关键词：中医药；二次开发；新契机

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关键词：内外资；HPV疫苗；市场

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关键词：新版低价药；保障机制

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关键词：冠昊生物；ACI技术

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Autonomic dysreflexia (AD), which induces excessive elevation of blood pressure, is a potentially life-threatening medical emergency that occurs in persons with spinal cord injury (SCI) at or above the mid-thoracic spinal cord segment. Since the most common source of stimulation that initiates AD is the genitourinary tract including bladder distention, followed by colorectal distension, elimination of activation of bladder sensory pathways during bladder distention could significantly reduce the incidence and/or degree of AD in SCI. Because previous studies have indicated that increased levels of nerve growth factor (NGF) in sensory pathways are one of the key factors to induce increased excitability of sensory pathways after SCI, anti-NGF therapy could be an attractive treatment of AD in SCI patients. However, systemic anti-NGF treatment such as the use of NGF antibodies reportedly induces some side effects. Therefore, we hypothesize that the local therapy of NGF antisense delivery using liposomes (LPs) in the bladder could reduce the activation of bladder sensory pathways, thereby suppressing AD during bladder distention after SCI. Using adult female rats with chronic spinal cord injury induced by Th4 spinal cord transection, we will investigate: (1) the contribution of hyperexcitable bladder sensory pathways in the emergence of AD in SCI (Aim 1), and (2) the effects of intravesical delivery of NGF antisense-liposome conjugate, which reduce NGF expression in the bladder, on AD in SCI (Aim 2). If successfully completed, this study directly addresses the feasibility of local NGF antisense treatment for SCI-induced AD and provides the foundation for future clinical translation of local NGF antisense therapy in military service members, their family members, and/or the U.S. veteran population, who suffer from autonomic dysreflexia due to SCI.

关键词：医药；治疗技术；脊髓损伤；反义治疗；军事人员

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There are several new emerging monitoring technologies for combat casualty care that can be used as platforms for decision assist (D-A) and closed loop resuscitation (CLR) algorithms. It is our goal to evaluate these and other novel technologies with algorithms for fluid resuscitation in hemorrhaged human volunteers and patient studies.

关键词：医药；治疗技术；流体输送系统；决策辅助；闭环系统

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The project is intended to determine whether a specific nitric oxide- mediated tumor stress response pathway that is initiated following a cytotoxic injury (1) is observed in prostate cancer xenografts and (2) can be inhibited by the administration of dietary glycine supplementation. The rationale is based upon prior preclinical studies establishing, for other solid tumor types, that upregulation of inducible nitric oxide synthase (iNOS) in activated macrophages recruited to the site of cytotoxic injury from radiation or chemotherapy leads to the production of NO that stabilizes hypoxia-inducible factor 1-alpha, which in turns leads to increased expression of vascular endothelial growth factor (VEGF). As a result of this signaling process, tumor angiogenesis is supported, leading to recovery from the initial cytotoxic injury. It is believed that inhibiting this NO-mediated process of angiogenesis can enhance the cytotoxicity of radiation or chemotherapy, and it is believed that glycine might be an effective.

关键词：医药；治疗技术；前列腺癌；甘氨酸；放射疗法

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Bone is the most common site of metastasis for human breast cancer (BCa), which results in significant morbidity and mortality in patients with advanced disease. A vicious cycle, arising due to the interaction of BCa cells and cells in the bone microenvironment results in the activation of osteoclasts and increased osteolytic bone destruction. The major treatment to reduce the burden of bone metastasis in BCa patients is bisphosphonate therapy. Despite significant efforts to improve the potency of bisphosphonates, the complications are only retarded but not prevented. Thus, development of newer therapies that can both ameliorate the threshold of bone destruction and increase survival of patients with metastatic breast disease will be highly beneficial. The central hypothesis of the proposed work is bone-targeted delivery of genetically-engineered MSC, over-expressing OPG, will prevent osteolytic bone damage and restore skeletal remodeling. Further, based on the requirement of angiogenesis for tumor growth in primary and metastatic sites, in combination with a systemically stable anti-angiogenic therapy, long-term survival will significantly increase. These hypotheses will be tested in this proposal using an immnocompetent, preclinical mouse model of BCa dissemination to all major bones as in human patients.

关键词：医药；治疗技术；乳腺癌；骨溶解；临床医学

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关键词：医药；治疗技术；乳腺癌；卡尔曼滤波；放疗

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Underlying mechanisms that account for the increased risk of aggressive, metastatic disease associated with basal type breast cancers compared to the more differentiated, luminal tumor subtype have not been well established. Our work demonstrates that the transcription factor GATA3, essential for luminal differentiation during mammary gland development, is sufficient to promote global changes in basal triple-negative breast cancer (BTNBC) cells resulting in both (1) reduced metastasis via LOX downregulation and (2) acquisition of luminal features, thus offering a direct link between these two processes. GATA3 promoted global alterations of the transcriptome of BTNBC cells resulting in molecular and cellular changes associated with a more differentiated, luminal tumor subtype and a concomitant reduction in primary tumor growth, lung metastasis, and macrophage recruitment at the metastatic site. Importantly, we demonstrate that the inhibition of metastases by GATA3 results from the suppression of lysyl oxidase (LOX) expression, a metastasis promoting matrix remodeling protein, via epigenetic changes. MDA-MB-231 breast cancer cells overexpressing GATA3 showed increased methylation at the LOX promoter compared to control cells. Expression of LOX and GATA3 in breast cancer cells were inversely correlated. Most importantly, elevated LOX and reduced GATA3 expression levels predicted poor survival in breast cancer patients. Thus, altering transcription factor expression that promotes differentiation may be an important approach to mitigate aggressive tumor characteristics and to identify therapeutic targets such as LOX for the prevention or treatment of metastatic disease.

关键词：医药；治疗技术；乳腺癌；预防医学；分化治疗

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