Background: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation.
View Article and Find Full Text PDFMultiple myeloma (MM) is the second most common hematologic malignancy. Bortezomib (BOR), a first-generation proteasome inhibitor, is the basic agent for the treatment of MM and has greatly improved the survival of patients with MM. However, the side effects of BOR ( peripheral neuropathy) occur frequently and almost all MM patients eventually develop resistance to BOR and go on to develop refractory relapsed multiple myeloma (RRMM).
View Article and Find Full Text PDFMacrophages (MΦs) are an abundant component in the multiple myeloma (MM) environment and contribute to MM drug resistance. We previously showed that interleukin-32 (IL-32) is highly expressed in MM patients and induces the immunosuppressive function of MΦs. The present study was designed to explore the role of IL-32 in MΦ-mediated MM drug resistance and the underlying mechanism.
View Article and Find Full Text PDFBackground: Multiple myeloma (MM) is the second most common hematologic malignancy with almost all patients eventually having relapse or refractory MM (RRMM), thus novel drugs or combination therapies are needed for improved prognosis. Chidamide and venetoclax, which target histone deacetylase and BCL2, respectively, are two promising agents for the treatment of RRMM.
Results: Herein, we found that chidamide and venetoclax synergistically exert an anti-myeloma effect in vitro in human myeloma cell lines (HMCLs) with a combination index (CI) < 1.
Multiple myeloma (MM) is characterized by an accumulation of monoclonal plasma cells within the bone marrow (BM). Macrophages are an abundant component of myeloma BM microenvironment and support survival of the malignant cells and foster myeloma development and progression by suppression of the immune response. In our previous study, we found that MM patients overexpress pro-inflammatory cytokine interleukin-32 (IL-32).
View Article and Find Full Text PDFMacrophages are critical mediators of tissue homeostasis, with the function of tissue development and repair, but also in defense against pathogens. Tumor-associated macrophages (TAMs) are considered as the main component in the tumor microenvironment and play an important role in tumor initiation, growth, invasion, and metastasis. Recently, metabolic studies have revealeded specific metabolic pathways in macrophages are tightly associated with their phenotype and function.
View Article and Find Full Text PDFThe outcomes of multiple myeloma (MM) have been improved significantly with the therapies incorporating proteasome inhibitors (PI), immunomodulatory drugs, monoclonal antibodies (MoAb) and stem cell transplantation. However, relapsed and refractory MM (RRMM) remains a major challenge. Novel agents and regimens are under active clinical development.
View Article and Find Full Text PDFDihydroartemisinin (DHA), an active metabolite and derivative of artemisinin, is the most effective antimalarial drug and has strong antitumor activity in various tumor types. It has recently been reported that DHA can induce autophagy and has significant effects on multiple myeloma (MM), but the mechanisms and the relationship between the autophagy and apoptosis induced by DHA remain to be elucidated. Herein, we demonstrated that DHA significantly induces cell death in a dose- and time-dependent manner via the extrinsic and intrinsic apoptosis pathways.
View Article and Find Full Text PDFE3 ubiquitin ligases primarily determine the substrate specificity of the ubiquitin-proteasome system and play an essential role in the resistance to bortezomib in multiple myeloma (MM). Neural precursor cell-expressed developmentally downregulated gene 4-1 (NEDD4-1, also known as NEDD4) is a founding member of the NEDD4 family of E3 ligases and is involved in the proliferation, migration, invasion and drug sensitivity of cancer cells. In the present study, we investigated the role of NEDD4-1 in MM cells and explored its underlying mechanism.
View Article and Find Full Text PDFHistone deacetylases are promising therapeutic targets in hematological malignancies. In the work herein, we investigated the effect of chidamide, a new subtype-selective histone deacetylase inhibitor that was independently produced in China, on multiple myeloma and its associated bone diseases using different models. The cytotoxicity of chidamide toward myeloma is due to its induction of cell apoptosis and cell cycle arrest by increasing the levels of caspase family proteins p21 and p27, among others.
View Article and Find Full Text PDFThe present study aimed to investigate the effect of resveratrol on inflammatory pain. Mice were injected intraperitoneally with lipopolysaccharide (LPS) for 5 consecutive days to induce subacute systemic inflammation. Acetic acid‑induced writhing tests and tail‑flick tests were performed following the final LPS injection.
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