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Experimental and Molecular Pathology

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https://www.readbyqxmd.com/read/30031020/ezh2-is-upregulated-in-the-proliferation-centers-of-cll-sll-lymph-nodes
#1
Kinga Szurián, Irén Csala, Dóra Marosvári, Hajnalka Rajnai, Katalin Dezső, Csaba Bödör, Violetta Piurkó, András Matolcsy, Lilla Reiniger
Lymph node involvement of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) is characterised by the diffuse infiltration of small neoplastic lymphocytes, which is accompanied by the presence of proliferation centres (PCs) comprising prolymphocytes and paraimmunoblasts. There is increasing evidence of accumulation of various molecular alterations in the tumour cells of PCs, which may explain why extended PCs are related to a less favourable prognosis. To further characterize PCs, we compared the expression level of EZH2 protein, the overexpression of which has recently been recognized as poor prognostic factor in CLL/SLL, in the PCs and the intervening small cell areas in lymph nodes of 15 patients with CLL/SLL...
July 18, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/30028961/circulating-tumor-cells-and-their-advances-to-promote-cancer-metastasis-and-relapse-with-focus-on-glioblastoma-multiforme
#2
REVIEW
Dimitry A Chistiakov, Vladimir P Chekhonin
In the late stages of their development, cancers can form metastases. Formation of metastases was found to be associated with the capacity of cancer cells to quit the tumor mass and journey through the circulation to distant organs. This cell population is called circulating tumor cells (CTCs). They exhibit several advanced properties such as epithelial-to-mesenchymal transition (EMT) and dormancy that are essential for supporting their survival in the bloodstream, radio- and chemoresistance, their escape from the anti-cancer immune response, and metastasis initiation...
July 17, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/30028960/phosphorylated-sirt1-as-a-biomarker-of-relapse-and-response-to-treatment-with-glatiramer-acetate-in-multiple-sclerosis
#3
Jonathan Ciriello, Alexandru Tatomir, Daniel Hewes, Dallas Boodhoo, Freidrich Anselmo, Violeta Rus, Horea Rus
We have previously shown that SIRT1 mRNA expression was significantly lower in relapsing MS patients compared to those in remission. Our goal was to longitudinally investigate the role of active, phosphorylated SIRT1 (p-SIRT1) as a potential biomarker of relapse and predictor for response to glatiramer acetate (GA) treatment in patients with relapsing remitting multiple sclerosis (MS). We also want to investigate the downstream effects of SIRT1 activation by measuring the trimethylation of histone 3 at lysine 9 (H3K9me3)...
July 17, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/30009774/piecemeal-necrosis-is-due-to-the-immunologic-synapse-formation-and-internalization-of-intact-tcr-mhc-ii-complexes-by-cd4-t-cells
#4
Samuel W French, Jiajie G Lu
The nature of the immunologic synapse in autoimmune hepatitis is defined. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the plasma membrane. This complex is quickly removed from the liver cell and taken into the T cell cytoplasm to be digested by the lysosome. The liver cell is gradually diminished to the point of its total removal by the lymphocytes binding to it.
July 12, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/30009773/immunohistochemistry-is-a-feasible-method-to-screen-braf-v600e-mutation-in-colorectal-and-papillary-thyroid-carcinoma
#5
Xiangyan Zhang, Lili Wang, Jigang Wang, Han Zhao, Jie Wu, Shuhong Liu, Lu Zhang, Yujun Li, Xiaoming Xing
AIMS: To investigate whether immunohistochemistry (IHC) could be used to screen BRAF mutation status in formalin-fixed paraffin-embedded (FFPE) colorectal carcinoma (CRC) and papillary thyroid carcinoma (PTC) samples. METHODS: Eight surgical resected samples, including 2 CRCs with mutated BRAF V600E, 2 PTCs with mutated BRAF V600E, 2 CRCs with wild-type BRAF and 2 PTCs with wild-type BRAF, were selected to explore the optimized IHC conditions for BRAF V600E (VE1) immunostaining using BenchmarkXT automated immunostainer VENTANA Medical System...
