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molecular subtyping

Uanderson Resende, César Cabello, Susana Oliveira Botelho Ramalho, Luiz Carlos Zeferino
OBJECTIVE: There is insufficient information on predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast carcinoma that also presented clinical complete response (cCR) evaluated in breast, axilla and breast and axilla. METHODS: This retrospective study included 310 women with breast carcinoma who received NAC from 1/1/13 to 12/31/15 with follow-up until 8/31/16. The factors analyzed to predict pCR and cCR were menopausal status, Ki67, estrogen receptor, histologic grade, molecular subtype, tumor size, axilla status, and stage...
July 19, 2018: Oncology
Uma Sharma, Sunil Gupta, S Venkatesh, Arvind Rai, A C Dhariwal, Mohammad Husain
It is important to study the molecular properties of vertically transmitted viruses in early infancy to understand disease progression. P24 having an important role in virus assembly and maturation was selected to explore the genotypic characteristics. Blood samples, obtained from 82 HIV-1 positive infants, were categorized into acute (≤ 6 months) and early (> 6-18 months) age groups. Of the 82 samples, 79 gave amplification results for p24, which were then sequenced and analysed. Amino acid heterogeneity analysis showed that substitutions were more frequent...
July 18, 2018: Virus Genes
Nadia Bougarne, Basiel Weyers, Sofie J Desmet, Julie Deckers, David W Ray, Bart Staels, Karolien De Bosscher
Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor of clinical interest as a drug target in various metabolic disorders. PPARα also exhibits marked anti-inflammatory capacities. The first generation PPARα agonists, the fibrates, have however been hampered by drug-drug interaction issues, statin drop-in and ill-designed cardiovascular intervention trials. Notwithstanding, understanding the molecular mechanisms by which PPARα works will enable control of its activities as a drug target for metabolic diseases with an underlying inflammatory component...
July 17, 2018: Endocrine Reviews
Sercan Ergun, Serkan Guney, Ebru Temiz, Nina Petrovic, Sezgin Gunes
Background In recent years, targeted cancer treatment methods at various molecular levels have been developed for non-small cell lung cancer (NSCLC), one of two major subtypes of lung cancer. miRNA-based clinical trials are currently the preferred targeted therapeutic strategy. Also, ceRNAs (competing endogenous RNA) would be the newest and the most effective approach to uncover novel interactions between mRNAs and miRNAs in NSCLC carcinogenesis. There are many factors influencing on efficiency of a miRNA to suppress or silence translation of the target mRNA...
July 17, 2018: Anti-cancer Agents in Medicinal Chemistry
Mary Lynn Chu, Ellen Moran
There has been an ever-expanding list of the Limb-Girdle Muscular Dystrophies (LGMD). There are currently 8 subtypes of autosomal dominant (AD) and 26 subtypes of autosomal recessive (AR) LGMD. Despite continued research efforts to conquer this group of genetic neuromuscular disease, patients continue to be treated symptomatically with the aim of prevention or addressing complications. Mouse models have been helpful in clarifying disease pathogenesis as well as strategizing pathways for treatment. Discoveries in translational research as well as molecular therapeutic approaches have kept clinicians optimistic that more promising clinical trials will lead the way to finding the cure for these devastating disorders...
