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Neoplasia: An International Journal for Oncology Research

Ariel Trink, Itamar Kanter, Naomi Pode-Shakked, Achia Urbach, Benjamin Dekel, Tomer Kalisky
Wilms' tumor is a pediatric malignancy that is thought to originate from faulty kidney development during the embryonic stage. However, there is a large variation between tumors from different patients in both histology and gene expression that is not well characterized. Here we use a meta-analysis of published microarray datasets to show that Favorable Histology Wilms' Tumors (FHWT's) fill a triangle-shaped continuum in gene expression space of which the vertices represent three idealized "archetypes"...
July 17, 2018: Neoplasia: An International Journal for Oncology Research
Federica Alessandrini, Laura Pezzè, Daniel Menendez, Michael A Resnick, Yari Ciribilli
Breast cancer treatment often includes Doxorubicin as adjuvant as well as neoadjuvant chemotherapy. Despite its cytotoxicity, cells can develop drug resistance to Doxorubicin. Uncovering pathways and mechanisms involved in drug resistance is an urgent and critical aim for breast cancer research oriented to improve treatment efficacy. Here we show that Doxorubicin and other chemotherapeutic drugs induce the expression of ETV7, a transcriptional repressor member of ETS family of transcription factors. The ETV7 expression led to DNAJC15 down-regulation, a co-chaperone protein whose low expression was previously associated with drug resistance in breast and ovarian cancer...
July 16, 2018: Neoplasia: An International Journal for Oncology Research
Francis Combes, Séan Mc Cafferty, Evelyne Meyer, Niek N Sanders
Solid tumors frequently coexist with a degree of local chronic inflammation. Recruited myeloid cells can therefore be considered as interesting vehicles for tumor-targeted delivery of therapeutic agents. Using in vivo imaging, the short-term accumulation of systemically injected monocytes, macrophages and myeloid-derived suppressor cells (MDSCs) was compared in mice bearing fat pad mammary carcinomas. Monocytes and macrophages demonstrated almost identical in vivo and ex vivo distribution patterns with maximal tumor-associated accumulation seen 48 hours after injection that remained stable over the 4-day follow-up period...
July 16, 2018: Neoplasia: An International Journal for Oncology Research
Chien-Hung Gow, Yi-Nan Liu, Huei-Ying Li, Min-Shu Hsieh, Shih-Han Chang, Sheng-Ching Luo, Tzu-Hsiu Tsai, Pei-Lung Chen, Meng-Feng Tsai, Jin-Yuan Shih
A kinesin family member 5b (KIF5B)-MET proto-oncogene, receptor tyrosine kinase (MET) rearrangement was reported in patients with lung adenocarcinoma but its oncogenic function was not fully evaluated. We used one-step reverse transcription-polymerase chain reaction for RNA samples to screen for the KIF5B-MET fusion in 206 lung adenocarcinoma and 28 pulmonary sarcomatoid carcinoma patients. Genomic breakpoints of KIF5B-MET were determined by targeted next-generation sequencing. Soft agar colony formation assays, proliferation assays, and a xenograft mouse model were used to investigate its oncogenic activity...
July 12, 2018: Neoplasia: An International Journal for Oncology Research
Ilgen Mender, Ryan LaRanger, Krishna Luitel, Michael Peyton, Luc Girard, Tsung-Po Lai, Kimberly Batten, Crystal Cornelius, Maithili P Dalvi, Michael Ramirez, Wenting Du, Lani F Wu, Steven J Altschuler, Rolf Brekken, Elisabeth D Martinez, John D Minna, Woodring E Wright, Jerry W Shay
Standard and targeted cancer therapies for late-stage cancer patients almost universally fail due to tumor heterogeneity/plasticity and intrinsic or acquired drug resistance. We used the telomerase substrate nucleoside precursor, 6-thio-2'-deoxyguanosine (6-thio-dG), to target telomerase-expressing non-small cell lung cancer cells resistant to EGFR-inhibitors and commonly used chemotherapy combinations. Colony formation assays, human xenografts as well as syngeneic and genetically engineered immune competent mouse models of lung cancer were used to test the effect of 6-thio-dG on targeted therapy- and chemotherapy-resistant lung cancer human cells and mouse models...
