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https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#1
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937603/proteome-stability-as-a-key-factor-of-genome-integrity
#2
REVIEW
Sentiljana Gumeni, Zoi Evangelakou, Vassilis G Gorgoulis, Ioannis P Trougakos
DNA damage is constantly produced by both endogenous and exogenous factors; DNA lesions then trigger the so-called DNA damaged response (DDR). This is a highly synchronized pathway that involves recognition, signaling and repair of the damage. Failure to eliminate DNA lesions is associated with genome instability, a driving force in tumorigenesis. Proteins carry out the vast majority of cellular functions and thus proteome quality control (PQC) is critical for the maintenance of cellular functionality. PQC is assured by the proteostasis network (PN), which under conditions of proteome instability address the triage decision of protein fold, hold, or degrade...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28916614/dysregulated-molecular-pathways-in-amyotrophic-lateral-sclerosis-frontotemporal-dementia-spectrum-disorder
#3
REVIEW
Fen-Biao Gao, Sandra Almeida, Rodrigo Lopez-Gonzalez
Frontotemporal dementia (FTD), the second most common form of dementia in people under 65 years of age, is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD overlaps extensively with the motor neuron disease amyotrophic lateral sclerosis (ALS), especially at the genetic level. Both FTD and ALS can be caused by many mutations in the same set of genes; the most prevalent of these mutations is a GGGGCC repeat expansion in the first intron of C9ORF72 As shown by recent intensive studies, some key cellular pathways are dysregulated in the ALS-FTD spectrum disorder, including autophagy, nucleocytoplasmic transport, DNA damage repair, pre-mRNA splicing, stress granule dynamics, and others...
September 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28899689/enhanced-expression-of-genes-related-to-xenobiotic-metabolism-in-the-skin-of-patients-with-atopic-dermatitis-but-not-with-ichthyosis-vulgaris
#4
Stefan Blunder, Sulev Kõks, Gea Kõks, Ene Reimann, Hubert Hackl, Robert Gruber, Verena Moosbrugger-Martinz, Matthias Schmuth, Sandrine Dubrac
Previous transcriptome analyses underscored the importance of immunological and skin barrier abnormalities in atopic dermatitis (AD). We sought to identify novel pathogenic pathways involved in AD by comparing the transcriptomes of AD patients stratified for filaggrin (FLG) null mutations to those of both healthy donors and patients with ichthyosis vulgaris (IV). We applied RNA-sequencing to analyze the whole transcriptome of nonlesional skin. Six-hundred and seven genes (476 up-regulated and 131 down-regulated by greater than 2-fold) and one-hundred and ninety-three genes (172 up-regulated and 21 down-regulated by greater than 2-fold) were differentially expressed when all AD or IV patients were compared to healthy donors, respectively...
September 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28871086/identification-of-hsp90-inhibitors-as-a-novel-class-of-senolytics
#5
Heike Fuhrmann-Stroissnigg, Yuan Yuan Ling, Jing Zhao, Sara J McGowan, Yi Zhu, Robert W Brooks, Diego Grassi, Siobhan Q Gregg, Jennifer L Stripay, Akaitz Dorronsoro, Lana Corbo, Priscilla Tang, Christina Bukata, Nadja Ring, Mauro Giacca, Xuesen Li, Tamara Tchkonia, James L Kirkland, Laura J Niedernhofer, Paul D Robbins
Aging is the main risk factor for many chronic degenerative diseases and cancer. Increased senescent cell burden in various tissues is a major contributor to aging and age-related diseases. Recently, a new class of drugs termed senolytics were demonstrated to extending healthspan, reducing frailty and improving stem cell function in multiple murine models of aging. To identify novel and more optimal senotherapeutic drugs and combinations, we established a senescence associated β-galactosidase assay as a screening platform to rapidly identify drugs that specifically affect senescent cells...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28860714/sensitization-of-gastric-cancer-cells-to-alkylating-agents-by-glaucocalyxin-b-via-cell-cycle-arrest-and-enhanced-cell-death
#6
Muhammad Saif Ur Rahman, Ling Zhang, Lingyan Wu, Yuqiong Xie, Chunchun Li, Jiang Cao
Severe side effects are major problems with chemotherapy of gastric cancer (GC). These side effects can be reduced by using sensitizing agents in combination with therapeutic drugs. In this study, the low/nontoxic dosage of glaucocalyxin B (GLB) was used with other DNA linker agents mitomycin C (MMC), cisplatin (DDP), or cyclophosphamide (CTX) to treat GC cells. Combined effectiveness of GLB with drugs was determined by proliferation assay. The molecular mechanisms associated with cell proliferation, migration, invasion, cell cycle, DNA repair/replication, apoptosis, and autophagy were investigated by immunoblotting for key proteins involved...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28854356/multilayered-reprogramming-in-response-to-persistent-dna-damage-in-c-%C3%A2-elegans
