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https://www.readbyqxmd.com/read/29656465/structural-characterization-of-the-interaction-of-the-fibroblast-growth-factor-receptor-with-a-small-molecule-allosteric-inhibitor
#1
Franziska Kappert, Sridhar Sreeramulu, Hendrik R A Jonker, Christian Richter, Vladimir V Rogov, Ewgenij Proschak, Bruno Hargittay, Krishna Saxena, Harald Schwalbe
The interaction of fibroblast growth factors (FGFs) with their fibroblast growth factor receptors (FGFRs) are important in the signaling network of cell growth and development. SSR128129E (SSR)[1,2], a ligand of small molecular weight with potential anti-cancer properties, acts allosterically on the extracellular domains of FGFRs. Up to now, the structural basis of SSR binding to the D3 domain of FGFR remained elusive. Here, we report the structural characterization of the interaction of SSR with one specific receptor, FGFR3 by NMR spectroscopy...
April 14, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29656442/treatment-emergent-hypertension-and-efficacy-in-the-phase-3-study-of-e7080-lenvatinib-in-differentiated-cancer-of-the-thyroid-select
#2
Lori J Wirth, Makoto Tahara, Bruce Robinson, Sanjeev Francis, Marcia S Brose, Mouhammed Amir Habra, Kate Newbold, Naomi Kiyota, Corina E Dutcus, Elton Mathias, Matthew Guo, Steven I Sherman, Martin Schlumberger
BACKGROUND: Hypertension (HTN) is an established class effect of vascular endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1, VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and stem cell factor receptor (KIT)...
April 14, 2018: Cancer
https://www.readbyqxmd.com/read/29651733/interaction-of-zn-with-losartan-activation-of-intrinsic-apoptotic-signaling-pathway-in-lung-cancer-cells-and-effects-on-alkaline-and-acid-phosphatases
#3
Valeria R Martínez, María V Aguirre, Juan S Todaro, Oscar E Piro, Gustavo A Echeverría, Luciana G Naso, Evelina G Ferrer, Patricia A M Williams
A new losartan [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol zinc(II) complex [Zn(Los)Cl], was synthesized and characterized. The crystal structure was determined by x-ray diffraction methods. When aqueous solutions of the ligand and the metal were mixed, the known and more soluble powder [Zn(Los)2 ].3H2 O (ZnLos) complex has been obtained. The interactions with phosphatases showed a concerted mechanism displayed by the Zn ions and ZnLos up to 500 μM concentration: a decrease of the acid phosphatase (AcP) associated with an increase in the alkaline phosphatase (ALP) activities...
April 12, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29651173/in-vitro-anticancer-activity-of-staphyloxanthin-pigment-extracted-from-staphylococcus-gallinarum-kx912244-a-gut-microbe-of-bombyx-mori
#4
Delicia Avilla Barretto, Shyam Kumar Vootla
The present study reports the in vitro biological nature of the pigment produced by Staphylococcus gallinarum KX912244, isolated as the gut microflora bacterium of the insect Bombyx mori . The purified pigment was characterized as Staphyloxanthin based on bio-physical characterization techniques like Fourier transform infrared spectroscopy, high performance liquid chromatography, Proton nuclear magnetic resonance spectroscopy (1 H NMR), Liquid chromatography-Mass spectroscopy and Gas chromatography-Mass spectroscopy...
June 2018: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/29650553/enduring-epigenetic-landmarks-define-the-cancer-microenvironment
#5
Ruth Pidsley, Mitchell G Lawrence, Elena Zotenko, Birunthi Niranjan, Aaron Statham, Jenny Song, Roman M Chabanon, Wenjia Qu, Hong Wang, Michelle Richards, Shalima S Nair, Nicola J Armstrong, Hieu T Nim, Melissa Papargiris, Preetika Balanathan, Hugh French, Timothy Peters, Sam Norden, Andrew Ryan, John Pedersen, James Kench, Roger J Daly, Lisa G Horvath, Phillip Stricker, Mark Frydenberg, Renea A Taylor, Clare Stirzaker, Gail P Risbridger, Susan J Clark
The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors; therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs)...
