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Until recently, 5-fluorouracil was the most widely used treatment for non-resectable pancreatic cancer. This treatment, however, only resulted in a median survival time of approximately 4 months. In the last few years, gemcitabine has rapidly become the new treatment benchmark, due more to its superior clinical benefit rather than to it conferring an increased median survival (approximately 5-6 months). Thus, the outlook for patients with pancreatic cancer is still relatively bleak. A number of new treatment options are presently being investigated. Some of these are combination therapies involving gemcitabine and other chemotherapeutic agents or radiation. Other novel treatment strategies are also already being evaluated in clinical studies. Some of the more promising treatments in development are discussed and evaluated in this article. 相似文献
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《Expert opinion on investigational drugs》2013,22(6):769-786
Until recently, 5-fluorouracil was the most widely used treatment for non-resectable pancreatic cancer. This treatment, however, only resulted in a median survival time of ~ 4 months. In the last few years, gemcitabine has rapidly become the new treatment benchmark, due more to its superior clinical benefit rather than to it conferring an increased median survival (~ 5 – 6 months). Thus, the outlook for patients with pancreatic cancer is still relatively bleak. A number of new treatment options are presently being investigated. Some of these are combination therapies involving gemcitabine and other chemotherapeutic agents or radiation. Other novel treatment strategies are also already being evaluated in clinical studies. Some of the more promising treatments in development are discussed and evaluated in this article. 相似文献
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García-Pérez ME Jean J Pouliot R 《Recent patents on inflammation & allergy drug discovery》2012,6(1):3-21
Psoriasis is a chronic recurring skin disorder affecting up to 2% of the world's population. Psoriatic lesions are generally visible, leading to significant emotional and social disabilities for patients. In the context of psoriasis, the orchestrated interplay between activated T cells, antigen-presenting cells and keratinocytes leads to the release of proinflammatory cytokines, chemokines and chemical mediators responsible for the perpetuation of this disease. Even though some therapies are available for psoriasis treatment, there is still no cure for this skin disorder and psoriatic patients are significantly unsatisfied, as demonstrated by recent worldwide surveys. Unlike other diseases, psoriasis does not have a generally accepted animal model, which complicates the successful introduction of new antipsoriatic drugs into clinical phases of development. Moreover, psoriasis affects infants, children and elderly patients which require long-term therapies. Thus, the development of new therapeutic approaches should consider multiple factors such as efficacy, dosing frequency, route of administration, toxicity as well as co-morbidities of patients. This article analyzes current challenges for the antipsoriatic drug development and reviews recent patent applications gathered from 2000 to 2011 for psoriasis treatment. Additionally, future perspectives for antipsoriatic drug development are summarized. 相似文献
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As molecular chaperones, heat-shock proteins (HSPs) function to limit protein aggregation, facilitate protein refolding and chaperone other proteins. Under conditions of cellular stress, intracellular HSP levels increase in order to provide cellular protection and maintain homeostasis. Evidence exists that the HSP family may be secreted into the circulation via lipid raft-mediated, granule-mediated or exosome-mediated exocytosis in haematopoietic and tumour cells. Extracellular HSPs exert immunomodulatory activities and play an important role in innate immune activation against pathogen infection. Membrane-bound Hsp70 in tumour cells or released chaperone-tumour associated antigen complex represent a target structure for the cytolytic attack by natural killer cells or T lymphocytes. Cellular stresses induce stress granule formation to evade detrimental cellular effects, mediating preconditioning phenotype. Therefore, induction of cellular stress tolerance by preconditioning (e.g., heat shock) might be potential therapeutic targets. 相似文献
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《Expert opinion on therapeutic targets》2013,17(5):759-769
