TREATMENT OF LARGE BASAL-CELL CARCINOMAS WITH INTRALESIONAL INTERFERON-ALPHA-2a

Grob, Jean-Jacques; Collet, A; Munoz, M.H.; Bonerandi, J. J.

doi:10.1016/s0140-6736(88)91620-0

Cited by 56 publications

(19 citation statements)

References 5 publications

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“…Thus, our data indicate that IFNa does reduce cell viability in ASZ001 cells. These data are consistent with IFN-based therapy of human BCCs that administration of IFNs results in tumor shrinkage (Grob et al, 1988;Chimenti et al, 1995;Hottiger et al, 1999). There are at least two possibilities through which cell viability is reduced: inhibition of cell proliferation (DNA synthesis) or promotion of apoptosis.…”

Section: Ifna-mediated Apoptosis In Bccssupporting

confidence: 85%

“…Amounting evidence supports that exogenous interferon (IFN)a or stimulating IFNa secretion is an effective way for BCC therapy, either intralesionally or topically (Grob et al, 1988;Chimenti et al, 1995;Hottiger et al, 1999). Intratumoral injection of recombinant interferons has been shown to result in complete remission in 47-86% of patients with BCC (Grob et al, 1988). An immune response modifier imiquimod (3M Pharmaceuticals Inc.), which mainly stimulates secretion of cytokines such as IFNa, is an effective BCC treatment (reviewed in Vander Straten et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

IFNα induces Fas expression and apoptosis in hedgehog pathway activated BCC cells through inhibiting Ras-Erk signaling

Chi

et al. 2003

Oncogene

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Basal cell carcinoma (BCC), the most common form of human cancer, is understood to be associated with activation of the sonic hedgehog pathway, through lossof-function mutations of tumor suppressor PTCH1 or gain-of-function mutations of smoothened. Interferon (IFN)-based therapy is quite effective in BCC treatment, but the molecular basis is not well understood. Here we report a novel mechanism by which IFNa mediates apoptosis in BCCs. In the presence of IFNa, we observed increased apoptosis in a BCC cell line ASZ001, in which PTC is null, and therefore with constitutive activation of the sonic hedgehog pathway. We demonstrate that SMO agonist Ag-1.4 mediates activation of extracellular signalregulated kinase (Erk) phosphorylation, which is abrogated by IFNa in sonic hedgehog responsive C3H10T1/2 cells. In transient transfection experiments, we demonstrate that IFNa inhibits Erk phosphorylation and serum response element activation induced by expression of SMO, Gli1, PDGFRa and activated Raf, but not activated mitogen-activated Erk-regulating kinase (Mek), suggesting that IFNa targets mainly on Mek function. We further show that IFNa induces expression of Fas in BCC cells through interfering with Mek function. The role of the Fas-L/Fas signaling axis in IFNa-mediated apoptosis is demonstrated by the fact that addition of Fas-L neutralizing antibodies, just as caspase-8 inhibitor Z-IETD-FMK, effectively prevents IFNa-mediated apoptosis. Thus, our data indicate that IFNa-based BCC therapy induces Fas expression and apoptosis through interfering with Mek function.

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Section: Ifna-mediated Apoptosis In Bccssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

IFNα induces Fas expression and apoptosis in hedgehog pathway activated BCC cells through inhibiting Ras-Erk signaling

Chi

et al. 2003

Oncogene

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“…Intra-lesional injections of interferon-α 2 involves tumor regression which can even be total and final, but an important morbidity and an important risk of repetition exists even if the initial improvement is encouraging [104, 105, 106]. …”

Section: Treatment Of Periocular Bccmentioning

confidence: 99%

Basal Cell Carcinomas of the Eyelids

Allali

D’Hermies

Renard³

2005

Ophthalmologica

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Basal cell carcinomas (BCC) are the more frequent malignant tumors seen in France as in other western countries. They represent 20% of eyelid tumors and 90% of eyelid malignancies. Due to their local growth, problems may arise when treating BCC, and curative exeresis must be the preferred choice each time it is possible. BCC of the eyelids have a high risk of recurrence. Recurrences are more aggressive, infiltrative and destructive and have a considerably poorer rate of cure than primary tumors. Eyelid reconstructions can entail use of complex methods which should only be carried out by a trained ophthalmologist who is also able to treat any associated age-related ocular pathologies. BCC is the most common cause leading to eyelid reconstructive surgery; a surgery which has a triple objective: tumor removal, functionality and an esthetic outcome.

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“…Results from several clinical trials indicate that interferon can be effective in the treatment of basal cell carcinoma. [2][3][4][5][6][7][8] Multiple intralesional injections of IFN-␣2 over a 3-week period induced overall remission rates of 70 to 100%. 3,9 Increased numbers of CD4 + T cells surrounding the BCC infiltrating tumor island in the dermis have been observed after intralesional IFN-␣ therapy.…”

Section: Introductionmentioning

confidence: 99%