Eribulin in Cancer Treatment Swami, Umang; Shah, Umang; Goel, Sanjay
Marine Drugs,
08/2015, Letnik:
13, Številka:
8
Journal Article, Book Review
Recenzirano
Odprti dostop
Halichondrin B is a complex, natural, polyether macrolide derived from marine sponges. Eribulin is a structurally-simplified, synthetic, macrocyclic ketone analogue of Halichondrin B. Eribulin was ...approved by United States Food and Drug Administration in 2010 as a third-line therapy for metastatic breast cancer patients who have previously been treated with an anthracycline and a taxane. It has a unique microtubule dynamics inhibitory action. Phase III studies have either been completed or are currently ongoing in breast cancer, soft tissue sarcoma, and non-small cell lung cancer. Phase I and II studies in multiple cancers and various combinations are currently ongoing. This article reviews the available information on eribulin with respect to its clinical pharmacology, pharmacokinetics, pharmacodynamics, mechanism of action, metabolism, preclinical studies, and with special focus on clinical trials.
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Understanding interparticle interactions in powder systems is crucial to pharmaceutical powder processing. Nevertheless, there remains a great challenge in identifying the key factors ...affecting interparticle interactions. Factors affecting interparticle interactions can be classified in three different broad categories: powder properties, environmental conditions, and powder processing methods and parameters. Although, each of these three categories listed is known to affect interparticle interactions, the challenge remains in developing a mechanistic understanding on how combination of these three categories affect interparticle interactions. This review focuses on the recent advances on understanding the effect of powder properties, particularly particle properties, its effect on interparticle interactions and ultimately on powder bulk behaviour. Furthermore, this review also highlights how particle properties are affected by the particle processing route and parameters. Recent advances in developing a particle processing route to prepare particles with desired properties allowing desired interparticle interaction to deliver favoured powder bulk behaviour are also discussed. Perspectives for the development of potential particle processing approaches to control interparticle interaction are presented.
Objective: Flavones occupy a special place in the realm of natural and synthetic organic chemistry owing to their diversified biological activities. In this study, a series of chalcone derivatives ...were synthesized and after cyclization of chalcone to synthesized various substituted flavone derivatives (2A-2L). 2 Methods: The reaction of 2-hydroxy acetophenone with substituted aromatic aldehydes produced chalcone by trituration (NaOH) and conventional methods (KOH/EtOH), which upon further cyclization with dimethyl sulfoxide/I resulted to form flavone derivatives.Results: The purity of compounds was ascertained by melting point and thin-layer chromatography. The synthesized compounds have been characterized by mass, infrared, and1H nuclear magnetic resonance spectral analysis.Conclusion: Based on spectral data, it was proved that all synthesized chalcones and flavones derivatives meet the standard values of various spectral techniques and further it will be evaluated for pharmacological activities.Keywords: Chalcone, Flavone, Trituration, Conventional, Claisen-Schmidt condensation.
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Particle bulk and surface properties are influenced by the powder processing routes. This study demonstrates the effect of milling temperatures on the particle surface properties, ...particularly surface energy and surface area, and ultimately on powder cohesion. An active pharmaceutical ingredient (API) of industrial relevance (brivanib alaninate, BA) was used to demonstrate the effect of two different, but most commonly used milling temperatures (cryogenic vs. ambient). The surface energy of powders milled at both cryogenic and room temperatures increased with increasing milling cycles. The increase in surface energy could be related to the generation of surface amorphous regions. Cohesion for both cryogenic and room temperature milled powders was measured and found to increase with increasing milling cycles. For cryogenic milling, BA had a surface area ∼5× higher than the one obtained at room temperature. This was due to the brittle nature of this compound at cryogenic temperature. By decoupling average contributions of surface area and surface energy on cohesion by salinization post-milling, the average contribution of surface energy on cohesion for powders milled at room temperature was 83% and 55% at cryogenic temperature.
Many natural and synthetic flavonoids have been studied and documented by inhibiting aromatase enzymes for their anti-cancer activity against breast carcinoma. The aromatase enzyme is a possible ...target for the estrogen's positive breast cancer receptor.
Hence, a series of flavonoids have been synthesized and assessed for their in vitro cytotoxicity and aromatase inhibitory activity.
39 Flavonoids were synthesized and characterized by spectroscopic techniques, and their computational study was performed using the maestro version of the Schrodinger. In silico ADME properties were checked by QikProp software. A total of 18 compounds were evaluated based on the docking score using cytotoxicity assay in human breast cancer cell line MCF-7.
