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Melanoma: HELP
Articles from Chile
Based on 97 articles published since 2010
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These are the 97 published articles about Melanoma that originated from Chile during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial Lentigo Maligna-Challenges, Observations, Imiquimod, Confocal Microscopy, and Personalized Treatment. 2018

Fosko, Scott W / Navarrete-Dechent, Cristian P / Nehal, Kishwer S. ·Department of Dermatology, Mayo Clinic Jacksonville, Jacksonville, Florida. · Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Dermatology, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. ·JAMA Dermatol · Pubmed #29847677.

ABSTRACT: -- No abstract --

2 Review Skin cancer: findings and role of high-resolution ultrasound. 2019

Catalano, Orlando / Roldán, Fernando Alfageme / Varelli, Carlo / Bard, Robert / Corvino, Antonio / Wortsman, Ximena. ·Radiology Unit, Istituto Diagnostico Varelli, via Cornelia dei Gracchi 65, 80126, Naples, Italy. orlando.catalano@istitutovarelli.it. · Hospital Universitario Puerta De Hierro Majadahonda, Madrid, Spain. · Radiology Unit, Istituto Diagnostico Varelli, via Cornelia dei Gracchi 65, 80126, Naples, Italy. · Bard Cancer Center, New York, NY, USA. · Department of Movement and Wellness Sciences, University of Naples Parthenope, Naples, Italy. · Department of Dermatology, Institute for Diagnostic Imaging and Research of the Skin and Soft Tissues Clinic, University of Chile and Pontifical Catholic University of Chile, Santiago, Chile. ·J Ultrasound · Pubmed #31069756.

ABSTRACT: Currently available high-resolution transducers allow a detailed ultrasound (US) assessment of skin tumors. US complements clinical examination, dermoscopy, and biopsy in the initial differential diagnosis, surgical planning, locoregional staging, and follow-up of patients with skin malignancies. It is important for dermatologists, skin surgeons, and US operators to be aware of the US imaging findings and to recognize the clinical scenarios where imaging is indicated in the management of skin cancer. The purpose of this review article is to address the most common indications for US in skin oncology and to provide a comprehensive guide to the gray-scale and color-Doppler findings in cutaneous malignant tumors.

3 Review Unusual Clinical Presentations of Malignant Melanoma: A Review of Clinical and Histologic Features with Special Emphasis on Dermatoscopic Findings. 2018

Cabrera, Raúl / Recule, Francisca. ·Department of Dermatology, Universidad del Desarrollo, Clínica Alemana, Manquehue Norte 1410, Vitacura, Santiago, Chile. rcabrera@alemana.cl. · Department of Dermatology, Universidad del Desarrollo, Clínica Alemana, Manquehue Norte 1410, Vitacura, Santiago, Chile. ·Am J Clin Dermatol · Pubmed #30374898.

ABSTRACT: This review presents the main challenges encountered when diagnosing unusual variants of malignant melanoma with the aim of raising awareness to allow application of the most appropriate treatment strategies. Although these melanomas are often rare, their misdiagnosis potentially jeopardizes patients' health and survival, and has medicolegal implications. The clinical and histologic presentations of melanoma vary greatly, and assessment of uncommon melanomas can be difficult for practitioners because of their scarcity and resemblance to other dermatologic entities. The most problematic melanoma types are desmoplastic melanoma, polypoid melanoma, primary dermal melanoma, verrucous malignant melanoma, pigmented epithelioid melanocytoma, mucosal melanoma, follicular melanoma and melanoma with non-melanocytic differentiation. The two most difficult-to-diagnose subtypes of melanoma are the nevoid and the amelanotic melanomas. Some specific attributes of these variants can be more easily recognized with digital dermatoscopy, facilitating early detection and possibly avoiding invasive procedures. Key cases with the most notable clinical, dermatoscopic, and histopathologic features are presented, highlighting the practical issues of making an accurate diagnosis and choosing the best therapy.

4 Review Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer. 2018

Rojas-Sepúlveda, Daniel / Tittarelli, Andrés / Gleisner, María Alejandra / Ávalos, Ignacio / Pereda, Cristián / Gallegos, Iván / González, Fermín Eduardo / López, Mercedes Natalia / Butte, Jean Michel / Roa, Juan Carlos / Fluxá, Paula / Salazar-Onfray, Flavio. ·Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Independencia 1027, building H, Third floor, 8380453, Santiago, Chile. · Millennium Institute on Immunology and Immunotherapy, Universidad de Chile, 8380453, Santiago, Chile. · Faculty of Science, Universidad San Sebastián, Lota 2465, 7510157, Santiago, Chile. · Pathological Anatomy Service, Clinic Hospital, Universidad de Chile, 8380456, Santiago, Chile. · Department of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, 8380492, Santiago, Chile. · Department of Surgery, Fundación Arturo López Pérez, Institute of Oncology, 7500921, Santiago, Chile. · Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, 8330023, Santiago, Chile. · Center for Investigation in Translational Oncology (CITO), Advanced Center for Chronic Diseases (ACCDiS), School of Medicine, Pontificia Universidad Católica de Chile, 8330023, Santiago, Chile. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Independencia 1027, building H, Third floor, 8380453, Santiago, Chile. fsalazar@u.uchile.cl. · Millennium Institute on Immunology and Immunotherapy, Universidad de Chile, 8380453, Santiago, Chile. fsalazar@u.uchile.cl. ·Cancer Immunol Immunother · Pubmed #29600445.

