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Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

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World Journal of Stem Cells 2024年第5期16卷 604-614页

作者： Edoardo Agosti marco zeppieri Mattia Ghidoni Tamara Ius Alessandro Tel marco Maria Fontanella Pier Paolo Panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy Clinic of Maxillofacial Surgery Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their im

关键词： Glioma stem cells Chemoresistance Radioresistance Molecular pathways Targeted therapies Systematic review

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Dual mobility in primary total hip arthroplasty:A temptation from the devil or a blessing from above

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World Journal of Orthopedics 2024年第6期15卷 512-519页

作者： Raymond Klumpp Linda Boerci Francesco Buonanotte marco zeppieri Unita Operativa Complessa Ortopedia e Traumatologia Ospedale Treviglio-Caravaggio ASSTBergamo Ovest 24047Italy Department of Orthopedics Universitàdegli Studi di Milano-BicoccaMonza 20090Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy

Dual mobility(DM)bearings have gained significant attention in the field of total hip arthroplasty(THA)as a valid treatment option in cases of revision for instability after THA whereas its use in primary THA is still a matter of debate.This manuscript explores the pathology,incidence,diagnosis,treatment options,prognosis,ongoing studies in the literature,and future perspectives related to the use of DM bearings employed in primary THA.DM bearings are primarily designed to address one of the major concerns in THA:Instability of the prosthetic hip.Instability is both for the surgeon and the patient a devastating postoperative complication,leading to significant pain and subsequent apprehension by the patient and may require revision surgeries.The use of DM implants poses the worry of wear-related complications,such as accelerated polyethylene wear and osteolysis,which also pose challenges to long-term implant survival.This technique has seen a steady rise in recent years,with multiple studies reporting favorable outcomes.The incidence of their utilization varies among institutions and surgeons,reflecting differing preferences and patient populations.The diagnosis of instability and wear-related complications in THA often involves clinical assessment,imaging modalities such as X-rays,computed tomography scans,and sometimes advanced imaging techniques like magnetic resonance imaging.DM bearings can be considered as an option when patients present neurologic pathologies such as Parkinson's disease or recurrent dislocations after THA.DM bearings provide an additional articulation point within the implant,facilitating a greater range of motion and inherent stability.This design allows for reduced risk of dislocation and improved functional outcomes.Various implant manufacturers offer different designs and sizes of DM bearings to suit individual patient needs.Current literature suggests that the use of DM bearings in primary THA has demonstrated promising outcomes in terms of enhanced stability,reduced dislocation rates

关键词： Dual mobility First implant Hip arthroplasty Surgical technique Differential diagnosis

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Current status and future perspectives on stem cell transplantation for spinal cord injury

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World Journal of Transplantation 2024年第1期14卷 189-209页

作者： Edoardo Agosti marco zeppieri Andrea Pagnoni marco Maria Fontanella Alessandro Fiorindi Tamara Ius Pier Paolo Panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Department of Medical and Surgical Specialties Radiological Sciencesand Public HealthUniversity of BresciaBrescia 25123BSItaly Neurosurgery Unit Head-Neck and NeuroScience DepartmentUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systematic reviews prioritize effectiveness,often overlooking safety and translational feasibility.This situation prompts inquiries regarding the readiness for clinical adoption.AIM To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for SCI.METHODS A systematic search was conducted across major medical databases[PubMed,Embase,Reference Citation Analysis(RCA),and Cochrane Library]up to October 14,2023.The search strategy utilized relevant Medical Subject Heading(MeSH)terms and keywords related to"spinal cord","injury","clinical trials","stem cells","functional outcomes",and"adverse events".Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI.RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,496 papers were initially identified,with 237 chosen for full-text analysis.Among them,236 were deemed eligible after excluding 170 for various reasons.These studies encompassed 1086 patients with varying SCI levels,with cervical injuries being the most common(42.2%).Bone marrow stem cells were the predominant stem cell type used(71.1%),with various administration methods.Follow-up durations averaged around 84.4 months.The 32.7%of patients showed functional improvement from American spinal injury association Impairment Scale(AIS)A to B,40.8%from AIS A to C,5.3%from AIS A to D,and 2.1%from AIS B to C.Sensory improvements were observed in 30.9%of patients.A relatively small number of adverse events were recorded,including fever(15.1%),headaches(4.3%),muscle tension(3.1%),and dizziness(2.6%),highlighting the potential for SCI recovery with stem cell therapy.CONCLUSION In the realm of SCI treatment,stem cell-based thera

