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报告分类:外文技术报告

  • 4681.光动力疗法治疗提高骨折愈合

    [医药制造业] [2013-12-26]

    Long bone fractures resulting from high impact trauma can result in delayed healing. Photodynamic therapy (PDT) is a non-surgical, non-ionizing minimally invasive local treatment currently used to treat cancer and skin diseases. Surprisingly, recent findings from studying the effect of PDT on spinal metastases have shown that PDT improved the strength and stiffness of the vertebrae. Although variability in fracture generation led to inconclusive findings with respect to bone generation in the closed tibia fracture model (n=17), higher local levels of VEGF were found in PDT treated animals. A critical size defect fracture of the femur was generated in 20 adult female Sprague-Dawley rats. PDT treatment was applied either 1d (n=6) or 7d (n=6) after fracture generation. Qualitatively, a larger callus was seen in the 7d- PDT group, suggesting an important effect of timing on PDT administration. Both PDT treated groups showed evidence of healing and closing of the fracture gap in this critical defect model. Preliminary, quantitative CT measurements support the qualitative findings. Additional CT based imaging and stereological analysis are underway. Histologic processing and analysis of the serum will also be conducted on these animals.
    关键词:医药;治疗技术;光动力疗法;骨折
  • 4682.以ETS基因融合作为预测生物标记来放疗治疗前列腺癌

    [医药制造业] [2013-12-26]

    The research goals of this grant proposal are to: (1) investigate the effect of ETS gene fusions on radiation phenotype in pre-clinical models of prostate cancer, (2) to explore the mechanism of interaction between ERG (the predominant ETS gene fusion product) and the DNA repair protein DNA-PK, and (3) to determine if ETS gene fusion status is a clinical biomarker of radioresistance for prostate cancer. The training goals of this grant proposal included a series of regular meetings with mentors, research seminars, journal clubs, and workshops, all of which are intended to help Dr. Feng develop as a translational scientist. This grant proposal was approved as a five-year award; the current annual report summarizes accomplishments over the second year of the grant, from July 15, 2011 to July 15, 2012. Overall, the first two years of this grant have been very successful. The work accomplished as a result of this grant resulted in two publications in very high impact journals, four national presentations, and three grants (two from the Prostate Cancer Foundation and one from Celgene). Additionally, Dr. Feng has met the training achievements specified in his original grant. The research proposed in this training grant represents an important area within the field of prostate cancer research. Because ETS gene fusions are thought to be driver alterations in over half of all prostate cancers, understanding the mecha-nistic and potential clinical implications of these gene fusions has significant ramifications, particularly in the context of radiation therapy, which represents a primary treatment modality for localized prostate cancer. In the second year of this grant period, we have generated bioluminescent ETS+ and ETS- cells in three different prostate cancer cell lines, and we havereceived institutional approval to proceed with the proposed animal studies and human biomarker tissue studies.
    关键词:医药;治疗技术;生物标记;前列腺癌
  • 4683.复合组织异体移植术之后对于神经再生和免疫调节的间充质干细胞治疗

    [医药制造业] [2013-12-26]

    Composite Tissue Allotransplantation (CTA) offers an alternative reconstructive strategy for complicated musculoskeletal injuries incurred during modern warfare where functional outcomes after multipe conventional reconstructions are suboptimal. Broader clinical application of CTA, however, continues to be hampered by requirement for long-term multi-drug immunosuppression to prevent graft rejection. Furthermore, unlike in solid organs, clinical success is dictated not only by graft acceptance, but also by functional outcome. Our study proposes a novel cell-based therapy utilizing mesenchymal stem cells (MSC) that can augment nerve regeneration while minimizing the need for immunosuppression. After transition from University of Pittsburgh to Johns Hopkins University, we optimized our isolation and culture protocol for MSCs. Immunophenotypic and functional characterization of cultured cells demonstrated potent immunomodulatory effects of MSCs in vitro. Preliminary functional outcome analysis using Catwalk showed convergent data with similar loss and return of function among groups. Similarly, compound muscle action potentials at early time points showed small non-significant increases in amplitude in experimental groups. In contrast, normalized gastrocnemius weights showed increased muscle weight in only the systemic injection group. Overall, we continue to monitor both functional and histological outcomes. Consistent with existing literature on nerve regeneration, we expect to observe more evident differences among groups with increased data over the longer term.
    关键词:医药;治疗技术;复合组织异体移植术;神经再生
  • 4684.肌肉干细胞疗法治疗DMD相关心肌病

