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https://www.readbyqxmd.com/read/28225457/rhoa-rock-pathway-inhibition-by-fasudil-suppresses-the-vasculogenic-mimicry-of-u2os-osteosarcoma-cells-in-vitro
#1
Yun Xia, Xianyi Cai, Jiquan Fan, Liling Zhang, Zhenyu Li, Jinghua Ren, Gang Wu, Fang Zhu
GTPase RhoA and its downstream Rho-associated coiled-coil-containing protein kinases (ROCKs) are frequently overexpressed in human cancers. Inhibition of the RhoA/ROCK pathway blocks angiogenesis mediated by the vascular endothelial growth factor, which led us to investigate the role of this pathway in vasculogenic mimicry (VM) - a process by which aggressive cancer cells form vessel-like structures that provide adequate blood supply for tumor growth. We showed that the expression of RhoA and its effector kinases ROCK1/2 was much higher in human osteosarcoma (OS) tissues and the human OS cell line U2OS than in nontumorous tissues and cell line hFOB 1...
February 20, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28218831/new-possibilities-for-magnetic-control-of-chemical-and-biochemical-reactions
#2
Anatoly Buchachenko, Ronald G Lawler
Chemistry is controlled by Coulomb energy; magnetic energy is lower by many orders of magnitude and may be confidently ignored in the energy balance of chemical reactions. The situation becomes less clear, however, when reaction rates are considered. In this case, magnetic perturbations of nearly degenerate energy surface crossings may produce observable, and sometimes even dramatic, effects on reactions rates, product yields, and spectroscopic transitions. A case in point that has been studied for nearly five decades is electron spin-selective chemistry via the intermediacy of radical pairs...
February 20, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28217708/aberrant-rna-splicing-and-mutations-in-spliceosome-complex-in-acute-myeloid-leukemia
#3
COMMENT
Jianbiao Zhou, Wee-Joo Chng
The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Leukemia stem cell (LSC) populations, although rare, are essential contributors of treatment failure and relapse. Recent researches have provided the compelling evidence that link the erratic spicing activity to the LSC phenotype in acute myeloid leukemia (AML)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28215223/the-functional-stability-of-foxp3-and-ror%C3%AE-t-in-treg-and-th17-and-their-therapeutic-applications
#4
J Ren, B Li
The balance of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) and effector T cells plays a key role in maintaining immune homeostasis, while the imbalance of them is related to many inflammatory diseases in both human and mice. Here we discuss about the plasticity of Tregs and Th17 cells, and the related human diseases resulted from the imbalance of them. Further, we will focus on the mechanisms regulating the plasticity between Tregs and Th17 cells and the potential therapeutic strategies by targeting regulators of the expression and activity of FOXP3 and RORγt or regulators of Treg/Th17 balance in autoimmune diseases, allergy, infection, and cancer...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28214899/therapeutic-targeting-of-epithelial-plasticity-programs-focus-on-the-epithelial-mesenchymal-transition
#5
Reem Malek, Hailun Wang, Kekoa Taparra, Phuoc T Tran
Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28213718/reprogramming-cell-fates-by-small-molecules
#6
REVIEW
Xiaojie Ma, Linghao Kong, Saiyong Zhu
Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our understanding of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on reprogramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for various applications, such as disease modeling and cell-based transplantation, but also hold great promise to be further developed as drugs to stimulate patients' endogenous cells to repair and regenerate in vivo...
February 17, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28209528/decellularized-human-colorectal-cancer-matrices-polarize-macrophages-towards-an-anti-inflammatory-phenotype-promoting-cancer-cell-invasion-via-ccl18
#7
M L Pinto, E Rios, A C Silva, S C Neves, H R Caires, A T Pinto, C Durães, F A Carvalho, A P Cardoso, N C Santos, C C Barrias, D S Nascimento, P Pinto-do-Ó, M A Barbosa, F Carneiro, M J Oliveira
Macrophages are frequently identified in solid tumors, playing important roles in cancer progression. Their remarkable plasticity makes them very sensitive to environmental factors, including the extracellular matrix (ECM). In the present work, we investigated the impact of human colorectal tumor matrices on macrophage polarization and on macrophage-mediated cancer cell invasion. Accordingly, we developed an innovative 3D-organotypic model, based on the decellularization of normal and tumor tissues derived from colorectal cancer patients' surgical resections...