July 17, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Florence M G Cavalli, Jens-Martin Hübner, Tanvi Sharma, Betty Luu, Martin Sill, Michal Zapotocky, Stephen C Mack, Hendrik Witt, Tong Lin, David J H Shih, Ben Ho, Mariarita Santi, Lyndsey Emery, Juliette Hukin, Christopher Dunham, Roger E McLendon, Eric S Lipp, Sridharan Gururangan, Andrew Grossbach, Pim French, Johan M Kros, Marie-Lise C van Veelen, Amulya A Nageswara Rao, Caterina Giannini, Sarah Leary, Shin Jung, Claudia C Faria, Jaume Mora, Ulrich Schüller, Marta M Alonso, Jennifer A Chan, Almos Klekner, Lola B Chambless, Eugene I Hwang, Maura Massimino, Charles G Eberhart, Matthias A Karajannis, Benjamin Lu, Linda M Liau, Massimo Zollo, Veronica Ferrucci, Carlos Carlotti, Daniela P C Tirapelli, Uri Tabori, Eric Bouffet, Marina Ryzhova, David W Ellison, Thomas E Merchant, Mark R Gilbert, Terri S Armstrong, Andrey Korshunov, Stefan M Pfister, Michael D Taylor, Kenneth Aldape, Kristian W Pajtler, Marcel Kool, Vijay Ramaswamy
Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors...
July 17, 2018: Acta Neuropathologica
Musalula Sinkala, Nicola Mulder, Darren Patrick Martin
Despite modern therapeutic advances, the survival prospects of pancreatic cancer patients have remained poor. Besides being highly metastatic, pancreatic cancer is challenging to treat because it is caused by a heterogeneous array of somatic mutations that impact a variety of signaling pathways and cellular regulatory systems. Here we use publicly available transcriptomic, copy number alteration and mutation profiling datasets from pancreatic cancer patients together with data on disease outcomes to show that the three major pancreatic cancer subtypes each display distinctive aberrations in cell signaling and metabolic pathways...
June 26, 2018: Oncotarget
Zining Jin, Lu Xu, Lei Zhang, Min Zhao, Dongbao Li, Lijun Ye, Ying Ma, Siyu Ren, Hailan Yu, Danyu Wang, Chunyan Liang, Bo Chen
Interleukin enhancer binding factor 2 (ILF2) participates in several aspects of DNA and RNA metabolism and regulates gene expression at multiple levels; however, its role in breast cancer remains undefined. The variant statuses of ILF2 in human breast cancer were evaluated using the COSMIC database. Altered ILF2 expression in normal breast tissue relative to cancer tissue and in breast cancer patients with different clinicopathological characteristics, molecular subtypes, clinical outcomes and chemotherapy responses were examined using the Oncomine, GOBO, Kaplan-Meier plotter and GEO datasets...
2018: American Journal of Translational Research
Irene Gullo, Joana Carvalho, Diana Martins, Diana Lemos, Ana Rita Monteiro, Marta Ferreira, Kakoli Das, Patrick Tan, Carla Oliveira, Fátima Carneiro, Patrícia Oliveira
BACKGROUND: Epstein-Barr Virus (EBV) positive and microsatellite unstable (MSI-high) gastric cancer (GC) are molecular subgroups with distinctive molecular profiles. We explored the transcriptomic differences between EBV+ and MSI-high GCs, and the expression of current GC immunotherapy targets such as PD-1, PD-L1, CTLA4 and Dies1/VISTA. METHODS: Using Nanostring Technology and comparative bioinformatics, we analyzed the expression of 499 genes in 46 GCs, classified either as EBV positive (EBER in situ hybridization) or MSI-high (PCR/fragment analysis)...
July 17, 2018: International Journal of Molecular Sciences
Divânia Dias da Silva França, Nativa Helena Alves Del-Rios, Megmar Aparecida Dos Santos Carneiro, Rafael Alves Guimarães, Karlla Antonieta Amorim Caetano, Monica Nogueira da Guarda Reis, Regina Maria Bringel Martins, Ana Rita Coimbra Motta-Castro, Mariane Martins de Araujo Stefani, Sheila Araujo Teles
Brazil has the largest cocaine market in South America, and crack cocaine use is closely associated with HIV-1 infection. This study investigated the prevalence, risk factors, and HIV-1 subtypes, including recombinant forms and mutations associated with drug resistance, among crack cocaine users in Central-West Brazil. We recruited 600 crack cocaine users admitted to a referral hospital in Goiânia for psychiatric disorders. The participants were interviewed; blood samples were collected for anti-HIV-1/2 serological screening...
