S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas.

Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression. Hyperphosphorylation of Replication Protein A (RPA), including phosphorylation of Ser4 and Ser8 of RPA2, is a well-known indicator of DNA damage and checkpoint activation. In this study, we utilize S4S8-RPA phosphorylation as a marker for cancer development and progression in oral squamous cell carcinomas (OSCC). S4S8-RPA phosphorylation was observed to be low in normal cells, high in dysplasias, moderate in early grade tumors, and low in late stage tumors, essentially supporting the model of the DDR as an early barrier to tumorigenesis in certain types of cancers. In contrast, overall RPA expression was not correlative to DDR activation or tumor progression. Utilizing S4S8-RPA phosphorylation to indicate competent DDR activation in the future may have clinical significance in OSCC treatment decisions, by predicting the susceptibility of cancer cells to first-line platinum-based therapies for locally advanced, metastatic and recurrent OSCC

Na mira do sucesso : estratégias de combate ao insucesso escolar de alunos estrangeiros

Trabalho de projeto de mestrado, Ciências da Educação (Área de especialização Formação de Adultos), Universidade de Lisboa, Instituto de Educação, 2017Considerando a importância da integração no contexto escolar e consequentemente no sucesso educativo, o presente trabalho projeto, desenvolvido no âmbito do Mestrado em Ciências da Educação, área de especialidade em Formação de Adultos, centra-se na integração de alunos estrangeiros no ensino português, assim como na dinamização de atividades de promoção do seu sucesso escolar. Deste modo, o relatório apresenta como principais temáticas a integração de estrangeiros em Portugal, o insucesso escolar dos alunos estrangeiros e as políticas educativas de combate a este fenómeno, culminando na definição e desenvolvimento de um projeto de combate ao insucesso escolar destinado a este público. O trabalho desenvolvido junto destes jovens nos últimos nove anos e o diagnóstico elaborado no Agrupamento de Escolas João de Barros permitiu compreender a importância de intervir junto da população estrangeira, fomentando o sucesso educativo e a integração no país de acolhimento, uma vez que a taxa de retenção destes jovens está muito acima dos seus colegas autóctones.Considering the importance of integration in the school context, and consequently in educational success, this project, developed in the scope of the master’s degree in Educational Sciences, specialization in Adult Education, focuses on foreign students’ integration at the Portuguese educational system and activities that could be developed to promote their school success. Therefore, the main themes of the report are the integration of foreigners in Portugal, the lack of academic experience from foreign students and educational policies to reduce this barrier, in order to define and develop a project to combat school failure among this cases. The work developed for the last nine years with this students, the diagnostic elaborated in João de Barros Group of Schools, allowed me to understand the importance of an intervention among foreign students, to foment educational success and integration in the host country, bearing in mind that the retention rate in those cases is far above the native students’ average

Forensic Pathology

xxii.565 hln.; ill.; 23.5 c

The great imitator: IgG4 periaortitis masquerading as an acute aortic syndrome on computed tomographic angiography

AbstractWe present the case of a 52-year-old woman who presented to the emergency department with chest and neck pain. Initial cervical spine magnetic resonance imaging shows an abnormal flow void in the left vertebral artery, which prompted a computed tomographic angiogram. This demonstrated a hyperdense thickened ascending aortic wall, which extended into the great vessel origins. Clinically and radiographically interpreted as an acute aortic syndrome and/or intramural hematoma, the patient underwent ascending aortic repair with graft. An unusual aortic and/or periaortic mass was encountered in surgery and final pathology demonstrated IgG4 periaortitis. A rare clinical disease, IgG4-mediated processes are often mimickers of other pathologic entities and frequently lead to misdiagnosis. All pathologically similar, IgG4-mediated disease processes can involve the pancreas, salivary glands, orbits, retroperitoneum, and the vasculature

Androgen Receptor, Although Not a Specific Marker For, Is a Novel Target to Suppress Glioma Stem Cells as a Therapeutic Strategy for Glioblastoma

