Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lentigo maligna is the in situ phase of lentigo maligna melanoma, and if left untreated it may progress to invasive melanoma. It most commonly occurs on the exposed sites of the face and neck of middle-aged or elderly patients. Conventional surgery using a 5-10 mm margin is the recommended treatment; however, lesions can be quite large and surgical removal may involve extensive plastic repair. We report an elderly patient with a large lentigo maligna on the scalp who was reluctant to have surgery. We tried topical imiquimod 5% cream (Aldara), a local immunomodulator, which has recently become available for the treatment of external genital and perianal warts. Initially used over a test area and then over the whole of the lesion, for a total of 7 months, the imiquimod cream resulted in complete clinical and histological cure. The patient has been followed up for 9 months without evidence of recurrence.
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PMID:Imiquimod: a novel treatment for lentigo maligna. 1106 69

Imiquimod is the first of a new class of drugs to emerge in the treatment of various dermatologic disorders. As an immune response modifier, it has been shown to have potent antiviral and antitumor properties through the stimulation of innate and cell mediated immune pathways. It is currently approved for the treatment of external genital and perianal warts, but has also been found to be an effective treatment for a host of other virus-associated dermatologic lesions, including common and flat warts, molluscum contagiosum and herpes simples 2. Oncological lesions showing improvement with the use of imiquimod include basal cell carcinoma, actinic keratosis, squamous cell carcinoma in situ, malignant melanoma, cutaneous T-cell lymphoma, and cutaneous extramammary Paget's disease. Recent case studies have also found this product to be effective for treating keloids, infantile hemangiomas, porokeratosis of Mibelli, leishmanisis, and tattoo removal. This extensive array of disorders treated successfully with imiquimod warrants further study of this novel and valuable drug.
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PMID:Novel dermatologic uses of the immune response modifier imiquimod 5% cream. 1254 25

The imidazoquinolines arose from efforts to develop a nucleoside analogue. Although molecularly similar to nucleosides, the imidazoquinolines did not have nucleoside-like activity. However, the imidazoquinolines induced immune modulatory cytokines, in part, because of their ability to activate toll receptors (TLR)s. Imiquimod, the first FDA-approved imidazoquinoline, has been marketed as a 5% cream, which is approved for the therapy of genital warts. The advantage of imiquimod therapy over other therapies for genital warts is the decrease in recurrence rate with the establishment of an adaptive immunological response or immunological memory/surveillance response. As tumours and viral infections are handled similarly by the immune system, there has been great interest in the use of topical imiquimod for the treatment of cutaneous neoplasms, particularly non-melanoma skin cancers. Future efforts in imidazoquinoline research is focused around the development of analogues with modifications in the immunological profiles, potency and penetration parameters that better focus these new analogues for the therapy of specific intracellular infections and neoplasms, as well as the development of imidazoquinolines for conditions related either directly or indirectly to patterns of immune dysregulation.
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PMID:The imidazoquinolines and their place in the therapy of cutaneous disease. 1283 37

Melanoma in situ of the lentigo maligna (LM) type is a precursor lesion of LM melanoma. It most commonly occurs in elderly individuals, on the head and neck. Although surgical excision is recommended, this may not be practical for large lesions at cosmetically sensitive sites. In addition, histological changes commonly extend beyond the clinical margins of the lesion. This study describes the use of imiquimod 5% cream as topical immunotherapy in the management of lentigo maligna. Twelve patients (average age 63 years, 10 female), of biopsy-proven facial LM were treated with topical imiquimod, three times a week for 6 weeks. In the absence of an inflammatory response, patients were asked to apply the treatment daily. Seven showed clearance of the LM clinically and histologically. A further three patients showed clearance histologically with persisting pigmentation due to dermal melanin and melanophages. Thus, 10 of 12 patients cleared with no relapse after a median follow-up of 6 months. Two patients failed to respond to imiquimod and their lesions were treated with surgical excision. Imiquimod was well tolerated, except in three patients who experienced an intense inflammatory response. Two of these also developed secondary infection. Imiquimod 5% cream appears to offer a potential noninvasive method for the treatment of lentigo maligna.
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PMID:Topical imiquimod immunotherapy in the management of lentigo maligna. 1472 12

Bypassing molecular mechanisms of apoptosis deficiency may be of great utility for the successful treatment of malignant tumors. We have discovered that imiquimod, a small-molecule immunomodulator, exerts rather tumor-selective direct pro-apoptotic activity in vivo and in vitro towards cutaneous metastases of malignant melanoma, an aggressive skin tumor. This pro-apoptotic activity was not detectable with resiquimod, a closely related structural analogue whose pro-inflammatory activity is even greater than that of imiquimod. Unresponsiveness of some melanoma metastases to imiquimod in vivo corresponded to resistance towards imiquimod-induced apoptosis in vivo and in vitro. At the molecular level, the pro-apoptotic activity of imiquimod was independent of membrane-bound death receptors, but depended on Bcl-2 expression as demonstrated by overexpression of Bcl-2 in melanoma cells. Imiquimod is the first topical compound with the potential to bypass molecular mechanisms of apoptosis deficiency, a concept that may be relevant for other tumors as well.
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PMID:Death receptor-independent apoptosis in malignant melanoma induced by the small-molecule immune response modifier imiquimod. 1514 Feb 51

