较快增长—1-8月份，医药制造业实现销售收入12723.6亿元，同比增长18.7%.商业贿赂—据中国医药企业管理协会副会长牛正乾介绍，从8月开始，此次反商业贿赂调查对行业的影响开始逐步显现，医药企业经营更加谨慎。并购热潮—今年以来医药上市公司的并购节奏明显加快，相关案例不下20个。中药颗粒—中药配方颗粒销售规模小、市场潜力大、主要生产企业均着手产能扩增。

《经济日报》、《每日经济新闻》综合报道，根据食药监总局2月7日发布的《创新医疗器械特别审批程序（试行）》（以下简称《特别审批程序》），自2014年3月1日起，食品药品监管部门对符合相应条件的医疗器械按该程序实施审评审批。对于经审查同意按特别程序审批的创新医疗器械，各级食品药品监督管理部门及相关技术机构，将根据各自职责和该程序规定，按照早期介入、专人负责、科学审批的原则，在标准不降低、程序不减少的前提下，对创新医疗器械予以优先办理，并加强与申请人的沟通交流。

Biosimilars are defined as the follow-on versions of original biological medicines. These are separately developed after the patent protecting the original product has expired. Biosimilar medicines are intended to have the same mechanism of action as original biological medicines, and are designed to treat the same diseases as the innovator’s product. However, biosimilars have many similarities, but are not identical to the reference biopharmaceutical product. This is mainly because the nature of the manufacturing process and the size and complexity of the active substances in biosimilars differ from the generic chemical products.

During the most recent period the Center of Excellence continued to collect and process human breast cancer tissues for patients receiving chemotherapy for metastatic disease. These tissues have been annotated clinically, examined by the study pathologist for QC/QA purposes, entered into our data analysis system, and distributed to the appropriate laboratory investigators for evaluation. An initial analysis of patients with metastatic breast cancer treated with the antimetabolite prodrug capecitabine was performed, and revealed striking correlations between thymidylate synthase (as measured by fluorescence in situ hybridization) and outcome.

In the current funding period, we completed studies on the protective effects of adenoviral induced VEGF-D and compared this effect to VEGF-C. These findings were correlated with lymphatic and blood vessel density and support our hypothesis that lymphatic vessel induction is protective in IBD. These findings support lymphatic expansion as a controlling element of blood vessel expansion. We next examined the effects of VEGFR-2 kinase inhibitor, SU1498 and a VEGFR-2 competitor antibody on acute erosive colitis. VEGFR-2 blockade was protective in some phases of colitis and appears to reflect suppression of blood vessels. We also explored whether and how blockade of the pro-lymphangiogenic VEGF receptor, VEGFR-3 (using MAZ51, a VEGFR-3 kinase blocker) would affect acute erosive colitis. We found that VEGFR-3 blockade lead to significant increases in gut tissue injury, particularly when given during the recovery phase of the DSS model. This suggests to us that lymphatics may exert protective influences colitis by hastening recovery from disease rather than preventing its induction.

Effective treatment of sensory neuropathies in peripheral neuropathies and spinal cord injury (SCI) is one of the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord is a logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the potential of transplant of cells to treat chronic pain. Cell lines derived from the human neuronal NT2 cell line parentage, the hNT2.17 and hNT2.19 lines,which synthesize and release the neurotransmitters gamma- aminobutyric acid (GABA) and serotonin (5HT), respectively, have been used to evaluate the potential of cell-based release of antinociceptive agents near the lumbar dorsal (horn) spinal sensory cell centers to relieve neuropathic pain after PNS (partial nerve and diabetes-related injury) and CNS (spinal cord injury) damage in rat models. Both cell lines transplants potently and permanently reverse behavioral hypersensitivity without inducing tumors or other complications after grafting. Functioning as cellular minipumps for antinociception, human neuronal precursors, like these NT2-derived cell lines, would likely provide a useful adjuvant or replacement for current pharmacological treatments for neuropathic pain.

Xavier University of Louisiana is in the unique position of developing capability in drug discovery especially in the areas of cancer and health disparities. A significant proportion of the funded research on Xavier s campus including collaborative projects involving Tulane University are related to cancer, drug design, synthesis, and drug delivery. This project expands the partnership between Xavier University and Tulane Cancer Center to develop and validate drugs for breast cancer therapy. The Drug Design Team at Xavier consists of experts in computer aided drug design methods and synthesis and has formed a productive partnership with the Cancer Drug Validation Team at the Tulane Cancer Center. This inter-university collaboration involves training Xavier researchers, including undergraduate students, to carryout the experiments necessary to determine if new compounds would be suitable as new drugs to treat breast cancer. Three separate studies are ongoing as subprojects: (1) Design and synthesis of novel ceramide analogs that potentially reverse chemotherapy drug resistance, (2) Design and synthesis of small molecule inhibitors of HER2 tyrosine kinase to suppress tumorigenesis, and (3) Identification of compounds with the potential for estrogen receptor activity.

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.

There is no cure for metastatic breast cancer, which kills 40,000 American women (and 500 men) each year: all presently available treatments are palliative. Gene therapy techniques are used to introduce chimeric immunoglobulin-T cell receptors (IgTCR) into autologous patient T cells to create designer T cells that redirect the T cell immune system in a new type of immuno-gene therapy against breast cancer. Designer T cells have been created against the carcinoembryonic antigen (CEA) that is prominently present on many metastatic breast tumors (30-60). This exceeds the fraction that are Her2/neu overexpressing (20-25), making CEA an even better immune target for attacking breast cancer. Building on a prior study of CEA designer T cells in breast and colon cancer, 2nd generation designer T cells were created by incorporating into the IgTCR a CD28 co-stimulation cassette that was shown to oppose activation-induced cell death (AICD) of the T cells after tumor contact. This advanced generation modification leads to improved designer T cell survival and improved anti-tumor potency in preclinical models. Although the 2nd generation designer T cells produce interleukin 2 (IL2) growth factor on contact with tumor, interleukin 2 (IL2) supplementation is anticipated still to be required for optimal clinical therapeutic effect. However, the CBER/FDA has mandated a Phase I.

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.

Operation brain trauma therapy (OBTT) is a multicenter, pre-clinical, drug screening and brain injury biomarker development consortium for TBI. OBTT includes investigators at the Safar Center (University of Pittsburgh), the University of Miami, WRAIR, Virginia Commonwealth University, and Banyan Biomarkers. Three rodent models (controlled cortical impact, parasagittal fluid percussion, and penetrating ballistic-like brain injury) are used for drug screening with the most promising candidates tested in a micropig model. We have completed studies with nicotinamide, erypthropoietin (EPO), and cyclosporine-A (CsA), and have just begun testing of simvastatin. We plan to test Minocycline and levetiracetam this year of funding. Studies with nicotinamide suggest some benefit of 50 mg/kg on motor outcomes, but variable benefit on cognitive outcomes. Studies with EPO did not appear promising. Studies with CsA have been completed; data analysis is ongoing. Studies of the serum brain injury biomarker GFAP from these rats have provided the first ever cross-model biomarker comparison and suggest that GFAP may be useful for drug screening, since nicotinamide treatment significantly reduced serum GFAP levels in two models. A consortium overview was published in Journal of Trauma and numerous abstracts were presented at the 2011 ATACCC, the 2012 NNT congress, and the 2012 MHSRS conference.