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Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

Oncology Research 2024年第8期32卷 1309-1322页

作者： ANA s.CVETANOVIC MATTEO LAMBERTINI KEVIN PUNIE GORANA G.MATOVINA BRKO NIKOLA D.ZIVKOVIC MAJA J.popovic MARIJANA M.MILOVIC KOVACEVIC lazar s.popovic Department for Oncology Medical Faculty NisUniversity of NisNis18000Serbia Clinic of Oncology University Clinical Centre NisNis18000Serbia Department of Internal Medicine and Medical sciences(DiMI) School of MedicineUniversity of GenovaGenova16100Italy Department of Medical Oncology U.O.C Clinica di Oncologia MedicaIRCCS Ospedale Policlinico San MartinoGenova16100Italy Department of General Medical Oncology and Multidisciplinary Breast Centre Leuven Cancer InstituteUniversity Hospitals LeuvenLeuven3001Belgium Department of Medical Oncology Oncology Institute of VojvodinaSremska Kamenica21208Serbia Department for Pathology Medical Faculty NisUniversity of NisNis18000Serbia Center for Pathology University Clinical Centre NisNis18000Serbia Faculty of Medicine University of Novi SadNovi Sad21000Serbia Department of Medical Oncology Institute of Oncology and Radiology SerbiaBelgrade11000Serbia

Oncofertility is an extremely signiﬁcant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but signiﬁcantly contributes to preserving life *** effect of chemotherapy can range from minimal effects to complete ovarian *** data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and *** ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufﬁciency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian ***,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological ***,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor *** addition,studies on hematological malignancies have yielded negative results;nevertheless,theﬁndings must be interpreted with caution owing to numerous *** guidelines from the American society of Clinical Oncology and EsMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not *** this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisﬁeld

关键词： Gonadotropin-releasing hormone agonists(GnRHa) Fertility preservation Premature ovarian insufficiency(POI) Premenopausal patients

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Targeting triple-negative breast cancer:A clinical perspective

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Oncology Research 2023年第3期31卷 221-238页

作者： lazar s.popovic GORANA MATOVINA-BRKO MAJA popovic KEVIN PUNIE ANA CVETANOVIC MATTEO LAMBERTINI Department of Medical Oncology Oncology Institute of VojvodinaSremska KamenicaSerbia Faculty of Medicine University of Novi SadNovi SadSerbia Department of General Medical Oncology and Multidisciplinary Breast Centre Leuven Cancer InstituteUniversity Hospitals LeuvenLeuvenBelgium Department for Oncology Medical Faculty NisUniversity of NisNisSerbia Clinic of Oncology Clinical Centre NisNisSerbia Department of Internal Medicine and Medical sciences(DiMI) School of MedicineUniversity of GenovaGenovaItaly Department of Medical Oncology U.O.C Clinica di Oncologia MedicaIRCCS Ospedale Policlinico San MartinoGenovaItaly

Triple-negative breast cancer(TNBC)is a disease with often an aggressive course and a poor prognosis compared to other subtypes of breast *** accounts for approximately 10%–15%of all diagnosed breast cancer cases and represents a high unmet need in the *** to just a few years ago,chemotherapy was the only systemic treatment option for this subtype(1).To date,TNBC is considered a heterogeneous *** of the existing classifications is based on the analysis of mRNA expression in 587 TNBC cases,in which Lehman et *** six subtypes of TNBC as follows:two basal-like(BL1 and BL2)subtypes,a mesenchymal(M)subtype,a mesenchymal stem-like(MsL)subtype,an immunomodulatory(IM)subtype,and a luminal androgen receptor(LAR)subtype(2).Later studies have demonstrated that the IM and MsL subtypes do not correlate with independent subtypes but reflect background expression by dense infiltration of tumor-infiltrating lymphocytes(TILs)or stromal *** to this finding,the classification of TNBC has been revised into the following four subtypes:basal 1,basal 2,LAR,and mesenchymal subtypes(3).Over the last years,several new strategies have been investigated for the treatment of patients with *** them,immunotherapy,antibody drug conjugates,new chemotherapy agents,and targeted therapy have been and are currently being *** present article aims to provide an updated overview on the different treatment options that are now available or are still under investigation for patients with TNBC.

