Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis.

Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. Here we report the generation of human trunk-like structures that model the co-morphogenesis, patterning and differentiation of the human spine and spinal cord. We identified differentiation conditions for human pluripotent stem cells favoring the formation of an embryo-like extending antero-posterior (AP) axis.

Propagation of Distinct α-Synuclein Strains Within Human Reconstructed Neuronal Network and Associated Neuronal Dysfunctions.

Aggregated alpha-synuclein (α-Syn) in neurons is a hallmark of Parkinson's disease (PD) and other synucleinopathies. Recent advances (1) in the production and purification of synthetic assemblies of α-Syn, (2) in the design and production of microfluidic devices allowing the construction of oriented and compartmentalized neuronal network on a chip, and (3) in the differentiation of human pluripotent stem cells (hPSCs) into specific neuronal subtypes now allow the study of cellular and molecular determinants of the prion-like properties of α-Syn in vitro. Here, we described the methods we used to reconstruct a cortico-cortical human neuronal network in microfluidic devices and how to take advantage of this cellular model to characterize (1) the prion-like properties of different α-Syn strains and (2) the neuronal dysfunctions and the alterations associated with the exposure to α-Syn strains or the nucleation of endogenous α-Syn protein in vitro.

The role of radiation therapy technologist in interventional radiotherapy (brachytherapy) in Italy: Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Association of Radiation Therapy and Medical Physics Technologists (AITRO) joint project.

Purpose: Interventional radiotherapy (IRT, brachytherapy and intra-operative radiotherapy) is a complex treatment approach that requires a multi-professional approach. The aim of this work was to assess the role of radiation therapy technologist (RTT) in IRT team, with a special focus on brachytherapy as well as to define more appropriate ways to improve skills and training to promote cooperation of multi-professional team.

Material And Methods: A nationwide survey consisting of 16 questions was proposed between April and May 2020, with collaboration between the Italian Association of Radiation Therapy and Medical Physics Technologists (AITRO) and the Interventional Radiotherapy Study Group of Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Neurogranin Regulates Adult-Born Olfactory Granule Cell Spine Density and Odor-Reward Associative Memory in Mice.

Neurogranin (Ng) is a brain-specific postsynaptic protein, whose role in modulating Ca/calmodulin signaling in glutamatergic neurons has been linked to enhancement in synaptic plasticity and cognitive functions. Accordingly, Ng knock-out (Ng-ko) mice display hippocampal-dependent learning and memory impairments associated with a deficit in long-term potentiation induction. In the adult olfactory bulb (OB), Ng is expressed by a large population of GABAergic granule cells (GCs) that are continuously generated during adult life, undergo high synaptic remodeling in response to the sensory context, and play a key role in odor processing.

Adjuvant vaginal interventional radiotherapy in early-stage non-endometrioid carcinoma of corpus uteri: a systematic review.

Purpose: This systematic review focused on rare histological types of corpus uteri malignancy, including uterine carcinosarcoma (UCS), uterine clear cell carcinoma (UCCC), and uterine papillary serous carcinoma (UPSC), and it is proposed to assist with clinical decision-making. Adjuvant treatment decisions must be made based on available evidences. We mainly investigated the role of vaginal interventional radiotherapy (VIRt) in UCS, UCCC, and UPSC managements.

The role of vaginal brachytherapy in stage I endometrial serous cancer: a systematic review.

Purpose: Serous adenocarcinoma (uterine serous carcinoma - USC) is a rare and aggressive histologic subtype of endometrial cancer, with a high-rate of recurrence and poor prognosis. The adjuvant treatment for stage I patients is unclear. The purpose of this study was to evaluate the outcomes of stage I USC treated exclusively with chemotherapy plus vaginal brachytherapy (VBT).

Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial.

Background: The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis.

Methods: In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I-III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0-2.

Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network.

Reappraisal of neuropathological studies suggests that pathological hallmarks of Alzheimer's disease and Parkinson's disease (PD) spread progressively along predictable neuronal pathways in the human brain through unknown mechanisms. Although there is much evidence supporting the prion-like propagation and amplification of α-synuclein (α-Syn) in vitro and in rodent models, whether this scenario occurs in the human brain remains to be substantiated. Here we reconstructed in microfluidic devices corticocortical neuronal networks using human induced pluripotent stem cells derived from a healthy donor.

CaMKIIα Expression Defines Two Functionally Distinct Populations of Granule Cells Involved in Different Types of Odor Behavior.

Granule cells (GCs) in the olfactory bulb (OB) play an important role in odor information processing. Although they have been classified into various neurochemical subtypes, the functional roles of these subtypes remain unknown. We used in vivo two-photon Ca imaging combined with cell-type-specific identification of GCs in the mouse OB to examine whether functionally distinct GC subtypes exist in the bulbar network.

Survey on gynecological cancer treatment by Piedmont, Liguria, and Valle d'Aosta group of AIRO (Italian Association of Radiation Oncology).

Purpose: We focused the attention on radiation therapy practices about the gynecological malignancies in Piedmont, Liguria, and Valle d'Aosta to know the current treatment practice and to improve the quality of care.

