Investigation of the Mechanisms Governing Doxorubicin and Irinotecan Release From Drug-Eluting Beads: Mathematical Modeling and Experimental Verification.

Investigation of the mechanisms governing doxorubicin and irinotecan release from drug-eluting beads: mathematical modeling and experimental verification.

J Mater Sci Mater Med. 2013 Jun 25;
Biondi M, Fusco S, Lewis AL, Netti PA

Drug-eluting beads (DEBs) are embolising devices in clinical use for the treatment of liver cancer by transarterial chemoembolisation. In this study, release kinetics of doxorubicin (DOX) and irinotecan (IRI) were investigated by experimental evaluations and mathematical modeling, based on Langmuir isotherm and two phenomenological models (Boyd/Bhaskar) developed to determine the actual mechanisms controlling drug release rate. The model was validated through release studies, in particular by assessing how drug loading, ionic strength of the release medium and device swelling during release influence drug release kinetics. Results demonstrated that IRI is released much faster than DOX, and that DEB volume strongly depends upon drug loading and fractional release. This effect was properly taken into account in developing the mathematical model. Experimental results were well fit by numerical simulations, and two different rate-controlling mechanisms were found to govern DOX and IRI delivery. HubMed – drug


MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects.

Tumour Biol. 2013 Jun 25;
Miao J, Wu S, Peng Z, Tania M, Zhang C

MicroRNAs (miRNAs) are small RNA molecules, which can interfere with the expression of several genes and act as gene regulator. miRNAs have been proved as a successful diagnostic and therapeutic tool in several cancers. In this review, the differential expression of miRNAs in osteosarcoma and their possibility to be used as diagnostic and therapeutic tools have been discussed. Osteosarcoma is the most common primary bone tumor that mainly affects children and adolescents. The current treatment of osteosarcoma remains difficult, and osteosarcoma causes many deaths because of its complex pathogenesis and resistance to conventional treatments. Several studies demonstrated that the differential expression patterns of miRNAs are a promising tool for the diagnosis and treatment of osteosarcoma. Although some aspect of the mechanism of action of miRNAs in controlling osteosarcoma has been identified (e.g., targeting the Notch signaling pathway), it is far beyond to the clear understanding of miRNA targets in osteosarcoma. Identification of the specific target of miRNAs may aid molecular targets for drug development and future relief of osteosarcoma. HubMed – drug


Evaluating stem and cancerous biomarkers in CD15(+)CD44 (+) KYSE30 cells.

Tumour Biol. 2013 Jun 25;
Rassouli FB, Matin MM, Bahrami AR, Ghaffarzadegan K, Cheshomi H, Lari S, Memar B, Kan MS

Digestive system cancers are listed among the ten top causes of cancer-related death worldwide. Cancer stem cells (CSCs) are malignant cells that share some of their characteristics with normal stem cells, including self-renewal and multipotency, and also cancer cells, such as drug resistance and metastasis. Despite many reports on CSCs with digestive system origin, identification and characterization of esophageal CSCs have remained elusive. To examine the validity of routine SC, cancer cell and CSC markers in KYSE30 cells, derived from esophageal carcinoma, cells were first characterized by immunofluorescence and RT-PCR techniques, and then the significance of candidate biomarkers was evaluated in retinoic acid-treated cells by flow cytometry and/or real-time RT-PCR. Meanwhile, to study CD15 (a newly introduced CSC marker) expression in digestive tract cancers, human normal and tumoral tissues of esophagus, stomach, and colon were analyzed by immunohistochemistry. Using several experimental approaches, we show that CD44, but not CD15, could serve as a reliable marker for undifferentiated malignant squamous cells of esophagus. In conclusion, our study confirms the role of CD44 as a CSC marker in KYSE30 cells, an esophageal squamous cell carcinoma cell line, and for the first time indicates the expression of CD15 in non-neural stem-like cancer cells. Although the importance of CD15 was not indicated in diagnosis of digestive cancers, further studies are needed to better understand the biological identity and function of this molecule in non-neural malignancies. HubMed – drug


Drug-Eluting Balloon in peripherAl inTErvention for Below the Knee Angioplasty Evaluation (DEBATE-BTK): A Randomized Trial in Diabetic Patients with Critical Limb Ischemia.

Circulation. 2013 Jun 24;
Liistro F, Porto I, Angioli P, Grotti S, Ricci L, Ducci K, Falsini G, Ventoruzzo G, Turini F, Bellandi G, Bolognese L

One-year restenosis rate after balloon angioplasty of long lesions in below-the-knee (BTK) arteries may be as high as 70%. Our aim was to investigate the efficacy of a paclitaxel drug-eluting balloon (DEB) vs. conventional percutaneous transluminal angioplasty (PTA) for the reduction of restenosis in diabetic patients with critical limb ischemia (CLI) undergoing endovascular intervention of BTK arteries.The Drug Eluting Balloon in peripherAl inTErvention (DEBATE)-BTK is a randomized, open label, single-center study comparing DEB vs. PTA. Inclusion criteria were: diabetes, critical limb ischemia (Rutherford ?4), significant stenosis or occlusion > 40mm of at least one BTK vessel with distal run-off, and life expectancy > 1 year. Binary in-segment restenosis at 1-year angiographic or ultrasonographic follow-up was the primary endpoint. Clinically-driven target lesion revascularization (TLR), major amputation and target vessel occlusion were the secondary endpoints. One hundred and thirty two patients with 158 infrapopliteal atherosclerotic lesions were enrolled. Mean length of the treated segments was 129±83mm in the DEB vs. 131±79mm in the PTA group (p=0.7). Binary restenosis, assessed by angiography in >90% of patients, occurred in 20/74 (27%) lesions in the DEB group vs. 55/74 (74%) lesions in the PTA group (p<0.001); TLR in 12(18%) vs. 29(43%) (p=0.002); and target vessel occlusion in 12 (17%) vs. 41 (55%) (p<0.001). Only 1 major amputation occurred, in the PTA group (p=0.9).DEB, as compared to PTA, strikingly reduce 1-year restenosis, target lesion revascularization, and target vessel occlusion in the treatment of BTK lesions in diabetic patients with CLI.; Identifier: NCT01558505. HubMed – drug