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The search for candidate genes associated with natural variation of grain Zn accumulation in barley.
s S Abstract Combating Hidden Hunger through molecular breeding of nutritionally enriched crops requires a better understanding of micronutrient accumulation. We studied natural variation in grain micronutrient accumulation in barley ( Hordeum vulgare L.) and searched for candidate genes by assessing marker trait associations (MTAs) and by analyzing transcriptional differences between low and high zinc (Zn) accumulating cultivars during grain filling. A collection of 180 barley lines was grown in three different environments. Our results show a pronounced variation in Zn accumulation, which was under strong genoty...
Source: The Biochemical Journal - June 4, 2019 Category: Biochemistry Authors: Detterbeck A, Nagel M, Rensch S, Weber M, Börner A, Persson DP, Schjoerring JK, Christov V, Clemens S Tags: Biochem J Source Type: research
Tubulin-VDAC Interaction: Molecular Basis for Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy
Tubulin is a well-established target of microtubule-targeting agents (MTAs), a widely used class of chemotherapeutic drugs. Yet, aside from their powerful anti-cancer efficiency, MTAs induce a dose-limiting and debilitating peripheral neurotoxicity. Despite intensive efforts in the development of neuroprotective agents, there are currently no approved therapies to effectively manage chemotherapy-induced peripheral neuropathy (CIPN). Over the last decade, attempts to unravel the pathomechanisms underlying the development of CIPN led to the observation that mitochondrial dysfunctions stand as a common feature associated with...
Source: Frontiers in Physiology - May 31, 2019 Category: Physiology Source Type: research
Protecting participants in health research: The South African Material Transfer Agreement.
This article explores the need for a uniform MTA in SA and discusses some aspects of the recently gazetted national MTA, which provides a framework that can serve as a safeguard for cross-border transfer of HBMs in the absence of the National Health Act's chapter 8 regulations in this regard. PMID: 31131804 [PubMed - in process] (Source: South African Medical Journal)
Source: South African Medical Journal - May 29, 2019 Category: African Health Tags: S Afr Med J Source Type: research
Genetic analyses of nitrogen assimilation enzymes in Brassica juncea (L.) Czern & Coss.
Genetic analyses of nitrogen assimilation enzymes in Brassica juncea (L.) Czern & Coss. Mol Biol Rep. 2019 May 21;: Authors: Gupta S, Akhatar J, Kaur P, Sharma A, Sharma P, Mittal M, Bharti B, Banga SS Abstract Nitrogen (N) is a critical input for plant growth and development. A better understanding of N uptake and utilization is important to develop plant breeding strategies for improving nitrogen use efficiency (NUE). With that objective in mind, we assayed a SNP-genotyped association panel comprising 92 inbred lines for the activities of nitrate reductase (NR), nitrite reductase (NIR), glutamin...
Source: Molecular Biology Reports - May 21, 2019 Category: Molecular Biology Authors: Gupta S, Akhatar J, Kaur P, Sharma A, Sharma P, Mittal M, Bharti B, Banga SS Tags: Mol Biol Rep Source Type: research
Evaluation and binding site determination of microtubule PET tracers [11C]MPC-6827 and [11C]HD-800 in cancer cell lines
Conclusions: We demonstrated specific bindings of [11C]MPC-6827 and [11C]HD-800 in breast cancer, GBM, and prostate cancer cell lines. Both tracers showed binding to taxane and colchicine sites of microtubule in MAD-MB-231 cells. This may be an advantage of these tracers for favoring high signal to noise ratio for in vivo imaging in cancer animal models. Combined with the previously established BBB permeability and in vivo binding specificity, [11C]MPC-6827 and [11C]HD-800 can be potential radiotracers for in vivo preclinical imaging of central and periphery cancers using PET. Research Support: Diane Goldberg Foundation (N...
Source: Journal of Nuclear Medicine - May 21, 2019 Category: Nuclear Medicine Authors: KUMAR, D., Hines, J., Norman, S., Prabhakaran, J., Mann, J., Mintz, A., Solingapuram Sai, K. K. Tags: Oncology, Basic and Translational (Basic Science) Posters Source Type: research
An overview of tubulin modulators deposited in protein data bank
AbstractMicrotubules are cytoskeletal polymers of tubulin and composed of α- and β-tubulin heterodimers, which are regarded as one of the most important, promising and successful targets for chemotherapeutic agents to treat cancer. With more and more tubulin-modulator co-crystal complex structures being solved, the mechanism of action (MOA) of microtubule targeting agen ts (MTAs) are well understood, which in turn inspired the development of more efficient tubulin modulators. By analyzing the reported tubulin modulators (most of them are inhibitors) that have been co-crystalized with tubulin and deposited in pro...
