Quantitative Evaluation of the Compressed L5 and S1 Nerve Roots in Unilateral Lumbar Disc Herniation by Using Diffusion Tensor Imaging.

BACKGROUND AND PURPOSE: Nerve root compression by lumbar disc herniation (LDH) induces a series of clinical symptoms, seriously affecting the patient's life and work. The purpose of this study is to investigate microstructural changes and fiber bundle abnormalities of the compressed L5 and S1 nerve roots in young patients with unilateral LDH by using diffusion tensor imaging (DTI). METHODS: Forty young patients with unilateral LDH and 17 healthy volunteers participated in the study, and 33 patients received follow-up DTI examination after one month of conservative treatment. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and trace weight (TraceW) values of the L5 and S1 nerve roots were measured on FA maps. RESULTS: The mean FA, ADC and TraceW values of the affected nerve roots were 0.259 ± 0.047, 1.79 ± 0.252 and 0.076 ± 0.025, respectively. Compared to the contralateral side and volunteers, the affected nerve roots showed a decreased FA (P < 0.01), an increased ADC (P < 0.01) and TraceW (P < 0.05). The compression severity had a moderately negative correlation with FA (r = -0.646, P < 0.01) and positive correlation with ADC (r = 0.408, P < 0.01) but not with TraceW (r = 0.298, P = 0.06). For 33 patients with follow-up study after conservative treatment, FA (0.286 ± 0.06) and ADC (1.630 ± 0.046) in the affected nerve roots showed an increasing and a decreasing trend, respectively. Moreover, FA values (14 cases; 0.246 ± 0.015, P = 0.213) in the severe compression group had no significant changes between initial and follow-up data. CONCLUSIONS: DTI is able to assess microstructural abnormalities of the compressed nerve roots and has potentially practical value for prognostic evaluation after treatment in patients with LDH.

Preclinical activity of DCZ3301, a novel aryl-guanidino compound in the therapy of multiple myeloma.

We synthesized a novel aryl-guanidino compound, DCZ3301, and found that it has potent cytotoxicity against multiple human cancer cell lines. The anticancer activity was most potent against multiple myeloma (MM). DCZ3301 induced cytotoxicity in MM cell lines, as well as patient myeloma cells, in part by decreasing mitochondrial membrane potential to induce apoptosis. In contrast, DCZ3301 had no cytotoxic effect on normal cells. DCZ3301 also inhibited cell cycling and caused a G2/M accumulation that corresponded with downregulation of Cdc25C, CDK1, and Cyclin B1. DCZ3301 retained its activity against MM cells in the presence of exogenous cytokines (IL-6 or VEGF) or bone marrow stromal cells (BMSCs) and reduced activity of multiple signaling pathways (STAT3, NFκB, AKT, ERK1/2) in MM but not normal cells. The STAT3 pathway played an important role in modulating DCZ3301-mediated cytotoxicity. Knockdown of STAT3 using siRNA in MM cells enhanced DCZ3301-induced cytotoxicity, whereas overexpression of STAT3 in MM cells partially protected them from apoptosis. In addition, DCZ3301 inhibited VEGF and IL-6 secretion in a dose-dependent fashion in a co-culture of MM cells and BMSCs. Combining DCZ3301 with bortezomib induced synergistic cytotoxicity in MM cell lines and primary MM cells. Finally, in vivo efficacy of DCZ3301 was confirmed in an MM xenograft mouse model. Together, these results provide a rationale for translation of this small-molecule inhibitor, either alone or in combination, to the clinic against MM.

CT and MRI findings of type I and type II epithelial ovarian cancer.

OBJECTIVE: To assess whether types I and II epithelial ovarian cancer (EOC) differ in CT and MRI imaging features. METHODS: For this retrospective study, we enrolled 65 patients with 68 ovarian lesions that have been pathologically proven to be EOC. Of these patients, 38 cases underwent MR examinations only, 15 cases underwent CT examinations only, and 12 cases completed both examinations. The clinical information [age, CA-125, menopausal status, and Ki-67] and imaging findings were compared between two types of EOCs. The diagnostic performance of image findings were assessed by receiver-operating characteristic curve(ROC) analysis. The association between EOC type and imaging features was assessed by multivariate logistic regression analysis. The random forest approach was used to build a classifier in differential diagnosis between two types of EOCs. RESULTS: Of the 68 EOC lesions, 24 lesions were categorized as types I and other 44 lesions as type II based on the immunohistochemical results, respectively. Patients in type I EOCs were more likely to involve menopausal women and showed lower CA-125 and Ki-67 values (Ki-67<30%) than patients in type II EOCs. The imaging characteristics of type II EOCs frequently demonstrated a solid or predominantly solid mass (38.6% vs. 12.5%, P<0.05), smaller lesions (diameter <6cm; 27.3% vs. 4.2%, P<0.05), absence of mural nodules (65.9% vs. 25.9%, P=0.001), and mild enhancement (84.1% vs. 54.2%, P<0.05) compared to type I EOCs. Combination of tumor size, morphology, mural nodule, enhancement degrees (AUC=0.808) has a higher specificity (87.50%) and positive predictive value (90.0%) than any single image finding alone in differential diagnosis between two types of EOCs. The multivariate logistic regression analysis showed that enhancement degrees(OR 0.200, P<0.05),mural nodule(OR 0.158, P<0.05) significantly influence EOC classification. Random forests model identified both as the most important discriminating variables. The diagnostic accuracy of the classifier was 73.53%. CONCLUSIONS: Differences in imaging characteristics existed between two types of EOCs. Combination of several image findings improved the preoperative diagnostic performance, which is helpful for the clinical treatment and prognosis evaluation.