scholarly journals Present and Future of Anti-Glioblastoma Therapies: A Deep Look into Molecular Dependencies/Features

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4641
Author(s):  
Hyeon Ji Kim ◽  
Do-Yeon Kim
Keyword(s):  
Standard Treatment ◽  
Patient Survival ◽  
Multiple Drug Resistance ◽  
Treatment Options ◽  
Surgical Techniques ◽  
Resistance Mechanisms ◽  
Multiple Drug ◽  
Therapeutic Approaches ◽  
Combined Radiochemotherapy ◽  
The Central Nervous System

Glioblastoma (GBM) is aggressive malignant tumor residing within the central nervous system. Although the standard treatment options, consisting of surgical resection followed by combined radiochemotherapy, have long been established for patients with GBM, the prognosis is still poor. Despite recent advances in diagnosis, surgical techniques, and therapeutic approaches, the increased patient survival after such interventions is still sub-optimal. The unique characteristics of GBM, including highly infiltrative nature, hard-to-access location (mainly due to the existence of the blood brain barrier), frequent and rapid recurrence, and multiple drug resistance mechanisms, pose challenges to the development of an effective treatment. To overcome current limitations on GBM therapy and devise ideal therapeutic strategies, efforts should focus on an improved molecular understanding of GBM pathogenesis. In this review, we summarize the molecular basis for the development and progression of GBM as well as some emerging therapeutic approaches.

scholarly journals Integrating the Human and Animal Sides of Mycoplasmas Resistance to Antimicrobials

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1216
Author(s):  
Sabine Pereyre ◽  
Florence Tardy
Keyword(s):  
One Health ◽  
Susceptibility Testing ◽  
Multiple Drug Resistance ◽  
Treatment Options ◽  
Resistance Mechanisms ◽  
Antimicrobial Treatment ◽  
Mycoplasma Species ◽  
Multiple Drug ◽  
Common Features ◽  
A Cell

Mycoplasma infections are frequent in humans, as well as in a broad range of animals. However, antimicrobial treatment options are limited, partly due to the lack of a cell wall in these peculiar bacteria. Both veterinary and human medicines are facing increasing resistance prevalence for the most commonly used drugs, despite different usage practices. To date, very few reviews have integrated knowledge on resistance to antimicrobials in humans and animals, the latest dating back to 2014. To fill this gap, we examined, in parallel, antimicrobial usage, resistance mechanisms and either phenotype or genotype-based methods for antimicrobial susceptibility testing, as well as epidemiology of resistance of the most clinically relevant human and animal mycoplasma species. This review unveiled common features and differences that need to be taken into consideration in a “One Health” perspective. Lastly, two examples of critical cases of multiple drug resistance are highlighted, namely, the human M. genitalium and the animal M. bovis species, both of which can lead to the threat of untreatable infections.

Abstract C216: Small molecule antitubulin drugs that evade multiple drug resistance mechanisms.

2011 ◽  
Author(s):  
Markos Leggas ◽  
Eleftheria Tsakalozou ◽  
Tamer Ahmed ◽  
Kuei-Ling Kuo ◽  
Jamie Horn ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Small Molecule ◽  
Multiple Drug Resistance ◽  
Resistance Mechanisms ◽  
Multiple Drug

scholarly journals Current and Future Concepts for the Treatment of Impaired Fracture Healing

2019 ◽  
Vol 20 (22) ◽  
pp. 5805 ◽  
Author(s):  
Carsten W. Schlickewei ◽  
Holger Kleinertz ◽  
Darius M. Thiesen ◽  
Konrad Mader ◽  
Matthias Priemel ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Regeneration ◽  
Treatment Options ◽  
Surgical Techniques ◽  
Therapeutic Approaches ◽  
Economic Implications ◽  
Complex Process ◽  
Number Of Patients ◽  
Evolutionarily Conserved ◽  
Future Concepts

Bone regeneration represents a complex process, of which basic biologic principles have been evolutionarily conserved over a broad range of different species. Bone represents one of few tissues that can heal without forming a fibrous scar and, as such, resembles a unique form of tissue regeneration. Despite a tremendous improvement in surgical techniques in the past decades, impaired bone regeneration including non-unions still affect a significant number of patients with fractures. As impaired bone regeneration is associated with high socio-economic implications, it is an essential clinical need to gain a full understanding of the pathophysiology and identify novel treatment approaches. This review focuses on the clinical implications of impaired bone regeneration, including currently available treatment options. Moreover, recent advances in the understanding of fracture healing are discussed, which have resulted in the identification and development of novel therapeutic approaches for affected patients.

Flavonoids overcome drug resistance to cancer chemotherapy by epigenetically modulating multiple mechanisms

2021 ◽  
Vol 21 ◽  
Author(s):  
Kenneth K.W. To ◽  
William C.S. Cho
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Chemotherapy ◽  
Animal Studies ◽  
Multiple Drug Resistance ◽  
Resistance Mechanisms ◽  
Multiple Drug ◽  
Full Potential ◽  
Cancer Proliferation ◽  
Genes Encoding

Drug resistance is the major reason accounting for the treatment failure in cancer chemotherapy. Dysregulation of the epigenetic machineries is known to induce chemoresistance. It was reported that numerous genes encoding the key mediators in cancer proliferation, apoptosis, DNA repair, and drug efflux are dysregulated in resistant cancer cells by aberrant DNA methylation. The imbalance of various enzymes catalyzing histone post-translational modifications is also known to alter chromatin configuration and regulate multiple drug resistance genes. Alteration in miRNA signature in cancer cells also gives rise to chemoresistance. Flavonoids are a large group of naturally occurring polyphenolic compounds ubiquitously found in plants, fruits, vegetables and traditional herbs. There has been an increasing research interest in the health-promoting effects of flavonoids. Flavonoids were shown to directly kill or re-sensitize resistant cancer cells to conventional anticancer drugs by epigenetic mechanisms. In this review, we summarize the current findings about the circumvention of drug resistance by flavonoids through correcting the aberrant epigenetic regulation of multiple resistance mechanisms. More investigations including the evaluation of synergistic anticancer activity, dosing sequence effect, toxicity in normal cells, and animal studies, are warranted to establish the full potential of the combination of flavonoids with conventional chemotherapeutic drugs in the treatment of cancer with drug resistance.

