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Molecules, Vol. 25, Pages 5845: A Pyranoxanthone as a Potent Antimitotic and Sensitizer of Cancer Cells to Low Doses of Paclitaxel
ssan Bousbaa Microtubule-targeting agents (MTAs) remain a gold standard for the treatment of several cancer types. By interfering with microtubules dynamic, MTAs induce a mitotic arrest followed by cell death. This antimitotic activity of MTAs is dependent on the spindle assembly checkpoint (SAC), which monitors the integrity of the mitotic spindle and proper chromosome attachments to microtubules in order to ensure accurate chromosome segregation and timely anaphase onset. However, the cytotoxic activity of MTAs is restrained by drug resistance and/or toxicities, and had motivated the search for new compounds and/or a...
Source: Molecules - December 10, 2020 Category: Chemistry Authors: F ábio França Patr ícia M. A. Silva Jos é X. Soares Ana C. Henriques Daniela R. P. Loureiro Carlos M. G. Azevedo Carlos M. M. Afonso Hassan Bousbaa Tags: Article Source Type: research

Microtubule-targeting agents and neurodegeneration.
Abstract The association of microtubule (MT) breakdown with neurodegeneration and neurotoxicity has provided an emerging therapeutic approach for neurodegenerative diseases. Tubulin binders are able to modulate MT dynamics and, as a result, are of particular interest both as potential therapeutics and experimental tools used to validate this strategy. Here, we provide a comprehensive overview of current knowledge and recent advancements regarding MT-targeting approaches for neurodegeneration and evaluate the potential application of MT-targeting agents (MTAs) based on available preclinical and clinical dat...
Source: Drug Discovery Today - December 3, 2020 Category: Drugs & Pharmacology Authors: Boiarska Z, Passarella D Tags: Drug Discov Today Source Type: research

The development and validation of a new Multidimensional Test Anxiety Scale (MTAS).
Although test anxiety has a long history in the educational and psychological literature there is a lack of census over its dimensionality. The aim of the present study was to clarify the dimensionality of test anxiety and develop a new instrument to reflect this dimensionality. Across two empirical studies we tested and refined a new multidimensional instrument comprising of two cognitive dimensions (Worry and Cognitive Interference) and two affective-physiological dimensions (Tension and Physiological Indicators). In both studies, four-correlated-factors and higher order models showed a good fit to the data. Test anxiety...
Source: European Journal of Psychological Assessment - September 10, 2020 Category: Psychiatry & Psychology Source Type: research

Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib
Conclusion: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.Oncology (Source: Oncology)
Source: Oncology - September 3, 2020 Category: Cancer & Oncology Source Type: research

Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib.
CONCLUSION: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN. PMID: 32882687 [PubMed - as supplied by publisher] (Source: Oncology)
Source: Oncology - September 2, 2020 Category: Cancer & Oncology Authors: Ando Y, Kawaoka T, Suehiro Y, Yamaoka K, Kosaka Y, Uchikawa S, Kodama K, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Fukuhara T, Mori N, Takaki S, Tsuji K, Nonaka M, Hyogo H, Aisaka Y, Masaki K, Honda Y, Moriya T, Naeshiro Tags: Oncology Source Type: research

Molecules, Vol. 25, Pages 3705: Intrinsic and Extrinsic Factors Affecting Microtubule Dynamics in Normal and Cancer Cells
Fabczak Microtubules (MTs), highly dynamic structures composed of α- and β-tubulin heterodimers, are involved in cell movement and intracellular traffic and are essential for cell division. Within the cell, MTs are not uniform as they can be composed of different tubulin isotypes that are post-translationally modified and interact with different microtubule-associated proteins (MAPs). These diverse intrinsic factors influence the dynamics of MTs. Extrinsic factors such as microtubule-targeting agents (MTAs) can also affect MT dynamics. MTAs can be divided into two main categories: microtubule...
Source: Molecules - August 13, 2020 Category: Chemistry Authors: Filip Borys Ewa Joachimiak Hanna Krawczyk Hanna Fabczak Tags: Review Source Type: research

Cancers, Vol. 12, Pages 1721: Beyond the Paclitaxel and Vinca Alkaloids: Next Generation of Plant-Derived Microtubule-Targeting Agents with Potential Anticancer Activity
ara Plants are an important source of chemically diverse natural products that target microtubules, one of the most successful targets in cancer therapy. Colchicine, paclitaxel, and vinca alkaloids are the earliest plant-derived microtubule-targeting agents (MTAs), and paclitaxel and vinca alkaloids are currently important drugs used in the treatment of cancer. Several additional plant-derived compounds that act on microtubules with improved anticancer activity are at varying stages of development. Here, we move beyond the well-discussed paclitaxel and vinca alkaloids to present other promising plant-derived MTAs with ...
Source: Cancers - June 28, 2020 Category: Cancer & Oncology Authors: Dangquan Zhang Arun Kanakkanthara Tags: Review Source Type: research

Genome-Wide SNP Identification and Association Mapping for Seed Mineral Concentration in Mung Bean (Vigna radiata L.)
The objectives of this research were three-fold, namely: to develop a genome-wide marker system for mung bean based on genotyping by sequencing (GBS), to evaluate diversity of mung beans available to breeders in the United States and finally, to perform a genome-wide association study (GWAS) for nutrient concentrations based on a seven mineral analysis using inductively coupled plasma (ICP) spectroscopy. All parts of our research were performed with 95 cultivated mung bean genotypes chosen from the USDA core collection representing accessions from 13 countries. Overall, we identified a total of 6,486 high quality single nu...
Source: Frontiers in Genetics - June 23, 2020 Category: Genetics & Stem Cells Source Type: research

