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Liquid biopsy and blood-based minimal residual disease evaluation in multiple myeloma

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Oncology Research 2023年第3期31卷 271-274页

作者： ALESSANDRO GOZZETTI MONICA BOCCHIA Division of Hematology University of SienaAzienda Ospedaliera UniversitariaSiena53100Italy

Novel drug availability has increased the depth of response and revolutionised the outcomes of multiple myeloma *** residual disease evaluation is a surrogate for progression-free survival and overall survival and has become widely used not-only in clinical trials but also in daily patient *** marrow aspiration is the gold standard for response evaluation,but due to the patchy nature of myeloma,false negatives are *** biopsy and blood-based minimal residual disease evaluation consider circulating plasma cells,mass spectrometry or circulating tumour *** approach is less invasive,can provide a more comprehensive picture of the disease and could become the future of response evaluation in multiple myeloma patients.

关键词： Myeloma Liquid biopsy Minimal residual disease

Study of cytoskeleton from microscopic point of view:Our experience

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BIOCELL 2022年第4期46卷 881-884页

作者： CINZIA SIGNORINI GIULIA COLLODEL ELENA MORETTI Department of Molecular and Developmental Medicine of University of siena SienaI-53100Italy

The manuscript deals with our studies and experiences in the assessment of cytoskeleton in different cellular models and *** immunofluorescent study of several cytoskeletal proteins was relevant in the evaluation of a therapy for osteoarthritis,in case of alkaptonuria and in testing the efficacy of docetaxel in neuroblastoma cancer cells leading to apoptosis.A relevant part of our experience focus on the study of cytoskeleton in seminiferous epithelium and spermatozoa,identifying alterations affecting blood-testis barrier after a silver nanoparticle treatment,chromosomal segregation in case of varicocele,sperm motility and diagnosing systematic sperm defects as“Primary ciliary dyskinesia”and“Dysplasia of the fibrous sheath”.The evaluation of cytoskeleton represents a specific and sensitive analysis in establishing the health status of different cells.

关键词： cytoskeleton Environment Immunocytochemistry Pathological condition

How to conjugate the stemness marker ALDH1A1 with tumor angiogenesis,progression,and drug resistance

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Cancer Drug Resistance 2020年第1期3卷 26-37页

作者： Valerio Ciccone Lucia Morbidelli Marina Ziche Sandra Donnini Department of Life Sciences University of SienaSiena 53100Italy Department of Medicine Surgery and NeuroscienceUniversity of SienaSiena 53100Italy

Cancer is the second leading cause of death *** survival of cancer patients depends on the efficacy of therapies and the development of *** are many mechanisms involved in the acquisition of drug resistance by cancer cells,including the acquisition of stem-like *** stem cells(CSCs)represent a major source of tumor progression and treatment *** are a subpopulation of cancer cells having the abilities to self-renew and form spheres in *** dehydrogenase 1A1(ALDH1A1)is a cytosolic enzyme involved in the detoxification of cells from toxic aldehydes and belongs to the ALDH *** ALDH1A1 activity is closely related to stemness phenotype of several tumors,possibly contributing to cancer progression and diffusion in the *** have documented the contribution of ALDH1A1 in tumor angiogenesis in breast cancer cells by the activation of hypoxia inducible factor-1αand vascular endothelial growth factor *** review discusses the involvement of ALDH1A1 in the development of different hallmarks of cancer to propose it as a novel putative target for cancer treatment to achieve better ***,we analyze the involvement of ALDH1A1 in the acquisition of stemness phenotype in tumor cells,the regulation of tumor angiogenesis and metastases,and the acquisition of anticancer drug resistance and immune evasion.

