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Liquid biopsy in colorectal cancer:No longer young,but not yet old

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World Journal of Gastroenterology 2022年第15期28卷 1503-1507页

作者： Giandomenico Roviello Daniele Lavacchi Lorenzo Antonuzzo Martina Catalano Enrico Mini Department of Health Sciences Section of Clinical Pharmacology and OncologyUniversity of FlorenceFirenze 50139Italy Clinical Oncology Unit AOU CareggiFirenze 50134Italy Department of Experimental and Clinical Medicine University of FirenzeFirenze 50134Italy School of Human Health Sciences University of FlorenceFlorence 50134Italy

Colorectal cancer(CRC)is one of the most prevalent cancers and the second leading cause of cancer-related deaths worldwide.The treatment strategy employed in CRC patients is becoming highly dependent on molecular characteristics present at diagnosis and during treatment.Liquid biopsy is an emerging field in the management of this cancer,and its relevance as a potential diagnostic,prognostic,monitoring,and therapeutic tool makes it a viable strategy in the clinical management of CRC patients.Liquid biopsy also has certain limitations,but these limitations seem to be at the reach of near-future technological development.In this letter,we focus on the clinical perspectives of liquid biopsy in CRC with particular regard to the various biomarkers recently identified that have been shown to be potentially useful in multiple aspects of early stage or metastatic CRC.

关键词： Colorectal cancer Liquid biopsy Circulating tumor DNA Diagnosis Prognosis Targeted therapy

Robotic approach with neoadjuvant chemotherapy in adult Wilms’ tumor: A feasibility study report and a systematic review of the literature

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Asian Journal of Urology 2023年第2期10卷 128-136页

作者： Simone Sforza Valeria Emma Palmieri Maria Rosaria Raspollini Giandomenico Roviello Alberto Mantovani Umberto Basso Maria Carmen Affinita Alberto D’Angelo Lorenzo Antonuzzo Marco Carini Andrea Minervini lorenzo Masieri Department of Oncologic Minimally-Invasive Urology and AndrologyCareggi HospitalUniversity of FlorenceFlorenceItaly Department of Pediatric Urology Meyer Children HospitalUniversity of FlorenceFlorenceItaly Clinical Oncologic Unit Careggi HospitalUniversity of FlorenceFlorenceItaly Histopathology and Molecular Diagnostics Careggi HospitalUniversity of FlorenceFlorenceItaly Medical Oncology Unit 1 Istituto Oncologico Veneto IOV IRCCSPaduaItaly Hematology Oncology Division Department of Women’s and Children’s HealthPadova University HospitalPaduaItaly Department of Biology and Biochemistry University of BathBathUK

Objective:The incidence of Wilms’tumor(WT)among adult individuals accounts for less than 1%of kidney cancer cases,with a prognosis usually less favorable when compared to younger individuals and an overall survival rate of 70%for the adult patients versus 90%for the pediatric cases.The diagnosis and treatment of WT are complex in the preoperative setting;neoadjuvant chemotherapy(NAC)or robotic surgery has rarely been described.This study aimed to review the literature of robotic surgery in WT and report the first adult WT management using both NAC and robotic strategy.Methods:We reported a case of WT managed in a multidisciplinary setting.Furthermore,according to Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations,a systematic review of the literature until August 2020 of WT treated with a robotic approach was carried out.Results:A 33-year-old female had a diagnosis of WT.She was scheduled to NAC,and according to the clinical and radiological response to a robotic radical nephrectomy with aortic lymph nodes dissection,she was managed with no intraoperative rupture,a favorable surgical outcome,and a follow-up of 25 months,which did not show any recurrence.The systematic review identified a total number of 230 cases of minimally invasive surgery reported in the literature for WT.Of these,approximately 15 patients were carried out using robotic surgery in adolescents while none in adults.Moreover,NAC has not been administered before minimally invasive surgery in adults up until now.Conclusion:WT is a rare condition in adults with only a few cases treated with either NAC or minimally invasive approach so far.The advantage of NAC followed by the robotic approach could lead to favorable outcomes in this complex scenario.Notwithstanding,additional cases of adult WT need to be identified and investigated to improve the oncological outcome.

