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https://www.readbyqxmd.com/read/28108623/tumor-induced-stromal-stat1-accelerates-breast-cancer-via-deregulating-tissue-homeostasis
#1
Victoria R Zellmer, Patricia M Schnepp, Sarah L Fracci, Xuejuan Tan, Erin N Howe, Siyuan Zhang
: The tumor microenvironment (TME) is a dynamic tissue space in which the tumor exists, plays a significant role in tumor initiation, and is a key contributor in cancer progression; however, little is known about tumor-induced changes in the adjacent tissue stroma. Herein, tumor-induced changes in the TME were explored at the morphological and molecular level to further understand cancer progression. Tumor-adjacent mammary glands (TAGs) displayed altered branching morphology, expansion of myofibroblasts, and increased mammosphere formation, broadly suggesting a tumor-induced field effect...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108330/pleiotropic-responses-to-methionine-restriction
#2
Gene Ables, Jay Johnson
Methionine restriction (MR) extends lifespan across different species. The main responses of rodent models to MR are well-documented in adipose tissue (AT) and liver, which have reduced mass and improved insulin sensitivity, respectively. Recently, molecular mechanisms that improve healthspan have been identified in both organs during MR. In fat, MR induced a futile lipid cycle concomitant with beige AT accumulation, producing elevated energy expenditure. In liver, MR upregulated fibroblast growth factor 21 and improved glucose metabolism in aged mice and in response to a high-fat diet...
January 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28108151/a-functional-genetic-screen-identifies-the-phosphoinositide-3-kinase-pathway-as-a-determinant-of-resistance-to-fibroblast-growth-factor-receptor-inhibitors-in-fgfr-mutant-urothelial-cell-carcinoma
#3
Liqin Wang, Tonći Šuštić, Rodrigo Leite de Oliveira, Cor Lieftink, Pasi Halonen, Marieke van de Ven, Roderick L Beijersbergen, Michel M van den Heuvel, René Bernards, Michiel S van der Heijden
Activating mutations and translocations of the FGFR3 gene are commonly seen in urothelial cell carcinoma (UCC) of the bladder and urinary tract. Several fibroblast growth factor receptor (FGFR) inhibitors are currently in clinical development and response rates appear promising for advanced UCC. A common problem with targeted therapeutics is intrinsic or acquired resistance of the cancer cells. To find potential drug targets that can act synergistically with FGFR inhibition, we performed a synthetic lethality screen for the FGFR inhibitor AZD4547 using a short hairpin RNA library targeting the human kinome in the UCC cell line RT112 (FGFR3-TACC3 translocation)...
January 17, 2017: European Urology
https://www.readbyqxmd.com/read/28107750/effect-of-clinically-approved-hdac-inhibitors-on-plasmodium-leishmania-and-schistosoma-parasite-growth
#4
Ming Jang Chua, Megan S J Arnold, Weijun Xu, Julien Lancelot, Suzanne Lamotte, Gerald F Späth, Eric Prina, Raymond J Pierce, David P Fairlie, Tina S Skinner-Adams, Katherine T Andrews
Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L...
