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Article: Circular STAG2 RNA Modulates Bladder Cancer Progression via miR-145-5p/TAGLN2 and Is Considered as a Biomarker for Recurrence.

Du, Chris / Waltzer, Wayne C / Wilusz, Jeremy E / Spaliviero, Massimiliano / Darras, Frank / Romanov, Victor

2024 Volume 16, Issue 5

Abstract: The current study aimed to elucidate the regulatory mechanisms of the circRNA hsa_circ_0139697 (circSTAG2(16-25)) in BCa and to consider the opportunity of using circSTAG2(16-25) isolated from BCa patient urine as a marker for disease development ... ...

Abstract	The current study aimed to elucidate the regulatory mechanisms of the circRNA hsa_circ_0139697 (circSTAG2(16-25)) in BCa and to consider the opportunity of using circSTAG2(16-25) isolated from BCa patient urine as a marker for disease development prediction. The selection of this circRNA was determined by the special role of its parental gene STAG2 in BCa biology. The circRNA hsa_circ_0139697 was chosen from 25 STAG2 circRNAs due to its differential expression in the urine of BCa patients and healthy volunteers. Higher levels of circSTAG2(16-25) were detected in urine samples obtained from patients with recurrent tumors. A higher expression of circSTAG2(16-25) was also detected in more tumorigenic BCa cell lines. The overexpression of circSTAG2(16-25) in BCa cells induced the elevation of proliferation, motility, and invasion. To study the mechanisms of circSTAG2(16-25) activity, we confirmed that circSTAG2(16-25) can bind miR-145-5p in vitro as was predicted by bioinformatic search. miR-145-5p was shown to suppress some genes that promoted BCa progression. One of these genes, TAGLN2, encodes the protein Transgelin 2, which plays a role in BCa cell motility and invasion. Therefore, the possible mechanism of action of circSTAG2(16-25) could be sponging the tumor suppressor miR-145-5p, which results in activation of TAGLN2. In addition, circSTAG2(16-25) might be considered as a potential biomarker for recurrence prediction.
Language	English
Publishing date	2024-02-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16050978
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Article ; Online: Experimental studies of the air conditioning system efficiency in the cab of “TORUM 785” combine harvester

Babenkov Yury / Ozersky Anatoly / Romanov Victor / Galka Galina / Morozov Maksim

E3S Web of Conferences, Vol 273, p

2021 Volume 07001

Abstract: The article presents the results of field tests and experimental studies of the efficiency of the climatic air conditioning system (ACS) in the cab of a combine harvester “TORUM 785”. The studies were carried out according to the Russian methods ... ...

Abstract	The article presents the results of field tests and experimental studies of the efficiency of the climatic air conditioning system (ACS) in the cab of a combine harvester “TORUM 785”. The studies were carried out according to the Russian methods recommended for use in field tests of tractors and self-propelled vehicles intended for agricultural work in the southern regions of Russia. In the course of the research, a sufficiently high efficiency of the climatic SCR of the cabin of the “TORUM 785” combine harvester was shown under various operating conditions. It is shown that the created climatic SCRs are not inferior to foreign models developed by such companies as John Deere, Claas and New Holland.
Keywords	Environmental sciences ; GE1-350
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	EDP Sciences
Document type	Article ; Online
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Article ; Online: Organoid model of urothelial cancer: establishment and applications for bladder cancer research.

Whyard, Terry / Liu, Jingxuan / Darras, Frank S / Waltzer, Wayne C / Romanov, Victor

BioTechniques

2020 Volume 69, Issue 3, Page(s) 193–199

Abstract: 3D cancer cell models are suitable for drug evaluation because they more precisely mimic tissue architecture than 2D cultures. To study cytotoxicity of anticancer agents, the most sensitive CellTiter-Glo 3D assay is used. However, this is an end point ... ...

Abstract	3D cancer cell models are suitable for drug evaluation because they more precisely mimic tissue architecture than 2D cultures. To study cytotoxicity of anticancer agents, the most sensitive CellTiter-Glo 3D assay is used. However, this is an end point assay, so it is not possible to consider the variance of the starting material amount in the final reading. It is difficult to maintain an even plating density of 3D organoids for cytotoxicity analysis. We present a simple, 3D bladder cancer culture that can be maintained, cryopreserved and used for molecular and drug response studies. We applied a simple modification of the drug response assay for 3D cultures by measuring the background signal with the CellTiter Blue assay before drug application.
MeSH term(s)	Humans ; Organoids/pathology ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/pathology ; Urothelium/pathology
Language	English
Publishing date	2020-07-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	48453-2
ISSN	1940-9818 ; 0736-6205
ISSN (online)	1940-9818
ISSN	0736-6205
DOI	10.2144/btn-2020-0068
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Article: Phage display selection and evaluation of cancer drug targets.

