p53 Activation Effect in the Balance of T Regulatory and Effector Cell Subsets in Patients With Thyroid Cancer and Autoimmunity

Carcinomas evade the host immune system by negatively modulating CD4+ and CD8+ T effector lymphocytes through forkhead box protein 3 (FOXP3) positive T regulatory cells' increased activity. Furthermore, interaction of the programmed cell death 1 (PD1) molecule and its ligand programmed cell death ligand 1 (PDL1) inhibits the antitumor activity of PD1+ T lymphocytes. Immunotherapy has become a powerful strategy for tailored cancer patients' treatment both in adult and pediatric patients aiming to generate potent antitumor responses. Nevertheless, immunotherapies can generate autoimmune responses. This study aimed to investigate the potential effect of the transformation-related protein 53 (p53) reactivation by a peptide-based inhibitor of the MDM2/MDM4 heterodimer (Pep3) on the immune response in a solid cancer, i.e., thyroid carcinoma frequently presenting with thyroid autoimmunity. In peripheral blood mononuclear cell of thyroid cancer patients, Pep3 treatment alters percentages of CD8+ and CD4+ T regulatory and CD8+ and CD4+ T effector cells and favors an anticancer immune response. Of note that reduced frequencies of activated CD8+ and CD4+ T effector cells do not support autoimmunity progression. In evaluating PD1 expression under p53 activation, a significant decrease of activated CD4+PD1+ cells was detected in thyroid cancer patients, suggesting a defective regulation in the initial activation stage, therefore generating a protective condition toward autoimmune progression

Stereotactic Radiotherapy and Androgen Deprivation Therapy for Localized Prostate Cancer: A Retrospective Mono-institutional Experience

Background/Aim: Stereotactic radiotherapy (SRT) is an effective treatment for localized prostate cancer. However, is it not clear whether the addition of androgen deprivation therapy (ADT) to SRT is beneficial. The aim of this study was to analyze the outcomes of a series of patients treated with SRT plus ADT for localized prostate cancer. Patients and Methods: Patients were treated with SRT with 42 Gy in 7 fractions with volumetric-modulated arc therapy plus Image Guided Radiotherapy (V-MAT IGRT) technique. ADT was administered to patients with intermediate unfavorable-and high-risk disease. Study endpoints were biochemical disease-free survival (bDFS), overall survival (OS), acute and late toxicity and patient-reported outcomes (PROs) using international prostate cancer symptoms scale (IPSS) and international index of erectile function (IIEF). Results: A total of 170 consecutive patients were identified, of which 49 (28.8%) with low-risk, 15 (8.8%) with favorable intermediate-risk 76 (44.7%) with unfavorable intermediate risk and 30 (17.6%) with high-risk class. All patients of unfavorable intermediate-and high-risk groups were for administered LHRH analogue concurrently to SRT and for at least 6 months. Patients with unfavorable intermediate and high-risk presented a 5-year bDFS of 81.7% and 76.9%, respectively. Conclusion: SRT consisting of 42 Gy in seven fractions with short-term ADT represents a safe and effective treatment for unfavorable intermediate and high risk prostate cancer. Our results support the need of high quality studies to test the efficacy of ADT combined with SRT for unfavorable intermediate-and high-risk localized prostate cancer

Fiducial markers in adjuvant setting for a patient affected by endometrial cancer: a case report

Introduction: Intermediate-high and high-risk endometrial cancer often require adjuvant treatments such as radiotherapy (RT) or brachitherapy (BT) to reduce the risk of loco-regional relapse. Inter- and intra-fraction variability of internal pelvic anatomy are possibly the largest source of error affecting pelvic RT. The implantation of Fiducial Makers (FMs) in the vaginal cuff of patients receiving RT or BT could help patient daily setup, image guidance and intra-fraction detection of the radiation targets. Clinical case: We have evaluated the case of an 80-year-old woman treated with surgery for endometrioid adenocarcinoma G2 (stage pT1b Nx LVSI+) who underwent adjuvant pelvic IMRT after the implantation of vaginal cuff FMs. Ct-simulation treatment planning and igrt strategy: Patient underwent planning CT scan 10 days after FMs implantation. RT consisted of 45Gy in 25 daily fractions to pelvic lymph nodes and surgical bed with simultaneous integrated boost up to 52.5Gy to the vaginal cuff and the upper two-thirds of the vagina. Cone beam Computed Tomography (CBCT) was acquired prior to every RT fraction for IGRT. Bladder and rectum were re-contoured on every CBCTs. Bladder and rectal volumes and median shifts were reported on a prospective database to quantify the impact of the pelvic organ variations. Results: The patient reported no discomfort during the FMs implantation, and no complications were seen. No evidence of FMs migration was reported. Bladder and rectal volumes planned contours were 245 and 55.3cc. Median bladder volumes for approved and "not acceptable" CBCTs were 222cc (range: 130-398) and 131cc (range: 65-326), respectively. Median rectal volumes for approved and "not acceptable" CBCTs were 75cc (range: 58-117) and 90cc (range: 54-189), respectively. The median values of the anterior-posterior, superior-inferior, lateral direction shifts were 3.4, 1.8 and 2.11 mm, respectively. Conclusion: In our clinical case, the implantation of FMs in the vaginal cuff of a patient who underwent pelvic adjuvant RT was well tolerated and reported no complications. The use of IGRT procedures based on FMs surrogating the vaginal vault may reduce inter-observer variability and pave the way for adaptive strategies or stereotactic treatments as external beam pelvic boost in gynecological field

