Not only P-glycoprotein: amplification of the ABCB1-containing chromosome region 7q21 confers multidrug resistance upon cancer cells by coordinated overexpression of an assortment of resistance-related proteins

The development of drug resistance continues to be a dominant hindrance toward curative cancer treatment. Overexpression of a wide-spectrum of ATP-dependent efflux pumps, and in particular of ABCB1 (P-glycoprotein or MDR1) is a well-known resistance mechanism for a plethora of cancer chemotherapeutics including for example taxenes, anthracyclines, Vinca alkaloids, and epipodopyllotoxins, demonstrated by a large array of published papers, both in tumor cell lines and in a variety of tumors, including various solid tumors and hematological malignancies. Upon repeated or even single dose treatment of cultured tumor cells or tumors in vivo with anti-tumor agents such as paclitaxel and doxorubicin, increased ABCB1 copy number has been demonstrated, resulting from chromosomal amplification events at 7q11.2-21 locus, leading to marked P-glycoprotein overexpression, and multidrug resistance (MDR). Clearly however, additional mechanisms such as single nucleotide polymorphisms (SNPs) and epigenetic modifications have shown a role in the overexpression of ABCB1 and of other MDR efflux pumps. However, notwithstanding the design of 4 generations of ABCB1 inhibitors and the wealth of information on the biochemistry and substrate specificity of ABC transporters, translation of this vast knowledge from the bench to the bedside has proven to be unexpectedly difficult. Many studies show that upon repeated treatment schedules of cell cultures or tumors with taxenes and anthracyclines as well as other chemotherapeutic drugs, amplification, and/or overexpression of a series of genes genomically surrounding the ABCB1 locus, is observed. Consequently, altered levels of other proteins may contribute to the establishment of the MDR phenotype, and lead to poor clinical outcome. Thus, the genes contained in this ABCB1 amplicon including ABCB4, SRI, DBF4, TMEM243, and RUNDC3B are overexpressed in many cancers, and especially in MDR tumors, while TP53TG1 and DMTF1 are bona fide tumor suppressors. This review describes the role of these genes in cancer and especially in the acquisition of MDR, elucidates possible connections in transcriptional regulation (co-amplification/repression) of genes belonging to the same ABCB1 amplicon region, and delineates their novel emerging contributions to tumor biology and possible strategies to overcome cancer MDR

Polytrichadelphus bolivianus una nueva especie de Polytrichaceae para el Noroeste de Argentina

Polytrichadelphus bolivianus Herzog, un musgo de los Bosques Montanos de Bolivia es registrado por primera vez para Argentina. Ha sido recolectado en 1997 y 1998 por Schiavone y otros en el norte de la provincia de Salta, pero hasta el momento no había sido identificado. Se presenta una descripción, ilustración y lectotipificación de la especie.Fil: Colotti, Maria T.. Fundación Miguel Lillo; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Suarez, Guillermo Martin. Fundación Miguel Lillo; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán; ArgentinaFil: Schiavone, María M.. Fundación Miguel Lillo; Argentina. Universidad Nacional de Tucuman. Facultad de Cs.naturales E Instituto Miguel Lillo. Instituto Miguel Lillo; Argentin

El género Holomitrium (Dicranaceae, Bryophyta), nuevo registro en Argentina y Uruguay

The genus Holomitrium Brid. is recorded for first time from Argentina and Uruguay. Only one species, H. arboreum, is present in the study area. A brief description, photographs and illustrations of the species are provided.El género Holomitrium (Dicranaceae, Bryophyta), nuevo registro en Argentina y Uruguay. El género Holomitrium Brid. es registrado por primera vez en Argentina y Uruguay. Sólo una especie, H. arboreum, está presente en el área de estudio. Se realiza una breve descripción y se proporcionan fotografías e ilustraciones de la especie.Fil: Suarez, Guillermo Martin. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schiavone, Maria M.. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Colotti, Maria T.. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentin

A macro-element based practical model for seismic analysis of steel-concrete composite high-rise buildings

This is the post-print version of the final paper published in Engineering Structures. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2012 Elsevier B.V.Seismic behaviour of steel–concrete composite high-rise buildings, composed of external steel frames (SFs) and internal concrete tube (CT), with rectangular plan is investigated in this paper. A macro-element based model is established for seismic analysis of composite high-rise buildings aiming at predicting their global responses under earthquakes. By employing this macro-element based model, natural frequencies and vibration modes, storey and inter-storey drifts, overturning moments and storey shear forces of composite structures, induced by earthquakes, are able to be obtained with much less computation time and cost compared with using micro-element based analytical models. To validate its efficiency and reliability, the macro-element based model is employed to analyse a 1/20 scaled-down model of a 25-storey steel–concrete composite high-rise building subjected to simulated earthquakes with various intensities through a shaking table. Natural frequencies and storey drifts of the model structure are obtained from numerical analyses and compared with those from shaking table test results. It has been found that the calculated dynamic responses of the composite model structure subjected to minor, basic, major and super strong earthquakes agree reasonably well with those obtained from experiments, suggesting that the proposed macro-element based model is appropriate for inelastic time-history analyse for global responses of steel–concrete composite high-rise structures subjected to earthquakes with satisfactory precision and reliability. This research thus provides a practical model for elastic and inelastic deformation check of high-rise composite buildings under earthquakes.Ministry of Science and Technology of Chin

Characterization of perfluorocarbon relaxation times and their influence on the optimization of fluorine-19 MRI at 3 tesla.

