Present and future challanges in the treatment of haemophilia: a clinician's perspective.
Ontology highlight
ABSTRACT:
SUBMITTER: Mannucci PM
PROVIDER: S-EPMC3853988 | biostudies-literature | 2013 Sep
REPOSITORIES: biostudies-literature
Publications
Present and future challanges in the treatment of haemophilia: a clinician's perspective.
Mannucci Pier Mannuccio PM Franchini Massimo M
Blood transfusion = Trasfusione del sangue 20130901
Similar Datasets
Project description:Polo-like kinase 1 (PLK1) is the principle member of the well conserved serine/threonine kinase family. PLK1 has a key role in the progression of mitosis and recent evidence suggest its important involvement in regulating the G2/M checkpoint, in DNA damage and replication stress response, and in cell death pathways. PLK1 expression is tightly spatially and temporally regulated to ensure its nuclear activation at the late S-phase, until the peak of expression at the G2/M-phase. Recently, new roles of PLK1 have been reported in literature on its implication in the regulation of inflammation and immunological responses. All these biological processes are altered in tumors and, considering that PLK1 is often found overexpressed in several tumor types, its targeting has emerged as a promising anti-cancer therapeutic strategy. In this review, we will summarize the evidence suggesting the role of PLK1 in response to DNA damage, including DNA repair, cell cycle progression, epithelial to mesenchymal transition, cell death pathways and cancer-related immunity. An update of PLK1 inhibitors currently investigated in preclinical and clinical studies, in monotherapy and in combination with existing chemotherapeutic drugs and targeted therapies will be discussed.
| S-EPMC9201472 | biostudies-literature
Project description:Retinoblastoma (RB) is the most common malignant intraocular tumor in children. In the last decade, basic research has led to a better understanding of events after two hits in RB susceptibility gene (RB1), molecular mechanism of tumor growth, the cell of origin of RB, etc. This would pave way to identify biomarkers and molecular targeted therapy for better treatment option in the future. Furthermore, improvement in molecular techniques has led to enhanced diagnostic methods for early diagnosis, genetic counseling, and prevention of the disease. This review will help to understand the essence of basic research work conducted in recent times and its implication in the management of RB in the future.
| S-EPMC4966369 | biostudies-literature
Project description:Modulation of the tumor microenvironment is becoming an increasingly popular research topic in the field of immunotherapy, and studies regarding immune checkpoint blockades and cancer immunotherapy have pushed cancer immunotherapy to a climax. Simultaneously, the manipulation of the immune regulatory pathway can create an effective immunotherapy strategy; however, the tumor microenvironment serves an important role in suppressing the antitumor immunity by its significant heterogeneity. A number of patients with cancer do not have a good response to monotherapy approaches; therefore, combination strategies are required to achieve optimal therapeutic benefits. Targeting the tumor microenvironment may provide a novel strategy for immunotherapy, break down the resistance of conventional cancer therapy and produce the foundation for personalized precision medicine. The present review summarized the research regarding cancer immunotherapy from the perspective of how the tumor microenvironment affects the immune response, with the aim of proposing a novel strategy for cancer immunotherapy and combination therapy.
| S-EPMC6126324 | biostudies-literature
Project description:With the discovery of novel diseases and pathways, as well as a new outlook on certain existing diseases, cellular trafficking disorders attract a great deal of interest and focus. Understanding the function of genes and their products in protein and lipid synthesis, cargo sorting, packaging, and delivery has allowed us to appreciate the intricate pathophysiology of these biological processes at the molecular level and the multi-system disease manifestations of these disorders. This article focuses primarily on lymphocyte intracellular trafficking diseases from a clinician's perspective. Familial hemophagocytic lymphohistiocytosis is the prototypical disease of abnormal vesicular transport in the lymphocytes. In this review, we highlight other mechanisms involved in cellular trafficking, including membrane contact sites, autophagy, and abnormalities of cytoskeletal structures affecting the immune cell function, based on a newer classification system, along with management aspects of these conditions.
| S-EPMC9885010 | biostudies-literature
Project description:Colon cancer is a common preventable cancer. With the adoption of widespread colon cancer screening in the developed countries, the incidence and mortality of colon cancer have decreased in the targeted population. But unfortunately, the incidence and mortality of colorectal cancer (CRC) have been increasing over the last 25 years in the young adults below the age of 50. There is disparity in benefit, i.e. reduction in risk of death between right-sided and left-sided colon cancer by screening colonoscopy. The reason could be multifactorial and various measures have been taken to decrease this disparity. Although most of the screened populations are average risk individuals, a minority of the population have various risk factors for developing colon cancer and need to follow specific colon cancer screening guidelines. Gene mutations (adenomatous polyposis coli (APC), deleted in colon cancer (DCC), K-ras, p53, B-Raf proto-oncogene serine/threonine kinase (BRAF), mismatch repair genes) and microsatellite instability lead to the development of colon cancer. Although various non-invasive methods of colon cancer screening are now available, colonoscopy remains the gold standard of colon cancer screening and adenoma detection rate is now being used as the quality metrics in screening colonoscopy. Although Multi-Society Task Force (MSTF) and American College of Physicians (ACP) recommend initiating screening colonoscopy at age 50 years in all individuals except African Americans who should begin screening colonoscopy at age 45 years, the American Cancer Society (ACS) recommends initiating screening colonoscopy at age 45 years in all individuals irrespective of race and ethnicity. Low-volume split-dose prep has been found to be as effective as high-volume split-dose prep and more tolerable to patients with increased compliance. Boston bowel preparation scale is recommended to measure the quality of colon cleansing. CRC is curative if it is diagnosed at an early stage but various palliative treatment options (endoscopic, oncologic and surgical) are available in advanced stages of this cancer. Adequate number of lymph node assessment during surgery is essential in accurate staging of CRC. Checkpoint inhibitors have been found to have dramatic response and durable clinical benefit in dMMR/MSI-H metastatic CRC. Different genetic and immune-oncologic research trials are ongoing for early detection and better management of CRC.
