عنوان ترانسليتريتد: Nouvelles immunotherapies du mélanome: mécanismes d'action, efficacité et prise en charge des toxicities.

المؤلفون: Moura B, Homicsko K, Berthod G, Cerottini JP, Guggisberg D, Gaide O, Maillard MH, Michielin O

المصدر: Revue medicale suisse [Rev Med Suisse] 2015 May 20; Vol. 11 (475), pp. 1108, 1110-4.

نوع المنشور: English Abstract; Journal Article; Review

بيانات الدورية: Publisher: Médecine et Hygiène Country of Publication: Switzerland NLM ID: 101219148 Publication Model: Print Cited Medium: Print ISSN: 1660-9379 (Print) Linking ISSN: 16609379 NLM ISO Abbreviation: Rev Med Suisse Subsets: MEDLINE

مواضيع طبية MeSH: Immunotherapy/*methods , Melanoma/*therapy , Skin Neoplasms/*therapy, Drug-Related Side Effects and Adverse Reactions/therapy ; Humans ; Immunotherapy/adverse effects ; Immunotherapy/trends ; Melanoma/immunology ; Signal Transduction/immunology ; Skin Neoplasms/immunology ; Therapies, Investigational/adverse effects ; Treatment Outcome ; Vaccines/adverse effects

مستخلص: In recent years the therapy of metastatic melanoma has been revolutionized from a disease with very few efficient treatment options to one with access to multiple therapies which can impact on patient survival. Two main classes of therapies have been developed: 1. Immunotherapy by immune checkpoint inhibitors and 2. Small molecule inhibitors of the MAPK pathway. Immunotherapies achieved by either inhibition of CTLA-4 or the PD1/PD-Ll axes are impacting the overall survival in an important fraction of patients. In addition, the side effects of these immune therapy approaches require early detection by all the specialists involved as well as early management according to precise guidelines for optimal outcome.

عنوان ترانسليتريتد: Mélanome: une nouvette ère thérapeutique.

المؤلفون: Berthod G; Centre pluridisciplinaire d'oncologie, CHUV, Lausanne. gregoire.berthod@chuv.ch, Homicsko K, Bouchaab H, Matter M, Cerottini JP, Guggisberg D, Speiser D, Leyvraz S, Michielin O

المصدر: Revue medicale suisse [Rev Med Suisse] 2011 May 25; Vol. 7 (296), pp. 1126-30.

نوع المنشور: English Abstract; Journal Article; Review

بيانات الدورية: Publisher: Médecine et Hygiène Country of Publication: Switzerland NLM ID: 101219148 Publication Model: Print Cited Medium: Print ISSN: 1660-9379 (Print) Linking ISSN: 16609379 NLM ISO Abbreviation: Rev Med Suisse Subsets: MEDLINE

مواضيع طبية MeSH: Antigens, CD/*drug effects , Melanoma/*drug therapy , Protein-Tyrosine Kinases/*antagonists & inhibitors , Skin Neoplasms/*drug therapy, Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; CTLA-4 Antigen ; Enzyme Inhibitors/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; Incidence ; Melanoma/epidemiology ; Skin Neoplasms/epidemiology ; Survival Rate ; Switzerland/epidemiology

مستخلص: Melanoma is the cancer with the fastest incidence increase in Switzerland. 30% of the cases arise before the age of 50 years. Once metastatic, the median survival under current systemic therapies is about 8 months, with less than 5% of patients alive at 5 years. Many efforts in the understanding of cellular biology, intracellular signaling pathways, as well as the role of cellular immunity have been made in the recent years. This has resulted in the development of novel and very promising therapies. In this review, we will cover the results obtained with targeted therapies such as "tyrosin kinase inhibitors" (TKI), as well as those obtained with a monoclonal antibody directed against the CTLA-4 receptor of lymphocytes.

المؤلفون: Speiser DE; Clinical Tumor Immune-Biology Unit, Ludwig Institute for Cancer Research, Lausanne branch, Switzerland. daniel.speiser@hospvd.ch, Schwarz K, Baumgaertner P, Manolova V, Devevre E, Sterry W, Walden P, Zippelius A, Conzett KB, Senti G, Voelter V, Cerottini JP, Guggisberg D, Willers J, Geldhof C, Romero P, Kündig T, Knuth A, Dummer R, Trefzer U, Bachmann MF

المصدر: Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2010 Oct; Vol. 33 (8), pp. 848-58.

