CXCR1/2 pathways in paclitaxel-induced neuropathic pain

Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain that represents a frequent and serious consequence of chemotherapy agents. Over the last years, significant progress has been achieved in elucidating the underlying pathogenesis of CIPN. The interference of taxanes with microtubule has been proposed as a mechanism that leads to altered axonal transport and to permanent neurological damages. The inflammatory process activated by chemotherapeutic agents has been considered as a potential trigger of nociceptive process in CIPN.In this study we investigated the effect of reparixin, an inhibitor of CXCR1/CXCR2, in suppressing the development of paclitaxel-induced nociception in rats. Moreover, reparixin activity in reversing the neurotoxic effects induced by paclitaxel or GRO/KC in F11 cells was also analyzed.Reparixin administered by continuous infusion ameliorated paclitaxel-induced mechanical and cold allodynia in rats. In F11 cells, reparixin was able to inhibit the increase of acetyladed α-tubulin induced both by paclitaxel and GRO/KC. The subsequent experiments were performed in order to dissect the signal transduction pathways under GRO/KC control, eventually modulated by paclitaxel and/or reparixin. To this aim we found that reparixin significantly counteracted p-FAK, p-JAK2/p-STAT3, and PI3K-p-cortactin activation induced either by paclitaxel or GRO/KC.Overall the present results have identified IL-8/CXCR1/2 pathway as a mechanism involved in paclitaxel-induced peripheral neuropathy. In particular, the obtained data suggest that the inhibition of CXCR1/2 combined with standard taxane therapy, in addition to potentiating the taxane anti-tumor activity can reduce chemotherapy-induced neurotoxicity, thus giving some insight for the development of novel treatments

The IASLC Lung Cancer Staging Project: A Renewed Call to Participation

Over the past two decades, the International Association for the Study of Lung Cancer (IASLC) Staging Project has been a steady source of evidence-based recommendations for the TNM classification for lung cancer published by the Union for International Cancer Control and the American Joint Committee on Cancer. The Staging and Prognostic Factors Committee of the IASLC is now issuing a call for participation in the next phase of the project, which is designed to inform the ninth edition of the TNM classification for lung cancer. Following the case recruitment model for the eighth edition database, volunteer site participants are asked to submit data on patients whose lung cancer was diagnosed between January 1, 2011, and December 31, 2019, to the project by means of a secure, electronic data capture system provided by Cancer Research And Biostatistics in Seattle, Washington. Alternatively, participants may transfer existing data sets. The continued success of the IASLC Staging Project in achieving its objectives will depend on the extent of international participation, the degree to which cases are entered directly into the electronic data capture system, and how closely externally submitted cases conform to the data elements for the project

Valutazione degli impatti e benefici ambientali della produzione e utilizzo di un biomattone costituito da calce e uno scarto agroalimentare.

Ormai da tempo si è a conoscenza del forte impatto ambientale ed economico provocato dal settore edilizio e del legame che intercorre tra il consumo energetico e la coibentazione degli edifici. Perciò già da molti anni si ricorre a particolari materiali, solitamente di origine minerale e sintetica, dalle ottime caratteristiche d’isolamento termico-acustico, che tuttavia presentano numerosi svantaggi soprattutto legati alla loro origine non rinnovabile e al loro smaltimento spesso difficoltoso. Pertanto, negli ultimi anni si sta cercando di sostituirli con alternative di origine vegetale più ecosostenibili, ma altrettanto efficienti, come canapa, paglia, pula di farro, unite a matrici leganti al fine di ottenere i biocompositi eccezionali. L’obiettivo della presente tesi è di valutare i danni ambientali originati dalla realizzazione, uso e fine vita di 1 m2 di parete composta di biomattoni in matrice legante e pula di farro, in rapporto 2:1. Tale produzione alternativa è stata oggetto di un’esperienza svolta in laboratorio presso il Dipartimento di Ingegneria “Enzo Ferrari” dell’Università di Modena e Reggio Emilia, durante la quale è stata appresa la procedura prevista per la realizzazione di un biomattone in matrice legante e pula di farro. È stata poi effettuata la valutazione di sostenibilità ambientale del m2 di parete in biomattoni mediante la metodologia Life Cycle Assessment (LCA) condotta con l’utilizzo del software SimaPro 8.5 e il metodo di valutazione IMPACT2002+ modificato dal gruppo di lavoro. I risultati ottenuti sono stati successivamente confrontati con quelli derivanti dalla procedura attualmente più in uso, che prevede l’impiego di laterizi e generalmente un rivestimento a cappotto, e con un’ulteriore alternativa che rappresenta una variante dell’impiego della miscela in calce e pula di farro, in altre parole la realizzazione di una parete composta da un’unica colata piuttosto che da singoli biomattoni

