Experimental Characteristics of Patients with Newly Diagnosed Multiple Myeloma.

Background: Multiple myeloma (MM), a malignant plasma cell proliferative disease, makes up to 1% of all cancers and somewhat exceeds 10% of all hematological cancers. Since it affects many organs, the signs and symptoms of myeloma vary greatly. This investigation was carried out to identify the clinical and laboratory characteristics of MM. Method: From January 1, 2014, to June 30, 2020, 169 in-patients who received a MM diagnosis for the first time at China-Japan Friendship Hospital in Beijing had their medical information examined. Results: Among 169 newly diagnosed patients, the median age was 60 years (26-84 years). Seven patients were younger than 40 years, and 16.0% (27/169) were 70 years or older. 40.8% (69/169) had IgG M-protein and 27.2% (46/169) had IgA. 84% (142/169) of patients were in the Durie Salmon stage 3. The major sign and symptoms at diagnosis were fatigue (100/169, 59.2%), bone pain (96/169, 56.8%), and weight loss (34/169, 20.1%). Anemia was present initially in 94.0% (159/169), high erythrocyte sedimentation rate in 92.7% (101/109), and thrombocytopenia in 26.6% (45/169). Similarly, hypercalcemia, renal insufficiency, and hypoalbuminemia were observed in 19.3% (31/161), 27.8%, and 75.7% respectively. Immunoparesis was found in 94% (110/117) of IgG, IgA, or IgM patients, and in 87% (33/38) of light chain myeloma patients. A localized band was found in 78.3% (123/157) of patients upon serum protein electrophoresis while monoclonal protein was detected by immunofixation in 91.5% (139/152) of patients. 4.1% (7/169) of the patients had non-secretory myeloma. The prevalence of light chain myeloma was 22.5% (38/169), and these individuals were more likely than other myeloma patients to have renal insufficiency (50% versus 21%, P < .05). In 84.8% of patients, the bone marrow had 10% or more plasma cells. Conclusion: The notable features that can be concluded from this study are the early onset of myeloma in the Chinese population and an advanced disease stage at the time of diagnosis with most of them accompanying anemia, hypoalbuminemia, and immunoparesis.

Changes in gamma-aminobutyric acid and glutamate/glutamine levels in the right thalamus of patients with episodic and chronic migraine: A proton magnetic resonance spectroscopy study.

OBJECTIVE: To explore gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the right thalamus of patients with episodic migraine (EM) and chronic migraine (CM) and their effects on the chronification of migraine. BACKGROUND: Migraine affects approximately 1 billion people worldwide, with 2.5%-3% of people with EM progressing to CM each year. Magnetic resonance spectroscopy studies have revealed altered GABA and Glx levels in the thalamus of patients with migraine without aura, but these neurometabolic concentrations are underexplored in the thalamus of patients with CM. METHODS: In this cross-sectional study, patients with EM and CM were recruited. Mescher-Garwood point resolved spectroscopy sequence was used to acquire neurotransmitter concentrations in the right thalamus of patients with EM and CM and matched healthy controls (HCs). RESULTS: A total of 26 patients (EM, n = 11; CM, n = 15) and 16 age- and sex-matched HCs were included in the analysis. There were significantly lower GABA+/Water levels in the right thalamus of the CM group (mean ± standard deviation: 2.27 ± 0.4 [institutional units]) than that of the HC group (2.74 ± 0.4) (p = 0.026; mean difference [MD] = -0.5 [i.u.]), and lower Glx/Cr levels in the EM group (mean ± SD: 0.11 ± < 0.1) than in the HCs (0.13 ± < 0.1) and CM group (0.13 ± < 0.1) (p = 0.023, MD < -0.1, and p = 0.034, MD < -0.1, respectively). The GABA+/Glx ratio was lower in the CM group (mean ± SD: 0.38 ± 0.1) compared to the EM group (0.47 ± 0.1) (p = 0.024; MD = -0.1). The area under the curve for GABA+/Water levels in differentiating patients with CM from HCs was 0.83 (95% confidence interval 0.68, 0.98; p = 0.004). Correlation analyses within the migraine group revealed no significant correlation between metabolite concentration levels and headache characteristics after Bonferroni correction. CONCLUSION: Reduced GABA+/Water levels and imbalance of excitation/inhibition in the right thalamus may contribute to migraine chronification.

Drug Repurposing Screen Identifies Novel Classes of Drugs with Anticancer Activity in Mantle Cell Lymphoma.

AIM AND OBJECTIVE: Mantle Cell Lymphoma (MCL) is typically an aggressive and rare disease with poor prognosis, therefore new effective therapeutics are urgently needed. Drug repurposing for cancer treatment is becoming increasingly more attractive as an alternative approach to discover clinically approved drugs that demonstrate antineoplastic effect. The objective of this study was to screen an approved drug library and identify candidate compounds with an antineoplastic effect in MCL cells using High-Throughput Screening (HTS) technique. MATERIALS AND METHODS: Using the HTS technique, nearly 3,800 clinically approved drugs and drug candidates were screened in Jeko and Mino MCL cell lines. We also demonstrated the selectivity window of the candidate compounds in six normal cell lines. Further validations were performed in caspase-3/7 apoptosis assay and three-dimensional (3D) multicellular aggregates model using Z138 cell line. RESULTS: We identified 98 compounds showing >50% inhibition in either MCL cell line screened, they were distributed across eight unique therapeutic categories and have different mechanisms of action (MOA). We selected alisertib, carfilzomib, pracinostat and YM155 for further validation based on their antiproliferative activity in two MCL cell lines, selectivity to normal cell lines, and drug developing stages in terms of clinical research. Alisertib and carfilzomib showed antiproliferative effect on MCL cell with EC50 = 6 nM and >100-fold selectivity to normal cell lines, especially for alisertib which demonstrated >1000-fold selectivity to 5 out of 6 normal cell lines. Pracinostat and YM155 had potency of 11 and 12 nM in MCL cell with >20-fold selectivity to normal cell lines. All four compounds had been tested in caspase-dependent apoptosis assay. We further validated and demonstrated their anti-MCL effect on cell proliferation and (3D) multicellular aggregates model using Z138 cell line. CONCLUSION: This is the first study to examine such a large library of clinically approved compounds for the identification of novel drug candidates for MCL treatment, the results could be rapidly translated into clinical practice in patients with MCL.