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Molecular Oncology

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https://www.readbyqxmd.com/read/29791786/matrine-suppresses-kras-driven-pancreatic-cancer-growth-by-inhibiting-autophagy-mediated-energy-metabolism
#1
Young-Ra Cho, Ji Hyeon Lee, Ji Hye Kim, So-Yeon Lee, Suna Yoo, Min-Kyo Jung, Su Jung Kim, Hyun Ju Yoo, Chang-Gi Pack, Jin Kyung Rho, Jaekyoung Son
Matrine is a natural compound extracted from the herb Sophora flavescens Ait which is widely used in traditional Chinese medicine for treating various diseases. Recently, matrine was reported to have antitumor effects against a variety of cancers without any obvious side effects; however, the molecular mechanisms of its antiproliferative effects on cancer are unclear. Here, we report that matrine inhibits autophagy-mediated energy metabolism, which is necessary for pancreatic cancer growth. We found that matrine significantly reduces pancreatic cancer growth in vitro and in vivo by insufficiently maintaining mitochondrial metabolic function and energy level...
May 23, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29791078/molecular-subtype-classification-of-urothelial-carcinoma-in-lynch-syndrome
#2
Christina Therkildsen, Pontus Eriksson, Mattias Höglund, Mats Jönsson, Gottfrid Sjödahl, Mef Nilbert, Fredrik Liedberg
Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas...
May 23, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29754406/targeting-twist1-through-loss-of-function-inhibits-tumorigenicity-of-human-glioblastoma
#3
Andrei M Mikheev, Svetlana A Mikheeva, Liza J Severs, Cory C Funk, Lei Huang, José L McFaline-Figueroa, Jeanette Schwensen, Cole Trapnell, Nathan D Price, Stephen Wong, Robert C Rostomily
Twist1 (TW) is a bHLH transcription factor (TF) and master regulator of the epithelial to mesenchymal transition (EMT). In vitro, TW promotes mesenchymal change, invasion and self-renewal in glioblastoma (GBM) cells. However the potential therapeutic relevance of TW has not been established through loss of function studies in human GBM cell xenograft models. The effects of TW loss of function (gene editing and knock down) on inhibition of tumorigenicity of U87MG and GBM4 glioma stem cells were tested in orthotopic xenograft models and conditional knockdown in established flank xenograft tumors...
May 13, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29741811/basal-like-breast-cancer-engages-tumor-supportive-macrophages-via-secreted-factors-induced-by-extracellular-s100a4
#4
Lina Prasmickaite, Ellen M Tenstad, Solveig Pettersen, Shakila Jabeen, Eivind Valen Egeland, Silje Nord, Abhilash Pandya, Mads Haugland Haugen, Vessela N Kristensen, Anne-Lise Børresen-Dale, Olav Engebråten, Gunhild M Maelandsmo
The tumor microenvironment (TME) may influence both cancer progression and therapeutic response. In breast cancer (BC), particularly in the aggressive triple-negative/basal-like subgroup, patient outcome is strongly associated with the tumor's inflammatory profile. Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the TME, shown to be linked to poor prognosis and therapeutic resistance. In this study we investigated the effect of the metastasis- and inflammation-associated microenvironmental factor S100A4 on breast cancer cells (BCCs) of different subtypes, and explored their further interactions with myeloid cells...
May 9, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29741809/exogenous-il6-induces-mrna-splice-variant-mbd2_v2-to-promote-stemness-in-tp53-wild-type-african-american-pca-cells
#5
Emily A Teslow, Bin Bao, Greg Dyson, Christophe Legendre, Cristina Mitrea, Wael Sakr, John D Carpten, Isaac Powell, Aliccia Bollig-Fischer
African American men (AAM) are at higher risk of being diagnosed with prostate cancer (PCa) and are at higher risk of dying from the disease compared to European American men (EAM).We sought to better understand PCa molecular diversity that may be underlying these disparities. We performed RNA-sequencing analysis on high-grade PCa to identify genes showing differential tumor versus noncancer adjacent tissue expression patterns unique to AAM or EAM. We observed that interleukin-6 (IL6) was upregulated in the nonmalignant adjacent tissue in AAM, but in EAM IL6 expression was higher in PCa tissue...