December 23, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28106545/the-alterations-of-serum-fgf-21-levels-metabolic-and-body-composition-in-early-breast-cancer-patients-receiving-adjuvant-endocrine-therapy
#5
Murat Akyol, Ahmet Alacacioglu, Leyla Demir, Yuksel Kucukzeybek, Yasar Yildiz, Zehra Gumus, Mete Kara, Tarik Salman, Umut Varol, Halil Taskaynatan, Utku Oflazoglu, Vedat Bayoglu, Mustafa Oktay Tarhan
BACKGROUND: In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. METHODS: A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28106541/cell-membrane-and-intracellular-expression-of-toll-like-receptor-9-tlr9-in-colorectal-cancer-and-breast-cancer-cell-lines
#6
Shadab Shahriari, Somayeh Rezaeifard, Hamid Reza Moghimi, Mohammad Reza Khorramizadeh, Zahra Faghih
BACKGROUND: Toll-like receptor 9 (TLR9) is a DNA receptor of innate immune system which plays a pivotal role in inflammatory response. Recent evidence reveals over-expression and functionality of TLR9 in a wide variety of cancer cells and its contribution to tumor cell proliferation and survival. OBJECTIVE: In this study, we assessed the aberrant cell surface expression of TLR9 in cancer using cell-lines model. METHODS: Three breast cancer cell-lines (MDA-MB-231, MCF7 and SKBR3) and five colorectal adenocarcinoma cell-lines (HT29, HT29/219, SW480, SW48 and SW1116) in addition to one primary foreskin isolated fibroblast cell were analyzed for cell surface and intracellular expression of TLR9 by flow cytometry method...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28106540/detection-of-human-breast-cancer-cells-using-a-2-deoxy-d-glucose-functionalized-superparamagnetic-iron-oxide-nanoparticles
#7
Xiu-Hong Shan, Peng Wang, Fei Xiong, Hao-Yue Lu, Hui Hu
BACKGROUND: Breast cancer is one of the most common type of female cancer worldwide and represents 14% of cancer-related deaths in women. Early detection is the most important factor for treatment and prognosis of breast cancer. In most countries, the women are currently screened with mammography only. Even though there has been considerable progress in the detection, surgical therapy, hormonal and target therapy of breast cancer, there are about ∼ 3500 000 women who die from breast cancer each year...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28106378/cell-selective-apoptosis-induced-by-polymorphic-alteration-of-self-assembled-silica-nano-webs
#8
Meysam Keshavarz, Bo Tan, Krishnan Venkatakrishnan
The biocompatibility of silicon-based nanomaterial makes it suitable for biophysical and biomedical applications. However, the application of silicon-based nanomaterials has been mainly restricted to nanoparticles (NPs) as a potential drug carrier and the extracellular matrix (ECM) as a platform for cell adhesion and proliferation. Here, we introduced silica NPs self-assembled into a 3D nano-web architecture that was shown to inherit the therapeutic and proliferative attributes of both NPs and ECMs. The self-assembled silica nano-web (SNW) has, therefore, not only shown targeted drug-like behavior in HeLa cells without the use of bio-markers but also has shown ECM characteristics...
January 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28105192/akt-dependent-activation-of-erk-by-cyclin-d1b-contributes-to-cell-invasiveness-and-tumorigenicity
#9
Chul Jang Kim, Yukihiro Tambe, Ken-Ichi Mukaisho, Hiroyuki Sugihara, Akihiro Kawauchi, Hirokazu Inoue
A total of two major isoforms, cyclin D1a and cyclin D1b, are generated from the human cyclin D1 gene by alternative splicing. Cyclin D1b is scarcely expressed in normal tissues; however, it is expressed at a high frequency in certain types of cancerous tissue. The present authors previously constructed cyclin D1b transgenic (Tg) mice and identified rectal tumors, including adenocarcinoma and sessile serrated adenoma, in 62.5% of female Tg mice. In addition, the present authors indicated that cyclin D1b expression enhances phosphorylation of extracellular signal-regulated kinase (Erk) in these rectal tumors, and in mouse embryonic fibroblast (MEF) cells and human 293T cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105147/fgfr3-silencing-by-sirna-inhibits-invasion-of-a549-cells
#10
Yuhua Li, Xiguang Liu, Hongjun Zhang, Tao Jiang, Wenjing Xiao, Shufen Zhao, Xiaoyun Yu, Fanjie Han
The present study identified that fibroblast growth factor receptor 3 (FGFR3) was significantly upregulated in bone metastasis of lung adenocarcinoma. RNA interference (RNAi) is a powerful approach for treating a wide range of human diseases, including cancer, through downregulating the expression of selected genes. In the present study, the invasiveness of A549 cells cultured in vitro was altered by small interfering (si)RNA targeting FGFR3, and the regulatory effect of silencing FGFR3 on the expression levels of E-cadherin and matrix metalloproteinase (MMP)9 was investigated...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28103615/radiation-induced-lung-metastasis-development-is-mt1-mmp-dependent-in-a-triple-negative-breast-cancer-mouse-model
#11
Gina Bouchard, Hélène Therriault, Sameh Geha, Rachel Bujold, Caroline Saucier, Benoit Paquette
BACKGROUND: The prognosis of triple-negative breast cancer (TNBC) is still difficult to establish. Some TNBC benefit from radiotherapy (RT) and are cured, while in other patients metastases appear during the first 3 years after treatment. In this study, an animal model of TNBC was used to determine whether the expression of the cell membrane protease MT1-MMP in cancer cells was associated with radiation-stimulated development of lung metastases. METHODS: Using invasion chambers, irradiated fibroblasts were used as chemoattractants to assess the invasiveness of TNBC D2A1 cell lines showing downregulated expression of MT1-MMP, which were compared with D2A1-wt (wild-type) and D2A1 shMT1-mock (empty vector) cell lines...
