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Jianwen Long, Qiqige Menggen, Qimige Wuren, Quan Shi, Xianming Pi
BACKGROUND Malignant melanoma is a class of malignant tumors derived from melanocytes. lncRNAs have been considered as pro-/anti-tumor factors in progression of cancers. The function of lncRNA TUG1 on growth of melanoma was investigated in this study. MATERIAL AND METHODS The TUG1 and miR-129-5p expression were examined via qRT-PCR. The protein expression was investigated by Western blotting assay. Luciferase reporter assay was used to assess if lncRNA TUG1 can bind to miR-129-5p and if miR-129-5p can target AEG1 mRNA...
March 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Wei Sun, Ju-Dong Luo, Hua Jiang, Dayue Darrel Duan
Tumor cells produce and secrete more nucleic acids, proteins and lipids than normal cells. These molecules are transported in the blood or around the cells in membrane-encapsulated exosomes. Tumor-derived or tumor-associated exosomes (usually 30-100 nm in diameter) contain abundant biological contents resembling those of the parent cells along with signaling messengers for intercellular communication involved in the pathogenesis, development, progression, and metastasis of cancer. As these exosomes can be detected and isolated from various body fluids, they have become attractive new biomarkers for the diagnosis and prognosis of cancer...
March 15, 2018: Acta Pharmacologica Sinica
Fernando Revert, Francisco Revert-Ros, Raül Blasco, Aida Artigot, Ernesto López-Pascual, Roberto Gozalbo-Rovira, Ignacio Ventura, Elain Gutiérrez-Carbonell, Nuria Roda, Daniel Ruíz-Sanchis, Jerónimo Forteza, Javier Alcácer, Alejandra Pérez-Sastre, Ana Díaz, Enrique Pérez-Payá, Juan F Sanz-Cervera, Juan Saus
Goodpasture antigen-binding protein (GPBP) is an exportable1 Ser/Thr kinase that induces collagen IV expansion and has been associated with chemoresistance following epithelial-to-mesenchymal transition (EMT). Here we demonstrate that cancer EMT phenotypes secrete GPBP (mesenchymal GPBP) which displays a predominant multimeric oligomerization and directs the formation of previously unrecognized mesh collagen IV networks (mesenchymal collagen IV). Yeast two-hybrid (YTH) system was used to identify a260 SHCIE264 motif critical for multimeric GPBP assembly which then facilitated design of a series of potential peptidomimetics...
February 16, 2018: Oncotarget
Tulika Mitra, Parash Prasad, Pritha Mukherjee, Susri Ray Chaudhuri, Urmi Chatterji, Sib S Roy
Ovarian cancer (OC) is the fourth most common gynecological malignancy due to its highly aggressive, recurrent, and drug-resistant nature. The last two features are rendered by the presence of cancer stem cells (CSCs). Factors like TGFβ1 and their downstream signaling pathways are upregulated in most cancers and are known to induce EMT and stemness, but the exact mechanisms underlying the process remain unelucidated. In our study, TGFβ1 induced enhanced stem-like properties like high expression of the pluripotent markers SOX2, OCT4a, and NANOG, along with CD44, and CD117 in the OC cells...
March 14, 2018: Journal of Cellular Biochemistry
Dong-Wook Kim, Keun-Cheol Kim, Kee-Beom Kim, Colin T Dunn, Kwon-Sik Park
The discovery of recurrent alterations in genes encoding transcription regulators and chromatin modifiers is one of the most important recent developments in the study of the small cell lung cancer (SCLC) genome. With advances in models and analytical methods, the field of SCLC biology has seen remarkable progress in understanding the deregulated transcription networks linked to the tumor development and malignant progression. This review will discuss recent discoveries on the roles of RB and P53 family of tumor suppressors and MYC family of oncogenes in tumor initiation and development...
