Poly(ADP-Ribose) Polymerase-1 Inhibitors Drug Discovery, Design, and Development as Anticancer Agents from Past to Present: A Mini-Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Arwa AlGhamdi ◽  
Hanine AlMubayedh
Keyword(s):  
Anticancer Agents ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Therapeutic Approaches ◽  
Repair Mechanism ◽  
Design And Development ◽  
Cancer Treatments ◽  
New Therapeutic Approaches ◽  
Life Threatening ◽  
Cancerous Cells

Abstract: Cancer treatments are known for their life-threatening toxicities attributed to their low selectivity; hence, new therapeutic approaches are being developed as alternatives. Among those approaches is the DNA repair mechanism, where its inhibition results selectively in the death of cancerous cells. Poly(ADP-Ribose) Polymerase (PARP) is one of the enzymes involved in the repair of damaged DNA. The inhibition of PARP shows to be a promising approach for effective targeted treatment of cancer, especially in tumours with pre-existing Homologous-Repair (HR) defects (i.e., BRCA). Nicotinamide, which is one of the PARP catalytic products, was the first identified PARP inhibitor (PARPi). The first FDA-approved PARPi was Olaparib in 2014 for the treatment of BRCA mutated advanced ovarian cancer. Several clinical trials have been conducted to further improve PARPi. However, there are some concerns related to drug resistance, PARPi sensitive-tumour identification, and toxic accumulation of PARPi. This report will review the uses of PARPi, drug design and development of PARPi from past to present, current issues, and prospective plans.

scholarly journals Approach to Hemoptysis in the Modern Era

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Sébastien Gagnon ◽  
Nicholas Quigley ◽  
Hervé Dutau ◽  
Antoine Delage ◽  
Marc Fortin
Keyword(s):  
Argon Plasma Coagulation ◽  
Argon Plasma ◽  
Regenerated Cellulose ◽  
Therapeutic Approaches ◽  
Antifibrinolytic Agents ◽  
Endoscopic Techniques ◽  
New Therapeutic Approaches ◽  
Life Threatening ◽  
Diagnostic Modalities ◽  
Modern Era

Hemoptysis is a frequent manifestation of a wide variety of diseases, with mild to life-threatening presentations. The diagnostic workup and the management of severe hemoptysis are often challenging. Advances in endoscopic techniques have led to different new therapeutic approaches. Cold saline, vasoconstrictive and antifibrinolytic agents, oxidized regenerated cellulose, biocompatible glue, laser photocoagulation, argon plasma coagulation, and endobronchial stents and valves are amongst the tools available to the bronchoscopist. In this article, we review the evidence regarding the definition, etiology, diagnostic modalities, and treatment of severe hemoptysis in the modern era with emphasis on bronchoscopic techniques.

SYSTEMIC THERAPY FOR ADVANCED OVARIAN CANCER IN BRCA1 MUTATION CARRIERS – NEW THERAPEUTIC APPROACHES: RESULTS OF A PROSPECTIVE NON-RANDOMIZED MULTI-CENTER STUDY

Pharmateca ◽  
2018 ◽  
Vol 7_2018 ◽  
pp. 57-63
Author(s):  
T.V. Gorodnova () Gorodnova ◽  
A.P. Sokolenko () Sokolenko ◽  
A.O. Ivantsov () Ivantsov ◽  
Kh.B. Kotiv () Kotiv ◽  
M.G. Yakovleva () Yakovleva ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Systemic Therapy ◽  
Brca1 Mutation ◽  
Advanced Ovarian Cancer ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Mutation Carriers ◽  
Multi Center Study ◽  
Center Study

scholarly journals Potent Killing of Pseudomonas aeruginosa by an Antibody-Antibiotic Conjugate

mBio ◽  
2021 ◽  
Author(s):  
Kimberly K. Kajihara ◽  
Homer Pantua ◽  
Hilda Hernandez-Barry ◽  
Meredith Hazen ◽  
Kiran Deshmukh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Clinical Success ◽  
Therapeutic Approaches ◽  
Preclinical Stage ◽  
Content Type ◽  
New Therapeutic Approaches ◽  
Life Threatening

Antibiotic treatment of life-threatening P. aeruginosa infections is associated with low clinical success, despite the availability of antibiotics that are active in standard microbiological in vitro assays, affirming the need for new therapeutic approaches. Antibiotics often fail in the preclinical stage due to insufficient efficacy against P. aeruginosa .

scholarly journals Immunomodulation as a Therapy for Aspergillus Infection: Current Status and Future Perspectives

