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https://www.readbyqxmd.com/read/28212337/synthesis-anti-breast-cancer-activity-and-molecular-docking-study-of-a-new-group-of-acetylenic-quinolinesulfonamide-derivatives
#1
Krzysztof Marciniec, Bartosz Pawełczak, Małgorzata Latocha, Leszek Skrzypek, Małgorzata Maciążek-Jurczyk, Stanisław Boryczka
In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay. The antiproliferative activity of the tested acetylenic quinolinesulfonamides is comparable to that of cisplatin. The bioassay results demonstrate that most of the tested compounds show potent antitumor activities, and that some compounds exhibit better effects than the positive control cisplatin against various cancer cell lines...
February 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28212293/targeting-angiogenesis-in-biliary-tract-cancers-an-open-option
#2
REVIEW
Valeria Simone, Oronzo Brunetti, Luigi Lupo, Mario Testini, Eugenio Maiorano, Michele Simone, Vito Longo, Christian Rolfo, Marc Peeters, Aldo Scarpa, Amalia Azzariti, Antonio Russo, Domenico Ribatti, Nicola Silvestris
Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212278/the-effect-of-the-human-peptide-ghk-on-gene-expression-relevant-to-nervous-system-function-and-cognitive-decline
#3
Loren Pickart, Jessica Michelle Vasquez-Soltero, Anna Margolina
Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions...
February 15, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28209968/activating-akt1-mutations-alter-dna-double-strand-break-repair-and-radiosensitivity
#4
S Oeck, K Al-Refae, H Riffkin, G Wiel, R Handrick, D Klein, G Iliakis, V Jendrossek
The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28206814/biomarkers-in-tumor-microenvironment-upregulation-of-fibroblast-activation-protein-%C3%AE-correlates-with-gastric-cancer-progression-and-poor-prognosis
#5
Mengmou Hu, Chengjia Qian, Ziwei Hu, Bojian Fei, Haibo Zhou
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recent evidence points to importance of cross talk between cancer cells and the surrounding stroma on gastric cancer progression. Tumor microenvironment biomarkers thus represent a new opportunity for diagnostics innovation. Reactive stromal fibroblasts selectively express the fibroblast activation protein alpha (FAP-α), a homodimeric integral membrane gelatinase that belongs to the serine protease family. We report here that FAP-α expression is significantly elevated in gastric cancer samples by more than fivefold (p < 0...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28202937/focal-adhesion-kinase-activity-is-required-for-actomyosin-contractility-based-invasion-of-cells-into-dense-3d-matrices
#6
Claudia T Mierke, Tony Fischer, Stefanie Puder, Tom Kunschmann, Birga Soetje, Wolfgang H Ziegler
The focal adhesion kinase (FAK) regulates the dynamics of integrin-based cell adhesions important for motility. FAK's activity regulation is involved in stress-sensing and focal-adhesion turnover. The effect of FAK on 3D migration and cellular mechanics is unclear. We analyzed FAK knock-out mouse embryonic fibroblasts and cells expressing a kinase-dead FAK mutant, R454-FAK, in comparison to FAK wild-type cells. FAK knock-out and FAK(R454/R454) cells invade dense 3D matrices less efficiently. These results are supported by FAK knock-down in wild-type fibroblasts and MDA-MB-231 human breast cancer cells showing reduced invasiveness...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202772/high-throughput-screening-of-tyrosine-kinase-inhibitor-cardiotoxicity-with-human-induced-pluripotent-stem-cells
#7
Arun Sharma, Paul W Burridge, Wesley L McKeithan, Ricardo Serrano, Praveen Shukla, Nazish Sayed, Jared M Churko, Tomoya Kitani, Haodi Wu, Alexandra Holmström, Elena Matsa, Yuan Zhang, Anusha Kumar, Alice C Fan, Juan C Del Álamo, Sean M Wu, Javid J Moslehi, Mark Mercola, Joseph C Wu
Tyrosine kinase inhibitors (TKIs), despite their efficacy as anticancer therapeutics, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen U.S. Food and Drug Administration-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28202677/cancer-associated-fibroblasts-modulate-growth-factor-signaling-and-extracellular-matrix-remodeling-to-regulate-tumor-metastasis
#8
REVIEW
Begum Erdogan, Donna J Webb
Cancer-associated fibroblasts (CAFs) are major components of the surrounding stroma of carcinomas that emerge in the tumor microenvironment as a result of signals derived from the cancer cells. Biochemical cross-talk between cancer cells and CAFs as well as mechanical remodeling of the stromal extracellular matrix (ECM) by CAFs are important contributors to tumor cell migration and invasion, which are critical for cancer progression from a primary tumor to metastatic disease. In this review, we discuss key paracrine signaling pathways between CAFs and cancer cells that promote cancer cell migration and invasion...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202523/cancer-stem-cells-regulate-cancer-associated-fibroblasts-via-activation-of-hedgehog-signaling-in-mammary-gland-tumors
