Search results for "death"
showing 10 items of 1744 documents
Prediction of Early Death and Severe Infections during Novel Agent-Based Induction Therapy in Newly-Diagnosed Multiple Myeloma: An Intergroup Analysi…
2021
Abstract Background: During the past decade, prognostic tools and outcomes of patients with newly-diagnosed multiple myeloma (NDMM) markedly improved. Data from clinical trials evaluating early morbidity and mortality including patients with transplant-eligible NDMM treated with novel agents are scarce. Thus, we aimed to analyze early morbidity and mortality in this patient cohort, devise and validate a predictive score to identify patients at risk. Patients and methods: Between July 2005 and January 2018, 1333 patients with transplant-eligible NDMM from three subsequent phase III trials, HD4, MM5 and HD6 from the German-speaking Myeloma Multicenter Group (GMMG), received a novel agent-base…
Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—A trial-level meta-analysis in PD-L1 selecte…
2021
BACKGROUND: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clinical setting. METHODS: We performed a systematic review and finally included eleven first-line randomized controlled trials to compare efficacy and safety outcomes among first-line IO treatment strategies versus standard platinum-based chemotherapy (CT) according to PD-L1 expression level (<1%, 1–49%, ≥50%). Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), over…
Death by Facial and Skull Injuries of a Motorcyclist Wearing a Full-Face Helmet: Case Report and Literature Review
2016
We describe a case of death by facial and skull fractures with brain injuries of a motorcyclist wearing a full-face helmet. A 40-year-old man driving a high-powered motorcycle crashed violently into the rear of a stopped car. The main results from the autopsy revealed the deformation of the left orbito-zygomatic and fronto-temporoparietal regions corresponding to bone fractures with laceration at the left temporal lobe. The CT scan of the helmet revealed the detachment of the energy-absorbing liner. Moreover an impact speed of 93 Km/h resulted from the analysis of accident dynamics. We analysed the literature regarding the effectiveness of full-face helmets in reducing the risk of fatality …
miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance
2015
AbstractThe ErbB tyrosine kinase receptor family has been shown to have an important role in tumorigenesis, and the expression of its receptor members is frequently deregulated in many types of solid tumors. Various drugs targeting these receptors have been approved for cancer treatment. Particularly, in breast cancer, anti-Her2/EGFR molecules represent the standard therapy for Her2-positive malignancies. However, in a number of cases, the tumor relapses or progresses thus suggesting that not all cancer cells have been targeted. One possibility is that a subset of cells capable of regenerating the tumor, such as cancer stem cells (CSCs), may not respond to these therapeutic agents. Accumula…
MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate
2019
Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…
Endoplasmic Reticulum Stress Inhibition Protects against Excitotoxic Neuronal Injury in the Rat Brain
2007
Elevated brain glutamate with activation of neuronal glutamate receptors accompanies neurological disorders, such as epilepsy and brain trauma. However, the mechanisms by which excitotoxicity triggers neuronal injury are not fully understood. We have studied the glutamate receptor agonist kainic acid (KA) inducing seizures and excitotoxic cell death. KA caused the disintegration of the endoplasmic reticulum (ER) membrane in hippocampal neurons and ER stress with the activation of the ER proteins Bip, Chop, and caspase-12. Salubrinal, inhibiting eIF2α (eukaryotic translation initiation factor 2 subunit α) dephosphorylation, significantly reduced KA-induced ER stress and neuronal deathin vivo…
Asymptomatic ventricular pre-excitation in children.
2009
ASYMPTOMATIC VENTRICULAR PREEXCITATION IN CHILDREN OBJECTIVE: This retrospective study was planned for a good risk assessment of asymptomatic patients affected by ventricular pre-excitation. METHODS: From 1985 to 2007, 124 patients with an atrioventricular pathway (electrocardiographic signs of ventricular pre-excitation) were admitted to our cardiology division. The average age was 7 years (range 1 month to 18 years). The mean follow-up period in the whole population of patients was 4.2 years (range 1-13 years). Four patients were lost during the follow-up. During this period, all patients remained in good health. In all of them, we performed a Holter evaluation every year. An intermittent…
Mapping palliative care provision in European prisons
2021
ObjectivesPrison populations around the world are ageing and numbers are rising, leading to greater demand for palliative care for prisoners approaching the end of life. This paper reports a survey that was undertaken by the European Association for Palliative Care Task Force on mapping palliative care provision for prisoners in Europe. The Task Force was established to begin to address the gap in research knowledge by exploring prison systems and care provision across different countries.MethodsThe survey, developed by the Task Force Steering Committee, consisted of 40 questions in six sections. It was completed through online searches; only data that were publicly available on the interne…
An in vitro procedure for evaluation of early stage oxidative stress in an established fish cell line applied to investigation of PHAH and pesticide …
2004
Oxidative stress by increased production of reactive oxygen species such as superoxide has been implicated in the toxicity of PCB's and non-target toxicity of many pesticides. We report the development of a microplate-based method for determination of early stage oxidative stress using an established cell line (EPC) from a skin tumour of carp Cyprinus carpio L. and 2',7'-dichlorodihydrofluorescein diacetate (H(2)-DCFDA) as a fluorescent probe for detection of reactive oxygen species (ROS) formation. Sublethal concentrations of the herbicide Paraquat, an established redox cycling agent and a crude PCB mixture, Arochlor 1254 elicited a linear increase in ROS formation over 2 h exposure which …
Neuroglobin and cytoglobin overexpression protects human SH-SY5Y neuroblastoma cells against oxidative stress-induced cell death
2006
Although reactive oxygen species (ROS) at physiological concentrations are required for normal cell function, excessive production of ROS is detrimental to cells. Neuroglobin and cytoglobin are two globins, whose functions are still a matter of debate. A potential role in the detoxification of ROS is suggested. The influence of neuroglobin and cytoglobin on cell death after oxidative stress in human neuroblastoma SH-SY5Y cells was evaluated. Exposure of SH-SY5Y cells to paraquat or H(2)O(2) resulted in a concentration- and time-dependent induction of apoptotic and necrotic cell death. H(2)O(2) was 16 times more potent to induce cell death as compared to paraquat. SH-SY5Y cells transfected w…