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Immune reaction and colorectal cancer:Friends or foes?

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World Journal of Gastroenterology 2014年第35期20卷 12407-12419页

作者： Vincenzo Formica Vittore Cereda Antonella Nardecchia Manfredi Tesauro mario roselli Medical Oncology Unit ‘Tor Vergata’ University Hospital Internal Medicine Department ‘Tor Vergata’ University Hospital

The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid *** cancer is one of the most studied neoplasms for the tumor-host immunity *** immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified,still no approved therapies based on host immunity intensification have so far been introduced in clinical ***,a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this *** aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.

关键词： Colitis-associated colorectal cancer Antitumor immunity Innate immunity Adaptive immunity

Obesity and colorectal cancer:Role of adipokines in tumor initiation and progression

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World Journal of Gastroenterology 2014年第18期20卷 5177-5190页

作者： Silvia Riondino mario roselli Raffaele Palmirotta David Della-Morte Patrizia Ferroni Fiorella Guadagni Department of Systems Medicine Medical OncologyTor Vergata Clinical CenterUniversity of Rome "Tor Vergata"00133 RomeItaly Biomarker Discovery and Advanced Technologies (BioDAT) Laboratory IRCCS San Raffaele Pisana-Research Center00166 RomeItaly

Obesity-associated diseases account for a large portion of public health challenges. Among obesity-related disorders, a direct and independent relationship has been ascertained for colorectal cancer (CRC). The evidence that adipocyte hypertrophy and excessive adipose tissue accumulation (mainly visceral) can promote pathogenic adipocyte and adipose tissue-related diseases, has led to formulate the concept of “adiposopathy”, defined as adipocyte and adipose tissue dysfunction that contributes to metabolic syndrome. Adipose tissue can, indeed, be regarded as an important and highly active player of the innate immune response, in which cytokine/adipokine secretion is responsible for a paracrine loop between adipocytes and macrophages, thus contributing to the systemic chronic low-grade inflammation associated with visceral obesity, which represents a favorable niche for tumor development. The adipocyte itself participates as a central mediator of this inflammatory response in obese individuals by secreting hormones, growth factors and proinflammatory cytokines, which are of particular relevance for the pathogenesis of CRC. Among adipocyte-secreted hormones, the most relevant to colorectal tumorigenesis are adiponectin, leptin, resistin and ghrelin. All these molecules have been involved in cell growth and proliferation, as well as tumor angiogenesis and it has been demonstrated that their expression changes from normal colonic mucosa to adenoma and adenocarcinoma, suggesting their involvement in multistep colorectal carcinogenesis. These findings have led to the hypothesis that an unfavorable adipokine profile, with a reduction of those with an anti-inflammatory and anti-cancerous activity, might serve as a prognostic factor in CRC patients and that adipokines or their analogues/antagonists might become useful agents in the management or chemoprevention of CRC.

关键词： Obesity Colorectal cancer Inflammation Adiponectin Leptin Resistin Ghrelin Cytokines

Prognostic value of glycated hemoglobin in colorectal cancer

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World Journal of Gastroenterology 2016年第45期22卷 9984-9993页

作者： Patrizia Ferroni Vincenzo Formica David Della-Morte Jessica Lucchetti Antonella Spila Roberta D'Alessandro Silvia Riondino Fiorella Guadagni mario roselli San Raffaele Roma Open University 00166 Rome Italy Interinstitutional Multidisciplinary Biobank (Bio BIM) IRCCS San Raffaele Pisana00166 Rome Italy Department of Systems Medicine Medical Oncology UnitTor Vergata Clinical CenterUniversity of Rome Tor Vergata00133 Rome Italy Department of Systems Medicine University of Rome Tor Vergata00133 RomeItaly

AIM To investigate the clinical significance of routinely used glycemic parameters in a cohort of colorectal cancer(CRC) *** Pre-treatment fasting blood glucose, insulin, Hb A1 c and homeostasis model of risk assessment(HOMA-IR) were retrospectively evaluated in a case-control study of 224 CRC and 112 control subjects matched for sex, obesity and diabetes frequency and blood lipid ***, the prognostic value of routinely used glycemic parameters towards progression-free(PFS) and overall survival(OS) was prospectively *** Fasting blood glucose, insulin, HOMA-IR and HbA 1c(all P < 0.0001) levels were higher in non-diabetic CRC patients compared with obesity-matched controls. All parameters were associated with increased CRC risk at ROC analysis, but no relationship with clinical-pathological variables or survival outcomes was observed for glycemia, insulinemia or HOMA-IR. Conversely, advanced CRC stage(P = 0.018) was an independent predictor of increased Hb A1 c levels, which were also higher in patients who had disease progression compared with those who did not(P = 0.05). Elevated Hb A1 c levels showed a negative prognostic value both in terms of PFS(HR = 1.24) and OS(HR = 1.36) after adjustment for major confounders, which was further confirmed in a subgroup analysis performed after exclusion of diabetic *** HbA 1c might have a negative prognostic value in CRC, thus suggesting that glycemic metabolic markers should be carefully monitored in these patients, independently of overt diabetes.

