Inhibition of hypoxia-inducible factor-1 function enhances the sensitivity of multiple myeloma cells to melphalan.

Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1.

Exosomes are small endosome-derived vesicles containing a wide range of functional proteins, mRNA, and miRNA. Exosomal miRNA from cancer cells helps modulate the microenvironment. In multiple myeloma (MM), the massive proliferation of malignant plasma cells causes hypoxia. To date, the majority of in vitro hypoxia studies of cancer cells have used acute hypoxic exposure (3-24 hours). Thus, we a...

Blockade of Hypoxia: The Impact on Tumor Growth in an Experimental Tumor Model

Background: Tumor microenvironment is an active factor participating in immunoregulation, thereby preventing immunosurveillance and limiting the efficacy of anticancer therapies. Hypoxia as a major characteristic of solid tumors causes the expression of Hypoxia-Inducible Factor-1α (HIF-1α). This is a transcription factor that mediates hypoxic responses of tumor cells and involves in the express...

Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy.

Drug resistance remains a critical problem in the treatment of patients with multiple myeloma. Recent studies have determined that Notch signaling plays a major role in bone marrow (BM) stroma-mediated protection of myeloma cells from de novo drug-induced apoptosis. Here, we investigated whether pharmacologic inhibition of Notch signaling could affect the viability of myeloma cells and their se...

The anti-tumoral effect of lenalidomide is increased in vivo by hypoxia-inducible factor (HIF)-1α inhibition in myeloma cells.

Metabolic signature identifies novel targets for drug resistance in multiple myeloma.

Drug resistance remains a major clinical challenge for cancer treatment. Multiple myeloma is an incurable plasma cell cancer selectively localized in the bone marrow. The main cause of resistance in myeloma is the minimal residual disease cells that are resistant to the original therapy, including bortezomib treatment and high-dose melphalan in stem cell transplant. In this study, we demonstrat...