Mechanisms of iron uptake from ferric phosphate nanoparticles in human intestinal Caco-2 cells

Food fortification programs to reduce iron deficiency anemia require bioavailable forms of iron that do not cause adverse organoleptic effects. Rodent studies show that nano-sized ferric phosphate (NP-FePO4) is as bioavailable as ferrous sulfate, but there is controversy over the mechanism of absorption. We undertook in vitro studies to examine this using a Caco-2 cell model and simulated gastrointestinal (GI) digestion. Supernatant iron concentrations increased inversely with pH, and iron uptake into Caco-2 cells was 2–3 fold higher when NP-FePO4 was digested at pH 1 compared to pH 2. The size and distribution of NP-FePO4 particles during GI digestion was examined using transmission electron microscopy. The d50 of the particle distribution was 413 nm. Using disc centrifugal sedimentation, a high degree of agglomeration in NP-FePO4 following simulated GI digestion was observed, with only 20% of the particles ≤1000 nm. In Caco-2 cells, divalent metal transporter-1 (DMT1) and endocytosis inhibitors demonstrated that NP-FePO4 was mainly absorbed via DMT1. Small particles may be absorbed by clathrin-mediated endocytosis and micropinocytosis. These findings should be considered when assessing the potential of iron nanoparticles for food fortificatio

Proton and photon radiotherapy in stage III NSCLC:Effects on hematological toxicity and adjuvant immune therapy

Background and purpose: Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment. Materials and methods: Prospectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients. Results: 271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0–4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9–12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16–0.79, P = 0.01). Conclusion: IMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab.</p

Hypofractionated simultaneous integrated boost (IMRT-SIB) with pelvic nodal irradiation and concurrent androgen deprivation therapy for high-risk prostate cancer: results of a prospective phase II trial

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Guía de bienes patrimoniales de Chacras de Coria: Un paisaje con identidad

La presente Guía es el resultado del trabajo conjunto entre un grupo de vecinos/as y distintos/as especialistas formados en patrimonio, por lo que recoge diversas voces y miradas cuyo tema en común es el compromiso y sensibilización en relación con los bienes tangibles e intangibles del distrito de Chacras de Coria en Luján de Cuyo, Mendoza. Los/as vecinos/as autoconvocados se reúnen periódicamente para intentar hacer frente, por medio de distintas acciones, a las transformaciones urbanas que consideran atentan contra su forma de vida y contra la experiencia de los/ as visitantes quienes gozan del entorno, la infraestructura y la historia de este lugar. Entre estas transformaciones se destacan la densificación acelerada mediante emprendimientos que no respetan las determinaciones del Código de Edificación, como son el F.O.S. (Factor de Ocupación del Suelo ) y el F.O.T. (Factor de Ocupación Total); la demolición de construcciones antiguas por falta de su reconocimiento y protección en el centro histórico; el proyecto impetuoso de ensanche de la Ruta Provincial n°82 (que afortunadamente se modificó debido a los reclamos); las excepciones municipales que permiten diversos proyectos que son implementados sin criterio y que atentan a la conformación urbana histórica del centro de Chacras de Coria y sus alrededores; la depredación forestal constante, entre otros. En los últimos meses, el descontento frente a estos cambios, ha llevado a realizar notas a distintos organismos, reclamos, marchas, reuniones, etc. Una suerte de movilización vecinal que sigue de cerca los nuevos proyectos y las transformaciones urbanas que no están acordes a lo que el grupo vecinal considera el espíritu del lugar.Fil: Esteves, Matias Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Cremaschi, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Martedi, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Raffa, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Videla, Eugenia. No especifíca;Fil: Suris, Estela María. Biblioteca Popular Chacras de Coria; ArgentinaFil: Del Monte, Julio César. Foro Mendocino para el Desarrollo Ferroviario; ArgentinaFil: Manzini Marchesi, Lorena Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Grau, María Amelia. Asociación Chacras para Todos; ArgentinaFil: Solanes, María Florencia. No especifíca;Fil: Copia, María Laura. Fundación Rayuela para la Cultura y la Educación; ArgentinaFil: Luis, Natalia Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Bianchi Palomares, Pablo Federico Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Moretti, Graciela. Gobierno de la Provincia de Mendoza. Ministerio de Cultura y Turismo. Dirección de Patrimonio Cultural y Museos; ArgentinaFil: Mendez, Valeria. No especifíca

Miradas desde la historia social y la historia intelectual: América Latina en sus culturas: de los procesos independistas a la globalización

Fil: Benito Moya, Silvano G. A. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; Argentina.Fil: Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; Argentina