#7
Diletta Edifizi, Hendrik Nolte, Vipin Babu, Laia Castells-Roca, Michael M Mueller, Susanne Brodesser, Marcus Krüger, Björn Schumacher
DNA damage causally contributes to aging and age-related diseases. Mutations in nucleotide excision repair (NER) genes cause highly complex congenital syndromes characterized by growth retardation, cancer susceptibility, and accelerated aging in humans. Orthologous mutations in Caenorhabditis elegans lead to growth delay, genome instability, and accelerated functional decline, thus allowing investigation of the consequences of persistent DNA damage during development and aging in a simple metazoan model. Here, we conducted proteome, lipidome, and phosphoproteome analysis of NER-deficient animals in response to UV treatment to gain comprehensive insights into the full range of physiological adaptations to unrepaired DNA damage...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28842471/isgylation-a-key-to-lock-the-cell-gates-for-preventing-the-spread-of-threats
#8
REVIEW
Carolina Villarroya-Beltri, Susana Guerra, Francisco Sánchez-Madrid
Interferon stimulated gene 15 (ISG15) is an ubiquitin-like protein whose expression and conjugation to targets (ISGylation) is induced by infection, interferon (IFN)-α and -β, ischemia, DNA damage and aging. Attention has historically focused on the antiviral effects of ISGylation, which blocks the entry, replication or release of different intracellular pathogens. However, recently, new functions of ISGylation have emerged that implicate it in multiple cellular processes, such as DNA repair, autophagy, protein translation and exosome secretion...
September 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28836369/wide-scale-comparative-analysis-of-longevity-genes-and-interventions
#9
Hagai Yanai, Arie Budovsky, Thomer Barzilay, Robi Tacutu, Vadim E Fraifeld
Hundreds of genes, when manipulated, affect the lifespan of model organisms (yeast, worm, fruit fly, and mouse) and thus can be defined as longevity-associated genes (LAGs). A major challenge is to determine whether these LAGs are model-specific or may play a universal role as longevity regulators across diverse taxa. A wide-scale comparative analysis of the 1805 known LAGs across 205 species revealed that (i) LAG orthologs are substantially overrepresented, from bacteria to mammals, compared to the entire genomes or interactomes, and this was especially noted for essential LAGs; (ii) the effects on lifespan, when manipulating orthologous LAGs in different model organisms, were mostly concordant, despite a high evolutionary distance between them; (iii) LAGs that have orthologs across a high number of phyla were enriched in translational processes, energy metabolism, and DNA repair genes; (iv) LAGs that have no orthologs out of the taxa in which they were discovered were enriched in autophagy (Ascomycota/Fungi), G proteins (Nematodes), and neuroactive ligand-receptor interactions (Chordata)...
August 24, 2017: Aging Cell
https://www.readbyqxmd.com/read/28829360/principal-aspects-regarding-the-maintenance-of-mammalian-mitochondrial-genome-integrity
#10
REVIEW
Panagiotis V S Vasileiou, Iordanis Mourouzis, Constantinos Pantos
Mitochondria have emerged as key players regarding cellular homeostasis not only due to their contribution regarding energy production through oxidative phosphorylation, but also due to their involvement in signaling, ion regulation, and programmed cell death. Indeed, current knowledge supports the notion that mitochondrial dysfunction is a hallmark in the pathogenesis of various diseases. Mitochondrial biogenesis and function require the coordinated action of two genomes: nuclear and mitochondrial. Unfortunately, both intrinsic and environmental genotoxic insults constantly threaten the integrity of nuclear as well as mitochondrial DNA...
August 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28801249/p53-stability-is-regulated-by-diverse-deubiquitinating-enzymes
#11
REVIEW
Seul-Ki Kwon, Madhuri Saindane, Kwang-Hyun Baek
The tumor suppressor protein p53 has a variety of roles in responses to various stress signals. In such responses, p53 activates specific transcriptional targets that control cell cycle arrest, DNA repair, angiogenesis, autophagy, metabolism, migration, aging, senescence, and apoptosis. Since p53 has been identified as the most frequently altered gene in human cancers, regulation and stabilization of its normal functions are important. Stability of p53 is regulated by the ubiquitin-proteasome pathway (UPP)...
