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Melanoma: HELP
Articles from Chile
Based on 65 articles published since 2008
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These are the 65 published articles about Melanoma that originated from Chile during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 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.

2 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.

3 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.

4 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.

5 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.

6 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.

7 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.

8 Clinical Trial Prolonged survival of dendritic cell-vaccinated melanoma patients correlates with tumor-specific delayed type IV hypersensitivity response and reduction of tumor growth factor beta-expressing T cells. 2009

López, Mercedes N / Pereda, Cristian / Segal, Gabriela / Muñoz, Leonel / Aguilera, Raquel / González, Fermín E / Escobar, Alejandro / Ginesta, Alexandra / Reyes, Diego / González, Rodrigo / Mendoza-Naranjo, Ariadna / Larrondo, Milton / Compán, Alvaro / Ferrada, Carlos / Salazar-Onfray, Flavio. ·Millennium Nucleus on Immunology and Immunotherapy, Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile. ·J Clin Oncol · Pubmed #19139436.

ABSTRACT: PURPOSE: The aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines. PATIENTS AND METHODS: Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records. RESULTS: The overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) beta+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001). CONCLUSION: Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFbeta+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.

9 Article Curcumin-loaded nanoemulsion: a new safe and effective formulation to prevent tumor reincidence and metastasis. 2018

Guerrero, Simón / Inostroza-Riquelme, Mariela / Contreras-Orellana, Pamela / Diaz-Garcia, Victor / Lara, Pablo / Vivanco-Palma, Andrea / Cárdenas, Areli / Miranda, Victor / Robert, Paz / Leyton, Lisette / Kogan, Marcelo J / Quest, Andrew F G / Oyarzun-Ampuero, Felipe. ·Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago 8380453, Chile. ·Nanoscale · Pubmed #30484463.

ABSTRACT: Curcumin is widely considered beneficial to human health, but insolubility and instability greatly hamper reproducible exploitation of the advantageous traits. Here we report on the development, characterization and evaluation of a curcumin-loaded nanoemulsion (CUR-NEM) that is highly effective in preventing post-surgery tumor reincidence and metastasis. The method of fabrication utilized safe excipients and generated particles of 200 nm (PDI ≤ 0.2) with negative zeta potential (-30 mV) and a high yield of curcumin (95%), which can be converted by lyophilization to a dry powder. In vitro assays showed that CUR-NEM is safe in non-cancerous human cells (HEK-293T) and preferentially cytotoxic in gastric (AGS), colon (HT29-ATCC, HT29-US), breast (MDA-MB-231) and melanoma (B16F10) cells. In addition, in melanoma cells the nanoformulation increases intracellular curcumin accumulation and reactive oxygen species (ROS) formation, while preventing cell-migration and invasion. In vivo studies in C57BL/6 mice demonstrated that a single dose, applied topically to the wounded area after surgical excision of primary tumors formed upon subcutaneous injection of syngeneic B16F10 cells, was sufficient to completely prevent reincident tumor growth and spontaneous lung metastasis, while in untreated animals 70% reincidence and metastasis were observed. In vivo experiments also showed that the fluorescence signal due to curcumin was maintained at least 15 days after topical application of CUR-NEM, while when administered in DMSO the curcumin signal disappeared within 4 days. Importantly, the administration of a dose 22 times larger than that applied topically to animals after tumor surgery did not alter biochemical parameters. Due to the safety and efficacy of the formulation, we envisage it as ideal for topical application in cancer patients following surgery, to prevent tumor reincidence and metastasis. In addition, other routes of administration/protocols could also be proposed to treat/prevent malignant tumors in patients.

10 Article Biomimetic quantum dot-labeled B16F10 murine melanoma cells as a tool to monitor early steps of lung metastasis by in vivo imaging. 2018

Díaz-García, Víctor Manuel / Guerrero, Simón / Díaz-Valdivia, Natalia / Lobos-González, Lorena / Kogan, Marcelo / Pérez-Donoso, José Manuel / Quest, Andrew Fg. ·Cellular Communication Laboratory, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Faculty of Medicine, Universidad de Chile, Santiago, Chile, aquest@med.uchile.cl. · Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago, Chile, aquest@med.uchile.cl. · BioNanotechnology and Microbiology Laboratory, Center for Bioinformatics and Integrative Biology (CBIB), Faculty of life Sciences, Universidad Andres Bello, Santiago, Chile, jose.perez@unab.cl. · Facultad de Ingeniería y Tecnología, Universidad San Sebastián, Concepción 4080871, Chile. · Department of Pharmacological and Toxicological Chemistry, Faculty of Chemical and Pharmaceutical Sciences, Universidad de Chile, Santiago, Chile. · Fundación Ciencia y Vida, Santiago, Chile. · Centro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile. ·Int J Nanomedicine · Pubmed #30410327.

