Evidence map›Paper›PMID 25073436›Full record

ArticleJournal of cancer research and clinical oncology2015

Keeping those telomeres short! an innovative intratumoral long-term drug delivery system.

B H Laster, C Isaacson, E Perets, M Msamra, E Priel, J Kalef-Ezra, J Kost

Open access · greenAbstract read
In one paragraph

Article in Journal of cancer research and clinical oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

1 citing paper in PubMed, 7 citations in OpenAlex.

  1. Review
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

7 authors at 2 institutions in 2 countries.

B H LasterJerry J. Cohen Radiobiology Research Laboratory, Ben Gurion University, 84105, Beer Sheva, Israel, blaster@bgu.ac.il.
C Isaacson
E Perets
M Msamra
E Priel
J Kalef-Ezra
J Kost
Ben-Gurion University of the Negev · ILUniversity of Ioannina · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTelomerase activation and an alternative lengthening of telomeres (ALT) mechanism are two telomere-lengthening cancer cell survival mechanisms elicited by both chemo- and/or radiotherapy. Telomere lengthening interferes with cell lethality and results in the immortalization of cancer cells. To counteract these mechanisms, we developed a drug delivery system (DDS) consisting of a polymeric implant that is inserted directly into tumors. The DDS releases, continuously and gradually, a cationic porphyrin (PdTMPyP4) for >30 days after a single application, and inhibits telomerase activation.

methodsThe PdTMPyP4 porphyrin is incorporated into a poly(co-glycolic lactic)acid (PLGA) polymer, solidified and cut into small rods. PdTMPyP4 release from the rods was measured spectrophotometrically over time. Uptake of Pd in the DNA of in L428 Hodgkins lymphoma cells was measured by ICP-MS, and telomerase activation by the TRAP assay. The rods were placed into the growth medium of cells whose growth rate was measured for 11 and 19 days. The cylinders were also inserted directly into KHJJ murine mammary tumors borne on the thighs of BALB/c mice and the tumor growth rate measured.

resultsIn vitro, >10(9)Pd atoms were measured in the DNA of each L428 cell and telomerase activity was reduced by ~15% within 24 h. A one-time application of the rod in the cell medium induced a factor of >5 greater lethality compared to a blank rod or untreated controls. In vivo, a one-time insertion of the rod into tumors resulted in the retardation of the growth rate by factors of 3-5 compared to untreated controls. Systemic uptake after intratumoral insertion of the rod was negligible.

conclusionThe results suggest that the direct intratumoral insertion of a PdTMPyP4-containing polymeric rod would be of benefit as an adjuvant treatment for patients undergoing chemo- or radiotherapy. By preventing the lengthening of telomeres and therefore the unrestricted growth of cancer cells, our DDS will provide a significant therapeutic advantage to these treatments without affecting normal tissues.

Indexed as

Drug Delivery SystemsAngiogenesis InhibitorsAnimalsCell ProliferationDNA, NeoplasmFemaleHodgkin DiseaseHumansLactic AcidMammary Neoplasms, AnimalMiceMice, Inbred BALB CPalladiumPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPorphyrinsAngiogenesis InhibitorsDNA, NeoplasmLactic AcidPalladiumPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPorphyrinsTelomerasetetra(4-N-methylpyridyl)porphine

Identifiers

PMID25073436
PMCPMC11824004
OpenAlexW2062382224

What OpenQuestion holds

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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.