ABSTRACT: Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. In these studies, 60% of stage IV melanoma DC-treated patients showed immunological responses correlating with improved survival. Further studies showed that an essential part of the clinical efficacy was associated with the use of conditioned lysates. Gallbladder cancer (GBC) is a high-incidence malignancy in South America. Here, we evaluated the feasibility of producing effective DCs using heat-conditioned cell lysates derived from gallbladder cancer cell lines (GBCCL). By characterizing nine different GBCCLs and several fresh tumor tissues, we found that they expressed some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and several carcinoembryonic antigens. Moreover, heat-shock treatment of GBCCLs induced calreticulin translocation and release of HMGB1 and ATP, both known to act as danger signals. Monocytes stimulated with combinations of conditioned lysates exhibited a potent increase of DC-maturation markers. Furthermore, conditioned lysate-matured DCs were capable of strongly inducing CD4

5 Review Sentinel lymph node biopsy plus wide local excision vs. wide location excision alone for primary cutaneous melanoma: a systematic review and meta-analysis. 2017

Santos-Juanes, J / Fernández-Vega, I / Galache Osuna, C / Coto-Segura, P / Martínez-Camblor, P. ·Dermatology II Department of Hospital Universitario Central de Asturias, Oviedo, Spain. · Pathology Department of Hospital Universitario Araba, Álava, Spain. · Departamento de Radiodiagnóstico, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. · Geisel School of Medicine at Dartmouth, Hanover, NH, USA. · Universidad Autónoma de Chile, Santiago, Chile. ·J Eur Acad Dermatol Venereol · Pubmed #27592851.

ABSTRACT: BACKGROUND: Sentinel lymph node biopsy and wide local excision of the primary melanoma (SLNB) is now a standard staging procedure for patients with melanomas 1 mm or more in thickness, but its therapeutic benefit is not clear. OBJECTIVE: To determine whether there is an association between performance of SLNB and patient prognosis. METHODS: Studies assessing the association between performance of SLNB and patient prognosis were pooled from MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews and Google Scholar. From each study, first author's last name, publication year, origin country, type of study design, characteristics of participants and the Hazard risk (HR) for melanoma specific survival (MSS) with the corresponding 95% confidence interval (95% CI) were collected. Methodological assessment of the studies was evaluated using the Newcastle-Ottawa scale (NOS) and the 'Risk of bias' tool detailed in the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses for the global HR were performed. In addition, in order to explore the sources of heterogeneity among the studies, sensitivity analyses are also provided. RESULTS: A total of six studies with 8764 patients who had undergone SLNB and 11054 patients who had undergone wide location excision alone (WLEA) were identified for the analysis. The indicators suggest that the heterogeneity is low: τ CONCLUSIONS: Although no significant survival difference was observed in four of the six series, the pooling summary data from all the studies that deal with this issue suggested that SLNB is associated with a significantly better outcome compared with WLEA for localized melanoma.

6 Review [Understanding current therapies in metastatic melanoma]. 2016

Rodríguez, Rocío / Parra, Angela / González, Sergio / Molgó, Montserrat / Droppelmann, Nicolás / Acevedo, Francisco / Peña, José / Uribe, Pablo. ·Unidad de Melanoma y Cáncer de Piel UC, Departamento de Anatomía Patológica, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. ·Rev Med Chil · Pubmed #28394962.

ABSTRACT: Cutaneous melanoma is a highly aggressive tumor developing from melanocytes, its incidence is increasing, and prognosis in advanced stages is daunting. New therapies have been approved during the recent years with unprecedented results, including inhibitors of MAPK/ERK pathway and immune checkpoint blockade (anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) as ipilimumab, anti-programmed cell death protein 1 (PD-L1) as pembrolizumab and anti-programmed cell death protein 1 ligand (PD-L1), among many others). The aim of this paper is to review currently available metastatic melanoma therapies focusing mainly on new therapies that have demonstrated effectiveness, after several decades of little progress in the treatment of this disease.

7 Review In vivo confocal microscopy for the oral cavity: Current state of the field and future potential. 2016

Maher, N G / Collgros, H / Uribe, P / Ch'ng, S / Rajadhyaksha, M / Guitera, P. ·The Melanoma Institute Australia, Sydney, Australia; The University of Sydney, Sydney, Australia. · Hospital Universitari, Germans Trias i Pujol, Badalona (Barcelona), Spain. · Department of Dermatology, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile; Melanoma and Skin Cancer Unit, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. · The Melanoma Institute Australia, Sydney, Australia; The University of Sydney, Sydney, Australia; Institute of Academic Surgery at Royal Prince Alfred Hospital, University of Sydney, New South Wales, Australia. · Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, USA. · The Melanoma Institute Australia, Sydney, Australia; The University of Sydney, Sydney, Australia; Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, Australia. Electronic address: pascale.guitera@melanoma.org.au. ·Oral Oncol · Pubmed #26786962.

ABSTRACT: Confocal microscopy (CM) has been shown to correlate with oral mucosal histopathology in vivo. The purposes of this review are to summarize what we know so far about in vivo CM applications for oral mucosal pathologies, to highlight some current developments with CM devices relevant for oral applications, and to formulate where in vivo CM could hold further application for oral mucosal diagnosis and management. Ovid Medline® and/or Google® searches were performed using the terms 'microscopy, confocal', 'mouth neoplasms', 'mouth mucosa', 'leukoplakia, oral', 'oral lichen planus', 'gingiva', 'cheilitis', 'taste', 'inflammatory oral confocal', 'mucosal confocal' and 'confocal squamous cell oral'. In summary, inclusion criteria were in vivo use of any type of CM for the human oral mucosa and studies on normal or pathological oral mucosa. Experimental studies attempting to identify proteins of interest and microorganisms were excluded. In total 25 relevant articles were found, covering 8 main topics, including normal oral mucosal features (n=15), oral dysplasia or neoplasia (n=7), inflamed oral mucosa (n=3), taste impairment (n=3), oral autoimmune conditions (n=2), pigmented oral pathology/melanoma (n=1), delayed type hypersensitivity (n=1), and cheilitis glandularis (n=1). The evidence for using in vivo CM in these conditions is poor, as it is limited to mainly small descriptive studies. Current device developments for oral CM include improved probe design. The authors propose that future applications for in vivo oral CM may include burning mouth syndrome, intra-operative mapping for cancer surgery, and monitoring and targeted biopsies within field cancerization.

