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Neoplasia: An International Journal for Oncology Research

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https://www.readbyqxmd.com/read/29462756/bag3-overexpression-and-cytoprotective-autophagy-mediate-apoptosis-resistance-in-chemoresistant-breast-cancer-cells
#1
Chandan Kanta Das, Benedikt Linder, Florian Bonn, Florian Rothweiler, Ivan Dikic, Martin Michaelis, Jindrich Cinatl, Mahitosh Mandal, Donat Kögel
Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity...
February 17, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29454261/frequency-of-somatic-tp53-mutations-in-combination-with-known-pathogenic-mutations-in-colon-adenocarcinoma-non-small-cell-lung-carcinoma-and-gliomas-as-identified-by-next-generation-sequencing
#2
Zahra Shajani-Yi, Francine B de Abreu, Jason D Peterson, Gregory J Tsongalis
The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective...
February 13, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29448085/plk2-loss-commonly-occurs-in-colorectal-carcinomas-but-not-adenomas-relationship-to-mtor-signaling
#3
Elizabeth M Matthew, Zhaohai Yang, Suraj Peri, Mark Andrake, Roland Dunbrack, Eric Ross, Wafik S El-Deiry
Plk2 is a target of p53. Our previous studies demonstrated that with wild-type p53, Plk2 impacts mTOR signaling in the same manner as TSC1, and Plk2-deficient tumors grew larger than control. Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop. We investigated Plk2's tumor suppressor functions in relationship to mTOR signaling. Archival specimens from 12 colorectal adenocarcinomas were stained for markers including Plk2, phosphorylated mTOR (serine 2448) and ribosomal S6 (Serine 235/236)...
February 12, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29448084/radiotherapy-controversies-and-prospective-in-head-and-neck-cancer-a-literature-based-critical-review
#4
REVIEW
Francesca De Felice, Antonella Polimeni, Valentino Valentini, Orlando Brugnoletti, Andrea Cassoni, Antonio Greco, Marco de Vincentiis, Vincenzo Tombolini
In treating head and neck cancer (HNC), the objectives are provided for best functional results and minimal risk of serious complications. The choice of appropriate management depends primarily on specific site and stage of primary tumor at diagnosis. Radiation therapy (RT) with or without concomitant chemotherapy represents a classical treatment option. In this review, we provide an update of recent research strategies to counteract the existing damage caused by RT and highlight clinical trials currently in progress...
February 12, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29444487/paracrine-fibroblast-growth-factor-initiates-oncogenic-synergy-with-epithelial-fgfr-src-transformation-in-prostate-tumor-progression
#5
Qianjin Li, Lishann Ingram, Sungjin Kim, Zanna Beharry, Jonathan A Cooper, Houjian Cai
Cross talk of stromal-epithelial cells plays an essential role in both normal development and tumor initiation and progression. Fibroblast growth factor (FGF)-FGF receptor (FGFR)-Src kinase axis is one of the major signal transduction pathways to mediate this cross talk. Numerous genomic studies have demonstrated that expression levels of FGFR/Src are deregulated in a variety of cancers including prostate cancer; however, the role that paracrine FGF (from stromal cells) plays in dysregulated expression of epithelial FGFRs/Src and tumor progression in vivo is not well evaluated...
February 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331888/a-longitudinal-analysis-of-ido-and-pdl1-expression-during-immune-or-targeted-therapy-in-advanced-melanoma
#6
Lukas Krähenbühl, Simone M Goldinger, Joanna Mangana, Katrin Kerl, Ines Chevolet, Liève Brochez, Christine Horak, Mitch Levesque, Reinhard Dummer, Phil F Cheng
A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT). We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT). Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331887/idh1r132h-promotes-malignant-transformation-of-benign-prostatic-epithelium-by-dysregulating-micrornas-involvement-of-igf1r-akt-stat3-signaling-pathway
#7
Lili Zhang, Mei Qi, Tingting Feng, Jing Hu, Lin Wang, Xinjun Li, Wei Gao, Hui Liu, Meng Jiao, Zhen Wu, Xinnuo Bai, Yifan Bie, Long Liu, Bo Han
Risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer (PCa). Mutations in isocitrate dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. Mutant IDH1 has been identified in various human malignancies, and IDH1R132H constituted the vast majority of mutational events of IDH1. Most recent studies suggested that IDH1 mutations define a methylator subtype in PCa...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331886/anti-cancer-effects-of-hnha-and-lenvatinib-by-the-suppression-of-emt-mediated-drug-resistance-in-cancer-stem-cells
#8
Yong Sang Lee, Seok-Mo Kim, Bup-Woo Kim, Ho Jin Chang, Soo Young Kim, Cheong Soo Park, Ki Cheong Park, Hang-Seok Chang
Anaplastic thyroid cancer (ATC) constitutes less than 2% of total thyroid cancers but accounts for 20-40% of thyroid cancer-related deaths. Cancer stem cell drug resistance represents a primary factor hindering treatment. This study aimed to develop targeted agents against thyroid malignancy, focusing on individual and synergistic effects of HNHA (histone deacetylase), lenvatinib (FGFR), and sorafenib (tyrosine kinase) inhibitors. Patients with biochemically and histologically proven papillary thyroid cancer (PTC) and ATC were included...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29287248/generating-the-abscopal-effect-by-combining-proapoptotic-peptides-with-il-12-based-immunotherapy
#9
Filipe Martins, Grégoire Stalder, Michel Obeid
No abstract text is available yet for this article.