May 9, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29738634/grp78-mediated-antioxidant-response-and-abc-transporter-activity-confers-chemoresistance-to-pancreatic-cancer-cells
#6
Patricia Dauer, Nikita S Sharma, Vineet K Gupta, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Chemoresistance is a major therapeutic challenge that plays a role in the poor statistical outcomes in pancreatic cancer. Unfolded Protein Response or UPR is one of the homeostasis mechanisms in cancer cells that have been correlated with chemoresistance in a number of cancers including pancreatic cancer. In the current study, we show that modulating glucose regulatory protein 78 (GRP78), the master regulator of the UPR, can have a profound effect on multiple pathways that mediate chemoresistance. Our study showed for the first time that silencing GRP78 can diminish efflux activity of ATP-binding cassette (ABC) transporters, and it can decrease the antioxidant response resulting in an accumulation of reactive oxygen species (ROS)...
May 8, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29738110/genotoxic-stress-induces-sca-1-expressing-metastatic-mammary-cancer-cells
#7
Jianlin Gong, Benjamin J Lang, Desheng Weng, Takanori Eguchi, Ayesha Murshid, Thiago J Borges, Sachin Doshi, Baizheng Song, Mary Ann Stevenson, Stuart K Calderwood
We describe a cell damage-induced phenotype in mammary carcinoma cells involving acquisition of enhanced migratory and metastatic properties. Induction of this state by radiation required increased activity of the Ptgs2 gene product cyclooxygenase 2 (Cox2), secretion of its bioactive lipid product prostaglandin E2 (PGE2) and the activity of the PGE2 receptor EP4. Although largely transient, decaying to low levels in a few days to a week, this phenotype was cumulative with damage and levels of cell markers Sca-1 and ALDH1 increased with treatment dose...
May 8, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29729076/genome-wide-binding-of-transcription-factor-snail1-in-triple-negative-breast-cancer-cells
#8
Varun Maturi, Anita Morén, Stefan Enroth, Carl-Henrik Heldin, Aristidis Moustakas
Transcriptional regulation mediated by the zinc finger protein Snail1 controls early embryogenesis. By binding to the epithelial tumor suppressor CDH1 gene, Snail1 initiates the epithelial-mesenchymal transition (EMT). The EMT generates stem-like cells and promotes invasiveness during cancer progression. Accordingly, Snail1 mRNA and protein is abundantly expressed in triple-negative breast cancers with enhanced metastatic potential and phenotypic signs of the EMT. Such high endogenous Snail1 protein levels permit quantitative chromatin immunoprecipitation-sequencing (ChIP-seq) analysis...
May 4, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29729074/liver-regeneration-accelerates-hepatitis-b-virus-related-tumorigenesis-of-hepatocellular-carcinoma
#9
Chiao-Fang Teng, Hong-Yi Chang, Hung-Wen Tsai, Wen-Chuan Hsieh, Yu-Hao Kuo, Ih-Jen Su, Yih-Jyh Lin
Although partial hepatectomy (PH) to remove tumors provides a potential cure of hepatocellular carcinoma (HCC), long-term survival of hepatitis B virus (HBV)-related HCC patients after PH remains a big challenge. Early recurrence within two years post-PH is associated with the dissemination of primary HCC. However, late recurrence after two years post-PH is supposed due to the de novo or a secondary tumor. Since PH initiates liver regeneration (LR), we hypothesize that LR may accelerate tumorigenesis through activation of pre-existing precancerous lesions in the remaining liver...
May 4, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29719937/a-novel-rna-sequencing-based-mirna-signature-predicts-with-recurrence-and-outcome-of-hepatocellular-carcinoma
#10
Bai Fumao, Huaibin Zhou, Mengni Ma, Chen Guan, Jianxin Lyu, Qing H Meng
Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the second leading cause of cancer-related deaths worldwide. Given that the rate of HCC recurrence 5 years after liver resection is as high as 70%, patient with HCC typically have a poor outcome. A biomarker or set of biomarkers that could predict disease recurrence would have a substantial clinical impact, allowing earlier detection of recurrence and more effective treatment. With the aim of identifying a new microRNA (miRNA) signature associated with HCC recurrence, we analyzed data on 306 HCC patients for whom both miRNA expression profiles and complete clinical information were available from The Cancer Genome Atlas (TCGA) database...
May 2, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29719936/induced-ptf1a-expression-in-pancreatic-ductal-adenocarcinoma-cellsactivates-acinar-gene-networks-reduces-tumorigenic-properties-and-sensitizes-cells-to-gemcitabine-treatment
#11
Brad L Jakubison, Patrick G Schweickert, Sarah E Moser, Yi Yang, Hongyu Gao, Kathleen Scully, Pamela Itkin-Ansari, Yunlong Liu, Stephen F Konieczny
Pancreatic acinar cells synthesize, package, and secrete digestive enzymes into the duodenum to aid in nutrient absorption and meet metabolic demands. When exposed to cellular stresses and insults acinar cells undergo a dedifferentiation process termed acinar-ductal metaplasia (ADM). ADM lesions with oncogenic mutations eventually give rise to pancreatic ductal adenocarcinoma (PDAC). In healthy pancreata, the basic helix-loop-helix (bHLH) factors MIST1 and PTF1a coordinate an acinar-specific transcription network that maintains the highly developed differentiation status of the cells, protecting the pancreas from undergoing a transformative process...