July 6, 2018: Neoplasia: An International Journal for Oncology Research
Srikanth Barkeer, Seema Chugh, Surinder K Batra, Moorthy P Ponnusamy
Aberrant glycosylation plays a critical role in tumor aggressiveness, progression, and metastasis. Emerging evidence associates cancer initiation and metastasis to the enrichment of cancer stem cells (CSCs). Several universal markers have been identified for CSCs characterization; however, a specific marker has not yet been identified for different cancer types. Specific glycosylation variation plays a major role in the progression and metastasis of different cancers. Interestingly, many of the CSC markers are glycoproteins and undergo differential glycosylation...
July 6, 2018: Neoplasia: An International Journal for Oncology Research
Iftikhar Ali Khawar, Jong Kook Park, Eun Sun Jung, Myung Ah Lee, Suhwan Chang, Hyo-Jeong Kuh
Interactions between cancer cells and cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) play an important role in promoting the profibrotic microenvironment and epithelial-mesenchymal transition (EMT), resulting in tumor progression and drug resistance in hepatocellular carcinoma (HCC). In the present study, we developed a mixed-cell spheroid model using Huh-7 HCC cells and LX-2 stellate cells to simulate the in vivo tumor environment with respect to tumor-CAF interactions. Spheroids were cultured from cancer cells alone (monospheroids) or as a mixture (mixed-cell spheroids) in ultra-low-attachment plates...
July 4, 2018: Neoplasia: An International Journal for Oncology Research
Kenza Mamouni, Shumin Zhang, Xin Li, Yanhua Chen, Yang Yang, Jaeah Kim, Michael G Bartlett, Ilsa M Coleman, Peter S Nelson, Omer Kucuk, Daqing Wu
The high prevalence and long latency period of prostate cancer (PCa) provide a unique opportunity to control disease progression with dietary and nutraceutical approaches. We developed ProFine, a standardized composition of luteolin, quercetin, and kaempferol, and investigated its potential as a nutraceutical for PCa in preclinical models. The three ingredients of ProFine demonstrated synergistic in vitro cytotoxicity and effectively induced apoptosis in PCa cells. ProFine markedly affected the transcriptome of PCa cells, suppressed the expression of androgen receptor, and inhibited androgen-regulated genes...
July 4, 2018: Neoplasia: An International Journal for Oncology Research
Chia-Hsin Hsieh, Shyh-Kuan Tai, Muh-Hwa Yang
Epithelial-mesenchymal transition (EMT) is a major event during cancer progression and metastasis; however, the definitive role of EMT in remodeling tumor microenvironments (TMEs) is unclear. Tumor-associated macrophages (TAMs) are a major type of host immune cells in TMEs, and they perform a wide range of functions to regulate tumor colonization and progression by regulating tumor invasiveness, local tumor immunity, and angiogenesis. TAMs are considered to have an M2-like, i.e., alternatively activated, phenotype; however, how these EMT-undergoing cancer cells promote M2 polarization of TAMs as a crucial tumor-host interplay during cancer progression is unclear...
July 2, 2018: Neoplasia: An International Journal for Oncology Research
Yu Cao, Han Liu, Liwei Gao, Ling Lu, Li Du, Han Bai, Jiang Li, Sherif Said, Xiao-Jing Wang, John Song, Natalie Serkova, Minjie Wei, Jing Xiao, Shi-Long Lu
Salivary gland tumor (SGT) is a rare tumor type, which exhibits broad-spectrum phenotypic, biological, and clinical heterogeneity. Currently, the molecular mechanisms that cause SGT pathogenesis remain poorly understood. A lack of animal models that faithfully recapitulate the naturally occurring process of human SGTs has hampered research progress on this field. In this report, we developed an inducible keratin 5-driven conditional knockout mouse model to delete gene(s) of interest in murine salivary gland upon local RU486 delivery...