Source: Medicinal Chemistry Research - May 7, 2019 Category: Chemistry Source Type: research
Basket Trials for Intractable Cancer
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - April 12, 2019 Category: Cancer & Oncology Source Type: research
Genetic analysis of drought response of wheat following either chemical desiccation or the use of a rain-out shelter.
Nagel M Abstract Simulating drought stress during the breeding process has been proposed as a way to select varieties under naturally non-stressful conditions. The aim of the study was to characterise the genetic basis of the response of 111 spring wheat (Triticum aestivum L.) varieties and landraces to chemical desiccation and to rain-out shelter drought. The effect of the rain-out shelter was a 15% reduction in plant height, spike length and thousand seed weight (TSW); in contrast, the desiccant treatment induced a 15% reduction in seed number, a 35-72% loss in TSW and a reduction in subsequent germination of 12...
Source: J Appl Genet - April 4, 2019 Category: Genetics & Stem Cells Authors: Tarawneh RA, Szira F, Monostori I, Behrens A, Alqudah AM, Thumm S, Lohwasser U, Röder MS, Börner A, Nagel M Tags: J Appl Genet Source Type: research
Molecular mechanism of crolibulin in complex with tubulin provides a rationale for drug design.
Abstract Microtubules (MTs) is one of the most important proteins in eukaryotic cells and plays a key role in the maintenance of cell morphology and cell division. The discovery and development of small molecule drugs targeting MTs has always been an important direction of anti-cancer research. Nowadays 4-Aryl-4H-chromenes have emerged as potent microtubule-targeting agents (MTAs) for various cancers. Crolibulin, a derivative of 4-Aryl-4H-chromenes, which has been progressed to Phase I/II clinical testing's for anaplastic thyroid cancer with the National Cancer Institute. However, the design and development of 4-A...
Source: Biochemical and Biophysical Research communications - February 22, 2019 Category: Biochemistry Authors: Zhang Z, Wang C, Ma L, Jiang X, Wu C, Wang Y, Jiang Y, Zheng W, Yang Y, Ma Y, Yang J Tags: Biochem Biophys Res Commun Source Type: research
Genetic dissection of grain morphology in hexaploid wheat by analysis of the NBRP-Wheat core collection.
Abstract We investigated the genetic diversity of the core collection of hexaploid wheat accessions in the Japanese wheat gene bank, NBRP-Wheat, with a focus on grain morphology. We scanned images of grains in the core collection, which consists of 189 accessions of Triticum aestivum, T. spelta, T. compactum, T. sphaerococcum, T. macha and T. vavilovii. From the scanned images, we recorded six metric characters (area size, perimeter length, grain length, grain width, length to width ratio and circularity) using the software package SmartGrain ver. 1.2. Statistical analyses of the collected data along with hundred-...
Source: Genes and Genetic Systems - January 10, 2019 Category: Genetics & Stem Cells Authors: Yoshioka M, Takenaka S, Nitta M, Li J, Mizuno N, Nasuda S Tags: Genes Genet Syst Source Type: research
Contrasting effects of microtubule destabilizers versus stabilizers on induction of death in G1 phase of the cell cycle.
Abstract Microtubule targeting agents (MTAs) have been reported to manifest their cytotoxic effects not only in mitosis but also in interphase. However, the relationship between phase-specific susceptibility and MTA concentration, especially with respect to microtubule integrity, remains poorly defined. In addition, whether microtubule stabilizers and destabilizers act similarly or differ in the ability to induce interphase death is unclear. In order to resolve these uncertainties, we report here the results of a systematic comparison of primary acute lymphoblastic leukemia (ALL) and HeLa cells treated with three ...
Source: Biochemical Pharmacology - December 19, 2018 Category: Drugs & Pharmacology Authors: Delgado M, Urbaniak A, Chambers TC Tags: Biochem Pharmacol Source Type: research
Genome-wide association mapping identifies markers associated with cane yield components and sucrose traits in the Louisiana sugarcane core collection.
Abstract Sugarcane is an economically important crop for both food and biofuel industries. Marker-assisted breeding in sugarcane is becoming a reality with the recent development and deployment of markers linked with disease resistance genes. Large linkage disequilibrium in sugarcane makes genome-wide association studies (GWAS) a better alternative to biparental mapping to identify markers associated with agronomic traits. GWAS was conducted on a Louisiana core collection to identify marker-trait associations (MTA) for 11 cane yield and sucrose traits using single nucleotide polymorphism (SNP) and insertion-deleti...
