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https://www.readbyqxmd.com/read/28343945/as-human-lung-microvascular-endothelia-achieve-confluence-src-family-kinases-are-activated-and-tyrosine-phosphorylated-p120-catenin-physically-couples-neu1-sialidase-to-cd31
#1
Sang W Hyun, Anguo Liu, Zhenguo Liu, Erik P Lillehoj, Joseph A Madri, Albert B Reynolds, Simeon E Goldblum
In postconfluent human pulmonary microvascular endothelial cell (HPMEC)s, NEU1 sialidase associates with and desialylates the src family kinase (SFK) substrate, CD31, and disrupts angiogenesis. We asked whether the NEU1-CD31 interaction might be SFK-driven. We found that normalized phospho-SFK (PY416) signal is increased in postconfluent HPMECs compared to subconfluent cells and prior SFK inhibition with PP2 or SU6656 completely blocked NEU1 association with and desialylation of CD31. Prior silencing of each of the four SFKs expressed in HPMECs, as well as CD31, dramatically reduced confluence-induced SFK activation...
March 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28340578/abcb1-and-abcg2-drug-transporters-are-differentially-expressed-in-non-small-cell-lung-cancers-nsclc-and-expression-is-modified-by-cisplatin-treatment-via-altered-wnt-signaling
#2
M Vesel, J Rapp, D Feller, E Kiss, L Jaromi, M Meggyes, G Miskei, B Duga, G Smuk, T Laszlo, I Karner, J E Pongracz
BACKGROUND: Lung cancer (LC) is still the most common cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all LC cases but is not a single entity. It is now accepted that, apart from the characteristic driver mutations, the unique molecular signatures of adeno- (AC) and squamous cell carcinomas (SCC), the two most common NSCLC subtypes should be taken into consideration for their management. Therapeutic interventions, however, frequently lead to chemotherapy resistance highlighting the need for in-depth analysis of regulatory mechanisms of multidrug resistance to increase therapeutic efficiency...
March 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28338194/lncrna-neat1-is-closely-related-with-progression-of-breast-cancer-via-promoting-proliferation-and-emt
#3
M Zhang, W-B Wu, Z-W Wang, X-H Wang
OBJECTIVE: Breast cancer (BC) is one of the most common cancers in females. Abnormal proliferation and metastasis are key reasons that cause mortality in BC patients. More and more evidence showed that lncRNA played an important role in the BC development, but the mechanism was not well established. PATIENTS AND METHODS: The expression of lncRNA NEAT1 was detected in 40 BC patients by qRT-PCR technology. MTT and Wound Healing assays were applied to detect the effect of lncRNA NEAT1 in proliferation and metastasis in BC...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28336164/expression-of-unusual-immunohistochemical-markers-in-mucinous-breast-carcinoma
#4
Rodrigo de Andrade Natal, Sophie F Derchain, Marina Pavanello, Geisilene R Paiva, Luis O Sarian, José Vassallo
BACKGROUND: Mucinous breast carcinoma is characterized by the production of variable amounts of mucin. Some studies have addressed immunohistochemical characterization of mucinous breast carcinoma using a limited set of antibodies. However, the purpose of the present study was to investigate a larger panel of markers not widely used in daily practice and to determine their pathological implications. METHODS: Forty patients diagnosed with mucinous breast carcinoma were enrolled...
