Radiotherapy of large target volumes in Hodgkin's lymphoma: normal tissue sparing capability of forward IMRT versus conventional techniques

<p>Abstract</p> <p>Background</p> <p>This paper analyses normal tissue sparing capability of radiation treatment techniques in Hodgkin's lymphoma with large treatment volume.</p> <p>Methods</p> <p>10 patients with supradiaphragmatic Hodgkin's lymphoma and planning target volume (PTV) larger than 900 cm³were evaluated. Two plans were simulated for each patient using 6 MV X-rays: a conventional multi-leaf (MLC) parallel-opposed (AP-PA) plan, and the same plan with additional MLC shaped segments (forward planned intensity modulated radiation therapy, FPIMRT). In order to compare plans, dose-volume histograms (DVHs) of PTV, lungs, heart, spinal cord, breast, and thyroid were analyzed. The Inhomogeneity Coefficient (IC), the PTV receiving 95% of the prescription dose (V95), the normal tissue complication probability (NTCP) and dose-volume parameters for the OARs were determined.</p> <p>Results</p> <p>the PTV coverage was improved (mean V95_AP-PA= 95.9 and IC_AP-PA= 0.4 vs. V95_FPIMRT= 96.8 and IC_FPIMRT= 0.31, <it>p </it>≤ 0.05) by the FPIMRT technique compared to the conventional one. At the same time, NTCPs of lung, spinal cord and thyroid, and the volume of lung and thyroid receiving ≥ 30 Gy resulted significantly reduced when using the FPIMRT technique.</p> <p>Conclusions</p> <p>The FPIMRT technique can represent a very useful and, at the same time, simple method for improving PTV conformity while saving critical organs when large fields are needed as in Hodgkin's lymphoma.</p

Maternal exposure to an enrichment environment promotes uterine vascular remodeling and prevents embryo loss in mice.

Implantation-related events are crucial for pregnancy success. In particular, defects in vascular remodeling at the maternal-fetal interface are associated with spontaneous miscarriage and recurrent pregnancy loss. Physical activity and therapies oriented to reduce stress improve pregnancy outcomes. In animal models, environmental stimulation and enrichment are associated with enhanced well-being, cognitive function and stress resilience. Here, we studied whether the exposure of BALB/c mice to an enriched environment (EE) regulates crucial events during early gestation at the maternal-fetal interface. Pregnant BALB/c mice were exposed to the EE that combines non-invasive stimuli from the sensory pathway with voluntary physical activity. The pregnancy rate was evaluated. Implantation sites were investigated microscopically and macroscopically. Vascular adaptation parameters at the maternal-fetal interface were analyzed. We found that exposure to the EE prevented pregnancy loss between gestational days 7 and 15. Also, it increased the diameter of the uterine artery and decreased the wall:lumen ratio of the mesometrial decidual vessels, suggesting that EE exposure promotes vascular remodeling. Moreover, it increased nitric oxide synthase activity and inducible nitric oxide synthase expression, as well as prostaglandin F2a production and endoglin expression in the implantation sites. Exposure of pregnant females to the EE regulates uterine physiology, promoting vascular remodeling during early gestation. These adaptations might contribute to preventing embryo loss. Our results highlight the importance of the maternal environment for pregnancy success. The design of an 'EE-like' protocol for humans could be considered as a new non-pharmacologic strategy to prevent implantation failure and recurrent miscarriage.Fil: de la Cruz Borthiry, Fernanda Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Schander, Julieta Aylen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Cella, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Beltrame, Jimena Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Franchi, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Ribeiro, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

PACE: A Probabilistic Atlas for Normal Tissue Complication Estimation in Radiation Oncology

