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

A 78-year-old male sought dermatologic consultation for multifocal persistent red lesions of the glans penis. Various topical treatments had proved unsuccessful. Histologic examination revealed penile intraepithelial neoplasia (PIN). Polymerase chain reaction (PCR) showed amplification of human papillomavirus type 16 (HPV-16) DNA. Urological consultants recommended amputation of the glans; the patient rejected this, as well as any other surgical procedure. Therefore, he was treated in our dermatologic practice with imiquimod 5 % cream administered daily over 12 weeks. After therapy was completed, no clinical or histologic evidence of residual tumor was found and HPV-16 DNA was no longer detectable. Local skin reactions such as erosions and edema of the glans accompanied by tingling and itching were well-tolerated by the patient. Imiquimod 5 % cream may represent an alternative local treatment option for multifocal PIN.
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PMID:[Multifocal penile intraepithelial neoplasia--targeted treatment with imiquimod]. 1682 14

Imiquimod (R-837) and Resiquimod (R-838), two novel small-molecular-weight immune response modifiers, have similar structure. They have anti-virus and anti-tumor activities and can be used as B lymphocyte activators and adjuvants. They are widely used in dermatology to treat virus dermatoses and cutaneous benign or malignant tumors.
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PMID:[Application of imiquimod and resiquimod in dermatology]. 1690 Jun 54

The "gold standard" of the gynecologic examinations is even today the classical clinical examination completed with the digital colposcopy, the Pap smears prepared from transport media and histological examination of biopsy material. Without these classical examinations one cannot evaluate the results of the molecular tests detecting papillomaviruses. The majority (70 to 90%) of the primary clinical symptoms caused by papillomaviruses recovers spontaneously. The recovery can be supported by, "imiquimod" (Aldara) which is an immunostimulant-inducing interferon gamma and the production of interleukins, since papillomavirus infection is able to prevent the production of these mediators through its blocking effect to the innate immunity. Prevention is the main aim of the contemporary public health facilitated by the modern gene technology. The tetravalent vaccine (types 6, 11, 16 and 18) is harmless, since no tumor inducing genes are included. The empty capsids are manufactured in yeast cells and purified to a high degree similar to that of hepatitis B vaccine. The tetravalent vaccine is a preventive vaccine. It will be useful for teenagers, who have not acquired yet the most common papillomavirus types. There is intensive research going on in order to create therapeutic vaccines, that might be effective also in people of older age who had acquired certain virus types before vaccination, and may possess clinical symptoms, too. Men are the source of papillomavirus infection of women. Therefore vaccination of both genders will be indicated. The importance of the classical diagnostic procedures will not be diminished even under the umbrella of vaccination, since the preventive efforts were shown to be fully effective, if the clinical examinations, colposcopy, pap smears and biopsies are regularly performed in the patients with clinical symptoms increasing the rate of recovery above 90%. About 13 to 15 subtypes of human papillomaviruses may induce malignant processes. These are also present and most frequent in Hungary both in sexually transmitted infections and in the cancers of head and neck.
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PMID:[Prevention of malignant tumors caused by human papilloma virus (HPV) by vaccination and with the methods of classical gynecologic diagnostics]. 1698 17

Imiquimod, an immune response modifier, is known to possess both anti-viral and anti-tumor effect. We report our experience of treating a large superficial spreading basal cell carcinoma with 5% imiquimod cream. A 65-year-old male had an asymptomatic, hyperpigmented, slowly progressive, indurated, 3 x 4 cm plaque on the left cheek for two months. Biopsy from the lesion showed features of basal cell carcinoma. The patient was treated with imiquimod 5% cream, topically three times a week for six months with complete resolution of the lesion and without any side-effects. There was no clinical or histological recurrence after three months of stopping the treatment.
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PMID:Superficial basal cell carcinoma on face treated with 5% imiquimod cream. 1705 Sep 35

Imiquimod, the lead compound of the imidazoquinoline family of nucleoside analogues, has shown good efficacy against a variety of tumors of different origin. The mode of action of imiquimod and related compounds, which we have begun to understand in some detail in recent years, is complex and interesting inasmuch as it appears to comprise several presumably mutually enhancing components. Predominant amongst its actions is the induction of pro-inflammatory cytokines through agonistic activity towards Toll-like receptor (TLR)-7 and TLR-8, and consecutively, activation of the central transcription factor NF-kappaB. This activity stimulates the production of pro-inflammatory cytokines, chemokines and other mediators resulting in activation of antigen-presenting cells and the mounting of a profound Th1-weighted antitumoral cellular immune response. In addition, there are a number of secondary effects on the molecular and cellular level that can be explained through the activation of NF-kappaB. The pro-inflammatory activity of imiquimod appears to be augmented by suppression of a negative regulatory feedback mechanism which normally limits inflammatory responses. This is achieved independent of TLR-7 and TLR-8 through interference with adenosine receptor signaling pathways, particularly the A(2A) subtype, and receptor-independent reduction of adenylyl cyclase activity. Finally, at higher, albeit therapeutically relevant concentrations, imiquimod exerts a pro-apoptotic activity against tumor cells. Induction of apoptosis by imiquimod appears to be dependent on Bcl-2 proteins and involves caspase activation. The combination of multiple, presumably synergistic anti-tumoral functions by a single compound represents an interesting principle of pathogenesis-oriented, anti-neoplastic therapy.
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PMID:The antitumoral mode of action of imiquimod and other imidazoquinolines. 1734 55