8 Review Tumor cell lysates as immunogenic sources for cancer vaccine design. 2014

González, Fermín E / Gleisner, Alejandra / Falcón-Beas, Felipe / Osorio, Fabiola / López, Mercedes N / Salazar-Onfray, Flavio. ·a Millennium Institute on Immunology and Immunotherapy; Institute of Biomedical Sciences; Faculty of Medicine ; University of Chile ; Santiago , Chile. ·Hum Vaccin Immunother · Pubmed #25625929.

ABSTRACT: Autologous dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) are a promising immunological tool for cancer therapy. These stimulate the antitumor response and immunological memory generation. Nevertheless, many patients remain refractory to DC approaches. Antigen (Ag) delivery to DCs is relevant to vaccine success, and antigen peptides, tumor-associated proteins, tumor cells, autologous tumor lysates, and tumor-derived mRNA have been tested as Ag sources. Recently, DCs loaded with allogeneic tumor cell lysates were used to induce a potent immunological response. This strategy provides a reproducible pool of almost all potential Ags suitable for patient use, independent of MHC haplotypes or autologous tumor tissue availability. However, optimizing autologous tumor cell lysate preparation is crucial to enhancing efficacy. This review considers the role of cancer cell-derived lysates as a relevant source of antigens and as an activating factor for ex vivo therapeutic DCs capable of responding to neoplastic cells. These promising therapies are associated with the prolonged survival of advanced cancer patients.

9 Clinical Trial Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial. 2018

Carlino, Matteo S / Long, Georgina V / Schadendorf, Dirk / Robert, Caroline / Ribas, Antoni / Richtig, Erika / Nyakas, Marta / Caglevic, Christian / Tarhini, Ahmed / Blank, Christian / Hoeller, Christoph / Bar-Sela, Gil / Barrow, Catherine / Wolter, Pascal / Zhou, Honghong / Emancipator, Kenneth / Jensen, Erin H / Ebbinghaus, Scot / Ibrahim, Nageatte / Daud, Adil. ·Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia; School of Medicine, University of Sydney, Sydney, NSW, Australia. Electronic address: Matteo.carlino@sydney.edu.au. · Melanoma Institute Australia, Sydney, NSW, Australia; Department of Medical Oncology and Translational Research, University of Sydney, Sydney, NSW, Australia; Royal North Shore Hospital, Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia. Electronic address: georgina.long@sydney.edu.au. · Department of Dermatology, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany. Electronic address: Dirk.Schadendorf@uk-essen.de. · Department of Oncology, Gustave Roussy, Villejuif, France; Paris-Sud University, Orsay, France. Electronic address: Caroline.Robert@igr.fr. · Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu. · Department of Dermatology, Medical University of Graz, Graz, Austria. Electronic address: erika.richtig@medunigraz.at. · Department of Clinical Cancer Research, Oslo University Hospital, Oslo, Norway. Electronic address: marnya@ous-hf.no. · Unit of Investigational Cancer Drugs, Instituto Oncologico Fundación Arturo López Pérez, Santiago, Chile. Electronic address: oncodemia@yahoo.com. · Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: tarhiniaa@upmc.edu. · Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands. Electronic address: c.blank@nki.nl. · Department of Dermatology, Medical University of Vienna, Vienna, Austria. Electronic address: christoph.hoeller@meduniwien.ac.at. · Division of Oncology, Rambam Health Care Campus, Haifa, Israel. Electronic address: g_barsela@rambam.health.gov.il. · Wellington Blood and Cancer Centre, Wellington Hospital, Wellington, New Zealand. Electronic address: Catherine.Barrow@ccdhb.org.nz. · Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. Electronic address: pascalwolter@hotmail.com. · Department of BARDS, Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: honghongz@gmail.com. · Companion Diagnostics, Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: kenneth.emancipator@merck.com. · LDS - Medical Communications, Merck & Co., Inc., North Wales, PA, USA. Electronic address: erin_jensen2@merck.com. · Department of Clinical Oncology, Merck & Co., Inc., North Wales, PA, USA. Electronic address: scot_ebbinghaus@merck.com. · Department of Clinical Oncology, Merck & Co., Inc., North Wales, PA, USA. Electronic address: nageatte.ibrahim@merck.com. · University of California, San Francisco, San Francisco, CA, USA. Electronic address: adaud@medicine.ucsf.edu. ·Eur J Cancer · Pubmed #30096704.

ABSTRACT: BACKGROUND: Predictive biomarkers of patients likely to benefit from anti-programmed death 1 inhibitor therapy have clinical relevance. We examined whether line of therapy or tumour programmed death ligand 1 (PD-L1) expression affects the efficacy and safety of pembrolizumab, compared with ipilimumab, in advanced melanoma. METHODS: Of 834 patients enrolled in the randomised, open-label phase III KEYNOTE-006 study, 833 were included in this analysis. Patients were randomly assigned 1:1:1 to receive pembrolizumab 10 mg/kg every 2 or 3 weeks (for 24 months) or ipilimumab 3 mg/kg every 3 weeks (for four doses) until disease progression/intolerable toxicity. This analysis evaluated progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Data cut-off: 03 November 2016. RESULTS: Of the patients, 60.3% were male, 65.9% were treatment naive and 80.6% had PD-L1-positive tumours (median follow-up was 33.9 months). Twenty-four-month survival rates were higher with pembrolizumab than with ipilimumab in treatment-naive (PFS 31.0% versus 14.6%; OS 58.0% versus 44.7%) and previously treated patients (PFS 25.7% versus 11.3%; OS 49.2% versus 37.9%). Twenty-four-month survival rates were higher with pembrolizumab than with ipilimumab in patients with PD-L1-positive tumours (PFS 33.2% versus 13.1%; OS 58.4% versus 45.0%) and similar in PD-L1-negative tumours (PFS 14.9% versus NR [no data at 24 months for a PFS estimate]; OS 43.6% versus 31.8%). Safety of pembrolizumab by subgroup was consistent with previous reports. CONCLUSIONS: Findings support pembrolizumab monotherapy as standard of care in patients with advanced melanoma, regardless of first- or second-line therapy or PD-L1 status. CLINICALTRIALS. GOV IDENTIFIER: NCT01866319.

