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Cancer Letters

Vania Vidimar, Cynthia Licona, Ricardo Cerón Camacho, Eric Guerin, Pierre Coliat, Aina Venkatasamy, Moussa Ali, Dominique Guenot, Ronan Le Lagadec, Alain C Jung, Jean-Noel Freund, Michel Pfeffer, Georg Mellitzer, Gianni Sava, Christian Gaiddon
Targeting specific tumor metabolic needs represents an actively investigated therapeutic strategy to bypass tumor resistance mechanisms. In this study, we describe an original approach to impact the cancer metabolism by exploiting the redox properties of a ruthenium organometallic compound. This organometallic complex induced p53-independent cytotoxicity and reduced size and vascularization of patients-derived tumor explants that are resistant to platinum drugs. At the molecular level, the ruthenium complex altered redox enzyme activities and the intracellular redox state by increasing the NAD+/NADH ratio and ROS levels...
October 16, 2018: Cancer Letters
Ying-Sheng Xiao, De Zeng, Yuan-Ke Liang, Yang Wu, Mei-Fang Li, Yu-Zhu Qi, Xiao-Long Wei, Wen-He Huang, Min Chen, Guo-Jun Zhang
Resistance to chemotherapy remains a significant problem in the treatment of breast cancer, especially for triple-negative breast cancer (TNBC), in which standard systemic therapy is currently limited to chemotherapeutic agents. Our study aimed to better understand the molecular mechanisms that lead to failure of chemotherapy in TNBC. Herein, we observed elevated expression of Notch1 and major vault protein (MVP) in MDA-MB-231DDPR cells compared to their parental counterparts. We demonstrated that Notch1 could positively regulate the expression of MVP...
October 15, 2018: Cancer Letters
Ning Ji, Yuqi Yang, Chao-Yun Cai, Zi-Ning Lei, Jing-Quan Wang, Pranav Gupta, Suneet Shukla, Suresh V Ambudkar, Dexin Kong, Zhe-Sheng Chen
Overexpression of ATP-binding cassette (ABC) transporters is one of the most important mechanisms responsible for the development of multidrug resistance (MDR). Selonsertib, a serine/threonine kinase inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). In this study, we investigated whether selonsertib could reverse MDR-mediated by ABC transporters, including ABCB1, ABCG2, ABCC1 and ABCC10. The results showed that selonsertib significantly reversed ABCB1- and ABCG2-mediated MDR, but not MDR-mediated by ABCC1 or ABCC10...
October 10, 2018: Cancer Letters
Jinlei Ding, Xiaonan Wang, Yuan Zhang, Xiaolin Sang, Jingyan Yi, Chongya Liu, Zundong Liu, Min Wang, Nan Zhang, Yijue Xue, Lanlin Shen, Wenzhi Zhao, Fuwen Luo, Pixu Liu, Hailing Cheng
Selective phosphatidylinositol 3 kinase (PI3K) inhibitors are being actively tested in clinical trials for ERα-positive (ER+) breast cancer due to the presence of activating PIK3CA mutations. However, recent studies have revealed that increased ERα transcriptional activity limits the efficacy of PI3K inhibitor monotherapy for ER+ breast cancers. Herein, we report the identification of BTF3 as an oncogenic transcription factor that regulates ERα expression in luminal breast cancers. Our TCGA analysis reveals high expression levels of BTF3 in luminal/ER+ breast cancer and cell line models harboring ERα overexpression...
October 10, 2018: Cancer Letters
Irene Appolloni, Francesco Alessandrini, Davide Ceresa, Daniela Marubbi, Eleonora Gambini, Daniele Reverberi, Fabrizio Loiacono, Paolo Malatesta
The mutual reshape of tumor and immune system cells during tumor progression is a widely accepted notion in different cancers including gliomas. The importance of this phenomenon in shaping glioma progression and the mechanisms governing it, however, are not fully elucidated. Taking advantage of a well-characterized in vivo glioma model we performed an analysis of glioma cells transcriptomes at different stages of progression and unveiled the reorganization of glioma-immune system interactions. Specifically, we show that the inability of low-grade glioma cells to orthotopically graft in syngeneic immunocompetent mice, positively correlates with the abundance of infiltrating lymphocytes in donor tumors and with a highly immunostimulatory transcriptional profile...
October 9, 2018: Cancer Letters
Wei-Yu Chen, Tao Zeng, Yu-Chng Wen, Hsiu-Lien Yeh, Kuo-Ching Jiang, Wei-Hao Chen, Qingfu Zhang, Jiaoti Huang, Yen-Nien Liu
Androgen receptor (AR) targeting is an important therapeutic strategy for treating prostate cancer. Most tumors progress to castration-resistant prostate cancer (CRPC) and develop the neuroendocrine (NE) phenotype under androgen deprivation therapy (ADT). The molecular basis for NE transdifferentiation after ADT remains incompletely understood. Herein, we show that an immunocyte expression protein, ZBTB46, induces inflammatory response gene expression and contributes to NE differentiation of prostate cancer cells...