#9
Giovanni Valenti, Hazel M Quinn, Guus Jje Heynen, Linxiang Lan, Jane D Holland, Regina Vogel, Annika Wulf-Goldenberg, Walter Birchmeier
Many tumors display intracellular heterogeneity, with subsets of cancer stem cells (CSC) that sustain tumor growth, recurrence, and therapy resistance. Cancer associated fibroblasts (CAF) have been shown to support and regulate CSC function. Here we investigated the interactions between CSCs and CAFs in mammary gland tumors driven by combined activation of Wnt/β-catenin and Hgf/Met signaling in mouse mammary epithelial cells. In this setting, CSCs secreted the hedgehog ligand SHH, which regulated CAFs via paracrine activation of Hedgehog signaling...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202520/evolution-of-cancer-stem-like-cells-in-endocrine-resistant-metastatic-breast-cancers-is-mediated-by-stromal-microvesicles
#10
Pasquale Sansone, Marjan Berishaj, Vinagolu K Rajasekhar, Claudio Ceccarelli, Qing Chang, Antonio Strillacci, Claudia Savini, Lauren Shapiro, Robert Bowman, Chiara Mastroleo, Sabrina De Carolis, Laura Daly, Alberto Benito-Martin, Fabiana Perna, Nicola Fabbri, John H Healey, Enzo Spisni, Monica Cricca, David Lyden, Massimiliano Bonafé, Jacqueline Bromberg
The hypothesis that microvesicle (MV)-mediated microRNA transfer converts non-cancer stem cells into cancer stem cells (CSCs) leading to therapy resistance remains poorly investigated. Here we provide direct evidence supporting this hypothesis, by demonstrating how MV derived from cancer associated fibroblasts (CAF) transfer miR-221 to promote hormonal therapy resistance (HTR) in models of luminal breast cancer. We determined that CAF-derived MV horizontally transferred miR221 to tumor cells and, in combination with hormone therapy activated an ERlo/Notchhi feed-forward loop responsible for the generation of CD133hi CSC...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202510/myc-mediates-large-oncosome-induced-fibroblast-reprogramming-in-prostate-cancer
#11
Valentina R Minciacchi, Cristiana Spinelli, Mariana Reis-Sobreiro, Lorenzo Cavallini, Sungyong You, Mandana Zandian, Xiaohong Li, Paola Chiarugi, Rosalyn M Adam, Edwin M Posadas, Giuseppe Viglietto, Michael R Freeman, Emanuele Cocucci, Neil A Bhowmick, Dolores Di Vizio
Communication between cancer cells and the tumor microenvironment results in the modulation of complex signaling networks that facilitate tumor progression. Here we describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell-derived, atypically large (1-10 μm) extracellular vesicles (EV). We demonstrate that, in the context of prostate cancer, LO harbor sustained AKT1 kinase activity, nominating them as active signaling platforms. Active AKT1 was detected in circulating EV from the plasma of metastatic prostate cancer patients and was LO specific...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198360/secreted-clic3-drives-cancer-progression-through-its-glutathione-dependent-oxidoreductase-activity
#12
Juan R Hernandez-Fernaud, Elena Ruengeler, Andrea Casazza, Lisa J Neilson, Ellie Pulleine, Alice Santi, Shehab Ismail, Sergio Lilla, Sandeep Dhayade, Iain R MacPherson, Iain McNeish, Darren Ennis, Hala Ali, Fernanda G Kugeratski, Heba Al Khamici, Maartje van den Biggelaar, Peter V E van den Berghe, Catherine Cloix, Laura McDonald, David Millan, Aoisha Hoyle, Anna Kuchnio, Peter Carmeliet, Stella M Valenzuela, Karen Blyth, Huabing Yin, Massimiliano Mazzone, Jim C Norman, Sara Zanivan
The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2)...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28196126/oxidative-stress-and-apoptosis-induction-in-human-thyroid-carcinoma-cells-exposed-to-the-essential-oil-from-pistacia-lentiscus-aerial-parts
#13
Simona Catalani, Francesco Palma, Serafina Battistelli, Serena Benedetti
BACKGROUND: Essential oils from the aerial parts (leaves, twigs and berries) of Pistacia lentiscus (PLEO) have been well characterized for their antibacterial and anti-inflammatory properties; however, poor information exists on their potential anticancer activity. METHODS: Increasing concentrations of PLEO (0.01-0.1% v/v, 80-800 μg/ml) were administered to a wide variety of cultured cancer cells from breast, cervix, colon, liver, lung, prostate, and thyroid carcinomas...