关键词： Nephroblastoma Nephrectomy Renal neoplasm Minimally invasive surgery Rare tumor

Orbital lesions,an exceedingly rare site of neuroendocrine tumor metastasis

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Journal of Cancer Metastasis and Treatment 2016年第1期2卷 341-344页

作者： Sara Pusceddu Massimo Milione Silvia Ortolani Alessio Pellegrinelli Marco Brugia Filippo de Braud Lorenzo Antonuzzo Department of Medical Oncology Fondazione IRCCS“Istituto Nazionale dei Tumori”20133 MilanItaly Department of Phatology Fondazione IRCCS“Istituto Nazionale dei Tumori”20133 MilanItaly Department of Medical Oncology Azienda Ospedaliera Universitaria IntegrataUniversity of Verona37134 VeronaItaly Department of Medical Oncology Azienda Ospedaliera Universitaria Careggi50134 FirenzeItaly Medical Genetics University of Siena53100 SienaItaly

Neuroendocrine tumors are rare neoplasms arising primarily in the gastrointestinal tract and lung.The liver is the most common site of metastases,but these tumors can rarely metastasize to atypical sites.Surgery is the only curative approach while the optimal medical treatment is debated.From this perspective,a multidisciplinary approach for each single case becomes very important.In this report we describe the case of a male affected by a single intraorbital metastasis from a midgut well differentiated neuroendocrine tumor.The patient refused surgical removal and therefore he was at first treated with stereotactic radiotherapy and systemic treatment with a somatostatin analog(SSA).After achieving a stable disease for four months he underwent primary tumor resection.Six years after the initial diagnosis,the patient is currently stable and receiving SSA at standard dose.

关键词： Neuroendocrine tumors orbital metastases somatostatin analogues

Molecular classifications of gastric cancers: Novel insights and possible future applications

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World Journal of Gastrointestinal Oncology 2017年第5期9卷 194-208页

作者： Silvio Ken Garattini Debora Basile Monica Cattaneo Valentina Fanotto Elena Ongaro Marta Bonotto Francesca V Negri Rosa Berenato Paola Ermacora Giovanni Gerardo Cardellino Mariella Giovannoni Nicoletta Pella Mario Scartozzi Lorenzo Antonuzzo Nicola Silvestris Gianpiero Fasola Giuseppe Aprile Department of Oncology University and General Hospital Medical Oncology University Hospital Medical Oncology National Cancer InstituteIRCCS Department of Oncology University Hospital

Despite some notable advances in the systemic management of gastric cancer(GC), the prognosis of patients with advanced disease remains overall poor and their chance of cure is anecdotic. In a molecularly selected population, a median overall survival of 13.8 mo has been reached with the use of human epidermal growth factor 2(HER2) inhibitors in combination with chemotherapy, which has soon after become the standard of care for patients with HER2-overexpressing GC. Moreover, oncologists have recognized the clinical utility of conceiving cancers as a collection of different molecularlydriven entities rather than a single disease. Several molecular drivers have been identified as having crucial roles in other tumors and new molecular classifications have been recently proposed for gastric cancer as well. Not only these classifications allow the identification of different tumor subtypes with unique features, but also they serve as springboard for the development of different therapeutic strategies. Hopefully, the application of standard systemic chemotherapy, specifictargeted agents, immunotherapy or even surgery in specific cancer subgroups will help maximizing treatment outcomes and will avoid treating patients with minimal chance to respond, therefore diluting the average benefit. In this review, we aim at elucidating the aspects of GC molecular subtypes, and the possible future applications of such molecular analyses.

