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https://www.readbyqxmd.com/read/27573852/assessing-intratumor-heterogeneity-and-tracking-longitudinal-and-spatial-clonal-evolutionary-history-by-next-generation-sequencing
#1
Yuchao Jiang, Yu Qiu, Andy J Minn, Nancy R Zhang
Cancer is a disease driven by evolutionary selection on somatic genetic and epigenetic alterations. Here, we propose Canopy, a method for inferring the evolutionary phylogeny of a tumor using both somatic copy number alterations and single-nucleotide alterations from one or more samples derived from a single patient. Canopy is applied to bulk sequencing datasets of both longitudinal and spatial experimental designs and to a transplantable metastasis model derived from human cancer cell line MDA-MB-231. Canopy successfully identifies cell populations and infers phylogenies that are in concordance with existing knowledge and ground truth...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27058661/combination-cancer-therapies-with-immune-checkpoint-blockade-convergence-on-interferon-signaling
#2
REVIEW
Andy J Minn, E John Wherry
Improving efficacy of immune checkpoint blockade for cancer can be facilitated by combining these agents with each other and/or with other conventional or targeted therapies. Interferon and innate immune signaling pathways in immune and tumor cells have emerged as intriguing determinants of response and resistance, often in complex and seemingly paradoxical ways.
April 7, 2016: Cell
https://www.readbyqxmd.com/read/26993130/erratum-to-pi3k-mtor-inhibition-can-impair-tumor-invasion-and-metastasis-in-vivo-despite-a-lack-of-antiproliferative-action-in-vitro-implications-for-targeted-therapy
#3
Seth A Wander, Dekuang Zhao, Alexandra H Besser, Feng Hong, Jianqin Wei, Tan A Ince, Clara Milikowski, Nanette H Bishopric, Andy J Minn, Chad J Creighton, Joyce M Slingerland
Erratum to: Breast Cancer Res Treat (2013),138:369–381,DOI 10.1007/s10549-012-2389-6. In the original publication of the article, the Fig. 4c and d were published erroneously. The revised Fig. 4 is given in this erratum.
April 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/26678335/getting-tumor-dendritic-cells-to-engage-the-dead
#4
COMMENT
Lisa Cucolo, Andy J Minn
The immunogenic effects of chemotherapy rely on effective activation of dendritic cells to present antigen to tumor-specific T cells. However, the signals that govern how dendritic cells seek out dying cancer cells to initiate this process are poorly understood. A recent study by Vacchelli et al. provides important insight.
December 14, 2015: Cancer Cell
https://www.readbyqxmd.com/read/26604042/interferons-and-the-immunogenic-effects-of-cancer-therapy
#5
REVIEW
Andy J Minn
Much of our understanding on resistance mechanisms to conventional cancer therapies such as chemotherapy and radiation has focused on cell intrinsic properties that antagonize the detrimental effects of DNA and other cellular damage. However, it is becoming clear that the immune system and/or innate immune signaling pathways can integrate with these intrinsic mechanisms to profoundly influence treatment efficacy. In this context, recent evidence indicates that interferon (IFN) signaling has an important role in this integration by influencing immune and intrinsic/non-immune determinants of therapy response...
November 2015: Trends in Immunology
https://www.readbyqxmd.com/read/26524530/tumour-exosome-integrins-determine-organotropic-metastasis
#6
Ayuko Hoshino, Bruno Costa-Silva, Tang-Long Shen, Goncalo Rodrigues, Ayako Hashimoto, Milica Tesic Mark, Henrik Molina, Shinji Kohsaka, Angela Di Giannatale, Sophia Ceder, Swarnima Singh, Caitlin Williams, Nadine Soplop, Kunihiro Uryu, Lindsay Pharmer, Tari King, Linda Bojmar, Alexander E Davies, Yonathan Ararso, Tuo Zhang, Haiying Zhang, Jonathan Hernandez, Joshua M Weiss, Vanessa D Dumont-Cole, Kimberly Kramer, Leonard H Wexler, Aru Narendran, Gary K Schwartz, John H Healey, Per Sandstrom, Knut Jørgen Labori, Elin H Kure, Paul M Grandgenett, Michael A Hollingsworth, Maria de Sousa, Sukhwinder Kaur, Maneesh Jain, Kavita Mallya, Surinder K Batra, William R Jarnagin, Mary S Brady, Oystein Fodstad, Volkmar Muller, Klaus Pantel, Andy J Minn, Mina J Bissell, Benjamin A Garcia, Yibin Kang, Vinagolu K Rajasekhar, Cyrus M Ghajar, Irina Matei, Hector Peinado, Jacqueline Bromberg, David Lyden
Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells...