ABSTRACT: Background: Numerous studies have proposed the use of fluorescent semiconductor nanoparticles or quantum dots (QDs) as novel tools to label cells and tumors. However, QD applications are limited by their toxicity in biological systems and little is known about whether QDs affect the capacity of cancer cells to metastasize. Previously, we described the "biomimetic" synthesis of CdTe-QDs (QDs-glutathione [GSH]) with increased biocompatibility and the potential utility in labeling cells. Purpose: In order to determine the feasibility of using QDs-GSH as a tool for tracking tumor cells during early metastasis, we characterized here for the first time, the in vitro and in vivo effects of the incorporation of green or red biomimetic QDs-GSH into B16F10 cells, a syngeneic mouse melanoma line for metastasis assays in C57BL/6 mice. Methods: B16F10 cells were labeled with green or red biomimetic QDs-GSH in the presence or absence of n-acetylcysteine. Then, migration, invasion and proliferation of labeled B16F10 were evaluated in vitro. Finally, the B16F10 cells labeled with red QDs-GSH were used to monitor in vivo lung metastasis at early time points (5 minutes to 24 hours) or after 21 days in C57BL/6 mice. Results: We developed a methodology that allows obtaining QDs-GSH-labeled B16F10 cells (nearly 100% viable labeled cells), which remained viable for at least 5 days and migrated similarly to control cells. However, proliferation, invasion, and the capacity to form metastatic nodules in the lungs were severely attenuated. Fluorescence imaging revealed that distribution/accumulation of QDs-GSH-labeled B16F10 cells could be tracked following injection into C57BL/6 mice (syngeneic preclinical metastasis model) and that these cells preferentially accumulated in the perialveolar area in lungs as early as 5 minutes post-injection. Conclusion: The methodology described here represents a useful alternative for monitoring initial events during tumor cell metastasis.

11 Article Viable Pregnancy in a patient with metastatic melanoma treated with double checkpoint immunotherapy. 2018

Burotto, Mauricio / Gormaz, Juan G / Samtani, Suraj / Valls, Nicolas / Silva, Ricardo / Rojas, Carlos / Portiño, Sergio / de la Jara, Carlos. ·Medical Oncology Service, Clínica Alemana de Santiago, Santiago, Chile. Electronic address: mburotto@alemana.cl. · Medical Oncology Service, Clínica Alemana de Santiago, Santiago, Chile. · Department of Anesthesia, Hospital clínico Universidad de Chile, Santiago, Chile. · Departamento de Ginecología y Obstetricia, Clínica Las Condes, Santiago Chile. ·Semin Oncol · Pubmed #30262400.

ABSTRACT: Metastatic cancers during pregnancy have historically been associated with dismal outcomes, with greater rates of tumor progression in part because of diminished treatment alternatives. Immunotherapy with T-cell checkpoint inhibitors has significantly impacted the survival of several metastatic tumors. However, given their mechanism of action, immune-related adverse events can occur, especially with combined immunotherapy treatments. During pregnancy, checkpoint pathways have a major role, providing immune tolerance to the fetal allograft. Furthermore, evidence suggests that inhibition of this pathway may be associated with an increased risk of miscarriage. We describe, to our knowledge, the first case reported in the literature of a patient 7 weeks pregnant, diagnosed with metastatic melanoma and treated with nivolumab plus ipilimumab. We also present the associated immune-related side effects and their treatment, as well as the oncologic results that lead to favorable pregnancy outcome.