August 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28796254/sunitinib-induces-genomic-instability-of-renal-carcinoma-cells-through-affecting-the-interaction-of-lc3-ii-and-parp-1
#12
Siyuan Yan, Ling Liu, Fengxia Ren, Quan Gao, Shanshan Xu, Bolin Hou, Yange Wang, Xuejun Jiang, Yongsheng Che
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ-H2AX, a marker for the DNA double-strand breaks (DSB)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28777374/high-mobility-group-a1-protein-modulates-autophagy-in-cancer-cells
#13
Andrea Conte, Simona Paladino, Gaia Bianco, Dominga Fasano, Raffaele Gerlini, Mara Tornincasa, Maurizio Renna, Alfredo Fusco, Donatella Tramontano, Giovanna Maria Pierantoni
High Mobility Group A1 (HMGA1) is an architectural chromatin protein whose overexpression is a feature of malignant neoplasias with a causal role in cancer initiation and progression. HMGA1 promotes tumor growth by several mechanisms, including increase of cell proliferation and survival, impairment of DNA repair and induction of chromosome instability. Autophagy is a self-degradative process that, by providing energy sources and removing damaged organelles and misfolded proteins, allows cell survival under stress conditions...
August 4, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28755993/breaching-barriers-in-glioblastoma-part-i-molecular-pathways-and-novel-treatment-approaches
#14
REVIEW
Ana Miranda, María Blanco-Prieto, João Sousa, Alberto Pais, Carla Vitorino
Glioblastoma multiforme (GBM) is the most common primary brain tumour, and the most aggressive in nature. The prognosis for patients with GBM remains poor, with a median survival time of only 1-2 years. The treatment failure relies on the development of resistance by tumour cells and the difficulty of ensuring that drugs effectively cross the dual blood brain barrier/blood brain tumour barrier. The advanced molecular and genetic knowledge has allowed to identify the mechanisms responsible for temozolomide resistance, which represents the standard of care in GBM, along with surgical resection and radiotherapy...
July 27, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28739596/correction-dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#15
Yan Ye, Ping Lin, Weidong Zhang, Shirui Tan, Xikun Zhou, Rongpeng Li, Qinqin Pu, Jonathan L Koff, Archana Dhasarathy, Feng Ma, Xin Deng, Jianxin Jiang, Min Wu
No abstract text is available yet for this article.
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28714027/enhanced-anticancer-effects-of-a-mixture-of-low-dose-mushrooms-and-panax-ginseng-root-extracts-in-human-colorectal-cancer-cells
#16
Mi So Lee, Mi-Sook Kim, Jae Kuk Yoo, Ji Young Lee, Jae Eun Ju, Youn Kyoung Jeong
Worldwide, colorectal cancer is the third most common cancer in men and the second most common in women. As conventional colorectal cancer therapies result in various side effects, there is a need for adjuvant therapy that can enhance the conventional therapies without complications. In this study, we investigated the anticancer effects of combined mixture of the several medicinal mushrooms and Panax ginseng root extracts (also called Amex7) as an adjuvant compound in the treatment of human colorectal cancer...
July 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28706161/the-molecular-mechanisms-of-chemoresistance-in-cancers
#17
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28696579/scrotal-insulation-and-sperm-production-in-the-boar
#18
REVIEW
John J Parrish, Kilby L Willenburg, Katelynn M Gibbs, Kylie B Yagoda, Megan M Krautkramer, Teyanna M Loether, Fabiana C S A Melo
Seasonal infertility is a limiting factor in boar fertility, and is increasingly important as climate changes. Spermatogenesis in the boar produces 256 spermatozoa per type A1 spermatogonium, but the process is inefficient such that only 10-30% of these potential spermatozoa are actually produced. Heat further impacts spermatogenesis by reducing the number of specific germ cells produced while increasing the fraction of abnormal sperm. Early studies used whole-animal exposure to simulate seasonal exposure to heat under production settings, but this approach is associated with many confounding factors that make assessment of the mechanisms of heat-induced damage to spermatogenesis difficult...
July 11, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28683561/ros-mediated-autophagy-defines-the-fate-of-cancer-stem-cells
#19
Matilde E Lleonart, Etna Abad, Dmitry Graifer, Alex Lyakhovich
SIGNIFICANCE: A fraction of tumorigenic cells, also known as tumor initiating or cancer stem cells, is thought to drive tumor growth, metastasis and chemoresistance. However, little is known regarding mechanisms that convey relevant pathways contributing to their self-renewal, proliferation and differentiation abilities. Recent Advances: Recent works on cancer stem cells provide evidence on the role of redox disruption and regulation of autophagic flux. This has been linked to increased DNA repair capacity and chemoresistance...
July 6, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28650265/autophagy-regulates-dna-repair-through-sqstm1-p62
#20
Yuchen Feng, Daniel J Klionsky
Macroautophagy/autophagy is primarily a degradative pathway that clears malfunctioning cellular components in response to various types of stress. Recent studies have indicated that autophagy also plays an important role in maintaining genome stability. Loss of autophagy is associated with increased damage to DNA, inappropriate amplification of genomic regions and abnormal chromosome number. In a recent paper by Wang et al. the authors uncover a mechanism through which autophagy regulates the ubiquitination of chromatin...
June 3, 2017: Autophagy
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