关键词： Triple-negative breast cancer Immunotherapy Antibody-drug conjugates Target therapy

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Drawing lines in the sand: The growing threat of obesity in type 1 diabetes

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World Journal of Diabetes 2024年第5期15卷 823-827页

作者： Theocharis Koufakis Dimitrios Patoulias Ioanna Zografou Nikolaos Papanas Djordje s.popovic second Propedeutic Department of Internal Medicine Aristotle University of ThessalonikiThessaloniki 54642Greece Diabetes Centre Second Department of Internal MedicineDemocritus University of ThraceAlexandroupolis 68100Greece Clinic for Endocrinology Diabetes and Metabolic DisordersClinical Center of VojvodinaMedical FacultyUniversity of Novi SadNovi Sad 21000Serbia

In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in *** focus on the epidemiological,pathophysiological,and clinical interplay between obesity and type 1 diabetes mellitus(T1DM).Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this *** exogenous insulin administration,genetic and epigenetic factors,and psy-chosocial and behavioral parameters,along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity,set the stage for the increasing obesity rates in *** our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands,it becomes clear that there are overlap zones in the pathophysiology of the two main types of *** regarding strict dividing lines between“autoimmune”and“metabolic”phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches,instead of individualized diabetes *** this context,the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM.

关键词： Obesity Overweight Type 1 diabetes Metabolic syndrome

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Effect of special types of bread with select herbal components on postprandial glucose levels in diabetic patients

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World Journal of Diabetes 2024年第4期15卷 664-674页

作者： Drasko M Gostiljac srdjan s.popovic Vesna Dimitrijevic-sreckovic sasa M Ilic Jelena A Jevtovic Dragan M Nikolic Ivan A soldatovic Clinic for Endocrinology Diabetes and Metabolic DiseasesUniversity Clinical Centre of SerbiaBelgrade 11000Serbia Faculty of Medicine University of BelgradeBelgrade 11000Serbia Clinic for Gastroenterology and Hepatology University Clinical Centre of SerbiaBelgrade 11000Serbia Clinic for Endocrinology Diabetes and Metabolic Diseases-Laboratory for Human Pancreatic Islets CultureUniversity Clinical Centre of SerbiaBelgrade 11000Serbia

BACKGROUND Nutrition recommendations in patients with type 2 diabetes mellitus(T2DM)are to consume rye or integral bread instead of white bread.A positive effect on glucoregulation has been achieved by enriching food with various biologically active substances of herbal origin,so we formulated an herbal mixture that can be used as a supplement for a special type of bread(sTB)to achieve better effects on postprandial glucose and insulin levels in patients with *** To compare organoleptic characteristics and effects of two types of bread on postprandial glucose and insulin levels in T2DM *** This trial included 97 patients with T2DM.A parallel group of 16 healthy subjects was also *** participants were given 50 g of rye bread and the same amount of a sTB with an herbal mixture on 2 consecutive *** blood glucose and insulin levels were compared at the 30^(th),60^(th),90^(th) and 120th min.A questionnaire was used for subjective estimation of the organoleptic and satiety features of the two types of *** Compared to patients who consumed rye bread,significantly lower postprandial blood glucose and insulin concentrations were found in T2DM patients who consumed *** relevant differences were found among the healthy *** estimated organoleptic and satiety characteristics are better for sTB than for rye *** sTB have better effects than rye bread on postprandial glucoregulation in T2DM *** estimated organoleptic and satiety characteristics are better for sTB than for rye ***,sTB can be recommended for nutrition in T2DM patients.

关键词： special types of bread Postprandial glucoregulation Insulin Nutrition Type 2 diabetes mellitus

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Appropriateness of Amikacin Dose Prescription, Monitoring and safety during Hospitalization as an Impact of Clinical Pharmacologist Intervention, in the Israeli Regional Hospital

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Journal of Biosciences and Medicines 2024年第3期12卷 337-354页

作者： Renata shihmanter Olga lazar Lidia Arcavi Clinical Pharmacology Unit Kaplan Medical Center Rehovot and Hebrew University Hadassah Medical School Jerusalem Israel Department of Medicine Kaplan Medical Center Rehovot and Hebrew University Hadassah Medical School Jerusalem Israel

Background: Use of inappropriate amikacin dose is one of the most important factors in inducing toxicity, prolonged hospitalization as well as in increasing patient’s mortality. Objective: The aims of this study are the analysis of amikacin dose, serum level and the examination of the effectiveness of the clinical pharmacologist (CP) therapeutic drug monitoring (TDM) intervention to guarantee the safety of amikacin use. Methods: This is a one-year retrospective observational chart review study, which evaluates amikacin dose, serum drug level, development of adverse effects in patients on amikacin with or without CP TDM consultation. Results: Amikacin was prescribed for 393 complex patients, with median age 83. Amikacin group (AG) included 140 (32%) courses with CP consultation (AG1) and 292 (68%) courses without CP consultation (AG2). The distribution of most study characteristics in both groups was similar including amikacin dose (9-10 mg/kg/day), renal failure (14%) and mortality (12%). Acceptance for CP consultation was in 46% of amikacin courses and dose changes were done in 63% after CP intervention. Prolonged antibiotic course (4.6 ± 1.5 vs 3.8 ± 1.6 days, p s hemodynamic instability (15% vs 7%, p = 0.01) were more frequent in the AG1 compared to the AG2. There was a strong association between CP consultation and prolonged hospitalization (p = 0.005), while no association between it and amikacin adverse effects, renal failure or mortality. Conclusions: There was no trend to reducing amikacin toxicity, days of hospitaliza tion or mortality in patients with CP consultation. CP TDM intervention was more in the management of complicated clinical situations. However, it is necessary to optimize it.

