Search

Your search keyword '"Molavi, Ommoleila"' showing total 263 results
Start Over Author "Molavi, Ommoleila"
263 results on '"Molavi, Ommoleila"'

11. Decoration of Anti-CD38 on Nanoparticles Carrying a STAT3 Inhibitor Can Improve the Therapeutic Efficacy Against Myeloma

Author

Huang, Yung-Hsing, Vakili, Mohammad Reza, Molavi, Ommoleila, Morrissey, Yuen, Wu, Chengsheng, Paiva, Igor, Soleimani, Amir Hasan, Sanaee, Forugh, Lavasanifar, Afsaneh, and Lai, Raymond

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Bioengineering, Nanotechnology, Rare Diseases, Biotechnology, Orphan Drug, Cancer, Hematology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, multiple myeloma, STAT3, S3I-1757, nanoparticle, CD38, Oncology and Carcinogenesis, Oncology and carcinogenesis
Abstract

STAT3 is an oncoprotein which has been shown to contribute to drug resistance in multiple myeloma (MM). Nonetheless, the clinical utility of STAT3 inhibitors in treating MM has been limited, partly related to some of their pharmacologic properties. To overcome these challenges, our group had previously packaged STAT3 inhibitors using a novel formulation of nanoparticles (NP) and found encouraging results. In this study, we aimed to further improve the pharmacologic properties of these NP by decorating them with monoclonal anti-CD38 antibodies. NP loaded with S3I-1757 (a STAT3 inhibitor), labeled as S3I-NP, were generated. S3I-NP decorated with anti-CD38 (labeled as CD38-S3I-NP) were found to have a similar nanoparticular size, drug encapsulation, and loading as S3I-NP. The release of S3I-1757 at 24 h was also similar between the two formulations. Using Cy5.5 labeling of the NP, we found that the decoration of anti-CD38 on these NP significantly increased the cellular uptake by two MM cell lines (p < 0.001). Accordingly, CD38-S3I-NP showed a significantly lower inhibitory concentration at 50% (IC50) compared to S3I-NP in two IL6-stimulated MM cell lines (p < 0.001). In a xenograft mouse model, CD38-S3I-NP significantly reduced the tumor size by 4-fold compared to S3I-NP on day 12 after drug administration (p = 0.006). The efficacy of CD38-S3I-NP in suppressing STAT3 phosphorylation in the xenografts was confirmed by using immunocytochemistry and Western blot analysis. In conclusion, our study suggests that the decoration of anti-CD38 on NP loaded with STAT3 inhibitors can further improve their therapeutic effects against MM.

Published
2019

38. Silibinin induces immunogenic cell death in cancer cells and enhances the induced immunogenicity by chemotherapy.

Author

Jafari, Sevda, Heydarian, Saba, Lai, Raymond, Aghdam, Elnaz Mehdizadeh, and Molavi, Ommoleila

Subjects
CELL death, CANCER cells, SILIBININ, IMMUNE response, HEAT shock proteins, CANCER chemotherapy
Abstract

Introduction: Silibinin is a natural flavonoid compound known to induce apoptosis in cancer cells. Despite silibinin's safety and efficacy as an anticancer drug, its effects on inducing immunogenic cell death (ICD) are largely unknown. Herein, we have evaluated the stimulating effects of silibinin on ICD in cancer cells treated with silibinin alone or in combination with chemotherapy. Methods: The anticancer effect of silibinin, alone or in combination with doxorubicin or oxaliplatin (OXP), was assessed using the MTT assay. Compusyn software was used to analyze the combination therapy data. Western blotting was conducted to examine the level of STAT3 activity. Flow cytometry was used to analyze calreticulin (CRT) and apoptosis. The heat shock protein (HSP70), high mobility group box protein1 (HMGB1), and IL-12 levels were assessed by ELISA. Results: Compared to the negative control groups, silibinin induced ICD in CT26 and B16F10 cells and significantly enhanced the induction of this type of cell death by doxorubicin, and these changes were allied with substantial increases in the level of damage-associated molecular patterns (DAMPs) including CRT, HSP70, and HMGB1. Furthermore, conditioned media from cancer cells exposed to silibinin and doxorubicin was found to stimulate IL-12 secretion in dendritic cells (DCs), suggesting the link of this treatment with the induction of Th1 response. Silibinin did not augment the ICD response induced by OXP. Conclusion: Our findings showed that silibinin can induce ICD and it potentiates the induction of this type of cell death induced by chemotherapy in cancer cells. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results