10 Clinical Trial Soluble PD-L1 as a Biomarker in Malignant Melanoma Treated with Checkpoint Blockade. 2017

Zhou, Jun / Mahoney, Kathleen M / Giobbie-Hurder, Anita / Zhao, Fengmin / Lee, Sandra / Liao, Xiaoyun / Rodig, Scott / Li, Jingjing / Wu, Xinqi / Butterfield, Lisa H / Piesche, Matthias / Manos, Michael P / Eastman, Lauren M / Dranoff, Glenn / Freeman, Gordon J / Hodi, F Stephen. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Melanoma Disease Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Center for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. · Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. · Immunologic Monitoring and Cellular Products Laboratory, Hillman Cancer Center Research Pavilion, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. · Biomedical Research Laboratories, Medicine Faculty, Catholic University of Maule, Talca, Chile. · Novartis Institutes for BioMedical Research, Cambridge, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. stephen_hodi@dfci.harvard.edu. ·Cancer Immunol Res · Pubmed #28522460.

ABSTRACT: Blockade of the pathway including programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers. Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myeloma. However, the regulatory roles and function of sPD-L1 particularly in connection with immune checkpoint blockade treatment are not fully understood. We identified four splice variants of PD-L1 in melanoma cells, and all of them are secreted. Secretion of sPD-L1 resulted from alternate splicing activities, cytokine induction, cell stress, cell injury, and cell death in melanoma cells. Pretreatment levels of sPD-L1 were elevated in stage IV melanoma patient sera compared with healthy donors. High pretreatment levels of sPD-L1 were associated with increased likelihood of progressive disease in patients treated by CTLA-4 or PD-1 blockade. Although changes in circulating sPD-L1 early after treatment could not distinguish responders from those with progressive disease, after five months of treatment by CTLA-4 or PD-1 blockade patients who had increased circulating sPD-L1 had greater likelihood of developing a partial response. Induction of sPD-L1 was associated with increased circulating cytokines after CTLA-4 blockade but not following PD-1 blockade. Circulating sPD-L1 is a prognostic biomarker that may predict outcomes for subgroups of patients receiving checkpoint inhibitors.

11 Clinical Trial Combined Anti-VEGF and Anti-CTLA-4 Therapy Elicits Humoral Immunity to Galectin-1 Which Is Associated with Favorable Clinical Outcomes. 2017

Wu, Xinqi / Li, Jingjing / Connolly, Erin M / Liao, Xiaoyun / Ouyang, Jing / Giobbie-Hurder, Anita / Lawrence, Donald / McDermott, David / Murphy, George / Zhou, Jun / Piesche, Matthias / Dranoff, Glenn / Rodig, Scott / Shipp, Margaret / Hodi, F Stephen. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Melanoma Disease Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Center for Immuno-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. · Department of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts. · Massachusetts General Hospital Cancer Center, Boston, Massachusetts. · Beth Israel Deaconess Medical Center, Boston, Massachusetts. · Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. · Biomedical Research Laboratories, Medicine Faculty, Catholic University of Maule, Talca, Chile. · Novartis Institutes for BioMedical Research, Cambridge, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. stephen_hodi@dfci.harvard.edu. ·Cancer Immunol Res · Pubmed #28473314.

ABSTRACT: The combination of anti-VEGF blockade (bevacizumab) with immune checkpoint anti-CTLA-4 blockade (ipilimumab) in a phase I study showed tumor endothelial activation and immune cell infiltration that were associated with favorable clinical outcomes in patients with metastatic melanoma. To identify potential immune targets responsible for these observations, posttreatment plasma from long-term responding patients were used to screen human protein arrays. We reported that ipilimumab plus bevacizumab therapy elicited humoral immune responses to galectin-1 (Gal-1), which exhibits protumor, proangiogenesis, and immunosuppressive activities in 37.2% of treated patients. Gal-1 antibodies purified from posttreatment plasma suppressed the binding of Gal-1 to CD45, a T-cell surface receptor that transduces apoptotic signals upon binding to extracellular Gal-1. Antibody responses to Gal-1 were found more frequently in the group of patients with therapeutic responses and correlated with improved overall survival. In contrast, another subgroup of treated patients had increased circulating Gal-1 protein instead, and they had reduced overall survival. Our findings suggest that humoral immunity to Gal-1 may contribute to the efficacy of anti-VEGF and anti-CTLA-4 combination therapy. Gal-1 may offer an additional therapeutic target linking anti-angiogenesis and immune checkpoint blockade.

12 Clinical Trial Heat-shock induction of tumor-derived danger signals mediates rapid monocyte differentiation into clinically effective dendritic cells. 2011

Aguilera, Raquel / Saffie, Carlos / Tittarelli, Andrés / González, Fermín E / Ramírez, Marcos / Reyes, Diego / Pereda, Cristián / Hevia, Daniel / García, Tamara / Salazar, Lorena / Ferreira, Arturo / Hermoso, Marcela / Mendoza-Naranjo, Ariadna / Ferrada, Carlos / Garrido, Paola / López, Mercedes N / Salazar-Onfray, Flavio. ·Institute of Biomedical Sciences, Faculty of Medicine, Clinical Hospital, University of Chile, Santiago, Chile. ·Clin Cancer Res · Pubmed #21292818.

