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33091.血管血液透析治疗
[专用设备制造业,医药制造业] [2013-12-24]
Therapeutic options for patients suffering from end-stage renal disease have improved tremendously over the last decades and can be divided into three categories: hemodialysis, peritoneal dialysis and kidney transplantation. Transplantation remains the treatment of choice, however, lack of donor organs results in the necessity of performing -temporary-dialysis therapies of which hemodialysis is carried out in the majority of patients. To facilitate adequate hemodialysis therapy a reliable vascular access is mandatory and can be provided by either surgically connecting an artery with a vein (arteriovenous fistula), surgically connecting an artery with a vein using an interposition of prosthetic graft material (arterioven-ous graft) or a central venous catheter. This chapter shortly reviews the condition of end-stage renal disease after which history of vascular access, different options to create a vascular access, pre-operative work-up, surgical procedure, monitoring and usage, post-operative complications and the role of hemodynamics will be discussed. Finally, some future directions for vascular access creation and management will be identified.
关键词:治疗技术;透析;血管
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33092.由于Type-I胰岛素样生长因子受体(IGF1R)-Estrogen受体(ER)的贡献,乳腺癌细胞抗雌激素在治疗中抵抗
[医药制造业,专用设备制造业] [2013-12-24]
Tamoxifen, the first targeted therapy, has shown great success in treating estrogen receptor (ER) positive breast cancer. However, both acquired and de novo resistance to this therapy prevents it from being effective in all situations. Multiple lines of evidence indicate that increased signaling through growth factor pathways, such as the IGF pathway, mediates resistance to tamoxifen. The link between ER and ICGF1R leads us to hypothesize that IGF system crosstalk with the ER contributes to tamoxifen resistance. Tamoxifen resistance has thus provided researchers with a reason to investigate other growth factor pathways involved in breast cancer. As new targeted therapies are being developed, it will be important to examine their benefit with existing therapies. In order to examine the effectiveness of anti-IGF1R inhibitors in vitro, tamoxifen resistant (TamR) cells were generated by culturing MCF-7L and T47D cells in the presence of 4-OH-tamoxifen for >6 months. TamR cells had dimished levels of IGF1R, with unchanged levels of insulin receptor (IR). Further, TamR cells failed to respond to IGF-I induced p-AKT activation, while retaining responsiveness to both insulin and IGF-II. Additionally, IGF-I failed to enhance the proliferation and anchorage-independent growth of TamR cells; however, both insulin and IGF-II were able to enhance proliferation in MCF
anchorage-independent growth. An IGF1R antibody was effective in inhibiting signaling, anchorage-independent growth, and proliferation in MCF-7L cells, but had no effect in TamR cells. In contract, an IGF1R/TR tyrosine kinase inhibitor was effective in both MCF-7L and TamR cells. In a xenograft model, an IGF1R antibody was able to inhibit estrogen stimulated tumor growth, but had no additive effect when combined with tamoxifen treatment. Further, tamoxifen-treated xenografts had diminished IGF1R levels.
关键词:治疗技术;胰岛素;乳腺癌细胞
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33093.互联网对抑郁的认知和大脑功能行为治疗的影响
[医药制造业,专用设备制造业] [2013-12-24]
Despite the elevated rates of psychiatric problems among returning combat veterans, available evidence suggests that as many as half of soldiers screening positive for mental health problems never seek treatment for these issues (Fikretoglu et al., 2008, Hoge et al., 2006). One promising treatment approach that has shown efficacy in preliminary research and which may address issues related to stigma and barriers to care, is the used of web-based treatment interventions. In particular, internet-based cognitive behavioral therapy (iCBT) is rapidly emerging as a potentially efficacious treatment option for many individuals with mild to moderate depression (Andersson and Cuijpers, 2009). Emerging evidence suggests that iCBT is a particularly promising and well-accepted approach for treating large numbers of individuals while minimizing cost and clinicians time demand. Recently, researchers from the School of Psychiatry at the University of New South Wales (UNSW) developed and validated several, clinician-assisted iCBT programs that have shown remarkable success in treating major depressive disorder (MDD), generalized anxiety disorder, social phobia, and panic disorder (Robinson et al., 2010, Titov et al., 2010, Titov et al., 2009).