October 9, 2018: Cancer Letters
Domenico Ribatti, Roberto Tamma
Angiogenesis is regulated by numerous "classic" factors such as vascular endothelial growth factor (VEGF) and many other endogenous "non-classic"peptides, including erythropoietin (Epo), and granulocyte-/granulocyte macrophage colony stimulating factor (G-/GM-CSF). The latter play an important regulatory role in angiogenesis, especially under pathological conditions and constitute a crosslink between angiogenesis and hematopoiesis. This article reviews studies on the ability of hematopoietic cytokines to affect several endothelial cell functions in tumor angiogenesis...
October 9, 2018: Cancer Letters
Jing Zheng, Yonggang Sha, Logan Roof, Oded Foreman, John Lazarchick, Jagadish Kummetha Venkta, Cleopatra Kozlowski, Cristina Gasparetto, Nelson Chao, Allen Ebens, Jianda Hu, Yubin Kang
Multiple myeloma remains an incurable disease, and continued efforts are required to develop novel agents and novel drug combinations with more effective anti-myeloma activity. Here, we show that the pan-PIM kinase inhibitors SGI1776 and CX6258 exhibit significant anti-myeloma activity and that combining a pan-PIM kinase inhibitor with the immunomodulatory agent lenalidomide in an in vivo myeloma xenograft mouse model resulted in synergistic myeloma cell killing without additional hematologic or hepatic toxicities...
October 9, 2018: Cancer Letters
Sri HariKrishna Vellanki, Rodrigo G B Cruz, Hanne Jahns, Lance Hudson, Giovanni Sette, Adriana Eramo, Ann M Hopkins
Overexpression of the tight junction protein Junctional Adhesion Molecule-A (JAM-A) has been linked to aggressive disease in breast and other cancers, but JAM-targeting drugs remain elusive. Screening of a natural compound library identified the antibiotic Tetrocarcin-A as a novel downregulator of JAM-A and human epidermal growth factor receptor-2 (HER2) protein expression in breast cancer cells. Lysosomal inhibition partially rescued the downregulation of JAM-A and HER2 caused by Tetrocarcin-A, and attenuated its cytotoxic activity...
October 9, 2018: Cancer Letters
Manuela Hugle, Sebastian Czaplinski, Karoline Habermann, Meike Vogler, Simone Fulda
Multidrug resistance (MDR) in cancer patients undergoing chemotherapy is preventing effective treatment of multiple cancer types including pediatric tumors. Resistance to chemotherapeutic drugs in cancer cells is frequently associated with high expression of p-glycoprotein, a transporter in the plasma membrane that can mediate cellular drug export. Here, we generated pediatric cancer cells with acquired resistance to the chemotherapeutic drug vincristine (VCR). In these cells, acquired resistance is associated with increased expression of p-glycoprotein...
October 9, 2018: Cancer Letters
Ana C Henriques, Diana Ribeiro, Joel Pedrosa, Bruno Sarmento, Patrícia M A Silva, Hassan Bousbaa
Current microtubule-targeting agents (MTAs) remain amongst the most important antimitotic drugs used against a broad range of malignancies. By perturbing spindle assembly, MTAs activate the spindle assembly checkpoint (SAC), which induces mitotic arrest and subsequent apoptosis. However, besides toxic side effects and resistance, mitotic slippage and failure in triggering apoptosis in various cancer cells are limiting factors of MTAs efficacy. Alternative strategies to target mitosis without affecting microtubules have, thus, led to the identification of small molecules, such as those that target spindle Kinesins, Aurora and Polo-like kinases...
October 9, 2018: Cancer Letters
Yang Luo, Jian-Jun Chen, Qiang Lv, Jun Qin, Yi-Zhou Huang, Min-Hao Yu, Ming Zhong
In recent years, accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are powerful factors influencing the progression of multiple malignancies. Although a relationship between the lncRNA NEAT1 (nuclear enriched abundant transcript 1) and colorectal cancer has previously been reported, the functional mechanism underlying the involvement of NEAT1 in colorectal cancer remains unknown. In this study, we report that NEAT1 expression is up-regulated in colorectal cancer tissues, which correlates with advanced clinical features, poor overall survival and disease free survival...
October 9, 2018: Cancer Letters
Vineet Kumar Gupta, Nikita S Sharma, Kousik Kesh, Patricia Dauer, Alice Nomura, Bhuwan Giri, Vikas Dudeja, Santanu Banerjee, Sanjoy Bhattacharya, Ashok Saluja, Sulagna Banerjee
Metabolic rewiring is an integral part of tumor growth. Among metabolic pathways, the Mevalonic-Acid-Pathway (MVAP) plays a key role in maintaining membrane architecture through cholesterol synthesis, thereby affecting invasiveness. In the current study, we show for the first time that CD133Hi pancreatic tumor initiating cells (TIC) have increased expression of MVAP enzymes, cholesterol-content and Caveolin expression. Further, we show that CD133 in these cells is localized in the lipid-rafts (characterized by Cav-1-cholesterol association)...
