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Implications of metabolism-driven myeloid dysfunctions in cancer therapy

Cellular & Molecular Immunology 2021年第4期18卷 829-841页

作者： Laura Strauss valentina Guarneri Alessandra Gennari Antonio Sica Department of Immunopharmacology and Immuno Oncology EMD Serono Research&Development InstituteInc.80119545A Middlesex TurnpikeBillericaMA 01821USA Department of Surgery Oncology and GastroenterologyUniversity of PadovaPadovaItaly Veneto Institute of Oncology-IRCCS PaduaItalyPadovaItaly Division of Oncology Department of Translational MedicineUniversity of Eastern PiedmontNovaraItaly Department of Pharmaceutical Sciences University of Eastern PiedmontA.Avogadrovia Bovio 6NovaraItaly Humanitas Clinical and Research Center IRCCSVia Manzoni 56RozzanoMilanItaly

Immune homeostasis is maintained by an adequate balance of myeloid and lymphoid *** chronic inflammatory states,including cancer,this balance is lost due to dramatic expansion of myeloid progenitors that fail to mature to functional inflammatory neutrophils,macrophages,and dendritic cells(DCs),thus giving rise to a decline in the antitumor effector lymphoid ***-related inflammation orchestrates the production of hematopoietic growth factors and cytokines that perpetuate recruitment and activation of myeloid precursors,resulting in unresolved and chronic *** pathologic inflammation creates profound alterations in the intrinsic cellular metabolism of the myeloid progenitor pool,which is amplified by competition for essential nutrients and by hypoxia-induced metabolic rewiring at the tumor ***,persistent myelopoiesis and metabolic dysfunctions contribute to the development of cancer,as well as to the severity of a broad range of diseases,including metabolic syndrome and autoimmune and infectious *** aims of this review are to(1)define the metabolic networks implicated in aberrant myelopoiesis observed in cancer patients,(2)discuss the mechanisms underlying these clinical manifestations and the impact of metabolic perturbations on clinical outcomes,and(3)explore new biomarkers and therapeutic strategies to restore immunometabolism and differentiation of myeloid cells towards an effector phenotype to increase host antitumor *** propose that the profound metabolic alterations and associated transcriptional changes triggered by chronic and overactivated immune responses in myeloid cells represent critical factors influencing the balance between therapeutic efficacy and immune-related adverse effects(irAEs)for current therapeutic strategies,including immune checkpoint inhibitor(ICI)therapy.

关键词： Myelopoiesis Tumor-associated macrophages Myeloid-derived suppressor cells Metabolism Cancer therapy

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The spectrum of pneumatosis intestinalis in the adult.A surgical dilemma

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World Journal of Gastrointestinal Surgery 2023年第4期15卷 553-565页

作者： Giuseppe Tropeano Marta Di Grezia Caterina Puccioni valentina Bianchi Gilda Pepe Valeria Fico Gaia Altieri Giuseppe Brisinda Emergency Surgery and Trauma Center Fondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy Department of Surgery UniversitàCattolica del Sacro CuoreRome 00168Italy

Pneumatosis intestinalis(PI) is a striking radiological diagnosis. Formerly a rare diagnostic finding, it is becoming more frequently diagnosed due to the wider availability and improvement of computed tomography scan imaging. Once associated only with poor outcome, its clinical and prognostic significance nowadays has to be cross-referenced to the nature of the underlying *** mechanisms of pathogenesis have been debated and multiple causes have been detected during the years. All this contributes to creating a broad range of clinical and radiological presentations. The management of patients presenting PI is related to the determining cause if it is identified. Otherwise, in particular if an association with portal venous gas and/or pneumoperitoneum is present, the eventual decision between surgery and non-operative management is challenging,even for stable patients, since this clinical condition is traditionally associated to intestinal ischemia and consequently to pending clinical collapse if not *** the wide variety of origin and outcomes, PI still remains for surgeons a demanding clinical entity. The manuscript is an updated narrative review and gives some suggestions that may help make the decisional process easier,identifying patients who can benefit from surgical intervention and those who can benefit from non-operative management avoiding unnecessary procedures.

关键词： Pneumatosis intestinalis Risk factors Treatment Portal venous gas Portomesenteric pneumatosis

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A long story for a short peptide:therapeutic efficacy of a cleavagespecific tau antibody

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Neural Regeneration Research 2021年第12期16卷 2417-2419页

作者： Giuseppina Amadoro valentina Latina Pietro Calissano Institute of Translational Pharmacology(IFT)-National Research Council(CNR) Via Fosso del Cavaliere 10000133-RomeItaly(Amadoro G)European Brain Research Institute(EBRI)Viale Regina Elena 29500161-RomeItaly

Tau is the prime participant in the Alzheimer’s disease(AD) neurodegeneration:AD,the main cause of dementia in elderly people,is a multifactorial neurodegenerative disorder characterized by a long prodromal phase(starting more than two decades before clinical symptoms appear)with brain accumulation/misfolding of amyloidβ(Aβ)in insoluble amyloid plaques and of tau protein in neurofibrillary tangles.

