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https://www.readbyqxmd.com/read/28342398/novel-phosphonate-analogs-of-sulforaphane-synthesis-in%C3%A2-vitro-and-in%C3%A2-vivo-anticancer-activity
#1
Mateusz Psurski, Łukasz Janczewski, Marta Świtalska, Anna Gajda, Tomasz M Goszczyński, Józef Oleksyszyn, Joanna Wietrzyk, Tadeusz Gajda
A library of over forty, novel, structurally diverse phosphonate analogs of sulforaphane (P-ITCs) were designed, synthesized and fully characterized. All compounds were evaluated for antiproliferative activity in vitro on Lovo and LoVo/DX colon cancer cell lines. All compounds exhibited high antiproliferative activity, comparable or higher to the activity of naturally occurring benzyl isothiocyanate and sulforaphane. Assessment of the mechanisms of action of selected compounds revealed their potential as inducers of G2/M cell cycle arrest and apoptosis...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#2
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28339036/fgf7-fgfr2-signal-promotes-invasion-and-migration-in-human-gastric-cancer-through-upregulation-of-thrombospondin-1
#3
Tingting Huang, Lei Wang, Dian Liu, Piao Li, Huihua Xiong, Liang Zhuang, Li Sun, Xianglin Yuan, Hong Qiu
Fibroblast growth factor 7 (FGF7) is a mesenchyme-specific heparin-binding growth factor that binds FGF receptor 2 (FGFR2) to regulate numerous cellular and physiological processes. FGF7/FGFR2 signal is associated with gastric cancer progression. In the present study, we investigated the molecular mechanism by which FGF7/FGFR2 promotes invasion and migration in human gastric cancer. We first demonstrated that increased FGFR2 expression in human gastric cancer tissues was significantly associated with tumor depth and clinical stage in human gastric cancer tissues...
March 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338113/antiproliferative-and-apoptotic-effects-of-lidocaine-on-human-hepatocarcinoma-cells-a-preliminary-study
#4
Ancuta Jurj, Ciprian Tomuleasa, Tiberiu T Tat, Ioana Berindan-Neagoe, Stefan V Vesa, Daniela C Ionescu
BACKGROUND AND AIMS: It is now well documented that certain anesthetic techniques may influence long term outcome in cancer patients undergoing surgery. More recently, local anesthetics proved certain antiproliferative effects in cancer cells. In our study, we aimed to investigate if lidocaine has antiproliferative effects in human hepatocarcinoma cells and to identify possible mechanisms of these effects. METHODS: We investigated the inhibitory effect of different concentrations of lidocaine on the proliferation of cultured HepG2 human hepatocarcinoma cells and LX2 normal liver fibroblasts...
March 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28337018/rheumatoid-arthritis-fibroblast-like-synoviocyte-suppression-mediated-by-pten-involves-survivin-gene-silencing
#5
Danna Chen, Dongdong Liu, Dan Liu, Min He, Anping Peng, Jiarui Xu, Li Lin, Fudong Luo, Lin Chen, Xianzhang Huang, Junhua Zhuang, Jianhua Xu
Survivin is a proto-oncogene biomarker known for its anti-apoptotic and cell cycle regulating properties induced by the activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. In the context of non-cancer pathology, such as rheumatoid arthritis (RA), survivin has emerged as a feature associated with severe joint damage and poor treatment response. Phosphatase and tensin homolog (PTEN) is a phosphatase antagonizing all classes of PI3K. The interplay between survivin oncogenic mechanisms and proliferation suppression networks in RA has remained largely elusive...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336372/doxorubicin-targets-multiple-players-a-new-view-of-an-old-problem
#6
REVIEW
Donato Cappetta, Francesca Rossi, Elena Piegari, Federico Quaini, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
Anthracycline cardiotoxicity remains a serious problem in paediatric and adult cancer survivors, and the advancement of cardio-oncology is a necessary step for an effective care of the patients that experience adverse cardiovascular effects. In this review, we discuss the multiple instruments used by clinicians that constitute the current strategies for primary and secondary prevention aiming at contrasting the onset of early and late doxorubicin-induced cardiotoxic events. The importance of early detection of cardiotoxicity and the following pharmacological therapy has been acknowledged with the emphasis put on impaired diastolic function, an increasingly recognized precocious sign of doxorubicin cardiotoxicity with an emerging scientific and clinical interest...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#7
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332630/pml-nuclear-bodies-contribute-to-the-basal-expression-of-the-mtor-inhibitor-ddit4
#8
Jayme Salsman, Alex Stathakis, Ellen Parker, Dudley Chung, Livia E Anthes, Kara L Koskowich, Sara Lahsaee, Daniel Gaston, Kimberly R Kukurba, Kevin S Smith, Ian C Chute, Daniel Léger, Laura D Frost, Stephen B Montgomery, Stephen M Lewis, Christopher Eskiw, Graham Dellaire
The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified. PML and PML NBs can also regulate mTOR and cell fate decisions in response to cellular stresses. We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal human diploid fibroblasts results in decreased expression of the mTOR inhibitor DDIT4 (REDD1)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330687/adipocyte-tumor-cell-metabolic-crosstalk-in-breast-cancer
#9
REVIEW
Andrew J Hoy, Seher Balaban, Darren N Saunders
The tumor stroma is a heterogeneous ecosystem comprising matrix, fibroblasts, and immune cells and has an important role in cancer progression. Adipocytes constitute a major component of breast stroma, and significant emerging evidence demonstrates a reciprocal metabolic adaptation between stromal adipocytes and breast cancer (BC) cells. Recent observations promote a model where adipocytes respond to cancer cell-derived endocrine and paracrine signaling to provide metabolic substrates, which in turn drive enhanced cancer cell proliferation, invasion, and treatment resistance...
