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

Melanoma lesions can be frozen in vivo, resulting in necrotic death of malignant cells and in tumor antigen release suitable for cross-presentation by professional antigen-presenting cells. Imiquimod is a small molecule with adjuvant pro-inflammatory effects that can be topically delivered as a cream. Local cryosurgery of B16/ovalbumin (OVA)-derived subcutaneous tumor nodules leads to curative destruction of the lesions. If imiquimod is repeatedly applied on the cryo-treated lesion, a conspicuous, leukocyte-rich inflammatory infiltrate appears during the days following treatment. Mice treated by cryosurgery plus imiquimod rejected rechallenges of B16/OVA in 90% of the cases, whereas cryosurgery alone failed to prevent tumor grafting in 70% of the cases. The combination treatment of B16/OVA tumors was also able to protect 60% of the mice against outgrowth of a lethal dose of non-transfected B16 tumor cells. Addition of imiquimod to cryosurgery results in increases of the cellular immune response against tumor antigens as measured by in vitro IFN-gamma production and T-cell proliferation in response to OVA. The potent memory response is not only directed against the OVA epitope, but also toward a broader range of B16 antigens. Our data indicate that these combined treatments turn the treated tumor lesion into an autologous tumor vaccine, which is even able to cause vitiligo in several cases. These preclinical data and the simplicity of the procedures warrant the design of a pilot clinical trial.
 ...
PMID:Imiquimod enhances the systemic immunity attained by local cryosurgery destruction of melanoma lesions. 1738 Jan 12

Lentigo maligna (LM) is an in situ variant of melanoma. Although LM has the potential for invasion, it often has a greatly protracted radial growth phase and may remain indolent for years. The current standard of care is surgical excision, but this often results in substantial morbidity; thus, nonsurgical approaches continue to be investigated. Imiquimod cream 5% is an immunomodulatory agent that previously has been reported to successfully eradicate LM. We evaluated the treatment course of topical imiquimod in 12 patients with LM. Data from patients with biopsy-proven LM were collected retrospectively, reviewed, and summarized. Patients ranged in age from 54 to 83 years. Most patients chose imiquimod cream as their initial form of treatment; however, other patients had a history of LM recurrence after excision or had positive histologic margins at the time of excision. Initial application regimens varied from 2 to 7 times weekly. The average duration of treatment was 15.7 weeks but ranged from 7 to 44 weeks. Results of posttreatment biopsies of the most clinically suspicious areas in 6 patients showed histologic clearance; 2 patients demonstrated single atypical melanocytes and 4 patients demonstrated clinical clearance without histologic confirmation. These findings suggest that imiquimod cream 5% may be an effective alternative treatment for LM.
 ...
PMID:Lentigo maligna (melanoma in situ) treated with imiquimod cream 5%: 12 case reports. 1738 18

Lentigo maligna (LM) is an in situ melanoma that occurs in sun-damaged skin on the head and neck of elderly patients. Surgical excision is the treatment of choice for LM. However, surgical options may be limited by the location of LM in cosmetically sensitive areas. We present a woman with a history of skin cancer with a large, asymmetrically pigmented lesion on her right superior cheek below her eyelid. The lesion had been present for approximately 15 years. Histologic analysis confirmed that the lesion was an LM. Imiquimod 5% cream was applied topically once daily. Approximately 5 months later, the previous LM had healed well and no new lesions were observed. Histologic clearance of the lentigo maligna was evident in skin biopsies. Imiquimod 5% cream appears effective in the treatment of lentigo maligna. We describe the treatment of a patient with facial LM with imiquimod 5% cream.
 ...
PMID:Treatment of lentigo maligna with imiquimod 5% cream. 1796 82

Imiquimod is an immune response modifier currently used as a topical treatment of genital warts, basal cell carcinoma, cutaneous metastasis of malignant melanoma, and vascular tumors. We developed more efficient killers from the same family of compounds that can induce apoptosis without the prominent pro-inflammatory response associated with imiquimod. Among these new products, tk;4EAPB0203, a member of the imidazo[1,2-a]quinoxalines, exhibits an important cytotoxic activity in vitro. HTLV-I-associated adult T-cell leukemia (ATL) and HTLV-I-negative peripheral T-cell lymphomas are associated with poor prognosis. Using potentially achievable concentrations of EAPB0203, we demonstrate inhibition of cell proliferation, G2/M cell- cycle arrest, and induction of apoptosis in HTLV-I-transformed and HTLV-I-negative malignant T cells and fresh ATL cells, whereas normal resting or activated T lymphocytes were resistant. EAPB0203 treatment significantly down-regulated the antiapoptotic proteins c-IAP-1 and Bcl-XL and resulted in a significant loss of mitochondrial membrane potential, cytoplasmic release of cytochrome c, and caspase-dependent apoptosis. Moreover, in HTLV-I-transformed cells only, EAPB0203 treatment stabilized p21 and p53 proteins but had no effect on NF-kappaB activation. These results support a potential therapeutic role for EAPB0203 in ATL and HTLV-I-negative T-cell lymphomas, either as a systemic or topical therapy for skin lesions.
 ...
PMID:EAPB0203, a member of the imidazoquinoxaline family, inhibits growth and induces caspase-dependent apoptosis in T-cell lymphomas and HTLV-I-associated adult T-cell leukemia/lymphoma. 1821 50