July 12, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/30009772/different-roles-of-fat10-foxo1-and-adra2a-in-hepatocellular-carcinoma-tumorigenesis-in-patients-with-alcoholic-steatohepatitis-ash-vs-non-alcoholic-steatohepatitis-nash
#6
Yue Jia, Barbara French, Brittany Tillman, Samuel French
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer related deaths worldwide. Among others, non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the two major risk factors as both of them may develop cirrhosis and hepatocellular carcinoma (HCC) if left untreated. However, patients with NASH progress to HCC at a rate around 0.5% annually, while 3-10% ASH patients may progress to HCC annually. The present study is to demonstrate the molecular differences in oncogenesis pathway between NASH and ASH...
July 12, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/30017658/therapy-related-acute-myeloid-leukemia-developing-14-years-after-allogeneic-hematopoietic-stem-cell-transplantation-from-a-persistent-r882h-dnmt3a-mutated-clone-of-patient-origin
#7
Iván Martín, Blanca Navarro, Eva Villamón, Carlos Solano, Alicia Serrano, Marisa Calabuig, Paula Amat, Fernando Domingo, Rosario Abellán, Francisca García, María Dolores Olivares, Francisco Javier Chaves, Mar Tormo, Juan Carlos Hernández-Boluda
BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) develops in patients with prior exposure to cytotoxic therapies. Selection of a pre-existing TP53 mutated clone prone to acquire additional mutational events has been suggested as the main pathogenic mechanism of t-AML. Here, we report a unique case of t-AML which developed from a pre-existing DNMT3A mutated clone that persisted in the patient for more than 10 years despite treatment with intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (alloHSCT)...
July 11, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/30003874/telocytes-role-during-the-postnatal-development-of-the-mongolian-gerbil-jejunum
#8
Bruno C Zani, Bruno D A Sanches, Juliana S Maldarine, Manoel F Biancardi, Fernanda C A Santos, Caroline N Barquilha, Mariele I Zucão, Carolina M B Baraldi, Sergio L Felisbino, Rejane M Góes, Patricia S L Vilamaior, Sebastião R Taboga
Telocytes are recently categorised CD34-positive interstitial cells that comprise the cells which were previously called interstitial Cajal-like cells (ICLCs). These were detected in the stroma of various organs such as the prostate, lungs, mammary glands, liver, gallbladder, and jejunum, among others. Several functions have been proposed for telocytes, such as a supportive role in smooth muscle contraction and immune function in adult organs, and tissue organisation and paracrine signalling during development, as well as others...
July 9, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29981754/renal-matrix-gla-protein-expression-increases-progressively-with-ckd-and-predicts-renal-outcome
#9
Kana N Miyata, Cynthia C Nast, Tiane Dai, Ramanath Dukkipati, Janine A LaPage, Jonathan P Troost, Leon J Schurgers, Matthias Kretzler, Sharon G Adler
BACKGROUND: Matrix Gla Protein (MGP) is a potent inhibitor of ectopic calcification and modulates bone morphogenesis. Little is known about MGP expression or function in kidney. METHODS: We investigated renal MGP expression in Sprague-Dawley rats after 5/6 nephrectomy (5/6 Nx) and in human kidney biopsies in the Nephrotic Syndrome Study Network (NEPTUNE) cohort. We analyzed associations between glomerular (n = 182) and tubulointerstitial (TI) (n = 219) MGP mRNA levels and the disease activity/histologic features in NEPTUNE patients...
July 5, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29909157/fullerenol-c-60-oh-36-at-relatively-high-concentrations-impairs-hippocampal-theta-oscillations-in-vivo-and-in-vitro-and-triggers-epilepsy-in-vitro-a-dose-response-study
#10
Paulina Kazmierska-Grebowska, Anna Kobrzycka, Renata Bocian, Tomasz Kowalczyk, Anita Krokosz, Jacek Grebowski
Since the first identification of fullerenes (C60 ) and their synthesis in 1985, those compounds have been extensively studied in the biomedical field. In particular, their water-soluble derivatives, fullerenols (C60 (OH)n, n = 2-48), have recently been the subject of numerous investigations concerning their antioxidant and prooxidant properties in biological systems. A small fraction of that research has focused on the possible use of C60 and C60 (OH)n in neuroscience and the therapy of pathologies such as dementia, amyloid-β (Aβ) formation, and Parkinson's disease...
