Use of therapeutic laser for prevention and treatment of oral mucositis

Oral mucositis (OM) affects patients who are submitted to hematopoietic stem cell transplantation (HSCT) due to high doses of chemotherapy and/or radiotherapy. The purpose of this investigation was to perform a comparative study of the frequency and evolution of OM among patients subjected to therapeutic laser and to the conventional therapy (use of mouthwash called "Mucositis Formula"). The patients were subjected to a myeloablative conditioning regimen before the allogeneic HSCT. Twenty-two patients were selected and divided into 2 groups: group I was irradiated with InGaAlP laser (660 nm) and GaAlAs laser (780 nm), 25 mW potency, 6.3J/cm² dose, in 10-s irradiation time, followed to conventional treatment; group II was subjected only to the conventional treatment. Both World Health Organization (WHO) scale and the Oral Mucositis Assessment Scale (OMAS) were used to evaluate the results. Data were analyzed by the non-parametric Wilcoxon test, with p<0.05 considered as statistically significant. Group I presented a lower frequency of OM (p=0.02) and lower mean scores, according to WHO and OMAS scales (p<0.01 and p=0.01, respectively). In conclusion, laser reduced the frequency and severity of OM, suggesting that therapeutic laser can be used both as a new form of prevention and treatment of OM.A mucosite oral (MO) afeta pacientes que são submetidos ao transplante de células-tronco hematopoéticas (TCTH) devido as altas doses de quimioterapia e/ou radioterapia. A proposta desta investigação foi realizar um estudo comparativo da freqüência e a evolução da MO entre os pacientes submetidos ao laser terapêutico e da terapia convencional (uso de solução de bochecho chamada "Fórmula para Mucosite").Os pacientes foram submetidos ao regime de condicionamento mieloablativo antes da realização do TCTH alogênico.Vinte e dois pacientes foram selecionados e divididos em 2 grupos: grupo I foi irradiado com laser AlGaInP (660 nm) e laser GaAlAs (780 nm), potência de 25 mW, dose de 6,3J/cm², tempo 10 s, seguido do tratamento convencional; grupo II submetido apenas ao tratamento convencional. Ambas as escalas da World Health Organization (WHO) e Oral Mucositis Assessment Scales (OMAS) foram utilizadas para avaliar os resultados. Os dados foram analizados pelo teste não-paramétrico de Wilcoxon, com p<0,05 considerado estatisticamente significante. O grupo I apresentou menor frequência de MO (p=0,02) e menor média de acordo com as escalas WHO e OMAS (p<0,01 e p=0,01, respectivamente). Em conclusão, o laser reduziu a frequência e gravidade da MO, sugerindo que o laser terapêutico pode ser usado para ambos como uma nova forma de prevenção e tratamento da MO

Philadelphia-negative myeloproliferative neoplasms as disorders marked by cytokine modulation

Background: Cytokines are key immune mediators in physiological and disease processes, whose increased levels have been associated with the physiopathology of hematopoietic malignancies, such as myeloproliferative neoplasms. Methods: This study examined the plasma cytokine profiles of patients with essential thrombocythemia, primary myelofibrosis, polycythemia vera and of healthy subjects, and analyzed correlations with JAK2 V617F status and clinical-hematological parameters. Results: The proinflammatory cytokine levels were increased in myeloproliferative neoplasm patients, and the presence of the JAK2 V617F mutation was associated with high IP-10 levels in primary myelofibrosis patients. Conclusions: Essential thrombocythemia, primary myelofibrosis, and polycythemia vera patients exhibited different patterns of cytokine production, as revealed by cytokine network correlations. Together, these findings suggest that augmented cytokine levels are associated with the physiopathology of myeloproliferative neoplasms.