T cell-mediated immunity to microbes and to cancer can be enhanced by the activation of dendritic cells (DCs) via TLRs. In this study, we evaluated the safety and feasibility of topical imiquimod, a TLR7 agonist, in a series of vaccinations against the cancer/testis Ag NY-ESO-1 in patients with malignant melanoma. Recombinant, full-length NY-ESO-1 protein was administered intradermally into imiquimod preconditioned sites followed by additional topical applications of imiquimod. The regimen was very well tolerated with only mild and transient local reactions and constitutional symptoms. Secondarily, we examined the systemic immune response induced by the imiquimod/NY-ESO-1 combination, and show that it elicited both humoral and cellular responses in a significant fraction of patients. Skin biopsies were assessed for imiquimod's in situ immunomodulatory effects. Compared with untreated skin, topical imiquimod induced dermal mononuclear cell infiltrates in all patients composed primarily of T cells, monocytes, macrophages, myeloid DCs, NK cells, and, to a lesser extent, plasmacytoid DCs. DC activation was evident. This study demonstrates the feasibility and excellent safety profile of a topically applied TLR7 agonist used as a vaccine adjuvant in cancer patients. Imiquimod's adjuvant effects require further evaluation and likely need optimization of parameters such as formulation, dose, and timing relative to Ag exposure for maximal immunogenicity.
 ...
PMID:Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. 1856 44

Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. The incidence of this entity increases with age, peaking at the age of 70 years. This study included 97 patients aged more than 65 years old, with a diagnosis of BCC. These patients were treated with imiquimod applied three times weekly for 6 weeks. Clinical remission was 67% after 10 weeks and was 49.5% after 1 year. Imiquimod is a highly interesting therapeutic modality in the elderly, in whom surgery is often contraindicated. This regimen eradicates a high percentage of tumors and reduces local adverse effects, which are poorly tolerated by aged skin.
 ...
PMID:[Alternative to surgery in basal cell carcinoma in the elderly population: imiquimod 5% cream]. 1928 64

Successful management of epithelial skin cancers with imiquimod 5% cream (Aldara), an immunomodulatory agent, led to speculation that it may promote an immune response against melanoma. Studies, mostly case reports, have assessed the value of imiquimod as a topical treatment for dermal melanoma metastases that prove difficult to manage surgically. The precise value of imiquimod, however, in treatment of dermal and subcutaneous metastases remains unclear. A case at our institution elucidates histopathologically that subcutaneous metastases may progress despite excellent treatment of superficial dermis in the same location. In preparation for a clinical trial using imiquimod to treat patients with dermal melanoma metastases, we have treated several patients off protocol. We present a case report in which the observed changes are documented photographically and histologically. The patient experienced dramatic improvement in the locally treated dermis with concurrent regional treatment failure in the subcutaneous space. Our experience supports growing evidence that imiquimod for some provides an effective option for dermal disease. The unique histological documentation we provide regarding the differential effectiveness of imiquimod in treating various tissue components may help guide future investigations regarding optimal clinical application of imiquimod therapy for melanoma metastases.
 ...
PMID:Effectiveness of imiquimod limited to dermal melanoma metastases, with simultaneous resistance of subcutaneous metastasis. 1960 71

Imiquimod, an immune response modifier, is marketed as Aldara 5% cream (Meda) and licensed for treating adults with small superficial basal cell carcinomas (BCCs).1 Numerous uses outside the licensed indications (i.e. 'off-label') have been proposed and practised, including as treatment for pre-cancerous conditions such as Bowen's disease (squamous cell carcinoma in situ) and lentigo maligna (an in situ precursor of melanoma).2,3 Here we review the use of imiquimod for small superficial primary BCC in adults, Bowen's disease and lentigo maligna.
 ...
PMID:Imiquimod for superficial and in situ skin malignancy. 1980 85

The prognosis for metastatic melanoma is grim, and treatment options are limited. Imiquimod is a topically applied immune modulator that has been used to treat superficial cutaneous melanoma, but has not been reported to treat metastatic melanoma. We report a patient whose liver and iliac fossa melanoma metastases regressed after topical application of imiquimod cream to overlying skin. This supports further investigation of the potential use of imiquimod for metastatic melanoma.
 ...
PMID:Regression of internal melanoma metastases following application of topical imiquimod to overlying skin. 2136 48

Low antigen expression and an absence of coimmunostimulatory signals may be partly responsible for the low immunogenicity of many tumors. It may be possible to overcome this situation by defining a combination of adjuvants and antigens that can activate a high-avidity antitumor response. Using the poorly immunogenic B16-OVA melanoma cells as tumor model, we tested different combinations of adjuvants and antigens to treat established tumors. In the absence of exogenous antigens, repeated administration of the TLR7 ligand Imiquimod together with anti-CD40 agonistic antibodies activated only innate immunity, which was insufficient to reject intradermal tumors. Administering this adjuvant combination together with OVA as a tumor antigen induced T-cell responses that delayed tumor growth. However, administering a combination of anti-CD40 plus TLR3 and TLR7 ligands, together with antigen targeting to dendritic cells through TLR4, was sufficient to induce tumor rejection in 50% of mice. This response was associated with a greater activation of innate immunity and induction of high-avidity polyfunctional CD8(+) T-cell responses, which each contributed to tumor rejection. This therapy activated T-cell responses not only against OVA, which conferred protection against a rechallenge with B16-OVA cells, but also activated T-cell responses against other melanoma-associated antigens. Our findings support the concept that multiple adjuvant combination and antigen targeting may be a useful immunotherapeutic strategy against poorly immunogenic tumors.
 ...
PMID:Adjuvant combination and antigen targeting as a strategy to induce polyfunctional and high-avidity T-cell responses against poorly immunogenic tumors. 2140 11


<< Previous 1 2 3 4 5 Next >>