Material And Methods: We proposed a cognitive survey to evaluate the standard practice patterns for gynecological cancer management, adopted from 2012 to 2014 by radiotherapy (RT) centers with a large amount of gynecological cancer cases. There were three topics: 1.

A role for dendritic translation of CaMKIIα mRNA in olfactory plasticity.

Local protein synthesis in dendrites contributes to the synaptic modifications underlying learning and memory. The mRNA encoding the α subunit of the calcium/calmodulin dependent Kinase II (CaMKIIα) is dendritically localized and locally translated. A role for CaMKIIα local translation in hippocampus-dependent memory has been demonstrated in mice with disrupted CaMKIIα dendritic translation, through deletion of CaMKIIα 3'UTR.

Transitory and activity-dependent expression of neurogranin in olfactory bulb tufted cells during mouse postnatal development.

Neurogranin (Ng) is a brain-specific postsynaptic calmodulin-binding protein involved in synaptic activity-dependent plasticity. In the adult olfactory bulb (OB), Ng is expressed by a large population of GABAergic interneurons in the granule cell layer. We show here that, during postnatal development, Ng is also expressed by OB neurons in the superficial external plexiform layer (sEPL) and glomerular layer (GL).

New striatal neurons in a mouse model of progressive striatal degeneration are generated in both the subventricular zone and the striatal parenchyma.

Acute striatal lesions increase proliferation in the subventricular zone (SVZ) and induce migration of SVZ neuroblasts to the striatum. However, the potential of these cells to replace acutely degenerated neurons is controversial. The possible contribution of parenchymal progenitors to striatal lesion-induced neurogenesis has been poorly explored.

From progenitors to integrated neurons: role of neurotransmitters in adult olfactory neurogenesis.

Adult neurogenesis is due to the persistence of pools of constitutive stem cells able to give rise to a progeny of proliferating progenitors. In rodents, adult neurogenic niches have been found in the subventricular zone (SVZ) along the lateral ventricles and in the subgranular zone of the dentate gyrus in the hippocampus. SVZ progenitors undergo a unique process of tangential migration from the lateral ventricle to the olfactory bulb (OB) where they differentiate mainly into GABAergic interneurons in the granule and glomerular layers.

Target volume delineation for preoperative radiotherapy of rectal cancer: inter-observer variability and potential impact of FDG-PET/CT imaging.

To analyze the inter-observer variability and the potential impact of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) imaging for target volume delineation in preoperative radiotherapy of rectal cancer. Gross tumor volume (GTV) and clinical target volume (CTV) in 2 cases of rectal cancer were contoured by 10 radiation oncologists, 5 on CT and 5 on PET/CT images. Resulting volumes were analyzed by coefficient of variation (CV) and concordance index (CI).

Expression and localization of the calmodulin-binding protein neurogranin in the adult mouse olfactory bulb.

Neurogranin (Ng) is a brain-specific postsynaptic protein involved in activity-dependent synaptic plasticity through modulation of Ca(2+)/calmodulin (CaM)-dependent signal transduction in neurons. In this study, using biochemical and immunohistochemical approaches, we demonstrate Ng expression in the adult mouse olfactory bulb (OB), the first relay station in odor information processing. We show that Ng is principally associated with the granule cell layer (GCL), which is composed of granule cell inhibitory interneurons.

In vitro and in vivo models for the evaluation of new inhibitors of human steroid sulfatase, devoid of residual estrogenic activity.

The goal of our research project is to develop a new class of orally active drugs, estrone sulfatase inhibitors, for the treatment of estrogen-dependent (receptor positive) breast cancer. Several compounds were synthesized and their pharmacological potencies explored. Based on encouraging preliminary results, three of them, TX 1299, TX 1492 and TX 1506 were further studied in vitro as well as in vivo.

Small cell carcinoma of the esophagus.

Small cell carcinoma of the esophagus (SCEC) is a rare tumor with its particular biologic features, distinct from squamous and glandular carcinoma of esophagus. Although initial symptoms can be similar (with metastatic dissemination and paraneoplastic syndromes at presentation more frequent in SCEC), differences in age and sex distribution, tumor location, radiological and endoscopic findings, clinical course and prognosis have been observed between SCEC and other esophageal malignancies. SCEC should be considered a systemic disease, and by analogy to bronchogenic small cell carcinoma, multimodality approach including chemotherapy is recommended.

[Role of radiotherapy in the combined treatment of invasive cancer of the vulva].

The authors review the literature on the different combinations of radiotherapy with chemotherapy and surgery with the aim of giving a state of art on the role of combined multimodality treatment of invasive vulvar carcinoma. From the data of the recent literature it appears that radiation integrated with surgery and chemotherapy can play an important role in reducing the risk of postoperative locoregional failure in patients with advanced primary or nodal disease and avoiding exenteration in patients with disease involving the anus or proximal urethra. This integrated multimodality therapy is a promising approach in the treatment of invasive vulvar carcinoma but further exploration in a larger number of patients is needed before giving consolidated data applicable in routine oncological clinical practice.