December 26, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29274508/a-heparin-binding-motif-rich-in-arginine-and-lysine-is-the-functional-domain-of-ykl-40
#10
Nipaporn Ngernyuang, Wei Yan, Lawrence M Schwartz, Dennis Oh, Ying-Bin Liu, Hongzhuan Chen, Rong Shao
The heparin-binding glycoprotein YKL-40 (CHI3L1) is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s) pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R) and lysine (K) (RRDK; residues 144-147); but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334-345) that does display strong heparin binding affinity...
December 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29272741/neurotensin-receptor-3-sortilin-contributes-to-tumorigenesis-of-neuroendocrine-tumors-through-augmentation-of-cell-adhesion-and-migration
#11
Ji Tae Kim, Dana L Napier, Heidi L Weiss, Eun Y Lee, Courtney M Townsend, B Mark Evers
Neurotensin (NTS), a 13-amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated...
December 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29248719/usp9x-promotes-survival-in-human-pancreatic-cancer-and-its-inhibition-suppresses-pancreatic-ductal-adenocarcinoma-in-vivo-tumor-growth
#12
Anupama Pal, Michele Dziubinski, Marina Pasca Di Magliano, Diane M Simeone, Scott Owens, Dafydd Thomas, Luke Peterson, Harish Potu, Moshe Talpaz, Nicholas J Donato
Usp9x has emerged as a potential therapeutic target in some hematologic malignancies and a broad range of solid tumors including brain, breast, and prostate. To examine Usp9x tumorigenicity and consequence of Usp9x inhibition in human pancreatic tumor models, we carried out gain- and loss-of-function studies using established human pancreatic tumor cell lines (PANC1 and MIAPACA2) and four spontaneously immortalized human pancreatic patient-derived tumor (PDX) cell lines. The effect of Usp9x activity inhibition by small molecule deubiquitinase inhibitor G9 was assessed in 2D and 3D culture, and its efficacy was tested in human tumor xenografts...
December 14, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29248718/proteomic-characterization-of-prostate-cancer-to-distinguish-nonmetastasizing-and-metastasizing-primary-tumors-and-lymph-node-metastases
#13
Ann-Kathrin Müller, Melanie Föll, Bianca Heckelmann, Selina Kiefer, Martin Werner, Oliver Schilling, Martin L Biniossek, Cordula Annette Jilg, Vanessa Drendel
Patients with metastatic prostate cancer (PCa) have a poorer prognosis than patients with organ-confined tumors. We strove to uncover the proteome signature of primary PCa and associated lymph node metastases (LNMs) in order to identify proteins that may indicate or potentially promote metastases formation. We performed a proteomic comparative profiling of PCa tissue from radical prostatectomy (RPE) of patients without nodal metastases or relapse at the time of surgical resection (n=5) to PCa tissue from RPE of patients who suffered from nodal relapse (n=5)...
December 14, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29247885/hypoxia-inducible-factors-modify-collagen-i-fibers-in-mda-mb-231-triple-negative-breast-cancer-xenografts
#14
Eibhlin Goggins, Samata Kakkad, Yelena Mironchik, Desmond Jacob, Flonne Wildes, Balaji Krishnamachary, Zaver M Bhujwalla
Hypoxia inducible factors (HIFs) are transcription factors that mediate the response of cells to hypoxia. HIFs have wide-ranging effects on metabolism, the tumor microenvironment (TME) and the extracellular matrix (ECM). Here we investigated the silencing effects of two of the three known isoforms, HIF-1α and HIF-2α, on collagen 1 (Col1) fibers, which form a major component of the ECM of tumors. Using a loss-of-function approach for HIF-1α or 2α or both HIF-1α and 2α, we identified a relationship between HIFs and Col1 fibers in MDA-MB-231 tumors...
December 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29247884/a-low-toxicity-dna-alkylating-n-mustard-quinoline-conjugate-with-preferential-sequence-specificity-exerts-potent-antitumor-activity-against-colorectal-cancer
#15
Tai-Lin Chen, Yi-Wen Lin, Yan-Bo Chen, Jing-Jer Lin, Tsann-Long Su, Chia-Ning Shen, Te-Chang Lee
Efficacy and safety are fundamental prerequisites for anticancer drug development. In the present study, we explored the anti-colorectal cancer (CRC) activity of SL-1, a DNA-directed N-mustard-quinoline conjugate. The N-mustard moiety in SL-1 induced DNA strand breaks, interstrand cross-links (ICLs), G2/M arrest, and apoptosis, whereas its quinoline moiety preferentially directed SL-1 to target the selective guanine sequence 5'-G-G/C-N-G-C/T-3'. Notably, SL-1 was highly cytotoxic to various CRC cell lines. Experiments using xenograft models revealed that SL-1 was more potent than 5-fluorouracil (5-FU) and oxaliplatin for suppressing the growth of RKO and RKO-E6 (oxaliplatin-resistant subline) cells as well as metastatic SW620 cells...