June 26, 2018: Neoplasia: An International Journal for Oncology Research
Jasmine H Francis, Nelli Roosipu, Ariana M Levin, Scott E Brodie, Ira J Dunkel, Y Pierre Gobin, David H Abramson
PURPOSE: To evaluate the management and outcomes of naïve bilateral retinoblastoma treated at a single-center over a 5-year period during the era of ophthalmic artery chemosurgery (OAC) and intravitreous chemotherapy. METHODS: Retrospective cohort study of 46 patients (92 eyes) with naïve bilateral retinoblastoma treated at Memorial Sloan Kettering Cancer Center between January 2012 and February 2017. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response...
June 21, 2018: Neoplasia: An International Journal for Oncology Research
Yang Li, Mingming Zhang, Robert G Dorfman, Yida Pan, Dehua Tang, Lei Xu, Zhenguo Zhao, Qian Zhou, Lixing Zhou, Yuming Wang, Yuyao Yin, Shanshan Shen, Bo Kong, Helmut Friess, Shimin Zhao, Lei Wang, Xiaoping Zou
Metastasis is the most important feature of gastric cancer (GC) and the most widely recognized reason for GC-related deaths. Unfortunately, the underlying mechanism behind this metastasis remains unknown. Mounting evidence suggests the dynamic regulatory role of sirtuin2 (SIRT2), a histone deacetylase (HDAC), in cell migration and invasion. The present study aims to evaluate the biological function of SIRT2 in GC and identify the target of SIRT2 as well as evaluate its therapeutic efficacy. We found that SIRT2 was upregulated in GC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival...
June 17, 2018: Neoplasia: An International Journal for Oncology Research
Catherine S Wegner, Anette Hauge, Trude G Simonsen, Jon-Vidar Gaustad, Lise Mari K Andersen, Einar K Rofstad
The purpose of this study was dual: to investigate (a) whether sunitinib may induce changes in tumor microvasculature and hypoxia in pancreatic ductal adenocarcinoma (PDAC) and (b) whether any changes can be detected by DCE-MRI. Sunitinib-treated and untreated control tumors of two PDAC xenograft models (BxPC-3 and Panc-1) were subjected to DCE-MRI before the imaged tumors were prepared for quantitative analysis of immunohistochemical preparations. Pimonidazole was used as a hypoxia marker, and fraction of hypoxic tissue (HFPim ), density of CD31-positive microvessels (MVDCD31 ), and density of αSMA-positive microvessels (MVDαSMA ) were measured...
July 2018: Neoplasia: An International Journal for Oncology Research
Floriana Morgillo, Marcello Dallio, Carminia Maria Della Corte, Antonietta Gerarda Gravina, Giuseppe Viscardi, Carmelina Loguercio, Fortunato Ciardiello, Alessandro Federico
No abstract text is available yet for this article.
July 2018: Neoplasia: An International Journal for Oncology Research
Mark C de Gooijer, Nienke A de Vries, Tessa Buckle, Levi C M Buil, Jos H Beijnen, Willem Boogerd, Olaf van Tellingen
The anticancer drug temozolomide is the only drug with proven activity against high-grade gliomas and has therefore become a part of the standard treatment of these tumors. P-glycoprotein (P-gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2) are transport proteins, which are present at the blood-brain barrier and limit the brain uptake of substrate drugs. We have studied the effect of P-gp and BCRP on the pharmacokinetics and pharmacodynamics of temozolomide, making use of a comprehensive set of in vitro transport experiments and in vivo pharmacokinetic and antitumor efficacy experiments using wild-type, Abcg2-/- , Abcb1a/b-/- , and Abcb1a/b;Abcg2-/- mice...
