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Molecular Oncology

Yongmei Yang, Ailin Qu, Rui Zhao, Mengmeng Hua, Xin Zhang, Zhaogang Dong, Guixi Zheng, Hongwei Pan, Hongchun Wang, Xiaoyun Yang, Yi Zhang
The current Tumor Node Metastasis (TNM) staging system is inadequate at identifying high-risk gastric cancer (GC) patients. Using a systematic and comprehensive-biomarker discovery and validation approach, we attempted to build a miRNA-recurrence classifier (MRC) to improve prognostic prediction of GC. We identified 312 differentially expressed miRNAs in 446 GC tissues compared to 45 normal controls by analyzing high-throughput data from The Cancer Genome Atlas (TCGA). Using Cox regression model, we developed an 11-miRNA signature that could successfully discriminate the high-risk patients in the training set (n=372; P<0...
September 22, 2018: Molecular Oncology
Hans-Olov Adami, Anton Berns, Julio E Celis, Elisabeth de Vries, Alexander Eggermont, Adrian Harris, Harald Zur Hausen, Pier Giuseppe Pelicci, Ulrik Ringborg
The European Academy of Cancer Sciences (EACS) is an independent advisory body of well-recognised medical specialists and researchers striving to create a compelling interactive continuum of cancer research, from innovative basic research to implementation of state-of-the-art evidence-based cancer care and prevention. Achieving the above will entail bridging high-quality basic and preclinical cancer research to research on prevention, early detection and therapeutics as well as improving coordination of translational research efforts across Europe...
September 21, 2018: Molecular Oncology
Stephanie S Liu, Karen Kl Chan, Daniel Kh Chu, Tina N Wei, Lesley Sk Lau, Siew F Ngu, Mandy My Chu, Ka Yu Tse, Philip Pc Ip, Enders Ko Ng, Annie Ny Cheung, Hextan Ys Ngan
Cervical cancer is one of the leading causes of cancer death in women globally, despite widespread use of cytology/Human Papillomavirus (HPV) screening. Here, we aimed to identify the potential role of miRNA as diagnostic biomarker in the detection of cervical pre-malignant lesions and cancer. In total, we recruited 582 patients with cervical diseases and 145 control individuals. The expression levels of six miRNAs (miR-20a, miR-92a, miR-141, miR-183*, miR-210 and miR-944) were found to be significantly up-regulated in cervical cancer and pre-malignant lesions as compared to normal cervical samples, indicating that they are oncogenic miRNAs...
September 17, 2018: Molecular Oncology
Peng Shen, Lucas C Reineke, Erik Knutsen, Meng Chen, Martin Pichler, Hui Ling, George A Calin
The anti-diabetic drug metformin has been associated with reduced colorectal cancer (CRC) risk and improved prognosis of CRC patients. However, the detailed mechanisms underlying such beneficial effects remain unknown. In this study, we aimed to evaluate metformin activity in CRC models, and unveil the underlying molecular mechanisms. We showed that metformin inhibits CRC cell proliferation by arresting cells in the G1 phase of the cell cycle, and dramatically reduce colony formation of CRC cells. We discovered that metformin causes a robust reduction of MYC protein level...
September 17, 2018: Molecular Oncology
Iris F Macheleidt, Priya S Dalvi, So-Young Lim, Sonja Meemboor, Lydia Meder, Olivia Käsgen, Marion Müller, Karolin Kleemann, Lingyu Wang, Peter Nürnberg, Vanessa Rüsseler, Stephan C Schäfer, Esther Mahabir, Reinhard Büttner, Margarete Odenthal
Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Despite the development of novel targeted and immune therapies, the five-year survival rate is still only 21%, necessitating more efficient treatment regimens. Lysine-specific demethylase 1 (LSD1) is an epigenetic eraser which modifies histone 3 methylation status, and is highly overexpressed in LUAD. Using representative human cell culture systems and two autochthonous transgenic mouse models, we investigated inhibition of LSD1 as a novel therapeutic option to treat LUAD...
