The 5-Lipoxygenase Inhibitory Activity of Zileuton in In Vitro and In Vivo Models of Antigen-Induced Airway Anaphylaxis

1994 ◽  
Vol 7 (2) ◽  
pp. 73-79 ◽  
Author(s):  
P.E. Malo ◽  
R.L. Bell ◽  
T.K. Shaughnessy ◽  
J.B. Summers ◽  
D.W. Brooks ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Vivo Models

scholarly journals Exploring the Antiangiogenic Potential of Solomonamide A Bioactive Precursors: In Vitro and in Vivo Evidences of the Inhibitory Activity of Solo F-OH During Angiogenesis

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 228 ◽  
Author(s):  
Carrillo ◽  
Martínez-Poveda ◽  
Cheng-Sánchez ◽  
Guerra ◽  
Tobia ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inhibitory Activity ◽  
Cyclic Peptide ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
Marine Sponges ◽  
Migration And Invasion ◽  
In Vivo Models

Marine sponges are a prolific source of bioactive compounds. In this work, the putative antiangiogenic potential of a series of synthetic precursors of Solomonamide A, a cyclic peptide isolated from a marine sponge, was evaluated. By means of an in vitro screening, based on the inhibitory activity of endothelial tube formation, the compound Solo F–OH was selected for a deeper characterization of its antiangiogenic potential. Our results indicate that Solo F–OH is able to inhibit some key steps of the angiogenic process, including the proliferation, migration, and invasion of endothelial cells, as well as diminish their capability to degrade the extracellular matrix proteins. The antiangiogenic potential of Solo F–OH was confirmed by means of two different in vivo models: the chorioallantoic membrane (CAM) and the zebrafish yolk membrane (ZFYM) assays. The reduction in ERK1/2 and Akt phosphorylation in endothelial cells treated with Solo F–OH denotes that this compound could target the upstream components that are common to both pathways. Taken together, our results show a new and interesting biological activity of Solo F–OH as an inhibitor of the persistent and deregulated angiogenesis that characterizes cancer and other pathologies.

Characterization and Optimization of Synthetic, VLDL Receptor Targeting, Antiangiogenic Peptides with TFPIc23-Like Activity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 531-531
Author(s):  
Todd Hembrough ◽  
Kevin Yin ◽  
Art Hanson ◽  
Elizabeth Hahn-Dantona ◽  
Dudley Strickland ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Receptor Binding ◽  
Antiproliferative Activity ◽  
Inhibitory Activity ◽  
Peptide Sequence ◽  
Wild Type ◽  
In Vivo Models ◽  
Vldl Receptor

Abstract We previously reported that a 23 amino acid fragment of tissue factor pathway inhibitor (TFPIc23) had significant antiangiogenic and antitumor activity in preclinical models. In in vitro studies, the very low density lipoprotein (VLDL) receptor was identified as the target for the activity of TFPIc23 (Blood103:3374). In order to confirm that the cellular target of TFPIc23 is the VLDL receptor, aortas from wildtype and VLDL receptor knockout (VLDLr −/−) mice were used for the ex vivo aorta ring model of angiogenesis. Vessel outgrowth from these rings was measured in the presence and absence of TFPIc23. In control studies, both wild type and VLDLr −/− mouse aorta rings grew vessels. When aorta rings from wild type mice were treated with TFPIc23, there was greater than 90% inhibition of vessel outgrowth. In contrast, VLDLr −/− aorta rings were insensitive to inhibition by the TFPIc23 peptide consistent with the hypothesis that the in vivo target of TFPIc23 activity is the VLDL receptor. To further assess the role of the VLDL receptor in angiogenesis, chemical modification of the TFPIc23 sequence was performed to define the structure activity relationships between the peptide sequence, peptide binding affinity for the VLDL receptor, and inhibitory activity in HUVEC proliferation assays. The goals were to define a minimal peptide structure which retained antiproliferative activity, confirm the VLDL receptor as the target of action, and modify the peptide sequence and architecture to increase activity and differentiate the peptide from the native sequence. 151 peptides were synthesized and screened for VLDL receptor binding affinity, as well as inhibitory activity in the HUVEC assay. Several peptides of 11–15 amino acids that retained both VLDL receptor affinity, and antiproliferative activity were identified. In the HUVEC assay the IC50 value of some of the novel peptides was decreased from 15uM for TFPIc23 to <1uM. The affinity of these peptides for the VLDL receptor was enhanced more than 10-fold. To confirm that the peptide’s antiproliferative activity was mediated by the VLDL receptor, blocking studies were performed with antibodies to the VLDL receptor. Blockade of the VLDL receptor abrogated the activity of several of the peptides with increase antiproliferative activity. Overall there was a good correlation between binding and activity, further supporting the VLDL receptor as mediating the antiangiogenic activity of these peptides. Several novel peptide analogs of TFPIc23 that exhibited improved antiproliferative activity and VLDL receptor binding in vitro were then assessed in in vivo models. In the Matrigel angiogenesis model, one of these peptides significantly inhibited angiogenesis by ~75% at 200mg/ml and in the Lewis lung carcinoma metastatic model inhibited metastatic tumor growth by >50% at 100mg/ml. In both cases these activities were significantly better than the activity of the parental TFPIc23 peptide. Taken together, these data show that SAR studies on novel synthetic peptides have yielded peptides with significantly better activity in preclinical tumor and angiogenesis models than TFPIc23. In addition, these results suggest that the VLDL receptor is a potential target for the development of antiangiogenic and antitumor agents.