Targeting androgen receptor (AR) has been shown to be promising in treating glioblastoma (GBM) in cell culture and flank implant models but the mechanisms remain unclear. AR antagonists including enzalutamide are available for treating prostate cancer patients in clinic and can pass the blood–brain barrier, thus are potentially good candidates for GBM treatment but have not been tested in GBM orthotopically. Our current studies confirmed that in patients, a majority of GBM tumors overexpress AR in both genders. Enzalutamide inhibited the proliferation of GBM cells both in vitro and in vivo. Although confocal microscopy demonstrated that AR is expressed but not specifically in glioma cancer stem cells (CSCs) (CD133+), enzalutamide treatment significantly decreased CSC population in cultured monolayer cells and spheroids, suppressed tumor sphere-forming capacity of GBM cells, and downregulated CSC gene expression at mRNA and protein levels in a dose- and time-dependent manner. We have, for the first time, demonstrated that enzalutamide treatment decreased the density of CSCs in vivo and improved survival in an orthotopic GBM mouse model. We conclude that AR antagonists potently target glioma CSCs in addition to suppressing the overall proliferation of GBM cells as a mechanism supporting their repurposing for clinical applications treating GBM

Aberrant expression of mucin core proteins and o-linked glycans associated with progression of pancreatic cancer

PURPOSE: Mucin expression is a common feature of most adenocarcinomas and features prominently in current attempts to improve diagnosis and therapy of pancreatic cancer and other adenocarcinomas. We investigated the expression of a number of mucin core proteins and associated O-linked glycans expressed in pancreatic adenocarcinoma (PA) – sialyl Tn (STn), Tn, T antigen, sialyl Lewis A (CA19-9), sialyl Lewis C (SLeC), Lewis X (LeX) and sialyl Lewis X (SLeX) – during the progression of pancreatic cancer from early stages to metastatic disease. EXPERIMENTAL DESIGN: Immunohistochemical analyses of mucin and associated glycan expression on primary tumor and liver metastatic tumor samples were performed with matched sets of tissues from 40 autopsy patients diagnosed with PA, 14 surgically resected tissue samples, and 8 normal pancreata. RESULTS: There were significant changes in mucin expression patterns throughout disease progression. MUC1 and MUC4 were differentially glycosylated as the disease progressed from early PanINs to metastatic disease. De novo expression of several mucins correlated with increased metastasis indicating a potentially more invasive phenotype, and we demonstrate the expression of MUC6 in acinar cells undergoing acinar to ductal metaplasia. A “cancer field-effect” that included changes in mucin protein expression and glycosylation in the adjacent normal pancreas was also seen. CONCLUSIONS: There are significant alterations in mucin expression and post-translational processing during progression of pancreatic cancer from early lesions to metastasis. The results are presented in the context of how mucins influence the biology of tumor cells and their microenvironment during progression of pancreatic cancer

Semiquantitative evaulation of protein expression levels based on immunohistochemical findings.

<p>Tumor cell (left) and stromal (right) expression levels of GLUT1, HK2, ALDOB, ENO3, PKM2, LDHA and IDH3A in pancreatic tumor (A), and liver (B), lung (C), lymph node (D) and diaphragm (E) metastatic lesions were graded on a scale of 0–3. The staining intensities are tabularized and indicated with gradations of red color.</p

Metabolic protein expression in primary and metastatic lesions of pancreatic adenocarcinomas.

<p>Immunohistochemical examination of GLUT1 (A) HK2 (B), ALDOB (C), ENO3 (D), PKM2 (E), LDHA (F) IDH3A (G) expression in uninvolved pancreas, pancreatic tumor, and liver, lung, lymph node and diaphragm metastatic lesions. The staining was performed with Fast-Red stain. The images were captured at 200× magnification. Tumor cell area (T), stromal cell area (S) and uninvolved region (U) are indicated in the IHC images.</p