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Article: To Explore the Stem Cells Homing to GBM: The Rise to the Occasion.

Tsibulnikov, Sergey / Drefs, Natalya M / Timashev, Peter S / Ulasov, Ilya V

2022 Volume 10, Issue 5

Abstract: Multiple efforts are currently underway to develop targeted therapeutic deliveries to the site of glioblastoma progression. The use of carriers represents advancement in the delivery of various therapeutic agents as a new approach in neuro-oncology. ... ...

Abstract	Multiple efforts are currently underway to develop targeted therapeutic deliveries to the site of glioblastoma progression. The use of carriers represents advancement in the delivery of various therapeutic agents as a new approach in neuro-oncology. Mesenchymal stem cells (MSCs) and neural stem cells (NSCs) are used because of their capability in migrating and delivering therapeutic payloads to tumors. Two of the main properties that carrier cells should possess are their ability to specifically migrate from the bloodstream and low immunogenicity. In this article, we also compared the morphological and molecular features of each type of stem cell that underlie their migration capacity to glioblastoma. Thus, the major focus of the current review is on proteins and lipid molecules that are released by GBM to attract stem cells.
Language	English
Publishing date	2022-04-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10050986
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Article ; Online: Refurbishment of NK cell effector functions through their receptors by depleting the activity of nTreg cells in Dalton's Lymphoma-induced tumor microenvironment: an in vitro and in vivo study.

Tomar, Munendra Singh / Singh, Rishi Kant / Ulasov, Ilya V / Kaushalendra / Acharya, Arbind

Cancer immunology, immunotherapy : CII

2022 Volume 72, Issue 6, Page(s) 1429–1444

Abstract: Natural killer (NK) cells play a crucial role in the anti-tumor transaction through cytolytic activity with the help of proportionate expression of their activating receptors (ARs) and inhibitory receptors (IRs). The proliferation, differentiation, and ... ...

Abstract	Natural killer (NK) cells play a crucial role in the anti-tumor transaction through cytolytic activity with the help of proportionate expression of their activating receptors (ARs) and inhibitory receptors (IRs). The proliferation, differentiation, and effector's functions of NK cells were affected and regulated by CD4
MeSH term(s)	Humans ; Killer Cells, Natural ; Lymphoma/metabolism ; T-Lymphocytes, Regulatory ; Transforming Growth Factor beta/metabolism ; Cell Line, Tumor ; Tumor Microenvironment
Chemical Substances	Transforming Growth Factor beta
Language	English
Publishing date	2022-12-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	195342-4
ISSN	1432-0851 ; 0340-7004
ISSN (online)	1432-0851
ISSN	0340-7004
DOI	10.1007/s00262-022-03339-6
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Zs.A 1237: Show issues

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Article: Combination of conservative and surgical methods in the treatment of giant lymphedema of the scrotum: A case report.

Istranov, Andrey L / Makarov, Ivan G / Makarova, Natalya V / Tulina, Inna / Ulasov, Ilya V / Isakova, Yuliya I

Frontiers in surgery

2023 Volume 10, Page(s) 1048159

Abstract: Objective: Genital lymphedema is a severe, disabling condition associated with a malfunction of the lymphatic system. Primary lymphedema of the scrotum is a variant of congenital dysplasia of lymphatic vessels. Secondary genital lymphedema is much more ... ...