关键词： tau Aβ Alzheimer

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The evolution of eccentricity in the eclipsing binary system AS Camelopardalis

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Research in Astronomy and Astrophysics 2018年第1期18卷 113-118页

作者： valentina Kozyreva Anatoly Kusakin Alexey Bogomazov M.V.Lomonosov Moscow State University P.K.Sternberg Astronomical Institute National Space Agency Fesenkov Astrophysical Institute

In 2002,2004 and 2017 we conducted high precision CCD photometry observations of the eclipsing binary system AS *** analysis of the light curves from 1967 to 2017（our data ＋ data from the literature） we obtained photometric elements of the system and found a change in the system＇s orbital eccentricity of ？e = 0.03 ± *** change can indicate that there is a third companion in the system in a highly inclined orbit with respect to the orbital plane of the central binary,and its gravitational influence may cause the discrepancy between observed and theoretical apsidal motion rates of AS Cam.

关键词： binaries:close binaries:eclipsing stars:individual(AS Cam)

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Terrestrial Temperature, Sea Levels and Ice Area Links with Solar Activity and Solar Orbital Motion

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Natural Science 2023年第9期15卷 233-255页

作者： valentina V. Zharkova Irina Vasilieva Department of MPEE Faculty of Engineering and Environment University of Northumbria Newcastle upon Tyne UK ZVS Research Enterprise Ltd. London UK Department of Solar Physics Main Astronomical Observatory Kyiv Ukraine

This paper explores the links between terrestrial temperature, sea levels and ice areas in both hemispheres with solar activity indices expressed through averaged sunspot numbers together with the summary curve of eigenvectors of the solar background magnetic field (SBMF) and with changes of Sun-Earth distances caused by solar inertial motion resulting from the gravitation of large planets in the solar system. Using the wavelet analysis of the GLB and HadCRUTS datasets two periods: 21.4 and 36 years in GLB, set and the period of about 19.6 years in the HadCRUTS are discovered. The 21.4-year period is associated with variations in solar activity defined by the summary curve of the largest eigenvectors of the SBMF. A dominant 21.4-year period is also reported in the variations of the sea level, which is linked with the period of 21.4 years detected in the GLB temperature and the summary curve of the SBMF variations. The wavelet analysis of ice and snow areas shows that in the Southern hemisphere, it does not show any links to solar activity periods while in the Northern hemisphere, the ice area reveals a period of 10.7 years equal to a usual solar activity cycle. The TSI in March-August of every year is found to grow with every year following closely the temperature curve, because the Sun moves closer to the Earth orbit owing to gravitation of large planets (solar inertial motion, SIM), while the variations of solar radiation during a whole year have more steady distribution without a sharp TSI increase during the last two centuries. The additional TSI contribution caused by SIM is likely to secure the additional energy input and exchange between the ocean and atmosphere.

关键词： Sun: Magnetic Field Sun: Solar Activity Sun: Inertial Motion Earth: Temperature Earth: Sea Level Earth: Ice Area

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Search of inhibitors of aldose reductase for treatment of diabetic cataracts using machine learning

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Advances in Ophthalmology Practice and Research 2023年第4期3卷 187-191页

作者： Trevor Chen Richard Chen Alvin You valentina L.Kouznetsova Igor F.Tsigelny MAP Program University of CaliforniaSan DiegoLa JollaCAUSA San Diego Supercomputer Center University of CaliforniaSan DiegoLa JollaCAUSA CureScience Institute San DiegoCAUSA Department of Neurosciences University of CaliforniaSan DiegoLa JollaCAUSA

Purpose:Patients with diabetes mellitus have an elevated chance of developing cataracts,a degenerative visionimpairing condition often needing *** process of the reduction of glucose to sorbitol in the lens of the human eye that causes cataracts is managed by the Aldose Reductase Enzyme(AR),and it is been found that AR inhibitors may mitigate the onset of diabetic *** exists a large pool of natural and synthetic AR inhibitors that can prevent diabetic complications,and the development of a machine-learning(ML)prediction model may bring new AR inhibitors with better characteristics into clinical ***:Using known AR inhibitors and their chemical-physical descriptors we created the ML model for prediction of new AR *** predicted inhibitors were tested by computational docking to the binding site of ***:Using cross-validation in order to find the most accurate ML model,we ended with final cross-validation accuracy of 90%.Computational docking testing of the predicted inhibitors gave a high level of correlation between the ML prediction score and binding free ***:Currently known AR inhibitors are not used yet for patients for several *** think that new predicted AR inhibitors have the potential to possess more favorable characteristics to be successfully implemented after clinical *** new inhibitors can improve patient well-being and lower surgical complications all while decreasing long-term medical expenses.

