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Article ; Online: Tumor Development and Angiogenesis in Adult Brain Tumor: Glioblastoma.

Ahir, Bhavesh K / Engelhard, Herbert H / Lakka, Sajani S

2020 Volume 57, Issue 5, Page(s) 2461–2478

Abstract: Angiogenesis is the growth of new capillaries from the preexisting blood vessels. Glioblastoma (GBM) tumors are highly vascularized tumors, and glioma growth depends on the formation of new blood vessels. Angiogenesis is a complex process involving ... ...

Abstract	Angiogenesis is the growth of new capillaries from the preexisting blood vessels. Glioblastoma (GBM) tumors are highly vascularized tumors, and glioma growth depends on the formation of new blood vessels. Angiogenesis is a complex process involving proliferation, migration, and differentiation of vascular endothelial cells (ECs) under the stimulation of specific signals. It is controlled by the balance between its promoting and inhibiting factors. Various angiogenic factors and genes have been identified that stimulate glioma angiogenesis. Therefore, attention has been directed to anti-angiogenesis therapy in which glioma proliferation is inhibited by inhibiting the formation of new tumor vessels using angiogenesis inhibitory factors and drugs. Here, in this review, we highlight and summarize the various molecular mediators that regulate GBM angiogenesis with focus on recent clinical research on the potential of exploiting angiogenic pathways as a strategy in the treatment of GBM patients.
MeSH term(s)	Adult ; Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Angiogenic Proteins/antagonists & inhibitors ; Angiogenic Proteins/physiology ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Brain Neoplasms/blood supply ; Brain Neoplasms/drug therapy ; Brain Neoplasms/pathology ; Cell Differentiation ; Cell Hypoxia ; Clinical Trials as Topic ; Glioblastoma/blood supply ; Glioblastoma/drug therapy ; Glioblastoma/pathology ; Humans ; Intercellular Signaling Peptides and Proteins/physiology ; Matrix Metalloproteinases/physiology ; Molecular Targeted Therapy ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/physiology ; Neoplastic Stem Cells/pathology ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/physiopathology ; Neovascularization, Pathologic/prevention & control ; Neovascularization, Physiologic/physiology ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/physiology
Chemical Substances	Angiogenesis Inhibitors ; Angiogenic Proteins ; Antineoplastic Agents ; Intercellular Signaling Peptides and Proteins ; Neoplasm Proteins ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2020-03-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-020-01892-8
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Zs.A 2411: Show issues

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Article ; Online: Elucidating the microRNA-203 specific biological processes in glioblastoma cells from comprehensive RNA-sequencing transcriptome profiling.

Ahir, Bhavesh K / Lakka, Sajani S

Cellular signalling

2018 Volume 53, Page(s) 22–38

Abstract: Glioblastoma (GBM) is the most common primary malignant intracranial adult brain tumor. Allelic deletion on chromosome 14q plays an essential role in GBM pathogenesis, and this chromosome 14q site was thought to harbor multiple tumor suppressor genes ... ...

