Silent Thrombotic Thrombocytopenic Purpura: PLASMIC, Lessons Learned, and Current Management Overview.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening autoimmune or hereditary thrombotic microangiopathy (TMA) that may be difficult to recognize given the wide spectrum of presenting symptoms. The clinical diagnosis of TTP is based on thrombocytopenia, microangiopathic hemolytic anemia and is confirmed by a disintegrin-like and metalloproteinase with thrombospondin type one motif, member 13 (ADAMTS13) <10%. However, the latter confirmation is not rapidly available, and treatment is typically initiated based on the degree of clinical suspicion.

Cauda Equina Syndrome as the Initial Presentation of Concurrent Plasmacytoma and Multiple Myeloma.

Multiple myeloma is a hematological malignancy characterized by an abnormal proliferation of monoclonal plasma cells. In some occurrences, plasma cell proliferation results in a solitary lesion (solitary bone plasmacytoma or extramedullary plasmacytoma with minimal bone marrow involvement). Approximately 50% of patients with solitary plasmacytoma develop multiple myeloma within 10 years after the initial diagnosis.

M011L-deficient oncolytic myxoma virus induces apoptosis in brain tumor-initiating cells and enhances survival in a novel immunocompetent mouse model of glioblastoma.

Background: Myxoma virus (MYXV) is a promising oncolytic agent and is highly effective against immortalized glioma cells but less effective against brain tumor initiating cells (BTICs), which are believed to mediate glioma development/recurrence. MYXV encodes various proteins to attenuate host cell apoptosis, including an antiapoptotic Bcl-2 homologue known as M011L. Such proteins may limit the ability of MYXV to kill BTICs, which have heightened resistance to apoptosis.

Anti-myeloma effect of pharmacological inhibition of Notch/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment.

Multiple myeloma (MM), a blood cancer characterized by the uncontrolled proliferation of plasma cells, remains incurable by current therapy. Notch signaling has been implicated in the growth and chemoresistance of various cancer types including MM, and therefore we hypothesized that targeting the Notch pathway could be beneficial for the treatment of this disease. Here, we report an anti-tumor effect of Notch/γ-secretase inhibitor RO4929097 in a pre-clinical model of MM.

Canonical Wnt pathway inhibitor ICG-001 induces cytotoxicity of multiple myeloma cells in Wnt-independent manner.

Canonical Wnt signaling has been implicated in the regulation of multiple myeloma (MM) growth. Here, we investigated whether the targeting of this pathway with a novel pharmacological inhibitor ICG-001 would result in an anti-tumor effect and improvement of chemosensitivity in MM. As expected, ICG-001 specifically down-regulated β-catenin/TCF-mediated transcription in MM cells.

In vitro screen of a small molecule inhibitor drug library identifies multiple compounds that synergize with oncolytic myxoma virus against human brain tumor-initiating cells.

Background: Brain tumor-initiating cells (BTICs) are stem-like cells hypothesized to form a disease reservoir that mediates tumor recurrence in high-grade gliomas. Oncolytic virotherapy uses replication-competent viruses to target and kill malignant cells and has been evaluated in clinic for glioma therapy with limited results. Myxoma virus (MyxV) is a safe and highly effective oncolytic virus (OV) in conventional glioma models but, as seen with other OVs, is only modestly effective for patient-derived BTICs.

Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells.

Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined.

Myeloid-derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow.

Myeloid-derived suppressor cells (MDSC) are one of the major factors limiting the immune response in cancer. However, their role in bone marrow (BM), the site of primary localization of multiple myeloma (MM), is poorly understood. In this study, we found a significant accumulation of CD11b(+)CD14(-)CD33(+) immunosuppressive MDSC in BM of patients with newly diagnosed MM.

Gamma-secretase inhibitor enhances the cytotoxic effect of bortezomib in multiple myeloma.

Background: Targeting of Notch signaling with γ-secretase inhibitors (GSIs) has been considered a promising strategy for the treatment of hematological malignancies including multiple myeloma (MM). Here we investigated whether the cytotoxic effect of bortezomib, an agent commonly used in MM, could be enhanced by the addition of a GSI.

Methods: MM cells were treated with GSI, bortezomib or the combination thereof.