关键词： Amikacin Therapeutic Drug Monitoring Appropriate Clinical Pharmacologist safety Adverse Effects

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Immunotherapy:A new standard in the treatment of metastatic clear cell renal cell carcinoma

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World Journal of Clinical Oncology 2022年第1期13卷 28-38页

作者： Maja popovic Gorana Matovina-Brko Masa Jovic lazar s.popovic Department of Medical Oncology Oncology Institute of VojvodinaUniversity of Novi SadSremska Kamenica Faculty of Medicine University of Novi SadNovi Sad 21000Serbia

Renal cell cancer(RCC)represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney(90%).In the mid-nineties of the last century,the standard of treatment for patients with metastatic RCC was *** and pazopanib were registered in 2007 and 2009,respectively,and have since been the standard first-line treatment for metastatic clear cell RCC(mccRCC).Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells,including CD8+T lymphocytes,dendritic cells,natural killer cells(NK)and *** observation led to the design of new clinical trials in which patients were treated with *** the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system,the idea of combining angiogenic drugs with immunotherapy has emerged,and new clinical trials have been *** the last few years,several therapeutic options have been approved[immunotherapy and immunotherapy/tyrosine kinase inhibitors(TKI)]for the first-line treatment of ***/ipilimumab is approved for the treatment of patients with intermediate and poor *** checkpoint inhibitors(pembrolizumab,nivolumab,avelumab)in combination with TKI(axitinib,lenvatinib,cabozantinib)are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 *** is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.

关键词： Renal cell carcinoma Immunotherapy Checkpoint inhibitors Biomarkers Tumor microenvironment Programmed cell death 1 receptor

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Immunotherapy in the treatment of lymphoma

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World Journal of stem Cells 2021年第6期13卷 503-520页

作者： lazar s.popovic Gorana Matovina-Brko Maja popovic Milica popovic Ana Cvetanovic Ivan Nikolic Biljana Kukic Dragana Petrovic Department for Medical Oncology Oncology Institute of VojvodinaUniversity of Novi SadNovi Sad 21000Serbia Department for Medical Oncology Oncology Institute of VojvodinaNovi Sad 21000Serbia Department for Nephrology and Clinical Immunology Clinical Center of VojvodinaUniversity of Novi SadNovi Sad 21000Serbia Department for Medical Oncology Clinical Center of NisUniversity of NisNis 18000Serbia

Relapsed or refractory non-Hodgkin’s lymphomas,especially diffuse large B-cell lymphoma as well as relapsed or refractory Hodgkin lymphomas are hard-to-treat *** who do not respond to initial therapy or experience relapse are treated with salvage regimens,and if eligible for aggressive therapy,treatment is continued with high-dose chemotherapy and autologous stem cell *** therapy options can cure substantial numbers of patients,however for some it is still an uncurable *** new drugs and cell therapies are being investigated for the treatment of relapsed or refractory *** types of immunotherapy options have shown promising results,and some have already become the standard of ***,we review immunotherapy options for the treatment of lymphoma and discuss the results,positions,practical aspects,and future directions of different drugs and cellular therapies for the treatment of this disease.

关键词： Immunotherapy Receptors Chimeric antigen Antibodies Monoclonal Immunoconjugates Hodgkin disease Lymphoma Large B-cell Diffuse

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Bio-organic adaptive photonic crystals enable supramolecular solvatochromism

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Nano Research 2023年第10期16卷 12092-12097页

作者： Jiahao Zhang Yan Zhang Yancheng Wang sigal Rencus-lazar Deqing Mei Ehud Gazit Kai Tao state Key Laboratory of Fluid Power and Mechatronic systems School of Mechanical EngineeringZhejiang UniversityHangzhou 310027China Zhejiang-Israel Joint Laboratory of self-Assembling Functional Materials Hangzhou Global Scientific and Technological Innovation CentreZhejiang UniversityHangzhou 311200China Key Laboratory of Advanced Manufacturing Technology of Zhejiang Province School of Mechanical EngineeringZhejiang UniversityHangzhou 310027China The shmunis school of Biomedicine and Cancer Research George S.Wise Faculty of Life SciencesTel Aviv UniversityTel Aviv 6997801Israel Department of Materials science and Engineering Iby and Aladar Fleischman Faculty of EngineeringTel Aviv UniversityTel Aviv 6997801Israel