12 Article Gold nanoparticles as tracking devices to shed light on the role of caveolin-1 in early stages of melanoma metastasis. 2018

Guerrero, Simón / Díaz-García, Victor Manuel / Contreras-Orellana, Pamela / Lara, Pablo / Palma, Sujey / Guzman, Fanny / Lobos-Gonzalez, Lorena / Cárdenas, Areli / Rojas-Silva, Ximena / Muñoz, Luis / Leyton, Lisette / Kogan, Marcelo J / Quest, Andrew Fg. ·Laboratory of Cellular Communication, Program of Cell & Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. · Center for Studies on Exercise Metabolism & Cancer (CEMC), University of Chile, Av. Independencia 1027, Santiago, Chile. · Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santos Dumont 964, Independencia, Santiago, Chile. · Facultad de Ingeniería y Tecnología, Universidad San Sebastián, Lientur 1457, Concepción 4080871, Chile. · Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santos Dumont 964, Independencia, Santiago, Chile. · Núcleo de Biotecnología Curauma (NBC), Universidad Católica de Valparaíso, Av. Universidad 330, Curauma, Valparaíso, Chile. · Centro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Avenida Las Condes 12.438, Lo Barnechea Santiago, Chile. · Escuela de Obstetricia y Puericultura, Facultad de Salud, Universidad Bernardo OHiggins, Avenida Viel 1497, Santiago, Chile. · Laboratorio de Análisis por Activación Neutrónica, Comisión Chilena de Energía Nuclear (CChEN), Nueva Bilbao 12501, Santiago, Chile. ·Nanomedicine (Lond) · Pubmed #29972676.

ABSTRACT: AIM: To track early events during lung metastasis, we labeled cells expressing (B16F10 METHODS: B16F10 expressing or lacking CAV1 were labeled with AuNPs-PEG-TAT. The physicochemical properties and cytotoxicity of these nanoparticles, as well as their effects on migration and invasiveness of B16F10 cells in vitro were evaluated. Ex vivo lung distribution of the labeled cells after tail vein injection into C57BL/6 mice was examined. RESULTS: AuNPs-PEG-TAT did not affect B16F10 viability, migration and invasiveness. The metastatic and tumorigenic capability of the labeled B16F10 was also not modified in comparison to unlabeled B16F10 cells. CAV1 expression favored the retention of B16F10 cells in the lungs of mice 2 h post injection, suggesting CAV1 promoted adherence to endothelial cells and transendothelial migration. CONCLUSIONS: We developed a protocol to label B16F10 cells with AuNPs-PEG-TAT that permits subsequent tracking of cells in mice. CAV1 overexpression was found to increase retention and transendothelial migration of B16F10 cells in the lung.

13 Article Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy. 2018

González, Fermín E / Chernobrovkin, Alexey / Pereda, Cristián / García-Salum, Tamara / Tittarelli, Andrés / López, Mercedes N / Salazar-Onfray, Flavio / Zubarev, Roman A. ·Laboratory of Experimental Immunology & Cancer, Faculty of Dentistry, Universidad de Chile, 8380492 Santiago, Chile. · Millennium Institute on Immunology and Immunotherapy, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile. · Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden. · Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, Chile. · Laboratory of Molecular Virology, Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, School of Medicine, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile. · Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile. ·J Immunol Res · Pubmed #29744371.

ABSTRACT: Autologous dendritic cells (DCs) loaded with cancer cell-derived lysates have become a promising tool in cancer immunotherapy. During the last decade, we demonstrated that vaccination of advanced melanoma patients with autologous tumor antigen presenting cells (TAPCells) loaded with an allogeneic heat shock- (HS-) conditioned melanoma cell-derived lysate (called TRIMEL) is able to induce an antitumor immune response associated with a prolonged patient survival. TRIMEL provides not only a broad spectrum of potential melanoma-associated antigens but also danger signals that are crucial in the induction of a committed mature DC phenotype. However, potential changes induced by heat conditioning on the proteome of TRIMEL are still unknown. The identification of newly or differentially expressed proteins under defined stress conditions is relevant for understanding the lysate immunogenicity. Here, we characterized the proteomic profile of TRIMEL in response to HS treatment. A quantitative label-free proteome analysis of over 2800 proteins was performed, with 91 proteins that were found to be regulated by HS treatment: 18 proteins were overexpressed and 73 underexpressed. Additionally, 32 proteins were only identified in the HS-treated TRIMEL and 26 in non HS-conditioned samples. One protein from the overexpressed group and two proteins from the HS-exclusive group were previously described as potential damage-associated molecular patterns (DAMPs). Some of the HS-induced proteins, such as haptoglobin, could be also considered as DAMPs and candidates for further immunological analysis in the establishment of new putative danger signals with immunostimulatory functions.

