significant increases in mRNA for interferon (IFN)-alpha, IFN-gamma and 2',5' oligoadenylate synthetase (2',5'-AS) as well as a tendency towards increases in tumor necrosis factor (TNF)-alpha and interleukin-12 p40. Significant increases in mRNA for CD4 and a trend toward increases in CD8 were also observed in imiquimod-treated patients, suggesting activation of a cell mediated immune response. Imiquimod administration was also associated with a significant decrease in viral load as measured by HPV DNA and L1 mRNA. The effects on HPV markers were accompanied by an apparent decrease in mRNA expression for markers of cell proliferation and an increase in mRNA for markers of keratinocyte differentiation and tumor suppressors.
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PMID:Enhancement of the innate and cellular immune response in patients with genital warts treated with topical imiquimod cream 5%. 1048 Feb 63

Langerhans cells are bone marrow derived dendritic cells that represent the major antigen-presenting cells in the skin. Langerhans cells take up and process antigen within the epidermis and present processed antigen to T lymphocyte in the regional lymph nodes and thus form an integral part of the cutaneous immune response. The cutaneous immune response can be modified by a number of pharmacologic agents, including corticosteroids, cyclosporine, and retinoids as well as physical agents, such as ultraviolet light. For the most part these agents act by suppressing immune function. A topical immune response modifier, imiquimod has been shown to enhance the cutaneous immune response. Imiquimod has anti-viral and anti-tumor effects in animal models and has been approved for the topical treatment of external genital and perianal warts in humans. The biologic activity of imiquimod in part is due to its effect as a cytokine inducer. Preliminary data suggested that imiquimod could have an effect on Langerhans cells. In order to clarify this effect on Langerhans cells, we examined Langerhans cell morphology and migration in imiquimod-treated skin. The density of Ia + cells decreased 2 d after treatment, falling to approximately 43% by day 10. The Ia positive in cells remaining in the skin appeared larger and more dendritic suggesting an activated state. ATPase staining of epidermal sheet confirmed the decreased number of Langerhans cells. To clarify status of Langerhans cells, the activation of B7 was examined. Activation of B7-1 or B7-2 was not detected. Imiquimod, however, did enhance Langerhans cell migration from skin to draining lymph nodes. This enhanced Langerhans cell migration was also associated with an enhanced allergic contact hypersensitivity. These results suggest that the mechanism of modulation of immune response by imiquimod is in part due to effects on Langerhans cells.
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PMID:Imiquimod, a topical immune response modifier, induces migration of Langerhans cells. 1062 Jan 29

Extramammary Paget's Disease (EMPD) is an uncommon neoplasm found in the genital, anorectal, or axillary area. Surgical excision is considered the standard treatment, although possible loss of tissue function and disease recurrence are seen. Other treatment modalities such as radiotherapy, topical chemotherapy, and photodynamic therapy are associated with varying degrees of effectiveness, but the search for an effective, safe treatment with minimal side effects proves to be challenging. We report a case where complete clinical and histological resolution of non-invasive EMPD of the penis was achieved with minimal adverse effects after six weeks of imiquimod (Aldara) application. As an immune system modifier that stimulates cytokine and interferon production, imiquimod may be a useful alternative or adjuvant in the treatment of EMPD.
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PMID:Successful treatment of extramammary Paget's disease with imiquimod. 1285 86

Imiquimod modulates the immune response, and is a new approach for treatment of papillomavirus-associated lesions, although it has not been approved for the treatment of intraepithelial neoplasia. We present a case of a patient treated with imiquimod on account of high-grade intraepithelial neoplasia in the vulva and other locations. The posterior biopsies confirm the absence of lesions but show drug-induced pemphigus as a side effect.
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PMID:Successful treatment of a high-grade intraepithelial neoplasia with imiquimod, with vulvar pemphigus as a side effect. 1526 68

Perianal Bowen's disease is a uncommon, slow growing, intraepidermal squamous-cell carcinoma (carcinoma in situ) of the anal region and may be a precursor to squamous carcinoma of the anus. It is associated with cervical and vulvar intraepithelial neoplasia and have human papillomavirus as a common cause. Both sexes and all races are affected, with the highest prevalence in patients aged 20 to 45 years. The symptoms of anal Bowen's disease are unspecific and the clinical findings are uncharacteristic and include pain, itching, bleeding and a disturbing lump. Biopsy and histopathologic examination is required for diagnosis and to distinguish other perianal dermatoses; thus an anogenital warts that fail to respond to conventional therapy, or change in appearance, warrant a biopsy and, where the technique is available, DNA typing to identify the viral pathogen. Infact the etiologic agent, the human papillomavirus (HPV), has been classified by DNA techniques into at least 42 types, of which 16 and 18 are considered to carry a high risk for cancer. The intraoperative findings is a lesion at the anocutaneous line: perianal or intra-anal tumor, erosion or ulceration as well as lichenoid lesion or hyperpigmentation. The disease has a proclivity for recurrence and there are many controversies concerning treatment that effectiveness remains uncertain and range from aggressive wide local excision with skin grafting when necessary to laser vaporization (argon or CO2), radiotherapy or a new immune response modifier (Imiquimod). We report a case of a 50-years-old woman with recurrence of Bowen's disease associated with vulvar HPV infection and review the literature.
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PMID:[Perianal Bowen's disease: a case report and review of the literature]. 1290 34

Vascular tumors occur in approximately 10% of all infants and may be associated with significant morbidity. Available therapies for vascular tumors, such as systemic corticosteroids, vincristine, and interferon-alpha, may cause toxicity, limiting their use to complicated cases. Using a mouse hemangioendothelioma model, we investigated the efficacy and mechanism of action of imiquimod, a topically applied inducer of cytokines. Application of imiquimod cream, whether initiated at the time of cell inoculation or when tumors became visible, significantly decreased tumor growth and increased animal survival in comparison with control mice. Imiquimod-treated tumors showed decreased tumor cell proliferation, increased tumor apoptosis, and increased expression of tissue inhibitor of matrix metalloproteinase-1 with decreased activity of matrix metalloproteinase-9. The demonstration that local application of imiquimod inhibits vascular tumor enlargement in the mouse vascular tumor model suggests a novel, less toxic means of treating infantile hemangioendotheliomas and perhaps other cutaneous vascular tumors.
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PMID:Topically applied imiquimod inhibits vascular tumor growth in vivo. 1470 27

Imiquimod is an immune-response modifier that has the potential to be useful in many dermatological indications (Table 1). To date, the approved use is for condyloma acuminata; approval for use in treating basal cell carcinoma (BCC) has been filed with the FDA and is expected to be approved in the coming months. In the interim, the expansion of the horizons for this immunomodulator depends on the application of the science and immunology behind the drug to the appropriate disease states. Recent investigations have presented explanations on the possible mechanisms behind the anti-tumor activity of imiquimod, more specifically for its use in treating superficial BCC. There are studies currently underway as well as anecdotal data published for its possible use in treating squamous cell carcinoma (SCC), although this is not as widely accepted for off-label use as BCC among many dermatologists. However, many patients who may not be surgical candidates that present with tumors other than BCC have been successfully treated with imiquimod. This is a case of an elderly patient who could not undergo surgery that presented with a large keratoacanthoma and was clear of her tumor after five months using imiquimod 5% cream on a daily basis.
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PMID:Imiquimod as a possible treatment for keratoacanthoma. 1496 50


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