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https://www.readbyqxmd.com/read/28647700/molecular-proteomic-characterization-of-a-pediatric-medulloblastoma-xenograft
#1
George T Tsangaris, Konstantinos Dimas, Angeliki Malamou, Angeliki Katsafadou, Chrissa Papathanasiou, Dimitrios J Stravopodis, Constantinos E Vorgias, Maria Gazouli, Athanasios K Anagnostopoulos
BACKGROUND/AIM: Medulloblastoma (MBL), an archetypal primitive neuroectodermal tumor of the cerebellum, is the most common pediatric central nervous system malignancy representing approximately 20% of all childhood brain tumors. Herein, we report on a new xenotransplantable tumor cell line, derived from a 6-year-old female patient with cerebellar medulloblastoma, and the completele proteome molecular characterization of subsequent tumors from MBL xenotrasplanted mice. MATERIALS AND METHODS: Tumors were grown in nude mice as subcutaneous xenografts (MBLX) composed of small round cells with hyperchromatic nuclei and scant cytoplasm...
July 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#2
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#3
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28645290/establishment-of-an-orthotopic-patient-derived-xenograft-mouse-model-using-uveal-melanoma-hepatic-metastasis
#4
Ken Kageyama, Masahiro Ohara, Kengo Saito, Shinji Ozaki, Mizue Terai, Michael J Mastrangelo, Paolo Fortina, Andrew E Aplin, Takami Sato
BACKGROUND: Metastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment...
June 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28643173/immunotherapy-and-targeted-therapy-for-small-cell-lung-cancer-there-is-hope
#5
REVIEW
Jonathan M Lehman, Mary E Gwin, Pierre P Massion
Small cell lung cancer (SCLC) is a devastating and aggressive neuroendocrine carcinoma of the lung. It accounts for ~15% of lung cancer mortality and has had no improvement in standard treatment options for nearly 30 years. However, there is now hope for change with new therapies and modalities of therapy. Immunotherapies and checkpoint inhibitors are entering clinical practice, selected targeted therapies show promise, and "smart bomb"-based drug/radioconjugates have led to good response in early clinical trials...
July 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28642484/mir-100-5p-inhibition-induces-apoptosis-in-dormant-prostate-cancer-cells-and-prevents-the-emergence-of-castration-resistant-prostate-cancer
#6
Noushin Nabavi, Nur Ridzwan Nur Saidy, Erik Venalainen, Anne Haegert, Abhijit Parolia, Hui Xue, Yuwei Wang, Rebecca Wu, Xin Dong, Colin Collins, Francesco Crea, Yuzhuo Wang
Carcinoma of the prostate is the most common cancer in men. Treatment of aggressive prostate cancer involves a regiment of radical prostectomy, radiation therapy, chemotherapy and hormonal therapy. Despite significant improvements in the last decade, the treatment of prostate cancer remains unsatisfactory, because a significant fraction of prostate cancers develop resistance to multiple treatments and become incurable. This prompts an urgent need to investigate the molecular mechanisms underlying the evolution of therapy-induced resistance of prostate cancer either in the form of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate cancer (NEPC)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637715/tyrosine-kinase-inhibitors-protect-the-salivary-gland-from-radiation-damage-by-inhibiting-activation-of-protein-kinase-c-%C3%AE
#7
Sten M Wie, Elizabeth Wellberg, Sana D Karam, Mary E Reyland
In patients undergoing irradiation therapy, injury to non-tumor tissues can result in debilitating, and sometimes permanent, side effects. We have defined Protein Kinase C-delta (PKCδ) as a regulator of DNA damage induced apoptosis and have shown that phosphorylation of PKCδ by c-Abl and c-Src activates its pro-apoptotic function.  Here we have explored the use of tyrosine kinase inhibitors (TKIs) of c-Src and c-Abl to block activation of PKCδ for radioprotection of the salivary gland.  Dasatinib, imatinib, and bosutinib all suppressed tyrosine phosphorylation of PKCδ and inhibited IR-induced apoptosis in vitro  To determine if TKIs can provide radioprotection of salivary gland function in vivo, mice were treated with TKIs and a single or fractionated doses of irradiation...
June 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28637687/inhibition-of-cdk4-6-by-palbociclib-significantly-extends-survival-in-medulloblastoma-patient-derived-xenograft-mouse-models
#8
Michelle L Cook Sangar, Laura A Genovesi, Madison W Nakamoto, Melissa J Davis, Sue E Knoblaugh, Pengxiang Ji, Amanda Millar, Brandon Wainwright, James M Olson
  <p>Bioinformatics analysis followed by in vivo studies in patient-derived xenograft models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly Group 3 MYC-amplified tumors which have the worst clinical prognosis.</p> <br />Experimental Design: <p>A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was used to identify potential novel therapeutic targets.  The top hit from this analysis was validated in vivo using patient-derived xenograft models of medulloblastoma implanted subcutaneously in the flank and orthotopically in the cerebellum of mice...
