scholarly journals External Basic Hyperthermia Devices for Preclinical Studies in Small Animals

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4628 ◽  
Author(s):  
Marjolein I. Priester ◽  
Sergio Curto ◽  
Gerard C. van Rhoon ◽  
Timo L. M. ten Hagen
Keyword(s):  
Solid Tumor ◽  
Low Cost ◽  
Treatment Strategies ◽  
Small Animals ◽  
Preclinical Studies ◽  
Research Groups ◽  
Tumor Treatment ◽  
Preclinical Testing ◽  
Mild Hyperthermia ◽  
New Treatment

Preclinical studies have shown that application of mild hyperthermia (40–43 °C) is a promising adjuvant to solid tumor treatment. To improve preclinical testing, enhance reproducibility, and allow comparison of the obtained results, it is crucial to have standardization of the available methods. Reproducibility of methods in and between research groups on the same techniques is crucial to have a better prediction of the clinical outcome and to improve new treatment strategies (for instance with heat-sensitive nanoparticles). Here we provide a preclinically oriented review on the use and applicability of basic hyperthermia systems available for solid tumor thermal treatment in small animals. The complexity of these techniques ranges from a simple, low-cost water bath approach, irradiation with light or lasers, to advanced ultrasound and capacitive heating devices.

scholarly journals Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5146
Author(s):  
Marjolein I. Priester ◽  
Sergio Curto ◽  
Ann L. B. Seynhaeve ◽  
Anderson Cruz Perdomo ◽  
Mohamadreza Amin ◽  
...  
Keyword(s):  
Electric Heating ◽  
Microwave Antenna ◽  
Small Animals ◽  
Preclinical Studies ◽  
High Resolution Imaging ◽  
Mild Hyperthermia ◽  
Resolution Imaging ◽  
Triggered Drug Release ◽  
Longitudinal Imaging ◽  
Insight Into

This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have confirmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and ensuing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave antenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.

scholarly journals Pharmacological Modulation of Toll-Like Receptors in Brain Disorders

2021 ◽  
Author(s):  
Tahani K. Alshammari ◽  
Nouf M. Alrasheed ◽  
Lina Alhushan ◽  
Reema Alhoutah ◽  
Anfal F. Bin Dayel ◽  
...  
Keyword(s):  
Common Factor ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Resistance Mechanisms ◽  
Preclinical Studies ◽  
Brain Disorders ◽  
Toll Like Receptors ◽  
Knowledge Gaps ◽  
Considerable Evidence ◽  
New Treatment

The knowledge regarding pathological and treatment resistance mechanisms involved in the pathology of complex brain disorders is far from understood. The neuroinflammation hypothesis of psychiatric, neurological, and neurodegenerative diseases is well-acknowledged. However, this hypothesis is far from understood. Toll-like receptors (TLRs) family is an innate immunity molecule implicated in neuroinflammation in complex brain disorders. This chapter reviews considerable evidence indicating that activation of endotoxins such as lipopolysaccharide is a common factor. Additionally, we report clinical and preclinical studies highlighting the link between lipopolysaccharide, TLRs, and different types of brain disorders. Also, we review the current pharmacological modulations of TLRs. Hoping we would help in filling our knowledge gaps and highlight potential links to tackle new angles in managing complex brain disorders. This chapter’s primary goal is to encourage scientists and researchers to conduct future studies characterizing the nature of endotoxin activation of TLRs in complex brain disorders, filling our knowledge gaps, and finding new treatment strategies.

Clinical Drug Development for the Treatment of Pulmonary Arterial Hypertension: Collaboration With the Pharmaceutical Industry and Regulatory Agencies

2010 ◽  
Vol 9 (4) ◽  
pp. 214-219
Author(s):  
Robyn J. Barst
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Drug Development ◽  
Phase 1 ◽  
Preclinical Studies ◽  
Phase 2 ◽  
Phase 3 ◽  
Preclinical Testing ◽  
New Drug ◽  
Pulmonary Arterial

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?

Humoral Immunity in Heart Failure

2019 ◽  
Vol 19 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Amrita Sarkar ◽  
Khadija Rafiq
Keyword(s):  
Heart Failure ◽  
Humoral Immunity ◽  
Treatment Strategies ◽  
Pathophysiological Mechanism ◽  
Peripheral Vascular ◽  
Cardiac Inflammation ◽  
Humoral Immune ◽  
Humoral Immune System ◽  
New Treatment ◽  
Immunity Function

Cardiovascular Disease (CVD) is a class of diseases that involve disorders of heart and blood vessels, including hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, which finally lead to Heart Failure (HF). There are several treatments available all over the world, but still, CVD and heart failure became the number one problem causing death every year worldwide. Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Cardiac inflammation is a major pathophysiological mechanism operating in the failing heart, regardless of HF aetiology. Disturbances of the cellular and humoral immune system are frequently observed in heart failure. This review describes how B-cells play a specific role in the heart failure states. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the humoral immunity function are essential and may suggest potential new treatment strategies.

scholarly journals Cardiooncology—dealing with modern drug treatment, long-term complications, and cancer survivorship

2021 ◽  
Author(s):  
Claudia de Wall ◽  
Johann Bauersachs ◽  
Dominik Berliner
Keyword(s):  
Side Effects ◽  
Checkpoint Inhibitors ◽  
Heart Diseases ◽  
Tumor Therapy ◽  
Treatment Strategies ◽  
Tumor Treatment ◽  
Cardiac Side Effects ◽  
Cardiovascular Side Effects ◽  
Modern Drug