14 Article Antitumor activity and carrier properties of novel hemocyanins coupled to a mimotope of GD2 ganglioside. 2018

Palacios, Miriam / Tampe, Ricardo / Del Campo, Miguel / Zhong, Ta-Ying / López, Mercedes N / Salazar-Onfray, Flavio / Becker, María Inés. ·Fundación Ciencia y Tecnología para el Desarrollo (FUCITED), Avenida Eduardo Castillo Velasco 2902, Santiago 7750269, 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. · Fundación Ciencia y Tecnología para el Desarrollo (FUCITED), Avenida Eduardo Castillo Velasco 2902, Santiago 7750269, Chile; Biosonda Corporation, Avenida Eduardo Castillo Velasco 2902, Santiago 7750269, Chile. Electronic address: mariaines.becker@fucited.cl. ·Eur J Med Chem · Pubmed #29524730.

ABSTRACT: Conjugation to carrier proteins is a way to improve the immunogenicity of peptides. Such is the case for peptides mimicking carbohydrate tumor-associated antigens in cancer vaccine development. The most used protein for this purpose is the keyhole limpet hemocyanin (KLH) from Megathura crenulata. Its limited bioavailability has prompted interest in finding new candidates; nevertheless, it is not known whether other hemocyanins might be equally efficient as carrier of carbohydrate peptide mimotopes to promotes anti-tumor responses. Here, we evaluated the carrier and antitumor activity of novel hemocyanins with documented immunogenicity obtained from Concholepas concholepas (CCH) and Fissurella latimarginata (FLH), coupled through sulfo-SMCC to P10, a mimetic peptide of GD2, the major ganglioside constituent of neuroectodermal tumors, and incorporating AddaVax as an adjuvant. The humoral immune responses of mice showed that CCH-P10 and FLH-P10 conjugates elicited specific IgM and IgG antibodies against P10 mimotope, similar to those obtained with KLH-P10, which was used as a positive control. The CCH-P10 and FLH-P10 antisera, exhibited cross-reactivity with murine and human melanoma cells, like anti-CCH and anti-FLH sera suggesting a cross-reaction of CCH and FLH glycosylations with carbohydrate epitopes on the tumor cell surfaces, similar to the KLH antisera. When mice were primed with each hemocyanin-P10 and challenged with melanoma cells, better antitumor effects were observed for FLH-P10 than for CCH-P10 and, as for KLH-P10, irrespective of conjugation. These data demonstrate that CCH and FLH are useful carriers of carbohydrate mimotopes; however, the best antitumor activity of FLH preparations, indicate that is a suitable candidate for further cancer vaccines research.

15 Article Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach. 2018

Ibacache, Juana Andrea / Faundes, Judith / Montoya, Margarita / Mejías, Sophia / Valderrama, Jaime A. ·Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Casilla 40, Santiago 9170022, Chile. juana.ibacache.r@usach.cl. · Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Casilla 40, Santiago 9170022, Chile. judith.faundes@usach.cl. · Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Casilla 40, Santiago 9170022, Chile. margarita.montoya@usach.cl. · Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Casilla 40, Santiago 9170022, Chile. sophia.mejias@usach.cl. · Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile. jaimeadolfov@gmail.com. ·Molecules · Pubmed #29462956.

ABSTRACT: The synthesis of five novel homodimers is reported based on the anilinoisoquinolinequinone scaffold. In these twin-drug derivatives, two units of the anilinoquinone pharmacophores are linked through a methylene spacer. The formation of dimers was achieved by reaction of isoquinolinequinones with 4, 4'-diaminodiphenylmethane via a sequence of two oxidative amination reactions. A preliminary in vitro screening of the homodimers reveals moderate to high cytotoxic activities against MDA-MB-21 breast adenocarcinoma and B16-F10 murine metastatic melanoma cell lines. The asymmetrical homodimer

16 Article Cytotoxicity of demalonyl thyrsiflorin A, a semisynthetic labdane-derived diterpenoid, to melanoma cells. 2018

Cardile, V / Avola, R / Graziano, A C E / Piovano, M / Russo, A. ·Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Via S. Sofia, 95123 Catania, Italy. · Department of Chemistry, University Técnica Federico Santa Maria, Casilla 110-V, Valparaìso, Chile. · Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. Electronic address: alrusso@unict.it. ·Toxicol In Vitro · Pubmed #29262311.