    [医药制造业] [2013-12-26]

    Project 1: Dilated cardiomyopathy affects approximately 1 in 2,500 individuals in the United States and is the 3rd most common cause of heart failure and the most frequent cause of heart transplantation. Patients that suffer from various muscle diseases, including Duchenne muscular dystrophy (DMD), develop progressive cardiomyopathy. Cellular cardiomyoplasty, which involves the transplantation of exogenous cells into the heart, is a possible approach by which to repair diseased or injured myocardium and improve cardiac function. Though there are a number of drugs prescribed to treat dilated cardiomyopathy, there is no cure and individuals eventually require a heart transplant; therefore the use of cardiomyoplasty to repair the hearts of individuals suffering from cardiomyopathy could possibly be an effective alternative to heart transplantation. Technical Objective No. 1: To investigate the effect of cell survival, proliferation, and differentiation on the regeneration/repair capacity of various human MDSC populations implanted into the heart of mdx/SCID mice. Technical Objective No. 2: To investigate the role that angiogenesis plays in the regeneration/repair capacity of human MDSCs injected into the hearts of mdx/SCID mice. Project 2: This project will determine the extent to which novel sources of hepatocytes can be used for regeneration and repair of injuries to the liver and liver failure. A more complete understanding of the extent to which donor liver cells can be resuscitated from non-traditional sources and expanded for application to reduce liver injury and toxin and/or cancer risk should enhance the number of areas where hepatic stem cell transplantation might be effectively applied. Technical Objectives: (1) to characterize and expand hepatocytes from patients with cirrhosis and end-stage liver disease in immune deficient hosts whose livers permit extensive repopulation with donor cells; (2); to determine the extent to which transplant.
    关键词:医药;治疗技术;肌肉干细胞疗法;心肌病
  • 4685.纤维瘤引起的恶性肿瘤联合治疗的临床前测试

    [医药制造业] [2013-12-26]

    This is the final report that shows the results obtained during the funding. The aim of this study was identify combinations of currently approved drugs that would be effective for treating MPNST. The resources attained along the first phase of this project were valuable for the subsequent drug screen performed in human MPNST cells and in vivo experiments. The inhibition of mammalian target of rapamycin (mTOR) by drugs (Rapamycin and RAD001) or RNA interference shows synergism with ionizing radiation decreasing human MPNST cell proliferation. Cell-based drug screen in combination with mTOR inhibitiors uncovers three potential candidates (toremifene, riluzole and bortezomib) with different mechanism of action. We further characterized the interaction between bortezomib, a proteasome inhibitor, and mTOR signaling inhibition in MPNST cells proliferation, cell cycle and apoptosis. Finally, dual targeting of proteasome and mTOR signaling associated with radiotherapy delay MPNST tumor growth in xenograft nude mice.
    关键词:医药;治疗技术;纤维瘤;临床前测试
  • 4686.在敏化前列腺癌细胞疗法中AR调制和VDR调制的作用

    [医药制造业] [2013-12-26]

    Epidemiological evidence has demonstrated an inverse association between serum vitamin D levels and sunlight exposure to prostate cancer incidence. In addition, serum androgen levels and biologically available testosterone decrease significantly in elder men while the incidence rate of prostate cancer increases. These findings lead to the hypothesis that androgen- and vitamin D-mediated signaling events may act together to inhibit prostate tumor initiation and/or development. Using concurrent microarray analyses, we demonstrated that testosterone and 1,25(OH)2D3 co-operate to regulate mRNA and miRNA expression, including some well-defined oncogenes and tumor suppressor genes. Pheno typically, this results in G0/G1 cell cycle arrest and increased neutral lipid accumulation in LNCaP cells, as a consequence of repression of various cell cycle regulators and the up-regulation of PPAR alpha; respectively. This suggests that the cross talk between T and 1,25(OH)2D3 induces cell cycle arrest and promotes cell differentiation in LNCaP cells. It is important ton ote that co-treatment of LNCaP cells with testosterone, 1, 25(OH)2D3 and other standard therapeutics, including bicalutamide, docetaxel and TRAIL did not affect the potencies of these treatments, though there were no synergistic effects either. This suggests that androgen andvitamin D supplementation slow disease progression without affecting the efficacy of standard therapies for prostate cancer. Further analysis is still required to elucidate the underlying mechanisms of T and 1,25(OH)2D3 to modulate key mRNA and miRNA and their significance in prostate tumorigenesis and therapeutic interventions.
    关键词:医药;治疗技术;前列腺癌;细胞疗法
  • 4687.STAT3对于纤维神经瘤肿瘤的治疗