June 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28635650/the-application-of-heptamethine-cyanine-dye-dz-1-and-indocyanine-green-for-imaging-and-targeting-in-xenograft-models-of-hepatocellular-carcinoma
#9
Caiqin Zhang, Yong Zhao, He Zhang, Xue Chen, Ningning Zhao, Dengxu Tan, Hai Zhang, Changhong Shi
Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28633632/antagonizing-mir-455-3p-inhibits-chemoresistance-and-aggressiveness-in-esophageal-squamous-cell-carcinoma
#10
Aibin Liu, Jinrong Zhu, Geyan Wu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Lili Jiang, Jueheng Wu, Mengfeng Li, Libing Song, Jun Li
BACKGROUND: The plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways. METHODS: A chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness...
June 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28629523/significance-of-erythropoietin-receptor-antagonist-emp9-in-cancers
#11
Yoshiko Yasuda, Mitsugu Fujita
We have clarified that cancer cells express their own erythropoietin (Epo) and its receptor (EpoR) mRNA levels, and the respective proteins, which are under the control of Epo-EpoR signaling. Then we explored to inhibit the Epo-EpoR signaling with an EpoR antagonist Epo mimetic peptide 9 (EMP9) that is a derivative of an Epo-mimicking peptide EMP1. In the study of the cancer cell lines in vitro, rhEpo accelerated the cancer cell growth, whereas the EMP9 inhibited the cell growth along with the inhibition of STAT5 tyrosine phosphorylation...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28625978/the-alkylating-chemotherapeutic-temozolomide-induces-metabolic-stress-in-idh1-mutant-cancers-and-potentiates-nad-depletion-mediated-cytotoxicity
#12
Kensuke Tateishi, Fumi Higuchi, Julie Miller, Mara V A Koerner, Nina Lelic, Ganesh M Shankar, Shota Tanaka, David E Fisher, Tracy Batchelor, A John Iafrate, Hiroaki Wakimoto, Andrew S Chi, Daniel P Cahill
IDH1-mutant gliomas are dependent upon the canonical coenzyme nicotinamide adenine dinucleotide (NAD+) for survival. It is known that Poly(ADP-ribose) polymerase (PARP) activation consumes NAD+ during base excision repair (BER) of chemotherapy-induced DNA damage. We therefore hypothesized that a strategy combining NAD+ biosynthesis inhibitors with the alkylating chemotherapeutic agent temozolomide (TMZ) could potentiate NAD+ depletion-mediated cytotoxicity in mutant IDH1 cancer cells. To investigate the impact of TMZ on NAD+ metabolism, patient-derived xenografts and engineered mutant IDH1-expressing cell lines were exposed to TMZ, in vitro and in vivo, both alone and in combination with nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which block NAD+ biosynthesis...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28625826/drug-discovery-and-therapeutic-delivery-for-the-treatment-of-b-and-t-cell-tumors
#13
Regan Stephenson, Ankur Singh
Hematological malignancies manifest as lymphoma, leukemia, and myeloma, and remain a burden on society. From initial therapy to endless relapse-related treatment, societal burden is felt not only in the context of healthcare cost, but also in the compromised quality of life of patients. Long-term therapeutic strategies have become the standard in keeping hematological malignancies at bay as these cancers develop resistance to each round of therapy with time. As a result, there is a continual need for the development of new drugs to combat resistant disease in order to prolong patient life, if not to produce a cure...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28625518/histone-chaperone-asf1a-predicts-poor-outcomes-for-patients-with-gastrointestinal-cancer-and-drives-cancer-progression-by-stimulating-transcription-of-%C3%AE-catenin-target-genes
#14
Xiuming Liang, Xiaotian Yuan, Jingya Yu, Yujiao Wu, Kailin Li, Chao Sun, Shuyan Li, Li Shen, Feng Kong, Jihui Jia, Magnus Björkholm, Dawei Xu
Epigenetic mechanisms play a key role in gastrointestinal cancer (GIC) development and progression, and most studies have been focused on aberrant DNA methylation and histone modifying enzymes. However, the histone H3-H4 chaperone ASF1A is an important factor regulating chromatin assembling and gene transcription, while it is currently unclear whether ASF1A is involved in cancer pathogenesis. The present study is thus designed to address this issue. Here we showed that ASF1A expression was widespread in GIC-derived cell lines and up-regulated in primary GIC...
June 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28625393/establishment-and-characterization-of-uterine-sarcoma-and-carcinosarcoma-patient-derived-xenograft-models
#15
Tine Cuppens, Jeroen Depreeuw, Daniela Annibali, Debby Thomas, Els Hermans, Ellen Gommé, Xuan Bich Trinh, David Debruyne, Philippe Moerman, Diether Lambrechts, Frédéric Amant
OBJECTIVE: Uterine sarcomas (US) and carcinosarcomas (CS) are rare, aggressive cancers. The lack of reliable preclinical models hampers the search for new treatment strategies and predictive biomarkers. To this end, we established and characterized US and CS patient-derived xenograft (PDX) models. METHODS: Tumor fragments of US and CS were subcutaneously implanted into immunocompromised mice. Engrafted xenograft and original tumors were compared by means of histology, immunohistochemistry, whole-genome low-coverage sequencing for copy number variations, and RNA sequencing...
June 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28624783/malignant-pericytes-expressing-gt198-give-rise-to-tumor-cells-through-angiogenesis
#16
Liyong Zhang, Yan Wang, Mohammad H Rashid, Min Liu, Kartik Angara, Nahid F Mivechi, Nita J Maihle, Ali S Arbab, Lan Ko
Angiogenesis promotes tumor development. Understanding the crucial factors regulating tumor angiogenesis may reveal new therapeutic targets. Human GT198 (PSMC3IP or Hop2) is an oncoprotein encoded by a DNA repair gene that is overexpressed in tumor stromal vasculature to stimulate the expression of angiogenic factors. Here we show that pericytes expressing GT198 give rise to tumor cells through angiogenesis. GT198+ pericytes and perivascular cells are commonly present in the stromal compartment of various human solid tumors and rodent xenograft tumor models...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623128/targeting-pi3k-akt-mtor-by-ly3023414-inhibits-human-skin-squamous-cell-carcinoma-cell-growth-in-vitro-and-in-vivo
#17
Ying Zou, Minggai Ge, Xuemin Wang
Abnormal activation of PI3K-AKT-mTOR signaling is detected in human skin squamous cell carcinoma (SCC). LY3023414 is a novel, potent, and orally bio-available PI3K-AKT-mTOR inhibitor. Its activity against human skin SCC cells was tested. We demonstrated that LY3023414 was cytotoxic when added to established (A431 line) and primary (patient-derived) human skin SCC cells. LY3023414 induced G0/1-S arrest and inhibited proliferation of skin SCC cells. Moreover, LY3023414 induced activation of caspase-3/-9 and apoptosis in skin SCC cells...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28622397/looking-for-the-most-suitable-orthotopic-retinoblastoma-mouse-model-in-order-to-characterize-the-tumoral-development
#18
Stéphanie Lemaitre, Florent Poyer, Sergio Marco, Paul Fréneaux, François Doz, Isabelle Aerts, Laurence Desjardins, Nathalie Cassoux, Carole D Thomas
Purpose: Because retinoblastoma therapies have many adverse effects, new approaches must be developed and evaluated on animal models. We describe orthotopic xenograft models of retinoblastoma using different strains of mice, suitable for this purpose. Methods: Human retinoblastoma tumors were established on immunodeficient mice by subcutaneous engraftment of tumors from enucleated eyes. The orthotopic model was obtained by subretinal injections of suspension cells into the right eye of immunodeficient (Swiss-nude, severe combined immunodeficiency [SCID]) and immunocompetent mice (C57BL/6N, B6Albino)...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28622299/a-circular-rna-promotes-tumorigenesis-by-inducing-c-myc-nuclear-translocation
#19
Qi Yang, William W Du, Nan Wu, Weining Yang, Faryal Mehwish Awan, Ling Fang, Jian Ma, Xiangmin Li, Yan Zeng, Zhenguo Yang, Jun Dong, Azam Khorshidi, Burton B Yang
Circular RNAs (circRNAs) are a subclass of noncoding RNAs widely expressed in mammalian cells. We report here the tumorigenic capacity of a circRNA derived from angiomotin-like1 (circ-Amotl1). Circ-Amotl1 is highly expressed in patient tumor samples and cancer cell lines. Single-cell inoculations using circ-Amotl1-transfected tumor cells showed a 30-fold increase in proliferative capacity relative to control. Agarose colony-formation assays similarly revealed a 142-fold increase. Tumor-take rate in nude mouse xenografts using 6-day (219 cells) and 3-day (9 cells) colonies were 100%, suggesting tumor-forming potential of every cell...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28622068/salmonella-typhimurium-a1-r-targeting-of-a-chemotherapy-resistant-braf-v600e-melanoma-in-a-patient-derived-orthotopic-xenograft-pdox-model-is-enhanced-in-combination-with-either-vemurafenib-temozlomide
#20
Kei Kawaguchi, Kentaro Igarashi, Bartosz Chmielowski, Takashi Murakami, Tasuku Kiyuna, Ming Zhao, Yong Zhang, Scott D Nelson, Tara A Russell, Sarah M Dry, Arun S Singh, Yunfeng Li, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
A metastatic melanoma obtained from the right chest wall of a patient was previously established orthotopically in the right chest wall of nude mice as a patient-derived orthotopic xenograft (PDOX) model. We previously showed that the combination of tumor targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) and chemotherapy was highly effective against the melanoma PDOX. In the present study, we investigated the mechanism of the high efficacy of this combination. Two weeks after implantation, 40 PDOX mouse models were randomized into four groups of 10 mice each: untreated control (n = 10); treated with S...
June 16, 2017: Cell Cycle
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