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Neoplasia: An International Journal for Oncology Research

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https://www.readbyqxmd.com/read/28501760/stromal-pdgfr-%C3%AE-activation-enhances-matrix-stiffness-impedes-mammary-ductal-development-and-accelerates-tumor-growth
#1
Anisha M Hammer, Gina M Sizemore, Vasudha C Shukla, Alex Avendano, Steven T Sizemore, Jonathan J Chang, Raleigh D Kladney, Maria C Cuitiño, Katie A Thies, Quinn Verfurth, Arnab Chakravarti, Lisa D Yee, Gustavo Leone, Jonathan W Song, Samir N Ghadiali, Michael C Ostrowski
The extracellular matrix (ECM) is critical for mammary ductal development and differentiation, but how mammary fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model to activate platelet derived growth factor receptor-alpha (PDGFRα) specifically in the stroma. Hyperactivation of PDGFRα in the mammary stroma severely hindered pubertal mammary ductal morphogenesis, but did not interrupt the lobuloalveolar differentiation program. Increased stromal PDGFRα signaling induced mammary fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid (HA) and collagen deposition...
May 11, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28500896/a-microrna-ubiquitin-ligase-feedback-loop-regulates-slug-mediated-invasion-in-breast-cancer
#2
Rajesh Kumar Manne, Yashika Agrawal, Anil Bargale, Asha Patel, Debasish Paul, Neha Anilkumar Gupta, Srikanth Rapole, Vasudevan Seshadri, Deepa Subramanyam, Praveenkumar Shetty, Manas Kumar Santra
The transformation of a normal cell to cancer requires the derail of multiple pathways. Normal signaling in a cell is regulated at multiple stages by the presence of feedback loops, calibration of levels of proteins by their regulated turnover, and posttranscriptional regulation, to name a few. The tumor suppressor protein FBXO31 is a component of the SCF E3 ubiquitin ligase and is required to arrest cells at G1 following genotoxic stresses. Due to its growth-suppression activity, it is underexpressed in many cancers...
May 9, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28499126/control-of-tumor-initiation-by-nkg2d-naturally-expressed-on-ovarian-cancer-cells
#3
Xin Cai, Andrea Caballero-Benitez, Mesfin M Gewe, Isaac C Jenkins, Charles W Drescher, Roland K Strong, Thomas Spies, Veronika Groh
Cancer cells may co-opt the NKG2D lymphocyte receptor to complement the presence of its ligands for autonomous stimulation of oncogenic signaling. Previous studies raise the possibility that cancer cell NKG2D may induce high malignancy traits, but its full oncogenic impact is unknown. Using epithelial ovarian cancer as model setting, we show here that ex vivo NKG2D(+) cancer cells have stem-like capacities, and provide formal in vivo evidence linking NKG2D stimulation with the development and maintenance of these functional states...
May 9, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28494349/trabectedin-and-campthotecin-synergistically-eliminate-cancer-stem-cells-in-cell-of-origin-sarcoma-models
#4
Lucia Martinez-Cruzado, Juan Tornin, Aida Rodriguez, Laura Santos, Eva Allonca, Maria Teresa Fernandez-Garcia, Aurora Astudillo, Juana Maria Garcia-Pedrero, Rene Rodriguez
Trabectedin has been approved for second-line treatment of soft tissue sarcomas. However, its efficacy to target sarcoma initiating cells has not been addressed yet. Here, we used pioneer models of myxoid/round cell liposarcoma (MRCLS) and undifferentiated pleomorphic sarcoma (UPS) developed from transformed human mesenchymal stromal/stem cells (MSCs) to evaluate the effect of trabectedin in the cell type responsible for initiating sarcomagenesis and their derived cancer stem cells (CSC) subpopulations. We found that low nanomolar concentrations of trabectedin efficiently inhibited the growth of sarcoma-initiating cells, induced cell cycle arrest, DNA damage and apoptosis...
May 8, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28494348/withaferin-a-inhibits-prostate-carcinogenesis-in-a-pten-deficient-mouse-model-of-prostate-cancer
#5
Jim Moselhy, Suman Suman, Mohammed Alghamdi, Balaji Chandarasekharan, Trinath P Das, Alatassi Houda, Murali Ankem, Chendil Damodaran
We recently demonstrated that AKT activation plays a role in prostate cancer progression and inhibits the pro-apoptotic function of FOXO3a and Par-4. AKT inhibition and Par-4 induction suppressed prostate cancer progression in preclinical models. Here, we investigate the chemopreventive effect of the phytonutrient Withaferin A (WA) on AKT-driven prostate tumorigenesis in a Pten conditional knockout (Pten-KO) mouse model of prostate cancer. Oral WA treatment was carried out at two different doses (3 and 5 mg/kg) and compared to vehicle over 45 weeks...