February 2018: Translational Lung Cancer Research
Jin-Cheng Huang, Zhi-Fei Cui, Shui-Mu Chen, Lian-Jun Yang, Hong-Kai Lian, Bin Liu, Zhi-Hai Su, Jin-Shi Liu, Min Wang, Zheng-Bo Hu, Jia-Yao Ouyang, Qing-Chu Li, Hai Lu
Osteosarcoma(OS) remains a major health concern in childhood and adolescence, although cisplatin is one of the gold standard chemotherapeutic drugs in the treatment of OS, chemoresistant to cisplatin is common. Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy regulates chemosensitivity incancer cells. In this study, we hypothesized that NVP-BEZ235, a dual inhibitor of PI3K/mTOR, could synergize cisplatin sensitivity in OS. In vitro , NVP-BEZ235 plus cisplatinexerted a synergistic effect on cell proliferation inhibition and apoptosis induction...
February 13, 2018: Oncotarget
Aleš Hnízda, Milan Fábry, Takaya Moriyama, Petr Pachl, Michael Kugler, Vítězslav Brinsa, David B Ascher, William L Carroll, Petr Novák, Markéta Žaliová, Jan Trka, Pavlína Řezáčová, Jun J Yang, Václav Veverka
Activating mutations in NT5C2, a gene encoding cytosolic purine 5'-nucleotidase (cN-II), confer chemoresistance in relapsed acute lymphoblastic leukemia. Here we show that all mutants became independent of allosteric effects of ATP and thus constitutively active. Structural mapping of mutations described in patients demonstrates that 90% of leukemia-specific allelles directly affect two regulatory hotspots within the cN-II molecule-the helix A region: residues 355-365, and the intersubunit interface: helix B (232-242) and flexible interhelical loop L (400-418)...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Song Xu, Kim De Veirman, Ann De Becker, Karin Vanderkerken, Ivan Van Riet
Multiple myeloma (MM) is a malignant plasma cell (PC) disorder, characterized by a complex interactive network of tumour cells and the bone marrow (BM) stromal microenvironment, contributing to MM cell survival, proliferation and chemoresistance. Mesenchymal stem cells (MSCs) represent the predominant stem cell population of the bone marrow stroma, capable of differentiating into multiple cell lineages, including fibroblasts, adipocytes, chondrocytes and osteoblasts. MSCs can migrate towards primary tumours and metastatic sites, implying that these cells might modulate tumour growth and metastasis...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Ling Ma, Qiao Cheng
Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid malignancies and resistant to chemotherapy. Little is known on the underlying mechanisms of ATC resistance to chemotherapy. In our work, we identified that 6-phosphogluconate dehydrogenase (6PGD) is critically involved in the development of ATC resistance to doxorubicin. We found that 6PGD mRNA, protein and enzyme activity levels are significantly upregulated in ATC cells during the prolonged exposure to doxorubicin in a time-dependent manner...
March 10, 2018: Biochemical and Biophysical Research Communications
M Fiorentzis, H Kalirai, P Katopodis, B Seitz, A Viestenz, S E Coupland
Electrochemotherapy (ECT) enhances responsiveness to cytotoxic drugs in numerous cell lines in vitro. Clinically ECT is widely applied for skin tumor ablation and has shown efficacy in treating non-resectable colorectal liver metastases. There is limited experience of ECT for ocular tumor therapy. We investigated the cytotoxic effect of bleomycin and cisplatin in combination with electroporation on chemoresistant human uveal melanoma (UM) cell lines in vitro. Four UM cell lines (Mel 270, 92-1, OMM-1, OMM-2...
2018: Neoplasma
Shuai Liu, Xingzhu Ju, Zheng Feng, Hao Wen, Junyan Xu, Xiaojun Chen, Xiaohua Wu
OBJECTIVE: Our study aimed to explore the prognostic influence of tumor-to-background ratios (TBRs) of the maximum standardized uptake value (SUVmax) in advanced high-grade serous ovarian cancer (HGSC) patients. PATIENTS AND METHODS: We retrospectively investigated 51 advanced HGSC patients who underwent PET/CT before primary surgery at our hospital between January 2010 and June 2015. None of these patients received neoadjuvant chemotherapy. SUVmax of ovarian tumor (SUVmax-P) and background (SUVmax-B) were measured using a PET/CT workstation...