June 23, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29940157/correlation-between-pai-1-leptin-and-ferritin-with-homa-in-hiv-aids-patients
#11
Gordana Dragović, Mirjana Sumarac-Dumanovic, Al Musalhi Khawla, Ivan Soldatović, Mladen Andjić, Djordje Jevtović, Devaki Nair
BACKGROUND: Data about correlation of interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFα), ferritin, C reactive protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim of this study was to evaluate the possible correlations of serum levels of PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients treated with combined antiretroviral therapy (cART)...
June 22, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29935954/global-dna-methylation-profile-in-medullary-thyroid-cancer-patients
#12
Lucieli Ceolin, Ana Paula Palauro Goularte, Carla Vaz Ferreira, Mírian Romitti, Ana Luiza Maia
BACKGROUND: Changes in global DNA methylation have been suggested to cause genomic instability leading to increased risk of cancer. The accumulation of epigenetic changes is believed to contribute to tumorigenesis and dedifferentiation, but the effects of such changes in thyroid cancer are still yet defined. OBJECTIVE: To evaluate the global DNA methylation levels in thyroid cancer patients. METHODS: Total DNA was extracted from peripheral blood leukocytes of the medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) patients and the methylation pattern was evaluated using the Imprint Methylated DNA Quantification kit (Sigma-Aldrich)...
June 21, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29909158/therapeutic-potential-of-vanillylacetone-against-ccl-4-induced-hepatotoxicity-by-suppressing-the-serum-marker-oxidative-stress-inflammatory-cytokines-and-apoptosis-in-swiss-albino-mice
#13
Mohammad Firoz Alam, Mohammed M Safhi, Tarique Anwer, Rahimullah Siddiqui, Gyas Khan, Sivakumar Sivagurunathan Moni
The aim of this research was to investigate the therapeutic potential of Vanillylacetone against carbon tetrachloride (CCl4 ) induced hepatotoxicity in mice through understanding the serum marker, oxidative stress mechanism and cytokine networks. Carbon tetrachloride is highly hepatotoxic used as research based on animal model. The mice were classified into five groups and each had eight mice. Group-I was controlled and the vehicle was given orally. Group-II was toxic and carbon tetrachloride (1.5 ml/kg) twice a week for 15 days was administered by intra-peritoneal injections...
June 20, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29859945/the-murine-hepatic-sequelae-of-long-term-ethanol-consumption-are-sex-specific-and-exacerbated-by-aldh1b1-loss
#14
Mike Freya Müller, Timothy James Kendall, David James Adams, Ying Zhou, Mark Johan Arends
Disease progression in alcoholic and non-alcoholic fatty liver disease shows sex-specific differences and is influenced by mechanisms linked to oxidative stress. Acetaldehyde plays a critical pathogenic role but its effects are mitigated by the activity of aldehyde dehydrogenases. Aldehyde dehydrogenase 1b1 (Aldh1b1) is the aldehyde dehydrogenase isoform with the second highest affinity for acetaldehyde after Aldh2, and is highly expressed in the intestine and liver. We examined sex differences and the effect of Aldh1b1 depletion in a murine model of chronic alcohol-induced liver disease...
June 1, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29856983/soft-agar-based-selection-of-spontaneously-transformed-rat-prostate-epithelial-cells-with-highly-tumorigenic-characteristics
#15
Martina Šrajer Gajdošik, Douglas C Hixson, Kate E Brilliant, DongQin Yang, Monique E De Paepe, Djuro Josić, David R Mills
The critical molecular and cellular mechanisms involved in the development and progression of prostate cancer remain elusive. In this report, we demonstrate that normal rat prostate epithelial cells (PEC) undergo spontaneous transformation at high passage (p > 85) evidenced by the acquisition of anchorage independent growth when plated on soft agar and tumorigenicity when injected into immunodeficient mice. In addition, we also report the discovery of a minor subpopulation of spontaneously transformed PEC derived from high passage PEC with the ability to migrate through a layer of 1% agar and form expanding colonies on the underlying plastic substratum...
