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#32791571   // To Up

Leaf Wax Lipid Extraction for Archaeological Applications.

Plant wax lipid molecules, chiefly normal (n-) alkanes and n-alkanoic acids, are frequently used as proxies for understanding paleoenvironmental and paleoclimatic change. These are regularly analyzed from marine and lake sediments and even more frequently in archaeological contexts, enabling the reconstruction of past environments in direct association with records of past human behavior. Carbon and hydrogen isotope measurements of these compounds are used to trace plant type and water-use efficiency, relative paleotemperature, precipitation, evapotranspiration of leaf and soil moisture, and other physiological and ecological parameters. Plant wax lipids have great potential for answering questions related to human-environment interactions, being for the most part chemically inert and easily recoverable in terrestrial sediments, including those dating back millions of years. The growing use of this technique, and comparison of such data with other paleoenvironmental proxies such as pollen and phytolith analysis and soil carbonate and tooth enamel isotope records, make it essential to establish consistent, best-practice protocols for extracting n-alkanes and n-alkanoic acids from archaeological sediments to provide comparable information for interpreting past climatic, ecosystem, and hydrological changes and their interaction with human societies. © 2020 The Authors. Basic Protocol 1: Total lipid extraction Support Protocol 1: Weighing the total lipid extract Support Protocol 2: Cleaning the PSE extraction cells Alternate Protocol 1: Soxhlet total lipid extraction Alternate Protocol 2: Ultrasonic total lipid extraction Basic Protocol 2: Separation of lipids by aminopropyl column chromatography Basic Protocol 3: Separation of lipids by silver-nitrate-infused silica gel column chromatography Support Protocol 3: Preparation of silica gel infused with 10% silver nitrate Basic Protocol 4: Methylation of n-alkanoic acids Basic Protocol 5: Gas chromatography mass spectrometry (GC-MS) Basic Protocol 6: Gas chromatography isotope ratio mass spectrometry (GC-IRMS).
Robert Patalano, Jana Zech, Patrick Roberts

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#32791559   2020/08/13 To Up

Identifying mismatch repair deficient colon cancer: near perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population-based series.

Establishing mismatch repair (MMR) status of colorectal cancers is important to enable detection of underlying Lynch syndrome and inform prognosis and therapy. Current testing typically involves either PCR-based microsatellite (MSI) testing or MMR protein immunohistochemistry (IHC). We aimed to compare these two approaches in a large, population-based cohort of stage 2 and 3 colon cancer cases in Northern Ireland.
Maurice B Loughrey, Jason McGrath, Helen G Coleman, Peter Bankhead, Perry Maxwell, Claire McGready, Victoria Bingham, Matthew P Humphries, Stephanie G Craig, Stephen McQuaid, Manuel Salto-Tellez, Jacqueline A James

2592 related Products with: Identifying mismatch repair deficient colon cancer: near perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population-based series.



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#32791549   2020/08/13 To Up

[Current diagnosis and treatment of chronic lymphocytic leukaemia].

Two major advances were made in the treatment of chronic lymphocytic leukaemia (CLL): the addition of the antibody rituximab to chemotherapy two decades ago and the introduction of the targeted agents during the last few years. Four targeted drugs with different mechanisms of action were added to the armamentarium of CLL treatment: the anti-CD20 antibody obinutuzumab, the two kinase inhibitors ibrutinib and idelalisib, which target the Bruton tyrosine kinase (BTK) and Phosphatidylinositiol-3-Kinase (PI3K) respectively in the B-cell receptor signalling pathway, as well as the Bcl2-antagonist venetoclax.Recently, the combination of venetoclax/obinutuzumab was approved for the first-line treatment of all CLL patients based on a phase-III trial in elderly unfit patients. This combination was shown to be clearly superior to chlorambucil/obinutuzumab and should become the preferred first-line treatment for the so called "slow-go" patients. Other options for these elderly, unfit patients are continuous ibrutinib or chlorambucil/obinutuzumab. Although data from phase-III studies are not yet available, venetoclax/obintuzumab may also be offered to younger, fit patients. Established therapeutic options for these so called "go go" patients are ibrutinib, fludarabin/cyclophosphamide/rituximab or bendemustine/rituximab (if > 65 years). Patients with the high-risk parameters deletion 17p or TP53mutation are known to poorly respond to chemo(immuno)therapy and should receive either ibrutinib or venetoclax/obinutuzumab.Thus, a choice has to be made between a continuous monotherapy with ibrutinib or a time-limited combination with either venetoclax/obinutuzumab (12 months) or chemoimmunotherapy (usually 6 months). In addition to disease-related factors (e. g. presence of deletion 17p/TP53 mutation, IgHV mutational status, prior therapies), comorbidities, co-medication and the specific side effects of the CLL therapies (myelosuppression, infections and secondary malignancies for chemoimmunotherapy; cardiac toxicity, bleeding and autoimmune disease for ibrutinib; tumour-lysis syndromes and infections for venetoclax) the patient's expectations need to be considered.
Paula Cramer, Julia von Tresckow, Barbara Eichhorst, Michael Hallek

2243 related Products with: [Current diagnosis and treatment of chronic lymphocytic leukaemia].

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#32791545   2020/08/13 To Up

[Diagnostic work-up in central retinal artery occlusion and ischemic optic neuropathy - what is important?]

