Disturbing mitotic progression via targeted anti-mitotic therapy is an attractive strategy for cancer treatment. Therefore, the exploration and elucidation of molecular targets and pathways in mitosis are critical for the development of anti-mitotic drugs. Here, we show that cell division cycle 5-like (Cdc5L), a pre-mRNA splicing factor, is a regulator of mitotic progression. Depletion of Cdc5L causes dramatic mitotic arrest, chromosome misalignments and sustained activation of spindle assembly checkpoint, eventually leading to mitotic catastrophe. Moreover, these defects result from severe impairment of kinetochore-microtubule attachment and serious DNA damage. Genome-wide gene expression analysis reveals that Cdc5L modulates the expression of a set of genes involved in the mitosis and the DNA damage response. We further found that the pre-mRNA splicing efficiency of these genes were impaired when Cdc5L was knocked down. Interestingly, Cdc5L is highly expressed in cervical tumors and osteosarcoma. Finally, we demonstrate that downregulation of Cdc5L decreases the cell viability of related tumor cells. These results suggest that Cdc5L is a key regulator of mitotic progression and highlight the potential of Cdc5L as a target for cancer therapy.
Objectives: We aim to evaluate the ethnic-specific relationship of total fat mass and anthropometric indices in Chinese. Design: Cross-section study. Setting: This study was performed at the College of Life Sciences, Hunan Normal University, P.R. China. Subjects and method: To increase our understanding of the relationship of total fat mass and anthropometric indices in Chinese, 793 females and 1091 males aged 20-40 years were randomly recruited from Changsha city of P. R. China. Hip circumference (HC) and waist circumference (WC) were measured using standardized equipments, and other three anthropometric indices of body mass index (BMI), waist-to-hip ratio (WHR), and conicity index (CI) were calculated using weight, height, HC and WC. Total body fatness (TBF) in kg was measured using a Hologic QDR 4500 W dual-energy X-ray absorptiometry (DEXA) scanner. Results: There was an increasing trend of TBF, %TBF (percent total body fatness) and the five anthropometric indices in successively older age groups. Compared with females, males generally had high average BMI, WC, HC, WHR and CI, but had low average TBF and %TBF. Except for some correlations in 25-29 years age groups, TBF and %TBF were significantly correlated with five anthropometric indices with the Pearson's correlation coefficients ranging from 0.07 to 0.87. Principal component analysis (PCA) was performed to form four principal components (PCs) that interpreted over 99% of the total variation of the five related anthropometric indices in all age groups, with over 53% of the total variation accounted for by the PC1. Multiple regression analyses showed that four PCs combined explained a greater variance (R 2 ¼ 55.2-80.8%) in TBF than did BMI alone (R 2 ¼ 40-74.9%). Conclusion: Our results suggest that there is an increasing trend of total fat mass and five anthropometric indices with aging; that age and sex have the important effects on influencing the correlations of TBF and the studied anthropometric indices; and that the accuracy of predicting the TBF using five anthropometric indices is higher than using BMI alone.
Two novel 46-chromosome doubled haploid lines, W66 and M17, derived from separate hexaploid triticale x bread wheat crosses, were characterised using cytological and biochemical markers. Both lines were shown to be relatively stable cytologically, over 11 and 8 generations of selfing, respectively. By examining mitotic and meiotic chromosomes, the stabilities of the two lines were shown to be similar with frequencies of 2n=46 in 74.2-85.5% of cells. However, over selfed generations, the rye chromosomes were shown to have lost some of their heterochromatin, which made it difficult to establish their continued presence using cytological techniques, such as C-banding alone. Cytological evidence from pairing studies, C-banding, and fluorescence in-situ hybridization, showed that both M17 and W66 are wheat/rye multi-addition lines with rye chromosome constitutions of 1R+6R, and 1R+4R, respectively. These conclusions were confirmed by isozyme and storage-protein analysis.
This study evaluated the clinical significance of traumatic anterior shoulder instability (TASI) classification using double-contrast computed tomography (CT) arthrography. Patient were randomly assigned to two groups: group 1 (n = 62); and group 2 (n = 63). TASI symptom severity in group 1 was assessed using physical signs of shoulder trauma and conventional X-ray, CT and magnetic resonance imaging; these patients received either conservative management (with physical rehabilitation) or standard surgery. Group 2 underwent doublecontrast CT arthrography to classify TASI; its findings formed the basis of subsequent management. At 24 months post-therapy, significant improvements in clinical outcomes were observed in group 2: Constant scores were higher and Western Ontario Shoulder Instability Index scores were lower. At 24 months, recurrence rates were 21.0% (13/62) in group 1 and 7.9% (5/63) in group 2. Findings suggested that TASI classification using double-contrast CT arthrography provided meaningful information thereby improving treatment efficacy.
The treatment for high-grade glioma remains an enigma. The standard treatment using surgery, radiation therapy and chemotherapy for such highly malignant lesions has only yielded modest results, in terms of survival and improving the quality of life of patients. Less than 10% of such patients survive beyond two years. All conventional therapies have failed to increase the survival beyond this extent. There has been a growing interest in the molecular approaches for the treatment of high-grade gliomas which include gene therapy, oncolytic virotherapy, and immunotherapy. These new therapies are in preclinical and investigational stages. They may not substitute the conventional therapies; they may not be the ultimate elixir for this deadly disease. However, in the coming years, they are likely to have synergistic and complimentary roles alongside conventional therapies. Through this paper, we have attempted to highlight the rationale behind gene therapy which can be used for cytotoxic approaches, immunomodulation strategy, and targeted toxin delivery in the tumor cell. We have reviewed current available literature and through this paper focus on reporting such therapeutic options, their potential usage, benefits and limitations.
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