April 12, 2018: Genome Research
https://www.readbyqxmd.com/read/29650269/current-perspectives-on-the-crosstalk-between-lung-cancer-stem-cells-and-cancer-associated-fibroblasts
#6
REVIEW
Cristina Alguacil-Núñez, Inés Ferrer-Ortiz, Elena García-Verdú, Pilar López-Pirez, Irene Maria Llorente-Cortijo, Bruno Sainz
Lung cancer, in particular non-small cell lung carcinoma (NSCLC), is the second most common cancer in both men and women and the leading cause of cancer-related deaths worldwide. Its prognosis and diagnosis are determined by several driver mutations and diverse risk factors (e.g. smoking). While immunotherapy has proven effective in some patients, treatment of NSCLC using conventional chemotherapy is largely ineffective. The latter is believed to be due to the existence of a subpopulation of stem-like, highly tumorigenic and chemoresistant cells within the tumor population known as cancer stem cells (CSC)...
May 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29649284/sulfasalazine-an-inhibitor-of-the-cystine-glutamate-antiporter-reduces-dna-damage-repair-and-enhances-radiosensitivity-in-murine-b16f10-melanoma
#7
Masaki Nagane, Eiichi Kanai, Yuki Shibata, Takuto Shimizu, Chie Yoshioka, Takuya Maruo, Tadashi Yamashita
The sodium-independent cystine-glutamate antiporter plays an important role in extracellular cystine uptake. It comprises the transmembrane protein, xCT and its chaperone, CD98. Because glutathione is only weakly cell membrane permeable, cellular uptake of its precursor, cystine, is known to be a key step in glutathione synthesis. Moreover, it has been reported that xCT expression affects the progression of tumors and their resistance to therapy. Sulfasalazine is an inhibitor of xCT that is known to increase cellular oxidative stress, giving it anti-tumor potential...
2018: PloS One
https://www.readbyqxmd.com/read/29649215/mobile-phone-specific-electromagnetic-fields-induce-transient-dna-damage-and-nucleotide-excision-repair-in-serum-deprived-human-glioblastoma-cells
#8
Halh Al-Serori, Franziska Ferk, Michael Kundi, Andrea Bileck, Christopher Gerner, Miroslav Mišík, Armen Nersesyan, Monika Waldherr, Manuel Murbach, Tamara T Lah, Christel Herold-Mende, Andrew R Collins, Siegfried Knasmüller
Some epidemiological studies indicate that the use of mobile phones causes cancer in humans (in particular glioblastomas). It is known that DNA damage plays a key role in malignant transformation; therefore, we investigated the impact of the UMTS signal which is widely used in mobile telecommunications, on DNA stability in ten different human cell lines (six brain derived cell lines, lymphocytes, fibroblasts, liver and buccal tissue derived cells) under conditions relevant for users (SAR 0.25 to 1.00 W/kg)...
2018: PloS One
https://www.readbyqxmd.com/read/29643956/serum-cytokines-in-early-prediction-of-anastomotic-leakage-following-low-anterior-resection
#9
Marek Zawadzki, Małgorzata Krzystek-Korpacka, Andrzej Gamian, Wojciech Witkiewicz
Introduction: Anastomotic leakage continues to be one of the most serious complications following low anterior resections. Early diagnosis of a leak is difficult but critical to minimize morbidity and mortality. Aim: To evaluate changes in serum concentrations of 27 different cytokines following low anterior resection, with the goal of finding new, early biomarkers of anastomotic leak. Material and methods: This is a prospective observational study that includes 32 patients undergoing elective low anterior resection for rectal cancer...
March 2018: Wideochirurgia i Inne Techniki Mało Inwazyjne, Videosurgery and Other Miniinvasive Techniques
https://www.readbyqxmd.com/read/29629709/modeling-cell-substrate-de-adhesion-dynamics-under-fluid-shear
#10
Renu Maan, Garima Rani, Gautam I Menon, Pramod A Pullarkat
Changes in cell-substrate adhesion are believed to signal the onset of
 cancer metastasis, but such changes must be quantified against background levels of
 intrinsic heterogeneity between cells. Intrinsic variations in cell-substrate adhesion
 strengths can be probed through biophysical measurements of cell detachment from
 substrates upon the application of an external force. Here, we investigate, theoretically
 and experimentally, the detachment of cells adhered to substrates when these cells are
 subjected to the fluid shear...
