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molecular subtyping

Daiki Hirano, Yuji Urabe, Shinji Tanaka, Koki Nakamura, Yuki Ninomiya, Ryo Yuge, Ryohei Hayashi, Shiro Oka, Yasuhiko Kitadai, Fumio Shimamoto, Koji Arihiro, Kazuaki Chayama
Serrated adenocarcinoma (SAC) is considered the end stage of the serrated neoplasia pathway. Although SAC prognosis is not widely recognized, the serrated pathway-associated subtype consistently exhibits unfavorable prognosis in genetic studies. Herein, we classified molecularly distinct subtypes of serrated adenocarcinomas and clarified their associated clinicopathological characteristics and genetic changes. We examined 38 early-stage colorectal SACs. Of these, 24 were classified into three molecularly distinct groups by colon cancer subtyping (CCS)...
2019: PloS One
David G P van IJzendoorn, Karoly Szuhai, Inge H Briaire-de Bruijn, Marie Kostine, Marieke L Kuijjer, Judith V M G Bovée
Based on morphology it is often challenging to distinguish between the many different soft tissue sarcoma subtypes. Moreover, outcome of disease is highly variable even between patients with the same disease. Machine learning on transcriptome sequencing data could be a valuable new tool to understand differences between and within entities. Here we used machine learning analysis to identify novel diagnostic and prognostic markers and therapeutic targets for soft tissue sarcomas. Gene expression data was used from the Cancer Genome Atlas, the Genotype-Tissue Expression data and the French Sarcoma Group...
February 20, 2019: PLoS Computational Biology
Anjelica Hodgson, Kay J Park
CONTEXT.—: Cervical adenocarcinomas are a heterogeneous group of tumors with varying morphologies, etiologies, molecular drivers, and prognoses, comprising approximately 25% of all cervical cancers. Unlike cervical squamous cell carcinoma, adenocarcinomas are not uniformly caused by high-risk human papillomavirus (HPV) infection and, therefore, would not necessarily be prevented by the HPV vaccine. OBJECTIVE.—: To provide a review of endocervical adenocarcinoma subtypes and, when appropriate, discuss precursor lesions, etiologies, molecular genetics, and ancillary studies within the context of clinical care...
January 2019: Archives of Pathology & Laboratory Medicine
Ye Yuanxin, Zhou Yanhong, Zheng Qin, Tang Sishi, Dai Yang, Zhou Yi, Wang Minjin, Zhou Juan, Lu Xiaojun, Wang Lanlan, Ying Binwu
The BCR-ABL fusion gene (BCR-ABL) has different subtypes such as p210 and p190 with p190 appear to lead to a worse prognosis. To explore the mechanism of difference in pathogenesis and prognosis in different BCR-ABL subtype-related leukemia, expression profile microarray analysis was conducted between p190 and p210 patients and verified by RT-PCR. The p21-activated kinase (PAK1) gene was chosen and regulation of the PAK1-STAT5 biological axis and its influence on proliferation and apoptosis in leukemia cells were also analyzed...
January 24, 2019: Leukemia Research
Eve R Schneider, Evan O Anderson, Viktor V Feketa, Marco Mastrotto, Yury A Nikolaev, Elena O Gracheva, Sviatoslav N Bagriantsev
A major challenge in biology is to link cellular and molecular variations with behavioral phenotypes. Here, we studied somatosensory neurons from a panel of bird species from the family Anatidae, known for their tactile-based foraging behavior. We found that tactile specialists exhibit a proportional expansion of neuronal mechanoreceptors in trigeminal ganglia. The expansion of mechanoreceptors occurs via neurons with intermediately and slowly inactivating mechanocurrent. Such neurons contain the mechanically gated Piezo2 ion channel whose expression positively correlates with the expression of factors responsible for the development and function of mechanoreceptors...
February 19, 2019: Cell Reports
Norihiko Yokoi, Georgi As Georgiev
Tear-film (TF) stability protects the ocular surface epithelium from desiccation and is ensured via cooperation between the ocular surface components including constituents of the TF and ocular surface epithelium. Thus, when those components are insufficient or impaired, the TF breakup that initiates dry eye occurs. Recently, new, commercially available eye drops have appeared in Japan that enable TF stabilization via targeted supplementation of deficient ocular surface components. Hence, a new layer-by-layer diagnosis and treatment concept for dry eye, termed tear-film-oriented diagnosis and tear-film-oriented therapy (TFOD and TFOT, respectively), have emerged and become widely accepted in Asian countries and beyond...
February 19, 2019: Japanese Journal of Ophthalmology
Thomas Albrecht, Alexander Harms, Stephanie Roessler, Benjamin Goeppert
NUT carcinoma is a rarely diagnosed, poorly differentiated subtype of squamous cell carcinoma, defined by chromosomal rearrangements of the gene encoding nuclear protein of the testis (NUT). It is characterized by extremely aggressive clinical behavior resulting in a dismal prognosis, with a median survival of 6.7 months. Though most frequently detected along the body midline, NUT carcinoma can arise in any organ. Fewer than 100 cases have been reported in medical literature with the majority of patients being children or young adults...