Photonic crystals(PCs)exhibit promising structural coloration properties and possess extensive application prospects in diverse optical ***,state-of-the-art inorganic or polymeric PCs show limited adaptivity as their configurations are fixed once ***,bio-organic adaptive PCs are fabricated via drop-casting of amphiphilic guanine-based peptide nucleic acid selfassembled *** high formation activation energy of up to 81.8 kJ·mol−1 suggests that the self-assembly step dominates the entire ***,the configurations along with the structural coloration of the supramolecular PCs are sensitive to self-assembly influencing parameters,showing temperature-encoded structural color evolution and solvent polaritydependent *** findings demonstrate that the supramolecular PCs are adaptive,thus showing promising potential for detection of organic solvents of different polarities in a visual and real-time manner for environmental protection or optical applications.

关键词： peptide nucleic acids molecular manufacturing supramolecular photonic crystals solvatochromic effects adaptivity

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Miniature,highly sensitive MOsCAP ring modulators in co-optimized electronic-photonic CMOs

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Photonics Research 2022年第1期10卷 I0001-I0007页

作者： HAYK GEVORGYAN ANATOL KHILO MARK T.WADE VLADIMIR M.sTOJANOVIC MILOs A.popovic Department of Electrical and Computer Engineering Boston UniversityBostonMassachusetts 02215USA Ayar Labs Inc. EmeryvilleCalifornia 94608USA Department of Electrical Engineering and Computer sciences University of California BerkeleyBerkeleyCalifornia 94709USA

Convergence of high-performance silicon photonics and electronics,monolithically integrated in state-of-the-art CMOs platforms,is the holy grail for enabling the ultimate efficiencies,performance,and scaling of electronicphotonic *** requires the emergence of platforms that combine state-of-the-art RF transistors with optimized silicon photonics,and a generation of photonic device technology with ultralow energies,increased operating spectrum,and the elimination of power-hungry thermal *** this paper,in a co-optimized monolithic electronics-photonics platform(GlobalFoundries 45 CLO),we turn the metal-oxide-semiconductor(MOs) field-effect transistor’s basic structure into a novel,highly efficient MOs capacitor ring *** has the smallest ring cavity(1.5 μm radius),largest corresponding spur-free free spectral range(FsR=8.5 THz),and record 30 GHz/V shift efficiency in the O-band among silicon modulators demonstrated to *** 1 V_(pp) RF drive,we show an open optical eye while electro-optically tuning the modulator to track over 400 pm(69 GHz) change in the laser wavelength(using 2.5 V_(DC) range).A 90 GHz maximum electro-optic resonance shift is demonstrated with under 40 nW of power,providing a strong nonthermal tuning mechanism in a CMOs photonics *** modulator has a separately optimized body layer but shares the gate device layer and the gate oxide with 45 nm transistors,while meeting all CMOs manufacturability design *** type of convergent evolution of electronics and photonics may be the future of platforms for high-performance systemson-chip.

关键词： tuning modulator electronic

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Dielectric and infrared properties of srTiO_3 single crystal doped by 3d (V,Mn,Fe,Ni) and 4f (Nd,sm,Er) ions

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Chinese Physics B 2014年第2期23卷 369-374页

作者： s.Maletic D.Maletic I.Petronijevic J.Dojcilovic D.M.popovic Faculty of Physics University of Belgrade Institute of Physics University of Belgrade

In this study, the effects of doping by 3d （V, Mn, Fe, Ni） and 4f （Nd, sm, Er） ions on dielectric and infrared properties of srTiO3 （sTO） single crystals are investigated. It is well known that doping of the srTiO3 can change the dielectric properties of the sTO from an insulator to an n-type semiconductor, and even to a metallic conductor. Dielectric and infrared （IR） properties of the undoped sTO and doped sTO single crystals are analyzed using dielectric spectroscopy （80 kHz-5 MHz）, transmission （200 cm^-1-4000 cm^-1）, and reflection spectroscopy （50 cm^-1-2000 cm^-1）. It is found that doping by the 3d ions reduces the value of dielectric permittivity, but the trend of temperature dependence of the dielectric permittivity remains almost unchanged. On the other hand, dielectric spectroscopy measurements for samples doped by 4f ions show the anomalous behaviors of the dielectric permittivity at temperatures around the temperature of the structural phase transition. There are two fractures of temperature dependences of inverse dielectric permittivity εr^-1 （T）. Transmittance spectroscopy measurements show that there are differences in the shape of the spectrum in the mid-IR region between the undoped sTO and the one doped by 4f ions. The differences in the reflectance spectrum between the sTO：Nd and sTO are analyzed in detail.

关键词： doping dielectric properties phase transitions infrared spectroscopy

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