Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: A double-blind, randomized, vehicle-controlled study*

Geisse, John K.; Rich, Phoebe; Pandya, Amit G.; Gross, Ken; Andres, Kara L.; Ginkel, Angie; Owens, Mary

doi:10.1067/mjd.2002.126215

Cited by 270 publications

(214 citation statements)

References 22 publications

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“…This model, which is IL-23 dependent, involves daily topical application of the TLR7 agonist imiquimod formulated in a commercially available cream, Aldara (28). Aldara has been used for some time in the treatment of a variety of dermal malignancies such as actinic keratoses and superficial basal cell carcinomas (29,30); however, a side effect of such treatment is the exacerbation of psoriatic lesions in some patients, even those with well controlled psoriasis (31,32). On the basis of this observation, use of Aldara in murine studies as an inducer of psoriasiform inflammation has come to be accepted as a clinically faithful model of psoriasis, particularly as the pathological manifestations induced bear striking similarities to human psoriasis but also because it is responsive to a range of the current frontline psoriasis therapies (9,10,28).…”

Section: Resultsmentioning

confidence: 99%

Toll IL-1R8/Single Ig IL-1–Related Receptor Regulates Psoriasiform Inflammation through Direct Inhibition of Innate IL-17A Expression by γδ T Cells

Russell

Stefańska

Kubica

et al. 2013

The Journal of Immunology

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Expression of the orphan receptor Toll IL-1R8/single Ig IL-1–related receptor has been reported to be reduced in the peripheral blood of psoriatic arthritis patients. However whether TIR8/SIGIRR activity plays a specific role in regulating psoriatic inflammation is unknown. We report that Tir8/Sigirr-deficient mice develop more severe psoriatic inflammation in both the chemical (Aldara)- and cytokine (rIL-23)-induced models of psoriasis. Increased disease severity was associated with enhanced infiltration of Vγ4+ γδ T cells that express significantly elevated levels of IL-17A. Critically, we also demonstrate that TIR8/SIGIRR activity directly suppressed innate IL-17A expression by γδ T cells in vitro and in vivo. Importantly, treatment of Tir8/Sigirr−/− mice with an IL-17A neutralization Ab reversed the enhanced disease severity observed in these mice. This study identifies TIR8/SIGIRR as a novel intrinsic negative regulator of innate IL-17A expression and characterizes a novel mechanism involved in the regulation of psoriatic inflammation.

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Section: Resultsmentioning

confidence: 99%

Toll IL-1R8/Single Ig IL-1–Related Receptor Regulates Psoriasiform Inflammation through Direct Inhibition of Innate IL-17A Expression by γδ T Cells

Russell

Stefańska

Kubica

et al. 2013

The Journal of Immunology

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“…Various regimens of imiquimod have been used in practice, including application twice daily, once daily, and every other day; applications have been performed with and without occlusion for treatment courses ranging from 6 to 16 weeks. 45,[64][65][66][67][68][69][70][71][72][73] Overall, rates of 3-to 12-month clinical and histologic cure have been reported to range from 60% to 80% in well-designed RCTs, with the highest rates reported for shorter follow-up and clinical J AM ACAD DERMATOL VOLUME jj, NUMBER j cure. Moderate-to-severe local treatment-associated adverse events include skin redness, swelling, erosions, crusts, vesicles, itching, and, occasionally, tingling sensations.…”

Section: Topical Therapiesmentioning

confidence: 99%

Guidelines of care for the management of basal cell carcinoma

Baum¹,

Bordeaux²,

Brown³

et al. 2018

Journal of the American Academy of Dermatology

326

219

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Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed. ( J Am Acad Dermatol

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“…Synthetic small molecules such as imidazoquinolines and certain nucleoside analogues activate TLR7 and/or TLR8 (3,24). Imiquimod, a TLR7 agonist, has been approved as a topical agent for the treatment of superficial basal cell carcinoma and actinic keratosis (25,26). Imidazoquinoline-based compounds cause side effects following systemic administration, however, and are commonly used only by topical application (27).…”

Section: Discussionmentioning

confidence: 99%

Antitumor Activity and Immune Response Induction of a Dual Agonist of Toll-Like Receptors 7 and 8

Wang

Precopio

Lan

et al. 2010

Molecular Cancer Therapeutics

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Viral and synthetic single-stranded RNAs are the ligands for Toll-like receptors 7 and 8 (TLR7 and TLR8). We have reported a novel class of synthetic oligoribonucleotides, referred to as stabilized immunemodulatory RNA compounds, which act as agonists of TLR7, TLR8, or both TLR7 and TLR8 depending on the sequence composition and the presence of specific chemical modifications. In the present study, we evaluated the antitumor activity of a dual TLR7/8 agonist in tumor-bearing mice with peritoneal disseminated CT26.CL25 colon and 3LL-C75 lung carcinomas. Peritoneal administration of dual TLR7/8 agonist in mice bearing CT26.CL25 colon carcinomas had potent dose-dependent antitumor activity, which was associated with a marked decrease in CD4 + CD25 + Foxp3 + T regulatory cells and a significant increase in tumor antigen-specific IFN-γ-secreting effector cell responses in splenocytes and local tumor-infiltrating cells. In 3LL-C75 lung carcinoma, dual TLR7/8 agonist induced strong immune responses and antitumor effects in C57BL/6 and TLR9 −/− mice, but not in TLR7 −/− and MyD88 −/− mice, indicating that the agonist induces immune responses via TLR7 and through the MyD88-dependent signaling pathway. TLR8 is not functional in mice. Additionally, s.c. administration of TLR7/8 agonist effectively prevented lung metastasis of tumors in the CT26.CL25 pulmonary metastasis model. These studies show that the dual TLR7/8 agonist induced Th1-type immune responses and potent antitumor activity in mice via TLR7 and through the MyD88-dependent pathway. Mol Cancer Ther; 9(6); 1788-97. ©2010 AACR.

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Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: A double-blind, randomized, vehicle-controlled study*

Cited by 270 publications

References 22 publications

Toll IL-1R8/Single Ig IL-1–Related Receptor Regulates Psoriasiform Inflammation through Direct Inhibition of Innate IL-17A Expression by γδ T Cells

Toll IL-1R8/Single Ig IL-1–Related Receptor Regulates Psoriasiform Inflammation through Direct Inhibition of Innate IL-17A Expression by γδ T Cells

Guidelines of care for the management of basal cell carcinoma

Antitumor Activity and Immune Response Induction of a Dual Agonist of Toll-Like Receptors 7 and 8

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