    [医药制造业] [2013-12-26]

    Neurofibromatosis type 1 patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). Growth factor receptors, particularly EGFR, have been implicated in neurofibroma formation and progression, but their precise roles and relevant signaling pathways remain unknown. We found that EGFR modifies neurofibroma-initiating cell number and promotes transformation to aggressive GEM-PNST. Unbiased insertional mutagenesis screening suggested that these effects were mediated by STAT3 signaling. Immunohistochemistry demonstrated phosphorylated STAT3 (Tyr705) in human and mouse tumors. A specific STAT3 inhibitor blocked neurofibroma-sphere formation in vitro, and reduced neurofibroma growth in vivo; STAT3 knockdown by shRNA prevented MPNST formation in vivo. Finally, reducing EGFR activity strongly reduces pSTAT3 in vivo. Thus, an EGFR-STAT3 pathway regulates neurofibroma number and neurofibroma growth, and promotes transformation.
    关键词:医药;治疗技术;STAT3;纤维神经瘤
  • 4688.治疗乳腺癌的常规方法RNAi

    [医药制造业] [2013-12-26]

    The goal of this innovator award is to continue to develop and apply RNAi-based screening methods to discover new routes toward breast cancer therapy. The project has three goals. The first is to integrate genomic and genetic information on available breast cancer cell lines to identify tumor- specific vulnerabilities and to understand genetic determinants of therapy resistance. The second is to probe the roles of breast cancer stem cells, with a particular emphasis on microRNAs. The third is to examine genomic regions that determine familial susceptibility to breast cancer using novel, focal re- sequencing methods developed in the laboratory.
    关键词:医药;治疗技术;RNAi;乳腺癌
  • 4689.慢性运动不完全脊髓损伤课题中机械性的身体负重运动训练和水生治疗疗法的比较

    [医药制造业] [2013-12-26]

    During the first year of this study, we have completed all case report forms, data collection sheets and informed consent documents. All necessary IRB approvals have been obtained, and all regulatory documents have been submitted to the Baltimore VA Medical Center Research Committee. A local IRB modification has been submitted to clarify exclusion criteria as it relates to the assessment of diabetic subjects. All personnel have obtained appropriate certifications in order to participate in research. Multiple meetings have occurred, both in person and via teleconference in order to coordinate activities between the Baltimore and the Atlanta sites. The research protocols have been initiated, with nine individuals screened and seven progressing to study participation. In Baltimore one participant completed 3 month outcome data assessment and crossed over to the other exercise arm. The other six individuals are in the first exercise arm. Two enrollees at the Baltimore site were withdrawn from the protocol, one because of a burning sensation in the left foot during Lokomat participation, and the other because of asymptomatic blood pressure elevation during Lokomat training. At the end of year one, the research has not as of yet produced any presentations or published reports, but this was not expected.
    关键词:医药;治疗技术;脊髓损伤;水生治疗
  • 4690.局部雷帕霉素治疗缓解皮肤结节性硬化综合症的表现

    [医药制造业] [2013-12-26]

    Tuberous Sclerosis Complex (TSC) is a genetic disorder resulting from mutations in either the TSC1 or TSC2 genes. TSC is characterized by abnormal skin pigmentation and tumor formation in multiple organ systems. TheTSC1andTSC2gene products are involved in cell signaling; in particular they are involved in the mammalian target of rapamycin (mTOR) signaling pathway. In TSC, the epidermal basal cells contain a mutant copy of either theTSC1orTSC2gene. A loss of heterozygosity results in constitutive activation of mTOR leading to production of epidermal cells at a faster rate than the ability to slough the dead cells. This overproduction of skin cells, in conjunction with angiogenesis, results in the formation of visible facial angiofibromas over time.
    关键词:医药;治疗技术;雷帕霉素;皮肤结节性硬化综合症
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