关键词:治疗技术;互联网;精神治疗
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33094.Mechanism-Based增强纳米粒子药物对乳腺癌的治疗
[医药制造业,专用设备制造业] [2013-12-24]
The endocytic trafficking pathway is the site of action for receptor- targeted drug-delivery strategies, including Antibody-Drug- Conjugates (ADCs) and nanoparticle drug-delivery systems. Effective drug-release requires trafficking of the endocytosed receptor-bound cargo into the lysosomes for efficient disintegration. However, cancer-cell specific alterations that lead to receptor recycling, instead of lysosomal-degradation, can dampen the efficiency of drug delivery. Such changes include receptor overexpression, increased association with the molecular chaperone, chaperones such as HSP90 or alterations in regulators of recycling versus lysosomal pathways (Rab GTPases, c-Src, deubiquitinases). While substantial effort has gone into designing receptor-targeted drug delivery systems, the consequence of factors leading to altered recycling versus lysosomal trafficking on the efficiency of drug delivery have not been considered. The receptor tyrosine kinases ErbB2 and EGFR, which are often overexpressed in breast cancer, are examples of cell surface receptors used for evaluating nanoparticle-based targeted drug delivery systems. However, several studies have established that the ErbB2 receptor is either endocytosis-impaired or undergoes rapid recycling, suggesting that the strategies to enhance receptor internalization and lysosomal routing could further enhance the efficacy of cytotoxic drug being delivered. While, the molecular chaperone HSP90 is critical for maintaining oncogenic ErbB2-activity, it also is thought to be responsible for the altered trafficking of the receptor. The objective of this synergistic DOD-IDEA grant proposal was to evaluate our innovative hypothesis that HSP90 inhibitors can facilitate ErbB2- targeted delivery of chemotherapeutic payloads.
关键词:治疗技术;纳米粒子;乳腺癌
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33095.随机二期试验的模拟肽疫苗佐剂WT-1恶性胸膜间皮瘤患者完成后的多学科治疗
[医药制造业] [2013-12-22]
The Wilms' tumor gene, WT1, encodes transcription factors that regulate cell proliferation, differentiation, and apoptosis. WT1 protein is highly expressed in malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a vaccine comprised of four WT1 heteroclitic peptides that are given together with Montanide and GM-CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial, and shown to be safe and immunogenic. We have chosen to test the efficacy of this vaccine in MPM patients who have minimal disease burden after completion of multimodality therapy, but remain at exceedingly high risk for recurrence. The specific aim of this project is to conduct a multicenter, blinded, randomized trial comparing treatment with the WT-1 peptide vaccine + Montanide/GM-CSF to treatment with Montanide/GM-CSF alone in patients with MPM who have completed multimodality therapy. The primary endpoint is progression free survival. The trial has opened at Memorial Sloan-Kettering and is actively enrolling patients.
关键词:疫苗;恶性胸膜间皮瘤;多学科治疗
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33096.杜兰/泽维尔疫苗研发工程项目
[医药制造业] [2013-12-22]
The Tulane/Xavier Biodefense Vaccine Development/Engineering project will develop new vaccines against biological threat agents to aid the war- fighter. Through the innovative use of nanotechnology, researchers and engineers from the Tulane University Schools of Medicine and Science & Engineering and the Xavier College of Pharmacy will fabricate nanoparticulate systems that are effective for transdermal and mucosal delivery of life-saving vaccines. One aim of this project will be to compare different nanocarriers (i.e., nanohydrogels, star copolymers, and spray-dried PLGA nanoparticles) for the ability to incorporate biological threat-relevant vaccine antigens and deliver those antigens through the stratum corneum to immuneresponsive cells in the epidermis. The specialized assembly of each type of nanocarrier gives each unique properties and different interactions within the lipid channels of the stratum corneum. The use of nanocarriers for vaccine delivery is a platform technology, applicable to delivery of a variety of existing and potential vaccines.
关键词:疫苗;抗原;纳米技术
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33097.FDA的简报文件:疫苗及相关生物制品顾问委员会会议2012年9月19日:从人类肿瘤衍生的疫苗生产细胞系
[医药制造业] [2013-12-22]
This meeting of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) is being held to discuss the use of cell lines derived from human tumors as substrates for the production of preventive viral vaccines. Over the last decade, it has become clear that the current repertoire of cell substrates is inadequate to manufacture the next generation of viral vaccines (i.e., certain viruses cannot be propagated or grow poorly in the available cell lines). Therefore, manufacturers have submitted additional cell lines to the FDA for consideration for use in the production of viral vaccines. All of the new mammalian cell lines being considered are immortal, having been transformed by various oncogenes or are spontaneously immortalized, and some are derived from human tumors. Over the last 15 years, when new types of cell substrates have been proposed, starting in 1998, CBER has presented its review approach to the Advisory Committee to address the issues raised first by the use of immortalized mammalian cell lines and then tumorigenic cell lines. The purpose of those discussions with the Advisory Committee was to obtain their input and to make public a discussion of the issues. This current VRBPAC meeting is a continuation of this process.
