scholarly journals Adrenocortical Carcinoma: Current Therapeutic State-of-the-Art

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Amir H. Lebastchi ◽  
John W. Kunstman ◽  
Tobias Carling
Keyword(s):  
Adrenocortical Carcinoma ◽  
Clinical Trial Design ◽  
Staging System ◽  
Rational Drug Design ◽  
Proper Role ◽  
Rational Drug ◽  
International Collaborations ◽  
Low Prevalence ◽  
Made In

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy that generally conveys a poor prognosis. Currently, surgical resection is considered the lone curative treatment modality. In addition, the low prevalence of ACC has limited effective clinical trial design to develop evidence-based approaches to ACC therapy. The proper role of radio- and chemotherapy treatment for ACC is still being defined. Similarly, the molecular pathogenesis of ACC remains to be fully characterized. Despite these challenges, progress has been made in several areas. After years of refinement, an internationally accepted staging system has been defined. International collaborations have facilitated increasingly robust clinical trials, especially regarding agent choice and patient selection for chemotherapeutics. Genetic array data and molecular profiling have identified new potential targets for rational drug design as well as potential tumor markers and predictors of therapeutic response. However, these advances have not yet been translated into a large outcomes benefit for ACC patients. In this paper, we summarize established therapy for ACC and highlight recent findings in the field that are impacting clinical practice.

The Expanding Role of NMR in Rational Drug Design

2004 ◽  
Vol 1 (1) ◽  
pp. 237-271
Author(s):  
Rickey P. Hicks ◽  
Daniel A. Nichols
Keyword(s):  
Drug Design ◽  
Rational Drug Design ◽  
Rational Drug

scholarly journals Structural investigations of cell-free expressed G protein-coupled receptors

2019 ◽  
Vol 401 (1) ◽  
pp. 97-116
Author(s):  
Lisa Maria Kögler ◽  
Jan Stichel ◽  
Annette G. Beck-Sickinger
Keyword(s):  
G Protein ◽  
Recombinant Expression ◽  
G Protein Coupled Receptors ◽  
Rational Drug Design ◽  
Structural Investigations ◽  
Rational Drug ◽  
Efficient Alternative ◽  
G Protein Coupled ◽  
Cell Free Protein Synthesis

Abstract G protein-coupled receptors (GPCRs) are of great pharmaceutical interest and about 35% of the commercial drugs target these proteins. Still there is huge potential left in finding molecules that target new GPCRs or that modulate GPCRs differentially. For a rational drug design, it is important to understand the structure, binding and activation of the protein of interest. Structural investigations of GPCRs remain challenging, although huge progress has been made in the last 20 years, especially in the generation of crystal structures of GPCRs. This is mostly caused by issues with the expression yield, purity or labeling. Cell-free protein synthesis (CFPS) is an efficient alternative for recombinant expression systems that can potentially address many of these problems. In this article the use of CFPS for structural investigations of GPCRs is reviewed. We compare different CFPS systems, including the cellular basis and reaction configurations, and strategies for an efficient solubilization. Next, we highlight recent advances in the structural investigation of cell-free expressed GPCRs, with special emphasis on the role of photo-crosslinking approaches to investigate ligand binding sites on GPCRs.

Collaborative approach to improve the detection and management of trichomoniasis in a low prevalence district

1998 ◽  
Vol 9 (3) ◽  
pp. 164-167 ◽  
Author(s):  
D J Waghorn ◽  
P K Tucker ◽  
Y Chia ◽  
S Spencer ◽  
G A Luzzi
Keyword(s):  
Trichomonas Vaginalis ◽  
Vaginal Swab ◽  
Further Education ◽  
Contact Tracing ◽  
Collaborative Approach ◽  
Sexually Transmitted ◽  
Low Prevalence ◽  
Microbiological Confirmation ◽  
Made In

We describe a simple collaborative approach developed by the departments of cytology, microbiology and genitourinary (GU) medicine for the detection, diagnosis and management of microbiologically confirmed Trichomonas vaginalis (TV) infection. Over a 2-year period, 54 (0.1%) of 52,440 cervical smears were reported to show TV, but microbiological confirmation was made in only 76% of 34 patients from whom a vaginal swab was subsequently taken. Trichomoniasis should not be diagnosed by cytology alone and clinicians need further education on the role of cytology in diagnosing sexually transmitted diseases (STDs). Over the same period, from a total of 96 cases of TV identified in the district, only 12 (13%) were first diagnosed in the department of GU medicine. Forty per cent of the other 84 patients were subsequently seen in the GU clinic for test of cure, contact tracing and screening for other STDs. Collaborations between departments may improve the management of trichomoniasis and other conditions in the community and their development should be encouraged.