Abstract	Glioblastoma (GBM) is the most common primary malignant intracranial adult brain tumor. Allelic deletion on chromosome 14q plays an essential role in GBM pathogenesis, and this chromosome 14q site was thought to harbor multiple tumor suppressor genes associated with GBM, a region that also encodes microRNA-203 (miR-203). This study was conducted to identify whole transcriptome profile changes associated with miR-203 expression by high-throughput RNA sequencing. Enrichment analyses for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that miR-203 expression had a strong, negative effect on a number of fundamental and interconnected biological processes involved in cell growth and proliferation. The biological processes mostly influenced were p53 signaling pathway, FoxO signaling pathway, DNA replication, cell cycle, MAPK signaling pathway, and apoptosis. In total, 847 upregulated and 345 downregulated differentially expressed genes were identified in control versus miR-203 expressing glioma cells. After GO enrichment, the downregulated differentially expressed genes such as BCL2, SPARC were found to be mainly enriched in cell cycle regulation and apoptosis processes, whereas the upregulated differentially expressed genes such as CCND1, E2F1 were involved in the DNA replication and cell cycle regulation. We also performed miR-203 target analysis and found BCL2, AKT, SPARC, ROBO1, c-JUN, PDGFA, and CREB were predicted target of miR-203 and miR-203 expression suppressed the protein and mRNA levels of these target genes by western blotting and qRT-PCR analysis. Moreover, co-transfection experiments using a luciferase-based reporter assay demonstrated that miR-203 directly regulated BCL-2 expression and BCL-2 overexpression suppressed miR-203 mediated glioma cell apoptosis. These results indicate that overexpression of miR-203 coordinately regulates several oncogenic pathways in GBM.
MeSH term(s)	Alternative Splicing ; Brain Neoplasms/genetics ; Cell Line, Tumor ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics ; Humans ; MicroRNAs/genetics ; Transcriptome
Chemical Substances	MIRN203 microRNA, human ; MicroRNAs
Language	English
Publishing date	2018-09-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2018.09.014
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Zs.A 2579: Show issues

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Article ; Online: Withdrawal: Blockade of tumor growth due to matrix metalloproteinase-9 inhibition is mediated by sequential activation of β1-integrin, ERK, and NF-κB.

Bhoopathi, Praveen / Chetty, Chandramu / Kunigal, Sateesh / Vanamala, Sravan K / Rao, Jasti S / Lakka, Sajani S

The Journal of biological chemistry

2020 Volume 295, Issue 45, Page(s) 15426

Language	English
Publishing date	2020-10-28
Publishing country	United States
Document type	Journal Article ; Retraction of Publication
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.W120.016338
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Article ; Online: Cerebral Microdialysis as a Tool for Assessing the Delivery of Chemotherapy in Brain Tumor Patients.

Pierce, Charles F / Kwasnicki, Amanda / Lakka, Sajani S / Engelhard, Herbert H

World neurosurgery

2020 Volume 145, Page(s) 187–196

Abstract: The development of curative treatment for glioblastoma has been extremely challenging. Chemotherapeutic agents that have seemed promising have failed in clinical trials. Drugs that can successfully target cancer cells within the brain must first traverse ...

Abstract	The development of curative treatment for glioblastoma has been extremely challenging. Chemotherapeutic agents that have seemed promising have failed in clinical trials. Drugs that can successfully target cancer cells within the brain must first traverse the brain interstitial fluid. Cerebral microdialysis (CMD) is an invasive technique in which interstitial fluid can be directly sampled. CMD has primarily been used clinically in the setting of head trauma and subarachnoid hemorrhage. Our goal was to review the techniques, principles, and new data pertaining to CMD to highlight its use in neuro-oncology. We conducted a literature search using the PubMed database and selected studies in which the investigators had used CMD in either animal brain tumor models or clinical trials. The references were reviewed for additional information. Studies of CMD have shown its importance as a neurosurgical technique. CMD allows for the collection of pharmacokinetic data on drug penetrance across the blood-brain barrier and metabolic data to characterize the response to chemotherapy. Although no complications have been reported, the current CMD technique (as with any procedure) has risks and limitations, which we have described in the present report. Animal CMD experiments have been used to exclude central nervous system drug candidates from progressing to clinical trials. At present, patients undergoing CMD have been monitored in the intensive care unit, owing to the requisite tethering to the apparatus. This can be expected to change soon because of advances in microminiaturization. CMD is an extremely valuable, yet underused, technique. Future CMD applications will have central importance in assessing drug delivery to tumor cells in vivo, allowing a pathway to successful therapy for malignant brain tumors.
MeSH term(s)	Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/therapeutic use ; Blood-Brain Barrier ; Brain Neoplasms/drug therapy ; Humans ; Microdialysis/instrumentation ; Microdialysis/methods
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2020-09-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2020.08.161
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Zs.A 1159: Show issues

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Article ; Online: Retraction: Specific interference of urokinase-type plasminogen activator receptor and matrix metalloproteinase-9 gene expression induced by double-stranded RNA results in decreased invasion, tumor growth, and angiogenesis in gliomas.

