SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein whose overexpression in malignant or tumor-stromal cells is often associated with increased aggressiveness and bad prognosis in a wide range of human cancer types, particularly melanoma. We established the impact that changes in the level of SPARC produced by malignant cells and neighboring stromal cells have on melanoma growth. Melanoma cell growth in monolayer was only slightly affected by changes in SPARC levels. However, melanoma growth in spheroids was strongly inhibited upon SPARC hyperexpression and conversely enhanced when SPARC expression was downregulated. Interestingly, SPARC overexpression in neighboring fibroblasts had no effect on spheroid growth irrespective of SPARC levels expressed by the melanoma cells, themselves. Downregulation of SPARC expression in melanoma cells induced their rejection in vivo through a mechanism mediated exclusively by host polymorphonuclear cells. On the other hand, SPARC hyperexpression enhanced vascular density, collagen deposition, and fibroblast recruitment in the surrounding stroma without affecting melanoma growth. In agreement with the in vitro data, overexpression of SPARC in co-injected fibroblasts did not affect melanoma growth in vivo. All the data indicate that melanoma growth is not subject to regulation by exogenous SPARC, nor by stromal organization, but only by SPARC levels produced by the malignant cells themselves.Facultad de Ciencias Veterinaria

SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein whose overexpression in malignant or tumor-stromal cells is often associated with increased aggressiveness and bad prognosis in a wide range of human cancer types, particularly melanoma. We established the impact that changes in the level of SPARC produced by malignant cells and neighboring stromal cells have on melanoma growth. Melanoma cell growth in monolayer was only slightly affected by changes in SPARC levels. However, melanoma growth in spheroids was strongly inhibited upon SPARC hyperexpression and conversely enhanced when SPARC expression was downregulated. Interestingly, SPARC overexpression in neighboring fibroblasts had no effect on spheroid growth irrespective of SPARC levels expressed by the melanoma cells, themselves. Downregulation of SPARC expression in melanoma cells induced their rejection in vivo through a mechanism mediated exclusively by host polymorphonuclear cells. On the other hand, SPARC hyperexpression enhanced vascular density, collagen deposition, and fibroblast recruitment in the surrounding stroma without affecting melanoma growth. In agreement with the in vitro data, overexpression of SPARC in co-injected fibroblasts did not affect melanoma growth in vivo. All the data indicate that melanoma growth is not subject to regulation by exogenous SPARC, nor by stromal organization, but only by SPARC levels produced by the malignant cells themselves.Facultad de Ciencias Veterinaria

SPARC Endogenous Level, rather than Fibroblast-Produced SPARC or Stroma Reorganization Induced by SPARC, Is Responsible for Melanoma Cell Growth

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein whose overexpression in malignant or tumor-stromal cells is often associated with increased aggressiveness and bad prognosis in a wide range of human cancer types, particularly melanoma. We established the impact that changes in the level of SPARC produced by malignant cells and neighboring stromal cells have on melanoma growth. Melanoma cell growth in monolayer was only slightly affected by changes in SPARC levels. However, melanoma growth in spheroids was strongly inhibited upon SPARC hyperexpression and conversely enhanced when SPARC expression was downregulated. Interestingly, SPARC overexpression in neighboring fibroblasts had no effect on spheroid growth irrespective of SPARC levels expressed by the melanoma cells, themselves. Downregulation of SPARC expression in melanoma cells induced their rejection in vivo through a mechanism mediated exclusively by host polymorphonuclear cells. On the other hand, SPARC hyperexpression enhanced vascular density, collagen deposition, and fibroblast recruitment in the surrounding stroma without affecting melanoma growth. In agreement with the in vitro data, overexpression of SPARC in co-injected fibroblasts did not affect melanoma growth in vivo. All the data indicate that melanoma growth is not subject to regulation by exogenous SPARC, nor by stromal organization, but only by SPARC levels produced by the malignant cells themselves

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy

Protein kinase C and cancer: what we know and what we do not

Since their discovery in the late 1970’s, protein kinase C (PKC) isozymes represent one of the most extensively studied signaling kinases. PKCs signal through multiple pathways and control the expression of genes relevant for cell cycle progression, tumorigenesis and metastatic dissemination. Despite the vast amount of information concerning the mechanisms that control PKC activation and function in cellular models, the relevance of individual PKC isozymes in the progression of human cancer is still a matter of controversy. Although the expression of PKC isozymes is altered in multiple cancer types, the causal relationship between such changes and the initiation and progression of the disease remains poorly defined. Animal models developed in the last years helped to better understand the involvement of individual PKCs in various cancer types and in the context of specific oncogenic alterations. Unraveling the enormous complexity in the mechanisms by which PKC isozymes impact on tumorigenesis and metastasis is key for reassessing their potential as pharmacological targets for cancer treatment

Genetic events in sporadic colorectal adenomas: K-ras and p53 heterozygous mutations are not sufficient for malignant progression.