关键词： Aldehyde dehydrogenase 1A1 angiogenesis drug resistance immune editing metastases stemness

Medieval Towns, Traffic and Urban Planning Half a Century since the First Pedestrian Zone in siena, Italy

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Journal of Traffic and Transportation Engineering 2016年第2期4卷 107-115页

作者： Stefano Maggi Department of Political and lnternational Science University of Siena Siena 1-53100 Italy

The Italian town is known as a collection of wails, gates, towers, palaces and cathedrals. The lanes and the squares were created in the Middle Ages, with an urban fabric suitable for horses and carriages, not for motor cars. At the beginning of the 1960s, it was no longer possible to delay a solution to the problem of traffic and the first ＂pedestrian isle＂ was realized in the centre of siena in 1965. Other towns in a few years followed this virtuous example. Acts against traffic avoided the building of urban motorways and the demolition of ancient buildings that would have given the ＂coup de grace＂ to several important historic centres.

关键词： Medieval town urban environment traffic and urban planning transport history.

Can Helicobacter pylori infection influence human reproduction?

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World Journal of Gastroenterology 2014年第19期20卷 5567-5574页

作者： Elena Moretti Natale Figura Giulia Collodel Antonio Ponzetto Collodel Department of Molecular and Developmental MedicineUniversity of Siena53100 SienaItaly Department of Medical Surgical and Neurological SciencesUniversity of Siena and Policlinico S Maria alle Scotte53100 SienaItaly Department of Internal Medicine University of Torino10126 TorinoItaly

Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction.

关键词： Antigenic mimicry Helicobacter pylori infection Human sperm Inflammatory cytokines Preeclampsia Reproductive disorders

Structural investigation of Rett-inducing MeCP2 mutations

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Genes & Diseases 2019年第1期6卷 31-34页

作者： Ottavia Spiga Simone Gardini Nicole Rossi Vittoria Cicaloni Francesco Pettini Neri Niccolai Annalisa Santucci Department of Biotechnology Chemistry and PharmacyUniversity of SienaSiena53100Italy GenomeUp SRL Rome00199Italy Toscana Life Sciences Foundation(TLS) Siena 53100Italy

X-ray structure of methyl-CpG binding domain(MBD)of MeCP2,an intrinsically disordered protein(IDP)involved in Rett syndrome,offers a rational basis for defining the spatial distribution for most of the sites where mutations responsible of Rett syndrome,RTT,*** have ascribed pathogenicity for mutations of amino acids bearing positively charged side chains,all located at the protein-DNA interface,as positive charge removal cause reduction of the MeCP2-DNA adduct *** of the frequent proline replacements,outside the DNA contact moiety of MBD,can be attributed to the role of this amino acid for maintaining both unfolded states for unbound MeCP2 and,at the same time,to favor some higher conformational order for stabilizing structural determinants required by protein *** hypotheses can be extended to transcription repressor domain,TRD,the other MeCP2-DNA interaction site and,in general,to all the IDP that interact with nucleic acids.

关键词： DNA binding domains MeCP2 Mutation distribution Protein structure Rett syndrome

Learning from the 2009 H1N1 pandemic:prospects for more broadly effective influenza vaccines

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Journal of Molecular Cell Biology 2011年第3期3卷 144-146页

作者： Ethan C.Settembre Philip R.Dormitzer Rino Rappuoli Novartis Vaccines and Diagnostics CambridgeMAUSASienaItaly

Calls to develop a universal influenza vaccine have increased in the wake of the 2009 H1N1 influenza *** demand comes at a time when analyses of the human antibody repertoire,informed by structures of complexes between broadly neutralizing antibodies and influenza hemagglutinin,have revealed the target of a class of broadly neutralizing *** studies suggest a path forward to more broadly protective influenza vaccines.

关键词： influenza vaccines protective

Ultrathin Descemet stripping automated endothelial keratoplasty versus Descemet membrane endothelial keratoplasty:a fellow-eye comparison

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Eye and Vision 2020年第1期7卷 241-249页

作者： Rita Mencucci Eleonora Favuzza Elisa Marziali Michela Cennamo Cosimo Mazzotta Ersilia Lucenteforte Gianni Virgili Stanislao Rizzo Eye Clinic Department of NeurosciencePsychologyPharmacology and Child Health(NEUROFARBA)University of FlorenceEye ClinicLargo Brambilla 350134 FlorenceItaly Department of Medicine Surgery and NeurosciencesOphthalmology UnitSiena UniversitySienaItaly siena Crosslinking Center SienaItaly Department of Clinical and Experimental medicine University of PisaPisaItaly