Abstract	Objective: Genital lymphedema is a severe, disabling condition associated with a malfunction of the lymphatic system. Primary lymphedema of the scrotum is a variant of congenital dysplasia of lymphatic vessels. Secondary genital lymphedema is much more common and can be caused by parasitic invasion (filariasis) or damage to the lymphatic system during the treatment of cancer (radiation therapy, lymphadenectomy). Healthcare providers are frequently unable to detect and treat this illness successfully in ordinary clinical practice. This paper uses the case of a patient with stage 3 secondary lymphedema (unknown genesis) of both lower extremities and lymphedema of the scrotum, complicated by recurrent erysipelas, a history of lymphorrhoea, impaired skin trophic and multiple papillomatosis, to demonstrate the efficacy of a combination of conservative and surgical methods in the treatment of giant lymphedema of the scrotum. Methods: In the treatment, the combination of decongestant physical therapy (CDPT, CDT) according to M. Földi was used at pre-surgery and post-surgery stages, combined with a reconstructive operation, including the removal of the affected tissues of the urogenital region, phalloplasty, and scrotoplasty with rotational skin flaps. Results: A decrease in the circumference of the lowest extremities in the lower leg area by 68 cm on the right and by 69 cm on the left was achieved by conservative treatment. Due to the combination of conservative and surgical treatment, the patient's body weight decreased by 69.4 kg, and the scrotum decreased by 63 cm. Subsequently, the patient fully recovered his sexual function. Conclusion: A combination of complex decongestive physical therapy and surgery is necessary for patients with advanced genital edema. The isolated use of surgical or conservative treatment does not provide a sufficient improvement in the patient's quality of life. Modern plastic surgery technologies enable patients to achieve complete functional and cosmetic recovery, while proper selection and usage of compression hosiery help preserve and improve the outcomes acquired following treatment.
Language	English
Publishing date	2023-04-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2773823-1
ISSN	2296-875X
ISSN	2296-875X
DOI	10.3389/fsurg.2023.1048159
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Article: Carbonic Anhydrase Inhibitors Induce Ferroptosis through Inhibition of AKT/FTH1 Signaling in Ewing Sarcoma Tumor Cells.

Fayzullina, Darya / Yakushov, Semyon / Kantserova, Kamilla / Belyaeva, Elizaveta / Aniskin, Denis / Tsibulnikov, Sergey / Fayzullina, Nafisa / Kalinin, Stanislav / Romantsova, Olga / Timashev, Peter S / Schroeder, Brett A / Ulasov, Ilya V

Cancers

2023 Volume 15, Issue 21

Abstract: Ewing sarcoma (ES) is one of the most frequent types of malignant tumors among children. The active metabolic state of ES cells presents a new potential target for therapeutic interventions. As a primary regulator of cellular homeostasis, carbonic ... ...

Abstract	Ewing sarcoma (ES) is one of the most frequent types of malignant tumors among children. The active metabolic state of ES cells presents a new potential target for therapeutic interventions. As a primary regulator of cellular homeostasis, carbonic anhydrases (CAs; EC 4.2.1.1) have emerged as promising molecular targets for the development of anticancer drugs. Within the present study, we tested the commercial drug acetazolamide and our previously discovered inhibitors to target the CAII isoform, which was overexpressed and positively correlated with ES patient relapse. We employed molecular biology tests to identify effective inhibitors of CAII that can induce ferroptosis by downregulating FTH1 expression in ES cells. In vitro, we have also demonstrated their ability to reduce cell proliferation, decrease invasion, and induce apoptosis- or autophagy-related cell death. Using Western blotting, we confirmed the induction of cathepsin B in cells treated with CA inhibitors. It was found that the suppression of cathepsin B expression during the treatment reduces the anticancer efficacy of selected CAII inhibitors. These experiments highlighted profound antitumor activity of CAII inhibitors attributive to their remarkable ability to trigger ferroptosis in Ewing sarcoma cells without causing substantial host damage. The obtained results suggest that cytosolic CAII may be a prospective target for ES treatment, and CAII inhibitors can be considered as potential single-agent or combination antitumor agents to be used in the treatment of ES.
Language	English
Publishing date	2023-10-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15215225
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Article: Human cytomegalovirus-mediated immunomodulation: Effects on glioblastoma progression.

Foster, Haidn / Ulasov, Ilya V / Cobbs, Charles S

Biochimica et biophysica acta. Reviews on cancer

2017 Volume 1868, Issue 1, Page(s) 273–276

Abstract: The presence of human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM), first established in 2002, has developed into an area of considerable interest and controversy. Numerous studies have found evidence of possible HCMV infection of GBM tumor ... ...