Source: Genomics - December 6, 2018 Category: Genetics & Stem Cells Authors: Fickett N, Gutierrez A, Verma M, Pontif M, Hale A, Kimbeng C, Baisakh N Tags: Genomics Source Type: research
Microtubule-Based Control of Motor-Clutch System Mechanics in Glioma Cell Migration
Publication date: 27 November 2018Source: Cell Reports, Volume 25, Issue 9Author(s): Louis S. Prahl, Patrick F. Bangasser, Lauren E. Stopfer, Mahya Hemmat, Forest M. White, Steven S. Rosenfeld, David J. OddeSummaryMicrotubule-targeting agents (MTAs) are widely used chemotherapy drugs capable of disrupting microtubule-dependent cellular functions, such as division and migration. We show that two clinically approved MTAs, paclitaxel and vinblastine, each suppress stiffness-sensitive migration and polarization characteristic of human glioma cells on compliant hydrogels. MTAs influence microtubule dynamics and cell traction fo...
Source: Cell Reports - November 28, 2018 Category: Cytology Source Type: research
Delayed adverse events in phase I trials of molecularly targeted and cytotoxic agents.
Conclusion: Overall AE incidence was lower in MTAs than CCs across six cycles. For MTAs, more frequent incidence of first grade 3/4 AEs after cycle 1 supports incorporation of delayed AEs into recommendations for Phase 2 dosing. PMID: 30338038 [PubMed] (Source: Oncotarget)
Source: Oncotarget - October 20, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Vinca alkaloids and analogues as anti-cancer agents: Looking back, peering ahead.
Abstract Cancer still represents a "nightmare" worldwide, causing annually millions of victims. Several antiproliferative molecules are currently used as drugs market and offer a pharmaceutical opportunity for attenuating and treating tumor manifestations. In this context, natural sources have a relevant role, since they provide the 60% of currently-used anticancer agents. Among the numerous natural products, acting via different mechanisms of action, microtubule-targeting agents (MTAs) have a high therapeutic potential, since they disrupt the abnormal cancer cell growth, interfering with the continuous ...
Source: Bioorganic and Medicinal Chemistry Letters - August 22, 2018 Category: Chemistry Authors: Martino E, Casamassima G, Castiglione S, Cellupica E, Pantalone S, Papagni F, Rui M, Siciliano AM, Collina S Tags: Bioorg Med Chem Lett Source Type: research
Provenance and risk in transfer of biological materials
by Jane Nielsen, Tania Bubela, Don R. C. Chalmers, Amber Johns, Linda Kahl, Joanne Kamens, Charles Lawson, John Liddicoat, Rebekah McWhirter, Ann Monotti, James Scheibner, Tess Whitton, Dianne Nicol Whereas biological materials were once transferred freely, there has been a marked shift in the formalisation of exchanges involving these materials, primarily through the use of Material Transfer Agreements (MTAs). This paper considers how risk aversion dominates MTA negotiations and the impact i t may have on scientific progress. Risk aversion is often based on unwarranted fears of incurring liability through the use of a ma...
Source: PLoS Biology: Archived Table of Contents - August 13, 2018 Category: Biology Authors: Jane Nielsen Source Type: research
Genome-wide association mapping of vitamins B1 and B2 in common wheat
Publication date: June 2018Source: The Crop Journal, Volume 6, Issue 3Author(s): Jieyun Li, Jindong Liu, Wei'e Wen, Pingzhi Zhang, Yingxiu Wan, Xianchun Xia, Yan Zhang, Zhonghu HeAbstractVitamin B is essential for maintaining normal life activities in humans and animals who have to intake the microelement from the outside, especially from cereal products. In the present study 166 Chinese and foreign wheat cultivars planted in two environments were characterized for variation in vitamin B1 and B2 contents. A genome-wide association study (GWAS) using the wheat 90 K SNP assay identified 17 loci for vitamin B1 and 7 for ...
Source: The Crop Journal - July 11, 2018 Category: Food Science Source Type: research
Microtubule-Targeting Agents: Strategies To Hijack the Cytoskeleton.
Abstract Microtubule-targeting agents (MTAs) such as paclitaxel and the vinca alkaloids are among the most important medical weapons available to combat cancer. MTAs interfere with intracellular transport, inhibit eukaryotic cell proliferation, and promote cell death by suppressing microtubule dynamics. Recent advances in the structural analysis of MTAs have enabled the extensive characterization of their interactions with microtubules and their building block tubulin. We review here our current knowledge on the molecular mechanisms used by MTAs to hijack the microtubule cytoskeleton, and discuss dual inhibitors t...