March 19, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#10
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Silvia Peppicelli, Elisabetta Tanganelli, Gabriella Fibbi, Lisa Giovannelli, Mario Del Rosso, Alessandra Mocali
Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4...
January 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28327938/targeting-the-fibroblast-growth-factor-receptor-2-in-gastric-cancer-promise-or-pitfall
#11
C Hierro, M Alsina, M Sánchez, V Serra, J Rodon, J Tabernero
Gastric cancer is the third leading cause of death from cancer worldwide. Systemic chemotherapy remains the mainstay therapeutic option for this poor prognosis cancer. Trastuzumab, the epidermal growth factor receptor 2 (ERBB2 or HER2)-antibody, is the only biological agent approved for the molecularly-selected population of HER2-positive gastric cancer patients. Over the last decade, several groups have been working for deepening into the molecular characterization of gastric cancer, shedding some light into the heterogeneity of this tumour...
March 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28326574/tumour-epithelial-and-stromal-characteristics-of-hepatocellular-carcinomas-with-abundant-fibrous-stroma-fibrolamellar-versus-scirrhous-hepatocellular-carcinoma
#12
Young-Joo Kim, Hyungjin Rhee, Jeong Eun Yoo, Venancio A F Alves, Gi Jeong Kim, Hye Min Kim, Paulo Herman, Aline Chagas, Haeryoung Kim, Young Nyun Park
AIMS: The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterised by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC. METHODS AND RESULTS: Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for K7, K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28326350/tumor-induced-osteomalacia-secondary-to-anaplastic-thyroid-carcinoma-a-case-report-and-review-of-the-literature
#13
Ejigayehu G Abate, Victor Bernet, Cherise Cortese, Hillary W Garner
CONTEXT: Tumor induced osteomalacia related to anaplastic thyroid cancer has never been reported. OBJECTIVE: We describe a case of tumor induced osteomalacia (TIO) in a patient with a fibroblast growth factor 23 (FGF-23) secreting anaplastic thyroid carcinoma. The current imaging modalities are reviewed. DESIGN AND INTERVENTION: Clinical, biochemical, and radiological assessments were done, including computer tomography (CT) of the neck and skull to thigh positron emission tomography (PET)/CT...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28325212/chemokine-receptor-signaling-and-the-hallmarks-of-cancer
#14
R A Lacalle, R Blanco, L Carmona-Rodríguez, A Martín-Leal, E Mira, S Mañes
The chemokines are a family of chemotactic cytokines that mediate their activity by acting on seven-transmembrane-spanning G protein-coupled receptors. Both the ability of the chemokines and their receptors to form homo- and heterodimers and the promiscuity of the chemokine-chemokine receptor interaction endow this protein family with enormous signaling plasticity and complexity that are not fully understood at present. Chemokines were initially identified as essential regulators of homeostatic and inflammatory trafficking of innate and adaptive leucocytes from lymphoid organs to tissues...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28325093/differences-in-intracellular-mobile-zinc-levels-affect-susceptibility-to-plasma-activated-medium-induced-cytotoxicity
#15
Hirokazu Hara, Sayako Sueyoshi, Miko Taniguchi, Tetsuro Kamiya, Tetsuo Adachi
There is growing evidence that plasma-activated medium (PAM), which is prepared by non-thermal plasma (NTP) irradiation of cell-free medium, is a beneficial tool for cancer therapy. PAM has been reported to preferentially kill cancer cells; however, its mechanism is not fully understood. Since PAM contains reactive oxygen species (ROS) and reactive nitrogen species, the anti-cancer effects of PAM are thought to be attributed to oxidative stress induced by these reactive molecules. Oxidative stress has been shown to release zinc (Zn(2+)) from intracellular Zn(2+) stores and provoke Zn(2+)-dependent cell death...