2017: PloS One
https://www.readbyqxmd.com/read/28193521/pharmacological-inhibition-of-magl-lipase-attenuates-experimental-colon-carcinogenesis
#14
Ester Pagano, Francesca Borrelli, Pierangelo Orlando, Barbara Romano, Martina Monti, Lucia Morbidelli, Gabriella Aviello, Roberta Imperatore, Raffaele Capasso, Fabiana Piscitelli, Lorena Buono, Vincenzo Di Marzo, Angelo A Izzo
Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. The role of MAGL was assessed in vivo by using the xenograft and the azoxymethane models of colon carcinogenesis; MAGL expression was evaluated by RT-PCR and immunohistochemistry; 2-AG levels were measured by liquid chromatography mass spectrometry; angiogenesis was evaluated in tumor tissues [by microvessel counting and by investigating the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) proteins] as well as in human umbilical vein endothelial cells (HUVEC); cyclin D1 was evaluated by RT-PCR...
February 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28193024/evaluating-tumor-associated-activity-of-extracellular-sulfatase-by-analyzing-naturally-occurring-substrate-in-tumor-microenvironment-of-hepatocellular-carcinoma
#15
Yue Yu, Hao Li, Yucai Yang, Yitao Ding, Zhaoxia Wang, Genxi Li
The progress of cancer is intimately connected with the activity of the extracellular matrix (ECM) enzymes. To evaluate the promoting effect of these enzymes on tumor development in a pathological biocontext, we propose in this work to analyze their natural substrates in the ECM. This strategy is demonstrated by studying heparan sulfate (HS), the substrate of ECM sulfatase, in the development of hepatocellular carcinoma (HCC). An assay is designed to study the abundance and sulfation of HS and to evaluate the interactions between HS and the growth factors, such as fibroblast growth factor 2 (FGF2)...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28192606/metformin-alleviates-aging-cellular-phenotypes-in-hutchinson-gilford-progeria-syndrome-dermal-fibroblasts
#16
Seul-Ki Park, Ok Sarah Shin
Metformin is a popular antidiabetic biguanide, which has been considered as a candidate drug for cancer treatment and aging prevention. Hutchinson-Gilford progeria syndrome (HGPS) is a devastating disease characterized by premature aging and severe age-associated complications leading to death. The effects of metformin on HGPS dermal fibroblasts remain largely undefined. In this study, we investigated whether metformin could exert a beneficial effect on nuclear abnormalities and delay senescence in fibroblasts derived from HGPS patients...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28192213/comment-on-a-col11a1-correlated-pan-cancer-gene-signature-of-activated-fibroblasts-for-the-prioritization-of-therapeutic-targets-cancer-lett-2016-nov-28-382-2-203-214
#17
https://www.readbyqxmd.com/read/28192057/tongue-and-taste-organ-biology-and-function-homeostasis-maintained-by-hedgehog-signaling
#18
Charlotte M Mistretta, Archana Kumari
The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28190458/detection-of-imprinted-genes-by-single-cell-allele-specific-gene-expression
#19
Federico A Santoni, Georgios Stamoulis, Marco Garieri, Emilie Falconnet, Pascale Ribaux, Christelle Borel, Stylianos E Antonarakis
Genomic imprinting results in parental-specific gene expression. Imprinted genes are involved in the etiology of rare syndromes and have been associated with common diseases such as diabetes and cancer. Standard RNA bulk cell sequencing applied to whole-tissue samples has been used to detect imprinted genes in human and mouse models. However, lowly expressed genes cannot be detected by using RNA bulk approaches. Here, we report an original and robust method that combines single-cell RNA-seq and whole-genome sequencing into an optimized statistical framework to analyze genomic imprinting in specific cell types and in different individuals...
February 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28186989/inhibiting-dna-pkcs-in-a-non-homologous-end-joining-pathway-in-response-to-dna-double-strand-breaks
#20
Jun Dong, Tian Zhang, Yufeng Ren, Zhenyu Wang, Clifton C Ling, Fuqiu He, Gloria C Li, Chengtao Wang, Bixiu Wen
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a distinct factor in the non-homologous end-joining (NHEJ) pathway involved in DNA double-strand break (DSB) repair. We examined the crosstalk between key proteins in the DSB NHEJ repair pathway and cell cycle regulation and found that mouse embryonic fibroblast (MEF) cells deficient in DNA-PKcs or Ku70 were more vulnerable to ionizing radiation (IR) compared with wild-type cells and that DSB repair was delayed. γH2AX was associated with phospho-Ataxia-telangiectasia mutated kinase (Ser1987) and phospho-checkpoint effector kinase 1 (Ser345) foci for the arrest of cell cycle through the G2/M phase...
February 7, 2017: Oncotarget
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