Romanov, Victor I

Current cancer drug targets

2003 Volume 3, Issue 2, Page(s) 119–129

Abstract: Techniques for the construction of phage display libraries of combinatorial proteins have dramatically improved. This has allowed researchers to expand the applications to the field of cancer biology. The most direct use of protein phage-displayed ... ...

Abstract	Techniques for the construction of phage display libraries of combinatorial proteins have dramatically improved. This has allowed researchers to expand the applications to the field of cancer biology. The most direct use of protein phage-displayed libraries is the selection of ligands for individual proteins. This includes identification of peptide ligands for receptor signaling molecules: integrins, cytokine and growth factor receptors. Selected peptides may be used as competitors for natural ligands and for the mapping of binding epitopes. This approach has been exploited for delineation of intracellular signal transduction pathways and for the selection of enzyme substrates and inhibitors. Recently, more complicated biological systems were used as targets for biopanning. This includes combination of soluble proteins, cellular surfaces and even the vasculature of whole organs. cDNA expression libraries in phage-based vectors have been recently introduced. The use of phage as a vector for targeted gene therapy is also considered. These and other applications of phage display for cancer research will be reviewed.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Humans ; Neoplasm Proteins/drug effects ; Neoplasm Proteins/genetics ; Neoplasms/drug therapy ; Neoplasms/genetics ; Peptide Library
Chemical Substances	Antineoplastic Agents ; Neoplasm Proteins ; Peptide Library
Language	English
Publishing date	2003-11-03
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2064824-8
ISSN	1873-5576 ; 1568-0096
ISSN (online)	1873-5576
ISSN	1568-0096
DOI	10.2174/1568009033482010
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Zs.A 5589: Show issues

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Article ; Online: Metabolic alterations in bladder cancer: applications for cancer imaging.

Whyard, Terry / Waltzer, Wayne C / Waltzer, Douglas / Romanov, Victor

Experimental cell research

2016 Volume 341, Issue 1, Page(s) 77–83

Abstract: Treatment planning, outcome and prognosis are strongly related to the adequate tumor staging for bladder cancer (BC). Unfortunately, a large discrepancy exists between the preoperative clinical and final pathologic staging. Therefore, an advanced imaging- ...

Abstract	Treatment planning, outcome and prognosis are strongly related to the adequate tumor staging for bladder cancer (BC). Unfortunately, a large discrepancy exists between the preoperative clinical and final pathologic staging. Therefore, an advanced imaging-based technique is crucial for adequate staging. Although Magnetic Resonance Imaging (MRI) is currently the best in vivo imaging technique for BC staging because of its excellent soft-tissue contrast and absence of ionizing radiation it lacks cancer-specificity. Tumor-specific positron emission tomography (PET), which is based on the Warburg effect (preferential uptake of glucose by cancer cells), exploits the radioactively-labeled glucose analogs, i.e., FDG. Although FDG-PET is highly cancer specific, it lacks resolution and contrast quality comparable with MRI. Chemical Exchange Saturation Transfer (CEST) MRI enables the detection of low concentrations of metabolites containing protons. BC is an attractive target for glucose CEST MRI because, in addition to the typical systemic administration, glucose might also be directly applied into the bladder to reduce toxicity-related complications. As a first stage of the development of a contrast-specific BC imaging technique we have studied glucose uptake by bladder epithelial cells and have observed that glucose is, indeed, consumed by BC cells with higher intensity than by non-transformed urothelial cells. This effect might be partly explained by increased expression of glucose transporters GLUT1 and GLUT3 in transformed cells as compared to normal urothelium. We also detected higher lactate production by BC cells which is another cancer-specific manifestation of the Warburg effect. In addition, we have observed other metabolic alterations in BC cells as compared to non-transformed cells: in particular, increased pyruvate synthesis. When glucose was substituted by glutamine in culture media, preferential uptake of glutamine by BC cells was observed. The preferential uptake of glucose by BC cells gives an opportunity to develop NMR based imaging procedures where glucose or its derivatives can serve as a contrasting agent. In addition, metabolic alterations observed in BC cells could provide the basis for development of new anti-cancer therapeutics.
MeSH term(s)	Glucose/metabolism ; Glutamine/metabolism ; Humans ; Molecular Imaging/methods ; Nuclear Magnetic Resonance, Biomolecular/methods ; Tumor Cells, Cultured ; Urinary Bladder Neoplasms/metabolism ; Urinary Bladder Neoplasms/pathology
Chemical Substances	Glutamine (0RH81L854J) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2016-01-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2016.01.005
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Article ; Online: Clostridium perfringens enterotoxin as a potential drug for intravesical treatment of bladder cancer.

