Imagiologia dos Tumores malignos do pâncreas

As neoplasias malignas do pâncreas englobam vários tipos histologicos com características ima giológicas e comportamentos que permitem distingui-los entre si numa boa percentagem de situações. Contudo, nem sempre a sua diferenciação se toma possível sem o recurso às técnicas anátomo-patoló gicas, constituindo um grande desafio à imagiologia o diagnóstico diferencial com lesões benignas, com referencia particular às massas inflamatórias. O adenocarcinoma constitui cerca de 95% das neo plasias pancreáticas e é uma das grandes causas de morte por cancro nos países desenvolvidos. As técnicas de imagem aplicadas no diagnóstico e no estadiamento dos principais tumores do pâncreas são muito diversificadas, englobando meios inócuos, como a ecografia, métodos invasivos utilizando técnicas angiográficas ou recurso aos meios endoscópicos para acesso endocavitário. A utilidade de cada uma destas variedades técnicas depende essencialmente do tipo de tumor a estudar, tomando-se fundamental o correcto e o completo conhecimento das possibilidades e limitações de cada uma, com vista à aplicação racional dos meios na imagiologia do pâncreas.

Biopsy case mix and diagnostic yield at a Malawian central hospital

Cancer is a major disease burden worldwide resulting in high morbidity and mortality. It is the leading cause of mortality in developed countries and is one of the three leading causes of death for adults in developing countries. Pathological examination of tissue biopsies with histological confirmation of a correct cancer diagnosis is central to cancer care. Without an accurate and specific pathologic diagnosis, effective treatment cannot be planned or delivered. In addition, there are marked geographical variations in incidence of cancer overall, and of the specific cancers seen. Much of the published literature on cancer incidence in developing countries reflects gross estimates and may not reflect reality. Performing baseline studies to understand these distributions lays the groundwork for further research in this area of cancer epidemiology. Our current study surveys and ranks cancer diagnoses by individual anatomical site at Queen Elizabeth Central Hospital (QECH) which is the largest teaching and referral hospital in Malawi. A retrospective study was conducted reviewing available pathology reports over a period of one full year from January 2010 to December 2010 for biopsies from patients suspected clinically of having cancer. There were 544 biopsies of suspected cancer, taken from 96 anatomical sites. The oesophagus was the most common biopsied site followed by breast, bladder, bone, prostate, bowel, and cervical lymph node. Malignancies were found in biopsies of the oesophagus biopsies (squamous cell carcinoma, 65.1%; adenocarcinoma, 11.6%), breast (57.5%), bladder (squamous cell carcinoma, 53.1%) and stomach (37.6%). Our study demonstrates that the yield of biopsy for clinically suspected malignancy was greater than 50% for the 11 most common sites and provides a current survey of cancer types by site present in the population reporting to our hospital.

A Importância de estudos dinâmicos em PET/CT para avaliação de doenças oncológicas

A Medicina Nuclear (MN) permite investigar o estado fisiológico dos tecidos de forma minimamente invasiva, usando radiofármacos (rf’s), moléculas compostas por um análogo biológico específico desses processos fisiológicos e um marcador radioativo (radionuclídeo). PET/CT (do acrónimo inglês Positron Emission Tomography/Computed Tomography), uma das modalidades de imagem em MN, está a expandir-se rapidamente em muitos Países. As imagens obtidas revelam a biodistribuição dos rf’s usados e permitem conhecer a sua distribuição precisa no organismo. 18F-Fluorodesoxiglicose (FDG), um análogo da glicose, é o rf mais comumente utilizado, isto porque em neoplasias as células são geralmente caracterizadas pelo aumento do metabolismo da glicose. A quantificação realizada em imagens de PET, tem por base uma estimativa quantitativa do metabolismo da glicose no tumor, utilizando o índice de captação estandardizado, SUV (do acrónimo inglês Standard Uptake Value). A realização de estudos dinâmicos em PET/CT, isto é, realizados em sequência temporal imediatamente após a administração endovenosa do rf e, durante um período de tempo pré-determinado (por exemplo, 15 minutos) permite que o registo da cinética inicial dos rf’s seja estudado. A análise dos dados obtidos com o estudo dinâmico permite compreender o grau e a perfusão tumoral. Habitualmente, quanto maior a captação de 18F-FDG num tumor, maior é a sua atividade metabólica glicolítica, o que tem sido traduzido em maior agressividade tumoral. Nesta investigação, realizaram-se estudos dinâmicos num grupo restrito de patologias oncológicas, nomeadamente: carcinoma da bexiga, carcinoma do colo do útero, carcinoma colorretal, carcinoma do endométrio, metástases hepáticas e adenocarcinoma pancreático. Realizaram-se estudos dinâmicos durante cerca de 10/15 minutos, com 1minuto por frame. O objetivo desta Investigação é tentar compreender se, tumores com maior perfusão respondem melhor à Radioterapia (RT), ou se, a resposta é independente da perfusão. Para avaliar os valores de SUV’s ao longo tempo, realizaram-se ROI’s (do acrónimo inglês Region of Interest), nas artérias femorais ou aorta e na lesão tumoral. Com estes dados, criaram-se gráficos de atividade/tempo onde, no eixo das abcissas é representado o tempo e no eixo das ordenadas os valores de SUV. A partir destes gráficos e dos dados neles contidos, calculou-se o Índice de Perfusão Tumoral através de 2 métodos: A, Método Trapezoidal de Aproximação que relaciona a razão entre a área perfusional do tumor e a área de fluxo arterial, até ao momento do cruzamento das curvas; B, mais simples, calculando o Índice de Perfusão do Tumor através da razão entre o valor de SUV máximo da curva tumoral e da curva arterial até ao momento do cruzamento das curvas. O Método de Comparação de Métodos de Altman&Bland, revelou que tanto o método A como o método B são semelhantes para o cálculo do Índice de Perfusão Tumoral. Em conclusão, apesar do número reduzido de indivíduos estudados, os dados apresentados indicam que existe uma tendência para que haja melhor resposta à RT por parte dos tumores com maior índice metabólico e maior índice de perfusão. Os tumores com menor índice metabólico e menor grau perfusional parece que respondem pior à RT.