March 20, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28328801/influence-of-polymorphisms-in-the-wnt-%C3%AE-catenin-pathway-genes-on-hepatocellular-carcinoma-risk-in-a-chinese-han-population
#5
Qing-Min Li, Feng-Qin Zhang, Ya-Feng Li, Qing-Jie Xian, Yan-Qiang Zhang, Peng Li
The Wnt/β-catenin pathway plays a vital role in initiating and sustaining hepatocellular carcinoma (HCC). However, few studies have investigated polymorphisms in the Wnt/β-catenin signaling pathway genes in the Chinese Han population. The aim of the present retrospective study was to investigate the correlations between polymorphisms of the Wnt/β-catenin signaling pathway genes (CTNNB1 and WNT2) and HCC susceptibility, development, and progression.Twenty tagging single nucleotide polymorphisms were chosen from HapMap data and genotyped in 320 patients with HCC, 320 chronic hepatitis B virus (HBV)-infected patients without HCC (N-HCC, including 95 liver cirrhosis, 164 chronic hepatitis B, and 61 asymptomatic HBV carriers), and 320 healthy controls...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28321124/combined-inhibition-of-%C3%AE-catenin-and-bcr-abl-synergistically-targets-tyrosine-kinase-inhibitor-resistant-blast-crisis-chronic-myeloid-leukemia-blasts-and-progenitors-in-vitro-and-in-vivo
#6
H Zhou, P Y Mak, H Mu, D H Mak, Z Zeng, J Cortes, Q Liu, M Andreeff, B Z Carter
Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent β-catenin activation remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of β-catenin in BC-CML stem/progenitor cells, particularly in GMP progenitors, and highest among a novel CD34(+)CD38(+)CD123(hi)Tim-3(hi) subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of β-catenin and its target CD44 in CML cells...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28318921/influence-of-tgf-%C3%AE-1-on-tumor-transition-in-oral-cancer-cell-and-bmsc-co-cultures
#7
F Böhrnsen, F Godek, J Kiesel, F J Kramer, P Brockmeyer, H Schliephake
OBJECTIVES: TGF-β1 signaling modulates epithelial mesenchymal transitions (EMT) of head and neck squamous cell carcinoma (HNSCC). Bone marrow mesenchymal stromal cells (BMSC) are able to exert a regulating influence on the expression of markers of EMT in HNSCC cells. It was thus the aim of this study to test the hypothesis that TGF-β1 modulates the interactions of tumor transition between BMSCs and HNSCC, affecting the expression of E-cadherin, Vimentin, Snail, Twist, MMP14 and beta-catenin...
February 17, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28318623/the-complexity-of-chronic-kidney-disease-mineral-and-bone-disorder-across-stages-of-chronic-kidney%C3%A2-disease
#8
Fabiana G Graciolli, Katia R Neves, Fellype Barreto, Daniela V Barreto, Luciene M Dos Reis, Maria E Canziani, Yves Sabbagh, Aluizio B Carvalho, Vanda Jorgetti, Rosilene M Elias, Susan Schiavi, Rosa M A Moysés
Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28317260/comparative-proteomic-analysis-of-trophoblast-cell-models-reveals-their-differential-phenotypes-potential-uses-and-limitations
#9
Paulina B Szklanna, Kieran Wynne, Marie Nolan, Karl Egan, Fionnuala Ní Áinle, Patricia B Maguire
Trophoblastic cell lines are widely used in in vitro studies of placental function as a surrogate for primary trophoblasts. To date, no reference proteomics dataset exists to directly compare the shared and unique characteristics of these cells. Here, we performed comparative proteomic profiling of the BeWo and HTR8/SVneo cell lines using label-free quantitative mass spectrometry. 1557 proteins were identified, which included 338 uniquely attributed to BeWo cells, and a further 304 specifically identified in HTR8/SVneo cells...
March 20, 2017: Proteomics
https://www.readbyqxmd.com/read/28314302/kras-mutant-status-may-be-associated-with-distant-recurrence-in-early-stage-rectal-cancer
#10
Michail Sideris, Jane Moorhead, Salvador Diaz-Cano, Amyn Haji, Savvas Papagrigoriadis
BACKGROUND/AIM: Total mesorectal excision combined with neo-adjuvant chemoradiotherary (CRT) and adjuvant chemotherapy, has been the standard treatment of locally advanced rectal cancer (LARC). Although TNM (Tumor, Node, Metastasis) classification for malignant Tumors is still the cornerstone in rectal cancer staging, there has been an effort to identify molecular biomarkers with additional prognostic or predictive value. MATERIALS AND METHODS: We retrospectively analyzed molecular biomarkers on prospectively collected histological specimens and clinical data from a cohort of 135 consecutive rectal cancer cases who underwent radical excision in a tertiary center between 2011-2014 (males=87, females=48, age range=22-89 years, mean=64,67 years, SD=13...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28299632/transgenic-expression-of-a-canonical-wnt-inhibitor-kallistatin-is-associated-with-decreased-circulating-cd19-b-lymphocytes-in-the-peripheral-blood
#11
Jeffrey D McBride, Xiaochen Liu, William L Berry, Ralf Janknecht, Rui Cheng, Kelu Zhou, Evangelos V Badiavas, Jian-Xing Ma
Members of the family of serine proteinase inhibitors, such as kallistatin, have been shown to inhibit canonical Wnt-TCF/LEF-β-catenin signaling via their interactions with the Wnt co-receptor LRP6. Yet the effects of transgenic overexpression of anti-Wnt serpins on hematopoiesis and lymphopoiesis are not well known. We studied the effects of human kallistatin (SERPINA4) on Wnt reporter activity in various cell types throughout the hematopoietic system and associated impacts on circulating white blood cell profiles...
