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Neoplasia: An International Journal for Oncology Research

Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
Elizabeth A Loughran, Annemarie K Leonard, Tyvette S Hilliard, Ryan C Phan, Madeleine G Yemc, Elizabeth Harper, Emma Sheedy, Yuliya Klymenko, Marwa Asem, Yueying Liu, Jing Yang, Jeff Johnson, Laura Tarwater, Zonggao Shi, Matthew Leevy, Matthew J Ravosa, M Sharon Stack
Ovarian cancer, the most deadly gynecological malignancy in U.S. women, metastasizes uniquely, spreading through the peritoneal cavity and often generating widespread metastatic sites before diagnosis. The vast majority of ovarian cancer cases occur in women over 40 and the median age at diagnosis is 63. Additionally, elderly women receive poorer prognoses when diagnosed with ovarian cancer. Despite age being a significant risk factor for the development of this cancer, there are little published data which address the impact of aging on ovarian cancer metastasis...
May 10, 2018: Neoplasia: An International Journal for Oncology Research
Chris P Miller, Connor Tsuchida, Ying Zheng, Jonathan Himmelfarb, Shreeram Akilesh
Tractable human tissue-engineered 3D models of cancer that enable fine control of tumor growth, metabolism, and reciprocal interactions between different cell types in the tumor microenvironment promise to accelerate cancer research and pharmacologic testing. Progress to date mostly reflects the use of immortalized cancer cell lines, and progression to primary patient-derived tumor cells is needed to realize the full potential of these platforms. For the first time, we report endothelial sprouting induced by primary patient tumor cells in a 3D microfluidic system...
May 7, 2018: Neoplasia: An International Journal for Oncology Research
Srinivas Pittala, Yakov Krelin, Varda Shoshan-Barmatz
Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide. Despite progress in identifying risk factors, the incidence of HCC is increasing. Moreover, therapeutic options are limited and survival is poor. Therefore, alternative and innovative therapeutic strategies are urgently required. R-Tf-D-LP4, a cell-penetrating peptide derived from the mitochondrial multifunctional protein the voltage-dependent anion channel (VDAC1), is identified here as a highly effective liver cancer treatment. Recently, we demonstrated that R-Tf-D-LP4 induced apoptosis and inhibited tumor growth in mouse models...
May 7, 2018: Neoplasia: An International Journal for Oncology Research
Xiaoxiao Wang, Xin Cao, Ruifang Sun, Charlene Tang, Alexandar Tzankov, Jun Zhang, Ganiraju C Manyam, Min Xiao, Yi Miao, Kausar Jabbar, Xiaohong Tan, Yuyang Pang, Carlo Visco, Yan Xie, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L Richards, Eric D Hsi, William W L Choi, J Han van Krieken, Jooryung Huh, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Ben M Parsons, Jane N Winter, Miguel A Piris, Shaoying Li, Roberto N Miranda, L Jeffrey Medeiros, Yong Li, Zijun Y Xu-Monette, Ken H Young
PTEN loss has been associated with poorer prognosis in many solid tumors. However, such investigation in lymphomas is limited. In this study, PTEN cytoplasmic and nuclear expression, PTEN gene deletion, and PTEN mutations were evaluated in two independent cohorts of diffuse large B-cell lymphoma (DLBCL). Cytoplasmic PTEN expression was found in approximately 67% of total 747 DLBCL cases, more frequently in the activated B-cell-like subtype. Nuclear PTEN expression was less frequent and at lower levels, which significantly correlated with higher PTEN mRNA expression...
May 3, 2018: Neoplasia: An International Journal for Oncology Research
Leandro S D'Abronzo, Paramita M Ghosh
Prostate cancer (PCa) progression involves a shift from endocrine to paracrine and eventually autocrine control resulting from alterations in molecular mechanisms in the cells. Deregulation of RNA translation is crucial for tumor cells to grow and proliferate; therefore, overactivation of the translation machinery is often observed in cancer. The two most important signal transduction pathways regulating PCa progression are PI3K/Akt/mTOR and Ras/MAPK. These two pathways converge on the eukaryotic translation initiation factor 4E (eIF4E) which binds to the protein scaffold eIF4G upon mechanistic target of rapamycin (mTOR) activation and is phosphorylated by the mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnk1/2)...
May 3, 2018: Neoplasia: An International Journal for Oncology Research
Chloé Philippe, Benoît Pinson, Jim Dompierre, Véronique Pantesco, Benoît Viollet, Bertrand Daignan-Fornier, Michel Moenner
AICAR (Acadesine) is a pharmacological precursor of purine nucleotide biosynthesis with anti-tumoral properties. Although recognized as an AMP mimetic activator of the protein kinase AMPK, the AICAR monophosphate derivative ZMP was also shown to mediate AMPK-independent effects. In order to unveil these AMPK-independent functions, we performed a transcriptomic analysis in AMPKα1/α2 double knockout murine embryonic cells. Kinetic analysis of the cellular response to AICAR revealed the up-regulation of the large tumor suppressor kinases (Lats) 1 and 2 transcripts, followed by the repression of numerous genes downstream of the transcriptional regulators Yap1 and Taz...
