Search

Supplementary Information - PDF file 145K, Supplementary Material and Methods; Supplementary Figure Legend S1 (Proliferation of tumor-specific CD4 T cells by matured DC pulsed with autologous tumor lysate.); Supplementary Figure Legend S2 (In breast tumors TEM and CD11c+ are distinct cell subsets.); Supplementary Tables S1 (Clinical and pathological features of tumors and patients (n=40)); Supplementary Tables S2 (CD11c+ DC and TEM from breast tumors were exposed to autologous CFSE-labeled T cells and their proliferation assessed five days later by flow cytometry.); Supplementary References

Supplementary figures - PDF file 1536K, Figure S1. Proliferation of tumor-specific CD4 T cells by matured DC pulsed with autologous tumor lysate; Figure S2. In breast tumors TEM and CD11c+ are distinct cell subsets

Background Increasing data support the role of BCSCs in recurrence and resistance to chemotherapy. However, detecting these cells specifically and targeting them therapeutically remain challenging. We set to identify miRNAs involved in chemoresistance of BCSCs in vitro and the results were assessed in the sera of healthy donors and breast cancer patients treated with neoadjuvant chemotherapy (NAC). Methods In vitro experiments were conducted in the MCF7 cell line grown as mammospheres (MS) in order to enrich a BCSC phenotype. After treatment with 5FU or Paclitaxel (Pac), microRNA profile of chemoresistant cells was analyzed by microarray. The results were compared to miRNAs found in immortalized non-tumorigenic MCF10A cells in order to exclude miRNAs related to normal stem cells. A signature of 6 miRNAs was identified. miR-363-3p, appearing the most relevant, was chosen for further assessment. By RT-qPCR, miR363-3p levels were 20- and 100-fold higher in ALDH+ sorted cells compared to ALDH- MCF7 and MDA-MB-231 cells, respectively. Moreover, overexpression of miR363-3p in MCF7 cells correlated with an increased number of ALDH+ cells and 1.5 more MS formed. In contrast, downregulation of miR363-3p levels induced a decrease in MS size and 2-fold reduction in number. Consistently, miR-363-3p downregulation decreased tumor growth and metastasis of MCF7 cells in an intraductal human-in-mice transplantation model. miRNA was quantified by RT-qPCR in tissue and sera collected prospectively from 40 breast cancer patients before and after NAC (anthracycline-taxane) and also from 25 healthy donors. Results Fifty percent of the patients had luminal A and B tumors (n=20), 32,5% (n=13) had triple negative breast cancer (TNBC), and 17.5% (n=7) had HER2 positive BC. Excluding one patient, who refused the surgical resection, 40% achieved pathological complete response (pCR). Six patients presented disease recurrence. In patients’ tumor before and after NAC, a higher level of miR363-3p was observed compared with benign tissue. In sera of the BC patients, miR363-3p levels were significantly higher than that of healthy donors. After NAC, the levels of miR363-3p remained high among patients who relapsed, whereas they were equivalent to the healthy donors in patients who remained in remission. No correlation between Ki-67, grade 1 or 2 and miR363-3p levels was observed. However, in grade 3 BC, low level of miR363-3p before and after NAC was correlated with pCR and remission. The level of miR363-3p correlated with remission and pCR in patients with TNBC and HER2 BC. Conclusions Assessment in the sera of patients and healthy donors confirms our previous data supporting the role of miR363-3p as predictive factor of resistance to neoadjuvant chemotherapy and disease recurrence. Further investigations are warranted to confirm the role of miR363-3p as a biomarker and potential therapeutic target. Citation Format: Stephanie Renaud, Athina Stravodimou, Maryse Fiche, Ioannis Xenarios, Scabia Valentina, Valerian Dormoy, Marie Galmiche, Cathrin Brisken, Jean-Francois Delaloye, Assia Treboux, Jean-Yves Meuwly, Nicolas Mermod, Khalil Zaman. miR363-3p mediates maintenance of breast cancer stem cells (BCSCs) and predicts resistance to neoadjuvant chemotherapy and disease recurrence [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-22.

El sistema presupuestario público se inscribe como uno de los pilares del proceso de las finanzas públicas. Se ocupa de organizar la gestión pública y vincular las responsabilidades del Estado en el cumplimiento de sus funciones y en la realización de los planes y programas proyectados. El presupuesto público es el límite de gastos que una entidad puede realizar durante un año, de acuerdo a los ingresos que espera recibir, y debe ser la expresión financiera de los programas y proyectos que ejecutará para alcanzar los objetivos del plan de gobierno. Permite estimar los recursos que se obtendrán y distribuirlos de acuerdo a las prioridades de gobierno, entre las distintas instituciones. En consecuencia, es el principal instrumento de política pública, a través del cual se concretan los objetivos de gobierno y se identifican a las entidades responsables, siendo asimismo un mecanismo redistributivo de la riqueza. El resultado esperado de este proceso es un presupuesto público idóneo como instrumento de gestión y de información de las políticas públicas previstas para el corto y mediano plazo y el grado de efectividad y eficiencia en su cumplimiento. Considerando el carácter federal de nuestro país, las políticas fiscales vinculadas con las jurisdicciones provinciales y municipales, y sus implicancias financieras, deben estar articuladas razonable y adecuadamente con sus propias realidades económicas y sociales, de modo de obtener un panorama multidimensional de la situación de los gobiernos sub-nacionales en el marco de las políticas públicas nacionales, definidas en el presupuesto nacional. Los presupuestos tienen impactos muy concretos en la vida de las personas y el ejercicio efectivo de sus derechos. Los más directos se vinculan con la forma en que se gastan los recursos públicos y las prioridades a las que se asignan los fondos. Pero también existen efectos indirectos como los impactos que un presupuesto tiene en cuestiones como el empleo o la inflación. Fil: Ameriso, Claudia C. Universidad Nacional de Rosario; Argentina