January 30, 2019: Pathology, Research and Practice
Yu-Lian Fang, Wei Wang, Ping Wang, Yu Zhao, Tong-Qiang Zhang, Xuan Li, Chao-Meng Fan, Shu-Xiang Lin
OBJECTIVE: To investigate the molecular epidemiological characteristics of norovirus (NoV) among children with acute gastroenteritis in Tianjin in 2017. METHODS: A total of 758 stool specimens were collected from the children with acute gastroenteritis possibly caused by viral infection in Tianjin Children's Hospital between January and December, 2017. Quantitative real-time RT-PCR was used for primary screening of NoV, and conventional RT-PCR was used for gene amplification, sequencing and genotype identification of the VP1 region of capsid protein in positive specimens...
February 2019: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Matthew W Turner, Leanna A Marquart, Paul D Phillips, Owen M McDougal
Nicotinic acetylcholine receptors (nAChRs) are found throughout the mammalian body and have been studied extensively because of their implication in a myriad of diseases. α-Conotoxins (α-CTxs) are peptide neurotoxins found in the venom of marine snails of genus Conus . α-CTxs are potent and selective antagonists for a variety of nAChR isoforms. Over the past 40 years, α-CTxs have proven to be valuable molecular probes capable of differentiating between closely related nAChR subtypes and have contributed greatly to understanding the physiological role of nAChRs in the mammalian nervous system...
February 13, 2019: Toxins
Jennifer Tse, Rashed Ghandour, Nirmish Singla, Yair Lotan
Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) is often regarded as one entity and is managed generally with similar principles. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is an established standard of care in UCB, strong evidence for a similar approach is lacking in UTUC. The longest survival is seen in patients with complete response (pT0) on pathological examination of the RC specimen, but impact of delayed RC in nonresponders may be detrimental. The rate of pT0 following NAC in UTUC is considerably lower than that in UCB due to differences in access and instrumentation...
February 13, 2019: International Journal of Molecular Sciences
Tomasz Urbaniak, Daniela Machová, Olga Janoušková, Witold Musiał
The past decade may be considered as revolutionary in the research field focused on the physiological function of macrophages. Unknown subtypes of these cells involved in pathological mechanisms were described recently, and they are considered as potential drug delivery targets. The innate ability to internalize foreign bodies exhibited by macrophages can be employed as a therapeutic strategy. The efficiency of this uptake depends on the size, shape and surface physiochemical properties of the phagocyted objects...
February 17, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Liping Guo, Guoji Chen, Wen Zhang, Lulin Zhou, Ting Xiao, Xuebing Di, Yipeng Wang, Lin Feng, Kaitai Zhang
PURPOSE: Breast cancer is a heterogeneous disease, and although advances in molecular subtyping have been achieved in recent years, most subtyping strategies target individual genes independent of one another and primarily concentrate on proliferative markers. The contributions of biological processes and immune patterns have been neglected in breast cancer subtype stratification. METHODS: We performed a gene set variation analysis to simplify the information on biological processes using hallmark terms and to decompose immune cell data using the immune cell gene terms on 985 breast invasive ductal/lobular carcinoma RNAseq samples in the TCGA database...
February 19, 2019: Breast Cancer Research and Treatment
V Guarneri, M V Dieci, G Bisagni, A Frassoldati, G V Bianchi, G L De Salvo, E Orvieto, L Urso, T Pascual, L Paré, P Galván, M Ambroggi, C A Giorgi, G Moretti, G Griguolo, R Vicini, A Prat, P F Conte
BACKGROUND: In HER2+ breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive vs negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-weeks letrozole. PATIENTS AND METHODS: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer...
February 18, 2019: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Paul Daniel, Siham Sabri, Ahmad Chaddad, Brian Meehan, Bertrand Jean-Claude, Janusz Rak, Bassam S Abdulkarim
Glioma are the most common type of malignant brain tumor, with glioblastoma (GBM) representing the most common and most lethal type of glioma. Surgical resection followed by radiotherapy and chemotherapy using the alkylating agent Temozolomide (TMZ) remain the mainstay of treatment for glioma. While this multimodal regimen is sufficient to temporarily eliminate the bulk of the tumor mass, recurrence is inevitable and often poses major challenges for clinical management due to treatment resistance and failure to respond to targeted therapies...