Abstract	The presence of human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM), first established in 2002, has developed into an area of considerable interest and controversy. Numerous studies have found evidence of possible HCMV infection of GBM tumor cells as well as myriad onco- and immunomodulatory properties exhibited by HCMV antigens and transcripts, while recent reports have failed to detect HCMV particles in GBM and question the virus' role in tumor progression. This review highlights the known immunomodulatory properties of HCMV, independent of GBM infection status, that help drive the virus from peripheral blood into the vital tissues and subsequently dampen local immune response, assisting GBM tumors in evading immune surveillance and contributing to the disease's poor prognosis. Emerging antiviral approaches to treating GBM, including antiviral drugs and immunotherapies directed against HCMV, are also examined.
MeSH term(s)	Brain Neoplasms/immunology ; Brain Neoplasms/pathology ; Brain Neoplasms/virology ; Cytomegalovirus/immunology ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/pathology ; Cytomegalovirus Infections/virology ; Disease Progression ; Glioblastoma/immunology ; Glioblastoma/pathology ; Glioblastoma/virology ; Humans ; Immunomodulation/immunology
Language	English
Publishing date	2017-05-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0304-419X ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0304-419X ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbcan.2017.05.006
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Uc I Zs.247: Show issues

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Article ; Online: The IL13α 2R paves the way for anti-glioma nanotherapy.

Ulasov, Ilya V / Borovjagin, Anton / Laevskaya, Anastasia / Kamynina, Margarita / Timashev, Peter / Cerchia, Laura / Rozhkova, Elena A

Genes & diseases

2021 Volume 10, Issue 1, Page(s) 89–100

Abstract: Glioblastoma (GBM) is one of the most aggressive (grade IV) gliomas characterized by a high rate of recurrence, resistance to therapy and a grim survival prognosis. The long-awaited improvement in GBM patients' survival rates essentially depends on ... ...

Abstract	Glioblastoma (GBM) is one of the most aggressive (grade IV) gliomas characterized by a high rate of recurrence, resistance to therapy and a grim survival prognosis. The long-awaited improvement in GBM patients' survival rates essentially depends on advances in the development of new therapeutic approaches. Recent preclinical studies show that nanoscale materials could greatly contribute to the improvement of diagnosis and management of brain cancers. In the current review, we will discuss how specific features of glioma pathobiology can be employed for designing efficient targeting approaches. Moreover, we will summarize the main evidence for the potential of the IL-13R alpha 2 receptor (IL13α2R) targeting in GBM early diagnosis and experimental therapy.
Language	English
Publishing date	2021-09-15
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2821806-1
ISSN	2352-3042 ; 2352-3042
ISSN (online)	2352-3042
ISSN	2352-3042
DOI	10.1016/j.gendis.2021.08.006
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Article ; Online: Isoforms of autophagy-related proteins: role in glioma progression and therapy resistance.

Belyaeva, Elizaveta / Kharwar, Rajesh Kumar / Ulasov, Ilya V / Karlina, Irina / Timashev, Petr / Mohammadinejad, Reza / Acharya, Arbind

Molecular and cellular biochemistry

2021 Volume 477, Issue 2, Page(s) 593–604

Abstract: Autophagy is the process of recycling and utilization of degraded organelles and macromolecules in the cell compartments formed during the fusion of autophagosomes with lysosomes. During autophagy induction the healthy and tumor cells adapt themselves to ...