Source: Trends in Cell Biology - June 2, 2018 Category: Cytology Authors: Steinmetz MO, Prota AE Tags: Trends Cell Biol Source Type: research
Radiosynthesis and in vivo evaluation of [11C]MPC-6827, the first brain penetrant microtubule PET ligand
Conclusions: We report the automated radiolabeling procedure for [11C]MPC-6827 with high radiochemical yield, purity and specific activity. In vivo studies in rodents indicated BBB penetration and binding of the radiotracer in brain and other organs. Combination of favorable kinetics and robust specific binding with excellent brain uptake may make [11C]MPC-6827 a suitable PET ligand for the in vivo quantification of MT inside and outside the brain. Lack of a suitable reference region is likely to be due to ubiquitous target distribution instead a specific property of this ligand. Grant support: Diane Goldberg Foundation (N...
Source: Journal of Nuclear Medicine - May 23, 2018 Category: Nuclear Medicine Authors: Solingapuram Sai, K. K., Prabhakaran, J., Oufkir, H., Ramanathan, G., Whitlow, C., Dileep, H., Mann, J. J., Mintz, A., Kumar, D. Tags: Probes for Neuroimaging Posters Source Type: research
miR-195 Potentiates the Efficacy of Microtubule-Targeting Agents in Non-Small Cell Lung Cancer
Microtubule-targeting agents (MTAs) are widely used for the treatment of non-small cell lung cancer (NSCLC). The response rate is only ∼25%, mainly attributable to drug resistance. To identify determinants of resistance in NSCLC, we performed a high-throughput screen using a library of miRNA mimics. Here we report that miR-195 synergizes with MTAs to inhibit the growth of NSCLC cells in vitro, that increased expression of miR-195 sensitizes NSCLC cells to MTAs and that repression of miR-195 confers resistance to MTAs. (Source: Cancer Letters)
Source: Cancer Letters - April 13, 2018 Category: Cancer & Oncology Authors: Xiaojie Yu, Yiqiang Zhang, Xiuye Ma, Alexander Pertsemlidis Tags: Original Articles Source Type: research
Meta-analysis of molecular targeted agents in the treatment of elderly patients with metastatic colorectal cancer: Does the age matter ?
Conclusions: The introduction of MTAs to therapies offered a survival benefit in elderly patients with mCRC. Further studies aimed at this specific patient population were still needed to watchfully monitor potential treatment-related toxicities to optimize the use of these drugs. (Source: Journal of Cancer Research and Therapeutics)
Source: Journal of Cancer Research and Therapeutics - March 26, 2018 Category: Cancer & Oncology Authors: Chuan Jie Zhao ShuLiang Li Qiang Liu Source Type: research
Regulation of E-cadherin localization by microtubule targeting agents: rapid promotion of cortical E-cadherin through p130Cas/Src inhibition by eribulin.
Authors: Dybdal-Hargreaves NF, Risinger AL, Mooberry SL Abstract Microtubule targeting agents (MTAs) are some of the most effective anticancer drugs used to treat a wide variety of adult and pediatric cancers. Building evidence suggests that these drugs inhibit interphase signaling events and that this contributes to their anticancer actions. The effects of diverse MTAs were evaluated following a 2 hour incubation with clinically relevant concentrations to test the hypothesis that these drugs rapidly and differentially disrupt epithelial-to-mesenchymal transition (EMT)-related signaling. The MTAs rapidly promoted t...
Source: Oncotarget - February 23, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Genetic dissection of wheat panicle traits using linkage analysis and a genome-wide association study.
This study provides potentially valuable information on the dissection of yield-component traits and valuable genetic alleles for molecular-design breeding or functional gene exploration. PMID: 29470622 [PubMed - as supplied by publisher] (Source: TAG. Theoretical and Applied Genetics)
Source: TAG. Theoretical and Applied Genetics - February 22, 2018 Category: Genetics & Stem Cells Authors: Liu K, Sun X, Ning T, Duan X, Wang Q, Liu T, An Y, Guan X, Tian J, Chen J Tags: Theor Appl Genet Source Type: research
Current Status and Future Prospects of Next-Generation Data Management and Analytical Decision Support Tools for Enhancing Genetic Gains in Crops.
Abstract Agricultural disciplines are becoming data intensive and the agricultural research data generation technologies are becoming sophisticated and high throughput. On the one hand, high-throughput genotyping is generating petabytes of data; on the other hand, high-throughput phenotyping platforms are also generating data of similar magnitude. Under modern integrated crop breeding, scientists are working together by integrating genomic and phenomic data sets of huge data volumes on a routine basis. To manage such huge research data sets and use them appropriately in decision making, Data Management Analysis &a...