May 29, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29856982/activation-of-foxo3a-reverses-5-fluorouracil-resistance-in-human-breast-cancer-cells
#16
Ying Song, Minying Lu, Huisi Qiu, Jiang Yin, Kai Luo, Zhijie Zhang, Xiaoting Jia, Guopei Zheng, Hao Liu, Zhimin He
Breast cancer is the most frequently diagnosed tumor type and the primary leading cause of cancer deaths in women worldwide. Drug resistance is the major obstacle for breast cancer treatment improvement. TRAIL-inducing compound 10 (Tic10), a novel activator of FOXO3, exhibits potent antitumor efficacy both in vitro and in vivo. In the present study, we investigated the resistance reversal effect of Tic10 on multidrug-resistant breast cancer cells T47D/5Fu derived from T47D breast cancer cells. We found that FOXO3a was significantly decreased in T47D/5-Fu cells, whereas treatment of Tic10 enhances FOXO3a expression and nuclear translocation...
May 29, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29852184/aberrant-expression-of-redox-regulatory-proteins-in-patients-with-concomitant-primary-sclerosing-cholangitis-inflammatory-bowel-disease
#17
Dennis R Petersen, David J Orlicky, James R Roede, Colin T Shearn
OBJECTIVE: Primary Sclerosing Cholangitis (PSC) is a severe cholestatic liver disease characterized by progressive peri-biliary tract inflammation, elevated oxidative stress and hepatocellular injury. A hallmark of PSC patients is the concurrent diagnosis of Inflammatory Bowel Disease occurring in approximately 70%-80% of PSC patients (PSC/IBD). We previously reported dysregulation of key anti-oxidant pathways in PSC/IBD. The objective of this study was to expand previous data by examining the abundance of thioredoxins (Trx) in PSC/IBD...
May 29, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29852185/loss-of-c-kit-expression-in-breast-cancer-correlates-with-malignant-transformation-of-breast-epithelium-and-is-mediated-by-kit-gene-promoter-dna-hypermethylation
#18
Radoslav Janostiak, Monika Vyas, Ali Fuat Cicek, Narendra Wajapeyee, Malini Harigopal
KIT Proto-Oncogene Receptor Tyrosine Kinase (KIT) is a transmembrane receptor tyrosine kinase which plays an important role in regulation of cell proliferation, survival and migration. Interestingly, the role of c-KIT in malignant transformation seems to be highly tissue-specific and it can act either as an oncogene or tumor suppressor gene. Here we analyzed the expression of c-KIT in normal breast tissues and tissues from different stages encompassing major steps of breast tumor development. Our study showed, that the c-KIT protein expression is gradually lost during the process of breast tissue transformation...
May 28, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29852183/intratumor-mapk-and-pi3k-signaling-pathway-heterogeneity-in-glioblastoma-tissue-correlates-with-creb-signaling-and-distinct-target-gene-signatures
#19
Paul M Daniel, Gulay Filiz, Martin J Tymms, Robert G Ramsay, Andrew H Kaye, Stanley S Stylli, Theo Mantamadiotis
Limitations in discovering useful tumor biomarkers and drug targets is not only due to patient-to-patient differences but also due to intratumor heterogeneity. Heterogeneity arises due to the genetic and epigenetic variation of tumor cells in response to microenvironmental interactions and cytotoxic therapy. We explored specific signaling pathway activation in glioblastoma (GBM) by investigating the intratumor activation of the MAPK and PI3K pathways. We present data demonstrating a striking preponderance for mutual exclusivity of MAPK and PI3K activation in GBM tissue, where MAPK activation correlates with proliferation and transcription factor CREB activation and PI3K activation correlates with CD44 expression...
May 28, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29847769/hotspot-mutations-in-cancer-genes-may-be-missed-in-routine-diagnostics-due-to-neighbouring-sequence-variants
#20
Stephan Bartels, Elisa Schipper, Britta Hasemeier, Hans Kreipe, Ulrich Lehmann
The detection of hotspot mutations in key cancer genes is now an essential part of the diagnostic work-up in molecular pathology. Nearly all assays for mutation detection involve an amplification step. A second single nucleotide variant (SNV) on the same allele adjacent to a mutational hotspot can interfere with primer binding, leading to unnoticed allele-specific amplification of the wild type allele and thereby false-negative mutation testing. We present two diagnostic cases with false negative sequence results for JAK2 and SRSF2...
May 27, 2018: Experimental and Molecular Pathology
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