Analyzing Digital Image by Deep Learning for Melanoma Diagnosis

Image classi cation is an important task in many medical applications, in order to achieve an adequate diagnostic of di erent le- sions. Melanoma is a frequent kind of skin cancer, which most of them can be detected by visual exploration. Heterogeneity and database size are the most important di culties to overcome in order to obtain a good classi cation performance. In this work, a deep learning based method for accurate classi cation of wound regions is proposed. Raw images are fed into a Convolutional Neural Network (CNN) producing a probability of being a melanoma or a non-melanoma. Alexnet and GoogLeNet were used due to their well-known e ectiveness. Moreover, data augmentation was used to increase the number of input images. Experiments show that the compared models can achieve high performance in terms of mean ac- curacy with very few data and without any preprocessing.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Análise bioquímica e microbiológica salivar no diagnóstico da doença periodontal, através de gêmeas univitelinas

Vários pesquisadores já isolaram marcadores biológicos da saliva, seja de origem bacteriana ou do hospedeiro e que se apresentaram como promissores para o diagnóstico periodontal, entre eles: elastase, colagenase e gelatinase. Além disso, a saliva tem sido considerada como excelente meio para detecção de periodontopatógenos. Este estudo mostra o caso clínico de duas pacientes gêmeas univitelinas, portadoras de periodontite do adulto severa, que se submeteram ao teste salivar para análise bioquímica e microbiológica antes e após a terapia periodontal convencional. Uma das irmãs, a Mz. C. O. foi medicada com Amoxicilina e Metronidazol após o primeiro teste salivar. Os periodontopatógenos encontrados no exame inicial desta paciente foram: 90% de Bacteróides forsythus, 75,8% de Actinobacillus actinomycemtecomitans, 70,5% de Porphiromonas gingivalis e 65,7% de Peptostreptococcus anaerobius e após terapia periodontal encontrou-se 15% de B. forsythus e 18% de A. actinomicemtecomitans. No exame inicial de Mr. C. O. os seguintes resultados foram obtidos: 95% de B. forsythos, 78,4% de A.actinomicemtecomitans, 75,5% de P. gingivalis e 70,5% de P. anaerobius e no segundo exame os resultados obtidos foram de 85% de B.forsythos, 50% de P. gingivalis e 15% de P.anaerobius. Vale ressaltar que as pacientes não haviam concluído o tratamento periodontal até a realização do segundo exame. Conclui-se portanto que o exame bioquímico e microbiológico salivar é válido para avaliação da condição periodontal e da terapia empregada

Balanço hidrológico da microbacia do córrego lageado, Município de Uberaba-MG, para o ano de 2012.

O manejo integrado em microbacia hidrográfica implementa uma nova maneira de se planejar e usar os recursos naturais, indo de encontro ao desenvolvimento sustentável. A compreensão do balanço hídrico, mesmo que de forma simplificada, é importante para o entendimento dos processos de degradação e conservação dos recursos naturais relacionados ao uso do solo e da água. Dentro deste contexto, o presente estudo teve por objetivo fazer o balanço hídrico da microbacia do córrego Lageado, situada no município de Uberaba, MG, para o ano de 2012. A escolha desta microbacia para este trabalho baseou-se na sua importância como terceiro maior manancial pertencente à APA (Área de Proteção Ambiental) do rio Uberaba e por estar parcialmente dentro do perímetro urbano. Nas últimas décadas, esta microbacia hidrográfica passou por intensas transformações relacionadas ao uso e à ocupação do solo

Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer

Phosphatases have long been regarded as tumor suppressors, however there is emerging evidence for a tumor initiating role for some phosphatases in several forms of cancer. Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP; acid phosphatase 1 [ACP1]) is an 18 kDa enzyme that influences the phosphorylation of signaling pathway mediators involved in cancer and is thus postulated to be a tumor-promoting enzyme, but neither unequivocal clinical evidence nor convincing mechanistic actions for a role of LMWPTP have been identified. In the present study, we show that LMWPTP expression is not only significantly increased in colorectal cancer (CRC), but also follows a step-wise increase in different levels of dysplasia. Chemical inhibition of LMWPTP significantly reduces CRC growth. Furthermore, downregulation of LMWPTP in CRC leads to a reduced migration ability in both 2D- and 3D-migration assays, and sensitizes tumor cells to the chemotherapeutic agent 5-FU. In conclusion, this study shows that LMWPTP is not only overexpressed in colorectal cancer, but it is correlated with the malignant potential of this cancer, suggesting that this phosphatase may act as a predictive biomaker of CRC stage and represents a rational novel target in the treatment of this disease.6108300831