To characterize and optimize javax.xml.bind.JAXBElement@7524a985 F MRI for different perfluorocarbons (PFCs) at 3T and quantify the loss of acquisition efficiency as a function of different temperature and cellular conditions. The T javax.xml.bind.JAXBElement@1ef4ca84 and T javax.xml.bind.JAXBElement@295b7e6f relaxation times of the commonly used PFCs perfluoropolyether (PFPE), perfluoro-15-crown-5-ether (PFCE), and perfluorooctyl bromide (PFOB) were measured in phantoms and in several different conditions (cell types, presence of fixation agent, and temperatures). These relaxation times were used to optimize pulse sequences through numerical simulations. The acquisition efficiency in each cellular condition was then determined as the ratio of the signal after optimization with the reference relaxation times and after optimization with its proper relaxation times. Finally, PFC detection limits were determined. The loss of acquisition efficiency due to parameter settings optimized for the wrong temperature and cellular condition was limited to 13%. The detection limits of all PFCs were lower at 24 °C than at 37 °C and varied from 11.8 ± 3.0 mM for PFCE at 24 °C to 379.9 ± 51.8 mM for PFOB at 37 °C. Optimizing javax.xml.bind.JAXBElement@30187e57 F pulse sequences with a known phantom only leads to moderate loss in acquisition efficiency in cellular conditions that might be encountered in in vivo and in vitro experiments. Magn Reson Med 77:2263-2271, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Doxorubicin and other anthracyclines in cancers: activity, chemoresistance and its overcoming

Anthracyclines have been important and effective treatments against a number of cancers since their discovery. However, their use in therapy has been complicated by severe side effects and toxicity that occur during or after treatment, including cardiotoxicity. The mode of action of anthracyclines is complex, with several mechanisms proposed. It is possible that their high toxicity is due to the large set of processes involved in anthracycline action. The development of resistance is a major barrier to successful treatment when using anthracyclines. This resistance is based on a series of mechanisms that have been studied and addressed in recent years. This work provides an overview of the anthracyclines used in cancer therapy. It discusses their mechanisms of activity, toxicity, and chemoresistance, as well as the approaches used to improve their activity, decrease their toxicity, and overcome resistance

Crystal structure of an eight-coordinate terbium(III) ion chelated by N,N′-bis­­(2-hy­dr­oxy­benz­yl)-N,N′-bis­­(pyridin-2-ylmeth­yl)ethyl­enedi­amine (bbpen2−) and nitrate

The reaction of terbium(III) nitrate pentahydrate in acetonitrile with N,N′-bis(2-hydroxybenzyl)-N,N′-bis(pyridin-2-ylmethyl)ethylenediamine (H2bbpen), previously deprotonated with triethylamine, produced the mononuclear compound [N,N′-bis(2-oxidobenzyl-κO)-N,N′-bis(pyridin-2-ylmethyl-κN)ethylenediamine-κ2N,N′](nitrato-κ2O,O′)terbium(III), [Tb(C28H28N4O2)(NO3)]. The molecule lies on a twofold rotation axis and the TbIII ion is eight-coordinate with a slightly distorted dodecahedral coordination geometry. In the symmetry-unique part of the molecule, the pyridine and benzene rings are both essentially planar and form a dihedral angle of 61.42 (7)°. In the molecular structure, the N4O4 coordination environment is defined by the hexadentate bbpen ligand and the bidentate nitrate anion. In the crystal, a weak C—H...O hydrogen bond links molecules into a two-dimensional network parallel to (001)

Sorcin in Cancer Development and Chemotherapeutic Drug Resistance

Simple Summary Sorcin is a protein that helps cells handle calcium. It is often found in high amounts in cancer cells, especially those that are resistant to treatment. Sorcin plays a key role in cancer growth and spread by helping cancer cells avoid the toxic effects of chemotherapy drugs, acting on multiple cellular mechanisms. This review will explore sorcin's structure and function, its role in cancer, and how we might be able to target it for new treatments.Abstract SOluble Resistance-related Calcium-binding proteIN (sorcin) earned its name due to its co-amplification with ABCB1 in multidrug-resistant cells. Initially thought to be an accidental consequence of this co-amplification, recent research indicates that sorcin plays a more active role as an oncoprotein, significantly impacting multidrug resistance (MDR). Sorcin is a highly expressed calcium-binding protein, often overproduced in human tumors and multidrug-resistant cancers, and is a promising novel MDR marker. In tumors, sorcin levels inversely correlate with both patient response to chemotherapy and overall prognosis. Multidrug-resistant cell lines consistently exhibit higher sorcin expression compared to their parental counterparts. Furthermore, sorcin overexpression via gene transfection enhances drug resistance to various chemotherapeutic drugs across numerous cancer lines. Conversely, silencing sorcin expression reverses drug resistance in many cell lines. Sorcin participates in several mechanisms of MDR, including drug efflux, drug sequestering, cell death inhibition, gene amplification, epithelial-to-mesenchymal transition, angiogenesis, and metastasis. The present review focuses on the structure and function of sorcin, on sorcin's role in cancer and drug resistance, and on the approaches aimed at targeting sorcin

Venezuela, la lezione di Allende

La tesi sostenuta qui, consta di due parti. La prima, condivisa da molti marxisti latinoamericani, rileva, fatte le debite proporzioni, le molte analogie esistenti fra gli attacchi dell’imperialismo nordamericano che hanno portato al colpo di Stato in Cile nel 1973, e quelli che hanno portato al golpe contro Hugo Chávez, nel 2002, e che sono proseguiti poi nel contesto delle cosiddette “guerre ibride”, o guerre di IV e V generazione contro il Venezuela. Questa interpretazione mostra anche co..

John Steinbeck's Doubts about Capitalism and the "Collective" in the First Third of the Dust Bowl Trilogy: In Dubious Battle

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