ABSTRACT: PURPOSE: This study characterizes, biologically and clinically, a novel type of dendritic cells (DC) produced in the short term and called tumor antigen-presenting cells (TAPCells). In particular, we identified factors present in a lysate derived from heat-shocked allogeneic melanoma cells (TRIMEL) that are associated with TAPCells' enhanced capability to induce CD8(+) T-cell responses in vitro and in vaccinated melanoma patients. EXPERIMENTAL DESIGN: First, extensive phenotypic and functional characterization of TAPCells was performed, followed by vaccination of 45 melanoma patients with four doses of TAPCells over a period of 2 months. Specific delayed-type hypersensitivity (DTH) reaction was analyzed posttreatment and correlated with overall survival rates. Furthermore, heat-shock (HS)-induced factors present in TRIMEL and their effects on DC activation were identified and studied. RESULTS: TRIMEL induced a committed, mature, DC-like phenotype in TAPCells and effectively activated melanoma-specific CD4(+) and CD8(+) T cells. Clinically, 64% of vaccinated patients showed positive DTH reaction against TRIMEL, and this was associated with improved overall survival. HS treatment of tumor cells increased calreticulin (CRT) plasma membrane translocation and induced the release of high-mobility group box 1 proteins (HMGB1). Both CRT and HMGB1 mobilization were associated with enhanced TAPCells' maturation and antigen (Ag) cross-presentation, respectively. DTH infiltration analysis revealed the presence of CD8(+)/CD45RO(+) T cells, thus confirming TAPCells' ability to cross-present Ags in vivo. CONCLUSIONS: Our results indicate that lysates derived from heat-shocked tumor cells are an optimal source of tumor-associated Ags, which are crucial for the generation of DCs with improved Ag cross-presentation capacity and clinically effective immunogenicity.

13 Article Eruptive disseminated Spitz nevi - a case report. 2019

Vargas, Pablo / Cárdenas, Rodrigo / Cullen, Roberto / Figueroa, Andrés. ·Department of Dermatology, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: pablovargas.med@gmail.com. · Clínica Alemana de Valdivia, Valdivia, Chile. · Department of Dermatology, Faculty of Medicine, University of Chile, Santiago, Chile. · Dermatology Service, University of Chile Clinical Hospital, University of Chile, Santiago, Chile. ·An Bras Dermatol · Pubmed #31899063.

ABSTRACT: Spitz nevus is a benign melanocytic lesion, which presents in several ways: solitary, agminated, or disseminated. The disseminated variant is uncommon; it may have a rapid evolution (the eruptive form) and be difficult to manage. This report presents the case of a 24-year-old patient with multiple papules on his limbs, which had appeared four years previously. On physical examination, 120 pink and skin-colored papules were seen, which under dermoscopy were observed to be homogeneous, pink vascular lesions. Histopathologic study revealed epithelioid cells arranged in groups or singly in the dermis and dermo-epidermal junction. They were HMB-45 positive in the superficial dermis, and Ki-67<1%. Given these findings, a diagnosis of eruptive disseminated Spitz nevi was made.

14 Article Lentigo maligna melanoma mapping using reflectance confocal microscopy correlates with staged excision: A prospective study. 2019

Navarrete-Dechent, Cristian / Cordova, Miguel / Aleissa, Saud / Liopyris, Konstantinos / Dusza, Stephen W / Kose, Kivanc / Busam, Klaus J / Hollman, Travis / Lezcano, Cecilia / Pulitzer, Melissa / Chen, Chih-Shan J / Lee, Erica H / Rossi, Anthony M / Nehal, Kishwer S. ·Department of Dermatology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile; Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Dermatology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: nehalk@mskcc.org. ·J Am Acad Dermatol · Pubmed #31812621.

ABSTRACT: BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) can present with subclinical extension that may be difficult to define preoperatively and lead to incomplete excision and potential recurrence. Preliminarily studies have used reflectance confocal microscopy (RCM) to assess LM/LMM margins. OBJECTIVE: To evaluate the correlation of LM/LMM subclinical extension defined by RCM compared to the gold standard histopathology. METHODS: Prospective study of LM/LMM patients referred for dermatologic surgery. RCM was performed at the clinically-defined initial surgical margin followed by margin-controlled staged excision with paraffin-embedded tissue and histopathology was correlated with RCM results. RESULTS: Seventy-two patients were included. Mean age was 66.8 years (SD 11.1; 38 - 89 years); 69.4% were males. 70/72 (97.2%) lesions were located on the head neck with mean largest clinical diameter of 1.3cm (0.3 - 5 cm). Diagnostic accuracy for detection of residual melanoma in the tumor debulk (after biopsy) had a sensitivity of 96.7% and a specificity of 66.7% when compared to the histopathology. RCM margin assessment revealed an overall agreement with final histopathology of 85.9% (kappa 0.71; p<0.001). LIMITATIONS: No RCM imaging beyond initial planned margins was performed. CONCLUSION: RCM showed moderate to excellent overall agreement between RCM imaging of LM/LMM and histopathology of staged excision margins.

15 Article Contemporary management of actinic keratosis. 2019

Navarrete-Dechent, Cristian / Marghoob, Ashfaq A / Marchetti, Michael A. ·Department of Dermatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. · Department of Medicine, Faculty of Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·J Dermatolog Treat · Pubmed #31621454.