ABSTRACT: Diterpenes are compounds with complex structure and due to their unique carbon skeleton and interesting biological activities, have been the focus of continuous studies for the development of new anticancer agents. The plants of the genus Calceolaria (Scrophulariaceae family), native of South America have also yielded several new diterpenes with the scopadulane skeleton, such as thyrsiflorin A. The present study was undertaken to investigate the effect of the semisynthetic compound, demalonyl thyrsiflorin A on human melanoma cells. In A375 cells compound demalonyl thyrsiflorin A showed a clear dose-response relationship in the range of 6.25-50μM concentrations. In addition, we demonstrated an apoptotic response after treatment of cancer cells with this semisynthetic phenolic labdane diterpene at 6.25 and 12.5μM concentrations that probably involves the reduction of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of the caspase cascade at higher concentrations, 25 and 50μM, correlated with additional reactive oxygen species increase, probably switched the mode of demalonyl thyrsiflorin A-induced cell death from apoptosis to necrosis.

17 Article Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis. 2018

Del Castillo Velasco-Herrera, Martin / van der Weyden, Louise / Nsengimana, Jeremie / Speak, Anneliese O / Sjöberg, Marcela K / Bishop, David Timothy / Jönsson, Göran / Newton-Bishop, Julia / Adams, David J. ·Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. · Leeds Institute of Cancer and Pathology, St James's University Hospital, University of Leeds, UK. · Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. · Division of Oncology and Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Sweden. ·Mol Oncol · Pubmed #29193607.

ABSTRACT: Metastasis is the leading cause of death in patients with advanced melanoma, yet the somatic alterations that aid tumour cell dissemination and colonisation are poorly understood. Here, we deploy comparative genomics to identify and validate clinically relevant drivers of melanoma metastasis. To do this, we identified a set of 976 genes whose expression level was associated with a poor outcome in patients from two large melanoma cohorts. Next, we characterised the genomes and transcriptomes of mouse melanoma cell lines defined as weakly metastatic, and their highly metastatic derivatives. By comparing expression data between species, we identified lunatic fringe (LFNG), among 28 genes whose expression level is predictive of poor prognosis and whose altered expression is associated with a prometastatic phenotype in mouse melanoma cells. CRISPR/Cas9-mediated knockout of Lfng dramatically enhanced the capability of weakly metastatic melanoma cells to metastasise in vivo, a phenotype that could be rescued with the Lfng cDNA. Notably, genomic alterations disrupting LFNG are found exclusively in human metastatic melanomas sequenced as part of The Cancer Genome Atlas. Using comparative genomics, we show that LFNG expression plays a functional role in regulating melanoma metastasis.

18 Article In vivo knockdown of antisense non-coding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization. 2018

Varas-Godoy, Manuel / Lladser, Alvaro / Farfan, Nicole / Villota, Claudio / Villegas, Jaime / Tapia, Julio C / Burzio, Luis O / Burzio, Veronica A / Valenzuela, Pablo D T. ·Fundación Ciencia & Vida, Santiago, Chile. · Center for Biomedical Research, Faculty of Medicine, Universidad de los Andes, Santiago, Chile. · Andes Biotechnologies SpA, Santiago, Chile. · Department of Biological Sciences, Universidad Andrés Bello, Santiago, Chile. · Department of Chemical and Biological Sciences, Faculty of Health, Universidad Bernardo O Higgins, Santiago, Chile. · Cell Transformation Laboratory, Department of Basic and Clinical Oncology, Faculty of Medicine, Universidad de Chile, Santiago, Chile. ·Pigment Cell Melanoma Res · Pubmed #28707763.

