Read by QxMD icon Read


Chiara Cremolini, Massimo Milione, Federica Marmorino, Federica Morano, Gemma Zucchelli, Alessia Mennitto, Michele Prisciandaro, Sara Lonardi, Alessio Pellegrinelli, Daniele Rossini, Francesca Bergamo, Giuseppe Aprile, Lucio Urbani, Luca Morelli, Marta Schirripa, Giovanni Gerardo Cardellino, Matteo Fassan, Gabriella Fontanini, Filippo de Braud, Vincenzo Mazzaferro, Alfredo Falcone, Filippo Pietrantonio
BACKGROUND: Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs...
March 13, 2018: British Journal of Cancer
Seyed Hossein Bassir, Isabelle Chase, Bruce J Paster, Leslie B Gordon, Monica E Kleinman, Mark W Kieran, David M Kim, Andrew Sonis
BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder with significant oral and dental abnormalities. Clinical symptoms include various features of accelerated aging such as alopecia, loss of subcutaneous fat, bone abnormalities, and premature cardiovascular disease. In addition, children with HGPS have been observed to suffer from generalized gingival recession. Whether periodontal manifestations associated with this syndrome are the results of changes in the oral flora is unknown...
February 19, 2018: Journal of Periodontology
Magda R Hamczyk, Ricardo Villa-Bellosta, Pilar Gonzalo, María J Andrés-Manzano, Paula Nogales, Jacob F Bentzon, Carlos López-Otín, Vicente Andrés
Background -Progerin, an aberrant protein that accumulates with age, causes the rare genetic disease Hutchinson-Gilford progeria syndrome (HGPS). HGPS patients with ubiquitous progerin expression exhibit accelerated aging and atherosclerosis, and die in their early teens mainly from myocardial infarction or stroke. The mechanisms underlying progerin-induced atherosclerosis remain unexplored, in part due to the lack of appropriate animal models. Methods -We generated an atherosclerosis-prone model of HGPS by crossing apolipoprotein E-deficient ( Apoe-/- ) mice with LmnaG609G/G609G mice ubiquitously expressing progerin...
February 28, 2018: Circulation
Patrick Tomkins, Minna Saaristo, Michael G Bertram, Marcus Michelangeli, Raymond B Tomkins, Bob B M Wong
The environmental impact of endocrine-disrupting chemicals (EDCs)-compounds that interfere with endocrine system function at minute concentrations-is now well established. In recent years, concern has been mounting over a group of endocrine disruptors known as hormonal growth promotants (HGPs), which are natural and synthetic chemicals used to promote growth in livestock by targeting the endocrine system. One of the most potent compounds to enter the environment as a result of HGP use is 17β-trenbolone, which has repeatedly been detected in aquatic habitats...
February 22, 2018: Environmental Pollution
Zeming Wu, Weiqi Zhang, Moshi Song, Wei Wang, Gang Wei, Wei Li, Jinghui Lei, Yu Huang, Yanmei Sang, Piu Chan, Chang Chen, Jing Qu, Keiichiro Suzuki, Juan Carlos Izpisua Belmonte, Guang-Hui Liu
Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting in the production of a truncated protein product-progerin. WS is caused by mutations in WRN gene, encoding a loss-of-function RecQ DNA helicase. Here, by gene editing we created isogenic human embryonic stem cells (ESCs) with heterozygous (G608G/+) or homozygous (G608G/G608G) LMNA mutation and biallelic WRN knockout, for modeling HGPS and WS pathogenesis, respectively...
February 23, 2018: Protein & Cell
Joon Tae Park, Hyun Tae Kang, Chi Hyun Park, Young-Sam Lee, Kyung A Cho, Sang Chul Park
In our previous study, we uncovered a novel mechanism in which amelioration of Hutchinson-Gilford progeria syndrome (HGPS) phenotype is mediated by mitochondrial functional recovery upon rho-associated protein kinase (ROCK) inhibition. However, it remains elusive whether this mechanism is also applied to the amelioration of normal aging cells. In this study, we used Y-27632 and fasudil as effective ROCK inhibitors, and examined their role in senescence. We found that ROCK inhibition induced the functional recovery of the mitochondria as well as the metabolic reprogramming, which are two salient features that are altered in normal aging cells...
February 20, 2018: Experimental Gerontology
Ray Kreienkamp, Simona Graziano, Nuria Coll-Bonfill, Gonzalo Bedia-Diaz, Emily Cybulla, Alessandro Vindigni, Dale Dorsett, Nard Kubben, Luis Francisco Zirnberger Batista, Susana Gonzalo
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by a truncated lamin A protein (progerin) that drives cellular and organismal decline. HGPS patient-derived fibroblasts accumulate genomic instability, but its underlying mechanisms and contribution to disease remain poorly understood. Here, we show that progerin-induced replication stress (RS) drives genomic instability by eliciting replication fork (RF) stalling and nuclease-mediated degradation. Rampant RS is accompanied by upregulation of the cGAS/STING cytosolic DNA sensing pathway and activation of a robust STAT1-regulated interferon (IFN)-like response...