Source: Advances in Biochemical Engineering Biotechnology - January 26, 2018 Category: Biotechnology Authors: Rathore A, Singh VK, Pandey SK, Rao CS, Thakur V, Pandey MK, Anil Kumar V, Das RR Tags: Adv Biochem Eng Biotechnol Source Type: research
Interactome Analysis of Microtubule-targeting Agents Reveals Cytotoxicity Bases in Normal Cells
Publication date: Available online 12 December 2017 Source:Genomics, Proteomics & Bioinformatics Author(s): Andrés Julián Gutiérrez-Escobar, Gina Méndez-Callejas Cancer causes millions of deaths annually and microtubule-targeting agents (MTAs) are the most commonly-used anti-cancer drugs. However, the high toxicity of MTAs on normal cells raises great concern. Due to the non-selectivity of MTA targets, we analyzed the interaction network in a non-cancerous human cell. Subnetworks of fourteen MTAs were reconstructed and the merged network was compared against a randomized network to eval...
Source: Genomics, Proteomics and Bioinformatics - December 16, 2017 Category: Bioinformatics Source Type: research
Revisiting the definition of dose-limiting toxicities in paediatric oncology phase I clinical trials: An analysis from the Innovative Therapies for Children with Cancer Consortium
Dose-escalation trials aim to identify the maximum tolerated dose and, importantly, the recommended phase II dose (RP2D) and rely on the occurrence of dose-limiting toxicities (DLTs) during the first treatment cycle. Molecularly targeted agents (MTAs) often follow continuous and prolonged administrations, displaying a distinct toxicity profile compared to conventional chemotherapeutics, and classical DLT criteria might not be appropriate to evaluate MTAs' toxicity. We investigated this issue in children. (Source: European Journal of Cancer)
Source: European Journal of Cancer - October 19, 2017 Category: Cancer & Oncology Authors: Francisco Bautista, Lucas Moreno, Lynley Marshall, Andrew D.J. Pearson, Birgit Geoerger, Xavier Paoletti Tags: Original Research Source Type: research
Genome-wide association mapping of vitamins B1 and B2 in common wheat
Publication date: Available online 4 October 2017 Source:The Crop Journal Author(s): Jieyun Li, Jindong Liu, Wei'e Wen, Pingzhi Zhang, Yingxiu Wan, Xianchun Xia, Yan Zhang, Zhonghu He Vitamin B is essential for maintaining normal life activities in humans and animals who have to intake the microelement from the outside, especially from cereal products. In the present study 166 Chinese and foreign wheat cultivars planted in two environments were characterized for variation in vitamin B1 and B2 contents. A genome-wide association study (GWAS) using the wheat 90K SNP assay identified 17 loci for vitamin B1 and 7 for vitamin ...
Source: The Crop Journal - October 5, 2017 Category: Food Science Source Type: research
Enhancing monoterpene alcohols in sweet potato shochu using the diglycoside-specific β-primeverosidase
Publication date: Available online 12 September 2017 Source:Journal of Bioscience and Bioengineering Author(s): Yuichiro Sato, Jinshun Han, Hisashi Fukuda, Shigeaki Mikami Monoterpene alcohols (MTAs) are characteristic flavour-imparting compounds in sweet potato shochu (Japanese distilled spirit) that are liberated following hydrolysis by specific enzymes during fermentation. In the present study, we evaluated the effect of an exogenously added diglycoside-specific β-glycosidase (β-primeverosidase) on aroma formation during shochu brewing using various sweet potato species to address whether MTAs are predominant...
Source: Journal of Bioscience and Bioengineering - September 13, 2017 Category: Biomedical Science Source Type: research
MTA1 expression in human cancers – Clinical and pharmacological significance
Publication date: November 2017 Source:Biomedicine & Pharmacotherapy, Volume 95 Author(s): Vijaya Lakshmi Malisetty, Vasudevarao Penugurti, Prashanth Panta, Suresh Kumar Chitta, Bramanandam Manavathi Remarkably, majority of the cancer deaths are due to metastasis, not because of primary tumors. Metastasis is one of the important hallmarks of cancer. During metastasis invasion of primary tumor cells from the site of origin to a new organ occurs. Metastasis associated proteins (MTAs) are a small family of transcriptional coregulators that are closely associated with tumor metastasis. These proteins are integral comp...
Source: Biomedicine and Pharmacotherapy - September 12, 2017 Category: Drugs & Pharmacology Source Type: research
MTA1 expression in human cancers - Clinical and pharmacological significance.
