This Statistical Brief provides descriptive statistics on expenditures for the top five therapeutic classes of outpatient prescription drugs, ranked by total expenses in 2009 for adults age 18 and older in the U.S. civilian noninstitutionalized population. Prescription drug therapeutic classes are defined according to the Multum Lexicon therapeutic classification system. In 2009, 18 broad therapeutic classifications were identified.

关键词：处方药;门诊;治疗;成年人;费用;人口;家庭

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Adoptive cell therapy (ACT) of cancer with ex vivo activated/expanded T-cells is one of the promising treatments currently being tested in patients. One challenge of the approach is that the transferred T cells become functionally anergic in the tumor environment, limiting their anti- tumor effect. We have investigated whether tumor-mediated immune suppression can be overcome by arming tumor-specific T cells with cytokine/immunostimulator- loaded nanoparticles carried by each cell. Specially, we have defined the role of CD70 and CD80/CD86 in dendritic cell-mediated activation of tumor tolerized CD8 T cells, discovered the effect of CD8 T cell responses in selecting for antigen-negative tumor cells, and develop a better prostate model for monitoring T cell responses to prostate cancer in mice. Findings from our studies identify molecular interactions that are important for maintaining T cell function in the tumor environment, suggesting possible interventions to enhance T cell functionality during ACT. Our results that CD8 T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells provide insights into the requirements for an effective cancer immunotherapy: not only inducing potent immune responses but also avoiding selection and outgrowth of antigen- negative tumor cells.

关键词：免疫疗法;前列腺癌;T淋巴细胞;细胞(生物学);细胞因子

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Nanomedicine is a relatively new field of science and technology. By interacting with biomolecules, therefore at nanoscale, nanotechnology opens up a vast field of research and application. Current and potential applications of nanotechnology in medicine range from research involving diagnostic devices, drug delivery vehicles to enhanced gene therapy and tissue engineering procedures. Its advantage over conventional medicine lies on its size. Operating at nanoscale allows to exploit physical properties different from those observed at microscale such as the volume/surface ratio. This allows drugs of nanosize be used in lower concentration and has an earlier onset of therapeutic action. It also provides materials for controlled drug delivery by directing carriers to a specific location. Inorganic nanomedicine is likely to remain one of the most prolific fields of nanomedicine, which refers to the use of inorganic or hybrid (inorganic-inorganic or inorganic-organic) nanomaterials (ESfMs) and nanoparticles (INPs) to achieve innovative medical advances for body parts implantation, drug and gene discovery and delivery, discovery of biomarkers, and molecular diagnostics. Among the most promising INMs being developed are metal, silica, dendrimers, organic-inorganic hybrids, ceramics (e.g. ZrO_2, TiO_2, Al_2O_3, etc.) and bioinorganic hybrids. Metal NP contrast agents enhance magnetic resonance imaging and ultrasound results in biomedical applications of in vivo imaging. Hollow and porous INMs have been exploited for drug and gene delivery, diagnostic imaging, and photothermal therapy. Biomolecular inorganic nanohybrids and nanostructured biomaterials have been exploited for targeted imaging and therapy, drug and gene delivery, and regenerative medicine. Potential uses for fluorescent quantum dots (QDs) include cell labeling, biosensing, in vivo imaging, bimodal magnetic-luminescent imaging, and diagnostics. Biocompatible QD conjugates have been used successfully for sentinel lymph node mapping, tumor targeting, tumor angiogenesis imaging, and metastasis cell tracking. This article outlines present developments and future prospects for the use of Ti-based NPs and NMs in experimental in vivo and in vitro studies and in engineering nanodevices and biosensors for clinical and investigative use in diagnosis and therapy in diverse fields of medical sciences, such as oncology, infection control, orthopedics, dentistry, dermatology, genetics, cardiology, ophthalmology, etc. Toxicological considerations of these INPs and INMs are also discussed.

