Linfoma renale del gatto:rilievi anatomopatologici, immunofenotipizzazione delle popolazioni linfocitarie ed espressione tissutale dell'antigene virale FeLV gp70.

Riassunto Il linfoma è una delle neoplasie più diffuse nel gatto. Questa neoplasia è stata classificata in base alla localizzazione anatomica nella forma Mediastinica (che interessa il timo e/o i linfonodi mediastinici), Alimentare, Multicentrica (che interessa diversi linfonodi e/o la milza e/o il fegato, Extranodale (che coinvolge i reni, SNC o la cute). Le cellule neoplastiche sono caratterizzate da diverse sottopopolazioni, che sono definite tramite immunofenotipizzazione ottenuta mediante tecniche immunoistochimiche (IHC), così che possano essere classificate come cellule B o T o non B/non T. I gatti infetti dal virus della leucemia felina (FeLV, Gammaretrovirus) presentano elevata incidenza di linfomi rispetto ai gatti non infetti. I meccanismi proposti di sviluppo neoplastico sono mutagenesi inserzionali o stimolazione persistente delle cellule immunitarie dell’ospite da parte di antigeni virali, i quali possono promuovere la trasformazione in senso maligno dei linfociti. Lo scopo di questo lavoro è stato esaminare i rilievi patologici, l’espressione di FeLV e l’immonofenotipo (B, T, nonB/nonT) nei reni felini affetti da linfoma. Abbiamo effettuato colorazione Ematossilina- Eosina ed Immunoistochimica per FeLV gp70, CD3 e CD79. Nello studio sono stati inclusi i tessuti di 49 gatti presentati all’Unità Operativa di Anatomia Patologica e Patologia Generale del Dipartimento di Scienze Medico Veterinarie dell’Università degli studi di Parma. Il 39% dei casi (19/49) sono caratterizzati dalla presenza di lesioni linfomatose a livello renale. Questa popolazione è costituita dal 52,6% 3 (10/19) maschi e dal 47,4% (9/19) femmine. L’età è compresa tra 8 mesi e 17 anni ed in particolare 26,6% (5/19) sono giovani (0-2 anni), 47,4% (9/19) sono adulti (2-10 anni) e 26,3% (5/19) sono anziani (>10 anni). Per quanto riguarda la classificazione anatomica la forma renale appare primitiva in 5 casi (25%), in 8 casi (42%) appare secondaria a linfomi multicentrici, in 3 casi (15,7%) a linfomi mediastinici e in altri 3 casi (15,7%) a linfomi gastrici e intestinali. Per quanto riguarda l’immunofenotipizzazione sono risultati CD3 positivi il 73,7% (14/19) e CD3 negativi il 27,3% (5/19); CD79 alpha positivi il 26,3% (5/19) e CD79 alpha negativi il 73,7% (14/19); l’espressione della proteina gp70 è stata individuata nel 78,9% (15/19) delle neoplasie renali, mentre il 21,1% (4/19) non presentava espressione della proteina. Nei 4 anni presi in considerazione nello studio si evince un’elevata incidenza della localizzazione anatomica renale sul totale di linfomi osservati. Non si è notata correlazione statistica tra linfomi renali, età e sesso dei soggetti presi in esame ma vi è un’elevata percentuale di animali adulti ed anziani affetti dalla patologia. Nella valutazione fenotipica dell’infiltrato neoplastico si è osservata l’elevata espressione di CD3, caratterizzando i linfociti come appartenenti alla sottopopolazione T. Inoltre si è evidenziato come un elevato numero di cellule neoplastiche esprimano gp70; ciò permette di affermare che i linfociti neoplastici sono infettati dal virus FeLV, il quale inoltre è in attiva replicazione. I marker CD3 e gp70 sono risultati fortemente correlati statisticamente; si può affermare perciò che l’espansione clonale dei linfociti T è correlata alla presenza e replicazione del virus.

Trasplante autólogo de progenitores hematopoyéticos (TAPH) en linfoma folicular (FL). Un análisis de muy largo seguimiento de los pacientes incluidos en el registro español Geltamo centrado en su eficacia y en la posibilidad de curación

Los pacientes con LF presentan un curso clínico indolente y una supervivencia relativamente prolongada, sin embargo el LF continúa considerándose una enfermedad incurable con los tratamientos convencionales y la recaída de los pacientes es la norma, alcanzando en las sucesivas recaídas un menor número de respuestas y de menor duración. Los enfermos con LF de alto riesgo intensificados con TAPH pueden alcanzar remisiones prolongadas, pero el mejor momento para dicho procedimiento es controvertido. Los enfermos trasplantados en primera remisión han demostrado un beneficio en la Supervivencia Libre de Progresión (SLP) en comparación con los tratados con la terapia convencional o con la inmunoquimioterapia. Sin embargo, ningún estudio randomizado (ER) ha demostrado todavía un beneficio en la Supervivencia Global (SG). No obstante, la mediana de seguimiento de los estudios fase III que evalúan el papel del TAPH es insuficiente para obtener beneficios en términos de SG. El único ER disponible que evalúa el rol del TAPH en pacientes con LF trasplantados en 2ª RC demuestra un beneficio en la SLP y la SG en comparación con la terapia convencional y ha sido confirmado en varios estudios retrospectivos con largos seguimientos...