2018: PloS One
Tong Liu, Jing Sui, Yan Zhang, Xiao-Mei Zhang, Wen-Juan Wu, Sheng Yang, Si-Yi Xu, Wei-Wei Hong, Hui Peng, Li-Hong Yin, Yue-Pu Pu, Ge-Yu Liang
Clear cell renal cell carcinoma (ccRCC) is the main subtype of malignant kidney cancer. Long non‑coding RNA (lncRNA) serves a key role in predicting survival in patients with cancer. The present study aimed to develop an lncRNA‑related signature of prognostic values for patients with ccRCC. RNA sequencing data of 454 patients were analyzed from The Cancer Genome Atlas (TCGA). To identify the differentially expressed lncRNAs, the patients from four groups classified by tumor stages were compared. The association between survival outcome and lncRNA expression profile was assessed by the univariate and multivariate Cox proportional hazards model...
July 2, 2018: Oncology Reports
Craig M Bielski, Ahmet Zehir, Alexander V Penson, Mark T A Donoghue, Walid Chatila, Joshua Armenia, Matthew T Chang, Alison M Schram, Philip Jonsson, Chaitanya Bandlamudi, Pedram Razavi, Gopa Iyer, Mark E Robson, Zsofia K Stadler, Nikolaus Schultz, Jose Baselga, David B Solit, David M Hyman, Michael F Berger, Barry S Taylor
Ploidy abnormalities are a hallmark of cancer, but their impact on the evolution and outcomes of cancers is unknown. Here, we identified whole-genome doubling (WGD) in the tumors of nearly 30% of 9,692 prospectively sequenced advanced cancer patients. WGD varied by tumor lineage and molecular subtype, and arose early in carcinogenesis after an antecedent transforming driver mutation. While associated with TP53 mutations, 46% of all WGD arose in TP53-wild-type tumors and in such cases was associated with an E2F-mediated G1 arrest defect, although neither aberration was obligate in WGD tumors...
July 16, 2018: Nature Genetics
Cláudia S Marques, Ana Rita Santos, Andreia Gameiro, Jorge Correia, Fernando Ferreira
BACKGROUND: The receptor CXCR4 and its ligand CXCL12 play crucial roles in breast cancer. Despite the fact that the spontaneous feline mammary carcinoma (FMC) is considered a suitable model for breast cancer studies, the importance of the CXCR4/CXCL12 axis in FMC is completely unknown. Therefore, this work aims to elucidate the role of CXCR4 and its ligand in the progression of FMC and metastatic disease. METHODS: CXCR4 and CXCL12 expression was analyzed by immunohistochemistry and immunofluorescence on primary tumors (PT), regional and distant metastases of female cats with mammary carcinoma and correlated with serum CXCL12 levels, tumor molecular subtypes and clinicopathological features...
July 16, 2018: BMC Cancer
Arti Nanda, Lu Liu, Hejab Al-Ajmi, Qasem A Al-Saleh, Suad Al-Fadhli, John T Anim, Linda Ozoemena, Jemima E Mellerio, John A McGrath
BACKGROUND: Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous blistering skin disease, but in countries such as Kuwait, there are very limited data on the clinical and molecular pathology of EB. To improve understanding of EB in Kuwait, we report the experience of a local tertiary referral center over a 17.5 year period (January 2000-June 2017) in establishing clinical and molecular diagnoses. METHODS: Review of hospital records and diagnostic reports...
