Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation.

BACKGROUND:Aberrant expression of cyclin-dependent protein kinases (CDK) is a hallmark of cancer. CDK11 plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 and CDK11 transcriptionally regulated genes are largely unknown. METHODS:In this study, we performed a global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional targets of CDK11. Clinical relevance and function of core-binding factor subunit beta (CBFβ) were further accessed in osteosarcoma. RESULTS:We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of CBFβ expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells. CONCLUSIONS:These data establish CBFβ as a mediator of CDK11p110 dependent oncogenesis and suggest that targeting the CDK11- CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment

Tree Ring-Based February–April Temperature Reconstruction for Changbai Mountain in Northeast China and Its Implication for East Asian Winter Monsoon

Long-term climatic records are scarce in the northeast Asia for understanding the behavior of the East Asian Winter Monsoon. Here we describe a 250-year February–April temperature reconstruction (TCBM) based on tree-ring widths of Korean Pines from the Changbai Mountain area, Northeast China. The reconstruction can account for 45.7% of the temperature variance in the instrumental period (1953 to 2001). Four cold periods including 1784–1815, 1827–1851, 1878–1889 and 1911–1945, and two warm periods of 1750–1783 and 1855–1877 were identified before the instrumental period. Four shifts were also detected at 1781, 1857, 1878 and 1989. Good agreements between TCBM and other temperature records of East Asia suggest that the reconstruction is of good reliability and captures the regional cold/warm periods of East Asia. Moreover, TCBM shows negative correlations with the instrumental or proxy-based EAWM intensity records. The known weakening of the EAWM in the late 1980s is in agreement with the shift at 1989 in TCBM. These comparisons suggest that the February–April temperature reconstruction may be a good indicator of the EAWM intensity

Dual-Octave Convolution for Accelerated Parallel MR Image Reconstruction

Magnetic resonance (MR) image acquisition is an inherently prolonged process, whose acceleration by obtaining multiple undersampled images simultaneously through parallel imaging has always been the subject of research. In this paper, we propose the Dual-Octave Convolution (Dual-OctConv), which is capable of learning multi-scale spatial-frequency features from both real and imaginary components, for fast parallel MR image reconstruction. By reformulating the complex operations using octave convolutions, our model shows a strong ability to capture richer representations of MR images, while at the same time greatly reducing the spatial redundancy. More specifically, the input feature maps and convolutional kernels are first split into two components (i.e., real and imaginary), which are then divided into four groups according to their spatial frequencies. Then, our Dual-OctConv conducts intra-group information updating and inter-group information exchange to aggregate the contextual information across different groups. Our framework provides two appealing benefits: (i) it encourages interactions between real and imaginary components at various spatial frequencies to achieve richer representational capacity, and (ii) it enlarges the receptive field by learning multiple spatial-frequency features of both the real and imaginary components. We evaluate the performance of the proposed model on the acceleration of multi-coil MR image reconstruction. Extensive experiments are conducted on an {in vivo} knee dataset under different undersampling patterns and acceleration factors. The experimental results demonstrate the superiority of our model in accelerated parallel MR image reconstruction. Our code is available at: github.com/chunmeifeng/Dual-OctConv.Comment: Proceedings of the 35th AAAI Conference on Artificial Intelligence (AAAI) 202

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient.</p> <p>Purpose</p> <p>To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted.</p> <p>Methods</p> <p>45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity.</p> <p>Results</p> <p>Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively).</p> <p>Conclusions</p> <p>Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.</p