Safety and efficacy of pomalidomide, dexamethasone and pegylated liposomal doxorubicin for patients with relapsed or refractory multiple myeloma

Cohen, Alexa; Spektor, Tanya M.; Stampleman, Laura; Bessudo, Alberto; Rosen, Peter J.; Klein, Leonard M.; Woliver, Thomas; Flam, Marshall S.; Eshaghian, Shahrooz; Nassir, Youram; Maluso, Tina; Swift, Regina A.; Vescio, Robert; Berenson, James R.

doi:10.1111/bjh.14992

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…Doxorubicin is widely used in the treatment of many tumors, including MM . However, development of resistance to the drug has been frequently found in clinic.…”

Section: Resultsmentioning

confidence: 99%

“…Doxorubicin is widely used in the treatment of many tumors, including MM. 19 However, development of resistance to the drug has been frequently found in clinic. Since miR-26a inhibited cell growth by suppressing CDK6 signaling, we then assessed whether miR-26a mimic affected the effect of doxorubicin on MM.…”

Section: Mir-26a Enhances the Cytotoxicity Of Doxorubicin In MM Cellsmentioning

confidence: 99%

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MicroRNA‐26a inhibits multiple myeloma cell growth by suppressing cyclin‐dependent kinase 6 expression

Song

Huang

et al. 2019

The Kaohsiung J of Med Scie

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MicroRNA‐26a (miR‐26a) has been reported to be involved in the tumorigenesis of several tumors, but its biological function and molecular mechanism in multiple myeloma (MM) are still unknown. In this study, we found that overexpression of miR‐26a obviously inhibited MM cell growth, and delayed tumor growth in xenografts. Further studies showed that overexpression of miR‐26a induced cell cycle arrest at G0/G1 phase in MM cells. MiR‐26a mimic down‐regulated the expression levels of CDK6 and E2F1, but up‐regulated p53 and p21 expression. In contrast, overexpression of CDK6 decreased the effect of miR‐26a mimic on MM cell survival. Moreover, miR‐26a targeted CDK6 mRNA and thus suppressed CDK6 protein expression. Overexpression of miR‐26a also enhanced the cytotoxic action of doxorubicin against MM. These results demonstrated that miR‐26a was involved in the development of MM through regulating CDK6 signaling pathway, and indicated that miR‐26a could be as a novel target for anti‐tumor therapy in clinic as a single strategy or in combination with other anti‐tumor drugs in MM.

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“…Doxorubicin is widely used in the treatment of many tumors, including MM . However, development of resistance to the drug has been frequently found in clinic.…”

Section: Resultsmentioning

confidence: 99%

Section: Mir-26a Enhances the Cytotoxicity Of Doxorubicin In MM Cellsmentioning

confidence: 99%

MicroRNA‐26a inhibits multiple myeloma cell growth by suppressing cyclin‐dependent kinase 6 expression

Song

Huang

et al. 2019

The Kaohsiung J of Med Scie

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“…More recently, targeting chemical therapeutic delivery consisting of cytotoxic drugs has shown much promise with their pharmacokinetic profile and therapeutic efficacy [31]. For example, PEGylated liposomeencapsulated DOX has been reported to significantly enhance the therapeutic index of DOX in preclinical [32,33] and clinical trials [34][35][36]. Unfortunately, particulate liposomes caused the encapsulated drugs to accumulate in mononuclear phagocytic system cells of the liver, spleen, and bone marrow, with the potential of being toxic to these tissues [37].…”

Section: Discussionmentioning

confidence: 99%

Development of a novel drug targeting delivery system for cervical cancer therapy

et al. 2018

Nanotechnology

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Targeting peptides' have demonstrated their value in diagnostic imaging and therapy and novel peptide probes specific to cervical cancer were developed. In the M13KE phage dodecapeptide (12-mer) peptide library, the phage clone S7 showed the best binding to the cancer cells as confirmed by immunofluorescence and flow cytometry assays, and was selected for continued studies. Its binding peptide, CSP3, was synthesized from the sequence of S7's 12-mer at the N-terminus of the minor coat protein pIII of this M13KE phage vector. The peptide's binding was analyzed by the same assays used for S7. It was also assessed using competitive inhibition and binding to a tissue chip. The results demonstrated that the CSP3 peptide bound to cervical carcinoma cells with high sensitivity and specificity. The positive results indicated that the peptide CSP3, conjugated with nanomaterials and chemotherapeutics, may be developed as a targeting vehicle for therapeutic drug delivery against cervical cancer, especially cervical cancer with multiple drug resistance. For this aim, we prepared a CSP3 conjugated liposome drug delivery system containing doxorubicin (DOX) and microRNA101 (miR101) expression plasmids (CSP3-Lipo-DOX-miR101), and the primary result showed that the system demonstrated significantly enhanced cytotoxicity to SiHa cells and DOX resistant SiHa cells, SiHa/ADR. Our results showed that CSP3 is a cervical cancer targeting 12aa peptide with high specificity and sensitivity, and the CSP3 conjugated drug delivery system, CSP3-Lipo-DOX-miR101 has promising potential for development as an efficient drug system for the therapy of cervical cancer.

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“…IMiDs and PIs constitute the first line therapy in newly diagnosed and also RRMM, and the combination of Vincristine/Adriamycin/Dexamethasone (VAD) is less and less used, due to high toxicity and poor efficacy. The topoisomerase 2 inhibitor, Doxorubicin, is still used in MM treatment as PEGylated liposomal doxorubicin form [ 62 ], moreover, recently, a study has been published using the combination VAD in newly diagnosed patients [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of HIF1α-Dependent Upregulation of Phospho-l-Plastin Resensitizes Multiple Myeloma Cells to Frontline Therapy

Bosseler

Marani

Broukou

et al. 2018

IJMS

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The introduction of novel frontline agents in multiple myeloma (MM), like immunomodulatory drugs and proteasome inhibitors, has improved the overall survival of patients. Yet, MM is still not curable, and drug resistance (DR) remains the main challenge. To improve the understanding of DR in MM, we established a resistant cell line (MOLP8/R). The exploration of DR mechanisms yielded an overexpression of HIF1α, due to impaired proteasome activity of MOLP8/R. We show that MOLP8/R, like other tumor cells, overexpressing HIF1α, have an increased resistance to the immune system. By exploring the main target genes regulated by HIF1α, we could not show an overexpression of these targets in MOLP8/R. We, however, show that MOLP8/R cells display a very high overexpression of LCP1 gene (l-Plastin) controlled by HIF1α, and that this overexpression also exists in MM patient samples. The l-Plastin activity is controlled by its phosphorylation in Ser5. We further show that the inhibition of l-Plastin phosphorylation restores the sensitivity of MOLP8/R to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). Our results reveal a new target gene of DR, controlled by HIF1α.

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Safety and efficacy of pomalidomide, dexamethasone and pegylated liposomal doxorubicin for patients with relapsed or refractory multiple myeloma

Cited by 9 publications

References 39 publications

MicroRNA‐26a inhibits multiple myeloma cell growth by suppressing cyclin‐dependent kinase 6 expression

MicroRNA‐26a inhibits multiple myeloma cell growth by suppressing cyclin‐dependent kinase 6 expression

Development of a novel drug targeting delivery system for cervical cancer therapy

Inhibition of HIF1α-Dependent Upregulation of Phospho-l-Plastin Resensitizes Multiple Myeloma Cells to Frontline Therapy

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