In radiation oncology, the need for a modern Normal Tissue Complication Probability (NTCP) philosophy to include voxel-based evidence on organ radio-sensitivity (RS) has been acknowledged. Here a new formalism (Probabilistic Atlas for Complication Estimation, PACE) to predict radiation-induced morbidity (RIM) is presented. The adopted strategy basically consists in keeping the structure of a classical, phenomenological NTCP model, such as the Lyman-Kutcher-Burman (LKB), and replacing the dose distribution with a collection of RIM odds, including also significant non-dosimetric covariates, as input of the model framework. The theory was first demonstrated in silico on synthetic dose maps, classified according to synthetic outcomes. PACE was then applied to a clinical dataset of thoracic cancer patients classified for lung fibrosis. LKB models were trained for comparison. Overall, the obtained learning curves showed that the PACE model outperformed the LKB and predicted synthetic outcomes with an accuracy &gt;0.8. On the real patients, PACE performance, evaluated by both discrimination and calibration, was significantly higher than LKB. This trend was confirmed by cross-validation. Furthermore, the capability to infer the spatial pattern of underlying RS map for the analyzed RIM was successfully demonstrated, thus paving the way to new perspectives of NTCP models as learning tools

Radiation therapy in primary orbital lymphoma: a single institution retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Primary orbital lymphoma is a rare disease that accounts for 10% of all orbital tumors. Radiotherapy on the orbital cavity is the treatment of choice for this unusual presentation of localized non-Hodgkin's lymphoma (NHL). The aim of this study is to retrospectively evaluate the effectiveness and the toxicity of radiation treatment in patients with primary orbital lymphoma.</p> <p>Methods</p> <p>Forty-seven consecutive patients having primary orbital lymphoma treated in our department between May 1983 and September 2006 were investigated in a retrospective study. Either ⁶⁰Co γ rays or 6 MV X rays were used to deliver daily fractions of 1.8 or 2.0 Gy, 5 times/week, with total doses ranging from 34.2 to 50 Gy. Forty-three patients had stage IE, three had stage II and one stage IV disease. Thirty-eight patients had marginal zone B-cell lymphoma, 5 diffuse large B cell lymphoma, 3 mantle cell lymphoma and 1 Burkitt lymphoma. Local control (LC), disease free survival (DFS), overall survival (OS) and late side effects were evaluated in all patients.</p> <p>Results</p> <p>With a median follow up of 45 months, LC was obtained in 100% of patients. The estimated 5- and 7-year DFS rates were 75.8% and 55.3%, and the 5- and 7-year OS rates were 88.7% and 79.9% respectively. Acute toxicity was minimal. Late toxicity such as cataract, keratitis, retinopathy and xerophthalmia occurred respectively in 12 (25.5%), 5 (10.6%), 1 (2.1%), and 9 (19.1%) patients.</p> <p>Conclusion</p> <p>Radiotherapy is an effective and at the same time well tolerated treatment for primary orbital lymphoma.</p

AVALIAÇÃO DE APRENDIZAGEM EM MEIO A PANDEMIA DO CORONAVÍRUS NO BRASIL.

O presente artigo tem como objetivo descrever sobre como está sendo a adaptação dos alunos em meio a pandemia do coronavírus e retratar&nbsp; métodos de avaliação de aprendizagem que os professores podem usar frente as aulas online. As avaliações de aprendizagens são de extrema importância, pois ajudam para a tomada de decisões a partir da análise das ações em desenvolvimento

Binding of Extracellular Maspin to 1 Integrins Inhibits Vascular Smooth Muscle Cell Migration

Maspin is a serpin that has multiple effects on cell behavior, including inhibition of migration. How maspin mediates these diverse effects remains unclear, as it is devoid of protease inhibitory activity. We have previously shown that maspin rapidly inhibits the migration of vascular smooth muscle cells (VSMC), suggesting the involvement of direct interactions with cell surface proteins. Here, using immunofluorescence microscopy, we demonstrate that maspin binds specifically to the surface of VSMC in the dedifferentiated, but not the differentiated, phenotype. Ligand blotting of VSMC lysates revealed the presence of several maspin-binding proteins, with a protein of 150 kDa differentially expressed between the two VSMC phenotypes. Western blotting suggested that this protein was the ß1 integrin subunit, and subsequently both a3ß1 and a5ß1, but not avß3, were shown to associate with maspin by coimmunoprecipitation. Specific binding of these integrins was also observed using maspin-affinity chromatography, using HT1080 cell lysates. Direct binding of maspin to a5ß1 was confirmed using a recombinant a5ß1-Fc fusion protein. Using conformation-dependent anti-ß1 antibodies, maspin binding to VSMC was found to lead to a decrease in the activation status of the integrin. The functional involvement of a5ß1 in mediating the effect of maspin was established by the inhibition of migration of CHO cells overexpressing human a5 integrin, but not those lacking a5 expression. Our observations suggest that maspin engages in specific interactions with a limited number of integrins on VSMC, leading to their inactivation, and that these interactions are responsible for the effects of maspin in the pericellular environment

transmitted drug resistance mutations and trends of hiv 1 subtypes in treatment naive patients a single centre experience

