La mayoría de los reportes realizados en los países con alta incidencias en melanoma de tipo cutáneos, son realizados en pacientes de raza blanca, con predominio del subtipo histológico, melanoma de extensión superficial, pero en países como latinoamericanos, africanos u orientales, existe una alta incidencia de melanomas de tipo lentiginoso acral, en los que predominan en pacientes de raza no blanca. En el Perú, existe pocos estudios relacionados con esta neoplasia, de ahí la realización de este estudio de tipo descriptivo y retrospectivo, con la finalidad de proporcionar información sobre las características histopatológicas, clínicas y la supervivencia asociado a factores pronósticos en pacientes que fueron diagnosticados en el Hospital Nacional Edgardo Rebagliati Martins, Lima-Perú, uno de los centros hospitalarios de referencia para pacientes asegurados, en el periodo comprendido desde el 01 enero del 2002 al 31 de diciembre 2011. Debido a que esta neoplasia representa un problema en el sector de salud por aumento en su incidencia, demora en el diagnóstico, poca respuesta al tratamiento de ciertos tipos histológicos de melanoma, se busca evitar que pacientes con factores de riesgo para desarrollar melanoma de tipo cutáneo o mucoso, progresen a la enfermedad; mediante la adopción de medidas profilácticas adecuadas o mediante las extirpaciones de lesiones premalignas, por tanto es importante el conocimiento y la difusión de información a la población sobre la enfermedad. / Trabajo académico

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / In this research paper, we proposed an extended model for the early detection of skin cancer... The purpose is reduce the waiting time to obtaining a diagnosis, in addition, the function of the dermatoscope has been digitized by using a Smartphone and magnifying lenses as an accessory the mobile device. The proposed model has five phases: 1. The patient is attended by a general practitioner or nurse previously trained in any health center which has WiFi or mobile network connectivity to record their data and capture the skin lesion that will be analyzed. 2) The image will be in the cloud storage, which at the same time feeds an exclusive access website of dermatologists.3) Images are analyzed in real time using an image recognition service provided by IBM, which is integrated into a cloud-hosted web platform and an-Android application. 4)The result of the image processing is visualized by the dermatologist who makes a remote diagnosis.5) This diagnosis is received by the general practitioner or nurse, responsible for transmitting the diagnosis and treatment to the patient. This model was validated in a group of 60 patients, where 28 suffer from skin cancer in the early stage, 12 in the late stage and 20 are healthy patients, in a network of clinics in Lima, Peru. The obtained result was 97.5% of assertiveness on the analyzed skin lesions and 95% in healthy patients. / Revisión por pares

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PURPOSE: Uveal melanoma (UM) is the most common intraocular malignancy in adults with an incidence of six per one million individuals each year. Globe conserving treatments are currently the standard of care, but unfortunately, despite successful local control, a substantial mortality risk exists due to eventual emergence of distant metastasis, which is invariably lethal. There is therefore an unmet need for novel, effective, targeted therapies for metastatic UM. Somatic mutations in the G-protein α subunits, Gαq and Gα, are present in a mutually exclusive pattern in approximately 80% of UMs, and they abolish the GTPase activity, resulting in a constitutively active protein. We have previously demonstrated that GNAQ-mutant (GNAQ^mt) UMs are addicted to the oncogenic effect of the mutant GNAQ protein and dissected the GNAQ pathway in an attempt to identify druggable targets. Our findings that the mutant GNAQ protein activates the PKC/PKD axis, which activates beta-catenin (β-Catenin), prompted us to investigate the role of PKC and β-Catenin in GNAQ^mt UM. EXPERIMENTAL DESIGN: The GNAQ^mt UM cell lines Mel202 and OMM1.3 were treated with either the PKC inhibitor bisindolylmaleimide I (BIM) alone, the Wnt/β-Catenin inhibitors FH535 or cardamonin alone, the Wnt/β-Catenin activator Wnt-3a alone, or siRNAs for β-Catenin in combination with BIM, and their viability was assessed with the MTT assay. Levels of β-Catenin, phosphorylated AKT, ERK1/2, caspase 3 and LC3BII were assessed with western blotting. β-Catenin mRNA levels were assessed with microarray analysis and RT-PCR. RESULTS: GNAQ^mt UM cells are very sensitive to PKC inhibition and respond with a decrease in cell viability that involves autophagy and cleavage and translocation of LC3BII in autophagosomes, but not caspase activation. PKC inhibition results in the upregulation of β-Catenin protein, but not mRNA levels, through a post-translational mechanism that involved the phosphorylation and activation of AKT, but not ERK1/2. β-Catenin inhibition by either small molecule inhibitors or siRNA resulted in a dose-dependent increase of cell proliferation, whereas β-Catenin activation by Wnt-3a had the opposite effects, resulting in a decrease in cell viability. CONCLUTIONS: Our study demonstrates that PKC is a mediator of the oncogenic effect of mutant Gα protein in UM through the Wnt-3/β-Catenin signaling pathway. These results open exciting opportunities for the development of personalized targeted therapies for UM in a genotype-dependent fashion.