May 3, 2018: Neoplasia: An International Journal for Oncology Research
Mingzhi Han, Ran Xu, Shuai Wang, Ning Yang, Shilei Ni, Qing Zhang, Yangyang Xu, Xin Zhang, Chao Zhang, Yuzhen Wei, Jianxiong Ji, Bin Huang, Di Zhang, Anjing Chen, Wenjie Li, Rolf Bjerkvig, Xingang Li, Jian Wang
Recent evidence suggests that dysregulation of iron regulatory factors may play essential roles in cancer pathophysiology. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a metalloreductase, which is vital for cellular iron uptake and homeostasis. However, the clinical significance and function of STEAP3 in the development of human gliomas remain unclear. Through analysis of publicly available databases, we found that STEAP3 was highly expressed in malignant gliomas, especially in the mesenchymal glioma molecular subtype and isocitrate dehydrogenase 1/2 (IDH1/2) wild-type gliomas...
May 3, 2018: Neoplasia: An International Journal for Oncology Research
Chuan Yan, Qiqi Yang, Zhiyuan Gong
Hepatocellular carcinoma (HCC) is one of the most common cancers and it usually develops from a background of liver fibrosis or inflammation. The crosstalk between tumor cells and stromal cells plays an important and stimulating role during tumor progression. Previously we found in a krasV12 -induced zebrafish HCC model that oncogenic hepatocytes activate hepatic stellate cells (HSCs) by up-regulation of serotonin and activate neutrophils and macrophages by up-regulation of cortisol. In the present study, we found a novel signaling transduction mechanism between oncogenic hepatocytes and HSCs...
April 9, 2018: Neoplasia: An International Journal for Oncology Research
Andrea A Hayes-Jordan, Xiao Ma, Brian A Menegaz, Salah-Eddine Lamhamedi-Cherradi, Charles V Kingsley, Jalen A Benson, Pamela E Camacho, Joseph A Ludwig, Cynthia R Lockworth, Gloria E Garcia, Suzanne L Craig
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies...
April 4, 2018: Neoplasia: An International Journal for Oncology Research
Giampaolo Morciano, Saverio Marchi, Claudia Morganti, Luigi Sbano, Mart Bittremieux, Martijn Kerkhofs, Mariangela Corricelli, Alberto Danese, Agnieszka Karkucinska-Wieckowska, Mariusz R Wieckowski, Geert Bultynck, Carlotta Giorgi, Paolo Pinton
Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are highly specialized subcellular compartments that are shaped by ER subdomains juxtaposed to mitochondria but are biochemically distinct from pure ER and pure mitochondria. MAMs are enriched in enzymes involved in lipid synthesis and transport, channels for calcium transfer, and proteins with oncogenic/oncosuppressive functions that modulate cell signaling pathways involved in physiological and pathophysiological processes. The term "cancer" denotes a group of disorders that result from uncontrolled cell growth driven by a mixture of genetic and environmental components...
April 4, 2018: Neoplasia: An International Journal for Oncology Research
Jianwei Wang, Rong Lu, Xinghui Fu, Zhou Dan, Yong-Guo Zhang, Xinxia Chang, Qisha Liu, Yinglin Xia, Xingyin Liu, Jun Sun
Salmonella infection is a major public health concern, and colonization in humans can be chronic and increases the risk of cancers. Wnt signaling is a key pathway for intestinal renewal and development, inflammation, and tumorigenesis. In the current study, we report a novel role of Wnt1 in infection and colon cancer using cell culture models, a Salmonella-colitis colon cancer model, and human samples. In contrast to the bacteria-induced increases in Wnt2 and Wnt11, Salmonella colonization significantly reduced the level of Wnt1 in intestinal epithelial cells in vivo and in vitro...
April 4, 2018: Neoplasia: An International Journal for Oncology Research
Susana P Egusquiaguirre, Jennifer E Yeh, Sarah R Walker, Suhu Liu, David A Frank
The transcription factor STAT3 is activated inappropriately in 70% of breast cancers, most commonly in triple negative breast cancer (TNBC). Although the transcriptional function of STAT3 is essential for tumorigenesis, the key target genes regulated by STAT3 in driving tumor pathogenesis have remained unclear. To identify critical STAT3 target genes, we treated TNBC cell lines with two different compounds that block STAT3 transcriptional function, pyrimethamine and PMPTP. We then performed gene expression analysis to identify genes whose expression is strongly down-regulated by both STAT3 inhibitors...