July 2018: Neoplasia: An International Journal for Oncology Research
Julia Hollingsworth, Angela Lau, Alicia Tone, Alexandra Kollara, Lisa Allen, Terence J Colgan, Valerie Dube, Barry Rosen, K Joan Murphy, Ellen M Greenblatt, Tomer Feigenberg, Carl Virtanen, Theodore J Brown
Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed epithelial ovarian cancer histotype. Other identified risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation, during which the FTE cells become transiently exposed to follicular fluid (FF). To test whether mtBRCA1 or mtBRCA2 nonmalignant FTE cells respond differently to periovulatory FF exposure than control patient FTE cells, gene expression profiles from primary FTE cultures derived from BRCA1 or BRCA2 mutation carriers or control patients were compared at baseline, 24 hours after FF exposure, and 24 hours after FF replacement with culture medium...
July 2018: Neoplasia: An International Journal for Oncology Research
M J A Weerts, E C Timmermans, A van de Stolpe, R H A M Vossen, S Y Anvar, J A Foekens, S Sleijfer, J W M Martens
The use of blood-circulating cell-free DNA (cfDNA) as a "liquid biopsy" in oncology is being explored for its potential as a cancer biomarker. Mitochondria contain their own circular genomic entity (mitochondrial DNA, mtDNA), up to even thousands of copies per cell. The mutation rate of mtDNA is several orders of magnitude higher than that of the nuclear DNA. Tumor-specific variants have been identified in tumors along the entire mtDNA, and their number varies among and within tumors. The high mtDNA copy number per cell and the high mtDNA mutation rate make it worthwhile to explore the potential of tumor-specific cf-mtDNA variants as cancer marker in the blood of cancer patients...
July 2018: Neoplasia: An International Journal for Oncology Research
Vicente Alonso, Pilar Escudero, Carlos Fernández-Martos, Antonia Salud, Miguel Méndez, Javier Gallego, Jose-R Rodriguez, Marta Martín-Richard, Julen Fernández-Plana, Hermini Manzano, José-Carlos Méndez, Monserrat Zanui, Esther Falcó, Mireia Gil-Raga, Federico Rojo, Miriam Cuatrecasas, Jaime Feliu, Xabier García-Albéniz, Joan Maurel
INTRODUCTION: The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. METHODS: We analyzed two prospective biomarker design trials of newly diagnosed RAS-WT mCRC patients treated with panitumumab-FOLFOX6 (PULSE trial; NCT01288339) or cetuximab plus either FOLFOX6/FOLFIRI (POSIBA trial; NCT01276379)...
July 2018: Neoplasia: An International Journal for Oncology Research
Hiroya Taniguchi, Yuji Baba, Yoji Sagiya, Masamitsu Gotou, Kazuhide Nakamura, Hiroshi Sawada, Kazunori Yamanaka, Yukiko Sakakibara, Ikuo Mori, Yukiko Hikichi, Junpei Soeda, Hideo Baba
Recent studies in RAS wild-type (WT) metastatic colorectal cancer (mCRC) suggest that the survival benefits of therapy using anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies combined with chemotherapy are maximized when the anti-EGFR antibody is given as first-line, followed by subsequent anti-VEGF antibody therapy. We report reverse-translational research using LIM1215 xenografts of RAS WT mCRC to elucidate the biologic mechanisms underlying this clinical observation...
July 2018: Neoplasia: An International Journal for Oncology Research
Ligia B Schmitd, Lauren J Beesley, Nickole Russo, Emily L Bellile, Ronald C Inglehart, Min Liu, Genevieve Romanowicz, Gregory T Wolf, Jeremy M G Taylor, Nisha J D'Silva
A diagnosis of perineural invasion (PNI), defined as cancer within or surrounding at least 33% of the nerve, leads to selection of aggressive treatment in squamous cell carcinoma (SCC). Recent mechanistic studies show that cancer and nerves interact prior to physical contact. The purpose of this study was to explore cancer-nerve interactions relative to clinical outcome. Biopsy specimens from 71 patients with oral cavity SCC were stained with hematoxylin and eosin and immunohistochemical (IHC; cytokeratin, S100, GAP43, Tuj1) stains...
July 2018: Neoplasia: An International Journal for Oncology Research
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