Imiquimod, the first member of the imidazoquinoline family of immune response modifiers, has proven good clinical efficacy against basal cell carcinomas and actinic keratoses in several independent studies. In addition, there is recent evidence that imiquimod is also efficacious against other tumors such as cutaneous metastases of malignant melanoma or vascular tumors. Imiquimod exerts its antitumoral effect, at least in part, through binding to TLR-7 and TLR-8 on dendritic cells followed by secretion of a multitude of proinflammatory cytokines. The net result of this proinflammatory activity is a profound tumor-directed cellular immune response. However, recent experimental and clinical data indicate that imiquimod also possesses considerable direct pro-apoptotic activity against tumor cells both in vitro and in vivo. This novel mode of action appears to be independent of membrane bound death receptors, but involves caspase activation. Induction of apoptosis by imiquimod is, at least in part, presumably mediated through Bcl-2-dependent release of mitochondrial cytochrome c and subsequent activation of caspase-9. The structural analogue, resiquimod, exhibited very limited, if any, such pro-apoptotic activity, possibly due to its lacking ability to enter the cell. Bypassing molecular mechanisms of apoptosis deficiency by a topical compound may be of great utility for treating certain cutaneous tumors.
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PMID:Immune modulation and apoptosis induction: two sides of the antitumoral activity of imiquimod. 1525 60

Imiquimod is a topical immune response modifier that has proved efficacious in the treatment of the superficial variant of basal cell carcinoma. The nodular variant of basal cell carcinoma has shown moderate response to imiquimod; other variants have not been tested. The mechanism of action is largely unknown; however, studies indicate the mechanism involves alteration of local cytokine production. The objective of this study is to evaluate the cytokine response of imiquimod in all variants of basal cell carcinoma. Ten patients were selected who had clinically and histologically proven basal cell carcinoma. All lesions were treated with imiquimod once a day, 5 days a week, for 3 weeks. After a 3-week rest period, the lesions were rebiopsied. All biopsy specimens were analyzed via polymerase chain reaction (PCR) for various cytokines. Nine of 10 lesions resolved clinically, which included nodular, superficial, infiltrative, adenoid, and micronodular variants. The cytokine with the greatest change pre- and post-treatment was IL-8, which decreased an average of 44 per cent (P = 0.06). We concluded that topical 5 per cent imiquimod is an effective treatment of various subtypes of basal cell carcinoma. IL-8, which plays an important role in the development and metastasis of melanoma, may be involved in the mechanism of action of imiquimod on cutaneous malignancies. Larger studies are needed to prove the efficacy of imiquimod on nonsuperficial variants of basal cell carcinoma and cutaneous melanoma metastasis.
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PMID:A preliminary study of imiquimod treatment in variants of basal cell carcinoma. 1621 49

Lentigo maligna (LM) is considered to be an in-situ stage of lentigo maligna melanoma. Clinically, it presents as a pigmented macule, irregular in shape and tone. 30% to 35% of untreated lentigo malignas can progress into lentigo maligna melanoma. The treatment of choice for this pathology is surgical excision with margins of 0.5 cm. of clinically normal skin around the lesion, or Mohs microsurgery. Imiquimod is a topical immunomodulator that stimulates both acquired and innate immunity. We present the case of a patient with LM, treated with 5% imiquimod cream, with an excellent therapeutic response.
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PMID:[Lentigo maligna treated with 5% imiquimod cream]. 1647 24

The treatment of skin metastases of melanoma can be difficult in many cases because of the patients age, as well as the number, size and location of the lesions. We present the case of an 82-year-old male with melanoma skin metastases on the scalp, which responded satisfactorily to treatment with 5 % imiquimod cream. Imiquimod is a topical immunomodulator with antiviral and antineoplastic action. This case, along with others that have recently been published, supports the usefulness of this treatment in selected cases of melanoma skin metastases, at least for palliative purposes.
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PMID:[Topical treatment of melanoma skin metastases with imiquimod]. 1647 96

Topical immune response modifiers include imiquimod and resiquimod. The mechanism of action of immune response modifiers is complex and not completely understood. It involves the stimulation of innate and cell-mediated immune responses through Toll-like receptor-mediated induction of cytokines. Imiquimod is approved for the treatment of actinic keratoses, superficial basal cell carcinomas and warts; it has also been documented to successfully treat other forms of skin cancer such as squamous cell carcinoma in situ, melanoma and extramammary Paget's disease.
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PMID:The role of topical immune response modifiers in skin cancer. 1697 32


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