May 2, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29704427/cancer-testis-antigen-plac1-promotes-invasion-and-metastasis-of-breast-cancer-through-furin-nicd-pten-signaling-pathway
#12
Yongfei Li, Jiahui Chu, Jun Li, Wanting Feng, Fan Yang, Yifan Wang, Yanhong Zhang, Chunxiao Sun, Mengzhu Yang, Shauna N Vasilatos, Yi Huang, Ziyi Fu, Yongmei Yin
Plac1 is a cancer-testis antigen that plays a critical role in promoting cancer initiation and progression. However, the clinical significance and mechanism of Plac1 in cancer progression remains elusive. Here we report that Plac1 is an important oncogenic and prognostic factor which physically interacts with Furin to drive breast cancer invasion and metastasis. We have shown that Plac1 expression positively correlates with clinical stage, lymph node metastasis, HR status and overall patient survival. Overexpression of Plac1 promoted invasion and metastasis of breast cancer cells in vitro and in vivo...
April 28, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29698587/selective-induction-of-cancer-cell-death-by-vdac1-based-peptides-and-their-potential-use-in-cancer-therapy
#13
Anna Shteinfer-Kuzmine, Zohar Amsalem, Tasleem Arif, Alexandra Zooravlov, Varda Shoshan-Barmatz
Mitochondrial VDAC1 mediates cross-talk between the mitochondria and other parts of the cell by transporting anions, cations, ATP, Ca2+ and metabolites, and serves as a key player in apoptosis. As such, VDAC1 is involved in two important hallmarks of cancer development, namely energy and metabolic reprograming and apoptotic cell death evasion. We previously developed cell-penetrating VDAC1-derived peptides that interact with hexokinase (HK), Bcl-2 and Bcl-xL to prevent the anti-apoptotic activities of these proteins and induce cancer cell death, with a focus on leukemia and glioblastoma...
April 26, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29698574/n-glycan-signatures-identified-in-tumor-interstitial-fluid-and-serum-of-breast-cancer-patients-association-with-tumor-biology-and-clinical-outcome
#14
Thilde Terkelsen, Vilde D Haakensen, Radka Saldova, Pavel Gromov, Merete Kjaer Hansen, Henning Stöckmann, Ole Christian Lingjaerde, Anne-Lise Børresen-Dale, Elena Papaleo, Åslaug Helland, Pauline M Rudd, Irina Gromova
Particular N-glycan structures are known to be associated with breast malignancies by coordinating various regulatory events within the tumor and corresponding microenvironment, thus implying that N-glycan patterns may be used for cancer stratification and as predictive or prognostic biomarkers. However, the association between N-glycans secreted by breast tumor and corresponding clinical relevance remain to be elucidated. We profiled N-glycans by HILIC UPLC across a discovery dataset composed of tumor interstitial fluids (TIF, n=85), paired normal interstitial fluids (NIF, n=54) and serum samples (n=28) followed by independent evaluation, with the ultimate goal of identifying tumor-related N-glycan patterns in blood of breast cancer patients...
April 26, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29689643/il-17a-promotes-the-invasion-metastasis-cascade-via-the-akt-pathway-in-hepatocellular-carcinoma
#15
Qing-Guo Xu, Jian Yu, Xing-Gang Guo, Guo-Jun Hou, Sheng-Xian Yuan, Yuan Yang, Yun Yang, Hui Liu, Ze-Ya Pan, Fu Yang, Fang-Ming Gu, Wei-Ping Zhou
We previously demonstrated that interleukin-17A (IL-17A) is associated with the progression of hepatocellular carcinoma (HCC). However, its role in the invasion-metastasis cascade of HCC and the efficacy of IL-17A-targeting therapeutics in HCC remain largely unknown. In this study, we found that IL-17A promoted intrahepatic and pulmonary metastasis of HCC cells in an orthotopic implant model. Moreover, our results showed that IL-17A induced epithelial-mesenchymal transition (EMT) and promoted HCC cell colonization in vitro and in vivo, and the role of IL-17A in invasion-metastasis was dependent on activation of the AKT pathway...