关键词： Colorectal cancer Type 2 diabetes Glycated hemoglobin Insulin resistance Prognostic value

Clinical significance of glycemic parameters on venous thromboembolism risk prediction in gastrointestinal cancer

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World Journal of Gastroenterology 2017年第28期23卷 5187-5195页

作者： Fiorella Guadagni Silvia Riondino Vincenzo Formica Girolamo Del Monte Anna Maria Morelli Jessica Lucchetti Antonella Spila Roberta D’Alessandro David Della-Morte Patrizia Ferroni mario roselli San Raffaele Roma Open University Interinstitutional Multidisciplinary Biobank IRCCS San Raffaele Pisana Department of Systems Medicine Medical Oncology UnitTor Vergata Clinical CenterUniversity of Rome Tor Vergata Department of Palliative Care San Raffaele CassinoClinical Center Department of Systems Medicine University of Rome Tor Vergata

To investigate the possible predictive role of routinely used glycemic parameters for a first venous thromboembolism (VTE) episode in gastrointestinal (GI) cancer ambulatory patients - with or without clinically diagnosed type 2 diabetes (T2D) or obesity - treated with ***-treatment fasting blood glucose, insulin, glycated hemoglobin (HbA1c) and homeostasis model of risk assessment (HOMA) were retrospectively evaluated in a cohort study of 342 GI cancer patients. Surgery was performed in 142 (42%) patients with primary cancer, 30 (21%) and 112 (79%) of whom received neoadjuvant and adjuvant therapies, respectively. First-line chemotherapy was administered in 200 (58%) patients with metastatic disease. The study outcome was defined as the occurrence of a first symptomatic or asymptomatic VTE episode during active *** glucose tolerance (IGT) or T2D were diagnosed in 30% of GI cancer patients, while overweight/obesity had an incidence of 41%. VTE occurred in 9.4% of patients (7% of non-diabetic non-obese), especially in those with a high ECOG score (P = 0.025). No significant association was found between VTE incidence and T2D, obesity, different tumor types, metastatic disease, Khorana class of risk, or different anti-cancer drugs, although VTE rates were substantially higher in patients receiving bevacizumab (17% vs 8%, P = 0.044). Conversely, all glucose metabolic indexes were associated with increased VTE risk at ROC analysis. Multivariate Cox proportional analyses confirmed that HOMA index (HR = 4.13, 95%CI: 1.63-10.5) or fasting blood glucose (HR = 3.56, 95%CI: 1.51-8.39) were independent predictors of VTE occurrence during *** results here reported demonstrate that evaluating glucose metabolic asset may allow for VTE risk stratification in GI cancer, helping to identify chemotherapy-treated patients who might benefit from thromboprophylaxis. Further multicenter prospective studies involv

关键词： Gastrointestinal cancer Type 2 diabetes Venous thromboembolism Chemotherapy Insulin resistance

Artificial intelligence for the study of colorectal cancer tissue slides

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Artificial Intelligence in Gastroenterology 2020年第3期1卷 51-59页

作者： Vincenzo Formica Cristina Morelli Silvia Riondino Nicola Renzi Daniele Nitti mario roselli Department of Systems Medicine Medical Oncology UnitTor Vergata University HospitalRome 00133Italy

Artificial intelligence(AI)is gaining incredible momentum as a companion diagnostic in a number of fields in *** the present mini-review,we summarize the main uses and findings of AI applied to the analysis of digital histopathological images of slides from colorectal cancer(CRC)*** learning tools have been developed to automatically and objectively recognize specific CRC subtypes,such as those with microsatellite instability and high lymphocyte infiltration that would optimally respond to specific ***,AI-based classification in distinct prognostic groups with no studies of the basic biological features of the tumor have been attempted in a methodological approach that we called“biology-agnostic”.