Genome-Wide Meta-Analysis Validates a Roless for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy.
Abstract Microtubule targeting agents (MTAs) are anticancer therapies commonly prescribed for breast cancer and other solid tumors. Sensory peripheral neuropathy (PN) is the major dose-limiting toxicity for MTAs and can limit clinical efficacy. The current pharmacogenomic study aimed to identify genetic variations that explain patient susceptibility and drive mechanisms underlying development of MTA-induced PN. A meta-analysis of genome-wide association studies (GWAS) from two clinical cohorts treated with MTAs (CALGB 40502 and CALGB 40101) was conducted using a Cox regression model with cumulative dose to...
Source: Clinical Pharmacology and Therapeutics - June 19, 2020 Category: Drugs & Pharmacology Authors: Chua KC, Xiong C, Ho C, Mushiroda T, Jiang C, Mulkey F, Lai D, Schneider BP, Rashkin SR, Witte JS, Friedman PN, Ratain MJ, McLeod HL, Rugo HS, Shulman LN, Kubo M, Owzar K, Kroetz DL Tags: Clin Pharmacol Ther Source Type: research

Microtubule-targeting agents and their impact on cancer treatment.
Abstract Microtubule-targeting agents (MTAs) constitute a diverse group of chemical compounds that bind to microtubules and affect their properties and function. Disruption of microtubules induces various cellular responses often leading to cell cycle arrest or cell death, the most common effect of MTAs. MTAs have found a plethora of practical applications in weed control, as fungicides and antiparasitics, and particularly in cancer treatment. Here we summarize the current knowledge of MTAs, the mechanisms of action and their role in cancer treatment. We further outline the potential use of MTAs in anti-me...
Source: European Journal of Cell Biology - April 30, 2020 Category: Cytology Authors: Čermák V, Dostál V, Jelínek M, Libusová L, Kovář J, Rösel D, Brábek J Tags: Eur J Cell Biol Source Type: research

Genome-Wide Association Study Reveals Novel Marker-Trait Associations (MTAs) Governing the Localization of Fe and Zn in the Rice Grain
Micronutrient malnutrition due to Fe and Zn, affects around two billion people globally particularly in the developing countries. More than 90% of the Asian population is dependent on rice-based diets, which is low in these micronutrients. In the present study, a set of 192 Indian rice germplasm accessions, grown at two locations, were evaluated for Fe and Zn in brown rice (BR) and milled rice (MR). A significant variation was observed in the rice germplasm for these micronutrients. The grain Fe concentration was in the range of 6.2–23.1 ppm in BR and 0.8–12.3 ppm in MR, while grain Zn concentration was found to be in ...
Source: Frontiers in Genetics - April 21, 2020 Category: Genetics & Stem Cells Source Type: research

A pooled analysis of molecularly targeted agents for treatment of metastatic oesophago-gastric cancer in elderly patients.
Conclusions: Our results indicate that the MTA-containing therapies significantly improve OS but not for PFS in elderly mOGC patients. Sub-group analysis shows that improved efficacy is only observed in the second-line setting and not in the first-line setting. Our findings support the use of angiogenesis as second-line treatment for elderly mOGC patients. PMID: 32190134 [PubMed] (Source: Archives of Medical Science)
Source: Archives of Medical Science - March 20, 2020 Category: General Medicine Tags: Arch Med Sci Source Type: research

Tubulin Maytansine Site Binding Ligands and Their Applications as MTAs and ADCs for Cancer Therapy.
CONCLUSION: The maytansine site binding agents are powerful MTAs for cancer chemotherapy. The maytansine site ligands-based ADCs are used in clinic or under clinical trials as cancer targeted therapy to improve their selectivity and to reduce their side effects. Further improvements in the delivery efficiency of the ADCs will benefit the patients in cancer targeted therapy. PMID: 32175831 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - March 15, 2020 Category: Chemistry Authors: Cao S, Dong YH, Wang DF, Liu ZP Tags: Curr Med Chem Source Type: research

Cancers, Vol. 12, Pages 97: Activation of PERK Contributes to Apoptosis and G2/M Arrest by Microtubule Disruptors in Human Colorectal Carcinoma Cells ‡
an Chen Microtubule-targeting agents (MTAs) are widely used in cancer chemotherapy, but the therapeutic responses significantly vary among different tumor types. Protein kinase RNA-like endoplasmic reticular (ER) kinase (PERK) is an ER stress kinase, and the role of PERK in the anticancer effects of MTAs is still undefined. In the present study, taxol (TAX) and nocodazole (NOC) significantly induced apoptosis with increased expression of phosphorylated PERK (pPERK; Tyr980) in four human colon cancer cell lines, including HCT-15, COLO205, HT-20, and LOVO cells. Induction of G2/M arrest by TAX and NOC with increases i...
Source: Cancers - December 29, 2019 Category: Cancer & Oncology Authors: Wu Chien Jargalsaikhan Ilsan Chen Tags: Article Source Type: research

Genetic dissection of zinc, iron, copper, manganese and phosphorus in wheat (Triticum aestivum L.) grain and rachis at two developmental stages
In this study, we report a genome-wide association using a wheat diversity panel to dissect the genetics controlling zinc, iron, copper, manganese and phosphorus concentrations in the grain and rachis during grain development and at physiological maturity.Significant marker-trait associations (MTAs) were identified for each nutrient using multi-locus mixed model methodologies. For mature grain, markers that showed significant pleiotropic effects were found on chromosomes 1A, 3B and 5B, of which those on chromosome 5B at ∼95.5 cM were consistent over two growing seasons. Co-located MTAs were identified for the nutrient ...
Source: Plant Science - December 11, 2019 Category: Biology Source Type: research