نوع المنشور: Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9706083 Publication Model: Print Cited Medium: Internet ISSN: 1537-4513 (Electronic) Linking ISSN: 15249557 NLM ISO Abbreviation: J Immunother Subsets: MEDLINE

مواضيع طبية MeSH: Cancer Vaccines* , Vaccines, Virus-Like Particle*, CD8-Positive T-Lymphocytes/*metabolism , Melanoma/*therapy , Skin Neoplasms/*therapy , T-Lymphocyte Subsets/*metabolism, Adult ; Aged ; Animals ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Cell Differentiation ; Cells, Cultured ; Female ; HLA-A2 Antigen/genetics ; HLA-A2 Antigen/metabolism ; Humans ; Immunologic Memory ; Lymphocyte Activation ; MART-1 Antigen/chemistry ; MART-1 Antigen/immunology ; Male ; Melanoma/immunology ; Melanoma/pathology ; Melanoma/physiopathology ; Mice ; Mice, Transgenic ; Middle Aged ; Nanoparticles/chemistry ; Oligodeoxyribonucleotides/chemistry ; Oligodeoxyribonucleotides/immunology ; Peptide Fragments/chemistry ; Peptide Fragments/immunology ; Skin Neoplasms/immunology ; Skin Neoplasms/pathology ; Skin Neoplasms/physiopathology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/pathology ; Treatment Outcome

مستخلص: Induction of cytotoxic CD8 T-cell responses is enhanced by the exclusive presentation of antigen through dendritic cells, and by innate stimuli, such as toll-like receptor ligands. On the basis of these 2 principles, we designed a vaccine against melanoma. Specifically, we linked the melanoma-specific Melan-A/Mart-1 peptide to virus-like nanoparticles loaded with A-type CpG, a ligand for toll-like receptor 9. Melan-A/Mart-1 peptide was cross-presented, as shown in vitro with human dendritic cells and in HLA-A2 transgenic mice. A phase I/II study in stage II-IV melanoma patients showed that the vaccine was well tolerated, and that 14/22 patients generated ex vivo detectable T-cell responses, with in part multifunctional T cells capable to degranulate and produce IFN-γ, TNF-α, and IL-2. No significant influence of the route of immunization (subcutaneous versus intradermal) nor dosing regimen (weekly versus daily clusters) could be observed. It is interesting to note that, relatively large fractions of responding specific T cells exhibited a central memory phenotype, more than what is achieved by other nonlive vaccines. We conclude that vaccination with CpG loaded virus-like nanoparticles is associated with a human CD8 T-cell response with properties of a potential long-term immune protection from the disease.

المؤلفون: Rimoldi D; Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland. Donata.Rimoldi@isrec.unil.ch, Lemoine R, Kurt AM, Salvi S, Berset M, Matter M, Roche B, Cerottini JP, Guggisberg D, Krischer J, Braun R, Willi JP, Antonescu C, Slosman D, Lejeune FJ, Liénard D

مؤلفون مشاركون: Groupe Mélanome Lémanique

المصدر: Melanoma research [Melanoma Res] 2003 Oct; Vol. 13 (5), pp. 511-20.

نوع المنشور: Comparative Study; Journal Article

بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: England NLM ID: 9109623 Publication Model: Print Cited Medium: Print ISSN: 0960-8931 (Print) Linking ISSN: 09608931 NLM ISO Abbreviation: Melanoma Res Subsets: MEDLINE

مواضيع طبية MeSH: Lymphatic Metastasis*, Melanoma/*diagnosis , Melanoma/*pathology , Skin Neoplasms/*diagnosis , Skin Neoplasms/*pathology, Biomarkers, Tumor ; Female ; Humans ; Immunohistochemistry ; Male ; Monophenol Monooxygenase/metabolism ; Neoplasm Metastasis ; RNA/chemistry ; Reverse Transcriptase Polymerase Chain Reaction ; Sentinel Lymph Node Biopsy/methods ; Treatment Outcome