Lakka, Sajani S / Gondi, Christopher S / Dinh, Dzung H / Olivero, William C / Gujrati, Meena / Rao, Velidi H / Sioka, Chrissa / Rao, Jasti S

The Journal of biological chemistry

2020 Volume 295, Issue 37, Page(s) 13135

Language	English
Publishing date	2020-09-11
Publishing country	United States
Document type	Journal Article ; Retraction of Publication
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RX120.015587
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Uc I Zs.108: Show issues

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Article ; Online: Retraction: RNA interference-directed knockdown of urokinase plasminogen activator and urokinase plasminogen activator receptor inhibits prostate cancer cell invasion, survival, and tumorigenicity

Pulukuri, Sai MuraliKrishna / Gondi, Christopher S / Lakka, Sajani S / Jutla, Aman / Estes, Norman / Gujrati, Meena / Rao, Jasti S

The Journal of biological chemistry

2020 Volume 295, Issue 37, Page(s) 13136

Language	English
Publishing date	2020-09-11
Publishing country	United States
Document type	Journal Article ; Retraction of Publication
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RX120.015588
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Uc I Zs.108: Show issues

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Article: SPARC overexpression alters microRNA expression profiles involved in tumor progression.

Ahir, Bhavesh K / Elias, Nasya M / Lakka, Sajani S

Genes & cancer

2016 Volume 8, Issue 1-2, Page(s) 453–471

Abstract: Medulloblastoma is the most common malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we ... ...

Abstract	Medulloblastoma is the most common malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we reported that SPARC expression significantly impairs medulloblastoma tumor growth
Language	English
Publishing date	2016-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2538519-7
ISSN	1947-6027 ; 1947-6019
ISSN (online)	1947-6027
ISSN	1947-6019
DOI	10.18632/genesandcancer.130
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Article ; Online: MicroRNAs in glioblastoma pathogenesis and therapy: A comprehensive review.

Ahir, Bhavesh K / Ozer, Howard / Engelhard, Herbert H / Lakka, Sajani S

Critical reviews in oncology/hematology

2017 Volume 120, Page(s) 22–33

Abstract: Glioblastoma (GBM), also known as grade IV astrocytoma, is the most aggressive primary intracranial tumor of the adult brain. MicroRNAs (miRNAs), a class of small non-coding RNA species, have critical functions across various biological processes. A ... ...

Abstract	Glioblastoma (GBM), also known as grade IV astrocytoma, is the most aggressive primary intracranial tumor of the adult brain. MicroRNAs (miRNAs), a class of small non-coding RNA species, have critical functions across various biological processes. A great deal of progress has been made recently in dissecting miRNA pathways associated with the pathogenesis of GBM. miRNA expression signatures called gene signatures also characterize and contribute to the phenotypic diversity of GBM subclasses through their ability to regulate developmental growth and differentiation. miRNA molecules have been identified as diagnostic and prognostic biomarkers for patient stratification and may also serve as therapeutic targets and agents. This review summarizes: (i) the current understanding of the roles of miRNAs in the pathogenesis of GBM, (ii) the potential use of miRNAs in GBM diagnosis and glioma grading, (iii) further prospects of developing miRNAs as novel biomarkers and therapeutic targets for GBM, and (iv) important practical considerations when considering miRNA therapy for GBM patients.
MeSH term(s)	Animals ; Biomarkers, Tumor/genetics ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Glioblastoma/genetics ; Glioblastoma/pathology ; Humans ; MicroRNAs/genetics
Chemical Substances	Biomarkers, Tumor ; MicroRNAs
Language	English
Publishing date	2017-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	605680-5
ISSN	1879-0461 ; 0737-9587 ; 1040-8428
ISSN (online)	1879-0461
ISSN	0737-9587 ; 1040-8428
DOI	10.1016/j.critrevonc.2017.10.003
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Zs.A 1931: Show issues