Gabig, Theodore G / Waltzer, Wayne C / Whyard, Terry / Romanov, Victor

Biochemical and biophysical research communications

2016 Volume 478, Issue 2, Page(s) 887–892

Abstract: The current intravesical treatment of bladder cancer (BC) is limited to a few chemotherapeutics that show imperfect effectiveness and are associated with some serious complications. Thus, there is an urgent need for alternative therapies, especially for ... ...

Abstract	The current intravesical treatment of bladder cancer (BC) is limited to a few chemotherapeutics that show imperfect effectiveness and are associated with some serious complications. Thus, there is an urgent need for alternative therapies, especially for patients with high-risk non-muscle invasive (NMIBC). Clostridium perfringens enterotoxin (CPE), cytolytic protein binds to its receptors: claudin 3 and 4 that are expressed in epithelial cells. This binding is followed by rapid cell death. Claudin 4 is present in several epithelial tissue including bladder urothelium and its expression is elevated in some forms of BC. In addition to directly targeting BC cells, binding of CPE to claudins increases urothelium permeability that creates conditions for better accession of the tumor. Therefore, we evaluated CPE as a candidate for intravesical treatment of BC using a cellular model. We examined cytotoxicity of CPE against BC cells lines and 3D cultures of cells derived from surgical samples. To better elucidate cellular mechanisms, activated by CPE and to consider the use of CPE non-toxic fragment (C-CPE) for combination treatment with other drugs we synthesized C-CPE, compared its cytotoxic activity with CPE and examined claudin 4 expression and intracellular localization after C-CPE treatment. CPE induced cell death after 1 h in low aggressive RT4 cells, in moderately aggressive 5637 cells and in the primary 3D cultures of BC cells derived from NMIBC. Conversely, non-transformed urothelial cells and cells derived from highly aggressive tumor (T24) survived this treatment. The reason for this resistance to CPE might be the lower expression of CLDNs or their inaccessibility for CPE in these cells. C-CPE treatment for 48 h did not affect cell viability in tested cells, but declined expression of CLDN4 in RT4 cells. C-CPE increased sensitivity of RT4 cells to Mitommycin C and Dasatinib. To better understand mechanisms of this effect we examined expression and phosphorylation status of EphA2 and Src after C-CPE treatment and found changes in expression and phosphorylated status of these regulatory molecules. These observations show that after additional preclinical studies CPE and C-CPE in combinations with other drugs can be considered as a potential modalities for intravesical treatment of BC because of its ability to effectively destroy BC cells expressing claudin 4 and low toxicity against normal urothelium.
MeSH term(s)	Administration, Intravesical ; Antineoplastic Agents/isolation & purification ; Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Claudin-4/genetics ; Claudin-4/metabolism ; Clostridium perfringens/chemistry ; Dasatinib/pharmacology ; Drug Evaluation, Preclinical ; Enterotoxins/biosynthesis ; Enterotoxins/isolation & purification ; Enterotoxins/pharmacology ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Mitomycin/pharmacology ; Models, Biological ; Molecular Targeted Therapy ; Protein Binding ; Receptor, EphA2/genetics ; Receptor, EphA2/metabolism ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/isolation & purification ; Recombinant Proteins/pharmacology ; Spheroids, Cellular/drug effects ; Spheroids, Cellular/metabolism ; Spheroids, Cellular/pathology ; Urinary Bladder Neoplasms/drug therapy ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/pathology ; Urothelium/drug effects ; Urothelium/metabolism ; Urothelium/pathology ; src-Family Kinases/genetics ; src-Family Kinases/metabolism
Chemical Substances	Antineoplastic Agents ; CLDN4 protein, human ; Claudin-4 ; Enterotoxins ; Recombinant Proteins ; enterotoxin, Clostridium ; Mitomycin (50SG953SK6) ; Receptor, EphA2 (EC 2.7.10.1) ; src-Family Kinases (EC 2.7.10.2) ; Dasatinib (RBZ1571X5H)
Language	English
Publishing date	2016--16
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2016.08.046
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Article: Preserved Cerebral Oxygen Metabolism in Astrocytic Dysfunction: A Combination Study of