مستخلص: The technique of sentinel lymph node (SLN) dissection is a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. Reverse transcription-polymerase chain reaction (RT-PCR) is emerging as a highly sensitive technique to detect micrometastases in SLNs, but its specificity has been questioned. A prospective SLN study in melanoma patients was undertaken to compare in detail immunopathological versus molecular detection methods. Sentinel lymphadenectomy was performed on 57 patients, with a total of 71 SLNs analysed. SLNs were cut in slices, which were alternatively subjected to parallel multimarker analysis by microscopy (haematoxylin and eosin and immunohistochemistry for HMB-45, S100, tyrosinase and Melan-A/MART-1) and RT-PCR (for tyrosinase and Melan-A/MART-1). Metastases were detected by both methods in 23% of the SLNs (28% of the patients). The combined use of Melan-A/MART-1 and tyrosinase amplification increased the sensitivity of PCR detection of microscopically proven micrometastases. Of the 55 immunopathologically negative SLNs, 25 were found to be positive on RT-PCR. Notably, eight of these SLNs contained naevi, all of which were positive for tyrosinase and/or Melan-A/MART-1, as detected at both mRNA and protein level. The remaining 41% of the SLNs were negative on both immunohistochemistry and RT-PCR. Analysis of a series of adjacent non-SLNs by RT-PCR confirmed the concept of orderly progression of metastasis. Clinical follow-up showed disease recurrence in 12% of the RT-PCR-positive immunopathology-negative SLNs, indicating that even an extensive immunohistochemical analysis may underestimate the presence of micrometastases. However, molecular analyses, albeit more sensitive, need to be further improved in order to attain acceptable specificity before they can be applied diagnostically.

عنوان ترانسليتريتد: Recommandations pour la prise en charge du mélanome.

المؤلفون: Guggisberg D; Département hospitalo-universitaire romand de dermatologie et vénéréologie, Lausanne et Genève., Cerottini JP, Krischer J, Braun R, Dietrich PY, Liénard D

مؤلفون مشاركون: Groupe Mélanome Lémanique

المصدر: Revue medicale de la Suisse romande [Rev Med Suisse Romande] 2002 Jan; Vol. 122 (1), pp. 5-8.

نوع المنشور: Guideline; Journal Article; Practice Guideline

بيانات الدورية: Publisher: Société médicale de la Suisse romande Country of Publication: Switzerland NLM ID: 0421524 Publication Model: Print Cited Medium: Print ISSN: 0035-3655 (Print) Linking ISSN: 00353655 NLM ISO Abbreviation: Rev Med Suisse Romande Subsets: MEDLINE

مواضيع طبية MeSH: Melanoma/*therapy , Skin Neoplasms/*therapy, Humans

المؤلفون: Berset M; Department of Dermatology (CHUV/DHURDV), Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Cerottini JP, Guggisberg D, Romero P, Burri F, Rimoldi D, Panizzon RG

المصدر: International journal of cancer [Int J Cancer] 2001 Jan 20; Vol. 95 (1), pp. 73-7.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print Cited Medium: Print ISSN: 0020-7136 (Print) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Melanoma/*diagnosis , Melanoma/*metabolism , Neoplasm Proteins/*biosynthesis , Skin Neoplasms/*diagnosis , Skin Neoplasms/*metabolism, Antigens, Neoplasm ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; MART-1 Antigen ; Male ; Multivariate Analysis ; Prognosis ; Time Factors

مستخلص: In this study we assessed the expression of the Melan-A/MART-1 antigen by immunohistochemistry using monoclonal antibody A103 in 73 primary cutaneous melanomas and its correlation with tumor staging and patient survival. Melan-A/MART-1 was expressed in 90% of primary tumors, with loss of expression increasing with Breslow thickness. Kaplan-Meier analysis demonstrated a significantly reduced disease-free interval and overall survival rate for patients not expressing this antigen. The poor prognosis of such patients was even worse for those presenting with a primary melanoma and a Breslow thickness of > or = 1 mm. Thus, Melan-A/MART-1 is not only a useful and specific additional marker for the diagnosis of primary cutaneous melanoma, but it may also help refine the prognosis of patients with malignant melanoma.
(Copyright 2001 Wiley-Liss, Inc.)

المؤلفون: Autier P; Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. pautier@ieo.it, Doré JF, Négrier S, Liénard D, Panizzon R, Lejeune FJ, Guggisberg D, Eggermont AM

المصدر: Journal of the National Cancer Institute [J Natl Cancer Inst] 1999 Aug 04; Vol. 91 (15), pp. 1304-9.