ABSTRACT: Actinic keratosis (AK) is a skin lesion characterized by itraepithelial keratinocyte dysplasia and molecular alterations shared with normal chronically sun-damaged skin and squamous cell carcinoma (SCC). AK can undergo spontaneous regression, stable existence, or malignant transformation to cutaneous SCC with progression rates to SCC ranging from 0% to 0.5% per lesion-year and AK spontaneous regression of 15-63%. As AK is a potential precursor of invasive SCC, it is commonly treated to mitigate the risk of malignant progression, including metastasis and death. There is a myriad of available spots (e.g. cryotherapy) and field (e.g. 5-fluorouracil, imiquimod photodynamic therapy) treatments for AK. Recently published randomized clinical trials have helped bridge the gap on AK management. In this viewpoint, we sought to summarize the most up-to-date evidence in the management of AK.

16 Article Cx43-Gap Junctions Accumulate at the Cytotoxic Immunological Synapse Enabling Cytotoxic T Lymphocyte Melanoma Cell Killing. 2019

Hofmann, Francisca / Navarrete, Mariela / Álvarez, Javiera / Guerrero, Israel / Gleisner, María Alejandra / Tittarelli, Andrés / Salazar-Onfray, Flavio. ·Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. fcah.vega@gmail.com. · Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. fcah.vega@gmail.com. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. mariela.navarrete.s@gmail.com. · Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. mariela.navarrete.s@gmail.com. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. jalvarezm1011@gmail.com. · Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. jalvarezm1011@gmail.com. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. israel.guerrero.l@gmail.com. · Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. israel.guerrero.l@gmail.com. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. alejandra.gleisner@gmail.com. · Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. alejandra.gleisner@gmail.com. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. tittarelli@gmail.com. · Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. tittarelli@gmail.com. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. fsalazar@u.uchile.cl. · Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. fsalazar@u.uchile.cl. ·Int J Mol Sci · Pubmed #31547237.

ABSTRACT: Upon tumor antigen recognition, cytotoxic T lymphocytes (CTLs) and target cells form specialized supramolecular structures, called cytotoxic immunological synapses, which are required for polarized delivery of cytotoxic granules. In previous reports, we described the accumulation of connexin 43 (Cx43)-formed gap junctions (GJs) at natural killer (NK) cell-tumor cell cytotoxic immunological synapse. In this report, we demonstrate the functional role of Cx43-GJs at the cytotoxic immunological synapse established between CTLs and melanoma cells during cytotoxicity. Using confocal microscopy, we evaluated Cx43 polarization to the contact site between CTLs isolated from pMEL-1 mice and B16F10 melanoma cells. We knocked down Cx43 expression in B16F10 cells and evaluated its role in the formation of functional GJs and the cytotoxic activity of CTLs, by calcein transfer and granzyme B activity assays, respectively. We found that Cx43 localizes at CTL/B16F10 intercellular contact sites via an antigen-dependent process. We also found that pMEL-1 CTLs but not wild-type naïve CD8

17 Article Telmisartan induces melanoma cell apoptosis and synergizes with vemurafenib 2019

Grahovac, Jelena / Srdić-Rajić, Tatjana / Francisco Santibañez, Juan / Pavlović, Marijana / Čavić, Milena / Radulović, Siniša. ·Laboratory for Experimental Pharmacology, Institute for Oncology and Radiology of Serbia, Belgrade 11000, Serbia. · Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgrade 11000, Serbia. · Integrative Center for Biology and Applied Chemistry (CIBQA), Bernardo O'Higgins University, Santiago 8370854, Chile. ·Cancer Biol Med · Pubmed #31516746.

ABSTRACT: Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPARγ, on melanoma cells as a potential agent for repurposing in melanoma treatment. Methods: Expression of AGTR1 and PPARγ mRNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index method. Results: Both AGTR1 and PPARγ mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. Conclusions: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression.

18 Article Isocordoin analogues promote apoptosis in human melanoma cells via Hsp70. 2019

Russo, Alessandra / Cardile, Venera / Avola, Rosanna / Graziano, Adriana / Montenegro, Iván / Said, Bastian / Madrid, Alejandro. ·Department of Drug Sciences, University of Catania, Catania, Italy. · Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy. · Escuela de Obstetricia y Puericultura, Facultad de Medicina, Campus de la Salud, Universidad de Valparaíso, Viña del Mar, Chile. · Departamento de Química, Universidad Técnica Federico Santa María, Santiago, Chile. · Laboratorio de Productos Naturales y Síntesis Orgánica (LPNSO), Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Valparaíso, Chile. ·Phytother Res · Pubmed #31489735.

ABSTRACT: Isocordin 1 and a series of 4-oxyalkyl-isocordoin analogues 2-8 were evaluated for their cytotoxicity effect against human melanoma cells (A2058). Analogues 4, 5, and 6 showed a higher inhibitory activity with IC

19 Article In vivo identification of amyloid and mucin in basal cell carcinoma (BCC) with combined reflectance confocal microscopy (RCM)- optical coherence tomography (OCT) device and direct histopathological correlation. 2019

Sahu, Aditi / Cordova, Miguel / Gill, Melissa / Alessi-Fox, Christi / Navarrete-Dechent, Cristián / González, Salvador / Iftimia, Nicusor / Rajadhyaksha, Milind / Marghoob, Ashfaq A / Chen, Chih-Shan J. ·Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; USA. · SkinMedical Research and Diagnostics, P.L.L.C., Dobbs Ferry, NY, USA and Department of Pathology, SUNY Downstate Medical Center, Brooklyn, NY, USA. · Caliber Imaging and Diagnostics Inc., 50 Methodist Hill Drive Suite 1000, Rochester, NY. · Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; USA; Department of Dermatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. · Medicine and Medical Specialities Department, Alcalá University, Spain. · Physical Sciences, Inc., 20 New England Business Ctr. Drive, Andover, MA. · Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; USA. Electronic address: chenc2@mskcc.org. ·J Am Acad Dermatol · Pubmed #31476338.