May 7, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28448802/ddk-promotes-tumor-chemoresistance-and-survival-via-multiple-pathways
#6
Nanda Kumar Sasi, Arjun Bhutkar, Nathan J Lanning, Jeffrey P MacKeigan, Michael Weinreich
DBF4-dependent kinase (DDK) is a two-subunit kinase required for initiating DNA replication at individual origins and is composed of CDC7 kinase and its regulatory subunit DBF4. Both subunits are highly expressed in many diverse tumor cell lines and primary tumors, and this is correlated with poor prognosis. Inhibiting DDK causes apoptosis of tumor cells, but not normal cells, through a largely unknown mechanism. Firstly, to understand why DDK is often overexpressed in tumors, we identified gene expression signatures that correlate with DDK high- and DDK low-expressing lung adenocarcinomas...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28433772/mesenchymal-stem-cells-induce-epithelial-to-mesenchymal-transition-in-colon-cancer-cells-through-direct-cell-to-cell-contact
#7
Hidehiko Takigawa, Yasuhiko Kitadai, Kei Shinagawa, Ryo Yuge, Yukihito Higashi, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama
We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow-derived mesenchymal stem cells (MSCs) migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28433771/a-versatile-tumor-gene-deletion-system-reveals-a-crucial-role-for-fgfr1-in-breast-cancer-metastasis
#8
Wei Wang, Yanling Meng, Bingning Dong, Jie Dong, Michael M Ittmann, Chad J Creighton, Yang Lu, Hong Zhang, Tao Shen, Jianghua Wang, David R Rowley, Yi Li, Fengju Chen, David D Moore, Feng Yang
RCAS avian viruses have been used to deliver oncogene expression and induce tumors in transgenic mice expressing the virus receptor TVA. Here we report the generation and characterization of a novel RCAS-Cre-IRES-PyMT (RCI-PyMT) virus designed to specifically knockout genes of interest in tumors generated in appropriate mutant mouse hosts. FGF receptor 1 (FGFR1) is a gene that is amplified in human breast cancer, but there have been no definitive studies on its function in mammary tumorigenesis, progression, and metastasis in vivo in spontaneous tumors in mice...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28431273/chromosomal-instability-in-gastric-cancer-biology
#9
REVIEW
Saffiyeh Saboor Maleki, Christoph Röcken
Gastric cancer (GC) is the fifth most common cancer in the world and accounts for 7% of the total cancer incidence. The prognosis of GC is dismal in Western countries due to late diagnosis: approximately 70% of the patients die within 5 years following initial diagnosis. Recently, integrative genomic analyses led to the proposal of a molecular classification of GC into four subtypes, i.e.,microsatellite-instable, Epstein-Barr virus-positive, chromosomal-instable (CIN), and genomically stable GCs. Molecular classification of GC advances our knowledge of the biology of GC and may have implications for diagnostics and patient treatment...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28431272/specific-microrna-mrna-regulatory-network-of-colon-cancer-invasion-mediated-by-tissue-kallikrein-related-peptidase-6
#10
Earlphia Sells, Ritu Pandey, Hwudaurw Chen, Bethany A Skovan, Haiyan Cui, Natalia A Ignatenko
Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28391030/metformin-triggers-autophagy-to-attenuate-drug-induced-apoptosis-in-nsclc-cells-with-minor-effects-on-tumors-of-diabetic-patients
#11
Zhiguang Xiao, Silvia Gaertner, Alicia Morresi-Hauf, Rebecca Genzel, Thomas Duell, Axel Ullrich, Pjotr G Knyazev
The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR targeted therapy and chemotherapy in 7 non-small cell lung cancer (NSCLC) cell lines and a cohort of lung cancer patients with/without T2D. In vitro cell viability assays indicated that metformin didn't potentiate the growth inhibitory effects of erlotinib at different doses in cell lines that are of distinct genetic background...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28385276/corrigendum-to-epidermal-growth-factor-cytoplasmic-domain-affects-erbb-protein-degradation-by-the-lysosomal-and-ubiquitin-proteasome-pathway-in-human-cancer-cells-neoplasia-14-2012-396-409
#12
Aleksandra Glogowska, Jörg Stetefeld, Ekkehard Weber, Saeid Ghavami, Cuong Hoang-Vu, Thomas Klonisch
No abstract text is available yet for this article.