Linfoma não Hodgkin da órbita : o sucesso de um caso raro

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

Abnormalities on 1q and 7q are associated with poor outcome in sporadic Burkitt's lymphoma. A cytogenetic and comparative genomic hybridization study.

Comparative genomic hybridization (CGH) studies have demonstrated a high incidence of chromosomal imbalances in non-Hodgkin's lymphoma. However, the information on the genomic imbalances in Burkitt's Lymphoma (BL) is scanty. Conventional cytogenetics was performed in 34 cases, and long-distance PCR for t(8;14) was performed in 18 cases. A total of 170 changes were present with a median of four changes per case (range 1-22). Gains of chromosomal material (143) were more frequent than amplifications (5) or losses (22). The most frequent aberrations were gains on chromosomes 12q (26%), Xq (22%), 22q (20%), 20q (17%) and 9q (15%). Losses predominantly involved chromosomes 13q (17%) and 4q (9%). High-level amplifications were present in the regions 1q23-31 (three cases), 6p12-p25 and 8p22-p23. Upon comparing BL vs Burkitt's cell leukemia (BCL), the latter had more changes (mean 4.3 +/- 2.2) than BL (mean 2.7 +/- 3.2). In addition, BCL cases showed more frequently gains on 8q, 9q, 14q, 20q, and 20q, 9q, 8q and 14q, as well as losses on 13q and 4q. Concerning outcome, the presence of abnormalities on 1q (ascertained either by cytogenetics or by CGH), and imbalances on 7q (P=0.01) were associated with a short survival.

Linfoma primário da vagina – revisão da literatura a propósito de um caso clínico

Os tumores primários malignos da vagina são raros, contribuindo apenas para cerca de 1%-2% dos cancros ginecológicos. O linfoma não-Hodgkin (LNH) primário da vagina é raríssimo (existindo aproximadamente 100 casos descritos na literatura). A sua associação com infecção pelo vírus Epstein Barr (VEB) foi descrita em escassos casos. Os autores pretendem fazer uma revisão da literatura de linfoma primário da vagina, com base num caso clínico de LNH-B de grandes células numa mulher nulípara de 25 anos de idade.

Desenvolvimento farmacotécnico de um radioimunoconjugado para terapia de linfoma não-Hodgkin

Tese (Doutorado em Tecnologia Nuclear)

Factores preditivos de linfoma no síndrome de Sjögren : a propósito de um caso clínico

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

Chemotherapy and zoledronate sensitize solid tumour cells to Vγ9Vδ2 T cell cytotoxicity

Combinations of cellular immune-based therapies with chemotherapy and other antitumour agents may be of significant clinical benefit in the treatment of many forms of cancer. Gamma delta (γδ) T cells are of particular interest for use in such combined therapies due to their potent antitumour cytotoxicity and relative ease of generation in vitro. Here, we demonstrate high levels of cytotoxicity against solid tumour-derived cell lines with combination treatment utilizing Vγ9Vδ2 T cells, chemotherapeutic agents and the bisphosphonate, zoledronate. Pre-treatment with low concentrations of chemotherapeutic agents or zoledronate sensitized tumour cells to rapid killing by Vγ9Vδ2 T cells with levels of cytotoxicity approaching 90%. In addition, zoledronate enhanced the chemotherapy-induced sensitization of tumour cells to Vγ9Vδ2 T cell cytotoxicity resulting in almost 100% lysis of tumour targets in some cases. Vγ9Vδ2 T cell cytotoxicity was mediated by perforin following TCR-dependent and isoprenoid-mediated recognition of tumour cells. Production of IFN-γ by Vγ9Vδ2 T cells was also induced after exposure to sensitized targets. We conclude that administration of Vγ9Vδ2 T cells at suitable intervals after chemotherapy and zoledronate may substantially increase antitumour activities in a range of malignancies.