2018 ◽  
Vol 4 (4) ◽  
pp. 137 ◽  
Author(s):  
Chris Lauruschkat ◽  
Hermann Einsele ◽  
Juergen Loeffler
Keyword(s):  
Immune Cell ◽  
Current Knowledge ◽  
Antifungal Drugs ◽  
Current Status ◽  
Remission Induction ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Life Threatening ◽  
Broad Variety ◽  
Immunological Recovery

Invasive aspergillosis (IA) is the most serious life-threatening infectious complication of intensive remission induction chemotherapy and allogeneic stem cell transplantation in patients with a variety of hematological malignancies. Aspergillus fumigatus is the most commonly isolated species from cases of IA. Despite the various improvements that have been made with preventative strategies and the development of antifungal drugs, there is an urgent need for new therapeutic approaches that focus on strategies to boost the host’s immune response, since immunological recovery is recognized as being the major determinant of the outcome of IA. Here, we aim to summarize current knowledge about a broad variety of immunotherapeutic approaches against IA, including therapies based on the transfer of distinct immune cell populations, and the administration of cytokines and antibodies.

Targeting Stem Cells with Hyperthermia: Translational Relevance in Cancer Patients

Oncology ◽  
2020 ◽  
Vol 98 (11) ◽  
pp. 755-762 ◽  
Author(s):  
Michele Ammendola ◽  
Giuseppe Currò ◽  
Riccardo Memeo ◽  
Lucia Stella Curto ◽  
Maria Luposella ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Survival ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
Biological Features ◽  
Expert Opinions ◽  
New Therapeutic Approaches ◽  
Radiotherapy Resistance ◽  
Small Subpopulation

<b><i>Background:</i></b> Tumor recurrences or metastases remain a major hurdle in improving overall cancer survival. In anticancer therapy, some patients inevitably develop chemo-/radiotherapy resistance at some point. Cancer stem cells are the driving force of tumorigenesis, recurrences, and metastases, contributing also to the failure of some cancer treatments. <b><i>Summary:</i></b> Emergent evidence suggests that stem cell diseases are at the base of human cancers, and tumor progression and chemo-/radiotherapy resistance may be dependent on just a small subpopulation of cancer stem cells. Hyperthermia can be a strong cancer treatment, especially when combined with radio- or chemotherapy. It is a relatively safe therapy, may kill or weaken tumor cells, and significantly increases the effectiveness of other treatments. However, these mechanisms remain largely unknown. A literature search was performed using PubMed including cited English publications. The search was last conducted in December 2019. Search phrases included “stem cells,” “hyperthermia,” “cancer,” and “therapy.” Abstracts, letters, editorials, and expert opinions were not considered for the drafting of the study. <b><i>Key Message:</i></b> Our goal was to focus on and to summarize different biological features of cancer stem cells and new therapeutic approaches using hyperthermia and its potential translation to human clinical trials.

scholarly journals Neutrophil Extracellular Trap-Driven Occlusive Diseases

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2208
Author(s):  
Kursat Oguz Yaykasli ◽  
Christine Schauer ◽  
Luis E. Muñoz ◽  
Aparna Mahajan ◽  
Jasmin Knopf ◽  
...  
Keyword(s):  
Stone Formation ◽  
Neutrophil Extracellular Trap ◽  
Treatment Modalities ◽  
Pancreatic Ducts ◽  
Tubular Structures ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
The Enlightenment ◽  
Life Threatening ◽  
Initial Idea

The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various diseases. The initial idea that NETs are a pivotal defense structure was gradually amended due to several deleterious effects in consecutive investigations. NETs formation is now considered a double-edged sword. The harmful effects are not limited to the induction of inflammation by NETs remnants but also include occlusions caused by aggregated NETs (aggNETs). The latter carries the risk of occluding tubular structures like vessels or ducts and appear to be associated with the pathologies of various diseases. In addition to life-threatening vascular clogging, other occlusions include painful stone formation in the biliary system, the kidneys, the prostate, and the appendix. AggNETs are also prone to occlude the ductal system of exocrine glands, as seen in ocular glands, salivary glands, and others. Last, but not least, they also clog the pancreatic ducts in a murine model of neutrophilia. In this regard, elucidating the mechanism of NETs-dependent occlusions is of crucial importance for the development of new therapeutic approaches. Therefore, the purpose of this review is to address the putative mechanisms of NETs-associated occlusions in the pathogenesis of disease, as well as prospective treatment modalities.

scholarly journals HSP90 and HSP70: Implication in Inflammation Processes and Therapeutic Approaches for Myeloproliferative Neoplasms

