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Neoplasia: An International Journal for Oncology Research

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https://www.readbyqxmd.com/read/28628795/knockout-of-the-nogo-b-gene-attenuates-tumor-growth-and-metastasis-in-hepatocellular-carcinoma
#1
Bo Zhu, Shaobo Chen, Xiaoding Hu, Xiaofeng Jin, Yichen Le, Lihuan Cao, Zhonghua Yuan, Zhen Lin, Songmin Jiang, Lichun Sun, Long Yu
Human hepatocellular carcinoma (HCC) is a malignant cancer. It is a challenge to develop anti-HCC drugs due to HCC's extreme aggressiveness and with the sensitivity of the liver to show severe adverse effects. More importantly, the precise mechanisms causing HCC pathogenicity are not known. Our previous study disclosed Nogo-B as a reticulon 4 (Rtn4) family member. In the present study, we first identified that Nogo-B played a critical role in HCC progression. We found, via in vitro and in vivo assays, that Nogo-B was expressed aberrantly in primary HCC tumor tissues and immortal HCC cells but was relatively scarce in the normal liver tissues or cells...
June 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28624626/alternative-polyadenylation-patterns-for-novel-gene-discovery-and-classification-in-cancer
#2
Oguzhan Begik, Merve Oyken, Tuna Cinkilli Alican, Tolga Can, Ayse Elif Erson-Bensan
Certain aspects of diagnosis, prognosis, and treatment of cancer patients are still important challenges to be addressed. Therefore, we propose a pipeline to uncover patterns of alternative polyadenylation (APA), a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we analyzed expression data for 1045 cancer patients and found a significant shift in usage of poly(A) signals in common tumor types (breast, colon, lung, prostate, gastric, and ovarian) compared to normal tissues...
June 15, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28609680/characterization-and-targeting-of-platelet-derived-growth-factor-receptor-alpha-pdgfra-in-inflammatory-breast-cancer-ibc
#3
Madhura Joglekar-Javadekar, Steven Van Laere, Michael Bourne, Manal Moalwi, Pascal Finetti, Peter B Vermeulen, Daniel Birnbaum, Luc Y Dirix, Naoto Ueno, Monique Carter, Justin Rains, Abhijit Ramachandran, Francois Bertucci, Kenneth L van Golen
PURPOSE: Inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer due to its rapid onset and highly invasive nature. IBC carries 5- and 10-year disease-free survival rates of ~45% and <20%, respectively. Multiple studies demonstrate that in comparison with conventional breast cancer, IBC has a unique molecular identity. Here, we have identified platelet-derived growth factor receptor alpha (PDGFRA) as being uniquely expressed and active in IBC patient tumor cells...
June 10, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28601643/heterogeneous-cadherin-expression-and-multicellular-aggregate-dynamics-in-ovarian-cancer-dissemination
#4
Yuliya Klymenko, Jeffrey Johnson, Brandi Bos, Rachel Lombard, Leigh Campbell, Elizabeth Loughran, M Sharon Stack
Epithelial ovarian carcinoma spreads via shedding of cells and multicellular aggregates (MCAs) from the primary tumor into peritoneal cavity, with subsequent intraperitoneal tumor cell:mesothelial cell adhesion as a key early event in metastatic seeding. Evaluation of human tumor extracts and tissues confirms that well-differentiated ovarian tumors express abundant E-cadherin (Ecad), whereas advanced lesions exhibit upregulated N-cadherin (Ncad). Two expression patterns are observed: "mixed cadherin," in which distinct cells within the same tumor express either E- or Ncad, and "hybrid cadherin," wherein single tumor cell(s) simultaneously expresses both cadherins...
June 8, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28587956/activated-natural-killer-cells-mediate-the-suppressive-effect-of-interleukin-4-on-tumor-development-via-stat6-activation-in-an-atopic-condition-melanoma-model
#5
Dong Ju Son, Yu Yeon Jung, Mi Hee Park, Hye Lim Lee, Min Ji Song, Hwan-Soo Yoo, Dae Youn Hwang, Sang Bae Han, Jin Tae Hong
A protective effect of allergy for cancer has been suggested, but the results are somewhat conflicting, and the mechanism remains elusive. Interleukin-4 (IL-4) signaling has been identified as a potentially important pathway in the development of allergies and the suppression of cancer development. To evaluate the allergy responses in IL-4-mediated tumor development, we compared the growth of B16F10 melanoma cells in 4% phthalic anhydride (PA)-treated IL-4/Luc/CNS-1 transgenic mice (IL-4 mice) and acetone-olive oil (AOO)-treated IL-4 mice as a control for 3 weeks...
June 3, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28582704/a-novel-antagonist-of-the-immune-checkpoint-protein-adenosine-a2a-receptor-restores-tumor-infiltrating-lymphocyte-activity-in-the-context-of-the-tumor-microenvironment
#6
Melanie Mediavilla-Varela, Julio Castro, Alberto Chiappori, David Noyes, Dalia C Hernandez, John Stagg, Scott J Antonia
BACKGROUND: Therapeutic strategies targeting immune checkpoint proteins have led to significant responses in patients with various tumor types. The success of these studies has led to the development of various antibodies/inhibitors for the different checkpoint proteins involved in immune evasion of the tumor. Adenosine present in high concentrations in the tumor microenvironment activates the immune checkpoint adenosine A2a receptor (A2aR), leading to the suppression of antitumor responses...
June 2, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28582703/the-cell-cycle-inhibitors-p21-cip1-and-p27-kip1-control-proliferation-but-enhance-dna-damage-resistance-of-glioma-stem-cells
#7
Olivia Morris-Hanon, Verónica Alejandra Furmento, María Soledad Rodríguez-Varela, Sofía Mucci, Damián Darío Fernandez-Espinosa, Leonardo Romorini, Gustavo Emilio Sevlever, María Elida Scassa, Guillermo Agustín Videla-Richardson
High-grade gliomas are the most prevalent and lethal primary brain tumors. They display a hierarchical arrangement with a population of self-renewing and highly tumorigenic cells called cancer stem cells. These cells are thought to be responsible for tumor recurrence, which make them main candidates for targeted therapies. Unbridled cell cycle progression may explain the selective sensitivity of some cancer cells to treatments. The members of the Cip/Kip family p21(Cip1) and p27(Kip1) were initially considered as tumor suppressors based on their ability to block proliferation...
June 2, 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
#8
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
#9
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
#10
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
#11
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/28535453/inhibition-of-neddylation-modification-sensitizes-pancreatic-cancer-cells-to-gemcitabine
#12
Hua Li, Weihua Zhou, Lihui Li, Jianfu Wu, Xiaoli Liu, Lili Zhao, Lijun Jia, Yi Sun
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA with a 5-year survival rate less than 3% to 5%. Gemcitabine remains as a standard care for PDAC patients. Although protein neddylation is abnormally activated in many human cancers, whether neddylation dysregulation is involved in PDAC and whether targeting neddylation would sensitize pancreatic cancer cells to gemcitabine remain elusive. Here we report that high expression of neddylation components, NEDD8 and NAE1, are associated with poor survival of PDAC patients...
June 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28501760/stromal-pdgfr-%C3%AE-activation-enhances-matrix-stiffness-impedes-mammary-ductal-development-and-accelerates-tumor-growth
#13
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...
June 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28448802/ddk-promotes-tumor-chemoresistance-and-survival-via-multiple-pathways
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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