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https://www.readbyqxmd.com/read/29784668/centrosome-linker-induced-tetraploid-segregation-errors-link-rhabdoid-phenotypes-and-lethal-colorectal-cancers
#1
Andrea Remo, Erminia Manfrin, Pietro Parcesepe, Alberto Ferrarini, Hye Seung Han, Mickys Ugnius, Carmelo Laudanna, Michele Simbolo, Donatella Malanga, Duarte Mendes Oliveira, Elisabetta Baritono, Tommaso Colangelo, Lina Sabatino, Jacopo Giuliani, Enrico Molinari, Marianna Garonzi, Luciano Xumerle, Massimo Delledonne, Guido Giordano, Claudio Ghimenton, Fortunato Lonardo, Fulvio D'angelo, Federica Grillo, Luca Mastracci, Giuseppe Viglietto, Michele Ceccarelli, Vittorio Colantuoni, Aldo Scarpa, Massimo Pancione
Centrosome anomalies contribute to tumorigenesis but it remains unclear how they are generated in lethal cancer phenotypes. Here, it is demonstrated that human microsatellite instable (MSI) and BRAF(V600E) mutant colorectal cancers with a lethal rhabdoid phenotype are characterized by inactivation of centrosomal functions. A splice site mutation that causes an unbalanced dosage of rootletin (CROCC), a centrosomal-linker component required for centrosome cohesion and separation at the chromosome 1p36.13 locus, resulted in abnormally shaped centrosomes in rhabdoid cells from human colon tissues...
May 21, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29783979/lynch-syndrome-associated-endometrial-carcinoma-with-mlh1-germline-mutation-and-mlh1-promoter-hypermethylation-a-case-report-and-literature-review
#2
Takanori Yokoyama, Kazuhiro Takehara, Nao Sugimoto, Keika Kaneko, Etsuko Fujimoto, Mika Okazawa-Sakai, Shinichi Okame, Yuko Shiroyama, Takashi Yokoyama, Norihiro Teramoto, Shozo Ohsumi, Shinya Saito, Kazuho Imai, Kokichi Sugano
BACKGROUND: Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer...
May 21, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29783097/regulation-of-phytosterol-biosynthetic-pathway-during-drought-stress-in-rice
#3
M S Sujith Kumar, Ibandalin Mawlong, Kishwar Ali, Aruna Tyagi
Plants respond to drought stress in the form of various physio-biochemical and molecular changes at both cellular and molecular levels. Drought stress causes the destruction of cell membranes by disintegration of membrane lipids. One of the major groups of membrane lipids that plays important role in preserving the integrity of cell membranes is phytosterols. HMG-CoA reductase (HMGR) is the principal enzyme in the biosynthesis of plant sterols, synthesized via mevalonic acid pathway. Phospholipid: sterol acyltransferase (PSAT) is another important enzyme that plays an important role in turnover of phytosterols into steryl esters and helps maintain homeostasis of membrane lipids...
May 15, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29782166/toxicokinetics-tissue-distribution-and-excretion-of-dufulin-racemate-and-its-r-s-enantiomers-in-rats
#4
Huaguo Chen, Xin Zhou, Baoan Song
Dufulin is a plant antiviral agent with a novel molecular structure and has been used widely to prevent and control tobacco and rice viral diseases. In this study, an UHPLC-MS/MS assay was developed for rapid determination of dufulin racemate (rac-DFL) and its R (S)-enantiomers in rat plasma, tissues, urine and feces. A MALDI-MSI method was further used to visual research on tissue distribution after oral administration of the three analytes. Toxicokinetic study showed that both (R)-enantiomers of dufulin ((R)-DFL) and (S)-enantiomers of dufulin ((S)-DFL) had a faster ability to reach Cmax than that of rac-DFL...
May 21, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29779068/new-insights-into-the-inflamed-tumor-immune-microenvironment-of-gastric-cancer-with-lymphoid-stroma-from-morphology-and-digital-analysis-to-gene-expression
#5
Irene Gullo, Patrícia Oliveira, Maria Athelogou, Gilza Gonçalves, Marta L Pinto, Joana Carvalho, Ana Valente, Hugo Pinheiro, Sara Andrade, Gabriela M Almeida, Ralf Huss, Kakoli Das, Patrick Tan, José C Machado, Carla Oliveira, Fátima Carneiro
BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment. METHODS: Twenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and PD-L1 copy number alterations...