关键词：分子的生物学免疫疗法胃的癌症分类指向的治疗

Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2014年第3期20卷 786-794页

作者： Andrea L Inghilesi Donatella Gallori Lorenzo Antonuzzo Paolo Forte Daniela Tomcikova Umberto Arena Stefano Colagrande Silvia Pradella Bernardo Fani Elena Gianni Luca Boni Giacomo Laffi Francesco Di Costanzo Fabio Marra Dipartimento di Medicina Sperimentale e Clinica Università degli Studi di Firenze Oncologia Medica Azienda Ospedaliero-Universitaria Careggi Gastroenterologia 2 Azienda Ospedaliero-Universitaria Careggi Centro per il Coordinamento delle Sperimentazioni Cliniche Istituto Toscano Tumoriand Azienda Ospedaliero-Universitaria Careggi Dipartimento di Scienze Biomediche Sperimentali e ClinicheUniversità degli Studi di Firenze

AIM:To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma(HCC)in patients with established cirrhosis.METHODS:From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled.According to the Barcelona Clinic Liver Cancer(BCLC)classification,patients were in the advanced stage(BCLC-C)or in the intermediate stage(BCLC-B)but unfit or unresponsive to other therapeutic strategies.Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo,and analyzed according to the modified Response Evaluation Criteria in Solid Tumors.Sorafenib was administered at 800 mg/d,until radiological progression or occurrence of unacceptable adverse events(AEs).Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.RESULTS:Forty-four patients were enrolled,15 had intermediate HCC and 14 a Child-Pugh score of B7.AEs caused treatment interruption in 19 patients(43%),and median treatment duration was shorter in this subset(5 wk vs 19 wk,P<0.001)and in the BCLC-C subgroup(13 wk vs 40 wk,P=0.015).No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years.After 16 wk of treatment,18 patients(41%)had stable disease or partial response.Patients with viral infection or BCLC-C were at higher risk of disease progression.ECOG,extrahepatic spread,macrovascular invasion,alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.CONCLUSION:In patients with cirrhosis and HCC treated with sorafenib,AEs are a common cause of early treatment withdrawal.Vascular invasion and extrahepatic spread condition early response to treatment and survival.Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter

关键词： Hepatocellular carcinoma Sorafenib Cirrhosis Adver

Growth associated protein 43 and neurofilament immunolabeling in the transected lumbar spinal cord of lizard indicates limited axonal regeneration

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Neural Regeneration Research 2022年第5期17卷 1034-1041页

作者： lorenzo Alibardi Comparative Histolab Padova and Department of Biology University of BolognaBolognaItaly

Previous cytological studies on the transected lumbar spinal cord of lizards have shown the presence of differentiating glial cells,few neurons and axons in the bridge region between the proximal and distal stumps of the spinal cord in some cases.A limited number of axons(20-50)can cross the bridge and re-connect the caudal stump of the spinal cord with small neurons located in the rostral stump of the spinal cord.This axonal regeneration appears to be related to the recovery of hind-limb movements after initial paralysis.The present study extends previous studies and shows that after transection of the lumbar spinal cord in lizards,a glial-connective tissue bridge that reconnects the rostral and caudal stumps of the interrupted spinal cord is formed at 11-34 days post-injury.Following an initial paralysis some recovery of hindlimb movements occurs within 1-3 months post-injury.Immunohistochemical and ultrastructural analysis for a growth associated protein 43(GAP-43)of 48-50 k Da shows that sparse GAP-43 positive axons are present in the proximal stump of the spinal cord but their number decreased in the bridge at 11-34 days post-transection.Few immunolabeled axons with a neurofilament protein of 200-220 k Da were seen in the bridge at 11-22 days post-transection but their number increased at 34 days and 3 months post-amputation in lizards that have recovered some hindlimb movements.Numerous neurons in the rostral and caudal stumps of the spinal cord were also labeled for GAP43,a cytoplasmic protein that is trans-located into their axonal growth cones.This indicates that GAP-43 biosynthesis is related to axonal regeneration and sprouting from neurons that were damaged by the transection.Taken together,previous studies that utilized tract-tracing technique to label the present observations confirm that a limited axonal re-connection of the transected spinal cord occurs 1-3 months post-injury in lizards.The few regenerating-sprouting axons within the bridge reconnect the caudal with the rostral stumps of the spina

