Search results for "Targeted Therapy"
showing 10 items of 297 documents
Therapeutic targets for overactive bladder other than smooth muscle
2015
For a long time, our concepts of regulation of urinary bladder function in health and disease as well as of the target structures of therapeutics have focused on detrusor smooth muscle cells. However, other structures including urothelium, afferent nerves and bladder blood vessels may also be important in pathophysiology and its treatment.Based on a selective review of literature, we discuss the role of urothelium, afferent nerve fibers and bladder blood vessels in bladder pathophysiology and as targets for treatment.There is solid evidence now that multiple anatomical structures within the urinary bladder contribute to the regulation of its function and hence may be targets for established…
Fatal Tumour Lysis Syndrome Induced by Brigatinib in a Lung Adenocarcinoma Patient Treated With Sequential ALK Inhibitors: A Case Report
2021
Tumour lysis syndrome (TLS) represents a group of fatal metabolic derangements resulting from the rapid breakdown of tumour cells. TLS typically occurs soon after the administration of chemotherapy in haematologic malignancies but is rarely observed in solid tumours. Here, we report a case of brigatinib-induced TLS after treatment with sequential anaplastic lymphoma kinase (ALK) inhibitors in a patient with advanced ALK-rearranged lung adenocarcinoma. The patient was treated sequentially with crizotinib, alectinib, and ensartinib. High-throughput molecular profiling after disease progression indicated that brigatinib may overcome ALK resistance mutations, so the patient was administered bri…
Manipulation of glycolysis in malignant tumors: fantasy or therapy?
2009
After Warburg stated his hypothesis on tumor cell metabolism about 80 years ago, the field of carbohydrate metabolism of cancer cells and solid tumors is experiencing a boom for the past few years. Numerous studies have been focused on the characteristics of cancer metabolism and its accessibility to novel therapeutic interventions. Malignant transformation is associated with an increase in glycolytic flux, mainly caused by an upregulation of numerous glycolysis-related genes in the majority of human cancers. As a consequence of these alterations, tumor cells are producing lactate at higher levels compared to non-malignant tissue, even in the presence of oxygen, a phenomenon termed “aerobic…
Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours
2019
BACKGROUND: Interferon-induced expression of programmed cell death ligands (PD-L1/PD-L2) may sustain tumour immuneevasion. Patients featuring MET amplification, a genetic lesion driving transformation, may benefit from anti-MET treatment. We explored if MET-targeted therapy interferes with Interferon-gamma modulation of PD-L1/PD-L2 in MET-amplified tumours.METHODS: PD-L1/PD-L2 expression and signalling pathways downstream of MET or Interferon-gamma were analysed in MET-amplified tumour cell lines and in patient-derived tumour organoids, in basal condition, upon Interferon-gamma stimulation, and after anti-MET therapy.RESULTS: PD-L1 and PD-L2 were upregulated in MET-amplified tumour cells up…
Neutrophil Extracellular Traps as a Drug Target to Counteract Chronic and Acute Inflammation
2019
Neutrophil extracellular traps (NET), extruded decondensated chromatin entangled with neutrophil proteases, have been first identified in neutrophils stimulated with bacteria or phorbol myristate acetate (PMA) via activation of NADPH oxidase and the generation of reactive oxygen species. Although the first findings demonstrated the beneficial role of NET formation by trapping the bacteria and limiting their dissemination, numerous studies in the recent decade revealed the multifunctional aspects of NET formation which manifests itself not only in the context of anti-microbial effect but also as a pathological trigger. Uncontrolled and exaggerated NET formation or inability to digest and rem…
Multi-output Model with Box-Jenkins Operators of Quadratic Indices for Prediction of Malaria and Cancer Inhibitors Targeting Ubiquitin- Proteasome Pa…
2016
The ubiquitin-proteasome pathway (UPP) is the primary degradation system of short-lived regulatory proteins. Cellular processes such as the cell cycle, signal transduction, gene expression, DNA repair and apoptosis are regulated by this UPP and dysfunctions in this system have important implications in the development of cancer, neurodegenerative, cardiac and other human pathologies. UPP seems also to be very important in the function of eukaryote cells of the human parasites like Plasmodium falciparum, the causal agent of the neglected disease Malaria. Hence, the UPP could be considered as an attractive target for the development of compounds with Anti-Malarial or Anti-cancer properties. R…
An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.
2016
Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub…
Translational Approaches In Cardiovascular Diseases by Omics.
2017
Cardiovascular diseases are among the leading causes of morbidity and mortality. Despite scientific and technical progress in risk prediction, diagnostics, prognostication and therapy of cardiovascular pathologies, new biomarkers and therapeutic targets remain the subject of intense research to reduce the burden of these diseases. High throughput analyses, termed "omics", are a promising avenue of research. These recently developed technical fields have revolutionized biological and medical research in a very short time. By their interdisciplinary nature, these new methods have already provided a wide vision of cell and tissue pathways and functions. Here, we review how these methods can he…
Does large NGS panel analysed using exome tumour sequencing improve the management of advanced non-small-cell lung cancers?
2020
Abstract Introduction Non-small-cell lung cancer (NSCLC) is one of the most common and deadly cancers. Several molecular drivers of oncogene addiction are now known to be strong predictive biomarkers for target therapies. Advances in large Next Generation Sequencing (LNGS) have improved the ability to detect potentially targetable mutations. However, the integration of LNGS into clinical management in an individualized manner remains challenging. Methods In this single-center observational study we included all patients with advanced NSCLC who underwent LNGS. Somatic and germline exome analysis was performed with a restriction on 323 cancer related genes. Variants were classified and Molecu…
Extracellular Heat Shock Proteins as Therapeutic Targets and Biomarkers in Fibrosing Interstitial Lung Diseases.
2021
Interstitial lung diseases (ILDs) include a large number of diseases and causes with variable outcomes often associated with progressive fibrosis. Although each of the individual fibrosing ILDs are rare, collectively, they affect a considerable number of patients, representing a significant burden of disease. Idiopathic pulmonary fibrosis (IPF) is the typical chronic fibrosing ILD associated with progressive decline in lung. Other fibrosing ILDs are often associated with connective tissues diseases, including rheumatoid arthritis-ILD (RA-ILD) and systemic sclerosis-associated ILD (SSc-ILD), or environmental/drug exposure. Given the vast number of progressive fibrosing ILDs and the dispariti…