关键词： Spinal cord injury Stem cell therapy Adverse events Functional outcomes Systematic review

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Unlocking the versatile potential:Adipose-derived mesenchymal stem cells in ocular surface reconstruction and oculoplastics

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World Journal of Stem Cells 2024年第2期16卷 89-101页

作者： Pier Luigi Surico Anna Scarabosio Giovanni Miotti Martina Grando Carlo Salati Pier Camillo Parodi Leopoldo Spadea marco zeppieri Schepens Eye Research Institute of Mass Eye and Ear Harvard Medical SchoolBostonMA 02114United States Department of Ophthalmology Campus Bio-Medico UniversityRome 00128Italy Department of Plastic Surgery University Hospital of UdineUdine 33100Italy Department of Internal Medicine Azienda Sanitaria Friuli OccidentaleSan Vito al Tagliamento 33078Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I“Sapienza”University of RomeRome 00142Italy

This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular and periocular enhancement,demands advanced solutions for tissue restoration,functional and aesthetic refinement,and aging.Investigating immunomodulatory,regenerative,and healing capacities of MSCs,this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside,addressing common unmet needs in the field of reconstructive and regenerative surgery.

关键词： Stem cells Adipose stem cell Ocular therapy Oculoplastics Regenerative

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Treatment for paraganglioma with stereotactic radiotherapy

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World Journal of Clinical Cases 2024年第16期12卷 2729-2737页

作者： Antonio Pontoriero Paola Critelli marco zeppieri Filippo Flavio Angileri Tamara Ius Radiation Oncology Unit Department of BiomedicalDental Science and Morphological and Functional ImagesUniversity of MessinaMessina 98125Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of BiomedicalDental Science and Morphological and Functional ImagesUniversity of MessinaMessina 98125Italy Neurosurgery Unit Head-Neck and NeuroScience DepartmentUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Paragangliomas(PG)are rare neoplasms of neuroendocrine origin that tend to be highly vascularized,slow-growing,and usually sporadic.To date,common treatment options are surgical resection(SR),with or without radiation therapy(RT),and a watch-and-wait approach.AIM To evaluate the local control and effectiveness of exclusive fractionated stereotactic RT(FSRT)treatment in unresectable PG(uPG).METHODS We retrospectively evaluated patients with uPG(medically inoperable or refused SR)treated with FSRT with a Cyberknife System(Accuray Incorporated,Sunnyvale,California).Toxicity and initial efficacy were evaluated.RESULTS From May 2009 to January 2023,6 patients with a median age of 68(range 20-84)were treated with FSRT.The median delivered dose was 21 Gy(range 20-30 Gy)at a median isodose line of 75.5%(range 70%-76%)in 4 fractions(range 3-5 fractions).The median volume was 13.6 mL(range 12.4-65.24 mL).The median cumulative biological effective dose and equivalent dose in 2-Gy fractions were 70 Gy and 37.10 Gy respectively.Site of origin involved were the timpa-nojugular glomus(4/6),temporal bone,and cervical spine.In 1 of the 6 patients,the follow-up was insufficient;5 of 6 patients showed a 5-year overall survival and 5-year progression-free survival of 100%.We observed negligible toxicities during and after RT.The majority of patients showed stable symptoms during follow-up.Only 1 patient developed spine metastases.CONCLUSION Our preliminary results on this small cohort of patients suggest that FSRT could be an effective and safe alternative to SR.

关键词： Unresectable paraganglioma Fractionated stereotactic radiation therapy Cyberknife Neurosurgery Metastasis

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Hepatitis B virus reactivation in patients treated with monoclonal antibodies

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World Journal of Virology 2024年第1期13卷 33-37页

作者： Silvia De Pauli Martina Grando Giovanni Miotti marco zeppieri Department of Internal Medicine Azienda Sanitaria Friuli OccidentaleSan Vito al TagliamentoPordenone 33170Italy Department of Plastic Surgery University Hospital of UdineUdine 33100Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy

Hepatitis B virus(HBV)reactivation poses a significant clinical challenge,espe-cially in patients undergoing immunosuppressive therapies,including mono-clonal antibody treatments.This manuscript briefly explores the complex rela-tionship between monoclonal antibody therapy and HBV reactivation,drawing upon current literature and clinical case studies.It delves into the mechanisms underlying this phenomenon,highlighting the importance of risk assessment,monitoring,and prophylactic measures for patients at risk.The manuscript aims to enhance the understanding of HBV reactivation in the context of monoclonal antibody therapy,ultimately facilitating informed clinical decision-making and improved patient care.This paper will also briefly review the definition of HBV activation,assess the risks of reactivation,especially in patients treated with monoclonal antibodies,and consider management for patients with regard to screening,prophylaxis,and treatment.A better understanding of patients at risk can help clinicians provide optimum management to ensure successful patient outcomes and prevent morbidity.

关键词： Hepatitis B virus Reactivation Acute infection Chronic infection Monoclonal antibodies

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Whole-eye transplantation: Current challenges and future perspectives

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World Journal of Transplantation 2024年第2期14卷 28-39页

作者： Anna Scarabosio Pier Luigi Surico Vlad Tereshenko Rohan Bir Singh Carlo Salati Leopoldo Spadea Glenda Caputo Pier Camillo Parodi Caterina Gagliano Jonathan M Winograd marco zeppieri Department of Plastic Surgery University Hospital of UdineUdine 33100Italy Department of Plastic Surgery Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States Schepens Eye Research Institute of Mass Eye and Ear Harvard Medical SchoolBostonMA 02114United States Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I"Sapienza"University of RomeRome 00142Italy Department of Medicine and Surgery University of Enna"Kore"Enna 94100Italy Eye Clinic Catania University San marco Hospital Viale Carlo Azeglio Ciampi 95121 CataniaItaly

Whole-eye transplantation emerges as a frontier in ophthalmology,promising a transformative approach to irreversible blindness.Despite advancements,formidable challenges persist.Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival.Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive,prompting the exploration of neurotrophic support and immunomodulatory interventions.Immunological tolerance,paramount for graft acceptance,confronts the distinc-tive immunogenicity of ocular tissues,driving research into targeted immunosup-pression strategies.Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks.Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities.Biomaterials,stem cell therapies,and precision immunomodulation represent promising avenues in this pursuit.Ultimately,the aim of this review is to critically assess the current landscape of whole-eye transplantation,elucidating the challenges and advancements while delineating future directions for research and clinical practice.Through concerted efforts,whole-eye transplantation stands to revolu-tionize ophthalmic care,offering hope for restored vision and enhanced quality of life for those afflicted with blindness.

关键词： Eye Transplantation Optic nerve Nerve regeneration Immunological tolerance

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Herpes simplex keratitis:A brief clinical overview

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World Journal of Virology 2024年第1期13卷 5-32页

作者： Mutali Musa Ehimare Enaholo Gladness Aluyi-Osa George Nnamdi Atuanya Leopoldo Spadea Carlo Salati marco zeppieri Department of Optometry University of BeninBenin 300283Nigeria Department of Ophthalmology Africa Eye Laser CentreKm 7Benin 300105Nigeria Department of Ophthalmology Centre for Sight AfricaNkpor 434101Nigeria Eye Clinic Policlinico Umberto I"Sapienza"University of RomeRome 00142Italy of Ophthalmology University Hospital of UdineUdine 33100Italy

The aim of our minireview is to provide a brief overview of the diagnosis,clinical aspects,treatment options,management,and current literature available regarding herpes simplex keratitis(HSK).This type of corneal viral infection is caused by the herpes simplex virus(HSV),which can affect several tissues,including the cornea.One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea.After the initial infection,the HSV can establish a latent infection in the trigeminal ganglion,a nerve cluster near the eye.The virus may remain dormant for extended periods.Periodic reactivation of the virus can occur,leading to recurrent episodes of HSK.Factors triggering reactivation include stress,illness,immunosuppression,or trauma.Recurrent episodes can manifest in different clinical patterns,ranging from mild epithelial involvement to more severe stromal or endothelial disease.The severity and frequency of recurrences vary among individuals.Severe cases of HSK,especially those involving the stroma and leading to scarring,can result in vision impairment or even blindness in extreme cases.The cornea's clarity is crucial for good vision,and scarring can compromise this,potentially leading to visual impairment.The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization.Antiviral medications,such as oral Acyclovir or topical Ganciclovir,may be prescribed for prophylaxis.The immune response to the virus can contribute to corneal damage.Inflammation,caused by the body's attempt to control the infection,may inadvertently harm the corneal tissues.Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation.In summary,the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

