Is there any relationship between interleukin-6/interleukin-6 receptor modulation and endogenous interleukin-6 release in metastatic malignant melanoma patients treated by biochemotherapy?

Mouawad, Roger; Khayat, David; Merle, S; Ec, Antoine; Gil-Delgado, M.; Soubrane, C.

doi:10.1097/00008390-199904000-00011

Cited by 19 publications

(10 citation statements)

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“…IL-6 acts as an autocrine growth factor in malignant melanomas [Mouawad et al, 1999] similar to KS and multiple myeloma, but is not of HHV-8 origin, as we demonstrated. As a major molecular mediator of in¯am-matory conditions, IL-6 is produced by a variety of cells including ®broblasts, endothelial cells, keratinocytes, T and B lymphocytes and macrophages [Kishimoto, 1989;Klein et al, 1989].…”

Section: Discussionsupporting

confidence: 69%

“…IL-6 has been reported to be an autocrine growth factor in different tumours like Kaposi sarcomas, multiple myelomas or malignant melanomas [Akira and Kishimoto, 1992;Suzuki et al, 1992;Mouawad et al, 1999]. A causative role in multiple myeloma, where HHV-8 has been detected in bone marrow dendritic cells [Rady et al, 1995;Chauhan et al, 1999], is currently under discussion.…”

Section: Discussionmentioning

confidence: 99%

“…As IL-6 is known to stimulate melanoma tumour cell proliferation [Mouawad et al, 1999], the tumourigenic gamma-herpesvirus HHV-8 could be involved in the development of anorectal melanomas and sought to identify HHV-8 DNA in formalin ®xed, paraf®n embedded tissue. Using a speci®c and highly sensitive polymerase chain reaction (PCR) protocol to amplify DNA of the viral minor capsid protein gene, genomic DNA samples from 12 primary anorectal melanomas were examined for the presence of HHV-8 DNA.…”

Section: Introductionmentioning

confidence: 99%

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Anorectal melanomas do not harbour the kaposi sarcoma‐associated human herpesvirus type 8 DNA

Helmke

Deichmann

Otto

2001

Journal of Medical Virology

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Anorectal melanomas are similar to cutaneous melanomas with regard to the mode of spread and to the immunophenotype. When compared with patients with cutaneous melanoma, those suffering from anorectal melanoma have a much worse outcome. The etiology of anorectal melanomas is as yet completely unknown. For anatomical reasons, ultra-violet (UV-B) radiation can not cause anorectal melanomas as in cutaneous tumours, that are associated with exposure of the skin to UV-B radiation. As the cytokine interleukin-6 (IL-6) is known to stimulate melanoma tumour cell proliferation and a functional homologue of human IL-6 has been identified recently in the HHV-8 genome, this tumorigenic virus might be involved in the pathogenesis of anorectal melanomas. Twelve formalin fixed and paraffin embedded primary anorectal melanomas from seven female and five male patients with a mean age at diagnosis of 71 years (range 38-88 years) were investigated for the presence of HHV-8 DNA. Using a specific and highly sensitive polymerase chain reaction protocol, this tumorigenic gamma-herpesvirus was not detectable in any tumour. This data indicates that HHV-8 is not involved in the development of anorectal melanomas.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anorectal melanomas do not harbour the kaposi sarcoma‐associated human herpesvirus type 8 DNA

Helmke

Deichmann

Otto

2001

Journal of Medical Virology

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“…In particular, IL-6 levels have been correlated with disease progression and poor prognosis in melanoma and other malignancies [13][14][15][16]. In our laboratory, we have shown that serum IL-6 levels in melanoma patients are derived from the tumour cells [22] and correlate with tumour burden [13]. In this study, we have identified that levels of IL-6 correlate with overall survival as well as with a number of established prognostic factors for metastatic malignant melanoma.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment serum interleukin-6 concentration as a prognostic factor of overall survival in metastatic malignant melanoma patients treated with biochemotherapy: a retrospective study

et al. 2005

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Biological response parameters during biochemotherapy, including chemotherapy with immune modulating agents, have been studied extensively. Of these parameters, interleukin-6 (IL-6) has been implicated in advanced stage disease and tumour recurrence. However, there is limited information available about the significance of IL-6 in metastatic malignant melanoma (MMM). In this study, we evaluated the possible relationship between serum IL-6 level and overall survival. This retrospective study included 125 patients with MMM. Pretreatment serum IL-6 levels were determined using a highly sensitive enzyme-linked immunosorbent assay (ELISA) test. Kaplan-Meier survival curves were constructed and compared using the log-rank test. Cox proportional analysis was performed to assess the predictors of overall survival, which was calculated from the beginning of biochemotherapy until death. In order to establish the possible relationship between IL-6 level and overall survival, patients were divided into two groups according to a cut-off of 5 pg/ml, corresponding to the first quartile obtained by descriptive statistics of the pretreatment IL-6 level in all patients. Thirty-five patients were in the low IL-6 group and 76 patients were in the high IL-6 group. Based on this stratification, overall survival was shown to be affected by IL-6 serum level: it was higher (24.6 months) in the low IL-6 group when compared with the high IL-6 group (9.7 months) (P=0.0006). Furthermore, Cox multivariate analysis including standard melanoma prognostic factors showed that IL-6, as a variable, lactate dehydrogenase (LDH) and tumour burden were significant prognostic factors for overall survival. On the basis of this evidence, the pretreatment serum IL-6 level is a predictive factor of overall survival in MMM.

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“…As mentioned before, TGF-␤ and IL-10 can convert T cells to Tregs, and IL-6 prevents anti tumor Th1 responses. High IL-6 levels correlate with unresponsiveness to immunotherapy and reduced survival of the patients [68,69]. Furthermore, reactive oxygen species produced by TAMs are related to decreased chain expression in TILs which leads to decreased responsiveness to TCR-stimulation [70,71].…”

Section: Tumor Stromamentioning

confidence: 99%

Immunosuppressive mechanisms in human tumors: Why we still cannot cure cancer

Groß

Walden

2008

Immunology Letters

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Is there any relationship between interleukin-6/interleukin-6 receptor modulation and endogenous interleukin-6 release in metastatic malignant melanoma patients treated by biochemotherapy?

Cited by 19 publications

References 0 publications

Anorectal melanomas do not harbour the kaposi sarcoma‐associated human herpesvirus type 8 DNA

Anorectal melanomas do not harbour the kaposi sarcoma‐associated human herpesvirus type 8 DNA

Pretreatment serum interleukin-6 concentration as a prognostic factor of overall survival in metastatic malignant melanoma patients treated with biochemotherapy: a retrospective study

Immunosuppressive mechanisms in human tumors: Why we still cannot cure cancer

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