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Genomics Pathologys

Dongjuan Yuan, Shiqi Luo, Lian Xu, Xingda Zeng, Zhongdao Wu
MicroRNA plays a vital role in the regulation of host-parasite interaction. In recent years, genomic and transcriptomic resources have become increasingly available for many helminths, but only a limited number of reports in this area are on the regulatory effects of host microRNAs on parasitic nematodes. In this work, we screened increased expression of host microRNAs after nematode infection from miRNA-seq data and predicted target genes by combined bioinformatics analysis and transcriptional profiling. We elucidated regulatory effects of one host miRNA on nematode infection using miRNA inhibitor and adeno-associated virus (AAV)-based TuD miRNA inhibitor...
February 11, 2019: Biochimica et biophysica acta. Gene regulatory mechanisms
Caitlin Murphy, Andrea Muscat, David Ashley, Violet Mukaro, Linda West, Yang Liao, David Chisanga, Wei Shi, Ian Collins, Sally Baron-Hay, Sujata Patil, Geoffrey Lindeman, Mustafa Khasraw
BACKGROUND: This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored. PATIENTS AND OUTCOME MEASURES: Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25...
2019: PloS One
Ya Zhang, Ao Li, Jie He, Minghui Wang
Glioblastoma Multiforme (GBM) is one of the most malignant brain tumors with very short prognosis expectation. To improve patients' clinical treatment and their life quality after surgery. Researches have developed tremendous in silico models and tools for predicting GBM prognosis based on molecular datasets and have earned great success. However, pathology still plays the most critical role in cancer diagnosis and prognosis in the clinic at present. Recent advancement of storing and processing histopathological images have drawn attention from researches...
February 11, 2019: IEEE Journal of Biomedical and Health Informatics
Krystal J Vail, Nicole M Tate, Tasha Likavec, Katie M Minor, Philippa M Gibbons, Raquel R Rech, Eva Furrow
A 2-year-old mixed breed goat was presented for a 1-day history of anorexia and 1 week of weight loss. Serum biochemistry disclosed severe azotemia. Abdominal ultrasound examination showed decreased renal corticomedullary distinction, poor visualization of the renal pelves, and dilated ureters. On necropsy, the kidneys were small, the pelves were dilated, and the medulla was partially effaced by variably sized yellow nephroliths. Histologically, cortical and medullary tubules were distended by yellow-brown, multilayered crystals...
February 13, 2019: Journal of Veterinary Internal Medicine
Jacek Sienko, Paweł Gaj, Krzysztof Czajkowski, Dominika Nowis
OBJECTIVES: Peroxiredoxins (PRDXs) constitute a family of antioxidant enzymes which are also involved in the process of carcinogenesis. They are composed of six identified isoforms (PRDX-1-6) and are supposed to play different roles in tumor progression, depending on type of cancer and member of the PRDX family. The aim of the study was to assess the prog- nostic value of PRDXs in ovarian cancer. MATERIAL AND METHODS: a dataset of patients with ovarian cancer from The Cancer Genome Atlas was analyzed...
2019: Ginekologia Polska
Xiuzhi Zhang, Chunyan Kang, Ningning Li, Xiaoli Liu, Jinzhong Zhang, Fenglan Gao, Liping Dai
Background: Alcohol-related hepatocellular carcinoma (HCC) was reported to be diagnosed at a later stage, but the mechanism was unknown. This study aimed to identify special key genes (SKGs) during alcohol-related HCC development and progression. Methods: The mRNA data of 369 HCC patients and the clinical information were downloaded from the Cancer Genome Atlas project (TCGA). The 310 patients with certain HCC-related risk factors were included for analysis and divided into seven groups according to the risk factors...
2019: PeerJ
Song Wu, Tong Ou, Nianzeng Xing, Jiang Lu, Shengqing Wan, Changxi Wang, Xi Zhang, Feiya Yang, Yi Huang, Zhiming Cai
Bladder cancer is one of the most common and highly vascularized cancers. To better understand its genomic structure and underlying etiology, we conduct whole-genome and targeted sequencing in urothelial bladder carcinomas (UBCs, the most common type of bladder cancer). Recurrent mutations in noncoding regions affecting gene regulatory elements and structural variations (SVs) leading to gene disruptions are prevalent. Notably, we find recurrent ADGRG6 enhancer mutations and FRS2 duplications which are associated with higher protein expression in the tumor and poor prognosis...