ABSTRACT: -- No abstract --

20 Article Coagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation. 2019

Arce, Maximiliano / Pinto, Mauricio P / Galleguillos, Macarena / Muñoz, Catalina / Lange, Soledad / Ramirez, Carolina / Erices, Rafaela / Gonzalez, Pamela / Velasquez, Ethel / Tempio, Fabián / Lopez, Mercedes N / Salazar-Onfray, Flavio / Cautivo, Kelly / Kalergis, Alexis M / Cruz, Sebastián / Lladser, Álvaro / Lobos-González, Lorena / Valenzuela, Guillermo / Olivares, Nixa / Sáez, Claudia / Koning, Tania / Sánchez, Fabiola A / Fuenzalida, Patricia / Godoy, Alejandro / Contreras Orellana, Pamela / Leyton, Lisette / Lugano, Roberta / Dimberg, Anna / Quest, Andrew F G / Owen, Gareth I. ·Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile. · Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile. · Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile. · Vicerrectoría de Investigación, Universidad Mayor, Santiago 7510041, Chile. · Comisión Chilena de Energía Nuclear (CCHEN), Santiago, Chile. · Institute of Biomedical Sciences, Faculty of Medicine, University de Chile, Santiago 8380453, Chile. · Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile. · Biomedical Research Consortium of Chile, Santiago 8331010, Chile. · Laboratory of Immunoncology, Fundación Ciencia & Vida, Santiago, Chile. · Regenerative Medicine Center, Faculty of Medicine, Clinica Alemana-Universidad Del Desarrollo, Santiago 7650568, Chile. · Immunology Institute, Faculty of Medicine, Universidad Austral de Chile, Valdivia 5110566, Chile. · Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA. · Laboratory of Cellular Communication, ICBM, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile. · Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden. · Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile. gowen@bio.puc.cl. · Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile. gowen@bio.puc.cl. · Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile. gowen@bio.puc.cl. · Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile. gowen@bio.puc.cl. ·Cancers (Basel) · Pubmed #31382462.

ABSTRACT: Hypercoagulable state is linked to cancer progression; however, the precise role of the coagulation cascade is poorly described. Herein, we examined the contribution of a hypercoagulative state through the administration of intravenous Coagulation Factor Xa (FXa), on the growth of solid human tumors and the experimental metastasis of the B16F10 melanoma in mouse models. FXa increased solid tumor volume and lung, liver, kidney and lymph node metastasis of tail-vein injected B16F10 cells. Concentrating on the metastasis model, upon coadministration of the anticoagulant Dalteparin, lung metastasis was significantly reduced, and no metastasis was observed in other organs. FXa did not directly alter proliferation, migration or invasion of cancer cells in vitro. Alternatively, FXa upon endothelial cells promoted cytoskeleton contraction, disrupted membrane VE-Cadherin pattern, heightened endothelial-hyperpermeability, increased inflammatory adhesion molecules and enhanced B16F10 adhesion under flow conditions. Microarray analysis of endothelial cells treated with FXa demonstrated elevated expression of inflammatory transcripts. Accordingly, FXa treatment increased immune cell infiltration in mouse lungs, an effect reduced by dalteparin. Taken together, our results suggest that FXa increases B16F10 metastasis via endothelial cell activation and enhanced cancer cell-endothelium adhesion advocating that the coagulation system is not merely a bystander in the process of cancer metastasis.

21 Article Use of paper tape to guide reflectance confocal microscopy navigation of large skin lesions. 2019

Navarrete-Dechent, Cristian / Cordova, Miguel / Aleissa, Saud / Kose, Kivanc / Lee, Erica H / Rossi, Anthony M / Nehal, Kishwer S. ·Department of Dermatology, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile; Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: nehalk@mskcc.org. ·J Am Acad Dermatol · Pubmed #31326468.

ABSTRACT: -- No abstract --

22 Article Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions. 2019

Falcón-Beas, Cristián / Tittarelli, Andrés / Mora-Bau, Gabriela / Tempio, Fabián / Pérez, Claudio / Hevia, Daniel / Behrens, Carolina / Flores, Iván / Falcón-Beas, Felipe / Garrido, Paola / Ascui, Gabriel / Pereda, Cristián / González, Fermín E / Salazar-Onfray, Flavio / López, Mercedes N. ·Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, 8380453 Santiago, Chile. · Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Laboratory of Experimental Immunology & Cancer, Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, 8380492 Santiago, Chile. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile; Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, 8380453 Santiago, Chile. Electronic address: melopez@me.com. ·Immunobiology · Pubmed #31221438.

ABSTRACT: BACKGROUND: Dendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses. METHODS: The effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined. RESULTS: Dexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4 CONCLUSIONS: These findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer.

23 Article Melanoma risk stratification of individuals with a high-risk naevus phenotype - A pilot study. 2019

Rishpon, Ayelet / Navarrete-Dechent, Cristian / Marghoob, Ashfaq A / Dusza, Stephen W / Isman, Gila / Kose, Kivanc / Halpern, Allan C / Marchetti, Michael A. ·Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Department of Dermatology, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. ·Australas J Dermatol · Pubmed #30941757.