ABSTRACT: The family of non-coding mitochondrial RNAs (ncmtRNA) is differentially expressed according to proliferative status. Normal proliferating cells express sense (SncmtRNA) and antisense ncmtRNAs (ASncmtRNAs), whereas tumor cells express SncmtRNA and downregulate ASncmtRNAs. Knockdown of ASncmtRNAs with oligonucleotides induces apoptotic cell death of tumor cells, leaving normal cells unaffected, suggesting a potential application for developing a novel cancer therapy. In this study, we knocked down the ASncmtRNAs in melanoma cell lines with a lentiviral-encoded shRNA approach. Transduction with lentiviral constructs targeted to the ASncmtRNAs induced apoptosis in murine B16F10 and human A375 melanoma cells in vitro and significantly retarded B16F10 primary tumor growth in vivo. Moreover, the treatment drastically reduced the number of lung metastatic foci in a tail vein injection assay, compared to controls. These results provide additional proof of concept to the knockdown of ncmtRNAs for cancer therapy and validate lentiviral-shRNA vectors for gene therapy.

19 Article A short hairpin RNA-based adjuvant targeting NF-κB repressor IκBα promotes migration of dermal dendritic cells to draining lymph nodes and antitumor CTL responses induced by DNA vaccination. 2017

Gálvez-Cancino, Felipe / Roco, Jonathan / Rojas-Colonelli, Nicole / Flores, Camila / Murgas, Paola / Cruz-Gómez, Sebastián / Oyarce, César / Varas-Godoy, Manuel / Sauma, Daniela / Lladser, Alvaro. ·Laboratorio de Inmunoterapia Génica, Fundación Ciencia & Vida, Av. Zañartu 1482, Santiago 7780272, Chile. · Centro de Investigación Biomédica, Facultad de Medicina, Universidad de los Andes, Santiago, Chile. · Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile. · Laboratorio de Inmunoterapia Génica, Fundación Ciencia & Vida, Av. Zañartu 1482, Santiago 7780272, Chile. Electronic address: alladser@cienciavida.org. ·Vaccine · Pubmed #28666759.

ABSTRACT: DNA vaccination is an attractive approach to elicit tumor-specific cytotoxic CD8

20 Article In Vivo Reflectance Confocal Microscopy for the Diagnosis of Melanoma and Melanotic Macules of the Lip. 2017

Uribe, Pablo / Collgros, Helena / Scolyer, Richard A / Menzies, Scott W / Guitera, Pascale. ·Department of Dermatology, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. · Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, Australia. · Melanoma Institute Australia, Sydney, New South Wales, Australia. · Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia. · The University of Sydney, Sydney, New South Wales, Australia. ·JAMA Dermatol · Pubmed #28467525.

ABSTRACT: Importance: Benign melanotic macules (MAC) are the most frequent cause of lip pigmentation and sometimes difficult to differentiate from lip melanoma (MEL). Objectives: To report in vivo reflectance confocal microscopy (RCM) features of normal lips of different phototypes and to identify features that assist in distinguishing MEL from MAC using dermoscopy and RCM. Design, Setting, and Participants: For this retrospective observational study, 2 groups of patients from 2 tertiary referral centers for melanoma (Sydney Melanoma Diagnostic Centre and Melanoma Institute Australia) were recruited between June 2007 and January 2015. Group 1 included patients with normal lips and different phototypes, and Group 2 consisted of patients with MAC and MEL; RCM and dermoscopy were used for lips analysis. Main Outcomes and Measures: Overall, 92 RCM features were correlated with clinical history, dermoscopic images, and histopathology in all patients with MEL and 5 patients with MAC. Results: Images from the vermillion and/or mucosal part of the lip were recorded from 10 patients with clinically normal lips (mean [SD] age, 34.5 [6.1] years), 16 patients with MAC (mean [SD] age, 49.6 [17.9] years), and 5 patients with 6 cases of MEL (1 patient had a recurrent lesion; mean [SD] age, 56.2 [15.5] years). In normal lips, the draped pattern-a previously described MAC RCM feature-was identified in all cases. In MEL, the following findings were frequent and significantly different from MAC: epidermal disarray; pagetoid infiltration of dendritic and/or round cells; a nonspecific architectural pattern at the dermoepidermal junction (DEJ); nonhomogenously distributed papillae; continuous (lentiginous) proliferation of cells with marked atypia at the DEJ, especially in interpapillary spaces; a higher number of dendritic cells (especially roundish); and atypical round cells at the DEJ. The cellular body area of dendritic cells was about the double in MEL compared with MAC. An RCM lip algorithm was developed that provided 100% sensitivity and 88% specificity for the diagnosis of MEL of the vermillion and mucosal part of the lip. With dermoscopy, MAC were correctly classified as benign in 13 of 16 cases (81%) and MEL were classified as equivocal or malignant in 5 of 6 cases (83%). Conclusions and Relevance: Reflectance confocal microscopy can assist in the differential diagnosis of lip MEL and MAC. An RCM Lip Score that we developed based on study results is proposed and needs to be validated on an independent data set.