February 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28209166/intra-tumor-heterogeneity-from-a-cancer-stem-cell-perspective
#8
REVIEW
Pramudita R Prasetyanti, Jan Paul Medema
Tumor heterogeneity represents an ongoing challenge in the field of cancer therapy. Heterogeneity is evident between cancers from different patients (inter-tumor heterogeneity) and within a single tumor (intra-tumor heterogeneity). The latter includes phenotypic diversity such as cell surface markers, (epi)genetic abnormality, growth rate, apoptosis and other hallmarks of cancer that eventually drive disease progression and treatment failure. Cancer stem cells (CSCs) have been put forward to be one of the determining factors that contribute to intra-tumor heterogeneity...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28205577/epigenetic-signatures-of-invasive-status-in-populations-of-marine-invertebrates
#9
Alba Ardura, Anastasija Zaiko, Paloma Morán, Serge Planes, Eva Garcia-Vazquez
Epigenetics, as a DNA signature that affects gene expression and enables rapid reaction of an organism to environmental changes, is likely involved in the process of biological invasions. DNA methylation is an epigenetic mechanism common to plants and animals for regulating gene expression. In this study we show, for the first time in any marine species, significant reduction of global methylation levels during the expansive phase of a pygmy mussel (Xenostrobus securis) recent invasion in Europe (two-year old), while in older introductions such epigenetic signature of invasion was progressively reduced...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205155/endocrine-disruptors-and-obesity
#10
REVIEW
Philippa D Darbre
PURPOSE OF REVIEW: The purpose of this review was to summarise current evidence that some environmental chemicals may be able to interfere in the endocrine regulation of energy metabolism and adipose tissue structure. RECENT FINDINGS: Recent findings demonstrate that such endocrine-disrupting chemicals, termed "obesogens", can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and as ingredients in personal care products...
February 15, 2017: Current Obesity Reports
https://www.readbyqxmd.com/read/28202626/cancer-cells-exhibit-clonal-diversity-in-phenotypic-plasticity
#11
Robert Austin Mathis, Ethan S Sokol, Piyush B Gupta
Phenotypic heterogeneity in cancers is associated with invasive progression and drug resistance. This heterogeneity arises in part from the ability of cancer cells to switch between phenotypic states, but the dynamics of this cellular plasticity remain poorly understood. Here we apply DNA barcodes to quantify and track phenotypic plasticity across hundreds of clones in a population of cancer cells exhibiting epithelial or mesenchymal differentiation phenotypes. We find that the epithelial-to-mesenchymal cell ratio is highly variable across the different clones in cancer cell populations, but remains stable for many generations within the progeny of any single clone-with a heritability of 0...
February 2017: Open Biology
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#12
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202513/myeloid-cells-that-impair-immunotherapy-are-restored-in-melanomas-which-acquire-resistance-to-braf-inhibitors
#13
Shannon M Steinberg, Tamer Shabaneh, Peisheng Zhang, Viktor Martyanov, Zhenghui Li, Brian Malik, Tammara Wood, Andrea Boni, Aleksey Molodtsov, Christina V Angeles, Tyler J Curiel, Michael Whitfield, Mary Jo Turk
Acquired resistance to BRAFV600E inhibitors (BRAFi) in melanoma remains a common clinical obstacle, as is the case for any targeted drug therapy that can be developed given the plastic nature of cancers. While there has been significant focus on the cancer cell-intrinsic properties of BRAFi resistance, the impact of BRAFi resistance on host immunity has not been explored. Here we provide preclinical evidence that resistance to BRAFi in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment initially reduced by BRAFi treatment...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198179/breast-reconstruction-after-mastectomy-for-breast-cancer-comparative-analysis-of-early-and-delayed-reconstruction
#14
William Seidel, Jorge Bins Ely, Daniel Ongaratto Barazzetti, Renata Della Giustina, Gustavo P Walter, Thiago A Ferri, Rosemeri Maurici, Janaína L Narciso-Schiavon
BACKGROUND: Early reconstruction after mastectomy for breast cancer with definitive implants has been widely used, especially with the evolution of conservative surgical breast cancer treatments. We aimed to identify different characteristics associated with plastic surgery, based on immediate or delayed reconstruction time and evaluate quality of life in patients undergoing mastectomy for cancer. METHODS: This is a cross-sectional analytical study that evaluated adult patients undergoing mastectomy for breast cancer and breast reconstruction in Plastic Surgery Service at a tertiary hospital...