February 20, 2018: Cell Reports
Ashwin Prakash, Leslie B Gordon, Monica E Kleinman, Ellen B Gurary, Joseph Massaro, Ralph D'Agostino, Mark W Kieran, Marie Gerhard-Herman, Leslie Smoot
Importance: Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare disorder associated with premature death due to cardiovascular events during the second decade of life. However, because of its rarity (107 identified living patients), the natural history of cardiac disease remains uncharacterized. Therefore, meaningful cardiac end points for clinical trials have been difficult to establish. Objective: To examine the course of appearance of cardiac abnormalities in patients with HGPS to identify meaningful cardiac end points for use in future clinical trials...
February 21, 2018: JAMA Cardiology
Natalia von Muhlinen, Izumi Horikawa, Fatima Alam, Kazunobu Isogaya, Delphine Lissa, Borek Vojtesek, David P Lane, Curtis C Harris
Cellular senescence is a hallmark of normal aging and aging-related syndromes, including the premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder caused by a single mutation in the LMNA gene that results in the constitutive expression of a truncated splicing mutant of lamin A known as progerin. Progerin accumulation leads to increased cellular stresses including unrepaired DNA damage, activation of the p53 signaling pathway and accelerated senescence. We previously established that the p53 isoforms ∆133p53 and p53β regulate senescence in normal human cells...
February 12, 2018: Oncogene
Aurora Paola Borroni, Andrea Emanuelli, Pooja Anil Shah, Nataša Ilić, Liat Apel-Sarid, Biagio Paolini, Dhanoop Manikoth Ayyathan, Praveen Koganti, Gal Levy-Cohen, Michael Blank
A-lamins, encoded by the LMNA gene, are major structural components of the nuclear lamina coordinating essential cellular processes. Mutations in the LMNA gene and/or alterations in its expression levels have been linked to a distinct subset of human disorders, collectively known as laminopathies, and to cancer. Mechanisms regulating A-lamins are mostly obscure. Here, we identified E3 ubiquitin ligase Smurf2 as a physiological regulator of lamin A and its disease-associated mutant form progerin (LAΔ50), whose expression underlies the development of Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging syndrome...
February 5, 2018: Aging Cell
Aline Guimarães Grana, Aline do Amaral Silva, Francisco Ronaldo Moura Filho, Raquel Rodrigues Ferreira Rocha de Alencar, Patrícia Chicre Bandeira de Melo
Hutchinson-Gilford progeria syndrome (HGPS) is one of the rarest human diseases, an autosomal dominant premature aging disorder 1 . Its incidence is 1-4 per 8 million newborns 2 . There are aging-associated symptoms, including lack of subcutaneous fat, hair loss, joint contractures, progressive cardiovascular disease resembling atherosclerosis, and death due to heart attacks and strokes in childhood. This article is protected by copyright. All rights reserved.
January 29, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Pieter-Jan van Dam, Sofie Daelemans, Elizabeth Ross, Yannick Waumans, Steven Van Laere, Emily Latacz, Roanne Van Steen, Christel De Pooter, Mark Kockx, Luc Dirix, Peter B Vermeulen
The encroachment of a growing tumor upon the cells and structures of surrounding normal tissue results in a series of histopathological growth patterns (HGPs). These morphological changes can be assessed in hematoxylin-and-eosin (H&E) stained tissue sections from primary and metastatic tumors and have been characterized in a range of tissue types including liver, lung, lymph node and skin. HGPs in different tissues share certain general characteristics like the extent of angiogenesis, but also appropriate tissue-specific mechanisms which ultimately determine differences in the biology of HGP subtypes...
January 17, 2018: Seminars in Cancer Biology
Leslie B Gordon, Susan E Campbell, Joseph M Massaro, Ralph B D'Agostino, Monica E Kleinman, Mark W Kieran, Marsha A Moses
BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare, fatal, segmental premature aging syndrome caused by the aberrant lamin A protein, progerin. The protein farnesyltransferase inhibitor, lonafarnib, ameliorates some aspects of cardiovascular and bone disease. STUDY DESIGN: We performed a prospective longitudinal survey of plasma proteins in 24 children with HGPS (an estimated 10% of the world's population at the time) at baseline and on lonafarnib therapy, compared to age and gender-matched controls using a multi-analyte, microsphere-based immune-fluorescent assay...
