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：医药；治疗技术；纳米粒子；乳腺癌

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Pharmaceutical is related to people's health and life safety directly, we can track and control pharmaceutical safety and quality by constructing the traceable system of pharmaceutical's whole life cycle, including raw materials, production, transportation and storage. This paper develops a pharmaceutical production management system based on RFID technology, the system realizes the drug security by RFID, puts forward a pharmaceutical coding method according to EPCgloble, constructs a scheduling method and a monitoring of the pharmaceutical production process, and then it will be traceable for the information of pharmaceutical production process.

关键词：医药；药品；RFID；管理系统

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The VA Office of Inspector General (OIG) Office of Healthcare Inspections conducted a review in follow up of its March 2011 report on radiation therapy (RT) at the VA Long Beach Healthcare System (facility) in Long Beach, CA. OIG also assessed the validity of new allegations related to the quality of radiation treatments. We conducted an unannounced inspection in December 2012 and an announced inspection in February 2013, observed the practices of radiation therapists, and examined departmental electronic and paper records that are accessible only onsite.

关键词：医药；治疗技术；放射；评估

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Despite intense research efforts, cancer remains the second leading cause of death in the United States. Mortality is seldom caused by primary tumors, but rather by the effect of metastases on distant organs. The lymphatic system serves as a common route of metastasis for many cancers of epithelial origin. There is growing evidence that lymphangiogenesis, the sprouting of new lymphatics from pre-existing lymphatics, facilitates the dissemination of cancer. Interestingly, vascular endothelial growth factor receptor-2 (VEGFR2) signaling has been shown to stimulate lymphangiogenesis in adult mice. However, the role VEGFR2 serves in the development of the lymphatic system has not been defined. Here we use the Cre-lox system to show that the proper development of the lymphatic vasculature requires VEGFR2 expression by lymphatic endothelium. This newly identified function of VEGFR2 further defines the molecular pathways controlling the development of the lymphatic vasculature and sheds light on how therapeutic agents targeting VEGFR2 can inhibit tumor lymphangiogenesis.

关键词：医药；治疗技术；淋巴系统；Anti-VEGF-A

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Over billions of years, the ocean is regarded as the origin of life on Earth, and the ocean includes the largest habitats hosting the most life forms. Competition among microorganisms for space and nutri ents in the marine environment is a powerful selective force, which has led to the evolution. The evolution prompts the marine micro organisms to generate multifarious enzyme systems to adapt to the complicated marine environments. Therefore, marine microbial enzymes can offer novel biocatalysts with extraordinary properties. This review deals with the research and development work done on the occurrence and bioprocessing of marine microbial enzymes.

关键词：医药；药品；食品；海洋微生物酶

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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：医药；治疗技术；类胰岛素生长因子受体；抗雌激素受体

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The broad objective of the proposed study is to empirically evaluate the efficacy of a cognitive behavioral intervention, titled, Post Admission Cognitive Therapy (PACT), for military personnel psychiatrically hospitalized due to a suicide-related event with either a recent or a lifetime suicide attempt. The primary outcomes will be incidence of repeat suicide attempt(s) and number of days until a repeat suicide attempt. Secondary outcomes include psychiatric symptoms, repeat number of psychiatric hospitalization(s), hope for one s future, and acceptability of treatment. A multi-site, single-blind, randomized controlled trial will be the research design. A total of 218 individuals will be recruited from the inpatient psychiatric and traumatic brain injury (TBI) units at the Walter Reed National Military Medical Center and Fort Belvoir Community Hospital. Participants will be randomized into one of two conditions: (1) PACT + Enhanced Usual Care (EUC) or (2) EUC. The PACT+EUC condition will consist of six 60-90 minute individual cognitive behavioral therapy sessions administered over preferably three days during the inpatient stay and up to four telephone booster sessions. The EUC condition will consist of usual psychiatric care patients receive during their hospitalization, the assessment services provided by MA and/or PhD level clinicians, and case management services provided for one year by Bachelor s level research personnel. Follow-up assessments will be conducted at 1, 3, 6, and 12-month post discharge by blind PhD level clinicians.

关键词：医药；治疗技术；认知治疗；随机实验

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Microbiological testing plays an ever increasing role in delivering high quality drug products to patients, whether it's practiced in the pharmaceutical laboratory and in the manufacturing environment. In response to the drive for continuous improvement and further economies, a variety of new methodologies have emerged in recent years which automate existing methods, make use of surrogate markers for growth, or are based on wholly new technologies. These new methodologies offer significant improvements in terms of the speed, accuracy, precision and specificity with which testing can be performed. However, in spite of the limitations of current culture methods, acceptance of new and potentially superior methods has only started to gain momentum within the pharmaceutical, biotechnology and medical device industries. We believe this continues to be due in part to a lack of clear guidance regarding the demonstration of their equivalence to existing methods acceptable to regulatory agencies and validation of the equipment associated with the new methods. In any case, many of these new rapid methods may have a role to play in other applications including missions in space where we want to know the impact of microorganisms on space travel, as well as what microorganisms might be waiting to be discovered.

关键词：医药；药品；微生物监测；制药工业

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This chapter will summarize current knowledge in renal replacement technologies in the treatment of critically ill patients with acute kidney injury. The mechanics of different treatment modalities with emphasis on continuous renal replacement therapies will be described, as well as the application of such technologies in the management of fluid overload and metabolic abnormalities. Appropriate composition of dialysate and replacement fluids, use of anticoagulation, choice of vascular access, and potential complications in the use of such technologies will be discussed. Finally, the chapter will compare the main features of the different currently available CRRT machines.

关键词：医药；治疗技术；肾脏；替代

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The sympathetic nervous system (SNS) is a major pathway activated by exposure to emotional stressors. We have demonstrated SNS hard-wiring in the form of sympathetic nerve fibers in 4T1 mammary tumors, a mouse model of metastatic breast cancer. We established that 4T1 tumor cells do not express functional - or -adrenergic receptors (AR), the receptors activated by norepinephrine (NE), the neurotransmitter of the SNS. Yet, manipulation of sympathetic neurotransmission in vivo by chemical ablation of sympathetic nerves to deplete NE decreased F480+ tumor associated macrophages and reduced tumor weight. Furthermore, chronic treatment with desipramine (DMI), an antidepressant that elevates synaptic NE, increased 4T1 tumor growth, but not metastasis. DMI-induced tumor growth was not associated with increased tumor angiogenesis, and pro-tumor cytokines VEGF, IL-6, RANTES, and MIP-2 were reduced by DMI. To further dissect the tumor response to NE, mice were treated with selective AR agonists. The 2-AR agonist dexmedetomidine (DEX) increased tumor growth and metastasis in the absence of alterations in VEGF, IL-6, RANTES, and MIP-2. Treatment with the -AR agonists isoproterenol and salmeterol did not significantly alter tumor growth/metastasis. In DMI- and DEX-treated mice, tumor collagen microstructure was uniquely altered in 4T1 tumors, suggesting a novel stromal-mediated mechanism whereby elevated NE and stimulation of AR may increase tumor growth. These results suggest that NE-induced tumor growth is mediated by 2-AR activation, but other AR pathways activated by elevated synaptic NE may modulate the tumor-promoting effect of 2-AR activation. Understanding how AR pathways regulate breast tumor pathogenesis will lead to new therapies to inhibit tumor growth and metastasis.

关键词：医药；治疗技术；乳腺癌；交感神经

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