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Signal Transducer and Activator of Transcription (STAT) 2 is one of seven members of the STAT family of transcription factors with dual roles in signal transduction and gene activation. STAT2 is a central transcription factor that regulates the antiviral, apoptotic and cell growth inhibitory effects of type I interferons (IFN-α/β), a small family of secreted glycoproteins induced by the host after sensing the presence of tumor cells and pathogens. The creation of Stat2-/- mice established the pivotal role of STAT2 in type I IFN signaling and in antiviral immunity. In vitro studies conducted in STAT2 deficient tumor cell lines suggested a role in suppressing tumor cell growth in response to IFN treatment. Based on these properties STAT2 is presumed to have tumor suppressor functions but data to support this notion in animal models of cancer are limited. To address the role of STAT2 in cancer, I used the murine B16-F1 tumor transplantation model of human melanoma. The B16-F1 melanoma cell line was established from a spontaneous tumor that arose in mice. I discovered that tumor cells transplanted subcutaneously in Stat2-/- mice grew more aggressively than in the counterpart wild type mice. Closer examination of B16-F1 tumors harvested from wild type and Stat2-/- mice revealed an unexpected dramatic similar reduction of STAT2 and STAT1 proteins. Yet soluble factors secreted by B16-F1 tumors established in Stat2-/- mice alone were sufficient to enhance proliferation of B16-F1 tumor cells. I further showed that tumor-bearing wild type mice treated with IFN-β developed smaller tumors compared to Stat2-/- mice, whose tumors continued to grow and hence were unresponsive to IFN intervention. Lastly, to elucidate a mechanism that leads to enhanced tumor growth in Stat2-/- mice, I questioned the involvement of the host immune response in restricting tumor growth. I found that tumor specific T cell priming by Stat2-/- dendritic cells (DCs) was defective since generated cytotoxic T cells (CD8+ T lymphocytes) produced low levels of IFN-γ and IL-2 and adoptive transfer of these B16-F1 tumor specific CD8+ T cells in B16-F1 bearing Stat2-/- mice did not cause tumor regression with IFN-β intervention. Collectively, my findings reveal that host STAT2 restricts the establishment of melanoma tumors. More importantly, type I IFN/STAT2 signaling on DCs plays a pivotal role in tumor antigen cross-presentation to CD8+ T cells and in the development of a protective antitumor response resulting in tumor rejection. To now address whether STAT2 expression in cancer cells could influence tumor establishment and the antitumor effects of type I IFNs, STAT2 expression was silenced in B16-F1 tumor cells. Contrary to my expectation, silencing STAT2 augmented the growth inhibitory effects of IFN-β both in vitro and in vivo. However, loss of STAT2 expression in the tumor did not cause B16-F1 tumor cells to grow more aggressively compared to control B16-F1 cells. Furthermore, compared to B16-F1 control cells, STAT2-silenced B16-F1 cells showed an initial delay but later persistent STAT activation and formation of the ISGF3 transcriptional complex (consisting of STAT1, STAT2 and IRF9). This observation paralleled with an initial delay and then later an increase in the expression of IFN regulated genes. In addition, reduced activation of STAT5 induced by IFN-β was observed in STAT2-silenced B16-F1 cells. This may partially explain the enhanced growth inhibitory effects of type I IFNs. Together these results shed light on the unexpected role of tumor STAT2 expression in diminishing the efficacy of type I IFN treatment of melanoma. / Biochemistry