Kenneth H. Shain
University of South Florida
Drug resistanceInternal medicineSurgeryOncologyImmunologyEx vivoLenalidomideTumor microenvironmentMultiple myelomaBortezomibMelphalanBone marrowDexamethasonePopulationTransplantationCancer researchMedicineBiologyGastroenterologyPharmacology
188Publications
28H-index
3,536Citations
Publications 189
Newest
Abstract null Interactions between the inhibitor of apoptosis protein antagonist LCL161 and the histone deacetylase inhibitor panobinostat (LBH589) were examined in human multiple myeloma (MM) cells. LCL161 and panobinostat interacted synergistically to induce apoptosis in diverse MM cell lines, including those resistant to bortezomib (PS-R). Similar interactions were observed with other histone deacetylase inhibitors (MS-275) or inhibitors of apoptosis protein antagonists (birinapant). These ev...
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Context.— null Measurable (minimal) residual disease (MRD) is an independent prognostic factor for survival outcomes in patients with lymphoid and plasma cell malignancies and has been incorporated into consensus criteria regarding treatment response, strategy, and clinical trial endpoints. clonoSEQ (a next-generation sequencing [NGS]-MRD assay) uses multiplex polymerase chain reaction and NGS to identify clonotypic rearrangements at the immunoglobulin (Ig) H, IgK, IgL, T-cell receptor (TCR)-β, ...
1 CitationsSource
#1Joel G. TurnerH-Index: 21
#2David A. Ostrov (UF: University of Florida)H-Index: 41
Last. Kenneth H. ShainH-Index: 28
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Introduction Certain cancers have been shown to express a specific type of drug-resistance involving the export of drug target proteins from the nucleus of the cell to the cytoplasm. This mechanism of drug-resistance has been shown to be important in multiple myeloma (MM) and recently a nuclear export inhibitor, selinexor, has received approval by the FDA in MM. However, general nuclear export signal (NES) inhibitors like selinexor exhibit off-target toxicities when used in patients. We have beg...
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#2Mark B. MeadsH-Index: 12
Last. Qi Zhang
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#1Jing GaoH-Index: 1
#2Michelle WangH-Index: 1
Last. Kenneth H. ShainH-Index: 28
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Despite significant progress in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), prognosis of patients with relapsed disease remains poor due to the emergence of drug resistance and subsequent disease progression. Identification of novel targets and therapeutic strategies for these diseases represents an urgent need. Here, we report that both MCL and DLBCL are exquisitely sensitive to transcription-targeting drugs, particular to THZ531, a coval...
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#1Metis Hasipek (Cleveland Clinic)H-Index: 4
#2Dale Grabowski (Cleveland Clinic)H-Index: 20
Last. Babal K. Jha (Cleveland Clinic)H-Index: 26
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Multiple myeloma is a genetically complex hematologic neoplasia in which malignant plasma cells constantly operate at the maximum limit of their unfolded protein response (UPR) due to a high secretory burden of immunoglobulins and cytokines. The endoplasmic reticulum (ER) resident protein disulfide isomerase, PDIA1 is indispensable for maintaining structural integrity of cysteine-rich antibodies and cytokines that require accurate intramolecular disulfide bond arrangement. PDIA1 expression analy...
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#1David C. KoomenH-Index: 1
#2Mark B. MeadsH-Index: 12
Last. Kenneth H. ShainH-Index: 28
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Multiple myeloma is an incurable hematological malignancy that impacts tens of thousands of people every year in the United States. Treatment for eligible patients involves induction, consolidation with stem cell rescue, and maintenance. High-dose therapy with a DNA alkylating agent, melphalan, remains the primary drug for consolidation therapy in conjunction with autologous stem-cell transplantation; as such, melphalan resistance remains a relevant clinical challenge. Here, we describe a proteo...
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#1Xiaohong ZhaoH-Index: 12
#2Michelle WangH-Index: 1
Last. Jianguo TaoH-Index: 21
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Summary Ibrutinib, a bruton’s tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease. Here, using genomic, chemical proteomic, and drug screen profiling, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the aggressive phenotypes of IR. Accordingly, IR MCL cells are vulnerable to inhibitors of the transcriptional m...
3 CitationsSource
#1Chen Hao LoH-Index: 4
#2Gemma ShayH-Index: 5
Last. Conor C. LynchH-Index: 25
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Multiple myeloma promotes systemic skeletal bone disease that greatly contributes to patient morbidity. Resorption of type-I-collagen rich bone matrix by activated osteoclasts (OCL) results in the release of sequestered growth factors that can drive progression of the disease. Matrix metalloproteinase-13 (MMP-13) is a collagenase expressed predominantly in the skeleton by mesenchymal stromal cells (MSC) and MSC-derived osteoblasts. Histochemical analysis of human multiple myeloma specimens also ...
1 CitationsSource