April 2018: Nuclear Medicine Communications
Shinwan Kany, Mathias Woschek, Niels Kneip, Ramona Sturm, Miriam Kalbitz, Marc Hanschen, Borna Relja
Osteosarcoma is the leading primary bone cancer in young adults and exhibits high chemoresistance rates. Therefore, characterization of both alternative treatment options and the underlying mechanisms is essential. Simvastatin, a cholesterol-lowering drug, has among its pleiotropic effects anticancer potential. Characterizing this potential and the underlying mechanisms in osteosarcoma is the subject of the present study. Human osteosarcoma cells (SaOS-2 and U2OS) were treated with simvastatin (4-66 µM) for 48 or 72 h...
April 2018: International Journal of Oncology
Jing Liu, Jia-Xin Shen, De He, Guo-Jun Zhang
PURPOSE: Dysregulation of microRNAs (miRNAs) are not only involved in the formation of malignant tumors but also in the processes of differentiation and aggressiveness. However, current methods for detecting miRNA expression have major disadvantages, such as being invasive and non-reproducible. The epithelial-mesenchymal transition (EMT) has been implicated as a pivotal event in the metastasis, stemness, and chemoresistance of malignant tumors. PROCEDURES: In our study, we constructed a new reporter gene, Luc2/tdT_miR200c_3TS, to examine the in vitro and in vivo expression of miR-200c, an EMT-associated miRNA...
March 12, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Xóchitl Zambrano-Estrada, Brianda Landaverde-Quiroz, Andrés A Dueñas-Bocanegra, Marco A De Paz-Campos, Gerardo Hernández-Alberto, Benjamín Solorio-Perusquia, Manuel Trejo-Mandujano, Laura Pérez-Guerrero, Evangelina Delgado-González, Brenda Anguiano, Carmen Aceves
BACKGROUND: Mammary cancer has a high incidence in canines and is an excellent model of spontaneous carcinogenesis. Molecular iodine (I2 ) exerts antineoplastic effects on different cancer cells activating re-differentiation pathways. In co-administration with anthracyclines, I2 impairs chemoresistance installation and prevents the severity of side effects generated by these antineoplastic drugs. This study is a random and double-blind protocol that analyzes the impact of I2 (10 mg/day) in two administration schemes of Doxorubicin (DOX; 30 mg/m2) in 27 canine patients with cancer of the mammary gland...
March 12, 2018: BMC Veterinary Research
Jun Won Park, Min-Sik Kim, Dominic C Voon, Su-Jin Kim, Jingi Bae, Dong-Gi Mun, Seung-Ik Ko, Hark Kyun Kim, Sang-Won Lee, Dae-Yong Kim
The molecular mechanisms underlying the pathogenesis of diffuse-type gastric cancer (DGC) have not been adequately explored due to a scarcity of appropriate animal models. A recently developed tool well suited for this line of investigation is the Pdx-1-Cre;Cdh1F/+ ;Trp53F/F ;Smad4F/F (pChe PS) mouse model that spontaneously develops metastatic DGC showing nearly complete E-cadherin loss. Here, we performed a proteogenomic analysis to uncover the molecular changes induced by the concurrent targeting of E-cadherin, p53, and Smad4 loss...