Abstract	Autophagy is the process of recycling and utilization of degraded organelles and macromolecules in the cell compartments formed during the fusion of autophagosomes with lysosomes. During autophagy induction the healthy and tumor cells adapt themselves to harsh conditions such as cellular stress or insufficient supply of nutrients in the cell environment to maintain their homeostasis. Autophagy is currently seen as a form of programmed cell death along with apoptosis and necroptosis. In recent years multiple studies have considered the autophagy as a potential mechanism of anticancer therapy in malignant glioma. Although, subsequent steps in autophagy development are known and well-described, on molecular level the mechanism of autophagosome initiation and maturation using autophagy-related proteins is under investigation. This article reviews current state about the mechanism of autophagy, its molecular pathways and the most recent studies on roles of autophagy-related proteins and their isoforms in glioma progression and its treatment.
MeSH term(s)	Apoptosis ; Autophagosomes/genetics ; Autophagosomes/metabolism ; Autophagy ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/metabolism ; Glioma/genetics ; Glioma/metabolism ; Glioma/therapy ; Humans ; Neoplasm Proteins/metabolism
Chemical Substances	Autophagy-Related Proteins ; Neoplasm Proteins
Language	English
Publishing date	2021-12-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-021-04308-w
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Zs.A 892: Show issues

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Article ; Online: KISS1 in breast cancer progression and autophagy.

Ulasov, Ilya V / Borovjagin, Anton V / Timashev, Peter / Cristofanili, Massimo / Welch, Danny R

Cancer metastasis reviews

2019 Volume 38, Issue 3, Page(s) 493–506

Abstract: Tumor suppressors are cellular proteins typically expressed in normal (non-cancer) cells that not only regulate such cellular functions as proliferation, migration and adhesion, but can also be secreted into extracellular space and serve as biomarkers ... ...

Abstract	Tumor suppressors are cellular proteins typically expressed in normal (non-cancer) cells that not only regulate such cellular functions as proliferation, migration and adhesion, but can also be secreted into extracellular space and serve as biomarkers for pathological conditions or tumor progression. KISS1, a precursor for several shorter peptides, known as metastin (Kisspeptin-54), Kisspeptin-14, Kisspeptin-13 and Kisspeptin-10, is one of those metastasis suppressor proteins, whose expression is commonly downregulated in the metastatic tumors of various origins. The commonly accepted role of KISS1 in metastatic tumor progression mechanism is the ability of this protein to suppress colonization of disseminated cancer cells in distant organs critical for the formation of the secondary tumor foci. Besides, recent evidence suggests involvement of KISS1 in the mechanisms of tumor angiogenesis, autophagy and apoptosis regulation, suggesting a possible role in both restricting and promoting cancer cell invasion. Here, we discuss the role of KISS1 in regulating metastases, the link between KISS1 expression and the autophagy-related biology of cancer cells and the perspectives of using KISS1 as a potential diagnostic marker for cancer progression as well as a new anti-cancer therapeutics.
MeSH term(s)	Animals ; Autophagy/physiology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Female ; Humans ; Kisspeptins/metabolism
Chemical Substances	Biomarkers, Tumor ; Kisspeptins
Language	English
Publishing date	2019-11-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604857-2
ISSN	1573-7233 ; 0167-7659
ISSN (online)	1573-7233
ISSN	0167-7659
DOI	10.1007/s10555-019-09814-4
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Zs.A 1812: Show issues

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Article ; Online: Cytomegalovirus as an oncomodulatory agent in the progression of glioma.

Joseph, Gabriel P / McDermott, Ryan / Baryshnikova, Maria A / Cobbs, Charles S / Ulasov, Ilya V

Cancer letters

2017 Volume 384, Page(s) 79–85

Abstract: Glioblastoma multiforme (GBM) is the most aggressive neoplastic brain tumor in humans with a median survival of less than 2 years. It is therefore critical to understand the mechanism of glioma progression and to identify future targets for intervention. ...

