Tumor Subtype Determines Therapeutic Response to Chimeric Polypeptide Nanoparticle-based Chemotherapy in Pten-deleted Mouse Models of Sarcoma:
Purpose:
Nanoparticle-encapsulated drug formulations can improve responses to conventional chemotherapy by increasing drug retention within the tumor and by promoting a more effective antitumor immune response than free drug. New drug delivery modalities are needed in sarcomas because they are often chemoresistant cancers, but the rarity of sarcomas and the complexity of diverse subtypes makes it challenging to investigate novel drug formulations.
Experimental Design:
New drug formulations can be tested in animal models of sarcomas where the therapeutic response of different formulations can be compared using mice with identical tumor-initiating mutations. Here, using Cre/loxP and CRISPR/Cas9 techniques, we generated two distinct mouse models of Pten-deleted soft-tissue sarcoma: malignant peripheral nerve sheath tumor (MPNST) and undifferentiated pleomorphic sarcoma (UPS). We used these models to test the efficacy of chimeric polypeptide doxorubicin (CP-Dox), a nanoscale micelle formulation, in comparison with free doxorubicin.
Results:
The CP-Dox formulation was superior to free doxorubicin in MPNST models. However, in UPS tumors, CP-Dox did not improve survival in comparison with free doxorubicin. While CP-Dox treatment resulted in elevated intratumoral doxorubicin concentrations in MPNSTs, this increase was absent in UPS tumors. In addition, elevation of CD8+ T cells was observed exclusively in CP-Dox–treated MPNSTs, although these cells were not required for full efficacy of the CP nanoparticle–based chemotherapy.
Conclusions:
These results have important implications for treating sarcomas with nanoparticle-encapsulated chemotherapy by highlighting the tumor subtype–dependent nature of therapeutic response.
Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com
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- International Journal of Molecular Sciences
- Antibiotics
- Spiritual care experiences by cancer pati
- Focused ultrasound robotic system for v
- Macrophage HIF-1{alpha} Is an Independent Prognost...
- Radiation with STAT3 Blockade Triggers Dendritic C...
- Rhabdoid Tumors Are Sensitive to the Protein-Trans...
- Tumor Subtype Determines Therapeutic Response to C...
- Editor's Note: The Pivotal Role of Integrin {beta}...
- Clinical variability in spinal muscular atrophy ty...
- Clinical Balance Testing to Screen for Patients Wi...
- The effectiveness of radiotherapy in the treatment...
- Prophet forecasting model: a machine learning appr...
- TET1 may contribute to hypoxia-induced epithelial ...
- Correlation of Radiologic Versus Endoscopic Visual...
- Consequences of Mastoidectomy on Bone Conducted So...
- Laterality of Audiovestibular Symptoms Predicts La...
- Visualizing Affected Nerve Bundles of Cranial Nerv...
- Malformations Associated With Pediatric Congenital...
- Definitive treatment of sporadic vestibular schwan...
- Long-term survival after cemented versus uncemente...
- giant retroperitoneal neurilemmoma
- Resveratrol prevents TNF-α-induced VCAM-1 and ICAM...
- Vocal trauma especially in females and children is...
- Brazilian butt lift (BBL) surgery
- Adipose-derived stem cell enrichment is counter-pr...
- Cognitive, language and motor development of infan...
- Prolonged Survival of a Patient with Chronic Myelo...
- Correlation between the Epworth Sleepiness Scale a...
- Iron induces cell death and strengthens the effica...
- Flumatinib versus Imatinib for Newly Diagnosed Chr...
- Immediate inhibition of spinal secretory phospholi...
- Eriodictyol produces antidepressant-like effects a...
- Electroacupuncture at GV24 and bilateral GB13 impr...
- Minimal incision superficialization of the brachia...
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