نوع المنشور: Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Oxford University Press Country of Publication: United States NLM ID: 7503089 Publication Model: Print Cited Medium: Print ISSN: 0027-8874 (Print) Linking ISSN: 00278874 NLM ISO Abbreviation: J Natl Cancer Inst Subsets: MEDLINE

مواضيع طبية MeSH: Life Style*, Melanoma/*prevention & control , Skin Neoplasms/*prevention & control , Sunlight/*adverse effects , Sunscreening Agents/*administration & dosage, Adult ; Double-Blind Method ; Female ; France ; Humans ; Male ; Melanoma/etiology ; Skin Neoplasms/etiology ; Switzerland ; Time Factors

مستخلص: Background: In epidemiologic studies, sunscreen use is associated with increased risk of cutaneous melanoma, basal cell skin cancer, and higher numbers of nevi. It has been proposed that sunscreens may encourage prolonged sun exposure because they delay sunburn occurrence. We examined whether, under habitual conditions of sunscreen use, the sun-protection factor (SPF) had an influence on sun-exposure duration.
Methods: Before the 1997 summer holidays, we randomly assigned 87 French and Swiss participants who were 18-24 years of age to receive an SPF 10 or an SPF 30 sunscreen. Neither medical personnel nor study participants were aware of their sunscreen assignment. Participants were asked to complete daily records of their sun exposure. To avoid influencing the recreational sun-exposure habits of the study participants, no recommendation was made about sun exposure or sun protection. Furthermore, participants were told that the trial end point was the number of pigmented skin lesions before and after the holidays. One subject was lost to follow-up. All statistical tests were two-sided.
Results: The SPF 10 (n = 44) and SPF 30 (n = 42) groups had equivalent mean holiday durations (19.4 days versus 20.2 days) and mean quantities of sunscreen used (72.3 g versus 71.6 g). The mean cumulative sun exposures for the two groups were 58.2 hours and 72.6 hours, respectively (P =.011). The mean daily durations of sunbathing were 2.6 and 3.1 hours, respectively (P =.0013), and, for outdoor activities, they were 3.6 and 3.8 hours, respectively (P =.62). There was no difference in sunburn experience between the two groups.
Conclusions: Use of higher SPF sunscreen seems to increase the duration of recreational sun exposure of young white Europeans.

عنوان ترانسليتريتد: Klinik und Pathologie des Melanoms.

المؤلفون: Panizzon RG; Service de Dermatologie et Vénéréologie, CHUV, Lausanne., Guggisberg D

المصدر: Therapeutische Umschau. Revue therapeutique [Ther Umsch] 1999 Jun; Vol. 56 (6), pp. 302-8.

نوع المنشور: English Abstract; Journal Article

بيانات الدورية: Publisher: Aerzteverlag medinfo AG Country of Publication: Switzerland NLM ID: 0407224 Publication Model: Print Cited Medium: Print ISSN: 0040-5930 (Print) Linking ISSN: 00405930 NLM ISO Abbreviation: Ther Umsch Subsets: MEDLINE

مواضيع طبية MeSH: Melanoma/*diagnosis , Skin Neoplasms/*diagnosis, Adult ; Aged ; Child ; Female ; Humans ; Infant ; Male ; Melanoma/classification ; Melanoma/pathology ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Skin/pathology ; Skin Neoplasms/classification ; Skin Neoplasms/pathology

مستخلص: The annual incidence of melanoma is continually increasing. Melanomas can easily be diagnosed because they are readily visible on the skin. The prognosis is excellent for melanoma when it is diagnosed in an early stage. The clinical diagnosis of melanomas is made by the simple A-B-C-D-E-rule. Clinically, we distinguish the following melanoma types by the order of frequency: the melanoma of the superficial spreading type (SSM), the melanoma with nodular type (NM), the lentigo maligna melanoma (LMM) and the acro-lentiginous melanoma (ALM). Other clinical subtypes of melanoma are congenital giant nevus and melanoma of the mucous membranes. With help of histogenesis, we can distinguish similar forms for melanoma of the SSM-type, melanoma of the NM-type, the lentigo maligna melanoma (LMM) and the melanoma of the ALM-type. In this case, it is preferable to use the terminology acanthotic-lentiginous melanoma since acro-lentiginous is the clinical expression and not a histopathological one. Further subtypes can be distinguished histopathologically such as the desmoplasic melanoma which has been recently described as melanoma from a dysplasic nevus as well as melanoma of the lichen cleanness type. Furthermore, due to histopathology other particular forms can be distinguished such as the melanoma of the nevus Spitz type and melanoma originating from a blue nevus. Most important for the histopathological report is the thickness of the melanoma in millimeters related to the Breslow index as well as the invasion level in the skin by the Clark classification since the melanoma thickness is the most important risk factor for the melanoma patient.