A natural compound, methyl angolensate, induces mitochondrial pathway of apoptosis in Daudi cells

Natural products discovered from medicinal plants have played an important role in the treatment of cancer. In an effort to identify novel small molecules which can affect the proliferation of lymphoma cells, we tested methyl angolensate (MA), a plant derived tetranortriterpenoid, purified from the crude extract of the root callus of Soymida febrifuga commonly known as Indian red wood tree. We have tested MA for its cytotoxic properties on Burkitt's lymphoma cell lines, using various cellular assays. We observed that MA induces cytotoxicity in Daudi cells in a dose-dependent manner using trypan blue, MTT and LDH assays. We find that the treatment with MA led to activation of DNA double-strand break repair proteins including KU70 and KU80, suggesting the activation of nonhomologous DNA end joining pathway in surviving cells. Further, we find that methyl angolensate could induce apoptosis by cell cycle analysis, annexin V-FITC staining, DNA fragmentation and PARP cleavage. Besides, MA treatment led to reactive oxygen species generation and loss of mitochondrial transmembrane potential. These results suggest the activation of mitochondrial pathway of apoptosis. Hence, we identify MA as a potential chemotherapeutic agent against Daudi cells.

Utilización de reacciones de cicloadición (3+2) en la síntesis de nuevas entidades químicas con actividad inhibitoria del proteasoma

250 p.

Study on bioactivity of extracts from marine sponges in Chinese Sea

The bioactivity screening of fractions from two inter-tidal sponges collected from the north of China Yellow Sea and one sponge collected from the South Chinese Sea was reported in this study. In sponge Hymeniacidon perleve there were 9 fractions out of 15 from CHCl3 extract with anti Staphylococcus aureus activity, 9 fractions out of 19 from BuOH extract with anti Escherichia coli activity, and three fractions from CHCl3 extract which had moderate to strong activity in inhibiting Bacillus subtilis, Candida albicans, and Aspergilus niger. The fractions of Reniochalina sp. showed bioactivity against bacteria and fungi. The fractions of Acanthella acuta Schmidt showed bioactivity against S. aureus and fungi. One compound from H. perleve obtained by the bioactively directing isolation was tested for bioactivity against the human hepatoma cell line Qgy7701 (IC50 10.1 mug/ml), Burkitt's lymphoma cell line Raji (IC50 9.76 mug/ml) and chronic myelogenous leukemia K562 (IC50 1.90 mug/ml). (C) 2003 Elsevier B.V. All rights reserved.

Manifestações orais em crianças em tratamento oncológico

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

DUB-3, a Cytokine inducible Deubiquitinating Enzyme That Blocks Profileration

Previous studies have identified the DUB family of cytokine-regulated murine deubiquitinating enzymes, which play a role in the control of cell proliferation and survival. Through data base analyses and cloning, we have identified a human cDNA (DUB-3) that shows significant homology to the known murine DUB family members. Northern blotting has shown expression of this gene in a number of tissues including brain, liver, and muscle, with two transcripts being apparent (1.6 and 1.7 kb). In addition, expression was observed in cell lines including those derived from a number of hematopoietic tumors such as the Burkitt's lymphoma cell line RAJI. We have also demonstrated that DUB-3, which was shown to be an active deubiquitinating enzyme, is induced in response to interleukin-4 and interleukin-6 stimulation. Finally, we have demonstrated that constitutive expression of DUB-3 blocks proliferation and can initiate apoptosis in both IL-3-dependent Ba/F3 cells and NIH3T3 fibroblasts. These findings suggest that human DUB-3, like the murine DUB family members, is transiently induced in response to cytokines and can, when constitutively expressed, block growth factor-dependent proliferation.

Hematopoietic malignancies associated with viral and alcoholic hepatitis

Hepatitis C virus (HCV) and hepatitis B virus (HBV) have been associated with hematopoietic malignancies, but data for many subtypes are limited. From the U.S. Surveillance, Epidemiology, and End Results-Medicare database, we selected 61,464 cases (=67 years) with hematopoietic malignancies and 122,531 population-based controls, frequency-matched by gender, age, and year (1993-2002). Logistic regression was used to compare the prevalence of HCV, HBV, and alcoholic hepatitis in cases and controls, adjusted for matching factors, race, duration of Medicare coverage, and number of physician claims. HCV, HBV, and alcoholic hepatitis were reported in 195 (0.3%), 111 (0.2%), and 404 (0.7%) cases and 264 (0.2%), 242 (0.2%), and 798 (0.7%) controls, respectively. HCV was associated with increased risk of diffuse large B-cell lymphoma [odds ratio (OR) 1.52, 95% confidence interval (95% CI) 1.05-2.18], Burkitt lymphoma (OR 5.21, 95% CI 1.62-16.8), follicular lymphoma (OR 1.88, 95% CI 1.17-3.02), marginal zone lymphoma (OR 2.20, 95% CI 1.22-3.95), and acute myeloid leukemia (OR 1.54, 95% CI 1.00-2.37). In contrast, HBV was unrelated to any hematopoietic malignancies. Alcoholic hepatitis was associated with decreased risk of non-Hodgkin lymphoma overall, but increased risk of Burkitt lymphoma. In summary, HCV, but not other causes of hepatitis, was associated with the elevated risk of non-Hodgkin lymphoma and acute myeloid leukemia. HCV may induce lymphoproliferative malignancies through chronic immune stimulation. Copyright © 2008 American Association for Cancer Research.


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