April 2, 2018: Neoplasia: An International Journal for Oncology Research
Juan Jin, Hehui Fang, Fang Yang, Wenfei Ji, Nan Guan, Zijia Sun, Yaqin Shi, Guohua Zhou, Xiaoxiang Guan
Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that poses a clinical challenge. Thus, new therapy strategies are urgently needed. The selective WEE1 inhibitor, AZD1775, has shown strong anti-proliferative effects on a variety of tumors. Here, we first demonstrate that inhibition of ATR by selective inhibitor AZD6738 can enhance AZD1775-caused growth inhibition in TNBC. Our results show that the enhanced cell death is attributed to repressed DNA damage repair and excessive replication stress, thereby causing increased DNA damage reflected by accumulation of the DNA double-strand-break marker γH2AX...
March 28, 2018: Neoplasia: An International Journal for Oncology Research
Luca Mologni, Mariantonia Costanza, Geeta Geeta Sharma, Michela Viltadi, Luca Massimino, Stefania Citterio, Stefania Purgante, Hima Raman, Alessandra Pirola, Massimo Zucchetti, Rocco Piazza, Carlo Gambacorti-Passerini
BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAFV600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current frontline therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactivation of MAPK signaling by several mechanisms has been shown to cause drug resistance and disease recurrence. In this work, we describe the co-occurrence of an in-frame deletion within an amplified BRAFV600E locus and a missense point mutation of the transcriptional repressor BCORL1 in vemurafenib-resistant A375 melanoma cells...
March 28, 2018: Neoplasia: An International Journal for Oncology Research
Junyang Li, Xiangjun Ji, Handong Wang
Emergent evidences revealed that long noncoding RNAs (lncRNAs) participate in neoplastic progression. HMMR is an oncogene that is highly expressed in glioblastoma (GBM) and supports GBM growth. Whether lncRNAs regulate HMMR in GBM remains unknown. Herein, we identify that an HMMR antisense lncRNA, HMMR-AS1, is hyperexpressed in GBM cell lines and stabilizes HMMR mRNA. Knockdown of HMMR-AS1 reduces HMMR expression; inhibits cell migration, invasion, and mesenchymal phenotypes; and suppresses GBM cell growth both in vitro and in vivo...
March 22, 2018: Neoplasia: An International Journal for Oncology Research
Simona Corso, Marilisa Cargnelutti, Stefania Durando, Silvia Menegon, Maria Apicella, Cristina Migliore, Tania Capeloa, Stefano Ughetto, Claudio Isella, Enzo Medico, Andrea Bertotti, Francesco Sassi, Ivana Sarotto, Laura Casorzo, Alberto Pisacane, Monica Mangioni, Antonino Sottile, Maurizio Degiuli, Uberto Fumagalli, Giovanni Sgroi, Sarah Molfino, Giovanni De Manzoni, Riccardo Rosati, Michele De Simone, Daniele Marrelli, Luca Saragoni, Stefano Rausei, Giovanni Pallabazzer, Franco Roviello, Paola Cassoni, Anna Sapino, Adam Bass, Silvia Giordano
Patient-Derived Xenografts (PDXs), entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer. More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV) positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas...
March 22, 2018: Neoplasia: An International Journal for Oncology Research
Raelene Endersby, Jacqueline Whitehouse, Hilary Hii, Sameer A Greenall, Terrance G Johns, Nicholas G Gottardo
Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors. The survival for patients with glioblastoma remains dismal. While the cure rate for medulloblastoma exceeds 70%, this figure has stagnated over the past few decades and survivors still contend with significant long-term debilitating side effects. The prognosis for pineoblastoma is age-dependent, with little chance of a cure for children younger than three years. More effective molecularly targeted strategies are urgently required to treat these cancers...
March 22, 2018: Neoplasia: An International Journal for Oncology Research
Paige N Dahlgren, Kanokwan Bishop, Shatovisha Dey, Brittney-Shea Herbert, Hiromi Tanaka
Excess telomere shortening has been observed in most cancer cells. The telomere quantitative polymerase chain reaction (qPCR) assay has become an important tool for epidemiological studies examining the effects of aging, stress, and other factors on the length of telomeres. Current telomere qPCR methods analyze the relative length of telomeres by amplifying telomere sequence products and normalizing with single-copy gene products. However, the current telomere qPCR does not always reflect absolute telomere length in cancer DNA...
March 21, 2018: Neoplasia: An International Journal for Oncology Research
Chun-Hua Wang, Shi-Xun Lu, Li-Li Liu, Yong Li, Xia Yang, Yang-Fan He, Shi-Lu Chen, Shao-Hang Cai, Hong Wang, Jing-Ping Yun
The ubiquitin-proteasome system is implicated in cell apoptosis that is frequently dysregulated in human cancers. POH1/rpn11/PSMD14, as a part of the 19S proteasomal subunit, contributes to the progression of malignancy, but its role in apoptosis remains unclear. Here, we showed that POH1 expression was increased and associated with poor outcomes in three independent cohorts of patients with hepatocellular carcinoma (HCC), esophageal cancer (EC), and colorectal cancer (CRC). The knockdown of POH1 significantly inhibited tumor cell proliferation and induced apoptosis mediated by the mitochondrial pathway in vitro...
March 21, 2018: Neoplasia: An International Journal for Oncology Research
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