January 17, 2018: Pediatric Research
Juan Carlos Rivera-Mulia, Romain Desprat, Claudia Trevilla-Garcia, Daniela Cornacchia, Hélène Schwerer, Takayo Sasaki, Jiao Sima, Tyler Fells, Lorenz Studer, Jean-Marc Lemaitre, David M Gilbert
Progeroid syndromes are rare genetic disorders that phenotypically resemble natural aging. Different causal mutations have been identified, but no molecular alterations have been identified that are in common to these diseases. DNA replication timing (RT) is a robust cell type-specific epigenetic feature highly conserved in the same cell types from different individuals but altered in disease. Here, we characterized DNA RT program alterations in Hutchinson-Gilford progeria syndrome (HGPS) and Rothmund-Thomson syndrome (RTS) patients compared with natural aging and cellular senescence...
December 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
Amalia Gabriela Diaconeasa
A critical analysis of the accelerated aging syndromes may explain what aging is, but also why some tissues and organs age at accelerated rates in comparison with aging rates of other tissues. Syndromes of accelerated aging are caused by mutations affecting the integrity of the genetic material. Among them, the most studied is Werner's syndrome, "adult progeria", caused by a recessive autosomal mutation with a frequency of 1 in 10 millions, which affects a helicase involved in DNA repair. In Werner syndrome, there is a loss of heterochromatin, though the stability of heterochromatin is also affected in "normal" aging...
November 16, 2017: Current Aging Science
Haji Mohammed Nazir, Akshiitha Ramesh Baabhu, Yuvaraj Muralidharan, Seena Cheppala Rajan
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare disease with a combination of short stature, bone abnormalities, premature ageing, and skin changes. Though the physical appearance of these patients is characteristic, there is little emphasis on the characteristic radiological features. In this paper, we report a 16-year-old boy with clinical and radiological features of this rare genetic disorder. He had a characteristic facial appearance with a large head, large eyes, thin nose with beaked tip, small chin, protruding ears, prominent scalp veins, and absence of hair...
2017: Case Reports in Radiology
Charlotte Strandgren, Gwladys Revêchon, Agustín Sola-Carvajal, Maria Eriksson
Hutchinson-Gilford progeria syndrome (HGPS, progeria) is an extremely rare premature aging disorder affecting children, with a disease incidence of ∼1 in 18 million individuals. HGPS is usually caused by a de novo point mutation in exon 11 of the LMNA gene (c.1824C>T, p.G608G), resulting in the increased usage of a cryptic splice site and production of a truncated unprocessed lamin A protein named progerin. Since the genetic cause for HGPS was published in 2003, numerous potential treatment options have rapidly emerged...
December 15, 2017: Biochemical Society Transactions
Claudia Compagnucci, Enrico Bertini
Premature aging disorders including Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome, are a group of rare monogenic diseases leading to reduced lifespan of the patients. Importantly, these disorders mimic several features of physiological aging. Despite the interest on the study of these diseases, the underlying biological mechanisms remain unknown and no treatment is available. Recent studies on HGPS (due to mutations of the LMNA gene encoding for the nucleoskeletal proteins lamin A/C) have reported disruptions in cellular and molecular mechanisms modulating genomic stability and stem cell populations, thus giving the nuclear lamina a relevant function in nuclear organization, epigenetic regulation and in the maintenance of the stem cell pool...
November 7, 2017: International Journal of Molecular Sciences
Diana Gabriel, Dinah Dorith Shafry, Leslie B Gordon, Karima Djabali
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic condition associated with mutations in the LMNA gene. This disease recapitulates some aspects of normal aging, such as hair loss, thin skin, joint stiffness, and atherosclerosis. The latter leads to heart attack or stroke that causes death at an average age of 14.6 years in children with HGPS. The typical LMNA mutation results in the production of a truncated prelamin A protein, progerin, that remains permanently farnesylated and abnormally associated with the nuclear envelope...
September 12, 2017: Oncotarget
Pieter-Jan van Dam, Eric P van der Stok, Laure-Anne Teuwen, Gert G Van den Eynden, Martin Illemann, Sophia Frentzas, Ali W Majeed, Rikke L Eefsen, Robert R J Coebergh van den Braak, Anthoula Lazaris, Maria Celia Fernandez, Boris Galjart, Ole Didrik Laerum, Roni Rayes, Dirk J Grünhagen, Michelle Van de Paer, Yves Sucaet, Hardeep Singh Mudhar, Michael Schvimer, Hanna Nyström, Mark Kockx, Nigel C Bird, Fernando Vidal-Vanaclocha, Peter Metrakos, Eve Simoneau, Cornelis Verhoef, Luc Y Dirix, Steven Van Laere, Zu-Hua Gao, Pnina Brodt, Andrew R Reynolds, Peter B Vermeulen
BACKGROUND: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs. METHODS: Guidelines for defining the HGPs were established by a large international team...
November 7, 2017: British Journal of Cancer
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"