May 19, 2018: Gastric Cancer
https://www.readbyqxmd.com/read/29776633/molecular-diagnostics-in-colorectal-carcinoma-advances-and-applications-for-2018
#6
REVIEW
Amarpreet Bhalla, Muhammad Zulfiqar, Martin H Bluth
The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29772224/pharmacokinetics-and-skin-tolerability-of-intracutaneous-zolmitriptan-delivery-in-swine-using-adhesive-dermally-applied-microarray-adam
#7
Joe Nguyen, Hayley Lewis, Ashley Queja, Anh Ngoc Diep, Guillaume Hochart, Mahmoud Ameri
Adhesive Dermally-Applied Microarray (ADAM) is a new drug delivery system that uses microprojections (340 μm long) for intracutaneous drug self-administration. We formulated zolmitriptan, a well-accepted and commonly used migraine medication, for administration using ADAM. In vivo studies were conducted in female prepubescent Yorkshire pigs using ADAM 1.9 mg zolmitriptan, applied to the inner thigh and left in place for 1 hour. Pharmacokinetic studies showed that the ADAM 1.9 mg zolmitriptan delivered with high efficiency (85%) and high absolute bioavailability (77%)...
May 14, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#8
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29767751/clinicopathological-and-molecular-differences-between-right-sided-and-left-sided-colorectal-cancer-in-japanese-patients
#9
Soichiro Natsume, Tatsuro Yamaguchi, Misato Takao, Takeru Iijima, Rika Wakaume, Keiichi Takahashi, Hiroshi Matsumoto, Daisuke Nakano, Shin-Ichiro Horiguchi, Koichi Koizumi, Michiko Miyaki
Background: The aim of this study was to clarify clinicopathological features, frequencies of molecular biomarkers, and prognoses in Japanese colorectal cancer patients and compare them with right-sided colon cancer (RCC) and left-sided colorectal cancer (LCRC). Methods: We consecutively selected 575 colorectal cancer patients who underwent surgical resection from 2008 to 2011. RCC was located from the cecum to the transverse colon, and LCRC was located from the splenic flexure to the rectum...
May 15, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29764494/precision-medicine-becomes-reality-tumor-type-agnostic-therapy
#10
REVIEW
Li Yan, Wei Zhang
Precision medicine just witnessed two breakthroughs in oncology in 2017. Pembrolizumab (Keytruda), Merck's anti-programmed cell death-1 (PD-1) monoclonal antibody (mAb), received accelerated approval in May 2017 by the US Food and Drug Administration for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR). Shortly after, nivolumab (Opdivo), Bristol-Myers Squibb's anti-PD-1 mAb, gained an accelerated approval in August 2017 for adult and pediatric patients with MSI-H or dMMR metastatic colorectal cancer that has progressed after standard chemotherapy...
March 31, 2018: Cancer communications
https://www.readbyqxmd.com/read/29764162/the-evolving-role-of-immune-oncology-in-colorectal-cancer
#11
Shaheenah Dawood
Metastatic colorectal cancer still remains an essentially non curable disease. However, with advances in chemotherapeutic and personalizing therapeutic approaches with the incorporation of targeted therapy such as anti-EGFR and anti-VEGF agents survival associated with metastatic colorectal cancer has certainly improved over the last two decades. Patients who are not amenable to surgery median survival remain approximately 2 to 3 years. In an attempt to improve prognostic outcome over the last decade research has focused on therapeutic options geared towards harnessing the immune system with success observed with the use of immune checkpoint inhibitors in the realm of a number of solid tumors including lung and renal cancer...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29761443/mass-spectrometry-imaging-msi-for-plant-metabolomics
#12
Berin A Boughton, Dinaiz Thinagaran
Mass spectrometry imaging (MSI) is a developing technique to measure the spatiotemporal distribution of many biomolecules in tissues. Over the preceding decade MSI has been adopted by plant biologists and applied in a broad range of areas including: primary metabolism, natural products, plant defense, plant responses to abiotic and biotic stress, plant lipids, and the developing field of spatial metabolomics. This methods chapter covers preparation of plant tissues for matrix-assisted laser desorption ionization (MALDI)-MSI, including sample embedding and freezing, sectioning, mounting, and matrix deposition using both sublimation and spray deposition prior to MSI analysis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29760388/cell-of-origin-and-mutation-pattern-define-three-clinically-distinct-classes-of-sebaceous-carcinoma
#13
Jeffrey P North, Justin Golovato, Charles J Vaske, J Zachary Sanborn, Andrew Nguyen, Wei Wu, Benjamin Goode, Meredith Stevers, Kevin McMullen, Bethany E Perez White, Eric A Collisson, Michele Bloomer, David A Solomon, Stephen C Benz, Raymond J Cho
Sebaceous carcinomas (SeC) are cutaneous malignancies that, in rare cases, metastasize and prove fatal. Here we report whole-exome sequencing on 32 SeC, revealing distinct mutational classes that explain both cancer ontogeny and clinical course. A UV-damage signature predominates in 10/32 samples, while nine show microsatellite instability (MSI) profiles. UV-damage SeC exhibited poorly differentiated, infiltrative histopathology compared to MSI signature SeC (p = 0.003), features previously associated with dissemination...