July 16, 2018: International Journal of Dermatology
Sadaf, Maria Habib, Mohammad Aasif Khan, Mohammad Zeeshan Najm, Mohd Nasar Mallick, Kumari Sunita, N K Shukla, S V S Deo, Syed Akhtar Husain
BACKGROUND: LATS2, a presumed tumor suppressor gene located on chromosome 13q11-12 is involved in cell growth related activity like regulation of cell cycle at G1/S. The reduced expression of LATS2 has been reported in many tumors; including tumors of Breast, which is to the best of our knowledge has not been studied in north Indian female breast cancer population. OBJECTIVE: Here, we looked upon the expression pattern and methylation status of the LATS2 gene in north Indian female breast cancer cases to further strengthen its role as a tumor suppressor gene and more importantly as a cancer biomarker...
July 12, 2018: Gene
Aya Masuda, Toshiaki Sumiyoshi, Tadatoshi Ohtaki, Jun Matsumoto
Blastocystis is an intestinal protist, commonly found in the human population and in a wide range of animals globally. Currently, isolates from mammalian and avian hosts are classified into 17 subtypes (STs) based on phylogeny of the small subunit rRNA gene (SSU rDNA), of which ten (ST1-9, 12) are reported in humans. ST10 is a major ST reported from livestock cattle. However, other STs including ST1, 3, 4, 5, and 6, which have the potential to be transmitted to humans, are also reported from cattle in several countries...
July 12, 2018: Parasitology International
Xiaosa Wu, Han-Shen Tae, Yen-Hua Huang, David J Adams, David J Craik, Quentin Kaas
The ribbon isomer of α-conotoxin AuIB has 10-fold greater potency than the wild-type globular isomer at inhibiting nicotinic acetylcholine receptors (nAChRs) in rat parasympathetic neurons, and unlike its globular isoform, ribbon AuIB only targets a specific stoichiometry of the α3β4 nAChR subtype. Previous electrophysiological recordings of AuIB indicated that ribbon AuIB binds to the α3(+)α3(-) interface within the nAChR extracellular domain, which is displayed by the (α3)3 (β4)2 stoichiometry but not by (α3)2 (β4)3 ...
July 12, 2018: Biochemical Pharmacology
Sarah A Best, Kate D Sutherland
Lung cancer remains one of the world's deadliest cancers, with effective targeted treatment options available for only a small subset of patients. The rapid expansion of cancer genomics in recent years has provided insight into the genetic landscape of all major lung cancer subtypes and led to new discoveries on the heterogeneous biology underlying lung tumorigenesis. Interestingly, these studies have revealed a high frequency of alterations in the Kelch-like ECG-associated protein 1 (KEAP1) - Nuclear factor erythoid - 2 - related factor 2 (NRF2) stress response pathway, for which no targeted treatments are currently available...
July 15, 2018: Cell Cycle
Pierre-Olivier Guichet, Konstantin Masliantsev, Gaëlle Tachon, Christos Petropoulos, Julie Godet, Delphine Larrieu, Serge Milin, Michel Wager, Lucie Karayan-Tapon
During the last decade, large-scale genomic analyses have clarified the somatic alterations in gliomas providing new molecular classification based on IDH1/2 mutations and 1p19q codeletion with more accurate patient prognostication. The Hippo pathway downstream effectors, YAP1 and TAZ, have recently emerged as major determinants of malignancy by inducing proliferation, chemoresistance, and metastasis in solid tumors. In this study, we investigated the expression of YAP1 in 117 clinical samples of glioma described according to the WHO 2016 classification...
July 15, 2018: Journal of Pathology
Xiaodu Wang, Rui Hua, Abu Ahsan, Qingwen Ni, Yehong Huang, Sumin Gu, Jean X Jiang
Hydration status significantly affects the toughness of bone. In addition to the collagen phase, recent evidence shows that glycosaminoglycans (GAGs) of proteoglycans (PGs) in the extracellular matrix also play a pivotal role in regulating the tissue-level hydration status of bone, thereby affecting the tissue-level toughness of bone. In this study, we hypothesized that the amount of GAGs in bone matrix decreased with age and such changes would lead to reduction in bound water and subsequently result in a decrease in the tissue-level toughness of bone...
May 2018: JBMR Plus
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