April 24, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29689640/haploid-genetic-screens-identify-genetic-vulnerabilities-to-microtubule-targeting-agents
#16
Nora M Gerhards, Vincent A Blomen, Merve Mutlu, Joppe Nieuwenhuis, Denise Howald, Charlotte Guyader, Jos Jonkers, Thijn R Brummelkamp, Sven Rottenberg
The absence of biomarkers to accurately predict anti-cancer therapy response remains a major obstacle in clinical oncology. We applied a genome-wide loss-of-function screening approach in human haploid cells to characterize genetic vulnerabilities to classical microtubule-targeting agents. Using docetaxel and vinorelbine, two well-established chemotherapeutic agents, we sought to identify genetic alterations sensitizing human HAP1 cells to these drugs. Despite the fact that both drugs act on microtubules, a set of distinct genes were identified whose disruption affect drug sensitivity...
April 24, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29689621/sall2-represses-cyclins-d1-and-e1-expression-and-restrains-g1-s-cell-cycle-transition-and-cancer-related-phenotypes
#17
Viviana Hermosilla, Ginessa Salgado, Elizabeth Riffo, David Escobar, Matías Hepp, Carlos Farkas, Mario Galindo, Violeta Morín, María A García-Robles, Ariel F Castro, Roxana Pincheira
SALL2 is a poorly characterized transcription factor that belongs to the Spalt-like family involved in development. Mutations on SALL2 have been associated with ocular coloboma and cancer. In cancers, SALL2 is deregulated, and is proposed as a tumor suppressor in ovarian cancer. SALL2 has been implicated in stemness, cell death, proliferation and quiescence. However, mechanisms underlying roles of SALL2 related to cancer remain largely unknown. Here, we investigated the role of SALL2 in cell proliferation by using mouse embryo fibroblasts (MEFs) derived from Sall2-/- mice...
April 24, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29689598/correlation-between-circulating-cell-free-pik3ca-tumor-dna-levels-and-treatment-response-in-patients-with-pik3ca-mutated-metastatic-breast-cancer
#18
Annette R Kodahl, Sidse Ehmsen, Niels Pallisgaard, Anne Marie B Jylling, Jeanette Dupont Jensen, Anne-Vibeke Laenkholm, Ann S Knoop, Henrik J Ditzel
Liquid biopsies focusing on the analysis of circulating cell-free tumor DNA (ctDNA) may have important clinical implications for personalized medicine, including early detection of cancer, therapeutic guidance and monitoring of recurrence. Mutations in the oncogene, PIK3CA, are frequently observed in breast cancer and have been suggested as a predictive biomarker for PI3K-selective inhibitor treatment. In this study, we analyzed the presence of PIK3CA mutations in formalin-fixed, paraffin-embedded, metastatic tissue and corresponding ctDNA from serum of patients with advanced breast cancer using a highly-sensitive, optimized droplet digital PCR (ddPCR) assay...
April 24, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29683256/the-immunoglobulin-like-domain-of-neuregulins-potentiates-erbb3-her3-activation-and-cellular-proliferation
#19
Ariana Centa, Ruth Rodríguez-Barrueco, Juan Carlos Montero, Atanasio Pandiella
The Neuregulins (NRGs) represent a large family of membrane-anchored growth factors, whose deregulation may contribute to the pathogenesis of several tumours. In fact, targeting of NRG-activated pathways has demonstrated clinical benefit. To improve the efficacy of anti-NRG therapies, it is essential to gain insights into the regions of NRGs that favour their pro-oncogenic properties. Here we have addressed the protumorigenic impact of different NRG domains. To do this, deletion mutants affecting different NRG domains were expressed in 293 and MCF7 cells...
April 23, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29675884/specific-breast-cancer-prognosis-subtype-distinctions-based-on-dna-methylation-patterns
#20
Shumei Zhang, Yihan Wang, Yue Gu, Jiang Zhu, Ce Ci, Zhongfu Guo, Chuangeng Chen, Yanjun Wei, Wenhua Lv, Hongbo Liu, Dongwei Zhang, Yan Zhang
Tumor heterogeneity is an obstacle to effective breast cancer diagnosis and therapy. DNA methylation is an important regulator of gene expression, thus characterizing tumor heterogeneity by epigenetic features can be clinically informative. In this study, we explored specific prognosis-subtypes based on DNA methylation status using 669 breast cancers from TCGA database. Nine subgroups were distinguished by consensus clustering using 3869 CpGs that significantly influenced survival. The specific DNA methylation patterns were reflected by different races, ages, tumor stages, receptor status, histological types, metastasis status and prognosis...
April 19, 2018: Molecular Oncology
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