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.
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PMID:Imiquimod enhances the systemic immunity attained by local cryosurgery destruction of melanoma lesions. 1738 Jan 12

Imiquimod (1-[2-methylpropyl]-1H-imidazo[4,5-c]quinolin-4-amine) is a widely used topical immune response modifier. This drug was initially developed as an antiviral agent and was found to have potent effects on the immune system. Because imiquimod causes the activation of antigen-presenting cells (APCs), it acts as an immunologic adjuvant. By triggering cytokine production, imiquimod enhances the ability of APC to present viral or tumor antigens to reactive T lymphocytes, and amplifies type 1 helper T cell (T(H) 1)-mediated immune responses (interferon [IFN] gamma production as well as other related cytokines). The cellular receptors for imiquimod and its analogues are toll-like receptors (TLR) 7 and 8. These 2 receptors are part of a larger family of TLRs that are critical components of innate immunity, which has evolved to detect dangerous bacterial, viral, fungal, and parasitic infections. Topical imiquimod is a U.S. Food and Drug Administration (FDA)-approved treatment for external genital warts, actinic keratoses (AKs), and superficial basal cell carcinomas (sBCCs). Because there are a number of cell types that express either TLR7 or receptors for cytokines induced by imiquimod, this agent has broad-reaching direct and indirect effects in the skin as well as the related skin immune system. Thus, imiquimod has been demonstrated to be useful in the treatment of a number of conditions beyond the FDA-approved indications (mostly neoplastic and infectious but also fibrotic and some degenerative conditions).
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PMID:Mechanism of action and other potential roles of an immune response modifier. 1750 94

Imiquimod (IMQ), a synthetic agonist to Toll-like receptor (TLR) 7, is being successfully used for the treatment of certain skin neoplasms, but the exact mechanisms by which this compound induces tumor regression are not yet understood. While treating basal cell carcinoma (BCC) patients with topical IMQ, we detected, by immunohistochemistry, sizable numbers of both myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) within the inflammatory infiltrate. Surprisingly, peritumoral mDCs stained positive for perforin and granzyme B, whereas infiltrating pDCs expressed tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The biological relevance of this observation can be deduced from our further findings that peripheral blood-derived CD11c(+) mDCs acquired antiperforin and anti-granzyme B reactivity upon TLR7/8 stimulation and could use these molecules to effectively lyse major histocompatibility complex (MHC) class I(lo) cancer cell lines. The same activation protocol led pDCs to kill MHC class I-bearing Jurkat cells in a TRAIL-dependent fashion. While suggesting that mDCs and pDCs are directly involved in the IMQ-induced destruction of BCC lesions, our data also add a new facet to the functional spectrum of DCs, ascribing to them a major role not only in the initiation but also in the effector phase of the immune response.
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PMID:Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. 1753 75

Basal cell carcinoma of the skin (BCC) is the most common skin tumor in Caucasians worldwide. Different therapeutic options are available to treat BCC, including topical immunotherapy. Imiquimod is topical Toll-like receptor 7 agonist that activates anti-tumor immune response and has been recently approved for the treatment of superficial BCC (sBCC). We sought to investigate the influence of imiquimod treatment on the members of the Notch signaling pathway, whose activity is known to be decreased in BCCs. Six patients with sBCC were evaluated for Notch1, Jagged1 and Delta1 expression before (pre-treatment) and after the beginning of the topical treatment (post-treatment) with imiquimod using real-time PCR and immunohistochemistry. We show selective transcriptional up-regulation of Notch pathway members (Notch1, Jagged1 and Delta1) in tumor cells of the sBCC post-treatment. Furthermore, we demonstrate minor increase of Notch1 protein expression on infiltrating cells as well as strong increase in Jagged1 protein expression in regressing sBCC tumors post-treatment. In this way, imiquimod may act as a stimulator of the Notch pathway in sBCC tumor cells by up-regulating protein expression of the Notch ligand, Jagged1. Via induction of Notch signaling imiquimod may exert tumor suppressor function, which together with its proinflammatory properties results in tumor regression.
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PMID:Induction of the members of Notch pathway in superficial basal cell carcinomas treated with imiquimod. 1792 28

The short-term and long-term outcomes of 108 patients with 122 nodular basal cell carcinomas (BCCs), morpheaform BCCs, or low-risk squamous cell carcinomas (SCCs) treated with imiquimod 5% cream at a community-based dermatology practice were retrospectively reviewed. The overall initial tumor clinical cure rate was 93.4% (114/122), with an initial clinical cure rate of 90% (72/80) for BCCs combined, and 100% (42/42) for SCCs combined. During a median follow-up time of 18 months, there was only 1 recurrence in the 114 tumors considered initially clinically cured. Imiquimod may be an appropriate initial treatment for these tumors in patients with good posttreatment follow-up.
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PMID:Clearance of basal cell and superficial squamous cell carcinomas after imiquimod therapy. 1850 36


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