Search results for " Pd"
showing 10 items of 651 documents
Primary and metastatic brain cancer genomics and emerging biomarkers for immunomodulatory cancer treatment
2018
Abstract: Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has revealed to further increase the clinical benefit observed with single agent, even at cost of higher toxicity. Since the brain is an immunological specialized area it's crucial to establish the specific composition of the brain tumors' micro environment in order to predict the potential activit…
Abilities of berberine and chemically modified berberines to interact with metformin and inhibit proliferation of pancreatic cancer cells.
2019
Abstract Pancreatic cancer is devastating cancer worldwide with few if any truly effective therapies. Pancreatic cancer has an increasing incidence and may become the second leading cause of death from cancer. Novel, more effective therapeutic approaches are needed as pancreatic cancer patients usually survive for less than a year after being diagnosed. Control of blood sugar levels by the prescription drug metformin in diseases such as diabetes mellitus has been examined in association with pancreatic cancer. While the clinical trials remain inconclusive, there is hope that certain diets and medications may affect positively the outcomes of patients with pancreatic and other cancers. Other…
Interrelationship between miRNA and splicing factors in pancreatic ductal adenocarcinoma
2021
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of diagnosis at late stage and inherent/acquired chemoresistance. Recent advances in genomic profiling and biology of this disease have not yet been translated to a relevant improvement in terms of disease management and patient’s survival. However, new possibilities for treatment may emerge from studies on key epigenetic factors. Deregulation of microRNA (miRNA) dependent gene expression and mRNA splicing are epigenetic processes that modulate the protein repertoire at the transcriptional level. These processes affect all aspects of PDAC pathogenesis and have great potential to unravel new therapeutic targets…
Type 5 phosphodiesterase (PDE5) and the vascular tree: from embryogenesis to aging and disease
2020
Highlights • Vascular development depends on the timely differentiation of endothelial and smooth muscle cells, that mutually influence their developmental fate. • Endothelial and vascular smooth muscle cell (VSMC) compartments can mutually influence cell and tissue modifications during vascular aging and in vascular disease. • Keeping in mind that PDE5 is mainly expressed in VSMCs, we surveyed the literature on the role of PDE5 in vascular development, aging and disease. • Although most results have been obtained by PDE5 pharmacological inhibition, no data are available, to date, on vascular development, aging or disease following PDE5 genetic ablation.
Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy.
2021
Purpose To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME). Cases and Methods Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intra-arterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel nu…
Retrospective Analysis of Checkpoint Inhibitor Therapy-Associated Cases of Bullous Pemphigoid From Six German Dermatology Centers
2021
Immune-related adverse events (irAEs) are a class-effect of checkpoint inhibitors (CIs). The development of a Bullous pemphigoid (BP)-like blistering disease, driven by autoantibodies against the hemidesmosomal protein BP180, is a potentially serious irAE whose incidence seems to be increasing. We therefore set out to characterize the clinical and (immuno)histopathological features and treatment responses of cases of BP which developed during or after CI therapy collated in six German tertiary referral centers between 2014 and 2018. We identified twelve cases of BP which emerged during and/or after CI therapy. The time interval between the initiation of CI therapy and the diagnosis of BP wa…
Conf-VLKA: A structure-based revisitation of the Virtual Lock-and-key Approach
2016
In a previous work, we developed the in house Virtual Lock-and-Key Approach (VLKA) in order to evaluate target assignment starting from molecular descriptors calculated on known inhibitors used as an information source. This protocol was able to predict the correct biological target for the whole dataset with a good degree of reliability (80%), and proved experimentally, which was useful for the target fishing of unknown compounds. In this paper, we tried to remodel the previous in house developed VLKA in a more sophisticated one in order to evaluate the influence of 3D conformation of ligands on the accuracy of the prediction. We applied the same previous algorithm of scoring and ranking b…
Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator
2017
17 páginas, 7 figuras, 1 tabla
Coordination of the biliverdin D-ring in bacteriophytochromes.
2018
Phytochrome proteins translate light into biochemical signals in plants, fungi and microorganisms. Light cues are absorbed by a bilin chromophore, leading to an isomerization and a rotation of the D-ring. This relays the signal to the protein matrix. A set of amino acids, which is conserved across the phytochrome superfamily, holds the chromophore in the binding pocket. However, the functional role of many of these amino acids is not yet understood. Here, we investigate the hydrogen bonding network which surrounds the D-ring of the chromophore in the resting (Pr) state. We use UV/vis spectroscopy, infrared absorption spectroscopy and X-ray crystallography to compare the photosensory domains…
Monoclonal antibodies for the treatment of non-hematological tumors: a safety review
2018
Introduction: The introduction of monoclonal antibodies (moAbs) into clinical practice revolutionized the treatment strategies in several solid tumors. These agents differ from cytotoxic chemotherapy for their mechanism of action and toxicity. By targeting specific antigens present on healthy cells and modulating immune system activity, these biological drugs are able to generate a wide spectrum of peculiar adverse events that can negatively impact on patients' quality of life. Areas covered: In this review, the main side effects associated with the use of moAbs have been described to show their incidence and current management strategies, which may drive clinicians in their daily practice.…