The Effects of Some Synthetic Compounds on In Vitro Fibrinolytic Activity Measured by Different Methods and the Relevance to Activity In Vivo

1972 ◽  
Vol 28 (03) ◽  
pp. 351-358
Author(s):  
A.J Baillie ◽  
A. K Sim
Keyword(s):  
Inhibitory Activity ◽  
Substrate Concentration ◽  
Fibrinolytic Activity ◽  
Synthetic Compounds ◽  
In Vitro Methods ◽  
Narrow Concentration Range

SummaryThe activity of several synthetic compounds, rated from good to poor (or inactive) fibrinolytic activators, has been assessed by two different commonly-used in vitro methods. Compounds shown to be active over a narrow concentration range in the hanging clot test were shown to be inhibitors of plasmin and trypsin in the casein-olytic test. The inhibitory activity of these compounds was shown to increase with increasing substrate concentration and apparent activity in the hanging clot test. Possible explanations and relevance of these observations are discussed.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases

2019 ◽  
Vol 26 (16) ◽  
pp. 2974-2986 ◽  
Author(s):  
Kwang-sun Kim
Keyword(s):  
New Host ◽  
In Vivo Models ◽  
Vector Borne Diseases ◽  
Novel Drugs ◽  
Huge Impact ◽  
Tick Borne Disease ◽  
Vector Borne ◽  
Living Organisms

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

2020 ◽  
Vol 26 (35) ◽  
pp. 4362-4372
Author(s):  
John H. Miller ◽  
Viswanath Das
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
In Vivo Models ◽  
Synthetic Compounds ◽  
Stabilizing Agents ◽  
Animal Models Of Disease ◽  
Model Studies ◽  
Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

A Review on Opuntia Species and its Chemistry, Pharmacognosy, Pharmacology and Bioapplications

2020 ◽  
Vol 16 (8) ◽  
pp. 1227-1244
Author(s):  
Dharmendra Kumar ◽  
Pramod K. Sharma
Keyword(s):  
Human Consumption ◽  
In Vivo Models ◽  
Sugar Amino Acids ◽  
Opuntia Species ◽  
Therapeutic Uses ◽  
Anti Inflammatory ◽  
Online Library ◽  
Different Parts

Background:: Opuntia species, locally known as prickly pear was used for various purposes as food, medicine, beverage, source of dye and animal food. Many studies have revealed its pharmacology activity from time to time. This review is a collection of chemistry, pharmacognosy, pharmacology and bioapplications of the cactus family. Methods: Many sources were used to collect information about Opuntia species such as Pub med, Google scholar, Agris, science direct, Embase, Merk index, Wiley online library, books and other reliable sources. This review contains studies from 1812 to 2019. Results: The plants from the cactus family offer various pharmacological active compounds including phenolic compounds, carotenoids, betalains, vitamins, steroids, sugar, amino acids, minerals and fibers. These bioactive compounds serve various pharmacological activities such as anticancer, antiviral, anti-diabetic, Neuroprotective, anti-inflammatory, antioxidant, Hepatoprotective, antibacterial, antiulcer and alcohol hangover. According to various studies, Opuntia species offer many bioapplications such as fodder for animal, soil erosion, prevention, human consumption and waste water decontamination. Finally, different parts of plants are used in various formulations that offer many biotechnology applications. Conclusion: Different parts of Opuntia plant (fruits, seeds, flowers and cladodes) are used in various health problems which include wound healing, anti-inflammatory and urinary tract infection from ancient times. Nowadays, researches have extended several pharmacological and therapeutic uses of Opuntia species as discussed in this review. Many in-vitro and in-vivo models are also discussed in this review as the proofs of research findings. Various research gaps have been observed in current studies that require attention in the future.

scholarly journals GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its Therapeutic Potential and Immune Modulatory Properties

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 610
Author(s):  
Robin Park ◽  
Andrew L. Coveler ◽  
Ludimila Cavalcante ◽  
Anwaar Saeed
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Potential ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
In Vivo Models ◽  
Gsk 3Β ◽  
Early Phase Clinical Trials

Glycogen synthase kinase-3 beta is a ubiquitously and constitutively expressed molecule with pleiotropic function. It acts as a protooncogene in the development of several solid tumors including pancreatic cancer through its involvement in various cellular processes including cell proliferation, survival, invasion and metastasis, as well as autophagy. Furthermore, the level of aberrant glycogen synthase kinase-3 beta expression in the nucleus is inversely correlated with tumor differentiation and survival in both in vitro and in vivo models of pancreatic cancer. Small molecule inhibitors of glycogen synthase kinase-3 beta have demonstrated therapeutic potential in pre-clinical models and are currently being evaluated in early phase clinical trials involving pancreatic cancer patients with interim results showing favorable results. Moreover, recent studies support a rationale for the combination of glycogen synthase kinase-3 beta inhibitors with chemotherapy and immunotherapy, warranting the evaluation of novel combination regimens in the future.

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