2019: Frontiers in Oncology
Parthopratim Dutta Majumder, Jyotirmay Biswas, Amod Gupta
Serpiginous choroiditis (SC) is an asymmetrically bilateral inflammation of the choroid that leads to loss of choriocapillaris atrophy or loss of overlying retinal pigment epithelium. Over the last few decades, SC has passed through a long evolution of nomenclature, etiologies and morphological variations. Initially diagnosed in patients with tuberculosis and syphilis, SC was predominantly considered as autoimmune process. With the advancement of molecular diagnosis, a new aspect of infectious subtypes of SC has emerged out...
March 2019: Indian Journal of Ophthalmology
Johann-Martin Hempel, Cornelia Brendle, Benjamin Bender, Georg Bier, Mareen Sarah Kraus, Marco Skardelly, Hardy Richter, Franziska Eckert, Jens Schittenhelm, Ulrike Ernemann, Uwe Klose
PURPOSE: The aim of the study was to assess the predictive value of preoperatively assessed diffusion kurtosis imaging (DKI) metrics as prognostic factors in the 2016 World Health Organization Classification of Tumors of the Central Nervous System integrated glioma groups. MATERIAL AND METHODS: Seventy-seven patients with histopathologically confirmed treatment-naïve glioma were retrospectively assessed between 08/2013 and 10/2017 using mean kurtosis (MK) and mean diffusivity (MD) histogram parameters from DKI, overall and progression-free survival, and relevant prognostic molecular data (isocitrate dehydrogenase, [IDH]; alpha-thalassemia/mental retardation syndrome X-linked, [ATRX]; chromosome 1p/19q loss of heterozygosity)...
March 2019: European Journal of Radiology
Raunak Shrestha, Noushin Nabavi, Yen-Yi Lin, Fan Mo, Shawn Anderson, Stanislav Volik, Hans H Adomat, Dong Lin, Hui Xue, Xin Dong, Robert Shukin, Robert H Bell, Brian McConeghy, Anne Haegert, Sonal Brahmbhatt, Estelle Li, Htoo Zarni Oo, Antonio Hurtado-Coll, Ladan Fazli, Joshua Zhou, Yarrow McConnell, Andrea McCart, Andrew Lowy, Gregg B Morin, Tianhui Chen, Mads Daugaard, S Cenk Sahinalp, Faraz Hach, Stephane Le Bihan, Martin E Gleave, Yuzhuo Wang, Andrew Churg, Colin C Collins
BACKGROUND: Malignant peritoneal mesothelioma (PeM) is a rare and fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM exist. Some immune checkpoint inhibitor studies of mesothelioma have found positivity to be associated with a worse prognosis. METHODS: To search for novel therapeutic targets for PeM, we performed a comprehensive integrative multi-omics analysis of the genome, transcriptome, and proteome of 19 treatment-naïve PeM, and in particular, we examined BAP1 mutation and copy number status and its relationship to immune checkpoint inhibitor activation...
February 18, 2019: Genome Medicine
Xin Wang, Gaochao Guo, Hui Guan, Yang Yu, Jie Lu, Jinming Yu
PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with positive PD-L1 expression. However, PD-1/PD-L1 checkpoint blockades have not achieved breakthroughs in treating glioblastoma because glioblastoma has a low immunogenic response and an immunosuppressive microenvironment caused by the precise crosstalk between cytokines and immune cells...
February 18, 2019: Journal of Experimental & Clinical Cancer Research: CR
Yizi He, Jiao Li, Ning Ding, Xiaogan Wang, Lijuan Deng, Yan Xie, Zhitao Ying, Weiping Liu, Lingyan Ping, Chen Zhang, Yuqin Song, Jun Zhu
BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma. Although durable remissions can be achieved in more than half of these patients, DLBCL remains a significant clinical challenge, with approximately 30% of patients not being cured. BCR-associated kinases (SYK, BTK, and PI3K) inhibitors have exhibited encouraging pre-clinical and clinical effects, as reported by many researchers. Early studies demonstrated that protein kinase C-β (PKCβ) inhibitors alter phosphorylation level the Bruton's tyrosine kinase (BTK), which leads to enhanced BTK signaling...
February 18, 2019: Journal of Experimental & Clinical Cancer Research: CR
E A Barbosa, N do C Fontes, S C L Santos, D J Lefeber, C Bloch, J M Brum, G D Brand
BACKGROUND: Type II Congenital Disorders of Glycosylation (CDG-II) are a group of diseases with challenging diagnostics characterized by defects in the processing of glycans in the Golgi apparatus. Mass Spectrometry (MS) has been a valuable tool in the definition of CDG-II subtypes. While some CDG-II subtypes are associated with specific N-glycan structures, others only produce changes in relative levels, reinforcing the demand for quantification methods. METHODS: Plasma samples from control individuals were pooled, derivatized with deuterated iodomethane (I-CD3 ), and used as internal standards for controls and patients whose glycans were derivatized with iodomethane (I-CH3 ), followed by MALDI MS, LC-MS and -MS/MS analyses...
February 15, 2019: Clinica Chimica Acta; International Journal of Clinical Chemistry
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