21 Article Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8 2017

Figueroa, Claudio / Gálvez-Cancino, Felipe / Oyarce, Cesar / Contreras, Francisco / Prado, Carolina / Valeria, Catalina / Cruz, Sebastián / Lladser, Alvaro / Pacheco, Rodrigo. ·Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile; Departamento de Ciencias Biológicas y Químicas, Facultad de Ciencia, Universidad San Sebastián, Providencia, 7510157 Santiago, Chile. · Laboratorio de Inmunoterapia Génica, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile; Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, 8370146 Santiago, Chile. · Laboratorio de Inmunoterapia Génica, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile. · Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile. · Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile; Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, 8370146 Santiago, Chile. Electronic address: rpacheco@cienciavida.org. ·J Neuroimmunol · Pubmed #28077213.

ABSTRACT: Dendritic cells (DCs) display the unique ability for cross-presenting antigens to CD8

22 Article Patterns and Timing of Initial Relapse in Pathologic Stage II Melanoma Patients. 2017

Lee, Ann Y / Droppelmann, Nicolas / Panageas, Katherine S / Zhou, Qin / Ariyan, Charlotte E / Brady, Mary S / Chapman, Paul B / Coit, Daniel G. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · New York University School of Medicine, New York, NY, USA. · Catholic University of Chile School of Medicine, Santiago, Chile. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. coitd@mskcc.org. ·Ann Surg Oncol · Pubmed #27804026.

ABSTRACT: PURPOSE: Pathologic stage II melanoma patients have variable outcomes when divided by substage. We hypothesized that an understanding of the patterns of initial relapse by substage will better inform follow-up guidelines. METHODS: We performed a retrospective review of 738 adult patients with pathologic stage II cutaneous melanoma treated at Memorial Sloan Kettering Cancer Center between 1993 and 2013. Clinical records were reviewed to determine time, location, and method of detection of initial relapse. RESULTS: At a median follow-up of 52 months, 219 patients relapsed. Relapses were detected more frequently in higher substages. Initial relapses were most commonly local/in-transit for IIA and IIB and systemic for IIC. Lung and brain were the most frequent sites of systemic relapse. Patient-detection was the most common method of relapse detection (59%) in all substages. The 5-year cumulative incidence for patient-detected relapse was 13.6% for IIA, 18.9% for IIB, and 23.3% for IIC and for image-detected relapse was 3.4, 7.9, and 16.6%, respectively. The 5-year cumulative incidence for physician-detected relapse was less than 10% across all substages and leveled off at 3 years for stage IIA and IIB and 2 years for stage IIC. CONCLUSIONS: Relapses were most frequently patient-detected in all stage II substages, highlighting the importance of patient education and self-examination. The highest yield for routine imaging is in stage IIC patients during the first 4 years. Physician examination is unlikely to detect relapses beyond 3 years for stage IIA and IIB and beyond 2 years for stage IIC patients.

23 Article Intralesional (incision) biopsy for melanoma diagnosis: the rules and the exception. 2017

Moscarella, Elvira / Argenziano, Giuseppe / Moreno, Claudia / Piana, Simonetta / Lallas, Aimilios / Lombardi, Mara / Longo, Caterina / Ferrara, Gerardo. ·Unit of Dermatology and Skin Cancer - elvira.moscarella@gmail.com. · st Medical Department, Arcispedale Santa Maria Nuova Institute for Research and Care, Reggio Emilia, Italy. · Department of Dermatology, Second University of Naples, Naples, Italy. · Department of Dermatology, Clinical Hospital University of Chile, Santiago, Chile. · Unit of Dermatology and Skin Cancer. · Department of Dermatopathology, Arcispedale Santa Maria Nuova Institute for Research and Care, Reggio Emilia, Italy. ·G Ital Dermatol Venereol · Pubmed #27096540.