Twenty-four sporadic colorectal adenomas were analysed for the presence of allelic loss on the short arm of chromosome 17 as well as mutations in the K-ras and p53 genes. Chromosome 17p13 allelic loss was not present in 14 out of 14 informative cases. K-ras mutations were observed in 15 out of 24 cases. A p53 gene mutation (GGC --> GAC at codon 245) was detected in two biopsies taken at a four year interval from a recurrent rectal villous adenoma. Both biopsies also contained the same K-ras gene mutation (GGT --> GTT at codon 12). The data from the recurrent rectal adenoma provide in vivo evidence that K-ras and p53 heterozygous mutations confer a proliferative advantage but together are not sufficient for malignant transformation

A Circadian Genomic Signature Common to Ketamine and Sleep Deprivation in the Anterior Cingulate Cortex

BackgroundConventional antidepressants usually require several weeks to achieve a full clinical response in patients with major depressive disorder, an illness associated with dysregulated circadian rhythms and a high incidence of suicidality. Two rapid-acting antidepressant strategies, low-dose ketamine (KT) and sleep deprivation (SD) therapies, dramatically reduce depressive symptoms within 24 hours in a subset of major depressive disorder patients. However, it is unknown whether they exert their actions through shared regulatory mechanisms. To address this question, we performed comparative transcriptomics analyses to identify candidate genes and relevant pathways common to KT and SD.MethodsWe used the forced swim test, a standardized behavioral approach to measure antidepressant-like activity of KT and SD. We investigated gene expression changes using high-density microarrays and pathway analyses (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis) in KT- and SD-treated mice compared with saline-treated control male mice.ResultsWe show that KT and SD elicit common transcriptional responses implicating distinct elements of the circadian clock and processes involved in neuronal plasticity. There is an overlap of 64 genes whose expression is common in KT and SD. Specifically, there is downregulation of clock genes including Ciart, Per2, Npas4, Dbp, and Rorb in both KT- and SD-treated mice.ConclusionsWe demonstrate a potential involvement of the circadian clock in rapid antidepressant responses. These findings could open new research avenues to help design chronopharmacological strategies to treat major depressive disorder

CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome

Background and ObjectivesTo investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study.MethodsAlbuminocytologic dissociation (ACD) was defined as an increased protein level (&gt;0.45 g/L) in the absence of elevated white cell count (&lt;50 cells/L). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%).ResultsIn 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, &gt;4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was &lt;5 cells/L in 1,005 patients (83%), 5-49 cells/L in 200 patients (16%), and ≥50 cells/L in 13 patients (1%).DiscussionACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/L, is compatible with GBS after a thorough exclusion of alternative diagnoses.Classification of EvidenceThis study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS.</p

Carta de Psicología No. 54

El capital psicológico y el engagement en el trabajo: revisión teórica / Angie Lorena Escobar Giraldo, Carol Valentina Londoño Pantoja y Laura Valentina Rojas Montealegre. Relación entre clima organizacional y engagement desde una mirada del modelo de Avalores en competencia / Karol Sunev Encinales y Angie Julieth Riaño. Relación de los estilos de liderazgo transformacional y transaccional en el clima organizacional: una revisión de la literatura / Leidy Tatiana Javela Avila y Angie Johana Maldonado Bejarano. El bienestar organizacional: una revisión teórica desde lo hedónico y lo eudaimónico / Astrid Carolina Rodríguez Prieto, Daniela Sthefania Pérez Arango y Laura Jimena Mondragón. Estudio comparativo de la normatividad en torno al acoso laboral / Magda Cardozo y Paola Andrea Rubiano. Análisis del estilo lingüístico prosocial y altruista / Luis Fernando Benedetti, Luisa Fernanda Martínez y Juan Camilo Carvajal-Builes. Violencia intrafamiliar como una problemática juvenil en Colombia / María José Saavedra Vargas y Daniela Barbosa Ardila. Análisis psicológico de la trata de personas con fines / María José Saavedra Vargas y Daniela Barbosa Ardila. Sobre el reciclaje: su debida ejecución y su importancia para el medio ambiente / María Camila Londoño Fernández y Camilo Jesús Alejandro Vivas Becerra. Estrategias de aprendizaje espacial con apoyo virtual en hombres y mujeres desde una visión evolutiva / Natalia Pareja Henao, J. Jacobo Pinto Galindo, Esteban Ayala Vargas, Ivonne Edith Alejo Castañeda y Tatiana Manrique Zuluaga. La música favorece la atención en niños / Manuela María del Rocío Pinzón, Laura Geraldine Cortés, Tatiana Manrique Zuluaga e Ivonne Edith Alejo Castañeda. La autorregulación y la autonomía, un abordaje desde la psicología del desarrollo infantil / Diana Paola Pardo Galvis, Lizeth Tatiana Herrera Toro y Julieth María Ospina Osorio. Importancia e incidencia de la vocación y la profesión en el sector social LGBTIQ / Lieen D. Guevara G. Sistema de Responsabilidad Penal para Niños o Adolescentes (SRPA) en Colombia / Diana Paola Pardo Galvis, Lizeth Tatiana Herrera Toro y Erika Natalia Algarra Martínez. Breve revisión de la importancia del desarrollo de los niños, niñas y adolescentes (NNA) y sus derechos de participación dentro del contexto sociopolítico / Daniela Barbosa Ardila y María José Saavedra Vargas. “Verdad y mentira”: conceptos relacionados con el ejercicio de la psicología del testimonio / María Paula Castro y Juan Camilo Carvajal-Builes. Comportamientos de violencia conyugal naturalizados por jóvenes universitarios de Bogotá / Daniela Alejandra Martínez Sarmiento, María Fernanda Nieto Ramírez, Laura Andrea Torres Pulido, María Emily Triana Jiménez y Darío León Rincó