March 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28284729/effects-of-di-2-ethylhexyl-phthalate-exposure-on-1-2-dimethyhydrazine-induced-colon-tumor-promotion-in-rats
#12
Hsin-Pao Chen, Min-Hsiung Pan, Yuan-Yi Chou, Chieh Sung, Kuo-Hsin Lee, Chung-Man Leung, Ping-Chi Hsu
Di(2-ethylhexyl)phthalate (DEHP) may cause carcinogenicity in the liver; however, few have detailed on the potential effects of DEHP exposure on colorectal cancer. Male Sprague-Dawley rats received i.p. injections of 1,2-dimethylhydrazine (DMH) once-a-week for the first 4 weeks, and rats in each group were treated with DEHP through oral gavage daily for either 7, 10 or 15 weeks; after which, all rats were euthanized and their colons were assessed (a) morphologically for aberrant crypt foci (ACF) or tumors, (b) cytologically for mitotic index (MI), and (c) immunohistochemically for the expression of β-catenin, cyclooygenase (COX)-2, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), cyclin D1, and c-myc...
March 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28283910/hyperglycemia-impedes-definitive-endoderm-differentiation-of-human-embryonic-stem-cells-by-modulating-histone-methylation-patterns
#13
A C H Chen, Y L Lee, S W Fong, C C Y Wong, E H Y Ng, W S B Yeung
Exposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency...
March 10, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28281553/ctnnb1-beta-catenin-mutation-identifies-low-grade-early-stage-endometrial-cancer-patients-at-increased-risk-of-recurrence
#14
Katherine C Kurnit, Grace N Kim, Bryan M Fellman, Diana L Urbauer, Gordon B Mills, Wei Zhang, Russell R Broaddus
Although the majority of low grade, early stage endometrial cancer patients will have good survival outcomes with surgery alone, those patients who do recur tend to do poorly. Optimal identification of the subset of patients who are at high risk of recurrence and would benefit from adjuvant treatment has been difficult. The purpose of this study was to evaluate the impact of somatic tumor mutation on survival outcomes in this patient population. For this study, low grade was defined as endometrioid FIGO grades 1 or 2, while early stage was defined as endometrioid stages I or II (disease confined to the uterus)...
March 10, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28278702/kr%C3%A3-ppel-like-factor-4-contributes-to-the-pathogenesis-of-mantle-cell-lymphoma
#15
Xin-Yu Li, Ling-Yun Geng, Xiang-Xiang Zhou, Na Wei, Xiao-Sheng Fang, Ying Li, Xin Wang
Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) with poor prognosis. Krüppel-like factor 4 (KLF4) has been reported as a bi-regulator in malignancies, but little is known about its role in MCL. Here, we showed that KLF4 was downregulated in three MCL cell lines and lymph nodes from MCL patients, which resulted in a negative prognosis. We also found that the regulation of KLF4 could inhibit the proliferation and induce apoptosis of Jeko-1 cells. The lentivirally over-expressed KLF4 protein was found bind to β-catenin and could inhibit downstream molecules such as cyclinD1 and c-Myc...