Abstract	Glioblastoma multiforme (GBM) is the most aggressive neoplastic brain tumor in humans with a median survival of less than 2 years. It is therefore critical to understand the mechanism of glioma progression and to identify future targets for intervention. We investigate the mechanisms of cytomegalovirus as an oncomodulatory agent implicated in glioma progression, as well as immunosuppression. This review provides a comprehensive evaluation of recent investigative developments concerning the role of CMV in cellular processes during glioma growth. The manners in which CMV and its viral products interact with regulatory cellular signaling pathways in the host are of primary interest. Here, we examine some of the most significant oncomodulatory effects that CMV can confer in brain tumors, including the inhibition of apoptosis and promoting the growth of glioma stem cells, which are tightly linked to tumor survival and recurrence.
MeSH term(s)	Animals ; Apoptosis ; Brain Neoplasms/epidemiology ; Brain Neoplasms/immunology ; Brain Neoplasms/pathology ; Brain Neoplasms/virology ; Cell Cycle ; Cell Proliferation ; Cell Transformation, Viral ; Cytomegalovirus/immunology ; Cytomegalovirus/metabolism ; Cytomegalovirus/pathogenicity ; Cytomegalovirus Infections/epidemiology ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/metabolism ; Cytomegalovirus Infections/virology ; Disease Progression ; Glioma/epidemiology ; Glioma/immunology ; Glioma/pathology ; Glioma/virology ; Host-Pathogen Interactions ; Humans ; Inflammation Mediators/metabolism ; Tumor Escape ; Tumor Virus Infections/epidemiology ; Tumor Virus Infections/immunology ; Tumor Virus Infections/metabolism ; Tumor Virus Infections/virology
Chemical Substances	Inflammation Mediators
Language	English
Publishing date	2017--01
Publishing country	Ireland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2016.10.022
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Zs.A 1177: Show issues

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Article ; Online: TMZ regulates GBM stemness via MMP14-DLL4-Notch3 pathway.

Ulasov, Ilya V / Mijanovic, Olja / Savchuk, Solomiia / Gonzalez-Buendia, Edgar / Sonabend, Adam / Xiao, Ting / Timashev, Petr / Lesniak, Maciej S

International journal of cancer

2019 Volume 146, Issue 8, Page(s) 2218–2228

Abstract: Glioblastoma (GBM) is one of the most aggressive primary brain tumors with frequent recurrences following the standard methods of treatment-temozolomide (TMZ), ionizing radiation and surgical resection. The objective of our study was to investigate GBM ... ...

Abstract	Glioblastoma (GBM) is one of the most aggressive primary brain tumors with frequent recurrences following the standard methods of treatment-temozolomide (TMZ), ionizing radiation and surgical resection. The objective of our study was to investigate GBM resistance mediated via MMP14 (matrix metalloproteinase 14). We used multiple PDX GBM models and established glioma cell lines to characterize expression and subcellular localization of MMP14 after TMZ treatment. We performed a Kiloplex ELISA-based array to evaluate changes in cellular proteins induced by MMP14 expression and translocation. Lastly, we conducted functional and mechanistic studies to elucidate the role of DLL4 (delta-like canonical notch ligand 4) in regulation of glioma stemness, particularly in the context of its relationship to MMP14. We detected that TMZ treatment promotes nuclear translocation of MMP14 followed by extracellular release of DLL4. DLL4 in turn stimulates cleavage of Notch3, its nuclear translocation and induction of sphering capacity and stemness.
MeSH term(s)	Animals ; Biomarkers, Tumor/biosynthesis ; Biomarkers, Tumor/metabolism ; Brain Neoplasms/drug therapy ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Early Growth Response Protein 1/metabolism ; Fibroblast Growth Factors/metabolism ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Matrix Metalloproteinase 14/biosynthesis ; Matrix Metalloproteinase 14/metabolism ; Membrane Proteins/metabolism ; Mice ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Receptor, Notch3/metabolism ; Signal Transduction/drug effects ; Temozolomide/pharmacology ; Xenograft Model Antitumor Assays
Chemical Substances	Biomarkers, Tumor ; EGR1 protein, human ; Early Growth Response Protein 1 ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; NOTCH3 protein, human ; Receptor, Notch3 ; delta protein ; Fibroblast Growth Factors (62031-54-3) ; MMP14 protein, human (EC 3.4.24.80) ; Matrix Metalloproteinase 14 (EC 3.4.24.80) ; Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2019-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.32636
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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