January 19, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28103575/piwil2-transfected-human-fibroblasts-are-cancer-stem-cell-like-and-genetically-unstable
#12
Deying Zhang, Xin Wu, Xing Liu, Chunhong Cai, Guangping Zeng, Jan Rohozinski, Yuanyuan Zhang, Guanghui Wei, Dawei He
Uncontrolled cell proliferation and inhibition of apoptosis are considered to be vital for cancer initiation, maintenance, infiltration, metastasis and recurrence after anti-cancer therapy. Here we report the generation of a novel cell line by reprogramming child foreskin fibroblast with the full length apoptosis inhibitor gene PIWIL2. The fibroblasts transfected with PIWIL2 expressed the stem cell markers OCT-4, NANOG, SOX-2, KLF-4 and C-MYC; endoderm marker AFP and GATA6; mesoderm markers ACTA2 and BRACHYURY; and ectoderm markers NESTIN and TUBB3...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103571/identification-of-aurintricarboxylic-acid-as-a-selective-inhibitor-of-the-tweak-fn14-signaling-pathway-in-glioblastoma-cells
#13
Alison Roos, Harshil D Dhruv, Ian T Mathews, Landon J Inge, Serdar Tuncali, Lauren K Hartman, Donald Chow, Nghia Millard, Holly H Yin, Jean Kloss, Joseph C Loftus, Jeffrey A Winkles, Michael E Berens, Nhan L Tran
The survival of patients diagnosed with glioblastoma (GBM), the most deadly form of brain cancer, is compromised by the proclivity for local invasion into the surrounding normal brain, which prevents complete surgical resection and contributes to therapeutic resistance. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) superfamily, can stimulate glioma cell invasion and survival via binding to fibroblast growth factor-inducible 14 (Fn14) and subsequent activation of the transcription factor NF-κB...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103135/reconstitution-of-a-metastatic-resistant-tumor-microenvironment-with-cancer-associated-fibroblasts-enables-metastasis
#14
Takuya Murata, Eisuke Mekada, Robert M Hoffman
The tumor microenvironment is critical for metastasis to occur. Subcutaneous xenografts of tumors in immunodeficient mice are usually encapsulated and rarely metastasize as opposed to orthotopic tumors which metastasize if the original tumor was metastatic. In the present report, we were able to reconstitute a metastatic tumor microenvironment by subcutaneously co-transplanting a human cervical cancer cell line and human cervical cancer-associated fibroblasts (CAFs), in athymic mice, which resulted in lymph node metastasis in 40% of the animals...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28102887/clinical-trial-of-nintedanib-in-patients-with-recurrent-or-metastatic-salivary-gland-cancer-of-the-head-and-neck-a-multicenter-phase-2-study-korean-cancer-study-group-hn14-01
#15
Youjin Kim, Su Jin Lee, Ji Yun Lee, Se-Hoon Lee, Jong-Mu Sun, Keunchil Park, Ho Jung An, Jae Yong Cho, Eun Joo Kang, Ha-Young Lee, Jinsoo Kim, Bhumsuk Keam, Hye Ryun Kim, Kyoung Eun Lee, Moon Young Choi, Ki Hyeong Lee, Myung-Ju Ahn
BACKGROUND: Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß)...