关键词： Herpes simplex virus Herpes simplex keratitis Acyclovir Neurotization Reactivation

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Uveal melanoma:Recent advances in immunotherapy

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World Journal of Clinical Oncology 2024年第1期15卷 23-31页

作者： Francesco Saverio Sorrentino Francesco De Rosa Patrick Di Terlizzi Giacomo Toneatto Andrea Gabai Lucia Finocchio Carlo Salati Leopoldo Spadea marco zeppieri Department of Surgical Sciences Unit of OphthalmologyOspedale MaggioreBologna 40100Italy Department of Oncology IRCCS Istituto Romagnolo per lo Studio dei Tumori“Dino Amadori”Meldola 47014Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I“Sapienza”University of RomeRome 00142Italy

Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection,up to 50%of UM patients develop metastases that usually involve the liver and are fatal within 1 year.To date,chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM,which is still characterized by poor prognosis.No standard therapeutic approaches for its prevention or treatment have been established.The application of immunotherapy agents,such as immune checkpoint inhibitors that are effective in cutaneous melanoma,has shown limited effects in the treatment of ocular disease.This is due to UM’s distinct genetics,natural history,and complex interaction with the immune system.Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations,UMs are usually triggered by a mutation in GNAQ or GNA11.As a result,more effective immunotherapeutic approaches,such as cancer vaccines,adoptive cell transfer,and other new molecules are currently being studied.In this review,we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.

关键词： Uveal melanoma Immunotherapy Ocular oncology Tumor Metastatic disease Genetic mutations

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Fat or fillers:The dilemma in eyelid surgery

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World Journal of Clinical Cases 2024年第17期12卷 2951-2965页

作者： Giovanni Miotti Luca De marco Davide Quaglia Martina Grando Carlo Salati Leopoldo Spadea Caterina Gagliano Mutali Musa Pier Luigi Surico Pier Camillo Parodi marco zeppieri Department of Plastic Surgery University Hospital of UdineUdine 33100Italy Department of Internal Medicine Azienda Sanitaria Friuli OccidentaleSan Vito al Tagliamento 33078Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I“Sapienza”University of RomeRome 00142Italy Department of Medicine and Surgery University of Enna“Kore”Enna 94100Italy Eye Clinic Catania University San marco Hospital Viale Carlo Azeglio CiampiCatania 95121Italy Department of Optometry University of BeninBenin 300283Nigeria Department of Ophthalmology Africa Eye Laser CentreKm 7Benin 300105Nigeria Schepens Eye Research Institute of Mass Eye and Ear Harvard Medical SchoolBostonMA 02114United States

The aging of the periocular region has always aroused great interest.A fresh,young,and attractive sight determined an ever-greater attention to surgical and non-surgical techniques to obtain this result.In particular,the change in the concept of a young look,considered then“full”,led to the increasing use of surgical(fat grafting)or medical(hyaluronic acid)filling techniques.Eyelid rejuvenation became increasingly popular in the field of cosmetic treatments,with a focus on achieving a youthful and refreshed appearance.Among the various techniques available,the choice between using fat grafting or fillers presented a clinical dilemma.In particular,what surgery considered of fundamental importance was a long-lasting result over time.On the other hand,aesthetic medicine considered it fundamental not to have to resort to invasive treatments.But what was the reality?Was there one path better than the other,and above all,was there a better path for patients?The minireview aims to explore the physiopathology,diagnosis,treatment options,prognosis,and future studies regarding this dilemma.We analyzed the literature produced in the last 20 years comparing the two techniques.Current literature reveals advancements in biomaterials,stem cell research and tissue engineering held promise for further enhancing the field of eyelid rejuvenation.The choice between fat grafting and fillers in eyelid cosmetic treatments presented a clinical dilemma.Understanding physiopathology,accurately diagnosing eyelid aging,exploring treatment options,assessing prognosis,and conducting future studies were essential for providing optimal care to patients seeking eyelid rejuvenation.

关键词： Stem cells Adipose stem cell Ocular therapy Oculoplastics Regenerative

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