September 16, 2018: Molecular Oncology
Yulan Deng, Shangyi Luo, Xinxin Zhang, Chaoxia Zou, Huating Yuan, Gaoming Liao, Liwen Xu, Chunyu Deng, Yujia Lan, Tingting Zhao, Xu Gao, Yun Xiao, Xia Li
Substantial cancer genome sequencing efforts have discovered many important driver genes contributing to tumorigenesis. However, very little is known about genetic alterations of long non-coding RNAs (lncRNAs) in cancer. There is thus a need for systematic surveys of driver lncRNAs. Through integrative analysis of 5,918 tumors across 11 cancer types, we revealed that lncRNAs have undergone dramatic genomic alterations, many of which are mutually exclusive with well-known cancer genes. Using the hypothesis of functional redundancy of mutual exclusivity, we developed a computational framework to identify driver lncRNAs associated with different cancer hallmarks...
September 14, 2018: Molecular Oncology
Wenbin Song, Dalin He, Yule Chen, Chiuan-Ren Yeh, Iawen Hsu, Qingbo Huang, Xu Zhang, Luke Sien-Shih Chang, Li Zuo, Jiasheng Chen, Karen M Doersch, Chawnshang Chang, Shuyuan Yeh
Renal cell carcinoma (RCC) has the third highest mortality rate among urological tumors, and 20-30% of RCC patients presented with metastatic RCC at the time of diagnosis. While recent studies have indicated that estrogen receptor beta (ERβ) might play key roles in RCC progression, the detailed mechanisms remain to be elucidated. Here we found that expression of ERβ, but not ERα, increases with tumor stage and grade, and also observed that modification of ERβ signals using estrogens/antiestrogens, shRNA knock-down of ERβ, and overexpression of ERβ using ectopic cDNA all affect RCC cell proliferation, migration, and invasion...
September 1, 2018: Molecular Oncology
Seongrak Kim, Sunyoung Ham, Kyungmi Yang, Kunhong Kim
Transforming growth factor β (TGFβ) is overexpressed in advanced cancers and promotes tumorigenesis by inducing epithelial-mesenchymal transition (EMT), which enhances invasiveness and metastasis. Although we previously reported that EMT could be induced by increasing CK2 activity alone, it is not known whether CK2 also plays an essential role in TGFβ-induced EMT. Therefore, in the present study, we investigated whether TGFβ signaling could activate CK2 and, if so, whether such activation is required for TGFβ-induced EMT...
September 1, 2018: Molecular Oncology
Lu-Qin Wang, Peng Yu, Bin Li, Yan-Hua Guo, Zi-Rui Liang, Ling-Ling Zheng, Jian-Hua Yang, Hui Xu, Shun Liu, Li-Si Zheng, Hui Zhou, Liang-Hu Qu
miR-372/373, a cluster of stem cell-specific microRNAs transactivated by the Wnt pathway, have been reported to be dysregulated in various cancers, particularly colorectal cancer (CRC); however, their unique role in cancer remains to be discovered. In this study, we characterized the up-regulation in expression of miR-372/373 in CRC tissues from TCGA data, and then showed that overexpression of miR-372/373 enhanced the stemness of CRC cells by enriching the CD26/CD24-positive cell population and promoting self-renewal, chemotherapy resistance and invasive potential of CRC cells...
September 1, 2018: Molecular Oncology
Inga H Rye, Anne Trinh, Anna B Saetersdal, Daniel Nebdal, Ole Christian Lingjaerde, Vanessa Almendro, Kornelia Polyak, Anne-Lise Børresen-Dale, Åslaug Helland, Florian Markowetz, Hege G Russnes
Targeted therapy for patients with HER2-positive (HER2+) breast cancer has improved overall survival, but many patients still suffer relapse and death from the disease. Intratumor heterogeneity of both estrogen receptor (ER) and HER2 expression has been proposed to play a key role in treatment failure, but little work has been done to comprehensively study this heterogeneity at the single-cell level. In this study, we explored the clinical impact of intratumor heterogeneity of ER protein expression, HER2 protein expression, and HER2 gene copy number alterations...