Ischemia of the retina in central retinal artery occlusion (CRAO) and of the optic nerve in ischemic optic neuropathy (ION) are common causes of irreversible vision loss in elderly patients and require a thorough diagnostic work-up. First and foremost, giant cell arteritis should be confirmed or ruled out. The further work-up of non-arteritic CRAO and non-arteritic ION (nAION) aims to determine the cardiovascular risk profile. Patients with nAION should be screened for sleep apnoea. In non-arteritic CRAO, the search for embolic sources is the most important diagnostic task. A "white spot sign" seen on transorbital ultrasound confirms the diagnosis of embolic CRAO and rules out an arteritic etiology of CRAO.
Christian Lottspeich, Marc J Mackert, Ulrich Hoffmann, Michael Czihal

2434 related Products with: [Diagnostic work-up in central retinal artery occlusion and ischemic optic neuropathy - what is important?]

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#32791542   2020/08/13 To Up

Targeted RNAseq of Formalin-Fixed Paraffin-Embedded Tissue to Differentiate Among Benign and Malignant Adrenal Cortical Tumors.

Lack of routine fresh or frozen tissue is a barrier to widespread transcriptomic analysis of adrenal cortical tumors and an impediment to translational research in endocrinology and endocrine oncology. Our group has previously pioneered the use of targeted amplicon-based next-generation sequencing for archival formalin-fixed paraffin-embedded (FFPE) adrenal tissue specimens to characterize the spectrum of somatic mutations in various forms of primary aldosteronism. Herein, we developed and validated a novel 194-amplicon targeted next-generation RNA sequencing (RNAseq) assay for transcriptomic analysis of adrenal tumors using clinical-grade FFPE specimens. Targeted RNAseq-derived expression values for 27 adrenal cortical tumors, including aldosterone-producing adenomas (APA; n=8), cortisol-producing adenomas (CPA; n=11), and adrenal cortical carcinomas (ACC; n=8), highlighted known differentially-expressed genes (DEGs; i. e., , , etc.) and tumor type-specific transcriptional modules (i. e., high cell cycle/proliferation transcript expression in ACC, etc.), and a subset of DEGs was validated orthogonally using quantitative reverse transcription PCR (qRT-PCR). Finally, unsupervised hierarchical clustering using a subset of high-confidence DEGs revealed three discrete clusters representing APA, CPA, and ACC tumors with corresponding unique gene expression signatures, suggesting potential clinical utility for a transcriptomic-based approach to tumor classification. Overall, these data support the use of targeted amplicon-based RNAseq for comprehensive transcriptomic profiling of archival FFPE adrenal tumor material and indicate that this approach may facilitate important translational research opportunities for the study of these tumors.
Samuel W Plaska, Chia-Jen Liu, Jung Soo Lim, Juilee Rege, Nolan R Bick, Antonio M Lerario, Gary D Hammer, Thomas J Giordano, Tobias Else, Scott A Tomlins, William E Rainey, Aaron M Udager

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#32791535   2020/08/13 To Up

Silibinin Inhibit Cell Migration through Downregulation of RAC1 Gene Expression in Highly Metastatic Breast Cancer Cell Line.

Triple negative breast cancer is the most invasive breast cancer subtype and possesses poor prognosis and survival. Rho GTPase famil, especially Rac1 participates in a number of signaling events in cells with crucial roles in malignancy, migration and invasion of tumor cells. Silibinin, a flavonoid antioxidant from milk thistle has attracted attention in the recent decades for chemoprevention and chemotherapy of tumor cells. In this study, the effect of silibinin on the migration capacity of MDA-MB-231 cells, a highly metastatic human breast cancer cell line was investigated by evaluation of Rac1 expression.
Hamed Esmaeil Lashgarian, Vahid Adamii, Vajihe Ghorbanzadeh, Leila Chodari, Fayze Kamali, Soheila Akbari, Hassan Dariushnejad

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#32791527   2020/08/13 To Up

Expression Profiling of Primary and Recurrent Glioblastomas Reveals a Reduced Level of Pentraxin 3 in Recurrent Glioblastomas.

Glioblastomas (GBM) are highly infiltrative tumors and despite intensive treatment tumor recurrence is inevitable. The immune microenvironment in recurrent GBM is poorly characterized, but it is potentially influenced by therapeutic interventions with surgery, radiotherapy, and chemotherapy. The aim of this study was to obtain a deeper insight in the immune microenvironment in primary and recurrent GBM. Primary and recurrent glioblastoma samples from 18 patients were identified and expression profiling of 770 myeloid innate immune-related markers was performed. Leukemia inhibitory factor and pentraxin 3 were expressed at lower levels in recurrent tumors. Using in silico data and immunohistochemical staining, this was validated for pentraxin 3. Both high leukemia inhibitory factor and pentraxin 3 expression appeared to be associated with shorter survival in primary and recurrent GBM using in silico data. In primary GBM, gene set analysis also showed higher expression of genes involved in metabolism, extracellular matrix remodeling and complement activation, whereas genes involved in T cell activation and checkpoint signaling were expressed at higher levels in recurrent GBM. The reduced level of pentraxin 3 in recurrent glioblastomas and the gene set analysis results suggest an altered microenvironment in recurrent GBM that might be more active.
Stine Asferg Petterson, Mia Dahl Sørensen, Bjarne Winther Kristensen

2620 related Products with: Expression Profiling of Primary and Recurrent Glioblastomas Reveals a Reduced Level of Pentraxin 3 in Recurrent Glioblastomas.

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