AbstractModern treatment strategies have improved prognosis and survival of patients with malignant diseases. The key components of tumor treatment are conventional chemotherapy, radiotherapy, targeted therapies, and immunotherapy. Cardiovascular side-effects may occur in the early phase of tumor therapy or even decades later. Therefore, knowledge and awareness of acute and long-lasting cardiac side effects of anti-cancer therapies are essential. Cardiotoxicity impairs quality of life and overall survival. The new cardiologic subspecialty ‘cardio-oncology’ deals with the different cardiovascular problems arising from tumor treatment and the relationship between cancer and heart diseases. Early detection and treatment of cardiotoxicity is of crucial importance. A detailed cardiac assessment of patients prior to administration of cardiotoxic agents, during and after treatment should be performed in all patients. The current review focusses on acute and long-term cardiotoxic side effects of classical cytotoxic and selected modern drug treatments such as immune checkpoint inhibitors and discusses strategies for the diagnosis of treatment-related adverse cardiovascular effects in cancer patients.

scholarly journals Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 265
Author(s):  
Maria-Luisa Pérez-Lozano ◽  
Annabelle Cesaro ◽  
Marija Mazor ◽  
Eric Esteve ◽  
Sabine Berteina-Raboin ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Natural Product ◽  
Treatment Strategies ◽  
Cartilage Degradation ◽  
Therapeutic Strategies ◽  
Clinical Models ◽  
Osteoarthritic Joint ◽  
Dietary Components ◽  
New Treatment ◽  
Review Current

Osteoarthritis (OA) is a complex degenerative disease in which joint homeostasis is disrupted, leading to synovial inflammation, cartilage degradation, subchondral bone remodeling, and resulting in pain and joint disability. Yet, the development of new treatment strategies to restore the equilibrium of the osteoarthritic joint remains a challenge. Numerous studies have revealed that dietary components and/or natural products have anti-inflammatory, antioxidant, anti-bone-resorption, and anabolic potential and have received much attention toward the development of new therapeutic strategies for OA treatment. In the present review, we provide an overview of current and emerging natural-product-based research treatments for OA management by drawing attention to experimental, pre-clinical, and clinical models. Herein, we review current and emerging natural-product-based research treatments for OA management.

scholarly journals The Optimal First-Line Therapy ofHelicobacter pyloriInfection in Year 2012

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chao-Hung Kuo ◽  
Fu-Chen Kuo ◽  
Huang-Ming Hu ◽  
Chung-Jung Liu ◽  
Sophie S. W. Wang ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Treatment Strategies ◽  
Sequential Therapy ◽  
Antibiotics Resistance ◽  
First Line ◽  
First Line Therapy ◽  
Metronidazole Resistance ◽  
Rescue Treatment ◽  
New Treatment ◽  
H Pylori

This paper reviews the literature about first-line therapies forH. pyloriinfection in recent years. First-line therapies are facing a challenge because of increasing treatment failure due to elevated antibiotics resistance. Several new treatment strategies that recently emerged to overcome antibiotic resistance have been surveyed. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential therapy, concomitant therapy, and hybrid therapy. Levofloxacin-based therapy shows impressive efficacy but might be employed as rescue treatment due to rapidly raising resistance. Rifabutin-based therapy is also regarded as a rescue therapy. Several factors including antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports. It is recommended that triple therapy should not be used in areas with high clarithromycin resistance or dual clarithromycin and metronidazole resistance.

scholarly journals “Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Cardiac Cells ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Micro Rnas ◽  
New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

scholarly journals Silencing of MEG3 attenuated the role of lipopolysaccharides by modulating the miR-93-5p/PTEN pathway in Leydig cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xu Zhou ◽  
Jingliang He ◽  
Jinbo Chen ◽  
Yu Cui ◽  
Zhenyu Ou ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Leydig Cells ◽  
Treatment Strategies ◽  
Pten Expression ◽  
Luciferase Reporter ◽  
Western Blots ◽  
New Treatment ◽  
Lps Treatment

Abstract Background Leydig cells reflect the activation of inflammation, decrease of androgen production, inhibition of cell growth and promotion of cell apoptosis under orchitis. Maternally expressed gene 3 (MEG3) exerts a crucial role in various human diseases, but under orchitis, the role and underlying molecular mechanism of MEG3 in Leydig cells remain unclear. Methods Lipofectamine 2000 was used for the cell transfections. qPCR and western blots assay were applied to assess the gene expression. ELISA assay was used to measure the TNFα, IL6 and testosterone secretion. CCK8 and EdU assay was employ to test the cell viability and proliferation respectively. Luciferase reporter and RIP assay were introduced to detect the binding of miR-93-5p with MEG3 and PTEN. Results Lipopolysaccharides (LPS) induced TNFα and IL6 secretion, lowered testosterone production, inhibited cell viability and proliferation, and induced cell apoptosis in Leydig cells. MEG3 was upregulated in Leydig cells treated with LPS and that knockdown of MEG3 inhibited the role of LPS in Leydig cells. MEG3 absorbed miR-93-5p and that suppression of miR-93-5p restored the role of silenced MEG3 in Leydig cells under LPS treatment. miR-93-5p inhibited PTEN expression and that over-expressed PTEN alleviated the effect of miR-93-5p in Leydig cells treated with LPS. LPS activated the MEG3/miR-93-5p/PTEN signalling pathway in Leydig cells. Conclusions This study revealed that MEG3 serves as a molecular sponge to absorb miR-93-5p, thus leading to elevation of PTEN expression in Leydig cells under LPS treatment, offering a theoretical basis on which to establish potential new treatment strategies for orchitis.

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