May 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29759594/liquid-chromatography-mass-spectrometry-based-metabolomics-and-lipidomics-reveal-toxicological-mechanisms-of-bisphenol-f-in-breast-cancer-xenografts
#14
Chao Zhao, Peisi Xie, Hailin Wang, Zongwei Cai
Bisphenol F (BPF) is a major alternative to bisphenol (BPA) and has been widely used. Although BPA exposure is known to generate various toxic effects, toxicity of BPF remains under-explored. A comprehensive method involving mass spectrometry (MS)-based global lipidomics and metabolomics, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)- MS imaging (MSI) was used to study toxic effects of BPF and the underlying mechanisms on tumor metastasis-related tissues (liver and kidney) in breast cancer xenografts...
May 5, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29752761/spatial-analysis-of-lipid-metabolites-and-expressed-genes-reveals-tissue-specific-heterogeneity-of-lipid-metabolism-in-high-and-low-oil-brassica-napus-l-seeds
#15
Shaoping Lu, Drew Sturtevant, Mina Aziz, Cheng Jin, Qing Li, Kent D Chapman, Liang Guo
Despite the importance of oilseeds to worldwide human nutrition, and more recently to the production of bio-based diesel fuels, the detailed mechanisms regulating seed oil biosynthesis remain partly understood, especially from a tissue-specific perspective. Here, we investigated the spatial distributions of lipid metabolites and transcripts involved in oil biosynthesis from seeds of two low-erucic acid genotypes of Brassica napus with high and low seed oil content. Integrated results from matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) of lipids in situ, lipidome profiling of extracts from seed tissues, and tissue-specific transcriptome analysis revealed complex spatial distribution patterns of lipids and transcripts...
May 11, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29752549/promising-new-agents-for-colorectal-cancer
#16
REVIEW
Satya Das, Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility...
May 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29747443/microsatellite-instability-occurs-rarely-in-patients-with-cholangiocarcinoma-a-retrospective-study-from-a-german-tertiary-care-hospital
#17
Ria Winkelmann, Markus Schneider, Sylvia Hartmann, Andreas A Schnitzbauer, Stefan Zeuzem, Jan Peveling-Oberhag, Martin Leo Hansmann, Dirk Walter
Immune-modulating therapy is a promising therapy for patients with cholangiocarcinoma (CCA). Microsatellite instability (MSI) might be a favorable predictor for treatment response, but comprehensive data on the prevalence of MSI in CCA are missing. The aim of the current study was to determine the prevalence of MSI in a German tertiary care hospital. Formalin-fixed paraffin-embedded tissue samples, obtained in the study period from 2007 to 2015 from patients with CCA undergoing surgical resection with curative intention at Johann Wolfgang Goethe University hospital, were examined...
May 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29745432/improved-spectra-for-maldi-msi-of-peptides-using-ammonium-phosphate-monobasic-in-maldi-matrix
#18
Yasemin Ucal, Aysel Ozpinar
MALDI mass spectrometry imaging (MSI) enables analysis of peptides along with histology. However, there are several critical steps in MALDI MSI of peptides, one of which is spectral quality. Suppression of MALDI matrix clusters by the aid of ammonium salts in MALDI experiments is well-known. It is asserted that addition of ammonium salts dissociates potential matrix adducts and thereafter decreases matrix cluster formation. Consequently, MALDI MS sensitivity and mass accuracy increases. Up to our knowledge, a limited number of MALDI MSI studies used ammonium salts as matrix additives to suppress matrix clusters and enhance peptide signals...
May 10, 2018: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29745066/site-specific-use-of-molecular-markers-could-be-a-promising-prognostic-tool-in-colorectal-cancer
#19
Petros Papagiorgis, Adamantia Zizi-Sermbetzoglou, Dimitrios Chaniotis, Nikolaos Thalassinos, Paraskevi Tziakou
Proximal and distal colorectal carcinomas (CRCs) are generally considered as genetically and clinicopathologically distinct disease entities. Tumor location has been proposed as an additional prognostic indicator and -more recently- as a factor with significant influence on the prognostic value of particular molecular markers and/or combination of markers (KRAS, MSI, APC/MSI), allowing the discrimination of specific disease subsets with considerably disparate outcome and the identification of high risk cases...
March 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29743854/microsatellite-instability-in-colorectal-cancer
#20
REVIEW
Jafar Nouri Nojadeh, Shahin Behrouz Sharif, Ebrahim Sakhinia
Colorectal cancer (CRC) is a heterogeneous disease that is caused by the interaction of genetic and environmental factors. Although it is one of the most common cancers worldwide, CRC would be one of the most curable cancers if it is detected in the early stages. Molecular changes that occur in colorectal cancer may be categorized into three main groups: 1) Chromosomal Instability (CIN), 2) Microsatellite Instability (MSI), and 3) CpG Island Methylator phenotype (CIMP). Microsatellites, also known as Short Tandem Repeats (STRs) are small (1-6 base pairs) repeating stretches of DNA scattered throughout the entire genome and account for approximately 3 % of the human genome...
2018: EXCLI journal
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