关键词:疫苗;人类肿瘤;FDA简报
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33098.TPD52:一种新型的前列腺癌疫苗
[医药制造业] [2013-12-22]
Tumor protein D52 (D52) is a novel self-onco-antigen involved in cellular transformation, proliferation and metastasis that is over-expressed in prostate cancer cells. The overall goal of this Award is to test the efficacy of D52-based vaccines in the TRAMP murine model of prostate cancer, and to characterize vaccine induced mechanisms of tumor immunity. Due to unforeseen circumstances during this funding period primarily involving the animal vendor and maternity leave for funded personnel we lost over 6 months of productivity. Consequently, we requested and were granted a no cost extension through 8/31/2012. Despite this unfortunate loss of time, over the past 12 months we made the following significant findings: Heterologous prime-boost vaccination induced more than 80protection from primary tumor challenge the best we have observed thus far, but only 30protection from secondary challenge about 8 months later. Similarly, if animals were immunized and rested for 8 months before challenge only about 50were protected from significant tumor growth suggesting that induction of a more durable response may require modulation of peripheral mechanisms of immune suppression as we previously reported. Finally, we demonstrated for the first time in vivo the critical importance of both CD4+ and CD8+ effector T cells in tumor protection following D52 immunization.
关键词:疫苗;前列腺癌;肿瘤蛋白
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33099.季节性流感疫苗的有效性早期的估计:美国,2013年1月。发病率和死亡率周报提前发布第62卷
[医药制造业] [2013-12-22]
In the United States, annual vaccination against seasonal influenza is recommended for all persons older than 26 months. Each season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent influenza-associated, medically attended acute respiratory infection (ARI). This season, early data from 1,155 children and adults with ARI enrolled during December 3, 2012-January 2, 2013 were used to estimate the overall effectiveness of seasonal influenza vaccine for preventing laboratory-confirmed influenza virus infection associated with medically attended ARI. After adjustment for study site, but not for other factors, the estimated vaccine effectiveness (VE) was 62(95confidence intervals (CIs) = 51-71). This interim estimate indicates moderate effectiveness, and is similar to a summary VE estimate from a meta-analysis of randomized controlled clinical trial data; final estimates likely will differ slightly. As of January 11, 2013, 24 states and New York City were reporting high levels of influenza-like illness, 16 states were reporting moderate levels, five states were reporting low levels, and one state was reporting minimal levels. CDC and the Advisory Committee on Immunization Practices routinely recommend that annual influenza vaccination efforts continue as long as influenza viruses are circulating. Persons older than 6 months who have not yet been vaccinated this season should be vaccinated. However, these early VE estimates underscore that some vaccinated persons will become infected with influenza; therefore, antiviral medications should be used as recommended for treatment in patients, regardless of vaccination status. In addition, these results highlight the importance of continued efforts to develop more effective vaccines.
关键词:疫苗;季节性流感;美国
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33100.融合乳腺癌和树突状细胞作为疫苗用于转移性乳腺癌的治疗,附录
[医药制造业] [2013-12-22]
The main objective of the study is to vaccinate patients with metastatic breast cancer with a viable dendritic cell (DC)/breast cancer fusions in conjuction with IL-12 to induce an immunological response with the hope that this combination would further enhance vaccine response by promoting Th1 cytokine induction and T cell activation. In this approach, the entire repertoire of tumor antigens, including those yet to be identified, are expressed with the immune-stimulating machinery of the DCs. The fusion cell vaccine allows for induction of helper T and CTL responses by class II presentation of exogenous protein and class I presentation of newly synthesized endogenous protein. Several of our clinical studies have demonstrated that vaccination with fusion cells was well tolerated, induced immunologic responses in a majority of patients, and results in disease regression in subset of patients. This brief report details the characterization of tumor cells and dendritic cells generated from patient BV01 with metastatic breast cancer following isolation from pleural effusions and leukapheresis, respectively.
关键词:疫苗;乳腺癌;树突状细胞