Linguateca: um centro de recursos distribuí­do para o processamento computacional da lí­ngua portuguesa

Neste artigo apresentamos uma panorâmica da actividade da Linguateca na criação e disponibilização de recursos e ferramentas para a língua portuguesa. Começamos por uma descrição dos objectivos e pressupostos da Linguateca e uma breve história da sua intervenção, e finalizamos com algumas considerações sobre a melhor forma de prosseguir na organização da área

GVHD-derived plasma as a priming strategy of mesenchymal stem cells

Background: Mesenchymal stem cell (MSC) therapy is an important alternative for GVHD treatment, but a third of patients fail to respond to such therapy. Therefore, strategies to enhance the immunosuppressive potential of MSCs constitute an active area of investigation. Here, we proposed an innovative priming strategy based on the plasma obtained from GVHD patients and tested whether this approach could enhance the immunosuppressive capacity of MSCs. Methods: We obtained the plasma from healthy as well as acute (aGVHD) and chronic (cGVHD) GVHD donors. Plasma samples were characterized according to the TNF-α, IFN-γ, IL-10, IL-1β, IL-12p40, and IL-15 cytokine levels. The MSCs primed with such plasmas were investigated according to surface markers, morphology, proliferation, mRNA expression, and the capacity to control T cell proliferation and Treg generation. Results: Interestingly, 57% of aGVHD and 33% of cGVHD plasmas significantly enhanced the immunosuppressive potential of MSCs. The most suppressive MSCs presented altered morphology, and those primed with cGHVD displayed a pronounced overexpression of ICAM-1 on their surface. Furthermore, we observed that the ratio of IFN-γ to IL-10 cytokine levels in the plasma used for MSC priming was significantly correlated with higher suppressive potential and Treg generation induction by primed MSCs, regardless of the clinical status of the donor. Conclusions: This work constitutes an important proof of concept which demonstrates that it is possible to prime MSCs with biological material and also that the cytokine levels in the plasma may affect the MSC immunosuppressive potential, serving as the basis for the development of new therapeutic approaches for the treatment of immune diseases

MLL2/KMT2D and MLL3/KMT2C expression correlates with disease progression and response to imatinib mesylate in chronic myeloid leukemia

Background Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm whose pathogenesis is linked to the Philadelphia chromosome presence that generates the BCR–ABL1 fusion oncogene. Tyrosine kinase inhibitors (TKI) such as imatinib mesylate (IM) dramatically improved the treatment efficiency and survival of CML patients by targeting BCR–ABL tyrosine kinase. The disease shows three distinct clinical-laboratory stages: chronic phase, accelerated phase and blast crisis. Although patients in the chronic phase respond well to treatment, patients in the accelerated phase or blast crisis usually show therapy resistance and CML relapse. It is crucial, therefore, to identify biomarkers to predict CML genetic evolution and resistance to TKI therapy, considering not only the effects of genetic aberrations but also the role of epigenetic alterations during the disease. Although dysregulations in epigenetic modulators such as histone methyltrasnferases have already been described for some hematologic malignancies, to date very limited data is available for CML, especially when considering the lysine methyltransferase MLL2/KMT2D and MLL3/KMT2C. Methods Here we investigated the expression profile of both genes in CML patients in different stages of the disease, in patients showing different responses to therapy with IM and in non-neoplastic control samples. Imatinib sensitive and resistant CML cell lines were also used to investigate whether treatment with other tyrosine kinase inhibitors interfered in their expression. Results In patients, both methyltransferases were either upregulated or with basal expression level during the chronic phase compared to controls. Interestingly, MLL3/KMT2C and specially MLL2/KMT2D levels decreased during disease progression correlating with distinct clinical stages. Furthermore, MLL2/KMT2D was decreased in patients resistant to IM treatment. A rescue in the expression of both MLL genes was observed in KCL22S, a CML cell line sensitive to IM, after treatment with dasatinib or nilotinib which was associated with a higher rate of apoptosis, an enhanced expression of p21 (CDKN1A) and a concomitant decrease in the expression of CDK2, CDK4 and Cyclin B1 (CCNB1) in comparison to untreated KCL22S control or IM resistant KCL22R cell line, which suggests involvement of p53 regulated pathway. Conclusion Our results established a new association between MLL2/KMT2D and MLL3/KMT2C genes with CML and suggest that MLL2/KMT2D is associated with disease evolution and may be a potential marker to predict the development of therapy resistance

Validation Of The Ebmt Risk Score In Chronic Myeloid Leukemia In Brazil And Allogeneic Transplant Outcome.