Abstract Remarkably, majority of the cancer deaths are due to metastasis, not because of primary tumors. Metastasis is one of the important hallmarks of cancer. During metastasis invasion of primary tumor cells from the site of origin to a new organ occurs. Metastasis associated proteins (MTAs) are a small family of transcriptional coregulators that are closely associated with tumor metastasis. These proteins are integral components of nuclear remodeling and deacetylation complex (NuRD). By virtue of being integral components of NuRD, these proteins regulate the gene expression by altering the epigenetic changes s...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - September 11, 2017 Category: Drugs & Pharmacology Authors: Malisetty VL, Penugurti V, Panta P, Chitta SK, Manavathi B Tags: Biomed Pharmacother Source Type: research
Molecularly targeted agents in oculoplastic surgery
Purpose of review:Significant advances have been made in oncology and rheumatology with the introduction of molecularly targeted agents (MTAs). MTAs consist of monoclonal antibodies and small molecule inhibitors. The purpose of this manuscript is to review the recent applications of MTAs to orbital, lacrimal, and eyelid disease. Recent findings:The use of monoclonal antibodies has been described in the treatment of orbital vascular lesions, lymphoma, and squamous cell carcinoma. Inflammatory conditions treated with monoclonal antibodies include thyroid eye disease, IgG4 disease, and granulomatosis with polyangiitis. Immun...
Source: Current Opinion in Ophthalmology - August 18, 2017 Category: Opthalmology Tags: OCULOPLASTIC AND ORBITAL SURGERY: Edited by Richard C. Allen Source Type: research
The novel microtubule targeting agent BAL101553 in combination with radiotherapy in treatment-refractory tumor models
Resistance to microtubule targeting agents (MTA) represents a major drawback in successful cancer therapy with MTAs. Here we investigated the combined treatment modality of the novel MTA BAL101553 in combination with radiotherapy in paclitaxel and epothilone-resistant tumor models. (Source: Radiotherapy and Oncology)
Source: Radiotherapy and Oncology - August 7, 2017 Category: Radiology Authors: Ashish Sharma, Angela Broggini-Tenzer, Van Vuong, Alessandra Messikommer, Katarzyna J. Nytko, Matthias Guckenberger, Felix Bachmann, Heidi A. Lane, Martin Pruschy Tags: Original article Source Type: research
The novel microtubule targeting agent BAL101553 in combination with radiotherapy in treatment-refractory tumor models.
CONCLUSIONS: BAL101553 is a promising alternative in taxane- and epothilone-refractory tumors as part of a combined treatment modality with ionizing radiation. Its potent antitumor effect is not only tumor cell-directed but also targets the tumor microenvironment. PMID: 28797699 [PubMed - as supplied by publisher] (Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology)
Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - August 7, 2017 Category: Radiology Authors: Sharma A, Broggini-Tenzer A, Vuong V, Messikommer A, Nytko KJ, Guckenberger M, Bachmann F, Lane HA, Pruschy M Tags: Radiother Oncol Source Type: research
Exploring the effect of end-binding proteins and microtubule targeting chemotherapy drugs on microtubule dynamic instability
Publication date: 21 September 2017 Source:Journal of Theoretical Biology, Volume 429 Author(s): Diana White, Stéphane Honoré, Florence Hubert Microtubules (MTs) play a key role in normal cell development and are a primary target for many cancer chemotherapy MT targeting agents (MTAs). As such, understanding MT dynamics in the presence of such agents, as well as other proteins that alter MT dynamics, is extremely important. In general, MTs grow relatively slowly and shorten very fast (almost instantaneously), an event referred to as a catastrophe. These dynamics, referred to as dynamic instability, have been...
Source: Journal of Theoretical Biology - June 27, 2017 Category: Biology Source Type: research
Association mapping to discover significant marker-trait associations for resistance against fusarium wilt variant 2 in pigeonpea [Cajanus cajan (L.) Millspaugh] using SSR markers.
Abstract Pigeonpea production is severely constrained by wilt disease caused by Fusarium udum. In the current study, we discover the putative genomic regions that control resistance response to variant 2 of fusarium wilt using association mapping approach. The association panel comprised of 89 diverse pigeonpea genotypes including seven varieties, three landraces and 79 germplasm lines. The panel was screened rigorously for 3 consecutive years (2013-14, 2014-15 and 2015-2016) against variant 2 in a wilt-sick field. A total of 65 pigeonpea specific hypervariable SSR markers (HASSRs) were screened representing ...
