التفاصيل البيبلوغرافية
| العنوان: |
Sonic-hedgehog pathway inhibition normalizes desmoplastic tumor microenvironment to improve chemo- and nanotherapy |
| المؤلفون: |
Mpekris, F., Papageorgis, P., Polydorou, C., Voutouri, C., Kalli, M., Pirentis, A. P., Stylianopoulos, T. |
| المساهمون: |
Stylianopoulos, T. [0000-0002-3093-1696] |
| المصدر: |
Journal of Controlled Release |
| بيانات النشر: |
Elsevier BV, 2017. |
| سنة النشر: |
2017 |
| مصطلحات موضوعية: |
Male, Pancreatic cancers, Pathology, Pyridines, medicine.medical_treatment, Diseases, fibroblast, Polyethylene Glycols, sonic hedgehog protein, Mice, Breast cancer, primary tumor, analogs and derivatives, 0302 clinical medicine, Mice, Inbred NOD, Antineoplastic Combined Chemotherapy Protocols, vismodegib, drug delivery system, Medicine, Enzyme activity, Sonic hedgehog, Tumor, pancreatic cancer cell line, gemcitabine, Hedgehog signaling pathway, 3. Good health, Nanomedicine, priority journal, Tumor microenvironment, 030220 oncology & carcinogenesis, Collagen, medicine.medical_specialty, Tumor perfusion, Hyaluronic acid, Sonic hedgehogs, Re-engineering cancer, Vismodegib, Antineoplastic Agents, pyridine derivative, anilide, SCID, doxorubicin, Article, pancreas tumor, animal tissue, 03 medical and health sciences, Pancreatic cancer, cancer combination chemotherapy, Humans, human, mouse, antagonists and inhibitors, Tumors, human cell, animal model, intracellular signaling, Fluid stress, Fibroblasts, medicine.disease, drug efficacy, Pancreatic Neoplasms, cell proliferation, 030104 developmental biology, tumor volume, Nanoparticles, Inbred NOD, Albumin-Bound Paclitaxel, hydraulic conductivity, Medical nanotechnology, 0301 basic medicine, transcription factor Gli1, transcription factor Gli2, Pharmaceutical Science, Mice, SCID, paclitaxel, Drug Delivery Systems, Blood vessels, Tumor Microenvironment, animal, Anilides, macrogol derivative, Extracellular matrices, antineoplastic agent, biology, breast tumor, nanoparticle, Extracellular Matrix, Enzyme inhibition, female, stroma cell, Female, medicine.drug, extracellular matrix, animal experiment, Breast Neoplasms, Cell Line, tissue pressure, male, Cell Line, Tumor, Chemotherapy, Animals, Young modulus, SCID mouse, controlled study, Hedgehog Proteins, drug screening, nonhuman, business.industry, nonobese diabetic mouse, tumor cell line, Cancer, Xenograft Model Antitumor Assays, tumor xenograft, pancreas adenocarcinoma, cancer associated fibroblast, Mechanical force, Doxorubicin, Drug delivery, Cancer research, biology.protein, pathology, Ki 67 antigen, Cell culture, alpha smooth muscle actin, business, metabolism |
| الوصف: |
Targeting the rich extracellular matrix of desmoplastic tumors has been successfully shown to normalize collagen and hyaluronan levels and re-engineer intratumoral mechanical forces, improving tumor perfusion and chemotherapy. As far as targeting the abundant cancer-associated fibroblasts (CAFs) in desmoplastic tumors is concerned, while both pharmacologic inhibition of the sonic-hedgehog pathway and genetic depletion of fibroblasts have been employed in pancreatic cancers, the results between the two methods have been contradictory. In this study, we employed vismodegib to inhibit the sonic-hedgehog pathway with the aim to i) elucidate the mechanism of how CAFs depletion improves drug delivery, ii) extent and evaluate the potential use of sonic-hedgehog inhibitors to breast cancers, and iii) investigate whether sonic-hedgehog inhibition improves not only chemotherapy, but also the efficacy of the most commonly used breast cancer nanomedicines, namely Abraxane® and Doxil®. We found that treatment with vismodegib normalizes the tumor microenvironment by reducing the proliferative CAFs and in cases the levels of collagen and hyaluronan. These modulations re-engineered the solid and fluid stresses in the tumors, improving blood vessel functionality. As a result, the delivery and efficacy of chemotherapy was improved in two models of pancreatic cancer. Additionally, vismodegib treatment significantly improved the efficacy of both Abraxane and Doxil in xenograft breast tumors. Our results suggest the use of vismodegib, and sonic hedgehog inhibitors in general, to enhance cancer chemo- and nanotherapy. © 2017 Elsevier B.V. 261 105 112 105-112 |
| تدمد: |
0168-3659 |
| الوصول الحر: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::064e94bb3e41b1f17f395234f6f126fcTest
https://doi.org/10.1016/j.jconrel.2017.06.022Test |
| حقوق: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....064e94bb3e41b1f17f395234f6f126fc |
| قاعدة البيانات: |
OpenAIRE |