关键词： GAP-43 immunocytochemistry lizard neurofilaments regeneration spinal cord

Brain network modulation in Alzheimer’s disease:clinical phenotypes and windows of opportunity

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Neural Regeneration Research 2023年第1期18卷 115-116页

作者： lorenzo Pini Padova Neuroscience Center University of PadovaPadovaItaly

Dementia,for which there is no cure or effective treatment,is the leading cause of disability and death worldwide.Due to the high global prevalence and economic impact on families,caregivers,and communities,this condition represents one of the most significant public health challenges of our time.Dementia is an umbrella term describing a range of progressive neurodegenerative diseases,including Alzheimer’s disease(AD),which is the most common cause of cognitive and functional impairment among older adults.The presence of misfolded protein aggregates characterizes neurodegenerative disorders(e.g.,amyloid-beta(Aβ)and tau in AD).

关键词： Alzheimer Aβ death tau

Immunodetection of ephrin receptors in the regenerating tail of the lizard Podarcis muralis suggests stimulation of differentiation and muscle segmentation

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Zoological Research 2019年第5期40卷 416-426页

作者： lorenzo Alibardi Comparative Histolab Padova and Department of Biology University of Bologna

Ephrin receptors are the most common tyrosine kinase effectors operating during development. Ephrin receptor genes are reported to be up-regulated in the regenerating tail of the Podarcis muralis lizard. Thus, in the current study, we investigated immunolocalization of ephrin receptors in the Podarcis muralis tail during regeneration. Weak immunolabelled bands for ephrin receptors were detected at 15–17 kDa, with a stronger band also detected at 60–65 kDa. Labelled cells and nuclei were seen in the basal layer of the apical wound epidermis and ependyma, two key tissues stimulating tail regeneration. Strong nuclear and cytoplasmic labelling were present in the segmental muscles of the regenerating tail, sparse blood vessels, and perichondrium of regenerating cartilage. The immunolocalization of ephrin receptors in muscle that gives rise to large portions of new tail tissue was correlated with their segmentation. This study suggests that the high localization of ephrin receptors in differentiating epidermis, ependyma, muscle, and cartilaginous cells is connected to the regulation of cell proliferation through the activation of programs for cell differentiation in the proximal regions of the regenerating tail. The lower immunolabelling of ephrin receptors in the apical blastema, where signaling proteins stimulating cell proliferation are instead present, helps maintain the continuous growth of this region.

关键词： Lizard Regenerating blastema Ephrin receptors Immunolabelling Western blotting

Tail regeneration reduction in lizards after repetitive amputation or cauterization reflects an increase of immune cells in blastemas

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Zoological Research 2018年第6期39卷 413-423页

作者： lorenzo Alibardi Comparative Histolab Padua Department of BiologyUniversity of Bologna

Lizards are key amniote models for studying organ regeneration. During tail regeneration in lizards, blastemas contain sparse granulocytes, macrophages, and lymphocytes among the prevalent mesenchymal cells. Using transmission electron microscopy to examine scarring blastemas after third and fourth sequential tail amputations, the number of granulocytes, macrophages, and lymphocytes increased at 3-4 weeks in comparison to the first regeneration. An increase in granulocytes and agranulocytes also occurred within a week after blastema cauterization during the process of scarring Blood at the third and fourth regeneration also showed a significant increase in white blood cells compared with that under normal conditions and at the first regeneration. The extracellular matrix of the scarring blastema, especially after cauterization, was denser than that in the normal blastema and numerous white blood cells and fibroblasts were surrounded by electron-pale, fine fibrinoid material mixed with variable collagen fibrils. In addition to previous studies, the present observations support the hypothesis that an increase in inflammation and immune reactions determine scarring rather than regeneration. These new findings verify that an immune reaction against mesenchymal and epidermal cells of the regenerative blastema is one of the main causes for the failure of organ regeneration in amniotes.

关键词： Lizard Tail Repetitive regeneration Blood Immune cells Ultrastructure