LIFE CYCLE ASSESSMENT OF A BRIDGE COLUMN MADE OF CONCRETE AND BIOCHAR

Within construction materials, research is moving towards the use of recycled waste for the production of more sustainable concretes. Some of these studies regard the addition of biochar, a solid carbonaceous by-product obtained from the thermochemical conversion of biomass, into concrete admixtures, and have shown that biochar can improve some physical and mechanical performances of concrete. Furthermore its “carbon-sink” property allows to fix carbon in a stable form in buildings for decades. In this work, an environmental analysis was conducted, using the Life Cycle Assessment methodology, of a hypothetical bridge column consisting of a concrete matrix containing biochar, which is characterized by an environmental damage principally caused by the production phase, mainly due to the steel rebars. In order to evaluate possible environmental advantages, the results obtained were compared with those relating to a bridge column composed of a traditional concrete matrix. The comparative analysis carried out by assuming the same mechanical performances has shown that the traditional scenario is characterized by slightly higher environmental damage

The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer

The IASLC Staging and Prognostic Factors Committee has collected a new database of 94,708 cases donated from 35 sources in 16 countries around the globe. This has now been analysed by our statistical partners at Cancer Research And Biostatistics and, in close collaboration with the members of the committee proposals have been developed for the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published late 2016. In this publication we describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition

The IASLC Thymic Epithelial Tumors Staging Project: unresolved issues to be addressed for the next 9th edition of the TNM classification of malignant tumors

: Thymic epithelial tumors are presently staged using a consistent tumor, node and metastasis (TNM) classification developed by the International Association for the Study of Lung Cancer (IASLC) and approved by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC). The stage classification is incorporated in the 8th edition of the TNM classification of thoracic malignancies. The IASLC Staging and Prognostic Factors Committee (SPFC) - Thymic Domain is in charge for the next (9th) edition expected in 2024. The present paper represents the mid-term report of the SPFC Thymic Domain: in particular, it describes the unresolved issues identified by the group in the current stage classification which are worth being addressed and discussed for the 9th edition of the TNM classification based on the available data collected in the central thymic database which will be managed and analyzed by Cancer Research And Biostatistics (CRAB). These issues are grouped into issues of general importance, and those specifically related to T, N, and M categories. Each issue is described in reference to the most recent reports on the subject, and the priority assigned by the IASLC SPFC-Thymic Domain for the discussion of the 9th edition is provided

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: An Overview of the Central Database Informing Revision of the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors

International audienceIntroduction: In 2014, a TNM-based system for thymic epithelial tumors was proposed. The TNM stage classification system was published as a result of a joint project from the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group for the eighth edition of the American Joint Commission on Cancer and the Union for International Cancer Control stage classification system. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer received the mandate to make proposals for the ninth edition of the TNM stage classification. Methods: A central thymic database was collected by the Cancer Research And Biostatistics with the contribution of the major thymic associations in the world. Results: A total of 11,347 patients were collected. Submitting organizations were the following: Japanese Association for Research in the Thymus, European Society of Thoracic Surgeons, Chinese Alliance for Research in Thymoma, Korean Association for Research in the Thymus, International Thymic Malignancy Interest Group, and Réseau tumeurs THYMiques et Cancer. Additional contributions came from centers in the United States, United Kingdom, Turkey, Australia, Spain, and Italy. A total of 9147 cases were eligible for analysis. Eligible cases for analysis came from Asia and Australia (5628 cases, 61.5%), Europe (3113 cases, 34.0%), and North America (406 cases, 4.4%). Conclusions: This report provides an overview of the database that has informed the proposals for the updated T, N, and M components and the stage groups for the ninth TNM of malignant tumors

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Proposal for the T Component for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors

International audienceIntroduction: A TNM-based stage classification system of thymic epithelial tumors was adopted for the eighth edition of the stage classification of malignant tumors. The Thymic Domain of the Staging and Prognostics Factor Committee of the International Association for the Study of Lung Cancer developed a new database with the purpose to make proposals for the ninth edition stage classification system. This article outlines the proposed definitions for the T categories for the ninth edition TNM stage classification of thymic malignancies. Methods: A worldwide collective database of 11,347 patients with thymic epithelial tumors was assembled. Analysis was performed on 9147 patients with available survival data. Overall survival, freedom-from-recurrence, and cumulative incidence of recurrence were used as outcome measures. Analysis was performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors. Results: Proposals for the T categories include the following: T1 category is divided into T1a (≤5 cm) and T1b (>5 cm), irrespective of mediastinal pleura invasion; T2 includes direct invasion of the pericardium, lung, or phrenic nerve; T3 denotes direct invasion of the brachiocephalic vein, superior vena cava, chest wall, or extrapericardial pulmonary arteries and veins; and T4 category remains the same as in the eighth edition classification, involving direct invasion of the aorta and arch vessels, intrapericardial pulmonary arteries and veins, myocardium, trachea, or esophagus. Conclusions: The proposed T categories for the ninth edition of the TNM classification provide good discrimination in outcome for the T component of the TNM-based stage system of thymic epithelial tumors

The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer

Introduction Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons. Methods Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and â\u80\u9cbestâ\u80\u9d stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases. Results The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage. Conclusions The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts