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Neoplasia: An International Journal for Oncology Research

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https://www.readbyqxmd.com/read/29245123/the-gdnf-family-a-role-in-cancer
#1
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/29227909/navigating-the-no-man-s-land-of-tki-failed-egfr-mutated-non-small-cell-lung-cancer-nsclc-a-review
#2
REVIEW
Bryan Oronsky, Patrick Ma, Tony R Reid, Pedro Cabrales, Michelle Lybeck, Arnold Oronsky, Neil Oronsky, Corey A Carter
As the leading cause of cancer-related mortality, lung cancer is a worldwide health issue that is overwhelmingly caused by smoking. However, a substantial minority (~25%) of patients with non-small cell lung cancer (NSCLC) has never smoked. In these patients, activating mutations of the epidermal growth factor receptor (EGFR) are more likely, which render their tumors susceptible for a finite period to treatment with EGFR tyrosine kinase inhibitors (TKIs) and confer a better prognosis than EGFR wild-type NSCLC...
December 8, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29216597/role-of-dopamine-receptors-in-the-anticancer-activity-of-onc201
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/29190493/bigh3-promotes-osteolytic-lesions-in-renal-cell-carcinoma-bone-metastasis-by-inhibiting-osteoblast-differentiation
#7
Tianhong Pan, Song-Chang Lin, Kai-Jie Yu, Guoyu Yu, Jian H Song, Valerae O Lewis, Justin E Bird, Bryan Moon, Patrick P Lin, Nizar M Tannir, Eric Jonasch, Christopher G Wood, Gary E Gallick, Li-Yuan Yu-Lee, Sue-Hwa Lin, Robert L Satcher
BACKGROUND: Bone metastasis is common in renal cell carcinoma (RCC), and the lesions are mainly osteolytic. The mechanism of bone destruction in RCC bone metastasis is unknown. METHODS: We used a direct intrafemur injection of mice with bone-derived 786-O RCC cells (Bo-786) as an in vivo model to study if inhibition of osteoblast differentiation is involved in osteolytic bone lesions in RCC bone metastasis. RESULTS: We showed that bone-derived Bo-786 cells induced osteolytic bone lesions in the femur of mice...
November 27, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29190492/determinants-for-effective-alecsat-immunotherapy-treatment-on-autologous-patient-derived-glioblastoma-stem-cells
#8
Anna Wenger, Katja Werlenius, Alexander Hallner, Fredrik Bergh Thorén, Dan Farahmand, Magnus Tisell, Anja Smits, Bertil Rydenhag, Asgeir S Jakola, Helena Carén
Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of less than 15 months, emphasizing the need for better treatments. Immunotherapy as a treatment for improving or aiding the patient's own immune defense to target the tumor has been suggested for GBM. A randomized clinical trial of adoptive cell transfer using ALECSAT (Autologous Lymphoid Effector Cells Specific Against Tumor Cells) is currently ongoing in Sweden. Here we performed a paired pre-clinical study to investigate the composition and in vitro effect of ALECSAT and identify determinants for the effect using autologous GBM-derived cancer stem cells (CSC), immunocytochemistry and flow cytometry...
November 27, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29175021/pten-dependent-stabilization-of-mtss1-inhibits-metastatic-phenotype-in-pancreatic-ductal-adenocarcinoma
#9
Ann E Zeleniak, Wei Huang, Melissa L Fishel, Reginald Hill
Pancreatic ductal adenocarcinoma (PDAC) presents at metastatic stage in over 50% of patients. With a survival rate of just 2.7% for patients presenting with distant disease, it is imperative to uncover novel mechanisms capable of suppressing metastasis in PDAC. Previously, we reported that the loss of metastasis suppressor protein 1 (MTSS1) in PDAC cells results in significant increase in cellular migration and invasion. Conversely, we also found that overexpressing MTSS1 in metastatic PDAC cell lines corresponds with not only decreased metastatic phenotype, but also greater overall survival...
November 22, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29172076/gemtuzumab-ozogamicin-go-inclusion-to-induction-chemotherapy-eliminates-leukemic-initiating-cells-and-significantly-improves-survival-in-mouse-models-of-acute-myeloid-leukemia
#10
Cathy C Zhang, Zhengming Yan, Bernadette Pascual, Amy Jackson-Fisher, Donghui Stephen Huang, Qing Zong, Mark Elliott, Conglin Fan, Nanni Huser, Joseph Lee, Matthew Sung, Puja Sapra
Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML). Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs)...
November 21, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29149667/tumor-acidosis-and-hypoxia-differently-modulate-the-inflammatory-program-measurements-in-vitro-and-in-vivo
#11
Anne Riemann, Sarah Reime, Oliver Thews
Inflammatory mediators produced by the tumor cells are of importance for immune response but also for malignant progression. The aim of the study was to analyze the expression of monocyte chemoattractant protein-1, interleukin-6 (IL-6), tumor necrosis factor-α, inducible isoform of nitric oxide synthase (iNOS), cyclooxygenase-2, and osteopontin in vitro in two different tumor cell lines under hypoxia (pO2≈1.5 mmHg) and/or acidosis (pH=6.6) for up to 24 hours since hypoxia and acidosis are common characteristics of solid tumors...
November 14, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29144989/cysteine-dioxygenase-1-mediates-erastin-induced-ferroptosis-in-human-gastric-cancer-cells
#12
Shihui Hao, Jiang Yu, Wanming He, Qiong Huang, Yang Zhao, Bishan Liang, Shuyi Zhang, Zhaowei Wen, Shumin Dong, Jinjun Rao, Wangjun Liao, Min Shi
BACKGROUND: Ferroptosis is a recently discovered form of iron-dependent nonapoptotic cell death. It is characterized by loss of the activity of the lipid repair enzyme, glutathione peroxidase 4 (GPX4), and accumulation of lethal reactive lipid oxygen species. However, we still know relatively little about ferroptosis and its molecular mechanism in gastric cancer (GC) cells. Here, we demonstrate that erastin, a classic inducer of ferroptosis, induces this form of cell death in GC cells and that cysteine dioxygenase 1 (CDO1) plays an important role in this process...
November 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29136529/yap-dependent-axl-overexpression-mediates-resistance-to-egfr-inhibitors-in-nsclc
#13
Elena Ghiso, Cristina Migliore, Vito Ciciriello, Elena Morando, Annalisa Petrelli, Simona Corso, Emmanuele De Luca, Gaia Gatti, Marco Volante, Silvia Giordano
The Yes-associated protein (YAP) is a transcriptional co-activator upregulating genes that promote cell growth and inhibit apoptosis. The main dysregulation of the Hippo pathway in tumors is due to YAP overexpression, promoting epithelial to mesenchymal transition, cell transformation, and increased metastatic ability. Moreover, it has recently been shown that YAP plays a role in sustaining resistance to targeted therapies as well. In our work, we evaluated the role of YAP in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer...
November 11, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29121598/novel-c-terminal-heat-shock-protein-90-inhibitors-ku711-and-ku757-are-effective-in-targeting-head-and-neck-squamous-cell-carcinoma-cancer-stem-cells
#14
C Subramanian, K J Kovatch, M W Sim, G Wang, M E Prince, T E Carey, R Davis, B S J Blagg, M S Cohen
Advanced head and neck squamous cell carcinoma (HNSCC) remains a therapeutic challenge due to the development of therapy resistance. Several studies have implicated the development of cancer stem cells as a possible mechanism for therapy resistance in HNSCC. Heat shock protein 90's (Hsp90's) molecular chaperone function is implicated in pathways of resistance in HNSCC. Therefore, in the present study, we investigated the efficacy of novel C-terminal Hsp90 inhibitors (KU711 and KU757) in targeting HNSCC cancer stem cells (CSCs)...
November 6, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29091800/nothing-but-net-a-review-of-neuroendocrine-tumors-and-carcinomas
#15
REVIEW
Bryan Oronsky, Patrick C Ma, Daniel Morgensztern, Corey A Carter
This review covers the diverse topic of neuroendocrine neoplasms (NENs), a relatively rare and heterogeneous tumor type, comprising ~2% of all malignancies, with a prevalence of <200,000 in the United States, which makes it an orphan disease (Basu et al., 2010).(1) For functional purposes, NENs are divided into two groups on the basis of clinical behavior, histology, and proliferation rate: well differentiated (low grade to intermediate grade) neuroendocrine tumors and poorly differentiated (high grade) neuroendocrine carcinoma (Bosman et al...
October 29, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29091799/molecular-classification-substitutes-for-the-prognostic-variables-stage-age-and-mycn-status-in-neuroblastoma-risk-assessment
#16
Carolina Rosswog, Rene Schmidt, André Oberthuer, Dilafruz Juraeva, Benedikt Brors, Anne Engesser, Yvonne Kahlert, Ruth Volland, Christoph Bartenhagen, Thorsten Simon, Frank Berthold, Barbara Hero, Andreas Faldum, Matthias Fischer
BACKGROUND: Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. METHODS: A cohort of 695 neuroblastoma patients was divided into a discovery set (n=75) for multigene predictor generation, a training set (n=411) for risk score development, and a validation set (n=209)...
October 26, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29069627/src-sumoylation-inhibits-tumor-growth-via-decreasing-fak-y925-phosphorylation
#17
Jing Wang, Rong Deng, Nan Cui, Hailong Zhang, Tianqi Liu, Jinzhuo Dou, Xian Zhao, Ran Chen, Yanli Wang, Jianxiu Yu, Jian Huang
Src, a non-receptor tyrosine kinase protein, plays a critical role in cell proliferation and tumorigenesis. SUMOylation, a reversible ubiquitination-like post-translational modification, is vital for tumor progression. Here, we report that the Src protein can be SUMOylated at lysine 318 both in vitro and in vivo. Hypoxia can induce a decrease of Src SUMOylation along with an increase of Y419 phosphorylation, a phosphorylation event required for Src activation. On the other hand, treatment with hydrogen peroxide can enhance Src SUMOylation...
October 22, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29091798/dna-barcoding-reveals-habitual-clonal-dominance-of-myeloma-plasma-cells-in-the-bone-marrow-microenvironment
#18
Duncan R Hewett, Kate Vandyke, David M Lawrence, Natasha Friend, Jacqueline E Noll, Joel M Geoghegan, Peter I Croucher, Andrew C W Zannettino
Multiple myeloma (MM) is a hematological malignancy resulting from the uncontrolled proliferation of antibody-producing plasma cells in the bone marrow. At diagnosis, independent plasma cell tumors are found throughout the skeleton. The recirculation of mutant plasma cells from the initial lesion and their recolonization of distant marrow sites are thought to occur by a process similar to solid tumor metastasis. However, the efficiency of this bone marrow homing process and the proportion of disseminated cells that actively divide and contribute to new tumor growth in MM are both unknown...
December 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28987998/monitoring-and-targeting-anti-vegf-induced-hypoxia-within-the-viable-tumor-by-19-f-mri-and-multispectral-analysis
#19
Yunzhou Shi, Jason Oeh, Anna Hitz, Maj Hedehus, Jeffrey Eastham-Anderson, Franklin V Peale, Patricia Hamilton, Thomas O'Brien, Deepak Sampath, Richard A D Carano
The effect of anti-angiogenic agents on tumor oxygenation has been in question for a number of years, where both increases and decreases in tumor pO2 have been observed. This dichotomy in results may be explained by the role of vessel normalization in the response of tumors to anti-angiogenic therapy, where anti-angiogenic therapies may initially improve both the structure and the function of tumor vessels, but more sustained or potent anti-angiogenic treatments will produce an anti-vascular response, producing a more hypoxic environment...
November 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28968550/esophageal-adenocarcinoma-derived-extracellular-vesicle-micrornas-induce-a-neoplastic-phenotype-in-gastric-organoids
#20
Xiquan Ke, Rong Yan, Zhenguo Sun, Yulan Cheng, Amy Meltzer, Nonghua Lu, Xu Shu, Zhe Wang, Binbin Huang, Xi Liu, Zhixiong Wang, Jee Hoon Song, Christopher K Ng, Sariat Ibrahim, John M Abraham, Eun Ji Shin, Shuixiang He, Stephen J Meltzer
There have been no reports describing the effects of cancer cell-derived extracellular vesicles (EVs) on three-dimensional organoids. In this study, we delineated the proneoplastic effects of esophageal adenocarcinoma (EAC)-derived EVs on gastric organoids (gastroids) and elucidated molecular mechanisms underlying these effects. EVs were identified using PKH-67 staining. Morphologic changes, Ki-67 immunochemistry, cell viability, growth rates, and expression levels of miR-25 and miR-210, as well as of their target mRNAs, were determined in gastroids co-cultured with EAC-derived extracellular vesicles (c-EVs)...
November 2017: Neoplasia: An International Journal for Oncology Research
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