Evidence map›Paper›PMID 28087981›Full record

ArticleThe journal of gene medicine2017

Humanized chondroitinase ABC sensitizes glioblastoma cells to temozolomide.

Alena Cristina Jaime-Ramirez, Nina Dmitrieva, Ji Young Yoo, Yeshavanth Banasavadi-Siddegowda, Jianying Zhang, Theresa Relation, Chelsea Bolyard, Jeffrey Wojton, Balveen Kaur

Abstract read
In one paragraph

Article in The journal of gene medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.2field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 50 citations in OpenAlex.

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  5. OncolyticTurkish journal of haematology : official journal of Turkish Society of Haematology · 2024
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  10. Proteoglycans: a common portal for SARS-CoV-2 and extracellular vesicle uptake.American journal of physiology. Cell physiology · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Alena Cristina Jaime-RamirezDepartment of Neurological Surgery, The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital, and Solove Research Institute, Columbus, OH, USA.
Nina DmitrievaDepartment of Neurological Surgery, The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital, and Solove Research Institute, Columbus, OH, USA.
Ji Young YooDepartment of Neurological Surgery, The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital, and Solove Research Institute, Columbus, OH, USA.
Yeshavanth Banasavadi-SiddegowdaDepartment of Neurological Surgery, The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital, and Solove Research Institute, Columbus, OH, USA.
Jianying ZhangCenter for Biostatistics Biomedical Informatics Department, The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital, and Solove Research Institute, Columbus, OH, USA.
Theresa RelationNeuroscience Graduate Program and The Medical Scientist Training Program, The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital, and Solove Research Institute, Columbus, OH, USA.
Chelsea BolyardDepartment of Neurological Surgery, The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital, and Solove Research Institute, Columbus, OH, USA.
Jeffrey WojtonDepartment of Neurological Surgery, The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital, and Solove Research Institute, Columbus, OH, USA.
Balveen KaurDepartment of Neurological Surgery, The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital, and Solove Research Institute, Columbus, OH, USA.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USNeurological Surgery · USThe Ohio State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI MICHAEL A CALIGIURI · 2013 to 2026
$26.0M
ONOCOLOGY TRAINING GRANTT32CA009338 · NCI · OHIO STATE UNIVERSITY · PI BYRD, JOHN C., POLLOCK, RAPHAEL E. · 1985 to 2018
$8.3M
Enhancing Viral Oncolysis with Vasculostatin Gene DeliveryR01CA150153 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KAUR, BALVEEN · 2011 to 2020
$4.0M
OV Therapy Induced Changes in Tumor Secretome and Their Impact on TherapyR01NS064607 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KAUR, BALVEEN · 2008 to 2018
$3.2M
Oncolytic virotherapy and immunotherapy in the treatment of brain tumorsF32CA186542 · NCI · OHIO STATE UNIVERSITY · PI JAIME-RAMIREZ, ALENA CRISTINA · 2015 to 2016
$113k
NCI NIH HHS F32 CA186542NCI NIH HHS P01 CA163205NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA150153NCI NIH HHS T32 CA009338NINDS NIH HHS R01 NS064607
6 · The paper itself

Abstract

backgroundMalignant gliomas (glioblastomas; GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extracellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM. Wild-type Chase ABC has limited stability and/or activity in mammalian cells; therefore, we created a mutant humanized version (Chase M) with enhanced function in mammalian cells.

methodsWe hypothesized that disruption of cell-cell and cell-ECM interactions by ChaseM and temozolomide (TMZ) will enhance the chemotherapeutic availability and sensitivity of glioma cells.

resultsUtilizing primary patient-derived neurospheres, we found that ChaseM decreases glioma neurosphere aggregation in vitro. Furthermore, an oncolytic HSV-1 virus expressing secreted ChaseM (OV-ChaseM) enhanced viral spread and glioma cell killing compared to OV-Control, in vitro. OV-ChaseM plus TMZ combinatorial treatment resulted in a significant synergistic enhancement of glioma cell killing accompanied by an increase in apoptotic cell death. Intracellular flow cytometric analysis revealed a significant reduction in the phosphorylation of the pro-survival AKT protein following OV-ChaseM plus TMZ treatment. Lastly, in nude mice bearing intracranial GBM30 glioma xenografts, intratumoral OV-ChaseM plus TMZ (10 mg/kg by oral gavage) combination therapy resulted in a significant (p < 0.02) enhancement of survival compared to each individual treatment alone.

conclusionsThese data reveal that OV-ChaseM enhances glioma cell viral susceptibility and sensitivity to TMZ.

Indexed as

AllelesAmino Acid SubstitutionAnimalsAntineoplastic Agents, AlkylatingApoptosisCell Line, TumorCell SurvivalChlorocebus aethiopsChondroitin ABC LyaseDacarbazineDisease Models, AnimalDrug Resistance, NeoplasmEnzyme ActivationGene ExpressionGenetic VectorsGlioblastomaAntineoplastic Agents, AlkylatingChondroitin ABC LyaseDacarbazineTemozolomideanimal modelbrain cancerchemotherapygene deliveryHSVoncolytic virusestumor biology

Identifiers

PMID28087981
PMCPMC5382089
OpenAlexW2579651244

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.