关键词： Diabetic cataracts Aldose reductase inhibitor Machine learning Deep learning

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Sensitivity of MCF-7 mammosphere CSCs to neutron radiation

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 28-41页

作者： valentina G.Shuvatova Yuliya P.Semochkina Alexander N.Strepetov Elizaveta Yu.Moskaleva Kurchatov Complex of NBICS Technologies National Research Centre“Kurchatov Institute”Moscow 123098Russia

Aim:Cancer stem cells(CSCs)are highly resistant to chemotherapy andγ-*** have a high linear energy transfer,which can lead to extensive damage to the DNA of tumor cells and *** aim of this work was to compare the sensitivity of MCF-7 human breast adenocarcinoma cells and CSCs toγ-andγ,***:To increase the number of CSCs,MCF-7 cells were cultured as mammospheres.γ-irradiation was carried out in a GUT-200M device(^(60)Co source)in the dose range of 1-8 Gy at a dose rate of 0.75 Gy/min.γ,n-irradiation was carried out in an IR-8 reactor in the dose range of 0.05-2 Gy at a dose rate of 0.06 Gy/*** DSB formation was assessed by the level ofγH2AX foci using fluorescence microscopy and flow *** were identified by flow cytometry as CD44^(+)/CD24^(-/low) ***:We showed thatγ,n-irradiation induced the formation ofγH2AX foci of a larger size than didγ-irradiation and led to more severe DNA damage per 1 ***,γ,n-radiation was found to have a high relative biological effectiveness(RBE)as assessed by the cell survival rate,the number of CSCs in culture,and the ability of CSCs to *** highest RBE of neutron radiation was observed at low doses,when cell survival rate decreased by only 5%-10%.With an increase in the radiation dose,the RBE value decreased for all studied parameters,but it remained as high as ***:γ,n-radiation is highly effective against *** results explain the efficacy of neutron therapy for resistant forms of breast cancer.

关键词： Cancer stem cells radioresistance neutron radiation gamma radiation relative biological effectiveness γH2AX foci mammospheres MCF-7 cells human breast adenocarcinoma

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Surgical complications of oncological treatments: A narrative review

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World Journal of Gastrointestinal Surgery 2023年第6期15卷 1056-1067页

作者： Valeria Fico Gaia Altieri Marta Di Grezia valentina Bianchi Maria Michela Chiarello Gilda Pepe Giuseppe Tropeano Giuseppe Brisinda Emergency Surgery and Trauma Center Fondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy Department of Surgery Azienda Sanitaria Provinciale di CosenzaCosenza 87100Italy Department of Medicine and Surgery Catholic School of MedicineRome 00168Italy

Gastrointestinal complications are common in patients undergoing various forms of cancer treatments,including chemotherapy,radiation therapy,and moleculartargeted *** complications of oncologic therapies can occur in the upper gastrointestinal tract,small bowel,colon,and *** mechanisms of action of these therapies are *** includes cytotoxic drugs,which block the activity of cancer cells by targeting intracellular DNA,RNA,or *** symptoms are very common during chemotherapy,due to a direct effect on the intestinal mucosa resulting in edema,inflammation,ulceration,and *** adverse events have been described as complications of molecular targeted therapies,including bowel perforation,bleeding,and pneumatosis intestinalis,which may require surgical *** is a local anti-cancer therapy,which uses ionizing radiation to cause inhibition of cell division and ultimately lead to cell *** related to radiotherapy can be both acute and *** therapies,including radiofrequency,laser,microwave,cryoablation,and chemical ablation with acetic acid or ethanol,can cause thermal or chemical injuries to the nearby *** of the different gastrointestinal complications should be tailored to the individual patient and based on the underlying pathophysiology of the ***,it is important to know the stage and prognosis of the disease,and a multidisciplinary approach is necessary to personalize the surgical *** purpose of this narrative review is to describe complications related to different oncologic therapies that may require surgical interventions.

关键词： Cancer Chemotherapy Radiotherapy Complications Bowel perforation Gastrointestinal bleeding

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Quality of nursing care,availability and accessibility of treatment and prevention of communicable and chronic diseases

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International Journal of Nursing Sciences 2017年第4期4卷 350-351页

作者： valentina Sarkisova Russian Nurses Association Russia European Forum of National Nursing and Midwifery Associations

*** care·Provision of primary care based on district approach(in resi-dential areas)·Networks of district outpatient clinics specifically working for adults and for children·Network of primary specialized outpatient clinics(women consultancy,cardiology)·Medical stations in rural territories with different staffing depending on population numbers-(doctor and nurse working jointly,or feldshers working alone/independent practice)·Medical rooms at schools and other education settings,large companies·Home visits.

关键词： prevention nurse district

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Health and nursing policy,regulation and legislation,leadership and management

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International Journal of Nursing Sciences 2017年第4期4卷 333-334页

作者： valentina Sarkisova Russian Nurses Association Russia European Forum of National Nursing and Midwifery Associations

*** system in Russian Federation System of Obligatory Health Insurance provides universal health *** obligatory system is complemented by the system of Voluntary health insurance.

关键词： nursing policy Health

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