Leccinum vulpinum Watling induces DNA damage, decreases cell proliferation and induces apoptosis on the human MCF-7 breast cancer cell line

The current work aimed to study the antitumour activity of a phenolic extract of the edible mushroom Leccinum vulpinum Watling, rich essentially in hydroxybenzoic acids. In a first approach, the mushroom extract was tested against cancer cell growth by using four human tumour cell lines. Given the positive results obtained in these initial screening experiments and the evidence of some studies for an inverse relationship between mushroom consumption and breast cancer risk, a detailed study of the bioactivity of the extract was carried out on MCF-7 cells. Once the selected cell line to precede the work was the breast adenocarcinoma cell line, the human breast non-malignant cell line MCF-10A was used as control. Overall, the extract decreased cellular proliferation and induced apoptosis. Furthermore, the results also suggest that the extract causes cellular DNA damage. Data obtained highlight the potential of mushrooms as a source of biologically active compounds, particularly with antitumour activity.

Endoscopic band ligation without resection in selected patients for small and superficial upper gastrointestinal tract lesions

Background and aim: The aim of this study was to evaluate the efficacy of endoscopic band ligation (EBL) in carefully selected patients who would benefit from this method of resection. Methods: Patients with early upper gastrointestinal and small (< 15 mm) lesions treated with EBL (Duette® Multi-Band Mucosectomy) were prospectively recruited and retrospectively analyzed between 2010 and 2015. All cases were discussed in a multidisciplinary cancer committee and it was concluded that, owing to patient conditions, surgery was not possible and that not conducting histology would not change the clinical management. A first endoscopic control with biopsies was planned at 4-8 weeks. If there was no persistence of the lesion, new controls were programmed at 6 and 12 months. Results: The group (n = 12) included 5 esophagus lesions (adenosquamous carcinoma, n = 1; carcinoma squamous, n = 2; adenocarcinoma, n = 2); 4 gastric lesions (high grade dysplasia, n = 1; adenocarcinoma, n = 2; neuroendocrine tumor [NET], n = 1), and 3 duodenal lesions (NETs) (n = 3). The mean tumor diameter was 9.6 ± 2.8 mm (range 4-15). Only one minor adverse event was described. At first follow-up (4-8 weeks), there was 91.6% and 75% of endoscopic and histological remission, respectively. At 6-month follow-up there was 70% of both endoscopic remission and negative biopsies. And at 12 months, there was 100% and 75% of endoscopic and histological remission, respectively. Persisting lesions were T1 cancers. The median follow-up was 30.6 months. Conclusion: EBL without resection is an easy and safe technique that should be considered in patients with multiple morbidities and small superficial UGI lesions.

Papel de C3G y p38α en la regulación de la migración, invasión tumoral en carcinoma de colon. Función de fibulina 3