August 22, 2018: Molecular Oncology
Odd L Gammelgaard, Mikkel G Terp, Birgitte Preiss, Henrik J Ditzel
Immunotherapy is one of the most promising cancer treatment modalities, but the lack of appropriate preclinical in vivo models hampers the development of novel immunotherapeutic strategies. Here, we studied the ability of transplanted human cancer cells to form primary tumors and metastasize in humanized immune system (HIS) mice created by transfer of CD34+ human hematopoietic stem cells. All tested transplanted cancer cell lines developed primary tumors that progressed nearly synchronously. Spontaneous lung and liver metastases developed from both orthotopic and ectopic transplanted cancer cells, and the ability to spread inversely correlated with the extent of CD8+ infiltration in the primary tumor...
August 18, 2018: Molecular Oncology
Steven P Rowe, Brandon Luber, Monique Makell, Patricia Brothers, JoAnn Santmyer, Megan D Schollenberger, Hannah Quinn, Daniel L Edelstein, Frederick S Jones, Karen B Bleich, William H Sharfman, Evan J Lipson
Melanoma currently lacks a reliable blood-based biomarker of disease activity, although circulating tumor DNA (ctDNA) may fill this role. We investigated the clinical utility (i.e., impact on clinical outcomes and interpretation of radiographic data) of measuring ctDNA in patients with metastatic or high-risk resected melanoma. Patients were prospectively accrued into ≥ 1 of three cohorts, as follows. Cohort A: patients with radiographically measurable metastatic melanoma who underwent comparison of ctDNA measured by a BEAMing digital PCR assay to tissue mutational status and total tumor burden; when appropriate, determinations about initiation of targeted therapy were based on ctDNA data...
August 16, 2018: Molecular Oncology
Sitai Liang, Edward A Medina, Boajie Li, Samy L Habib
Loss of Von Hippel-Lindau (VHL) in renal carcinoma cells results in up regulation of the activity of Hypoxia-Inducible Factor (HIF-α), a major transcription factor involved in kidney cancer. Rapamycin as mTOR inhibitor and 5-aminoimidazole-4-carboxamide (AICA)-riboside (AICAR) as AMPK activator are separately used to treat cancer patients. In the current study, the possible additive effect of drug combinations in reducing kidney tumorigenesis was investigated. Treatment with drug combinations significantly decreased cell proliferation, increased cell apoptosis, and abolished Akt phosphorylation and HIF-2α expression in RCC cells, including primary cells isolated from kidney cancer patients...
August 14, 2018: Molecular Oncology
Sanam Sane, Andre Hafner, Rekha Srinivasan, Daniall Masood, John L Slunecka, Collin J Noldner, Alex D Hanson, Taylor Kruisselbrink, Xuejun Wang, Yiyang Wang, Jun Yin, Khosrow Rezvani
Overexpression of oncoproteins is a major cause of treatment failure using current chemotherapeutic drugs. Drug-induced degradation of oncoproteins is feasible and can improve clinical outcomes in diverse types of cancers. Mortalin-2 (mot-2) is a dominant oncoprotein in several tumors, including colorectal cancer (CRC). In addition to inactivating the p53 tumor suppressor protein, mot-2 enhances tumor cell invasion and migration. Thus, mot-2 is considered a potential therapeutic target in several cancer types...
