BSD2000 Deep Hyperthermia Combined with Chemotherapy of PT regimen in Patients with Non-small Cell Lung Cancer

Background and objective The aim of this study is to determine the short-term efficacy, toxicity and the rate of life-quality improvement of BSD2000 deep hyperthermia combined with chemotherapy of PT regimen in patients with non-small cell lung cancer (NSCLC) by comparation with PT regimen alone. Methods Sixty patients with NSCLC were randomly divided into the treatment group and control group, with 30 each. The treatment group was treated with chemotherapy (paclitaxel:135mg/m2 ivdirp 3 h qd d1+cisplatin: 20 mg/m2 ivdirp qd d1-5) in combination with BSD2000 deep hyperthermia, and hyperthermia was positioned precisely and maintained for 60 min (2 times a cycle: d1, 4 after the end of chemotherapy within two hours). The control group was treated with chemotherapy alone. Treatment response in both groups were evaluated as well as side-effects after 3 cycles. By observing the results, comparing response rate, toxic side effects and quality of life improvement rate in two groups. Results The efficiency and the rate of life-quality improvement in the treatment group were 63.33%, 76.67% respectively, and 36.67%, 40.00% in the control group respectively. There were significant differences between two groups (P < 0.05). The main side-effects were myelosuppression and gastrointestinal reactions, no significant difference between two groups (P > 0.05). Conclusion BSD2000 deep hyperthermia combined with chemotherapy in patients with NSCLC can significantly increase the efficacy, response rate and quality of life improvement and without increasing sideeffects compared to chemotherapy alone

Gamified Live-streaming: Is Avatar Better than Human Being?

Live-streaming has emerged as a popular direct selling channel to foster synchronous interaction between streamers and consumers, with the avatar streamer largely underexplored. Using the data from a fashion retailer, we adopt the Generalized Synthetic Control (GSC) method to examine the effect of gamified and human live-streaming on product sales and return rate. We find that (1) the gamified live-streaming reduces product sales and the return rate simultaneously; (2) human live-streaming boosts product sales but increases the return rate, and (3) the dual-type live-streaming can increase product sales and decrease return rates. Furthermore, we proposed that the reason for the differentiated effects between gamified and human live-streaming could be driven by the impulse-buying behavior of viewers only in human live-streaming. Our findings contribute to the growing literature on the business value of AI technology and gamification in live-streaming and shed light on practical decisions made by online retailers

Study of Protein Arginine Methyltransferase 6 in Medulloblastoma

https://openworks.mdanderson.org/sumexp21/1180/thumbnail.jp

Cautiously-Optimistic Knowledge Sharing for Cooperative Multi-Agent Reinforcement Learning

While decentralized training is attractive in multi-agent reinforcement learning (MARL) for its excellent scalability and robustness, its inherent coordination challenges in collaborative tasks result in numerous interactions for agents to learn good policies. To alleviate this problem, action advising methods make experienced agents share their knowledge about what to do, while less experienced agents strictly follow the received advice. However, this method of sharing and utilizing knowledge may hinder the team's exploration of better states, as agents can be unduly influenced by suboptimal or even adverse advice, especially in the early stages of learning. Inspired by the fact that humans can learn not only from the success but also from the failure of others, this paper proposes a novel knowledge sharing framework called Cautiously-Optimistic kNowledge Sharing (CONS). CONS enables each agent to share both positive and negative knowledge and cautiously assimilate knowledge from others, thereby enhancing the efficiency of early-stage exploration and the agents' robustness to adverse advice. Moreover, considering the continuous improvement of policies, agents value negative knowledge more in the early stages of learning and shift their focus to positive knowledge in the later stages. Our framework can be easily integrated into existing Q-learning based methods without introducing additional training costs. We evaluate CONS in several challenging multi-agent tasks and find it excels in environments where optimal behavioral patterns are difficult to discover, surpassing the baselines in terms of convergence rate and final performance.Comment: 13 pages, 19 figures, 6 tables, to be published in AAAI 202

REST-Dependent Downregulation of Von Hippel-Lindau Tumor Suppressor Promotes Autophagy in SHH-Medulloblastoma

The RE1 silencing transcription factor (REST) is a driver of sonic hedgehog (SHH) medulloblastoma genesis. Our previous studies showed that REST enhances cell proliferation, metastasis and vascular growth and blocks neuronal differentiation to drive progression of SHH medulloblastoma tumors. Here, we demonstrate that REST promotes autophagy, a pathway that is found to be significantly enriched in human medulloblastoma tumors relative to normal cerebella. In SHH medulloblastoma tumor xenografts, REST elevation is strongly correlated with increased expression of the hypoxia-inducible factor 1-alpha (HIF1α)-a positive regulator of autophagy, and with reduced expression of the von Hippel-Lindau (VHL) tumor suppressor protein - a component of an E3 ligase complex that ubiquitinates HIF1α. Human SHH-medulloblastoma tumors with higher REST expression exhibit nuclear localization of HIF1α, in contrast to its cytoplasmic localization in low-REST tumors. In vitro, REST knockdown promotes an increase in VHL levels and a decrease in cytoplasmic HIF1α protein levels, and autophagy flux. In contrast, REST elevation causes a decline in VHL levels, as well as its interaction with HIF1α, resulting in a reduction in HIF1α ubiquitination and an increase in autophagy flux. These data suggest that REST elevation promotes autophagy in SHH medulloblastoma cells by modulating HIF1α ubiquitination and stability in a VHL-dependent manner. Thus, our study is one of the first to connect VHL to REST-dependent control of autophagy in a subset of medulloblastomas

REST upregulates gremlin to modulate diffuse intrinsic pontine glioma vasculature

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive glial tumor that occurs in children. The extremely poor median and 5-year survival in children afflicted with DIPG highlights the need for novel biology-driven therapeutics. Here, we have implicated the chromatin remodeler and regulator of brain development called RE1 Silencing Transcription Factor (REST), in DIPG pathology. We show that REST protein is aberrantly elevated in at least 21% of DIPG tumors compared to normal controls. Its knockdown in DIPG cell lines diminished cell growth and decreased their tumorigenicity in mouse intracranial models. DIPGs are vascularized tumors and interestingly, REST loss in DIPG cells also caused a substantial decline in tumor vasculature as measured by a decrease in CD31 and VEGFR2 staining. These observations were validated in vitro, where a significant decline in tube formation by human umbilical vein endothelial cells (HUVEC) was seen following REST-loss in DIPG cells. Mechanistically, REST controlled the secretion of a pro-angiogenic molecule and ligand for VEGFR2 called Gremlin-1 (GREM-1), and was associated with enhanced AKT activation. Importantly, the decline in tube formation caused by REST loss could be rescued by addition of recombinant GREM-1, which also caused AKT activation in HUVECs and human brain microvascular endothelial cells (HBMECs). In summary, our study is the first to demonstrate autocrine and paracrine functions for REST in DIPG development. It also provides the foundation for future investigations on anti-angiogenic therapies targeting GREM-1 in combination with drugs that target REST-associated chromatin remodeling activities