BackgroundThe aim of the study was to identify risk factors for positive surgical margins in breast-conserving surgery for breast cancer and to evaluate the influence of surgical experience in obtaining complete resection.MethodsAll lumpectomies for invasive breast carcinoma and ductal carcinoma in situ (DCIS) between April 2008 and March 2010 were selected from the database of a single institution. Re-excision rates for positive margins as well as patient and histopathologic tumor characteristics were analyzed. Surgical experience was staged by pairs made of Resident plus Specialist or Consultant. Two periods were defined. During period A, the majority of operations were performed by Residents under supervision of Specialist or Consultant. During period B, only palpable tumors were operated by Residents.ResultsThe global re-excision rate was 27% (50 of 183 patients). The presence of DCIS increased the risk for positive margins: 60% (nine of 15 patients) in the case of sole DCIS compared to 26% (41 of 160 patients) for invasive cancer (p = 0.005) and 35% (42 of 120 patients) in the case of peritumoral DCIS compared to 11% (seven of 62 patients) in the case of sole invasive cancer (p = 0.001). Re-excision rate decreased from 36% (23 of 64 patients) during period A to 23% (27 of 119 patients) during period B (p = 0.055). There was no significant difference between the surgical pairs.ConclusionIn our study, DCIS was the only risk factor for positive surgical margins. Breast-conserving surgery for non-palpable tumors should be performed by Specialists, however, palpable tumors can be safely operated by Residents under supervision.

Las finanzas públicas constituyen la rama del conocimiento que se ocupa del funcionamiento económico del Estado. Por lo tanto, su importancia crece en la medida en que el sector público se vuelve más relevante para la actividad económica. En una economía con un Estado poco desarrollado, las finanzas públicas tendrán un papel poco significativo. En cambio, en una economía con un sector público importante, en términos cuantitativos y cualitativos, éstas juegan un rol decisivo. La tributación es un componente esencial de las políticas públicas, siendo los impuestos la fuente fundamental del financiamiento de los programas de gasto público. Si están adecuadamente diseñados, los sistemas impositivos pueden mejorar la gobernanza, la transparencia y la rendición de cuentas. La presión tributaria es un indicador que hace referencia al “peso” que ejerce el Estado sobre una economía al detraer recursos privados de manera coercitiva para el financiamiento de sus actividades. El monitoreo de cerca de la gestión pública, colabora con el uso adecuado de los recursos públicos e induce un mejor desempeño del Estado, por ello el trabajo aborda la evolución de este indicador a nivel nacional, en el contexto de algunos países americanos para derivar, en particular, en la presión fiscal provincial, focalizando en la provincia de Santa Fe, lo que nos permite concluir que la presión impositiva real en Santa Fe es baja en relación con la de otras provincias argentinas, encontrándose en la décima posición dentro de las 13 provincias que cuentan con información disponible. Fil: Ameriso, Claudia C. Universidad Nacional de Rosario; Argentina Fil: Treboux, Javier. Universidad Nacional de Rosario; Argentina

It is widely accepted that deep neural networks are very efficient for object detection in images. They reach their limit when multiple long line instances have to be detected in very high resolution images. In this paper, we present an original methodology for the recognition of vine lines in high resolution aerial images. The process consists in combining a neural network with a subclassifier. We first compare a traditional U-Net architecture with a U-Net architecture designed for precision agriculture. We then highlight the significant improvement in vine line detection when a DTE is added after the customized U-Net. This methodology addresses the complex task of dissociating vine lines from other agricultural objects. The trained model is not sensitive to the orientation of the lines. Therefore, our experiments have improved the precision by around 15% compared to our improved neural network.

Invasive lobular carcinoma (ILC) is the most frequent special histological subtype of breast cancer, typically characterized by loss of E‐cadherin. It has clinical features distinct from other estrogen receptor‐positive (ER+) breast cancers but the molecular mechanisms underlying its characteristic biology are poorly understood because we lack experimental models to study them. Here, we recapitulate the human disease, including its metastatic pattern, by grafting ILC‐derived breast cancer cell lines, SUM‐44 PE and MDA‐MB‐134‐VI cells, into the mouse milk ducts. Using patient‐derived intraductal xenografts from lobular and non‐lobular ER+ HER2− tumors to compare global gene expression, we identify extracellular matrix modulation as a lobular carcinoma cell‐intrinsic trait. Analysis of TCGA patient datasets shows matrisome signature is enriched in lobular carcinomas with overexpression of elastin, collagens, and the collagen modifying enzyme LOXL1. Treatment with the pan LOX inhibitor BAPN and silencing of LOXL1 expression decrease tumor growth, invasion, and metastasis by disrupting ECM structure resulting in decreased ER signaling. We conclude that LOXL1 inhibition is a promising therapeutic strategy for ILC., Intraductal xenografts of invasive lobular carcinoma (ILC) cells faithfully model this breast cancer subtype, and reveal tumor cell intrinsic ECM remodeling as a critical feature of disease progression that can be exploited therapeutically by targeting LOXL1.