| S-EPMC7011914 | biostudies-literature
Project description:Stroke remains one of the leading causes of mortality and long-term and permanent disability worldwide despite technological innovations and developments in pharmacotherapy. In the last few decades, the growing data have evidenced the role of the circadian system in brain vulnerability to damage, the development and evolution of stroke, and short-term and long-term recovery. On the other hand, the stroke itself can affect the circadian system via direct injury of specific brain structures involved in circadian regulation (i.e., hypothalamus, retinohypothalamic tracts, etc.) and impairment of endogenous regulatory mechanisms, metabolic derangement, and a neurogenic inflammatory response in acute stroke. Moreover, the disruption of circadian rhythms can occur or exacerbate as a result of exogenous factors related to hospitalization itself, the conditions in the intensive care unit and the ward (light, noise, etc.), medication (sedatives and hypnotics), and loss of external factors entraining the circadian rhythms. In the acute phase of stroke, patients demonstrate abnormal circadian variations in circadian biomarkers (melatonin, cortisol), core body temperature, and rest-activity patterns. The approaches aimed at the restoration of disrupted circadian patterns include pharmacological (melatonin supplementation) and non-medication (bright light therapy, shifting feeding schedules, etc.) interventions; however, their effects on short- and long-term recovery after stroke are not well understood.
| S-EPMC10209385 | biostudies-literature
Project description:The discovery that ultrasound waves could be focused inside the skull and heated to high temperatures at a focal point goes back to 1944. However, because the skull causes the ultrasound waves to attenuate and scatter, it was believed that application of this technology would be difficult, and that it would be impossible to use this approach in the surgical treatment of intracranial diseases. Eventually, magnetic resonance image guided focused ultrasound (MRgFUS) surgery began being used to treat uterine fibroids, breast cancer and bone metastasis and locally confined prostate cancer. In the first ten years of the 21st century, new developments in this technology have been achieved, broadening the scope of practical application, and treatment is now being performed in various countries around the world. In 2011, third-generation transcranial focused ultrasound made it possible to use thermocoagulation and create intracranial lesions measuring 2 to 6 mm in diameter with a precision of around 1 mm. It was also possible to produce MR images which relay information of temperature changes in real time, enabling a shift from reversible test heating to irreversible therapeutic heating. This gave rise to the possibility of a minimally-invasive treatment with outcomes similar to those of conventional brain surgery. This method is paving the way to a new future not only in functional neurosurgery, but in cranial neurosurgery targeting conditions such as epilepsy and brain tumors, among others. In this paper, we describe the current state and future outlook of magnetic resonance image guided focused ultrasound, which uses computed tomography (CT) bone images in combination with MRI monitoring of brain temperature.
| S-EPMC5566697 | biostudies-other
Project description:Obesity now presents one of the biggest health problems of our times. Diet and exercise are best for both prevention and treatment; unfortunately, both require much discipline and are difficult to maintain. Medications offer a possible adjunct, but their effect is modest, they are limited by side effects, and the weight loss lasts only as long as the drug is being taken, since as soon as treatment is stopped, the weight is regained. Sibutramine, a sympathomimetic medication which was available for long-term treatment, is the most recent of the drugs to be withdrawn from the market due to side effects; in this case it was an increased risk of cardiovascular events. This paper reviews those medications which are available for treatment of obesity, including many of those recently taken off the market. It also discusses some of the newer treatments that are currently being investigated.
| S-EPMC3038640 | biostudies-literature
Project description:Coronary artery disease (CAD) is the major cause of fatality and disability among all cardiovascular diseases (CVD). Intricate interactions of genes and environment dictate the outcomes of CAD. Technological advances in the different fields of genetics including linkage studies (LS), candidate gene studies (CGS) and genome-wide association studies (GWA studies) have augmented the knowledge of pathogenesis of CAD. LS were more successful in identifying genetic variants among monogenic disease. GWA studies were relatively popular in identification of variation in polygenic disease. Until now, GWA studies recognized about 50 loci determining around 6% of the heritability in CAD. Clinical utility of the above knowledge would result in better CAD management, but validation of the variants in native population is warranted for active adoption into the clinic. The major aim of this review is to provide an adequate perspective of our current understanding and advances of genetics in CAD.
| S-EPMC4310966 | biostudies-literature
Project description:Cholangiocarcinoma (CCA) is an orphan cancer with limited understanding of its genetic and genomic pathogenesis. Typically, it is highly treatment-refractory and patient outcome is dismal. Currently, there are no approved therapeutics for CCA and surgical resection remains the only option with curative intent. Clinical trials are currently being performed in a mixed cohort of biliary tract cancers that includes intrahepatic CCA, extrahepatic/perihilar CCA, distal extrahepatic CCA, gallbladder carcinoma and, in rare cases, even pancreatic cancers. Today, clinical trials fail primarily because they are underpowered mixed cohorts and designed without intent to enrich for markers to optimize success for targeted therapy. This review aims to emphasize current clinical attempts for targeted therapy of CCA, as well as highlight promising new candidate pathways revealed by translational genomics.
| S-EPMC3997260 | biostudies-literature