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Article ; Online: Retraction: Down-regulation of integrin α

Adachi, Yoshiaki / Lakka, Sajani S / Chandrasekar, Nirmala / Yanamandra, Niranjan / Gondi, Christopher S / Mohanam, Sanjeeva / Dinh, Dzeng H / Olivero, William C / Gujrati, Meena / Tamiya, Takashi / Ohmoto, Takashi / Kouraklis, Gregory / Aggarwal, Bharat / Rao, Jasti S

The Journal of biological chemistry

2020 Volume 295, Issue 37, Page(s) 13134

Language	English
Publishing date	2020-09-11
Publishing country	United States
Document type	Journal Article ; Retraction of Publication
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RX120.015586
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Uc I Zs.108: Show issues

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Article ; Online: Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery.

Willis, Alexander J / Pernal, Sebastian P / Gaertner, Zachary A / Lakka, Sajani S / Sabo, Michael E / Creighton, Francis M / Engelhard, Herbert H

International journal of nanomedicine

2020 Volume 15, Page(s) 4105–4123

Abstract: Background: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP- ... ...

Abstract	Background: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP-enhanced drug delivery. MNP clusters can be rotated and moved across surfaces at clinically relevant distances in response to a rotating magnet. Limited data are available regarding issues affecting MNP delivery by this mechanism, such as adhesion to a cellular wall. Research reported here was initiated to better understand the fundamental principles important for successful implementation of rotational magnetic drug targeting (rMDT). Methods: Translational movements of four different iron oxide MNPs were tested, in response to rotation (3 Hz) of a neodymium-boron-iron permanent magnet. MNP clusters moved along biomimetic channels of a custom-made acrylic tray, by surface walking. The effects of different distances and cellular coatings on MNP velocity were analyzed using videography. Dyes (as drug surrogates) and the drug etoposide were transported by rotating MNPs along channels over a 10 cm distance. Results: MNP translational velocities could be predicted from magnetic separation times. Changes in distance or orientation from the magnet produced alterations in MNP velocities. Mean velocities of the fastest MNPs over HeLa, U251, U87, and E297 cells were 0.24 ± 0.02, 0.26 ± 0.02, 0.28 ± 0.01, and 0.18 ± 0.03 cm/sec, respectively. U138 cells showed marked MNP adherence and an 87.1% velocity reduction at 5.5 cm along the channel. Dye delivery helped visualize the effects of MNPs as microdevices for drug delivery. Dye delivery by MNP clusters was 21.7 times faster than by diffusion. MNPs successfully accelerated etoposide delivery, with retention of chemotherapeutic effect. Conclusion: The in vitro system described here facilitates side-by-side comparisons of drug delivery by rotating MNP clusters, on a human scale. Such microdevices have the potential for augmenting drug delivery in a variety of clinical settings, as proposed.
MeSH term(s)	Biological Transport ; Cell Death/drug effects ; Cell Line, Tumor ; Diffusion ; Drug Delivery Systems/instrumentation ; Etoposide/pharmacology ; Humans ; Magnetite Nanoparticles/chemistry ; Microspheres ; Microtechnology/instrumentation ; Particle Size ; Rotation ; Tomography, X-Ray Computed
Chemical Substances	Magnetite Nanoparticles ; Etoposide (6PLQ3CP4P3)
Language	English
Publishing date	2020-06-11
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2364941-0
ISSN	1178-2013 ; 1176-9114
ISSN (online)	1178-2013
ISSN	1176-9114
DOI	10.2147/IJN.S247985
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