Violacein Induces Death of Resistant Leukaemia Cells via Kinome Reprogramming, Endoplasmic Reticulum Stress and Golgi Apparatus Collapse

It is now generally recognised that different modes of programmed cell death (PCD) are intimately linked to the cancerous process. However, the mechanism of PCD involved in cancer chemoprevention is much less clear and may be different between types of chemopreventive agents and tumour cell types involved. Therefore, from a pharmacological view, it is crucial during the earlier steps of drug development to define the cellular specificity of the candidate as well as its capacity to bypass dysfunctional tumoral signalling pathways providing insensitivity to death stimuli. Studying the cytotoxic effects of violacein, an antibiotic dihydro-indolone synthesised by an Amazon river Chromobacterium, we observed that death induced in CD34(+)/c-Kit(+)/P-glycoprotein(+)/MRP1(+) TF1 leukaemia progenitor cells is not mediated by apoptosis and/or autophagy, since biomarkers of both types of cell death were not significantly affected by this compound. To clarify the working mechanism of violacein, we performed kinome profiling using peptide arrays to yield comprehensive descriptions of cellular kinase activities. Pro-death activity of violacein is actually carried out by inhibition of calpain and DAPK1 and activation of PKA, AKT and PDK, followed by structural changes caused by endoplasmic reticulum stress and Golgi apparatus collapse, leading to cellular demise. Our results demonstrate that violacein induces kinome reprogramming, overcoming death signaling dysfunctions of intrinsically resistant human leukaemia cells.TopInstitute pharma (The Netherlands)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Dutch Cancer SocietyErasmus MC Univ Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Ctr Expt & Mol Med, NL-1105 AZ Amsterdam, NetherlandsUniv Estadual Campinas, Brazil UNICAMP, Dept Biochem, Inst Biol, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Biochem, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Cell Biol, São Paulo, BrazilUniv Grande Rio UNIGRANRIO, Heath Sci Sch, Multidisciplinary Lab Dent Res, Rio de Janeiro, BrazilNatl Inst Metrol Qual & Technol Inmetro, Biotechnol Lab, Bioengn Sect, Rio de Janeiro, BrazilUniv Campinas UNICAMP, Inst Chem, Biol Chem Lab, Rio de Janeiro, BrazilUniv Groningen, Univ Med Ctr Groningen, Dept Pediat Oncol, Beatrix Childrens Hosp, Groningen, NetherlandsFed Univ São Paulo UNIFESP, Dept Biochem, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Cell Biol, São Paulo, BrazilDutch Cancer Society: EMCR 2010-4737Web of Scienc

Discovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors

Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) regulates the proliferation and differentiation of neuronal progenitor cells during brain development. Consequently, DYRK1A has attracted interest as a target for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD) and Down's syndrome. Recently, the inhibition of DYRK1A has been investigated as a potential treatment for diabetes, while DYRK1A's role as a mediator in the cell cycle has garnered interest in oncologic indications. Structure-activity relationship (SAR) analysis in combination with high-resolution X-ray crystallography leads to a series of pyrazolo[1,5-b]pyridazine inhibitors with excellent ligand efficiencies, good physicochemical properties, and a high degree of selectivity over the kinome. Compound 11 exhibited good permeability and cellular activity without P-glycoprotein liability, extending the utility of 11 in an in vivo setting. These pyrazolo[1,5-b]pyridazines are a viable lead series in the discovery of new therapies for the treatment of diseases linked to DYRK1A function