Abstract Background Transmitted drug resistances (TDRs) and HIV-1 diversity could affect treatment efficacy and clinical outcomes. Here we describe the circulating viral subtypes and estimate the prevalence of resistance among drug naive patients attending Sapienza University Hospital in Rome from 2006-2017. Methods Genotypic resistance test (GRT) was performed on 668 ART-naive patients. GRT were conducted in integrase (n = 52), protease and reverse transcriptase (n = 668) sequences. Results Twenty-one different subtypes and Circulating Recombinant Forms (CRFs) were identified. Subtype B was the most common (67%), followed by CRF02_AG (8.3%), subtypes C and F (6%). We found a significantly increased overtime in the proportion of non-B strains and in the rates of non-Italian patients (p  Minor or accessory INSTI mutations were detected in 17.3% of patients. No significant decrease of TDR prevalence was documented overtime. Conclusion The significant increase of non-B subtypes suggests that the molecular epidemiology of HIV-1 is changing. The detection of a major INSTI mutation in two naive patients highlights the importance of performing GRT before commencing treatment. This finding and the lack of a significant reduction of TDR underline the importance of a continuous surveillance of resistance mutations

Range margin reduction in carbon ion therapy: potential benefits of using radioactive ion beams

Radiotherapy with heavy ions, in particular, 12C beams, is one of the most advanced forms of cancer treatment. Sharp dose gradients and high biological effectiveness in the target region make them an ideal tool to treat deep-seated and radioresistant tumors, however, at the same time, sensitive to small errors in the range prediction. Safety margins are added to the tumor volume to mitigate these uncertainties and ensure its uniform coverage, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully exploit the benefits of a sharp Bragg peak, a large effort is put into establishing precise range verification methods for the so-called image-guided radiotherapy. Despite positron emission tomography being widely in use for this purpose in 12C ion therapy, the low count rates, biological washout, and broad shape of the activity distribution still limit its precision to a few millimeters. Instead, radioactive beams used directly for treatment would yield an improved signal and a closer match with the dose fall-off, potentially enabling precise in vivo beam range monitoring. We have performed a treatment planning study to estimate the possible impact of the reduced range uncertainties, enabled by radioactive 11C beams treatments, on sparing critical organs in the tumor proximity. We demonstrate that (i) annihilation maps for 11C ions can in principle reflect even millimeter shifts in dose distributions in the patient, (ii) outcomes of treatment planning with 11C beams are significantly improved in terms of meeting the constraints for the organs at risk compared to 12C plans, and (iii) less severe toxicities for serial and parallel critical organs can be expected following 11C treatment with reduced range uncertainties, compared to 12C treatments

The role of anandamide during pregnancy : A short tale about the endocannabinoid system

The success of any species depends on its reproductive efficiency. Sexual procreation is initiated by interactions between a sperm and an egg leading to fertilization. The fertilized egg (embryo) undergoes several mitotic cell divisions, ultimately producing the blastocyst. The nurturing of an offspring within the body and production of a live birth is an enduring task, requiring safeguard regulatory systems at various critical steps. At the moment, there is still a significant knowledge gap in understanding the mechanisms by which a successful pregnancy is achieved. It is difficult to define the hierarchical landscape of the molecular pathways during human pregnancy, because of experimental difficulties and ethical restrictions on research with human embryos. It is hoped that experiments on mice and other animal models that bear certain reproductive similarities with humans combined with those feasible experiments in humans would generate meaningful information to address this critical issue. A deeper insight into these processes will help to generate new ideas and concepts for improving fertility and pregnancy-associated health issues in humans. During the last years, several studies have provided evidence that lipid mediators are important signaling molecules in coordinating a series of events during pregnancy. Increasing evidence points toward the pathophysiological significance of endocannabinoids, a group of bioactive lipid-signaling molecules, in both female and male fertility.Sociedad Argentina de Fisiologí