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Margaux Sevin ◽  
François Girodon ◽  
Carmen Garrido ◽  
Aurélie de Thonel
Keyword(s):  
Heat Shock ◽  
Anticancer Agents ◽  
Inflammatory Responses ◽  
Myeloproliferative Neoplasms ◽  
Therapeutic Approaches ◽  
Hsp90 Inhibitors ◽  
Critical Pathway ◽  
New Therapeutic Approaches ◽  
Shock Proteins ◽  
Hsp70 Inhibitors

Myeloproliferative neoplasms (MPN) are clonal stem cell disorders that lead to the excessive production of one or more blood cell lineages. It has been reported that, in most MPN, inflammatory cytokines are frequently increased, indicating that inflammation plays a crucial role in these disorders. Heat shock proteins (HSP) are induced in response to many stressful conditions from heat shock to hypoxia and inflammation. Besides their chaperone and cytoprotective functions, HSPs are key players during inflammation, hence the term “chaperokine.” Through their chaperone activity, HSP90, a stabilizer of many oncogenes (e.g., JAK2), and HSP70, a powerful antiapoptotic chaperone, tightly regulate Nuclear Factor-kappa B signalling, a critical pathway in mediating inflammatory responses. In light of this potential, several HSP90 inhibitors have been generated as anticancer agents able to degrade oncogenes. As it turns out, however, these drugs are also potent inhibitors of the inflammatory response in various diseases. Given the chaperone potential of HSP70 and the fact that HSP90 inhibitors induce HSP70, interest in HSP70 inhibitors is also increasing. Here, we focus on the implication of HSP90 and HSP70 in inflammatory responses and on the emergence of new therapeutic approaches in MPN based on HSP inhibitors.

New therapeutic approaches for polymyositis and dermatomyositis

2011 ◽  
Vol 152 (39) ◽  
pp. 1552-1559 ◽  
Author(s):  
Katalin Dankó ◽  
Melinda Vincze
Keyword(s):  
Immunosuppressive Agents ◽  
Inflammatory Myopathy ◽  
Proximal Muscle ◽  
Therapeutic Approaches ◽  
First Line ◽  
New Therapeutic Approaches ◽  
Remission Period ◽  
Immune Mediated ◽  
Systemic Manifestations ◽  
Line Of Therapy

Inflammatory myopathies are chronic, immune-mediated diseases characterized with progressive proximal muscle weakness. They encompass a variety of syndromes with protean manifestations. The aims of therapy are to increase muscle strength, prevent the development of contractures, and to manage the systemic manifestations of the disease. This is a complex treatment which requires routine and wide knowledge. The most important task is to recognize the disease and guide the patient to immunologic center. Although the first line of therapy continues to include corticosteroids, there are a multitude of agents available for treating patients with myositis. There are several different immunosuppressive agents which may be applied alone or in combination with each other, as well as an increasing number of novel and exciting biologic agents targeting molecules participating in the pathogenesis of inflammatory myopathy. Physiotherapy and rehabilitation in the remission period may significantly improve the functional outcome of patients with these disorders. Orv. Hetil., 2011, 152, 1552–1559.

Alteraciones sistémicas y metabólicas producidas por lesión medular

2019 ◽  
Vol 1 (1) ◽  
pp. 59-75
Author(s):  
Gabriel Guízar Sahagún
Keyword(s):  
Spinal Cord ◽  
Daily Living ◽  
Autonomic Function ◽  
Clinical Presentation ◽  
Scientific Literature ◽  
International Standards ◽  
Therapeutic Approaches ◽  
Cord Injury ◽  
Life Threatening ◽  
The Impact

Besides the well-known loss of motor and sensory capabilities, people with spinal cord injury (SCI) experience a broad range of systemic and metabolic abnormalities including, among others, dysfunction of cardiovascular, respiratory, gastrointestinal, urinary, and endocrine systems. These alterations are a significant challenge for patients with SCI because such disorders severely interfere with their daily living and can be potentially life-threatening. Most of these disorders are associated with impairment of regulation of the autonomic nervous system, arising from disruption of connections between higher brain centers and the spinal cord caudal to the injured zone. Thus, the higher and more complete the lesion, the greater the autonomic dysfunction and the severity of complications.This article summarizes the medical scientific literature on key systemic and metabolic alterations derived of SCI. It provides information primarily focused on the pathophysiology and clinical presentation of these disorders, as well as some guides to prevent and alleviate such complications. Due to the impact of these alterations, this topic must be a priority and diffuse to those involved with the care of people with SCI, including the patient himself/herself. We consider that any collaborative effort should be supported, like the development of international standards, to evaluate autonomic function after SCI, as well as the development of novel therapeutic approaches.

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