August 14, 2018: Molecular Oncology
Chi Pan, Ines Stevic, Volkmar Müller, Qingtao Ni, Leticia Oliviera Ferrer, Klaus Pantel, Heidi Schwarzenbach
Specific microRNAs (miRNAs) are packaged in exosomes that regulate processes in tumor development and progression. The current study focusses on the influence of exosomal miRNAs in the pathogenesis of epithelial ovarian cancer (EOC). MiRNA profiles were determined in exosomes from plasma of 106 EOC patients, 8 ovarian cystadenoma patients and 29 healthy women by TaqMan real-time PCR-based miRNA array cards containing 48 different miRNAs. In cell culture experiments the impact of miR-200b and miR-320 was determined on proliferation and apoptosis of ovarian cancer cell lines...
August 14, 2018: Molecular Oncology
Paula Moreno, Carla Jiménez-Jiménez, Martín Garrido-Rodríguez, Mónica Calderón-Santiago, Susana Molina, Maribel Lara-Chica, Feliciano Priego-Capote, Ángel Salvatierra, Eduardo Muñoz, Marco A Calzado
Although metabolomics has enjoyed considerable attention in the field of lung cancer detection and management, only a very limited number of works have applied it to tissues. As such, the aim of this study was the thorough analysis of metabolic profiles of relevant lung cancer tissues, including the most important histological subtypes (adenocarcinoma and squamous cell lung carcinoma). Mass spectrometry-based metabolomics, along with gene expression and histological analyses, were performed as part of the widest study to date to identify metabolic alterations in tumors of the most relevant histological subtypes in lung...
August 12, 2018: Molecular Oncology
Yumei Diao, Mohammed Ferdous-Ur Rahman, Yuri Vyatkin, Ani Azatyan, Georges St Laurent, Philipp Kapranov, Peter G Zaphiropoulos
Hedgehog (HH) signaling is involved in many physiological processes, and pathway deregulation can result in a wide range of malignancies. Glioma-associated oncogene 1 (GLI1) is a transcription factor and a terminal effector of the HH cascade. Despite its crucial role in tumorigenesis, our understanding of the GLI1 cellular targets is quite limited. In this study, we identified multiple new GLI1 target genes using a combination of different genomic surveys and then subjected them to in-depth validation in human cancer cell lines...
August 11, 2018: Molecular Oncology
Cristina Aguirre-Portolés, Jaime Feliu, Guillermo Reglero, Ana Ramírez de Molina
At the time of diagnosis, 20% of patients with colorectal cancer (CRC) present with metastasis. Among individuals with primary lesions, 50% of them will develop distant tumors with time. Therefore, early diagnosis and prediction of aggressiveness is crucial for therapy design and disease prognosis. Tumoral cells must undergo significant changes in energy metabolism to meet increased structural and energetic demands for cell proliferation, and metabolic alterations are considered to be a hallmark of cancer. Here, we present ABCA1, a regulator of cholesterol transport, as a new marker for invasion and colorectal cancer survival...
August 11, 2018: Molecular Oncology
Chun-Yu Liu, Chia-Chi Hsu, Tzu-Ting Huang, Chia-Han Lee, Ji-Lin Chen, Shung-Haur Yang, Jeng-Kai Jiang, Wei-Shone Chen, Kuan-Der Lee, Hao-Wei Teng
Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogene, and its expression has been correlated with the prognosis of patients with cancer. In this study, we aimed to explore the relationship between ER stress-related ATF signaling and CIP2A...
July 31, 2018: Molecular Oncology
Samira Benhadjeba, Lydia Edjekouane, Karine Sauvé, Euridice Carmona, André Tremblay
Ovarian cancer (OC) is one of the most intractable diseases, exhibiting tremendous molecular heterogeneity and lacking reliable methods for screening, resulting in late diagnosis and widespread peritoneal dissemination. Menopausal estrogen replacement therapy is a well-recognized risk factor for OC, but little is known about how estrogen might contribute to this disease at the cellular level. This study identifies chemokine receptor CXCR7/ACKR3 as an estrogen-responsive gene, whose expression is markedly enhanced by estrogen through direct recruitment of ERα and transcriptional active histone modifications in OC cells...
July 27, 2018: Molecular Oncology
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