Macaisa, Carla Mari / Watabe, Tadashi / Liu, Yuwei / Romanov, Victor / Kanai, Yasukazu / Horitsugi, Genki / Kato, Hiroki / Shimosegawa, Eku / Hatazawa, Jun

Brain sciences

2019 Volume 9, Issue 5

Abstract: Fluorocitrate (FC) is a specific metabolic inhibitor of the tricarboxylic acid (TCA) cycle in astrocytes. The purpose of this study was to evaluate whether inhibition of the astrocyte TCA cycle by FC would affect the oxygen metabolism in the rat brain. ... ...

Abstract	Fluorocitrate (FC) is a specific metabolic inhibitor of the tricarboxylic acid (TCA) cycle in astrocytes. The purpose of this study was to evaluate whether inhibition of the astrocyte TCA cycle by FC would affect the oxygen metabolism in the rat brain. At 4 h after the intracranial FC injection, the rats (
Language	English
Publishing date	2019-05-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci9050101
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Article ; Online: Evaluation of the total distribution volume of

Romanov, Victor / Isohashi, Kayako / Alobthani, Galal / Beshr, Rouaa / Horitsugi, Genki / Kanai, Yasukazu / Naka, Sadahiro / Watabe, Tadashi / Shimosegawa, Eku / Hatazawa, Jun

Annals of nuclear medicine

2019 Volume 34, Issue 3, Page(s) 155–162

Abstract: Objective: Boron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[: Methods: Six healthy volunteers were injected with : Results: The Ichise MA2 model showed the best fit among all ...

Abstract	Objective: Boron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[ Methods: Six healthy volunteers were injected with Results: The Ichise MA2 model showed the best fit among all models. Akaike Information Criterion (AIC) was the lowest for the Ichise's MA2 in all regions (mean AIC value - 14.0) comparing to the other models (Logan plot mean AIC 31.4; Ichise MA1 model mean AIC - 4.2). Mean Vt values of the Ichise MA2 model ranged from 0.94 ± 0.14 ml/ml in the pancreas to 0.16 ± 0.02 ml/ml in the right lung. Estimated boron concentration for Conclusion: The Trail registry: The UMIN clinical trial number: UMIN000022850.
MeSH term(s)	Adult ; Boron Compounds/administration & dosage ; Boron Compounds/chemical synthesis ; Boron Compounds/pharmacokinetics ; Boron Neutron Capture Therapy/methods ; Dose-Response Relationship, Radiation ; Female ; Fluorine Radioisotopes/chemistry ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; Neoplasms/diagnostic imaging ; Neoplasms/radiotherapy ; Phenylalanine/administration & dosage ; Phenylalanine/analogs & derivatives ; Phenylalanine/chemical synthesis ; Phenylalanine/pharmacokinetics ; Positron Emission Tomography Computed Tomography
Chemical Substances	Boron Compounds ; Fluorine Radioisotopes ; Phenylalanine (47E5O17Y3R) ; Fluorine-18 (GZ5I74KB8G) ; 4-boronophenylalanine (UID84303EL)
Language	English
Publishing date	2019-12-05
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1146984-5
ISSN	1864-6433 ; 0914-7187
ISSN (online)	1864-6433
ISSN	0914-7187
DOI	10.1007/s12149-019-01427-9
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Article ; Online: Protein misfolding and aggregation in neurodegenerative diseases: a review of pathogeneses, novel detection strategies, and potential therapeutics.

Gandhi, Jason / Antonelli, Anthony C / Afridi, Adil / Vatsia, Sohrab / Joshi, Gunjan / Romanov, Victor / Murray, Ian V J / Khan, Sardar Ali

Reviews in the neurosciences

2019 Volume 30, Issue 4, Page(s) 339–358

Abstract: Protein folding is a complex, multisystem process characterized by heavy molecular and cellular footprints. Chaperone machinery enables proper protein folding and stable conformation. Other pathways concomitant with the protein folding process include ... ...