Of the 18 compounds tested, 07 compounds, namely 2b, 8b, 14b, 15b, 19b, 24b, and 30b flavonoids were found to be more active with their IC50 values of 20.73 μM, 1.636 μM, 16.08 μM, 22.02 μM, 15.75 μM, 0.345 μM and 16.08 μM, respectively, compared with the reference drug letrozole. The in vitro aromatase inhibitory activity of six compounds 2b, 8b, 14b, 19b, 24b, and 30b was conducted using a fluorogenic assay kit. The values of IC50 for compounds 2b and 24b were found to be 0.31 μM and 0.36 μM, respectively.
Therefore, it was concluded that compounds 2b and 24b had a potent inhibitory effect of aromatase compared with letrozole with an IC50 value of 0.86 μM. At the same time, the other compounds 8b, 14b, 30b, and 19b were considered to have similar aromatase inhibitory activity. Hence, their essential aromatase inhibitory activities make them good lead candidates for developing potent inhibitors of aromatase.
The outstanding research outcomes and registrations of myriads of probiotic strains have flooded the health market with various innovative probiotic-based products and their patents. The study of ...patented formulations of probiotics can give an overall insight into its existing application. A landscaping review of patents for probiotic-based preparations is presented in the current work. The patent search was performed over commercially available patent databased and analysis tool—PatSeer Pro®. Search strings containing words "Formulation" and "Composition" resulted in more than 3700 patents. Landscaping review of 400 + patents from the last 20 years (2000–2020) was performed using the Text-Mining approach. Text-Mining helped to identify 19 technological clusters which represent these patents. These clusters include the patents of probiotic preparations on animal feed, human food, cosmetics, antimicrobial, antidiabetic, arthritis, etc. A review of this massive number of patents unveiled many exciting preparations. Probiotic-based innovative products for depression, diabetes, Parkinson's, tumor, acne, and animal husbandry are reviewed comprehensively. The present work also unravels a few new-flanged products like probiotic layered condoms, products for acute alcoholism, and traditional Chinese medicine with probiotics. The patent landscape of probiotic-based preparations has presented a whole scenario of probiotic-based preparations. It has also revealed many unexplored areas where innovation can be excelled.
•The Discovery Lab fosters independent learning through creativity, critical thinking, and adaptive motivation.•Employed strategies were distilled into a framework which has been validated.•The ...framework can easily be transferred to other experiential learning contexts.
We have conceptualized the Discovery Laboratory at Imperial College London into an educational framework that enables independent learning among students. The study demonstrates an effective implementation of the framework with associated benefits for the learner in the areas of cognitive skills (creativity and critical thinking), metacognitive skills (ability to reflect on the entire learning process) and affective skills (adaptive motivation). Key supportive elements were transferring ownership of the learning process to students and incorporating assessment criteria that reward creativity. The framework can be easily adapted to other experiential learning contexts.
Purpose: The purpose of this in vitro research project was to evaluate and compare the wear behavior of human tooth enamel opposing monolithic zirconia and other different ceramic restorative ...materials and also to observe the tetragonal to monoclinic phase transformation in zirconia-based ceramics that may occur while simulating wear occurring at room temperature in a wet environment.
Materials and Methods: A total of sixty samples were prepared for this study. Fifteen discs of glazed zirconia, 15 discs of polished zirconia without glaze, 15 discs of metal ceramic, and 15 discs of lithium disilicate were fabricated. Sixty extracted premolars were collected and randomly divided into four groups of 15 each. The discs and extracted human premolars were placed onto holders on a two-body wear machine under a constant load of 5 kg to simulate the oral wear cycle. A diffractometer was used to analyze phase transformation. One-way analysis of variance and Tukey's post hoc tests was used.
Results: The mean loss of height of tooth samples and its standard deviation for Group I (monolithic zirconia with glaze), Group II (mechanically polished monolithic zirconia without glaze), Group III (porcelain fused to metal), and Group IV (glazed monolithic lithium disilicate) was obtained as 0.2716 ± 0.1409, 0.1240 ± 0.0625, 0.1567 ± 0.0996, and 0.2377 ± 0.1350, respectively. The highest mean loss in height was observed in Group I and the least was observed in Group II.
Conclusion: Mechanically polished zirconia showed the least amount of enamel wear followed by porcelain fused to metal and glazed monolithic lithium disilicate, whereas glazed monolithic zirconia showed the highest enamel wear.
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