March 12, 2018: Molecular Carcinogenesis
Kathrin Oehl, Jelena Kresoja-Rakic, Isabelle Opitz, Bart Vrugt, Walter Weder, Rolf Stahel, Peter Wild, Emanuela Felley-Bosco
Experimental models closely representing in vivo conditions allow investigating mechanisms of resistance. Our aims were to establish a live-cell biobank of malignant pleural mesothelioma (MPM) samples and to obtain proof of principle that primary culture chemoresistant models, mimicking tumor progression observed in patients, can be obtained in vitro , providing a useful tool to investigate underlying mechanisms. Primary mesothelioma cultures were established from 235 samples between 2007 and 2014. Of two MPM patients, primary cultures obtained at different time points: at initial diagnosis, after neoadjuvant treatment at surgery and/or after tumor recurrence, were deeply investigated...
2018: Frontiers in Oncology
Jun Li, Hui-Chen Hsu, John D Mountz, John G Allen
Fucosylation is a biological process broadly observed in vertebrates, invertebrates, plants, bacteria, and fungi. Fucose moieties on cell-surface glycans are increasingly recognized as critical to many cell-cell interaction and signaling processes. One of the characteristic roles of fucose is its regulation of selectin-dependent leukocyte adhesion that has been well studied over the last two decades. Recent studies of fucose in immune cell development and function regulation have significantly expanded the contemporary understanding of fucosylation...
February 24, 2018: Cell Chemical Biology
Xiaojie Deng, Zhen Liu, Xiong Liu, Qiaofen Fu, Tongyuan Deng, Juan Lu, Yiyi Liu, Zixi Liang, Qingping Jiang, Chao Cheng, Weiyi Fang
This study aimed to identify mechanisms by which microRNA 296-3p (miR-296-3p) functions as a tumor suppressor to restrain nasopharyngeal carcinoma (NPC) cell growth, metastasis, and chemoresistance. Mechanistic studies revealed that miR-296-3p negatively regulated by nicotine directly targets the oncogenic protein mitogen-activated protein kinase-activated protein kinase-2 (Mapkapk2) (MK2). Suppression of MK2 downregulated Ras/Braf/Erk/Mek/c-Myc and phosphoinositide-3-kinase (PI3K)/Akt/c-Myc signaling and promoted cytoplasmic translocation of c-Myc, which activated miR-296-3p expression by a feedback loop...
February 3, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Hongsheng Wang, Wei Sun, Mengxiong Sun, Zeze Fu, Chenghao Zhou, Chongren Wang, Dongqing Zuo, Zifei Zhou, Gangyang Wang, Tao Zhang, Jing Xu, Jian Chen, Zhuoying Wang, Fei Yin, Zhenfeng Duan, Francis J Hornicek, Zhengdong Cai, Yingqi Hua
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. The abilities of chemotherapy resistance are major roadblock in the successful treatment of OS. The clarification of mechanism regarding cell survival during OS chemotherapy are important. Here, we examined HER4 expression by immunohistochemistry in a large series of OS tissues, and found HER4 expression correlated with tumor characteristics and patient survival rates. HER4 knockdown by shRNA inhibited OS cell growth and tumorigenesis, and induced cell senescence and apoptosis in vitro and in vivo...
March 7, 2018: Biochimica et Biophysica Acta
Sarah Bertoli, Muriel Picard, Emilie Bérard, Emmanuel Griessinger, Clément Larrue, Pierre-Luc Mouchel, François Vergez, Suzanne Tavitian, Edwige Yon, Jean Ruiz, Eric Delabesse, Isabelle Luquet, Laetitia Karine Linares, Estelle Saland, Martin Carroll, Gwenn Danet-Desnoyers, Audrey Sarry, Françoise Huguet, Jean-Emmanuel Sarry, Christian Récher
Patients with acute myeloid leukemia and a high white blood cell count are at increased risk for early death and relapse. Because mediators of inflammation contribute to leukostasis and chemoresistance, dexamethasone added to chemotherapy could improve outcomes. This retrospective study evaluated the impact of adding or not adding dexamethasone to chemotherapy in a cohort of 160 patients with at least 50x109 white blood cells. In silico studies, primary samples, leukemic cell lines, and xenograft mouse models were used to explore the antileukemic activity of dexamethasone...
March 8, 2018: Haematologica
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