ABSTRACT: BACKGROUND/OBJECTIVES: High a naevus counts and atypical naevi are risk factors for cutaneous melanoma. However, many individuals with a high-risk naevus phenotype do not develop melanoma. In this study, we describe the clinical and dermoscopic attributes of naevi associated with melanoma in a high-risk naevus phenotype population. METHODS: This single-centre, hospital-based case-control study included 54 prospectively enrolled adult patients ≥18 years old with a high-risk naevus phenotype (18 cases with a history of melanoma and 36 age- and gender-matched controls without a history of melanoma). We analysed clinical and dermoscopic images of the 20 largest naevi for each participant. RESULTS: Cases had a higher mean age than controls (48.2 vs. 39.1 years, P = 0.007) but there was no difference in the male-to-female ratio between groups. Nearly, all participants (97%) were Fitzpatrick skin type II or III. Naevi in cases were more likely to be truncal, (72.6% vs. 53.6%, P = 0.01), particularly anterior truncal, (29.2% vs. 14.4%, P < 0.001) and larger than 8 mm (17.4% vs. 7.8%%, P = 0.01) compared to controls. CASH score of naevi did not differ between groups. Naevi in cases were more likely to have a multicomponent dermoscopic pattern than in controls (18.4% vs. 12.6%, P = 0.02). CONCLUSION: Larger naevi, truncal naevi, and naevi, with a multicomponent dermoscopic pattern may be risk factors for melanoma among individuals with a high-risk naevus phenotype. Further studies are needed to validate these findings.

24 Article Antigrowth activity and induction of apoptosis in human melanoma cells by Drymis winteri forst extract and its active components. 2019

Russo, Alessandra / Cardile, Venera / Graziano, Adriana C E / Avola, Rosanna / Montenegro, Ivan / Cuellar, Mauricio / Villena, Joan / Madrid, Alejandro. ·Department of Drug Sciences, University of Catania, Via S. Sofia 64, 95125, Catania, Italy. Electronic address: alrusso@unict.it. · Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Via S. Sofia, 89, 95123, Catania, Italy. · Escuela de Obstetricia y Puericultura, Facultad de Medicina, Campus de la Salud, Universidad de Valparaíso, Angamos 655, Reñaca, Viña del Mar, 2520000, Chile. · Facultad de Farmacia, Universidad de Valparaíso, Av. Gran Bretaña N 1093, Valparaíso, 2340000, Chile. · Facultade de Medicina Universidad de Valparaiso, Valparaíso blanco 951, Chile. · Departamento de Química, Facultad de CienciasNaturales y Exactas, Universidad de PlayaAncha, Avda. Leopoldo Carvallo 270, PlayaAncha, Valparaíso, 2340000, Chile. ·Chem Biol Interact · Pubmed #30935903.

ABSTRACT: Melanoma is a highly invasive cancer that resists most conventional treatments. Therefore, there is an urgent need to identify alternative anticancer agents able to affect new molecular targets. Drimys winteri (Winteraceae) is a medicinal plant, employed in Brazil and many countries, in folk medicine against a variety of ailments, especially for the treatment of fevers, ulcers, pains, affections of respiratory tract and cancers. Previous phytochemical studies have isolated and identified the presence of diverse classes of secondary metabolites in this plant such as sesquiterpenes. In an ongoing to identify new natural anticancer compounds for the treatment and/or prevention of melanoma, we study the effects of Drimys winteri bark ethyl acetate extract and its sesquiterpenes drimenol, nordrimenone, isonordrimenone and polygodial on human melanoma cells. The treatment of melanoma cells with extract, drimenol, isordrimenone and polygodial resulted in a significant reduction in cell viability. But, polygodial showed the highest inhibitory growth activity. In addition, we reported an apoptotic response after treatment with drimenol, isordrimenone and polygodial that probably involves the reduction of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of caspase cascade at higher concentrations, correlated with additional reactive oxygen species increase, probably switches natural product-induced cell death from apoptosis to necrosis. Therefore, this evidence provides a scientific support for the anticancer employ of Drimys winteri in traditional medicinal and suggests that active molecules can be considered potential candidates to be tested also in in vivo models, alone or in combination with chemotherapy agents, for the management of melanoma.

25 Article Activating PTEN Tumor Suppressor Expression with the CRISPR/dCas9 System. 2019

Moses, Colette / Nugent, Fiona / Waryah, Charlene Babra / Garcia-Bloj, Benjamin / Harvey, Alan R / Blancafort, Pilar. ·Cancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia. · Cancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Molecular Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia. · Cancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia. · Cancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Medicine, Faculty of Science, Universidad Mayor, Camino la Piramide 5750, Huechuraba 8580745, Santiago, Chile. · School of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia; Perron Institute for Neurological and Translational Science, 8 Verdun Street, Nedlands, WA 6009, Australia. · Cancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia. Electronic address: pilar.blancafort@uwa.edu.au. ·Mol Ther Nucleic Acids · Pubmed #30654190.

ABSTRACT: PTEN expression is lost in many cancers, and even small changes in PTEN activity affect susceptibility and prognosis in a range of highly aggressive malignancies, such as melanoma and triple-negative breast cancer (TNBC). Loss of PTEN expression occurs via multiple mechanisms, including mutation, transcriptional repression and epigenetic silencing. Transcriptional repression of PTEN contributes to resistance to inhibitors used in the clinic, such as B-Raf inhibitors in BRAF mutant melanoma. We aimed to activate PTEN expression using the CRISPR system, specifically dead (d) Cas9 fused to the transactivator VP64-p65-Rta (VPR). dCas9-VPR was directed to the PTEN proximal promoter by single-guide RNAs (sgRNAs), in cancer cells that exhibited low levels of PTEN expression. The dCas9-VPR system increased PTEN expression in melanoma and TNBC cell lines, without transcriptional regulation at predicted off-target sgRNA binding sites. PTEN activation significantly repressed downstream oncogenic pathways, including AKT, mTOR, and MAPK signaling. BRAF V600E mutant melanoma cells transduced with dCas9-VPR displayed reduced migration, as well as diminished colony formation in the presence of B-Raf inhibitors, PI3K/mTOR inhibitors, and with combined PI3K/mTOR and B-Raf inhibition. CRISPR-mediated targeted activation of PTEN may provide an alternative therapeutic approach for highly aggressive cancers that are refractory to current treatments.

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