WNT activates the AAK1 kinase to promote clathrin-mediated endocytosis of LRP6 and establish a negative feedback loop

beta-Catenin-dependent WNT signal transduction governs development, tissue homeostasis, and a vast array of human diseases. Signal propagation through a WNT-Frizzled/LRP receptor complex requires proteins necessary for clathrin-mediated endocytosis (CME). Paradoxically, CME also negatively regulates WNT signaling through internalization and degradation of the receptor complex. Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer, inhibits WNT signaling. Reciprocally, AAK1 genetic silencing or its pharmacological inhibition using a potent and selective inhibitor activates WNT signaling. Mechanistically, we show that AAK1 promotes clearance of LRP6 from the plasma membrane to suppress the WNT pathway. Time-course experiments support a transcription-uncoupled, WNT-driven negative feedback loop; prolonged WNT treatment drives AAK1-dependent phosphorylation of AP2M1, clathrin-coated pit maturation, and endocytosis of LRP6. We propose that, following WNT receptor activation, increased AAK1 function and CME limits WNT signaling longevity2617993FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2013/50724-5; 2016/17469-0M.B.M. acknowledges support from the NIH (RO1-CA187799 and U24-DK116204-01). M.J.A. received financial support from NIH T32 Predoctoral Training Grants in Pharmacology (T32-GM007040-43 and T32-GM007040-42), an Initiative for Maximizing Student Diversity Grant (R25-GM055336-16), and the NIH National Cancer Institute (NCI) NRSA Predoctoral Fellowship to Promote Diversity in Health-Related Research (F31CA228289). M.P.W. received support from the Lymphoma Research Foundation (337444) and the NIH (T32-CA009156-35). Y.N. was supported by grants-in-aid from the Japan Society for the Promotion of Science (JSPS) (15KK0356 and 16K11493). T.T. was supported by the Howard Hughes Medical Institute Gilliam Fellowship for Advanced Study. M.V.G. was supported by Cancer Research UK (grants C7379/A15291 and C7379/A24639 to Mariann Bienz). The UNC Flow Cytometry Core Facility is supported in part by Cancer Center Core Support Grant P30 CA016086 to the UNC Lineberger Comprehensive Cancer Center, and research reported in this publication was supported by the Center for AIDS Research (award number 5P30AI050410), and the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The Structural Genomics Consortium (SGC) is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, the Canada Foundation for Innovation, the Eshelman Institute for Innovation, Genome Canada, the Innovative Medicines Initiative (European Union [EU]/European Federation of Pharmaceutical Industries and Associations [EFPIA]) (ULTRA-DD grant no. 115766), Janssen, Merck & Company, Merck KGaA, Novartis Pharma AG, the Ontario Ministry of Economic Development and Innovation, Pfizer, the São Paulo Research Foundation (FAPESP) (2013/50724-5), Takeda, and the Wellcome Trust (106169/ZZ14/Z). R.R.R. received financial support from FAPESP (2016/17469-0). We would also like to thank Claire Strain-Damerell and Pavel Savitsky for cloning various mutants of AAK1 and BMP2K proteins that were used in the crystallization trials. Additionally, we thank Dr. Sean Conner for providing the AAK1 plasmids, Dr. Stephane Angers for kindly providing the HEK293T DVL TKO cells, and Dr. Mariann Bienz for providing comments and feedback. We would like to thank members of the Major laboratory for their feedback and expertise regarding experimental design and project directio

Anti-inflammatory effect of diclofenac diethylammonium gel on acute phase of ligature induced periodontitis in rats

This study aimed to evaluate the effect of a diclofenac diethylammonium gel 10 mg/g (DD) on acute phase of ligature induced periodontitis model in rats. Experimental Periodontitis Disease (EPD) was induced in 30 Wistar rats subjected to ligature placement on left molars. Animals were treated with (DD), immediately after (EPD) induction. Saline-based gel (SG) was utilized as negative control and DD gel 10 mg/g was the tested substance. Animals were randomly assigned into the groups. The periodontium and the surrounding gingiva were examined at histopathology, as well as the neutrophil influx into the gingiva was assayed using myeloperoxidase activity levels by ELISA method. DD treatment reduced tissue lesion at histopathology coupled to decreased myeloperoxidase activity production in gingival tissue when compared to the saline gel control group (p < 0.05). The DD gel was able to provide a significant myeloperoxidase decreasing in gingiva tissue confirming to be effective in reducing gingival inflammation in this model.Colegio de Farmacéuticos de la Provincia de Buenos Aire