As molecular chaperones, heat-shock proteins (HSPs) function to limit protein aggregation, facilitate protein refolding and chaperone other proteins. Under conditions of cellular stress, intracellular HSP levels increase in order to provide cellular protection and maintain homeostasis. Evidence exists that the HSP family may be secreted into the circulation via lipid raft-mediated, granule-mediated or exosome-mediated exocytosis in haematopoietic and tumour cells. Extracellular HSPs exert immunomodulatory activities and play an important role in innate immune activation against pathogen infection. Membrane-bound Hsp70 in tumour cells or released chaperone-tumour associated antigen complex represent a target structure for the cytolytic attack by natural killer cells or T lymphocytes. Cellular stresses induce stress granule formation to evade detrimental cellular effects, mediating preconditioning phenotype. Therefore, induction of cellular stress tolerance by preconditioning (e.g., heat shock) might be potential therapeutic targets. 相似文献
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All cells, from bacterial to human, have a common, intricate response to stress that protects them from injury. Heat shock proteins (Hsps), also known as stress proteins and molecular chaperones, play a central role in protecting cellular homeostatic processes from environmental and physiologic insult by preserving the structure of normal proteins and repairing or removing damaged ones. An understanding of the interplay between Hsps and cell stress tolerance will provide new tools for treatment and drug design that maximise preservation or restoration of health. For example, the increased vulnerability of tissues to injury in some conditions, such as ageing, diabetes mellitus and menopause, or with the use of certain drugs,, such as some antihypertensive medications, is associated with an impaired Hsp response. Additionally, diseases that are associated with tissue oxidation, free radical formation, disorders of protein folding, or inflammation, may be improved therapeutically by elevated expression of Hsps. The accumulation of Hsps, whether induced physiologically, pharmacologically, genetically, or by direct administration of the proteins, is known to protect the organism from a great variety of pathological conditions, including myocardial infarction, stroke, sepsis, viral infection, trauma, neurodegenerative diseases, retinal damage, congestive heart failure, arthritis, sunburn, colitis, gastric ulcer, diabetic complications and transplanted organ failure. Conversely, lowering Hsps in cancer tissues can amplify the effectiveness of chemo- or radiotherapy. Treatments and agents that induce Hsps include hyperthermia, heavy metals (zinc and tin), salicylates, dexamethasone, cocaine, nicotine, alcohol, alpha-adrenergic agonists, PPAR-gamma agonists, bimoclomol, geldanamycin, geranylgeranylacetone and cyclopentenone prostanoids. Compounds that suppress Hsps include quercetin (a bioflavinoid), 15-deoxyspergualin (an immunosuppressive agent) and retinoic acid. Researchers who are cognisant of the Hsp-related effects of these and other agents will be able to use them to develop new therapeutic paradigms. 相似文献
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Infections due to Staphylococcus aureus are a major cause of morbidity and mortality worldwide. Antimicrobial resistance in strains of S. aureus is a continually evolving problem, including widespread methicillin resistance in hospitals, increasing methicillin resistance in community strains, and the recent acquisition of glycopeptide resistance. New antimicrobials with activity against S. aureus have recently entered the market or are in the late stages of development. In addition, there has been significant interest in the development of novel and immune-based strategies for prevention or treatment of S. aureus infections. This review describes established and emerging therapies for S. aureus infections, and considers the safety profiles and likely impact on present treatment standards of novel agents either undergoing clinical development or emerging onto the market. 相似文献
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Woodis CB 《Journal of pharmacy practice》2010,23(6):540-547
Nearly 50 million women each year are projected to reach menopause by 2030. Many of these women will experience vasomotor symptoms such as night sweats and hot flashes as they enter the menopausal transition. Up until the release of the findings of the Women's Health Initiative (WHI) studies, women were frequently prescribed hormone therapy (HT) to alleviate bothersome and sometimes debilitating menopausal symptoms as well as to prevent osteoporosis and coronary heart disease (CHD). Although the WHI studies were the first large, randomized, controlled trials that contradicted what was historically believed about the benefits of HT in postmenopausal women, important limitations including baseline demographics of WHI participants and investigation of only one HT strength/dosage form exist. HT may be a reasonable pharmacotherapy option for the management of menopausal symptoms following complete patient evaluation by experienced clinicians. Updated recommendations addressing management of menopausal symptoms, a new HT product containing the spironolactone-analogue drospirenone (DRSP), and discontinuation methods of HT are also discussed in this review. 相似文献