Source: J Appl Genet - June 3, 2017 Category: Genetics & Stem Cells Authors: Patil PG, Dubey J, Bohra A, Mishra RK, Saabale PR, Das A, Rathore M, Singh NP Tags: J Appl Genet Source Type: research
Genome-wide association study for agronomic and physiological traits in spring wheat evaluated in a range of heat prone environments.
Abstract KEY MESSAGE: We identified 27 stable loci associated with agronomic traits in spring wheat using genome-wide association analysis, some of which confirmed previously reported studies. GWAS peaks identified in regions where no QTL for grain yield per se has been mapped to date, provide new opportunities for gene discovery and creation of new cultivars with desirable alleles for improving yield and yield stability in wheat. We undertook large-scale genetic analysis to determine marker-trait associations (MTAs) underlying agronomic and physiological performance in spring wheat using genome-wide association s...
Source: TAG. Theoretical and Applied Genetics - June 2, 2017 Category: Genetics & Stem Cells Authors: Ogbonnaya FC, Rasheed A, Okechukwu EC, Jighly A, Makdis F, Wuletaw T, Hagras A, Uguru MI, Agbo CU Tags: Theor Appl Genet Source Type: research
Mechanisms of the anti-tumor activity of Methyl 2-(-5-fluoro-2-hydroxyphenyl)-1 H-benzo[d]imidazole-5-carboxylate against breast cancer in vitro and in vivo.
In this study, we demonstrated that MBIC exhibits greater toxicity towards non-aggressive breast cancer cell-line, MCF-7 (IC50 = 0.73 ± 0.0 μM) compared to normal fibroblast cell-line, L-cells (IC50 = 59.6 ± 2.5 μM). The IC50 of MBIC against the aggressive breast cancer cell-line, MDA-MB-231 was 20.4 ± 0.2 μM. We hypothesized that the relatively high resistance of MDA-MB-231 cells to MBIC is associated with p53 mutation. We investigated p53 and three of its downstream proteins: survivin, cyclin dependent kinase (Cdk1) and cyclin B1. Following treatment with MBIC, survivin co-immunoprecipitated...
Source: Oncotarget - April 12, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Dendritic Cell Strategies for Eliciting Mutation-Derived Tumor Antigen Responses in Patients
Abstract: Dendritic cells (DCs) are equipped for sensing danger signals and capturing, processing, and presenting antigens to naive or effector cells and are critical in inducing humoral and adaptive immunity. Successful vaccinations are those that activate DCs to elicit both cellular and humoral responses, as well as long-lasting memory response against the target of interest. Recently, it has become apparent that tumor cells can provide new sources of antigens through nonsynonymous mutations or frame-shift mutations, leading to potentially hundreds of mutation-derived tumor antigens (MTAs) or neoantigens. T cells recogni...
Source: The Cancer Journal - March 1, 2017 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Dendritic Cell Strategies for Eliciting Mutation-Derived Tumor Antigen Responses in Patients.
Abstract Dendritic cells (DCs) are equipped for sensing danger signals and capturing, processing, and presenting antigens to naive or effector cells and are critical in inducing humoral and adaptive immunity. Successful vaccinations are those that activate DCs to elicit both cellular and humoral responses, as well as long-lasting memory response against the target of interest. Recently, it has become apparent that tumor cells can provide new sources of antigens through nonsynonymous mutations or frame-shift mutations, leading to potentially hundreds of mutation-derived tumor antigens (MTAs) or neoantigens. T cells...
Source: Cancer Journal - March 1, 2017 Category: Cancer & Oncology Authors: Balan S, Finnigan J, Bhardwaj N Tags: Cancer J Source Type: research
Suppression of Spindly Delays Mitotic Exit and Exacerbates Cell Death Response of Cancer Cells Treated with Low Doses of Paclitaxel
Microtubule-targeting agents (MTAs) are used extensively for the treatment of diverse types of cancer. They block cancer cells in mitosis through the activation of the spindle assembly checkpoint (SAC), the surveillance mechanism that ensures accurate chromosome segregation at the onset of anaphase. However, the cytotoxic activity of MTAs is limited by premature mitotic exit (mitotic slippage) due to SAC silencing. Here we have explored the dual role of the protein Spindly in chromosome attachments and SAC silencing to analyze the consequences of its depletion on the viability of tumor cells treated with clinically relevan...