October 2, 2018: Cancer Letters
Shuyang Wang, Zhiyuan Xiao, Zexuan Hong, Hongli Jiao, Shaowei Zhu, Yali Zhao, Jiaxin Bi, Junfeng Qiu, Dan Zhang, Junyu Yan, Lingjie Zhang, Chengmei Huang, Tingting Li, Li Liang, Wenting Liao, Yaping Ye, Yanqing Ding
Forkhead box F1 (FOXF1) has been recently implicated in the progression and metastasis of lung cancer and breast cancer. However, the biological functions and underlying mechanisms by which FOXF1 regulates the progression of colorectal cancer (CRC) are largely unknown. As shown in our previous study, FOXF1 is upregulated in 182 CRC tissues, and elevated FOXF1 expression is significantly associated with microvessel density and advanced TNM (T = primary tumour; N = regional lymph nodes; M = distant metastasis) stages...
September 22, 2018: Cancer Letters
Jie Luo, Jing Tian, FuJu Chou, Changyi Lin, Emily Zixin Xing, Li Zuo, Yuanjie Niu, Shuyuan Yeh, Chawnshang Chang
Chemotherapy with docetaxel remains as the effective therapy to suppress castration resistant prostate cancer (CRPC) in some patients. However, most chemotherapy with docetaxel eventually fails with the development of docetaxel resistance after 18-weeks of treatment. Here we found docetaxel treatment might have adverse effect of increasing the androgen receptor (AR) protein level in the CRPC cells, and combined docetaxel with anti-AR therapy using AR-shRNA or the AR degradation enhancer ASC-J9 may increase docetaxel sensitivity to better suppress the CRPC cell growth...
September 21, 2018: Cancer Letters
Daniela De Martino, Emrullah Yilmaz, Arturo Orlacchio, Michela Ranieri, Ke Zhao, Antonio Di Cristofano
Anaplastic thyroid cancer (ATC) is among the most lethal malignancies. The mitotic kinase PLK1 is overexpressed in the majority of ATCs and PLK1 inhibitors have shown preclinical efficacy. However, they also cause mitotic slippage and endoreduplication, leading to the generation of tetraploid, genetically unstable cell populations. We hypothesized that PI3K activity may facilitate mitotic slippage upon PLK1 inhibition, and thus tested the effect of combining PLK1 and PI3K inhibitors in ATC models, in vitro and in vivo...
September 19, 2018: Cancer Letters
Kotryna Seip, Kjetil Jørgensen, Marco Vincent Haselager, Marco Albrecht, Mads Haugland Haugen, Eivind Valen Egeland, Philippe Lucarelli, Olav Engebraaten, Thomas Sauter, Gunhild Mari Mælandsmo, Lina Prasmickaite
Cancer cells' phenotypic plasticity, promoted by stromal cells, contributes to intra-tumoral heterogeneity and affects response to therapy. We have disclosed an association between fibroblast-stimulated phenotype switching and resistance to the clinically used BRAF inhibitor (BRAFi) vemurafenib in malignant melanoma, revealing a challenge in targeting the fibroblast-induced phenotype. Here we compared molecular features and drug sensitivity in melanoma cells grown as co-cultures with fibroblasts versus mono-cultures...
September 18, 2018: Cancer Letters
G Ratnayake, A L Bain, N Fletcher, C B Howard, K K Khanna, K J Thurecht
RNA interference (RNAi) therapy is an emerging class of biopharmaceutical that has immense potential in cancer medicine. RNAi medicines are based on synthetic oligonucleotides that can suppress a target protein in tumour cells with high specificity. This review explores the attractive prospect of using RNAi as a radiosensitiser by targeting the DNA damage response. There are a multitude of molecular targets involved in the detection and repair of DNA damage that are suitable for this purpose. Recent developments in delivery technologies such nanoparticle carriers and conjugation strategies have allowed RNAi therapeutics to enter clinical trials in the treatment of cancer...
September 18, 2018: Cancer Letters
Yuanjie Niu, Changcheng Guo, Simeng Wen, Jing Tian, Jie Luo, Keliang Wang, Hao Tian, Shuyuan Yeh, Chawnshang Chang
Prostate cancer (PCa) is the most common cancer and the 2nd leading cause of cancer-related deaths among men in the United States. Androgen-deprivation-therapy (ADT) with antiandrogens to target the androgens/androgen receptor (AR) signals remains the standard therapy for advanced PCa. However, most of the PCa patients who received ADT with antiandrogens, including the recently developed Enzalutamide (Enz) that might extend PCa patients survival an extra 4.8 months, will still develop the castration (or antiandrogen) resistance...
September 15, 2018: Cancer Letters
Xiaoyang Li, Nicole A Seebacher, Francis J Hornicek, Tao Xiao, Zhenfeng Duan
Bone and soft tissue sarcomas account for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. Sarcomas are divided into more than 50 subtypes. Each subtype is highly heterogeneous and characterized by significant morphological and phenotypic variability. Currently, sarcoma characterization is based on tissue biopsies. However, primary and invasive tissue biopsies may not accurately reflect the current disease condition following treatment as is may cause marked changes to the tumor cells...
September 14, 2018: Cancer Letters
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