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Introduction: Amyotrophic lateral sclerosis (ALS), one in a family of age-related neurodegenerative disorders, is marked by predominantly cryptogenic causes, partially elucidated pathophysiology, and elusive treatments. The challenges of ALS are illustrated by two decades of negative drug trials.Areas covered: In this article, we lay out the current understanding of disease genesis and physiology in relation to drug development in ALS, stressing important accomplishments and gaps in knowledge. We briefly consider clinical ALS, the ongoing search for biomarkers, and the latest in trial design, highlighting major recent and ongoing clinical trials; and we discuss, in a concluding section on future directions, the prion-protein hypothesis of neurodegeneration and what steps can be taken to end the drought that has characterized drug discovery in ALS.Expert opinion: Age-related neurodegenerative disorders are fast becoming major public health problems for the world’s aging populations. Several agents offer promise in the near-term, but drug development is hampered by an interrelated cycle of obstacles surrounding etiological, physiological, and biomarkers discovery. It is time for the type of government-funded, public-supported offensive on neurodegenerative disease that has been effective in other fields. 相似文献
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Knowles RG 《Current pharmaceutical design》2011,17(7):699-702
The pharmaceutical industry is interested in developing new treatments for severe asthma (SA), recognising that there is a substantial unmet clinical need in this area. However, it faces a significant set of barriers in attempting to do so, including a) problems arising from the way SA is defined, b) the heterogeneity of this condition, c) poor understanding of its aetiology, d) the absence of validated animal and tissue or cellular models, e) the need for biomarkers and experimental clinical models of severe asthma and its sub-groups, and f) the length and size of the clinical trials likely to be required to obtain approval and reimbursement. The discovery and validation of novel biomarkers and surrogates is likely to be a crucial part of meeting these challenges, and many academic groups and pharmaceutical companies working in this area are increasingly turning to pre-competitive, highly collaborative ways of working to address them. 相似文献
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Yanaka K Sugimoto K Yasuda M Asakawa H Kamezaki T Kato N Matsumaru Y Nose T 《Drugs of today (Barcelona, Spain : 1998)》2001,37(2):75-84
Stroke is the third leading cause of death in the adult population. Numerous neuroprotective agents and procedures have been developed and a new wave of therapies is now on the horizon with the potential to minimize ischemic brain damage. On the other hand, surgical treatment has also played an important role in the treatment of stroke. This article highlights recent advances in stroke treatment, including surgical and neurointerventional radiological procedures, as well as potential new therapies. (c) 2001 Prous Science. All rights reserved. 相似文献
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Cancer is the leading cause of death in the United States among people younger than 85 years, and for the first time has surpassed heart disease as the number one killer. This worrisome statistic has resulted not from an increase in the incidence of cancer, but because deaths from heart disease have dropped nearly in half while the number of cancer-related deaths has remained about the same. This fact accentuates the need for a new generation of more effective therapies for cancer. In this review, the development of new therapies will be discussed in the context of advances in nanotechnologies related to cancer detection, analysis, diagnosis, and therapeutic intervention. First, several nanoanalytical methods, such as the use of quantum dots in detection and imaging of cancer, will be described. These techniques will be essential to the process of precisely describing cancer at the level of the cell and whole organism. Second, examples of how nanotechnologies can be used in the development of new therapies will be given, including methods that might allow for more efficient and accurate drug delivery and rationally designed, targeted drugs. Finally, a new initiative--the National Cancer Institute Alliance for Nanotechnology in Cancer--will be described and discussed with respect to the scientific issues, policies, and funding. 相似文献
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目的:探讨影响更年期症状的相关因素及相对应的社区护理对策。方法:选取本院2009年1月~2010年12月本院下辖社区卫生服务中心管辖的具有更年期症状患者260例,回顾性分析影响更年期症状的相关因素及社区护理对策。结果:影响更年期症状的相关因素包括年龄、受教育程度、职业、社交活动频率等,采取社区护理后,患者症状改善率达90.76%(P〈0.05)。结论:有效综合的社区护理干预能明显改善、消除更年期症状,值得临床推广。 相似文献
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