December 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29245123/the-gdnf-family-a-role-in-cancer
#16
REVIEW
Graeme C Fielder, Teresa Wen-Shan Yang, Mahalakshmi Razdan, Yan Li, Jun Lu, Jo K Perry, Peter E Lobie, Dong-Xu Liu
The glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFLs) comprising of GDNF, neurturin, artemin, and persephin plays an important role in the development and maintenance of the central and peripheral nervous system, renal morphogenesis, and spermatogenesis. Here we review our current understanding of GFL biology, and supported by recent progress in the area, we examine their emerging role in endocrine-related and other non-hormone-dependent solid neoplasms. The ability of GFLs to elicit actions that resemble those perturbed in an oncogenic phenotype, alongside mounting evidence of GFL involvement in tumor progression, presents novel opportunities for therapeutic intervention...
December 12, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29216597/role-of-dopamine-receptors-in-the-anticancer-activity-of-onc201
#17
Christina Leah B Kline, Marie D Ralff, Amriti R Lulla, Jessica M Wagner, Phillip H Abbosh, David T Dicker, Joshua E Allen, Wafik S El-Deiry
ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes early activation of the integrated stress response. Its promising safety profile and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in several advanced malignancies. Binding and reporter assays have shown that ONC201 is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2 and DRD3. We hypothesized that ONC201's interaction with DRD2 plays a role in ONC201's anticancer effects. Using cBioportal and quantitative reverse-transcription polymerase chain reaction analyses, we confirmed that DRD2 is expressed in different cancer cell types in a cell type-specific manner...
December 5, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29195127/rapamycin-synergizes-with-cisplatin-in-antiendometrial-cancer-activation-by-improving-il-27-stimulated-cytotoxicity-of-nk-cells
#18
Wen-Jie Zhou, Kai-Kai Chang, Ke Wu, Hui-Li Yang, Jie Mei, Feng Xie, Da-Jin Li, Ming-Qing Li
Natural killer (NK) cell function is critical for controlling initial tumor growth and determining chemosensitivity of the tumor. A synergistic relationship between rapamycin and cisplatin in uterine endometrial cancer (UEC) in vitro has been reported, but the mechanism and the combined therapeutic strategy for endometrial cancer (EC) are still unknown. We found a positive correlation between the level of IL-27 and the differentiated stage of UEC. The increase of IL-27 in uterine endometrial cancer cell (UECC) lines (Ishikawa, RL95-2 and KLE) led to a high cytotoxic activity of NK cells to UECC in the co-culture system...
November 28, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29195126/stimulation-of-interferon-stimulated-gene-20-by-thyroid-hormone-enhances-angiogenesis-in-liver-cancer
#19
Syuan-Ling Lin, Sheng-Ming Wu, I-Hsiao Chung, Yang-Hsiang Lin, Ching-Ying Chen, Hsiang-Cheng Chi, Tzu-Kang Lin, Chau-Ting Yeh, Kwang-Huei Lin
Thyroid hormone, 3,3',5-triiodo-l-thyronine (T3), mediates several physiological processes, including embryonic development, cellular differentiation and cell proliferation, via binding to its nuclear thyroid receptors (TR). Previous microarray and Chromatin immunoprecipitation (ChIP)-on-ChIP analyses have revealed that interferon-stimulated gene 20 kDa (ISG20), an exoribonuclease involved in the antiviral function of interferon, is up-regulated by T3 in HepG2-TR cells. However, the underlying mechanisms of ISG20 action in tumor progression remain unknown to date...
November 28, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29190494/fus-chop-promotes-invasion-in-myxoid-liposarcoma-through-a-src-fak-rho-rock-dependent-pathway
#20
Juan Tornin, Francisco Hermida-Prado, Ranjit Singh Padda, M Victoria Gonzalez, Carlos Alvarez-Fernandez, Veronica Rey, Lucia Martinez-Cruzado, Oscar Estupiñan, Sofia T Menendez, Lucia Fernandez-Nevado, Aurora Astudillo, Juan P Rodrigo, Fabrice Lucien, Yohan Kim, Hon S Leong, Juana Maria Garcia-Pedrero, Rene Rodriguez
Deregulated SRC/FAK signaling leads to enhanced migration and invasion in many types of tumors. In myxoid and round cell liposarcoma (MRCLS), an adipocytic tumor characterized by the expression of the fusion oncogene FUS-CHOP, SRC have been found as one of the most activated kinases. Here we used a cell-of-origin model of MRCLS and an MRCLS cell line to thoroughly characterize the mechanisms of cell invasion induced by FUS-CHOP using in vitro (3D spheroid invasion assays) and in vivo (chicken chorioallantoic membrane model) approaches...
November 27, 2017: Neoplasia: An International Journal for Oncology Research
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