January 19, 2017: Cancer
https://www.readbyqxmd.com/read/28102840/cancer-associated-fibroblasts-enact-field-cancerization-by-promoting-extratumoral-oxidative-stress
#16
Jeremy Soon Kiat Chan, Ming Jie Tan, Ming Keat Sng, Ziqiang Teo, Terri Phua, Chee Chong Choo, Liang Li, Pengcheng Zhu, Nguan Soon Tan
Histological inspection of visually normal tissue adjacent to neoplastic lesions often reveals multiple foci of cellular abnormalities. This suggests the presence of a regional carcinogenic signal that spreads oncogenic transformation and field cancerization. We observed an abundance of mutagenic reactive oxygen species in the stroma of cryosectioned patient tumor biopsies, indicative of extratumoral oxidative stress. Diffusible hydrogen peroxide (H2O2) was elevated in the conditioned medium of cultured skin epithelia at various stages of oncogenic transformation, and H2O2 production increased with greater tumor-forming and metastatic capacity of the studied cell lines...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28101903/development-and-characterization-of-anti-glycopeptide-monoclonal-antibodies-against-human-podoplanin-using-glycan-deficient-cell-lines-generated-by-crispr-cas9-and-talen
#17
Mika K Kaneko, Takuro Nakamura, Ryusuke Honma, Satoshi Ogasawara, Yuki Fujii, Shinji Abe, Michiaki Takagi, Hiroyuki Harada, Hiroyoshi Suzuki, Yasuhiko Nishioka, Yukinari Kato
Human podoplanin (hPDPN), which binds to C-type lectin-like receptor-2 (CLEC-2), is involved in platelet aggregation and cancer metastasis. The expression of hPDPN in cancer cells or cancer-associated fibroblasts indicates poor prognosis. Human lymphatic endothelial cells, lung-type I alveolar cells, and renal glomerular epithelial cells express hPDPN. Although numerous monoclonal antibodies (mAbs) against hPDPN are available, they recognize peptide epitopes of hPDPN. Here, we generated a novel anti-hPDPN mAb, LpMab-21...
January 19, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28101374/arginine-methylation-of-usp9x-promotes-its-interaction-with-tdrd3-and-its-anti-apoptotic-activities-in-breast-cancer-cells
#18
Nithya Narayanan, Zhihao Wang, Ling Li, Yanzhong Yang
The Tudor domain-containing proteins are characterized by their specific interactions with methylated protein motifs, including methyl-arginines and methyl-lysines. The Tudor domain-containing protein 3 (TDRD3) is one of the major methyl-arginine effector molecules that recognizes methylated arginine residues on histones and the C-terminal domain of RNA polymerase II, and activates transcription. However, majority of the cellular TDRD3 localizes to the cytoplasm and its functions there are still elusive. Here, we have identified ubiquitin-specific protease 9 X-linked (USP9X) as a TDRD3-interacting protein by GST (glutathione S-transferase) pull-down and co-immunoprecipitation...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28099917/cleavage-of-fibulin-2-by-the-aggrecanases-adamts-4-and-adamts-5-contributes-to-the-tumorigenic-potential-of-breast-cancer-cells
#19
Tania Fontanil, Saúl Álvarez-Teijeiro, M Ángeles Villaronga, Yamina Mohamedi, Laura Solares, Angela Moncada-Pazos, José A Vega, Olivia García-Suárez, Marcos Pérez-Basterrechea, Juana M García-Pedrero, Alvaro J Obaya, Santiago Cal
Fibulin-2 participates in the assembly of extracellular matrix components through interactions with multiple ligands and promotes contacts between cells and their surrounding environment. Consequently, identification of processes that could lead to an altered Fibulin-2 could have a major impact not only in the maintenance of tissue architecture and morphogenesis but also in pathological situations including cancer. Herein, we have investigated the ability of the secreted metalloproteases ADAMTS-4 and ADAMTS-5 to digest Fibulin-2...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099150/elimination-of-quiescent-slow-cycling-cells-via-reducing-quiescence-depth-by-natural-compounds-purified-from-ganoderma-lucidum
#20
Jian Dai, Matthew A Miller, Nicholas J Everetts, Xia Wang, Peng Li, Ye Li, Jian-Hua Xu, Guang Yao
The medical mushroom Ganoderma lucidum has long been used in traditional Chinese medicine and shown effective in the treatment of many diseases including cancer. Here we studied the cytotoxic effects of two natural compounds purified from Ganoderma lucidum, ergosterol peroxide and ganodermanondiol. We found that these two compounds exhibited cytotoxicity not only against fast proliferating cells, but on quiescent, slow-cycling cells. Using a fibroblast cell-quiescence model, we found that the cytotoxicity on quiescent cells was due to induced apoptosis, and was associated with a shallower quiescent state in compound-treated cells, resultant from the increased basal activity of an Rb-E2F bistable switch that controls quiescence exit...
January 13, 2017: Oncotarget
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