March 21, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28323412/temporary-single-cell-coating-for-bioprocessing-via-a-cationic-polymer
#16
Ricardo Da Conceicao Ribeiro, Deepali Pal, David Jamieson, Kenneth Samora Rankin, Matthew Benning, Kenneth W Dalgarno, Ana Marina Ferreira
Temporary single cell coating is a useful tool for cell processing, allowing manipulation of cells to prevent cell attachment and agglomeration, before re-establishing normal cell function. In this paper, a speckled coating method using a known polycation (poly-L-lysine, PLL) is described to induce cell surface electrostatic charges on three different cell types - two bone cancer cell lines and fibroblasts. The morphology of the PLL speckled coating on the cell surface, internalization and metabolization of the polymer, and prevention of cellular aggregations are reported...
March 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28323116/the-effect-of-g3-pamam-dendrimer-conjugated-with-b-group-vitamins-on-cell-morphology-motility-and-atp-level-in-normal-and-cancer-cells
#17
Łukasz Uram, Magdalena Szuster, Maria Misiorek, Aleksandra Filipowicz, Stanisław Wołowiec, Elżbieta Wałajtys-Rode
In a search for the safe vitamin carrier the PAMAM G3 dendrimer covalently substituted with 9 and 10 molecules of vitamin B7 (biotin) and B6 (pyridoxal), respectively (BC-PAMAM) was investigated. Dendrimer substitution with B-group vitamins significantly alters its biological properties as compared to native form. Observed effects on investigated cell parameters including morphology, adhesion, migration and ATP level were different for normal human fibroblasts (BJ) and squamous cell carcinoma (SCC-15) cell lines...
March 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28320388/exploring-the-fgfr3-related-oncogenic-mechanism-in-bladder-cancer-using-bioinformatics-strategy
#18
Wei Cao, Enguang Ma, Li Zhou, Tan Yuan, Chunying Zhang
BACKGROUND: Aberrant activation of fibroblast growth factor receptor 3 (FGFR3) is frequently observed in bladder cancer, but how it involved in carcinogenesis is not well understood. The current study was aimed to investigate the underlying mechanism on the progression of bladder cancer. METHODS: The GSE41035 dataset downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) between bladder cancer cell line RT112 with or without depletion of FGFR3, and gene ontology enrichment analysis was performed...
March 20, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28320095/dt-13-a-saponin-monomer-13-of-the-dwarf-lilyturf-tuber-synergized-with-vinorelbine-to-induce-mitotic-arrest-via-activation-of-erk-signaling-pathway-in-nci-h1299-cells
#19
Hongyang Li, Li Sun, Hang Li, Xiaodan Lv, Herve Semukunzi, Ruiming Li, Jun Yu, Shengtao Yuan, Sensen Lin
Vinorelbine (NVB) is a semi-synthetic vinca alkaloid that is approved for the clinical therapy of lung cancer. However, the clinical application of NVB was limited because of the acquisition of resistance and inacceptable toxicity. Therefore, it is of great interest to develop low-cytotoxic drugs that can synergize with NVB. DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, showed inhibitory effects on tumor metastasis and angiogenesis in the previous studies. Here, we found that DT-13 combined with NVB exhibited synergistic effect to inhibit the cell proliferation in human lung cancer NCI-H1299 cells rather than human embryonic lung fibroblasts WI-38...
March 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319088/reference-component-analysis-of-single-cell-transcriptomes-elucidates-cellular-heterogeneity-in-human-colorectal-tumors
#20
Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan, Kok Hao Chen, Jolene Jie Lin Goh, Say Li Kong, Clarinda Chua, Lim Kiat Hon, Wah Siew Tan, Mark Wong, Paul Jongjoon Choi, Lawrence J K Wee, Axel M Hillmer, Iain Beehuat Tan, Paul Robson, Shyam Prabhakar
Intratumoral heterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA-seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs)...
March 20, 2017: Nature Genetics
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