February 12, 2019: Nature Communications
Shelly Applen Clancey, Emily J Ciccone, Marco A Coelho, Joie Davis, Li Ding, Renee Betancourt, Samuel Glaubiger, Yueh Lee, Steven M Holland, Peter Gilligan, Julia Sung, Joseph Heitman
The region encompassing the Pacific Northwest (PNW), Vancouver Island, Oregon, and Washington has been the location of an ongoing Cryptococcus gattii outbreak since the 1990s, and there is evidence that the outbreak is expanding along the West Coast into California. Here we report a clinical case of a 69-year-old, HIV-negative man from North Carolina who was diagnosed with a fungal brain mass by magnetic resonance imaging (MRI) and pathology. He had traveled to Seattle and Vancouver 3 years earlier and to Costa Rica 4 months prior to presentation...
February 12, 2019: MBio
Sho Takatori, Wenbo Wang, Akihiro Iguchi, Taisuke Tomita
The accumulation of aggregated amyloid β (Aβ) peptides in the brain is deeply involved in Alzheimer disease (AD) pathogenesis. Mutations in APP and presenilins play major roles in Aβ pathology in rare autosomal-dominant forms of AD, whereas pathomechanisms of sporadic AD, accounting for the majority of cases, remain unknown. In this chapter, we review current knowledge on genetic risk factors of AD, clarified by recent advances in genome analysis technology. Interestingly, TREM2 and many genes associated with disease risk are predominantly expressed in microglia, suggesting that these risk factors are involved in pathogenicity through common mechanisms involving microglia...
2019: Advances in Experimental Medicine and Biology
Tihana Ibrahimpasic, Ronald Ghossein, Jatin P Shah, Ian Ganly
BACKGROUND: Poorly differentiated thyroid cancer (PDTC) is a rare but clinically highly significant entity because it accounts for most fatalities from non-anaplastic follicular cell-derived thyroid cancer. Due to the relative rarity of the disease and heterogeneous diagnostic criteria, studies on PDTC have been limited. In light of the evolution of ultra deep next-generation sequencing (NGS) technologies and through correlation of clinico-pathological and genomic characteristics of PDTC, an improved understanding of the biology of PDTC has been facilitated...
February 12, 2019: Thyroid: Official Journal of the American Thyroid Association
Boxuan Li, Ke Pu, Xinan Wu
Hepatocellular carcinoma (HCC) is a highly malignant tumor found in the bile duct epithelial cells, and the second most common tumor of the liver. However, the pivotal roles of most molecules of tumorigenesis in HCC are still unclear. Hence, it is essential to detect the tumorigenic mechanism and develop novel prognostic biomarkers for clinical application. The data of HCC mRNA-seq and clinical information from The Cancer Genome Atlas (TCGA) database were analyzed by weighted gene co-expression network analysis (WGCNA)...
February 11, 2019: Journal of Cellular Biochemistry
Dane Cheasley, Na Li, Simone M Rowley, Kenneth Elder, G Bruce Mann, Sherene Loi, Peter Savas, David L Goode, Tanjina Kader, Magnus Zethoven, Tim Semple, Stephen B Fox, Jia-Min Pang, David Byrne, Lisa Devereux, Carolyn Nickson, Pietro Procopio, Grant Lee, Siobhan Hughes, Hugo Saunders, Kenji M Fujihara, Keilly Kuykhoven, Jacquie Connaughton, Paul A James, Kylie L Gorringe, Ian G Campbell
Breast cancer (BC) diagnosed after a negative mammogram but prior to the next screening episode is termed an "interval breast cancer" (IBC). Understanding the molecular differences between IBC and screen-detected breast cancers (SDBC) could improve mammographic screening and management options. Therefore, we assessed both germline and somatic genomic aberrations in a prospective cohort. Utilizing the Lifepool cohort of >54,000 women attending mammographic screening programs, 930 BC cases with screening status were identified (726 SDBC and 204 IBC)...
February 11, 2019: Journal of Pathology
Xiangbo Chen, Yisen Huang, Yubin Wang, Qiuli Wu, Shunzhong Hong, Zicheng Huang
Gastric cancer (GC), a common and lethal cancer in the world, has a high risk of metastasis. Our study was to explore the effects of THBS4 on GC progress and metastasis and the underlying mechanisms. The proliferations of MGC-803 and BGC-823 cells were analyzed via cell count, MTT, and soft agar colony formation assay. The migration and invasion of transfected GC cells was investigated via transwell migration and invasion assay. The mRNA abundance of THBS4 and KLF9 was detected by quantitative real-time PCR (qPCR)...