scholarly journals Warm antibody autoimmune hemolytic anemia

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 690-697 ◽  
Author(s):  
Theodosia A. Kalfa
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Standard Treatment ◽  
Treatment Options ◽  
Common Type ◽  
Therapeutic Approaches ◽  
Blood Disorder ◽  
Appropriate Treatment ◽  
Antiglobulin Test ◽  
Delays In Diagnosis

Abstract Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type, comprising ∼70% to 80% of all adult cases and ∼50% of pediatric cases. About half of the w-AIHA cases are called primary because no specific etiology can be found, whereas the rest are secondary to other recognizable underlying disorders. This review will focus on the postulated immunopathogenetic mechanisms in idiopathic and secondary w-AIHA and report on the rare cases of direct antiglobulin test–negative AIHA, which are even more likely to be fatal because of inherent characteristics of the causative antibodies, as well as because of delays in diagnosis and initiation of appropriate treatment. Then, the characteristics of w-AIHA associated with genetically defined immune dysregulation disorders and special considerations on its management will be discussed. Finally, the standard treatment options and newer therapeutic approaches for this chronic autoimmune blood disorder will be reviewed.

Hyaluronic acid and Regenerative medicine: New insights into the stroke therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Maryam Shahi ◽  
Daruosh Mohammadnejad ◽  
Mohammad Karimipour ◽  
Seyed Hossein Rasta ◽  
Reza Rahbarghazi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Regenerative Medicine ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Stroke Therapy ◽  
Therapeutic Approaches ◽  
Normal Tissues ◽  
Inflammatory Processes

: Stroke is known as one of very important public health problems which are related to a societal burden and tremendous economic. It has been showed, there are few therapeutic approaches in the treatment of this disease. In this regard, present therapeutic platforms aim to obtain neuroprotection, reperfusion, and neurorecovery. Among these therapies, regenerative medicine-based therapies have been appeared as new ways in stroke therapy. Hyaluronic acid (HA) is a new candidate which could be applied as regerenative medicine-based therapy in the treatment of stroke. HA is a glycosaminoglycan which is formed of repeating disaccharide units (D-glucuronic acid and N-acetyl-D-glucosamine). Multiple lines evidence demonstrated that HA has critical roles in normal tissues. It can be key players in different physiological and pathophysiological conditions such as water homeostasis, multiple drug resistance, inflammatory processes, tumorigenesis, angiogenesis, and changed viscoelasticity of extracellular matrix. HA has very important physicochemical properties (i.e., availability of reactive functional groups and its solubility which makes it as a biocompatible material for applying in the regenerative medicine. Given that HA-based bioscaffolds and biomaterials do not induce inflammation or allergies and are hydrophilic which have introduced them as soft tissue fillers and injectable dermal. Several studies indicated that HA could be employed as new therapeutic candidate in the treatment of stroke. These studies documented that HA and HA-based therapies exert their pharmacology effects via affecting on stroke-related processes. Herein, we have summarized the role of extracellular matrix in stroke pathogenesis. Moreover, we highlighted the HA-based therapies in the treatment of stroke.

scholarly journals Overcoming PARP inhibitor resistance in ovarian cancer: what are the most promising strategies?

2020 ◽  
Vol 302 (5) ◽  
pp. 1087-1102
Author(s):  
Daniel Martin Klotz ◽  
Pauline Wimberger
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Multiple Drug Resistance ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Resistance Mechanisms ◽  
Therapeutic Options ◽  
Parp Inhibition ◽  
Multiple Drug ◽  
Platinum Based Chemotherapy

Abstract Purpose Ovarian cancer is the most lethal gynaecological malignancy. Despite the introduction of bevacizumab, standard chemotherapy has remained largely unchanged and the vast majority of patients will relapse within the first two years of diagnosis. However, results from recent clinical trials demonstrating clinical benefits of PARP inhibitor treatment are rapidly changing therapeutic options for many patients with ovarian cancer. Methods Given the introduction of new therapeutic options in the treatment of ovarian cancer, we critically review key clinical trials, areas of scientific research and its clinical relevance. Results Most notably, patients with BRCA1/2 mutant ovarian cancer benefit from maintenance treatment with PARP inhibitors after (complete or partial) response to platinum-based chemotherapy. Here, we discuss the mechanism of PARP inhibition, multiple drug resistance mechanisms, including BRCA reverse mutations, altered PARP expression, changes in DNA repair pathways, kinase activation and additional drug targets that may augment PARP inhibition. Conclusion Although the use of PARP inhibitors is a huge step forward, it is apparent that patients, both with and without BRCA-mutant ovarian cancer, will eventually become resistant to PARP inhibitors. Therefore, novel combination therapies may enhance PARP inhibitor efficacy and overcome resistance mechanisms.

scholarly journals Overcoming multiple drug resistance mechanisms in medulloblastoma

2014 ◽  
Vol 2 (1) ◽  
Author(s):  
Ramadhan T Othman ◽  
Ioanna Kimishi ◽  
Tracey D Bradshaw ◽  
Lisa CD Storer ◽  
Andrey Korshunov ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Resistance Mechanisms ◽  
Multiple Drug
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