February 14, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28197531/targeting-sox9-for-degradation-to-inhibit-chemoresistance-metastatic-spread-and-recurrence
#15
Aldwin Suryo Rahmanto, Fredrik J Swartling, Olle Sangfelt
Cancer cells with stem-like properties are believed to contribute to treatment resistance, dissemination, and recurrence. SOX9 controls stem cell plasticity and its deregulation may provide a basis for tumor progression. Here, we summarize our findings of targeted SOX9 destruction by SCF(FBW7) (Skp1/Cul1/F-box) in medulloblastoma and its potential for therapeutic intervention.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28197369/the-transcriptome-of-lung-tumor-infiltrating-dendritic-cells-reveals-a-tumor-supporting-phenotype-and-a-microrna-signature-with-negative-impact-on-clinical-outcome
#16
Lotte Pyfferoen, Elisabeth Brabants, Celine Everaert, Nancy De Cabooter, Kelly Heyns, Kim Deswarte, Manon Vanheerswynghels, Sofie De Prijck, Glenn Waegemans, Melissa Dullaers, Hamida Hammad, Olivier De Wever, Pieter Mestdagh, Jo Vandesompele, Bart N Lambrecht, Karim Y Vermaelen
Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the biology of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogeneous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs are emerging as clinically relevant parameters in lung cancer. In this study, we used an orthotopic preclinical model of lung cancer to dissect how the lung tumor micro-environment affects tissue-resident DCs and extract novel biologically and clinically relevant information...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194541/undermining-plastic-surgery-as-a%C3%A2-possible-option-for-treating-basal-cell-carcinoma-of-the-forehead
#17
Georgi Tchernev, Ivan Pidakev, Ilia Lozev, Torello Lotti, Jose Carlos Cardoso, James W Patterson
Basal cell carcinoma (BCC) is the most common cutaneous cancer. Although most cases can be cured with simple surgical procedures and are associated with a good prognosis, a minority of BCCs may pose significant therapeutic challenges. This occurs mostly in cases of so-called advanced BCC, which a loosely defined term that encompasses locally advanced lesions and tumors with metastatic spread. Treatment of these cases is often complex and sometimes may need combinations of therapeutic modalities, including surgery, radiotherapy and/or targeted therapy directed towards sonic hedgehog (SHH) signaling pathways, such as vismodegib...
February 13, 2017: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28191771/linking-pluripotency-reprogramming-and-cancer
#18
Juan Manuel Iglesias, Juan Gumuzio, Angel G Martin
Tumor development and the generation of induced pluripotent stem cells are highly comparable processes with striking similarities. Cellular plasticity is inherent to tumor evolution, rendering cells that acquire a stem cell-like phenotype, for which Sox2 activation has proved instrumental for the plastic acquisition of stemness properties in tumor cells. Understanding the molecular mechanisms underlying both events might uncover novel approaches for the development of anticancer therapeutics and constitute model systems for understanding tumor generation and ensuring the biosafety of cell-based therapies...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28191467/effects-of-tibolone-on-the-central-nervous-system-clinical-and-experimental-approaches
#19
REVIEW
Rodolfo Pinto-Almazán, Julia J Segura-Uribe, Eunice D Farfán-García, Christian Guerra-Araiza
Hormone replacement therapy (HRT) increases the risk of endometrial and breast cancer. A strategy to reduce this incidence is the use of tibolone (TIB). The aim of this paper was to address the effects of TIB on the central nervous system (CNS). For the present review, MEDLINE (via PubMed), LILACS (via BIREME), Ovid Global Health, SCOPUS, Scielo, and PsycINFO (ProQuest Research Library) electronic databases were searched for the results of controlled clinical trials on peri- and postmenopausal women published from 1990 to September 2016...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28190919/heterogeneity-of-tumor-cells-in-terms-of-cancer-initiating-cells
#20
REVIEW
Eiichi Morii
Tumors derive from a single cell clone but consist of heterogeneous cell subpopulations with diverse features and functions. A limited number of subclones with a selective advantage can initiate tumors when inoculated into immunocompromised mice, and are called cancer-initiating cells (CICs). CICs can be isolated from the bulk of tumors on the basis of their characteristics, such as high reagent efflux, degradation of reactive oxygen species, and aldehyde dehydrogenase (ALDH) activity. Under normal conditions, new CICs are produced by existing CICs rather than non-CICs...
January 2017: Journal of Toxicologic Pathology
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