Colorectal cancer (CRC) represents the third most common cancer type and the second leading cause of cancer-related death in the western world. CRC results from the accumulation of both acquired genetic and epigenetic changes that transform normal glandular epithelium into adenocarcinoma (Lao and Grady 2011), affecting several genes such as Apc, K-ras, dcc/Smad4 and p53 or DNA mismatch repair genes (Pancione et al. 2012). p38 MAPKs are a subfamily of Serine-Threonine kinases activated by different stimuli that control fundamental cellular processes such as cell growth, proliferation, differentiation, migration and apoptosis (Dhillon et al. 2007, Nebreda and Porras 2000, Wagner and Nebreda 2009). There are four p38 MAPKs isoforms in mammals: α, β, δ and γ. p38α MAPK is ubiquitously expressed and is the most abundant isoform (Cuenda and Rousseau 2007). p38α is involved in the regulation of many cellular functions, among them, cell migration and invasion. In cancer, it can act as either a promoter or a suppressor of tumor growth, playing different roles during tumor progression (del Barco Barrantes and Nebreda 2012). C3G is a guanine nucleotide exchange factor (GEF) mainly for the Ras family members: Rap1 (Gotoh et al. 1995) and R-Ras (Gotoh et al. 1997), but it can also act through GEF independent mechanisms. C3G regulates several cellular functions such as cell death, adhesion, migration and invasion (Radha et al. 2011). In collaboration with Dr. Carmen Guerrero’s group (Centro del Investigación del Cáncer de Salamanca), our group has found a new functional relationship between C3G and p38α MAPK involved in the regulation of cell death in MEFs (Gutierrez-Uzquiza et al. 2010) and in the chronic myeloid leukemia (CML) K562 cell line (Maia et al. 2009). Moreover, C3G and p38α act through a common regulatory pathway to control cell adhesion in K562 cells regulating focal adhesion proteins (Maia et al. 2013)...

Carcinoma colóide do pâncreas : a propósito de um caso não associado a neoplasia mucinosa papilar intraductal

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Functional analysis of a transcriptional variant of matrix gla protein (MGP)

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014

Utilização de murganhos no estudo de novos alvos da terapia oncológica anti-angiogénica

Tese de Doutoramento em Ciências Veterinárias na Especialidade de Ciências Biológicas e Biomédicas

Marine photosynthetic organisms from the Portuguese coast as sources of antitumoural compounds

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Transport in the blood of an anti-tumor water-soluble rutheniun cyclopentadienyl complex: a fluorescence study on albumin binding

Dissertação de mestrado, Qualidade em Análises, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014

Validación del antígeno prostático específico [PSA] y densidad del PSA [PSAD] en el diagnóstico precoz del cáncer de próstata: Determinación del PSA sérico y PSAD, en correlación con el tacto rectal y ecografía transrectal de próstata para el diagnóstico precoz del cáncer de próstata, Hospital Vicente Corral Moscoso,1999 - 2001. Cuenca-Ecuador

El adenocarcinoma de próstata, es una patología que ha ido ganando espacio en nuestro medio, por esta razón este trabajo de investigación se dedicó al estudio del PSA sérico, importante marcador tumoral y a su método alternativo de interpretación PSAD, para el diagnóstico como son el tacto digital y la ecografía transrectal, de próstata [ETRP]. Se incluyeron en este estudio 63 pacientes hombres mayores de 45 años, con síntomas y signos de protatismo, con PSA igual o mayor a 10 ng/ml, PSAD igual o mayor a 0.15, con alteraciones sospechosas al tacto rectal y a la ecografía transrectal, todos se sometieron a biopsia transrectal de próstata. Se trata de un estudio comparativo cuasi experimental entre los diferentes procedimientos para el diagnóstico precoz del cáncer de próstata. La selección de los pacientes se realizó durante dos años [1999-2000], en la consulta externa de urología del Hospital Vicente Corral Moscoso, valorados por el autor de esta tesis y sus análisis realizados en un solo laboratorio clínico [Hospital de Solca ], y en mismo centro radiológico. De este total de pacientes el 25.39 por ciento presentaron cáncer de próstata, la sensibilidad y especificidad de la PSAD supera en forma significativa a la del PSA sérico, ya que sus valores aumentan en pacientes con lesiones sospechosas al tacto rectal y la ETRP, siendo de utilidad sobre todo en pacientes con PSA entre 4-10 ng/ml reduciendo así el número de biopsias prostáticas negativas. Al relacionar niveles de PSA y PSAD con biopsia prostática se determinó que el PSA tiene una sensibilidad del 87.5 por ciento y una especificidad del 63.82 por ciento, siendo superado por la PSAD que presenta una sensibilidad del 93.75 por ciento y una especificidad del 65.95 por ciento para el diangóstico precoz del cáncer de próstata. Importante decir que toda próstata sospechosa al tacto rectal y a la ETRP, independiente de los resultados del PSA y PSAD debería realizarse biopsia prostática para descartar neoplasia, ya que cerca del 20 por ciento de pacientes con cáncer de próstata localizado presenta un PSA por debajo de 4 ng/ml

Characterization of silver nanoparticles prepared by wet chemical method and their antibacterial and cytotoxicity activities