Background:To compare the visual outcome and patients’satisfaction after ultrathin Descemet stripping automated endothelial keratoplasty(UT-DSAEK)and Descemet membrane endothelial keratoplasty(DMEK)performed on fellow eyes of the same ***:In this retrospective study,the records of 18 pseudophakic patients affected by Fuchs endothelial dystrophy who underwent DMEK in one eye and UT-DSAEK in the fellow eye were *** corrected visual acuity(BCVA),corneal pachymetry,keratometry,corneal aberrations,photopic and mesopic contrast sensitivity,and endothelial cell counts measured 12 months after surgery in either eye were analyzed and *** results of a satisfaction questionnaire were also ***:Twelve months after surgery,BCVA was not significantly different in UT-DSAEK and DMEK eyes(0.10±0.04 and 0.07±0.07 logMAR,respectively);at both 4-and 6 mm optical zones total and posterior corneal higher order aberrations(HOAs),posterior astigmatism and total coma were significantly lower after DMEK;BCVA in both groups was significantly correlated mainly with anterior corneal aberrations;contrast sensitivity was higher after DMEK especially in mesopic conditions and at medium spatial frequencies;the endothelial cell density was similar,although slightly higher in the UT-DSAEK group(p=0.10).The satisfaction questionnaire showed that although patients were highly satisfied from both procedures,more than half of them preferred DMEK and reported a more comfortable and quicker postoperative ***:DMEK and UT-DSAEK showed no evidence of difference in terms of postoperative BCVA,although DMEK had a better performance in terms of contrast sensitivity,posterior corneal aberrations and overall patient satisfaction.

关键词： DMEK UT-DSAEK DSAEK Descemet stripping automated endothelial keratoplasty Ultra-thin Descemet stripping automated endothelial keratoplasty Descemet membrane endothelial keratoplasty

Effects of major ozonated autohemotherapy in the treatment of dry age related macular degeneration: a randomized controlled clinical study

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International Journal of Ophthalmology(English edition) 2012年第6期5卷 708-713页

作者： Emma Borrelli Angelica Diadori Alessandro Zalaffi Velio Bocci Department of Surgery and Bioengineering Policlinico LeScotte University of Siena Ophthalmological Ambulatory Territorial Health Unit 7 Department of Ophthalmological and Neurological Sciences Policlinico Le Scotte University of Siena Department of Physiology University of Siena

AIM: To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS: This study was a randomized, controlled clinical study. One hundred and forty patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen, were randomly assigned in a 1:1 ratio to either receive 27 major ozonated autohemotherapy treatments during 12-month period, or a standardized multi-vitamin therapy. Primary outcome was the change in best corrected visual acuity (mean logMar change) between the baseline and 6 and 12 months, end point of the study. In addition, to investigate the safety of prolonged ozonated autohaemotherapy, we measured the routine haemato- chemical parameters and biochemical oxidative stress values at baseline and after 12 months treatment time. RESULTS: The mean baseline best corrected visual acuity in study eyes was 0.36 in the treatment group and 0.38 in the control group (difference not statistically significant). At the primary endpoint, 6 months post-baseline, the mean logMAR change in the treated group improved by 0.1 and the values of the control group at the same time impaired by 0.2 respect to the baseline. Four percent and twenty-five percent of eyes in the group treated with O3-AHT gained 1 or more lines after 6 and 12 months respectively compared to 0% in the eyes which received no treatment (P <0.05 at 12 months). None of the treated patients experienced a loss in visual acuity in their study eye at 6 and 12 months, compared to 16% and 40 % of patients in the control group who lost 2 lines or more at 6 months and 12 months respectively (P <0.05 treated vs control group)). Major ozonated autohemotherapy was shown to be safe and well- tolerated by the patients. Moreover, the haematochemical parameters showed a decrease in the Reactive Oxygen Metabolites (300±10.1 UCARR at 12 months compared to a baseline value of 380±10.4 UCARR, P <0.05

关键词： retinopathy ozone therapy macular degeneration