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Record W2173414413 · doi:10.1089/104303403322124783

Antiangiogenic Cancer Therapy with Microencapsulated Cells

2003· article· en· W2173414413 on OpenAlex
Pasquale Cirone, Jacqueline M. Bourgeois, Patricia L. Chang

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueHuman Gene Therapy · 2003
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAngiogenesis and VEGF in Cancer
Canadian institutionsMcMaster University
FundersCanadian Institutes of Health ResearchMcMaster UniversityCancer Research Institute
KeywordsAngiostatinCancer researchAngiogenesisCancer cellAngiogenesis inhibitorNeovascularizationApoptosisMedicineCancerEndostatinBiologyPathologyImmunologyInternal medicineBiochemistry

Abstract

fetched live from OpenAlex

Inhibition of angiogenesis has led to tumor suppression in several cancer models. Although administering purified recombinant antiangiogenic product is effective, alternative approaches through genetic manipulation may be more cost-effective. We propose to implant nonautologous recombinant cells secreting angiostatin for systemic delivery of angiostatin in cancer treatment. These cells are protected from graft rejection in alginate microcapsules to function as "micro-organs" to deliver angiostatin in vivo. This approach was tested by implanting encapsulated mouse myoblast C2C12 cells genetically modified to secrete angiostatin into mice bearing solid tumor. Angiostatin was detected in sera of the treated mice. Efficacy was demonstrated by suppression of palpable tumor growth and improved survival. At autopsy, angiostatin localized to residual tumors and high levels of angiostatic activity were detected in tumor extracts. Tumor tissues showed increased apoptosis and necrosis compared with those from untreated or mock-treated mice. Immunohistochemical staining against von Willebrand factor, an endothelial cell marker, showed that within tumors from the treated mice, the neovasculature was poorly defined by endothelial cells, many of which were undergoing apoptosis. However, the tumors eventually developed neovasculature independent of endothelial cells. Such vascular mimicry would account for the lack of long-term efficacy despite persistent angiostatin delivery. In conclusion, implantation with nonautologous microencapsulated cells is feasible for systemic delivery of angiostatin, resulting in localization of angiostatin to tumors and targeted apoptosis of the endothelial cells. Clinical efficacy was demonstrated by suppression of tumor growth and extension of life span. Although the potential of this cell-based approach for angiostatin-mediated cancer therapy is confirmed, long-term efficacy must take into account the possible escape by some tumors from angiogenesis inhibition.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.141
Threshold uncertainty score0.792

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.020
GPT teacher head0.268
Teacher spread0.248 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it