关键词： Artificial intelligence Colorectal cancer Digital pathology Deep learning Machine learning Tumor-infiltrating lymphocytes

Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： Marta García-Juan mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

Psychic euosmia and obsessive compulsive personality disorder

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World Journal of Psychiatry 2018年第3期8卷 105-107页

作者： Massimo Pasquini Annalisa Maraone Valentina roselli Lorenzo Tarsitani Department of Human Neurosciences Sapienza University Department of Neuro- sciences and Mental Health Umberto I General Hospital

Patients with obsessive compulsive personality disorder(OCPD) often refer to a prompt mood improvement upon encountering good scents in general, or fresh laundry borax on their clothes, pillows or home settings. The Authors propose the new term psychic euosmia in the mean of an overstated psychological predisposition for a real pleasant smell that elicits an immediate sense of pleasure, order and calm. The prompt reactions to a pleasant odor might be explained by the involvement of rhinencephalon and its proximity to mood-related limbic circuits, which bypass the cognitive awareness. Cleanliness may not preclude a subject to enjoy a good smell, even if we are representing smells that resemble freshness, in other words order. A potentially even more important argument is given by the continuum of personality disorders and their variability. Not all personality characteristics led to disturbed behaviors. In evolutionary perspectives having the ability to differentiate between unpleasant and pleasant odors should have made the difference in surviving. On the other hand, psychic euosmia could be considered a normal reaction, but in our clinical experience it is over-represented among OCPD subjects with marked orderliness and disgust. Therefore, detecting psychic euosmia might vicariously confirm the relevance of disgust as a cognitive driver of OCPD. Hereby we support research to characterize psychic euosmia as a feature of orderliness and cleanliness for OCPD.

关键词： Psychic euosmia Obsessive compulsive personality disorder Orderliness Pleasure Positive emotion Pesonality

A digital earth platform for sustainability

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International Journal of Digital Earth 2017年第4期10卷 342-355页

作者： mario Hernandez Engagement Committee Future EarthMexico CityMexico International Society for Digital Earth Mexico CityMexico

Based on the experience of the International Society for Digital Earth(ISDE),this paper describes some challenges foreseen in order to develop a Digital Earth platform that can support the implementation of the Sustainable Development *** use of ready-to-use derived geospatial information is *** Earth’s methodology of‘co-design’aims to bring together natural,social scientists and decision makers to plan and carry out research for *** implies transdisciplinary research,but in order for scientists of different disciplines to work together,they will need to be able to share,access and use common *** is by far not simple!While the good will to share data might exist,the associated technological,ethical and privacy issues are difficult to *** adequate e-infrastructure will be *** could consider to use the SDGs is the basis to develop the desired Digital Earth *** paper,by no means,covers everything for a Digital Earth platform,it aims to trigger research discussions and to have a good view about a starting point.

关键词： Digital earth platform sustainable development Sustainable Development Goals future earth

Telomerase reactivation is associated with hepatobiliary and pancreatic cancers

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Hepatobiliary & Pancreatic Diseases International 2020年第5期19卷 420-428页

作者： Vito Sansone Marco Le Grazie Jenny roselli Simone Polvani Andrea Galli Francesco Tovoli Mirko Tarocchi Department of Medical and Surgical Sciences University of BolognaBolognaItaly Department of Experimental and Clinical Biomedical Sciences"mario Serio" University of Florence50139 FirenzeItaly

Background:Human telomerase reverse transcriptase(hTERT)and its components play a significant role in cancer progression,but recent data demonstrated that telomeres and telomerase alterations could be found in other diseases;increasing evidence suggests a key role of this enzyme in the fields of hepatobiliary and pancreatic *** sources:We performed a PubMed search with the following keywords:telomerase,hepatocellular carcinoma,cholangiocarcinoma,pancreatic adenocarcinoma by December *** reviewed the relevant publications that analyzed the correlation between telomerase activity and hepatobiliary and pancreatic ***:Telomerase reactivation plays a significant role in the development and progression of hepatobiliary and pancreatic tumors and could be used as a diagnostic biomarker for hepatobiliary and pancreatic cancers,as a predictor for prognosis and a promising therapeutic ***:Our review summarized the evidence about the critical role of hTERT in cancerous and precancerous lesions of the alteration and its activity in hepatobiliary and pancreatic diseases.

关键词： Telomerase Telomere Cancer Hepatobiliary and pancreatic disease