February 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28275053/inhibiting-clathrin-mediated-endocytosis-of-the-leucine-rich-g-protein-coupled-receptor-5-diminishes-cell-fitness
#16
Joshua C Snyder, Lauren K Rochelle, Caroline Ray, Thomas F Pack, Cheryl B Bock, Veronica Lubkov, H Kim Lyerly, Alan S Waggoner, Larry S Barak, Marc G Caron
The leucine-rich G protein-coupled receptor-5 (LGR5) is expressed in adult tissue stem cells of many epithelia and its overexpression is negatively correlated with cancer prognosis. LGR5 potentiates WNT/β-catenin signaling through its unique constitutive internalization property that clears negative regulators of the WNT-receptor complex from the membrane. However, both the mechanism and physiological relevance of LGR5 internalization is unclear. Therefore, a natural product library was screened to discover LGR5 internalization inhibitors and gain mechanistic insight into LGR5 internalization...
March 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28244648/salvianolic-acid-b-regulates-gene-expression-and-promotes-cell-viability-in-chondrocytes
#17
Xiaohong Yang, Shaojie Liu, Siming Li, Pengzhen Wang, Weicong Zhu, Peihong Liang, Jianrong Tan, Shuliang Cui
Articular chondrocytes reside in lacunae distributed in cartilage responsible for the remodelling of the tissue with limited ability of damage repairing. The in vitro expanded chondrocytes enhanced by factors/agents to obtain large numbers of cells with strengthened phenotype are essential for successful repair of cartilage lesions by clinical cell implantation therapies. Because the salvianolic acid B (Sal B), a major hydrophilic therapeutic agent isolated from Salvia miltiorrhiza, has been widely used to treat diseases and able to stimulate activity of cells, this study examines the effects of Sal B on passaged chondrocytes...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28239825/upregulated-serum-sclerostin-level-in-the-t2dm-patients-with-femur-fracture-inhibits-the-expression-of-bone-formation-remodeling-associated-biomarkers-via-antagonizing-wnt-signaling
#18
Y Wu, S-Y Xu, S-Y Liu, L Xu, S-Y Deng, Y-B He, S-C Xian, Y-H Liu, G-X Ni
OBJECTIVE: Bone formation/remodeling-associated biomarkers, such as osteocalcin, amino pro-peptide of type 1 collagen (P1NP) and CrossLaps (CTX) have been deregulated in type 2 diabetes mellitus (T2DM) patients. In particular, the T2DM-associated sclerostin markedly inhibits the bone formation, suppresses the osteoblast activity and downregulates the bone turnover. PATIENTS AND METHODS: In the present study, we examined the serum levels of sclerostin, osteocalcin, P1NP and CTX in the T2DM patients...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28239820/long-non-coding-rna-neat1-acts-as-oncogene-in-nsclc-by-regulating-the-wnt-signaling-pathway
#19
S-J Sun, Q Lin, J-X Ma, W-W Shi, B Yang, F Li
OBJECTIVE: The present study aimed to explore the role of long non-coding RNA NEAT1 (NEAT1) in mediating non-small cell lung cancer (NSCLC) cell migration and invasion, as well as the underlying regulatory mechanisms. PATIENTS AND METHODS: The NEAT1 expression in NSCLC tissues and cell lines was measured using reverse transcription‑quantitative polymerase chain reaction (RT-qPCR). The relationships between NEAT1 expression and clinicopathological parameters were examined by chi-square test...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28237397/sox17-regulates-cholangiocyte-differentiation-and-acts-as-a-tumor-suppressor-in-cholangiocarcinoma
#20
M Merino-Azpitarte, E Lozano, M J Perugorria, A Esparza-Baquer, O Erice, A Santos-Laso, C J O'Rourke, J B Andersen, R Jiménez-Agüero, A Lacasta, M D'Amato, O Briz, N Jalan-Sakrikar, R C Huebert, K M Thelen, S A Gradilone, A M Aransay, J L Lavín, M G Fernández-Barrena, A Matheu, M Marzioni, G J Gores, L Bujanda, J J G Marin, J M Banales
BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a biliary malignancy linked to genetic and epigenetic abnormalities, such as hypermethylation of SOX17 promoter. Here, the role of SOX17 in cholangiocyte differentiation and cholangiocarcinogenesis was studied. METHODS: SOX17 expression/function was evaluated along the differentiation of human induced pluripotent stem cells (iPSC) into cholangiocytes, in the dedifferentiation process of normal human cholangiocytes (NHC) in culture and in cholangiocarcinogenesis...
February 22, 2017: Journal of Hepatology
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