关键词：纳米技术;无机纳米钛(Ti),二氧化钛(TiO_2);无机NPs(输入)

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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：药物;基因;目标;凋亡;细胞(生物学);临床医学,药物测试

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CXCR4 and its chemokine ligand CXCL12 are potential targets for molecular therapy of ovarian cancer. Receptor CXCR4 is expressed by ovarian cancer cells in approximately 50of patients. High levels of CXCL12 are present in ascites of patients with ovarian cancer, providing a local source of chemokine ligand in the tumor microenvironment. CXCL12 signaling through CXCR4 activates pathways that could promote tumor growth, invasion, metastasis, and resistance to chemotherapy. To advance clinical translation of CXCR4 inhibitors for therapy of ovarian cancer, we developed molecular imaging reporters for CXCR4 signaling that can be used for cell-based assays and real-time imaging studies in mouse xenograft models of ovarian cancer. After validating that these reporters correspond with biochemical measures of CXCL12-CXCR4 signaling, we used optical imaging to quantify pharmacodynamics of therapy for CXCR4 targeted inhibitors in mice with ovarian cancer. Treatment studies established that inhibiting CXCR4 prolonged survival of mice with ovarian cancer and potentially could improve treatment efficacy of a standard chemotherapeutic drug, cisplatin.

关键词：细胞(生物学),化疗药物,临床医学;卵巢癌;生物化学

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Brain metastasis occurs in30of metastatic breast cancer patients. The prognosis is extremely poor, with a median survival of 4-6 months even with aggressive treatment. Thus, there is an urgent need to develop new treatments that target brain metastases. Radioimmunotherapy (RIT) is a targeted therapy that uses radiolabeled antibodies against tumor-specific antigens to treat lymphoma patients. However, success of RIT in the therapy of solid tumors has generally been limited due to heterogeneous tumor expression of the target antigens and cross-reactivity with normal cells. In preliminary studies, we have demonstrated that phosphatidylserine (PS) is exposed exclusively on tumor vascular endothelium of brain metastases in mouse models. A novel PS-targeting antibody, PGN635, a fully human monoclonal antibody, was used to target exposed PS in the brain metastases. Our data show that PGN635 binds specifically to tumor vascular endothelial cells in multi-focal brain metastases throughout the whole mouse brain. Vascular endothelium in normal brain tissues is negative. Furthermore, pretreatment with 10Gy of whole brain radiation significantly increased PGN635 binding to tumor vascular endothelial cells and tumor cells by increasing their exposure of PS. Vasculature in irradiated normal brain remained negative for exposed PS.

关键词：乳腺癌;转移;抗体、抗原;血管;脑;心血管系统

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The proposed work aims to address three major challenges to the field of regenerative medicine: (1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, (2) supportive vascular supply for large tissue engineered constructs, and (3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bear on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation.

关键词：细胞培养;组织(生物学);器官;生物再生;临床医学;体内分析

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Many studies revealed the high potential of multifunctional nanoparticles for biomedical applications. Since these nanoparticles can be designed for combining imaging and remotely controlled therapeutic activity, image-guided therapy which rests on the induction of nanoparticles toxicity by external stimulus when the nanoparticles content is both high in the diseased zone and low in the healthy tissue can be envisaged, especially for fighting cancer (one of the most important cause of mortality in several countries). Image-guided therapy should lead to valuable improvements in radiation-based therapy provided that the multifunctional radiosensitizing nanoparticles developed for increasing the selectivity of the radiotherapy (and therefore the efficiency) meet the criteria imposed by in vivo applications and by the physical principles of the interaction between radiation and the matter.

关键词：纳米粒子；放射治疗；生物医学；图像引导

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Mental health disorders affect a person's emotional, social, and behavioral well-being. As a result of the Patient Protection and Affordable Care Act, beginning in 2014, mental health disorder services will be part of the essential benefits package, a set of health care service categories that must be covered by certain plans, including all insurance policies that will be offered through state-based exchanges and Medicaid. This Statistical Brief presents estimates based on the Household Component of the Medical Expenditure Panel Survey (MEPS-HC) on the use of and expenditures for all medical care, ambulatory care (office-based provider and hospital outpatient visits), and prescribed medicines to treat mental health disorders among school-age children in the U.S. civilian noninstitutionalized population. Average annual estimates for 2007-2009 are shown by type of service and source of payment.

关键词：卫生保健支出;精神障碍;儿童;平民人口管控

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This summary will tell you about DMARDs, a type of medicine for people with PsA. It will also discuss the possible side effects of these medicines. It will tell you what research has found about how well DMARDs work to treat PsA. This summary can help you talk with your doctor about whether one of these medicines might be right for you. This summary does not discuss treatments for the skin condition of psoriasis.

关键词：银屑病关节炎;药物疗法;成年人;医药;银屑病;皮肤病

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