scholarly journals Quantitative structure-cytotoxic activity relationship of phenylthiourea derivatives from ChemBL database on sirtuin-1 receptor by in silico

2019 ◽  
Vol 4 (1) ◽  
pp. 25
Author(s):  
Anindi Lupita Nasyanka
Keyword(s):  
Cytotoxic Activity ◽  
In Silico ◽  
Rational Drug Design ◽  
Sirtuin 1 ◽  
Anticancer Compounds ◽  
A Value ◽  
Rational Drug ◽  
Drug Receptor ◽  
Relationship Of

Rational drug design becomes a necessity amid the development of drugs that are inefficient and time-consuming. Hansch's QSAR helps reduce these shortcomings supported by the role of biocomputation. Some of the roles of biocomputation that can be used include in silico testing and the availability of databases for new drug-receptor and ligand candidates. This study aims to determine the QSAR through the search for the best equations analyzed by ANOVA statistics between cytotoxic activity in silico (Log 1/c) anticancer compounds derived from phenylthiourea stored in the ChemBL database with lipophilic parameters (ALPP and AlogP) , electronic (ACDpKa), and its sterics (PMW). The best equation is obtained Log 1/c = -46,194 - 0,152 PMW- 3,769 ALogP - 1,336 ACDpKa with a value of N = 28; F = 20,866; r = 0,850;  P = 0,000; SE = 5.82160. In the future, this equation can be used to find other new phenylthiourea derivatives that have better cytotoxic activity.

Molecular mechanics approaches for rational drug design: forcefields and solvation models

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Boris D. Bekono ◽  
Alfred N. Sona ◽  
Donatus B. Eni ◽  
Luc C. O. Owono ◽  
Eugène Megnassan ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Molecular Mechanics ◽  
In Silico ◽  
Drug Target ◽  
Energy Equation ◽  
Rational Drug Design ◽  
Rational Drug ◽  
Structures And Properties ◽  
Solvation Models

Abstract The use of molecular mechanics (MM) in understanding the energy and target of a drug, its structures, and properties has increased recently. This is achieved by the formulation of a simple MM energy equation, which represents the sum of the different energy interactions, often referred to as “forcefields” (FFs). The concept of FFs is now widely used as one of the fundamental tools for the in silico prediction of drug-target interactions. To generate more accurate predictions in the in silico drug discovery projects, the solvent effects are often taken into account. This review seeks to present an introductory guide for the reader on the fundamentals of MM with special emphasis on the role of FFs and the solvation models.

ASPECTS IN BUILDING A COMPANY WEB-SITE AND ITS ROLE FOR THE DEVELOPMENT OF BUSINESS

2018 ◽  
pp. 117-124
Author(s):  
Petar Halachev ◽  
Victoria Radeva ◽  
Albena Nikiforova ◽  
Miglena Veneva
Keyword(s):  
Life Cycle ◽  
Web Site ◽  
The Internet ◽  
A Company ◽  
The Web ◽  
Design Construction ◽  
Made In ◽  
Site Types

This report is dedicated to the role of the web site as an important tool for presenting business on the Internet. Classification of site types has been made in terms of their application in the business and the types of structures in their construction. The Models of the Life Cycle for designing business websites are analyzed and are outlined their strengths and weaknesses. The stages in the design, construction, commissioning, and maintenance of a business website are distinguished and the activities and requirements of each stage are specified.

Aboutness

2014 ◽  
Author(s):  
Stephen Yablo
Keyword(s):  
Subject Matter ◽  
Philosophy Of Language ◽  
Mental States ◽  
Library Science ◽  
Philosophical Methodology ◽  
Major Advance ◽  
Truth Conditions ◽  
Ways Of Being ◽  
Made In

Aboutness has been studied from any number of angles. Brentano made it the defining feature of the mental. Phenomenologists try to pin down the aboutness features of particular mental states. Materialists sometimes claim to have grounded aboutness in natural regularities. Attempts have even been made, in library science and information theory, to operationalize the notion. However, it has played no real role in philosophical semantics, which is surprising. This is the first book to examine through a philosophical lens the role of subject matter in meaning. A long-standing tradition sees meaning as truth conditions, to be specified by listing the scenarios in which a sentence is true. Nothing is said about the principle of selection—about what in a scenario gets it onto the list. Subject matter is the missing link here. A sentence is true because of how matters stand where its subject matter is concerned. This book maintains that this is not just a feature of subject matter, but its essence. One indicates what a sentence is about by mapping out logical space according to its changing ways of being true or false. The notion of content that results—directed content—is brought to bear on a range of philosophical topics, including ontology, verisimilitude, knowledge, loose talk, assertive content, and philosophical methodology. The book represents a major advance in semantics and the philosophy of language.

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