ABSTRACT: Intralesional (incision) biopsy for melanoma diagnosis can be warranted for large lesions or for those lesions whose in-toto excision leads to cosmetic and/or functional impairment. However, this diagnostic approach carries a risk of underdiagnosis, if a clinicopathologic diagnostic approach is not implemented. As a rule, in large pigmented lesions from special body areas (scalp and acral skin), clinicodermoscopic differential diagnosis of melanoma includes non-melanocytic skin lesions, traumatic skin changes, and nevi. The unique indication to incision biopsy for the differential diagnosis between nevus and melanoma is a relatively small nodular proliferation developing within a medium-large congenital nevus.

24 Article Pigmented basal cell carcinoma mimicking a superficial spreading melanoma. 2016

Hasbún Acuña, Paula / Cullen Aravena, Roberto / Maturana Donaire, César / Ares Mora, Raúl / Porras Kusmanic, Ninoska. ·Teledermatología, Centro de especialidades San Lázaro, Puente Alto, Santiago, Chile. Address: Centro de especialidades primarias San Lázaro, Sargento Menadier 1092, Puente Alto, Santiago, Chile. Email: hasbuna@gmail.com. · Facultad de Medicina, Universidad de los Andes, Santiago, Chile. · Anatomía Patológica, Hospital Clínico Metropolitano La Florida Doctora Eloísa Díaz Insunza, Santiago, Chile. · Departamento de Dermatología, Hospital Clínico Metropolitano La Florida Doctora Eloísa Díaz Insunza, Santiago, Chile. ·Medwave · Pubmed #28076343.

ABSTRACT: Basal cell carcinoma is the most common form of skin cancer, especially in elderly people. Pigmented basal cell carcinoma is a rare subtype and has been described in the literature as a nodular and hyperpigmented lesion; rarely, it can appear as an extensive pigmented plate, which may be clinically indistinguishable from superficial spreading melanoma and Bowen disease. Dermatoscopy has a high sensitivity in the diagnosis of basal cell carcinoma. When Menzies criteria are used; however, the final diagnosis is made by histopathology. The objective of the present report is to analyze the case of a patient with pigmented basal cell carcinoma simulating a superficial spreading melanoma.

25 Article Melanocytoma-like melanoma may be the missing link between benign and malignant uveal melanocytic lesions in humans and dogs: a comparative study. 2016

Zoroquiain, Pablo / Mayo-Goldberg, Erin / Alghamdi, Sarah / Alhumaid, Sulaiman / Perlmann, Eduardo / Barros, Paulo / Mayo, Nancy / Burnier, Miguel N. ·aHenry C Witelson Ocular Pathology Laboratory, Department of Pathology Departments of bEpidemiology cOphthalmology, McGill University, Montreal, Quebec, Canada dDepartment of Pathology, School of Medicine, Pontificial Catholic University of Chile, Santiago, Chile. ·Melanoma Res · Pubmed #27571324.

ABSTRACT: The cutoff presented in the current classification of canine melanocytic lesions by Wilcock and Pfeiffer is based on the clinical outcome rather than morphological concepts. Classification of tumors based on morphology or molecular signatures is the key to identifying new therapies or prognostic factors. Therefore, the aim of this study was to analyze morphological findings in canine melanocytic lesions based on classic malignant morphologic principles of neoplasia and to compare these features with human uveal melanoma (HUM) samples. In total, 64 canine and 111 human morphologically malignant melanocytic lesions were classified into two groups (melanocytoma-like or classic melanoma) based on the presence or absence of M cells, respectively. Histopathological characteristics were compared between the two groups using the χ-test, t-test, and multivariate discriminant analysis. Among the 64 canine tumors, 28 (43.7%) were classic and 36 (56.3%) were melanocytoma-like melanomas. Smaller tumor size, a higher degree of pigmentation, and lower mitotic activity distinguished melanocytoma-like from classic tumors with an accuracy of 100% for melanocytoma-like lesions. From the human series, only one case showed melanocytoma-like features and had a low risk for metastasis characteristics. Canine uveal melanoma showed a morphological spectrum with features similar to the HUM counterpart (classic melanoma) and overlapped features between uveal melanoma and melanocytoma (melanocytoma-like melanoma). Recognition that the subgroup of melanocytoma-like melanoma may represent the missing link between benign and malignant lesions could help explain the progression of uveal melanoma in dogs; these findings can potentially be translated to HUM.

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