Purpose: To investigate the efficiency of silver nanoparticles synthesized by wet chemical method, and evaluate their antibacterial and anti-cancer activities. Methods: Wet chemical method was used to synthesize silver nanoparticles (AgNPs) from silver nitrate, trisodium citrate dehydrate (C6H5O7Na3.2H2O) and sodium borohydride (NaBH4) as reducing agent. The AgNPs and the reaction process were characterized by UV–visible spectrometry, zetasizer, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS). The antibacterial and cytotoxic effects of the synthesized nanoparticles were investigated by agar diffusion method and MTT assay respectively. Results: The silver nanoparticles formed were spherical in shape with mean size of 10.3 nm. The results showed good antibacterial properties, killing both Gram-positive and Gram-negative bacteria, and its aqueous suspension displayed cytotoxic activity against colon adenocarcinoma (HCT-116) cell line. Conclusion: The findings indicate that silver nanoparticles synthesized by wet chemical method demonstrate good cytotoxic activity in colon adenocarcinoma (HCT-116) cell lines and strong antibacterial activity against various strains of bacteria.

Cytotoxic, anti-inflammatory and antioxidant activities of four different extracts of Galega officinalis L (Goat’s rue)

Purpose: To evaluate the cytotoxic, anti-inflammatory and antioxidant activities of four different solvent extracts obtained from the aerial parts of Galega officinalis L Methods: The hexane, DCM, methanol and water extracts of G. officinalis were successively obtained by soxhlet extraction method. The cytotoxic activity of the extracts was assessed against human lung carcinoma (A-549), human colorectal adenocarcinoma (HT-29), human brain glioblastoma (U-87), and colon adenocarcinoma (DLD-1) by Resazurine test. The antioxidant activity of extracts were determined by Folin-Ciocalteau, oxygen radical absorbing capacity (ORAC), and 2’.7’-dichlorofluorescin-diacetate (DCFH-DA) cell-based assay while their anti-inflammatory activity was determined by nitric oxide (NO) assay. Results: DCM extract showed strong cytotoxic activity against lung adenocarcinoma and brain glioblastoma cell lines, with IC50 (concentration inhibiting 50 % of cell growth) values of 11 ± 0.4 and 16 ± 3 μg/mL, respectively. The hexane extract showed moderate anticancer activity against the same cell lines (59 ± 13 and 63 ± 16 μg/mL, respectively). DCM extract also showed significant anti-inflammatory activity, inhibiting NO release by 86.7 % at 40 μg/mL in lipopolysaccharide (LPS) - stimulated murine RAW 264.7 macrophages. Of all test extracts, the methanol extract of G. officinalis showed the highest antioxidant activity with 2.33 ± 0.09 μmol Trolox/mg , 7.10 ± 0.9 g tannic acid equivalent (TAE), and IC50 of 44 ± 4 μg/mL. Conclusion: The findings of this study suggest that DCM extract may possess anticancer effect against lung adenocarcinoma and brain glioblastoma, as well as serve as an anti-inflammatory agent.

Correlación entre estudio citológico y estudio histopatológico en el diagnóstico de Neoplasia Tiroidea. SOLCA - Cuenca. 2009- 2013

La neoplasia tiroidea impulsa la búsqueda de métodos diagnósticos para obtener un dictamen precoz y tratamiento oportuno que permitan mayor supervivencia y mejor calidad de vida. Objetivo: determinar la correlación entre estudio citológico e histopatológico en el diagnóstico de Neoplasia Tiroidea en pacientes atendidos en SOLCA – Cuenca, periodo 2009-2013. Metodología: estudio observacional, retrospectivo, analítico y de correlación diagnóstica, elaborado con historias clínicas de pacientes en quienes se realizó punciones (PAAF) para la citología, según el Sistema Bethesda, y con histopatología, para diagnosticar neoplasia tiroidea. Resultados: investigación desarrollada con 415 pacientes con neoplasia tiroidea. Caracterizada por 89.2% de mujeres; edad promedio de 51.8 ± 15.2 años, de 41-55 años fue la mayor categoría (36,9%); 47.2% procedieron de Cuenca y el 37.8% de las provincias vecinas. Estado civil casado/a fue más frecuente, 269 (64,8%), y de profesión “amas de casa” fueron las más afectadas 231 (55,7%). El 96.4% de diagnósticos citológicos Bethesda categoría 6, fueron confirmados por histología. Hubo correlación (r = 0.49) significativa y concordancia moderada (kappa = 0.337) entre citología e histología. Sensibilidad=63% (IC95%: 58 – 69), Especificidad=94% (IC95%: 89 – 98), RVP=10.9 (IC95%: 5 – 22) y RVN=0.39 (IC95%: 0.3 – 0.4). Conclusiones: la citología por PAAF es una herramienta para el estudio, diagnóstico de pacientes con afecciones tiroideas. Una punción realizada por expertos es una técnica rápida, económica, bien tolerada, y produce resultados confiables. La categorización Bethesda representa un sistema confiable, válido para reportar citología de tiroides