Source: Cancer Letters - February 26, 2017 Category: Cancer & Oncology Authors: Patr ícia M.A. Silva, Nilza Ribeiro, Raquel T. Lima, Cláudia Andrade, Vânia Diogo, Joana Teixeira, Cláudia Florindo, Álvaro Tavares, M. Helena Vasconcelos, Hassan Bousbaa Tags: Original Articles Source Type: research
Abstract P5-14-07: Impact of time to treatment (TTT) on recurrence free survival in non metastatic invasive breast cancer
Microtubule targeting agents (MTAs) continue to be some of the most valuable drugs used to treat breast cancer. While decades of research have shown that these drugs cause mitotic arrest in cells by suppressing the dynamic instability of microtubules, recent evidence demonstrates that the ability of MTAs to disrupt microtubule-dependent transport of key signaling components, including proteins and microRNAs, in interphase cells likely contributes to their anticancer actions. TGF-β signaling is a driver of oncogenesis and epithelial-to-mesenchymal transition (EMT) that involves multiple protein trafficking and intracel...
Source: Cancer Research - February 14, 2017 Category: Cancer & Oncology Authors: SR Tiwari, P Elson, K Tullio, GT Budd Tags: Poster Session Abstracts Source Type: research
Determinants of the recommended phase 2 dose of molecular targeted agents
CONCLUSIONSIn the past decade, there has been a dominance of a nonclassical approach using multiple endpoints with or without toxicity or single nontoxicity endpoints to define RPTD in MTA monotherapy phase 1 trials. Nonclassically defined RP2Ds for MTAs appear to be associated with a higher rate of FDA drug approval. Cancer 2017. © 2017 American Cancer Society. (Source: Cancer)
Source: Cancer - February 9, 2017 Category: Cancer & Oncology Authors: Aaron R. Hansen, Natalie Cook, Eitan Amir, Lillian L. Siu, Albiruni Ryan Abdul Razak Tags: Original Article Source Type: research
Marine Derived Anticancer Drugs Targeting Microtubule.
CONCLUSION: The marine derived MTAs hold great potential in the field of cancer therapeutics and are gradually advancing in the clinical set up. A deeper understanding of the molecular mechanisms combined with innovative therapeutic regimen would lead to great advances in the field. PMID: 28067173 [PubMed - as supplied by publisher] (Source: Recent Patents on Anti-Cancer Drug Discovery)
Source: Recent Patents on Anti-Cancer Drug Discovery - January 12, 2017 Category: Cancer & Oncology Tags: Recent Pat Anticancer Drug Discov Source Type: research
Cancer: Microtubule-straightening compound widens the therapeutic window
Nature Reviews Drug Discovery 16, 17 (2017). doi:10.1038/nrd.2016.275 Author: Alexandra Flemming Microtubule-targeting agents (MTAs) are standard-of care chemotherapeutics for a wide range of cancers, but their use is limited by side effects such as neuropathy. Now, reporting in Science Translational Medicine, Brouhard, Roulston and colleagues present a novel small-molecule MTA that has potent antitumour activity (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 29, 2016 Category: Drugs & Pharmacology Authors: Alexandra Flemming Tags: Research Highlight Source Type: research
Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines
Microtubules are currently ranked one of the most validated targets for chemotherapy; with clinical use of microtubule targeting agents (MTAs) extending beyond half a century. Recent research has focused on the development of novel MTAs to combat drug resistance and drug associated toxicities. Of particular interest are compounds structurally different to those currently used within the clinic. The pyrrolo-1, 5-benzoxazepines (PBOXs) are a structurally distinct novel group of anti-cancer agents, some of which target tubulin. Herein, we review the chemistry, mechanism of action, preclinical development of the PBOXs and comp...
Source: Journal of Cancer - December 23, 2016 Category: Cancer & Oncology Authors: LM Greene, S Butini, G Campiani, DC Williams, DM Zisterer Tags: Review Source Type: research
Randomized phase II trial comparing molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer: cross-over analysis from the SHIVA trial
ConclusionsThe cross-over analysis of the SHIVA trial identified 37% of patients who crossed-over from TPC to MTA with a PFSMTA/PFSTPC ratio exceeding 1.3. (Source: Annals of Oncology)
Source: Annals of Oncology - December 19, 2016 Category: Cancer & Oncology Source Type: research
The efficacy and safety of platinum plus gemcitabine (PG) chemotherapy with or without molecular targeted agent (MTA) in first-line treatment of non-small cell lung cancer (NSCLC)
Conclusion: The combination of PG plus MTA was superior to PG alone in terms of PFS and ORR but not in OS. The combination chemotherapy also showed a higher frequency of grade 3 or higher toxic effects in patients with advanced NSCLC than PG chemotherapy. (Source: Medicine)
Source: Medicine - December 1, 2016 Category: Internal Medicine Tags: Research Article: Systematic Review and Meta-Analysis Source Type: research