April 9, 2018: Physical Biology
https://www.readbyqxmd.com/read/29629369/discovery-of-c-3-tethered-2-oxo-benzo-1-4-oxazines-as-potent-antioxidants-bio-inspired-based-design-synthesis-biological-evaluation-cytotoxic-and-in-silico-molecular-docking-studies
#11
Vashundhra Sharma, Pradeep K Jaiswal, Mukesh Saran, Dharmendra Kumar Yadav, Saloni, Manas Mathur, Ajit K Swami, Sanjeev Misra, Mi-Hyun Kim, Sandeep Chaudhary
The discovery of C-3 tethered 2-oxo-benzo[1,4]oxazines as potent antioxidants is disclosed. All the analogs 20a-20ab have been synthesized via "on water" ultrasound-assisted irradiation conditions in excellent yields (upto 98%). All the compounds have been evaluated for their in vitro antioxidant activities using DPPH free radical scavenging assay as well as FRAP assay. The result showed promising antioxidant activities having IC50 values in the range of 4.74 ± 0.08 to 92.20 ± 1.54 μg/mL taking ascorbic acid (IC50 = 4...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29629338/metabolic-symbiosis-and-immunomodulation-how-tumor-cell-derived-lactate-may-disturb-innate-and-adaptive-immune-responses
#12
REVIEW
Alexandre Morrot, Leonardo Marques da Fonseca, Eduardo J Salustiano, Luciana Boffoni Gentile, Luciana Conde, Alessandra Almeida Filardy, Tatiany Nunes Franklim, Kelli Monteiro da Costa, Celio Geraldo Freire-de-Lima, Leonardo Freire-de-Lima
The tumor microenvironment (TME) is composed by cellular and non-cellular components. Examples include the following: (i) bone marrow-derived inflammatory cells, (ii) fibroblasts, (iii) blood vessels, (iv) immune cells, and (v) extracellular matrix components. In most cases, this combination of components may result in an inhospitable environment, in which a significant retrenchment in nutrients and oxygen considerably disturbs cell metabolism. Cancer cells are characterized by an enhanced uptake and utilization of glucose, a phenomenon described by Otto Warburg over 90 years ago...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29628498/tumor-infiltrating-b-cells-their-role-and-application-in-anti-tumor-immunity-in-lung-cancer
#13
REVIEW
Si-Si Wang, Wei Liu, Dalam Ly, Hao Xu, Limei Qu, Li Zhang
Evidence indicates that lung cancer development is a complex process that involves interactions between tumor cells, stromal fibroblasts, and immune cells. Tumor-infiltrating immune cells play a significant role in the promotion or inhibition of tumor growth. As an integral component of the tumor microenvironment, tumor-infiltrating B lymphocytes (TIBs) exist in all stages of cancer and play important roles in shaping tumor development. Here, we review recent clinical and preclinical studies that outline the role of TIBs in lung cancer development, assess their prognostic significance, and explore the potential benefit of B cell-based immunotherapy for lung cancer treatment...
April 8, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29626470/exosomal-mir-675-from-metastatic-osteosarcoma-promotes-cell-migration-and-invasion-by-targeting-caln1
#14
Liangzhi Gong, Qiyuan Bao, Chuanzhen Hu, Jun Wang, Qi Zhou, Li Wei, Lei Tong, Weibin Zhang, Yuhui Shen
Exosomal microRNAs(miRNAs) transfer from tumor to stromal cells is reportedly associated with cancer progression and metastasis in various epithelial cancers. However, the role of exosomal miRNA in the metastasis of osteosarcoma(OS) -the most common bone malignancy-still largely remains unknown. In this study, we purified exosomes with a median size close to 100 nm from cell culture media as well as patient serum, and proved that exosomes derived from the metastatic, but not the non-metastatic OS cells increase the migration and invasion of non-malignant fibroblast cells (hFOB1...
April 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29626418/bergamot-natural-products-eradicate-cancer-stem-cells-cscs-by-targeting-mevalonate-rho-gdi-signalling-and-mitochondrial-metabolism
#15
Marco Fiorillo, Maria Peiris-Pagès, Rosa Sanchez-Alvarez, Lucia Bartella, Leonardo Di Donna, Vincenza Dolce, Giovanni Sindona, Federica Sotgia, Anna Rita Cappello, Michael P Lisanti
Here, we show that a 2:1 mixture of Brutieridin and Melitidin, termed "BMF", has a statin-like properties, which blocks the action of the rate-limiting enzyme for mevalonate biosynthesis, namely HMGR (3-hydroxy-3-methylglutaryl-CoA-reductase). Moreover, our results indicate that BMF functionally inhibits several key characteristics of CSCs. More specifically, BMF effectively i) reduced ALDH activity, ii) blocked mammosphere formation and iii) inhibited the activation of CSC-associated signalling pathways (STAT1/3, Notch and Wnt/beta-catenin) targeting Rho-GDI-signalling...