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28334634/e3-ubiquitin-ligase-cbl-b-prevents-tumor-metastasis-by-maintaining-the-epithelial-phenotype-in-multiple-drug-resistant-gastric-and-breast-cancer-cells
#13
Ling Xu, Ye Zhang, Xiujuan Qu, Xiaofang Che, Tianshu Guo, Ying Cai, Aodi Li, Danni Li, Ce Li, Ti Wen, Yibo Fan, Kezuo Hou, Yanju Ma, Xuejun Hu, Yunpeng Liu
Multiple drug resistance (MDR) and metastasis are two major factors that contribute to the failure of cancer treatment. However, the relationship between MDR and metastasis has not been characterized. Additionally, the role of the E3 ubiquitin ligase Cbl-b in metastasis of MDR gastric and breast cancer is not well known. In the present study, we found that MDR gastric and breast cancer cells possess a typical mesenchymal phenotype and enhanced cell migration capacity. Additionally, Cbl-b is poorly expressed in MDR gastric and breast cancer cells...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#14
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319809/abt-737-synergizes-with-cisplatin-bypassing-aberration-of-apoptotic-pathway-in-non-small-cell-lung-cancer
#15
Eun Young Kim, Ji Ye Jung, Arum Kim, Yoon Soo Chang, Se Kyu Kim
A subset of non-small cell lung cancer (NSCLC), which does not have a druggable driver mutation, is treated with platinum-based cytotoxic chemotherapy, but it develops resistance triggered by DNA damage responses. Here, we investigated the effect of activation of STAT3 by cisplatin on anti-apoptotic proteins and the effectiveness of a co-treatment with cisplatin and a BH3 mimetic, ABT-737. We analyzed the relationship between cisplatin and STAT3 pathway and effect of ABT-737, when combined with cisplatin in NSCLC cells and K-ras mutant mouse models...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319808/identifying-regulatory-posttranslational-modifications-of-pd-l1-a-focus-on-monoubiquitinaton
#16
Henrick Horita, Andy Law, Soonjin Hong, Kim Middleton
A set of high-affinity, high-specificity posttranslational modification (PTM) enrichment tools was developed to generate an unbiased snapshot of four key PTM profiles (tyrosine phosphorylation, acetylation, ubiquitination, and SUMOylation 2/3) for the clinically important protein programmed cell death ligand 1 (PD-L1). The results showed that epidermal growth factor (EGF) treatment induced tyrosine phosphorylation, acetylation, and ubiquitination of PD-L1. Further characterization of EGF-induced PD-L1 ubiquitination revealed a significant increase in mono- and multiubiquitination of PD-L1 that occurred on glycosylated PD-L1...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#17
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28315615/mir155-regulation-of-ubiquilin1-and-ubiquilin2-implications-in-cellular-protection-and-tumorigenesis
#18
Sanjay Yadav, Nishant Singh, Parag P Shah, David A Rowbotham, Danial Malik, Ankita Srivastav, Jai Shankar, Wan L Lam, William W Lockwood, Levi J Beverly
Ubiquilin (UBQLN) proteins are adaptors thought to link ubiquitinated proteins to the proteasome. However, our lab has recently reported a previously unappreciated role for loss of UBQLN in lung cancer progression. In fact, UBQLN genes are lost in over 50% of lung cancer samples examined. However, a reason for the loss of UBQLN has not been proposed, nor has a selective pressure that could lead to deletion of UBQLN been reported. Diesel Exhaust Particles (DEP) are a major concern in the large cities of developing nations and DEP exposed populations are at an increased risk of developing a number of illnesses, including lung cancer...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28285180/noninvasive-bioluminescence-imaging-of-akt-kinase-activity-in-subcutaneous-and-orthotopic-nsclc-xenografts-correlation-of-akt-activity-with-tumor-growth-kinetics
#19
Karina Suchowski, Thomas Pöschinger, Alnawaz Rehemtulla, Michael Stürzl, Werner Scheuer
Aberrant signaling through the AKT kinase mediates oncogenic phenotypes including cell proliferation, survival, and therapeutic resistance. Here, we utilize a bioluminescence reporter for AKT kinase activity (BAR) to noninvasively assess the therapeutic efficacy of the EGFR inhibitor erlotinib in KRAS-mutated lung cancer therapy. A549 non-small cell lung cancer cell line, engineered to express BAR, enabled the evaluation of compounds targeting the EGFR/PI3K/AKT pathway in vitro as well as in mouse models. We found that erlotinib treatment of resistant A549 subcutaneous and orthotopic xenografts resulted in significant AKT inhibition as determined by an 8- to 13-fold (P < ...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28284059/reactivating-p53-and-inducing-tumor-apoptosis-rita-enhances-the-response-of-rita-sensitive-colorectal-cancer-cells-to-chemotherapeutic-agents-5-fluorouracil-and-oxaliplatin
#20
Armin Wiegering, Niels Matthes, Bettina Mühling, Monika Koospal, Anne Quenzer, Stephanie Peter, Christoph-Thomas Germer, Michael Linnebacher, Christoph Otto
Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and inducing tumor apoptosis (RITA) is described as an activator of wild-type and reactivator of mutant p53 function, resulting in elevated levels of p53 protein, cell growth arrest, and cell death...
April 2017: Neoplasia: An International Journal for Oncology Research
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