February 12, 2019: Journal of Physiology and Biochemistry
Tomohiro Tobita, Daiji Kiyozumi, Masanaga Muto, Taichi Noda, Masahito Ikawa
Preeclampsia is a systemic disease caused by abnormal placentation that affects both mother and fetus. It was reported that Laeverin (LVRN, also known as Aminopeptidase Q) was up-regulated in the placenta of preeclamptic patients. However, physiological and pathological functions of LVRN remained to be unknown. Here we characterized Lvrn function during placentation in mice. RT-PCR showed that Lvrn is expressed in both fetus and placenta during embryogenesis, and several adult tissues. When we overexpressed Lvrn in a placenta-specific manner using lentiviral vectors, we did not see any defects in both placentae and fetuses...
February 10, 2019: Journal of Reproduction and Development
Serena Imperato, Carmela Mistretta, Maria Marone, Ilaria Migliaccio, Ilaria Pulcinelli, Maria Rosaria Faraone Mennella
Increased DNA damage and the propension to cancer development, depend on the modulation of the mechanisms to control and maintain genomic integrity. Poly(ADP-Ribose)Polymerase activation and automodification are early responses to genotoxic stress. Upon binding to DNA strand breaks, the enzyme, a molecular DNA nick sensor, is hyperactivated: this is the first step in a series of events leading to either DNA repair or apoptosis. Enzyme hyperactivation and automodification can be easily measured and are widely used to look at DNA damage extent in the cell...
February 8, 2019: Cells
Michiel Van Bulck, Ana Sierra-Magro, Jesus Alarcon-Gil, Ana Perez-Castillo, Jose A Morales-Garcia
Neurodegenerative disorders affect around one billion people worldwide. They can arise from a combination of genomic, epigenomic, metabolic, and environmental factors. Aging is the leading risk factor for most chronic illnesses of old age, including Alzheimer's and Parkinson's diseases. A progressive neurodegenerative process and neuroinflammation occur, and no current therapies can prevent, slow, or halt disease progression. To date, no novel disease-modifying therapies have been shown to provide significant benefit for patients who suffer from these devastating disorders...
February 8, 2019: International Journal of Molecular Sciences
Eva Xepapadaki, Giuseppe Maulucci, Caterina Constantinou, Eleni A Karavia, Evangelia Zvintzou, Bareket Daniel, Shlomo Sasson, Kyriakos E Kypreos
High density lipoprotein (HDL) has attracted the attention of biomedical community due to its well-documented role in atheroprotection. HDL has also been recently implicated in the regulation of islets of Langerhans secretory function and in the etiology of peripheral insulin sensitivity. Indeed, data from numerous studies strongly indicate that the functions of pancreatic β-cells, skeletal muscles and adipose tissue could benefit from improved HDL functionality. To better understand how changes in HDL structure may affect diet-induced obesity and type 2 diabetes we aimed at investigating the impact of Apoa1 or Lcat deficiency, two key proteins of peripheral HDL metabolic pathway, on these pathological conditions in mouse models...
February 8, 2019: Biochimica et biophysica acta. Molecular basis of disease
K Michael Pollard, David M Cauvi, Christopher B Toomey, Per Hultman, Dwight H Kono
BACKGROUND: Human exposure to mercury leads to a variety of pathologies involving numerous organ systems including the immune system. A paucity of epidemiological studies and suitable diagnostic criteria, however, has hampered collection of sufficient data to support a causative role for mercury in autoimmune diseases. Nevertheless, there is evidence that mercury exposure in humans is linked to markers of inflammation and autoimmunity. This is supported by experimental animal model studies, which convincingly demonstrate the biological plausibility of mercury as a factor in the pathogenesis of autoimmune disease...
February 8, 2019: Biochimica et biophysica acta. General subjects
Laurent Fasano, Irene Sanchez-Martin, Xavier Caubit
Microarrays and RNA-seq (RNA sequencing) are powerful techniques to assess transcript abundance in biological samples and to improve our understanding of the relationship between genotype and phenotype. Tshz3+/- heterozygous mouse is a model for a human 19q12 syndrome characterized by autistic traits and renal tract defects (Caubit et al., Nat Genet 48:1359-1369, 2016). To unravel renal tract pathological mechanisms, we took advantage of Tshz3 mouse and performed comparative genome-wide expression profiling on embryonic ureter and/or kidney...
2019: Methods in Molecular Biology
Ting-Tai Yen, Tian-Li Wang, Amanda N Fader, Ie-Ming Shih, Stéphanie Gaillard
Recent advances in molecular studies, especially genome-wide analyses, have revealed the landscape of genomic alterations present in endometrial carcinomas, and have provided valuable insight into the pathogenesis of this disease. The current challenges are in developing a molecular-morphologic classification system to enhance traditional pathologic diagnosis and in determining the optimal approach to using this new information to guide clinical management. Molecular assays may be particularly beneficial in allowing the earlier detection of endometrial cancer or precursor lesions and in guiding personalized treatment approaches...
February 7, 2019: International Journal of Gynecological Pathology
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