April 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29626120/a-new-method-for-tumor-imaging-by-targeting-cancer-associated-fibroblasts
#16
Anastasia Loktev, Thomas Lindner, Walter Mier, Jürgen Debus, Annette Altmann, Dirk Jäger, Frederik Giesel, Clemens Kratochwil, Philippe Barthe, Christian Roumestand, Uwe Haberkorn
The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the focus is notably on a subpopulation of stromal cells, known as cancer-associated fibroblasts (CAFs), which are present in more than 90% of epithelial carcinomas including pancreatic, colon and breast cancer. CAFs feature a high expression of fibroblast activation protein (FAP), which is not detectable in adult normal tissue but associated with a poor prognosis in cancer patients...
April 6, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29626119/development-of-quinoline-based-theranostic-ligands-for-the-targeting-of-fibroblast-activation-protein
#17
Thomas Lindner, Anastasia Loktev, Annette Altmann, Frederik Giesel, Clemens Kratochwil, Jürgen Debus, Dirk Jäger, Walter Mier, Uwe Haberkorn
Fibroblast activation protein (FAP) is overexpressed in cancer associated fibroblasts and is involved in a variety of tumor promoting activities such as matrix remodeling, angiogenesis, chemotherapy resistance and immunosuppression. Since FAP shows low expression in most normal organs it presents an interesting target for imaging and endoradiotherapy. In this paper, FAP inhibitors were modified and optimized for their use as theranostic tracers. Methods: FAP inhibitors (FAPIs) based on a quinoline structure were synthesized and characterized with respect to binding, internalization and efflux in cells expressing human and murine FAP as well as CD26...
April 6, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29624862/the-oxidoreductase-p66shc-acts-as-tumor-suppressor-in-brafv600e-transformed-cells
#18
Tobias Furlan, Sana Khalid, Anh-Vu Nguyen, Julia Günther, Jakob Troppmair
Metabolic reprogramming, as exemplified by the shift from oxidative phosphorylation to glycolysis, is a common feature of transformed cells. In many tumors, altered metabolism is also reflected in increased ROS levels, which contribute to proliferation and survival signaling. However, despite high ROS levels, cancer cells can be efficiently killed by further increasing ROS production. We have shown previously that both wild type (wt) and oncogenic C- and BRAF prevent excessive mitochondrial ROS production. Subsequently, it has been demonstrated that raising ROS levels in BRAFV600E-transformed melanoma cells by inhibiting BRAF or MEK rendered them susceptible to cell death induction...
April 6, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29623473/copper-complex-derived-from-s-benzyldithiocarbazate-and-3-acetylcoumarin-induced-apoptosis-in-breast-cancer-cell
#19
Jhi Biau Foo, May Lee Low, Ji Hui Lim, Yan Zhi Lor, Rusyidah Zainol Abidin, Vilasini Eh Dam, Napsiah Abdul Rahman, Chaw Yee Beh, Lee Chin Chan, Chee Wun How, Yin Sim Tor, Latifah Saiful Yazan
Copper complexes have been widely studied for the anti-tumour application as cancer cells are reported to take up greater amounts of copper than normal cells. Preliminary study revealed that the newly synthesised copper complex [Cu(SBCM)2 ] displayed marked anti-proliferative towards triple-negative MDA-MB-231 breast cancer cells. Therefore, Cu(SBCM)2 has great potential to be developed as an agent for the management of breast cancer. The present study was carried out to investigate the mode of cell death induced by Cu(SBCM)2 towards MDA-MB-231 breast cancer cells...
April 5, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29621774/role-of-alpha-smooth-muscle-actin-and-fibroblast-activation-protein-alpha-in-ovarian-neoplasms
#20
Ana Carolinne da Silva, Millena Prata Jammal, Renata Margarida Etchebehere, Eddie Fernando Candido Murta, Rosekeila Simões Nomelini
BACKGROUND/AIMS: Studies show that tumor growth is not just determined by the presence of malignant cells, since interactions between cancer cells and stromal microenvironment have important impacts on the cancer growth and progression. Cancer-associated fibroblasts play a prominent role in this process. The aims of the study were to investigate 2 cancer-associated fibroblasts markers, alpha-smooth muscle actin (α-SMA), and fibroblast activation protein alpha (FAP) in the stromal microenvironment of benign and malignant ovarian epithelial neoplasms, and to relate their tissue expression with prognostic factors in ovarian cancer...
April 5, 2018: Gynecologic and Obstetric Investigation
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