title: Serum caspase-1 levels in metastatic melanoma patients: relationship with tumour burden and non-response to biochemotherapy.
abstract: Interleukin-1beta converting enzymes (ICEs/caspases) are involved in programmed cell death (apoptosis). This study sought to quantify the caspase-1 level in metastatic malignant melanoma patients and to try to establish a correlation between the level of caspase-1 and different parameters related to this pathology. In addition, we evaluated the possible relationship between the clinical response to biochemotherapy and the caspase-1 level. The serum caspase-1 level was determined in 81 metastatic malignant melanoma patients and 50 normal volunteers using enzyme-linked immunosorbent assay (ELISA). Patients received cisplatin, recombinant interleukin-2 (Proleukin) and alpha-interferon (Roferon A) in two induction cycles, and assessment of clinical response was performed according to World Health Organization (WHO) criteria. The median caspase-1 level in melanoma patients was significantly higher (P = 0.0035) than in control samples. Interestingly, a positive correlation between caspase-1 level and the tumour burden was shown (rs = 0.629, P = 0.009). When the clinical response was taken into consideration, the level of caspase-1 was significantly higher in biochemorefractory patients compared with responding ones (P = 0.04). After treatment, the caspase-1 level remained very high in biochemorefractory patients, while in responding ones no change was observed. Furthermore, a positive correlation between the clinical response and the caspase-1 level was established (rs = 0.404, P = 0.024). In conclusion, we observed an elevated caspase-1 level in metastatic malignant melanoma patients. In addition, the correlations obtained between the caspase-1 level and both the tumour burden and the clinical response to the treatment support the concept that disrupted apoptosis pathways might be involved in the progressive disease of advanced melanoma and/or may confer resistance to treatment.
authors.affiliation: Medical Oncology Department, Salpêtrière Hospital, AP-HP, 47 Boulevard de l'Hopital, 75013 Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Mouawad
authors.forename: E-C
authors.initials: EC
authors.lastname: Antoine
authors.forename: M
authors.initials: M
authors.lastname: Gil-Delgado
authors.forename: D
authors.initials: D
authors.lastname: Khayat
authors.forename: C
authors.initials: C
authors.lastname: Soubrane
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood; D020170:Caspase 1 / Q000097:blood* / Q000502:physiology; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood* / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007155:Immunologic Factors; D016898:Interferon-alpha; D007376:Interleukin-2; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D007770:L-Lactate Dehydrogenase; D020170:Caspase 1; D002945:Cisplatin