The management of chronic myeloid leukemia (CML) has changed radically since the introduction of imatinib therapy. The decision of whether to offer a patient a hematopoietic stem cell transplant (HSCT) must be based on the probability of success of the procedure. The aim of this retrospective analysis of 1,084 CML patients who received an allogeneic HSCT in 10 Brazilian Centers between February 1983 and March 2003 was to validate the EBMT risk score. The study population comprised 647 (60%) males and 437 (40%) females, with a median age of 32 years old (range 1 - 59); 898 (83%) were in chronic phase, 146 (13%) were in accelerated phase and 40 (4%) were in blast crisis; 151 (14%) were younger than 20 years old, 620 (57%) were between 20 and 40 and 313 (29%) were older than 40; 1,025 (94%) received an HLA fully matched sibling transplant and only 59 (6%) received an unrelated transplant. In 283 cases (26%) a male recipient received a graft from a female donor. The interval from diagnosis to transplantation was less than 12 months in 223 (21%) cases and greater in 861 (79%). The overall survival, disease-free survival, transplant-related mortality and relapse incidence were 49%, 50%, 45% and 25%, respectively. Of the 1084 patients, 179 (17%) had a risk score of 0 or 1, 397 (37%) had a score of 2, 345 (32%) had a score of 3, 135 (12%) had a score of 4 and 28 (2%) a score of 5 or 6. The overall survival (OS) rate in patients with risk scores 0-1 and 2 was similar (58% and 55%, respectively) but significantly better than that in patients with scores 3 or more (score 3 - 44%, 4 - 36 % and 5-6 - 27%, respectively) pp<0.001). Disease-free survival (DFS) and transplant related mortality (TRM) in a patients with a score of 3 or more were 46% and 49%, respectively and the relapse rate beyond score 5-6 was 77%. Disease status had a negative impact on all outcomes (OS, DFS, TRM, and relapse). The OS rate for male recipients of a graft from a female donor was 40% compared to 52% among the other donor-recipient pairs (p=0.004). DFS and TRM were significant for disease phase and female donor-male recipient (p<0.001 and p<0.003, respectively). In our experience, age and interval between diagnosis and transplant did influence OS, DFS, TRM, and relapse rate. Our results validate the EBMT risk score in the context of a developing country and confirm its usefulness for making point decisions in the imatinib era.90232-

Linfoma subcutâneo de células T paniculite-símile Subcutaneous panniculitis-like T-cell lymphoma

Linfoma subcutâneo de células T paniculite-símile foi recentemente reconhecido como entidade clínico-patológica. Paciente do sexo feminino, 17 anos, relatou nodosidades eritêmato-violáceas e depressões nos membros e abdome há três anos e discreta perda ponderal, sem outros sintomas gerais. Adenomegalia, visceromegalias e infiltração da medula óssea estavam ausentes, e a histopatologia da pele mostrou densa infiltração de linfócitos atípicos CD3/CD8 no subcutâneo. A quimioterapia interrompeu o surgimento de novas lesões com remissão das pré-existentes no seguimento de oito meses. Aspectos imunofenotípicos e moleculares são relevantes para elucidação diagnóstica e avaliação do prognóstico.<br>Subcutaneous panniculitis-like T-cell lymphoma is extremely rare and has recently been recognized as a clinicopathological entity. Young female, 17 years old, has complained of subcutaneous nodules and plaques in the limbs and abdomen for three years, accompanied of mild weight loss without other constitutional symptoms. Nodal, visceral and bone marrow involvement was absent, and subcutaneous CD3/CD8 atypical lymphocyte infiltration was observed in the skin sample. Chemotherapy interrupted the onset of new lesions and led to remission in the 8-month follow-up. Immunophenotypic and molecular aspects were relevant to the diagnosis and as prognosis makers

Importance of monitoring and early switch to second generation tyrosine kinase inhibitors for the prognosis of patients with chronic myeloid leukemia with imatinib resistance or intolerance

Imatinib mesylate was the first BCR-ABL-target agent approved for the treatment of chronic myeloid leukemia. Although most patients respond well to imatinib therapy, the literature shows that one third develops resistance or intolerance. The timing of second-line treatment after failure of initial treatment may have a significant impact on long-term outcome. Thus, appropriate monitoring to identify resistance and/or intolerance is crucial to early intervention with second generation tyrosine kinase inhibitors and attainment of better result