Abstract	Protein folding is a complex, multisystem process characterized by heavy molecular and cellular footprints. Chaperone machinery enables proper protein folding and stable conformation. Other pathways concomitant with the protein folding process include transcription, translation, post-translational modifications, degradation through the ubiquitin-proteasome system, and autophagy. As such, the folding process can go awry in several different ways. The pathogenic basis behind most neurodegenerative diseases is that the disruption of protein homeostasis (i.e. proteostasis) at any level will eventually lead to protein misfolding. Misfolded proteins often aggregate and accumulate to trigger neurotoxicity through cellular stress pathways and consequently cause neurodegenerative diseases. The manifestation of a disease is usually dependent on the specific brain region that the neurotoxicity affects. Neurodegenerative diseases are age-associated, and their incidence is expected to rise as humans continue to live longer and pursue a greater life expectancy. We presently review the sequelae of protein misfolding and aggregation, as well as the role of these phenomena in several neurodegenerative diseases including Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, transmissible spongiform encephalopathies, and spinocerebellar ataxia. Strategies for treatment and therapy are also conferred with respect to impairing, inhibiting, or reversing protein misfolding.
MeSH term(s)	Animals ; Humans ; Neurodegenerative Diseases/diagnosis ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/pathology ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding ; Proteolysis ; Proteostasis Deficiencies/diagnosis ; Proteostasis Deficiencies/drug therapy ; Proteostasis Deficiencies/pathology ; Treatment Outcome
Chemical Substances	Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2019-01-24
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	639035-3
ISSN	2191-0200 ; 0334-1763
ISSN (online)	2191-0200
ISSN	0334-1763
DOI	10.1515/revneuro-2016-0035
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Article ; Online: A claudin 3 and claudin 4-targeted Clostridium perfringens protoxin is selectively cytotoxic to PSA-producing prostate cancer cells.

Romanov, Victor / Whyard, Terry C / Waltzer, Wayne C / Gabig, Theodore G

Cancer letters

2014 Volume 351, Issue 2, Page(s) 260–264

Abstract: Prostate cancer is the second leading cause of non-cutaneous cancer-related death in males, and effective strategies for treatment of metastatic disease are currently limited. The tight junction proteins, claudin 3 and claudin 4, serve as cell-surface ... ...

Abstract	Prostate cancer is the second leading cause of non-cutaneous cancer-related death in males, and effective strategies for treatment of metastatic disease are currently limited. The tight junction proteins, claudin 3 and claudin 4, serve as cell-surface receptors for the pore-forming Clostridium perfringens enterotoxin [CPE]. Most prostate cancer cells overexpress claudin 3 and claudin 4, and claudins are aberrantly distributed over the plasma membrane, making these cells particularly sensitive to cytolysis by CPE. Prostate cancer cells secrete PSA locally that is proteolytically active; however, circulating PSA is inactivated via binding to protease inhibitors. To overcome systemic toxicity of CPE, a modified protoxin was constructed with a tethered ligand attached to the C-terminus connected by a flexible linker containing a PSA-specific protease cleavage site. This engineered protoxin selectively and efficiently lyses PSA-producing prostate cancer cells whereas CLDN3 and CLDN4 positive cells that do not express PSA are resistant to cytolysis.
MeSH term(s)	Amino Acid Sequence ; Cell Line, Tumor ; Claudin-3/genetics ; Claudin-3/metabolism ; Claudin-4/genetics ; Claudin-4/metabolism ; Cloning, Molecular ; Clostridium perfringens/metabolism ; Enterotoxins/genetics ; Enterotoxins/pharmacokinetics ; Enterotoxins/pharmacology ; Humans ; Kallikreins/biosynthesis ; Male ; Molecular Sequence Data ; Molecular Targeted Therapy ; Prostate-Specific Antigen/biosynthesis ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/pharmacokinetics ; Recombinant Fusion Proteins/pharmacology ; Transfection
Chemical Substances	CLDN3 protein, human ; CLDN4 protein, human ; Claudin-3 ; Claudin-4 ; Enterotoxins ; Recombinant Fusion Proteins ; enterotoxin, Clostridium ; KLK3 protein, human (EC 3.4.21.-) ; Kallikreins (EC 3.4.21.-) ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2014-06-18
Publishing country	Ireland
Document type	Journal Article ; 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.2014.06.009
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