November 19, 2015: Nature
https://www.readbyqxmd.com/read/25925584/linking-primary-and-metastatic-tumour-re-initiation
#7
COMMENT
Barzin Y Nabet, Andy J Minn
Whether the cancer cells responsible for the growth of primary tumours are also able to re-initiate tumour growth after seeding to distant organs is unclear. The characterization of breast cancer cells with both of these attributes now identifies the functional and molecular determinants necessary to mediate primary tumour formation and re-initiation at the secondary site.
May 2015: Nature Cell Biology
https://www.readbyqxmd.com/read/25799953/awakening-the-immune-system-with-radiation-optimal-dose-and-fractionation
#8
REVIEW
Saumil J Gandhi, Andy J Minn, Robert H Vonderheide, E John Wherry, Stephen M Hahn, Amit Maity
The importance of ionizing radiation has historically been limited to achieving local control of tumor cells. However, emerging evidence over the last decade suggests an increasingly important role for radiation in amplifying the antitumor immune response elicited by immunomodulatory agents. Combination of radiation with immunotherapy has been shown to elicit powerful systemic responses in several pre-clinical tumor models. Additionally, recent clinical observations support the use of radiation therapy for augmenting antitumor immunity in the metastatic setting...
November 28, 2015: Cancer Letters
https://www.readbyqxmd.com/read/25754329/radiation-and-dual-checkpoint-blockade-activate-non-redundant-immune-mechanisms-in-cancer
#9
Christina Twyman-Saint Victor, Andrew J Rech, Amit Maity, Ramesh Rengan, Kristen E Pauken, Erietta Stelekati, Joseph L Benci, Bihui Xu, Hannah Dada, Pamela M Odorizzi, Ramin S Herati, Kathleen D Mansfield, Dana Patsch, Ravi K Amaravadi, Lynn M Schuchter, Hemant Ishwaran, Rosemarie Mick, Daniel A Pryma, Xiaowei Xu, Michael D Feldman, Tara C Gangadhar, Stephen M Hahn, E John Wherry, Robert H Vonderheide, Andy J Minn
Immune checkpoint inhibitors result in impressive clinical responses, but optimal results will require combination with each other and other therapies. This raises fundamental questions about mechanisms of non-redundancy and resistance. Here we report major tumour regressions in a subset of patients with metastatic melanoma treated with an anti-CTLA4 antibody (anti-CTLA4) and radiation, and reproduced this effect in mouse models. Although combined treatment improved responses in irradiated and unirradiated tumours, resistance was common...
April 16, 2015: Nature
https://www.readbyqxmd.com/read/25417103/exosome-transfer-from-stromal-to-breast-cancer-cells-regulates-therapy-resistance-pathways
#10
Mirjam C Boelens, Tony J Wu, Barzin Y Nabet, Bihui Xu, Yu Qiu, Taewon Yoon, Diana J Azzam, Christina Twyman-Saint Victor, Brianne Z Wiemann, Hemant Ishwaran, Petra J Ter Brugge, Jos Jonkers, Joyce Slingerland, Andy J Minn
Stromal communication with cancer cells can influence treatment response. We show that stromal and breast cancer (BrCa) cells utilize paracrine and juxtacrine signaling to drive chemotherapy and radiation resistance. Upon heterotypic interaction, exosomes are transferred from stromal to BrCa cells. RNA within exosomes, which are largely noncoding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent antiviral signaling. In parallel, stromal cells also activate NOTCH3 on BrCa cells...
October 23, 2014: Cell
https://www.readbyqxmd.com/read/24368849/mir-218-opposes-a-critical-rtk-hif-pathway-in-mesenchymal-glioblastoma
#11
Lijoy K Mathew, Nicolas Skuli, Vera Mucaj, Samuel S Lee, Pascal O Zinn, Pratheesh Sathyan, Hongxia Z Imtiyaz, Zhongfa Zhang, Ramana V Davuluri, Shilpa Rao, Sriram Venneti, Priti Lal, Justin D Lathia, Jeremy N Rich, Brian Keith, Andy J Minn, M Celeste Simon
Glioblastoma multiforme (GBM) and the mesenchymal GBM subtype in particular are highly malignant tumors that frequently exhibit regions of severe hypoxia and necrosis. Because these features correlate with poor prognosis, we investigated microRNAs whose expression might regulate hypoxic GBM cell survival and growth. We determined that the expression of microRNA-218 (miR-218) is decreased significantly in highly necrotic mesenchymal GBM, and orthotopic tumor studies revealed that reduced miR-218 levels confer GBM resistance to chemotherapy...
January 7, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/24169826/the-myc-mir-17-92-axis-amplifies-b-cell-receptor-signaling-via-inhibition-of-itim-proteins-a-novel-lymphomagenic-feed-forward-loop
#12
James N Psathas, Patrick J Doonan, Pichai Raman, Bruce D Freedman, Andy J Minn, Andrei Thomas-Tikhonenko
The c-Myc oncoprotein regulates >15% of the human transcriptome and a limited number of microRNAs (miRNAs). Here, we establish that in a human B-lymphoid cell line, Myc-repressed, but not Myc-stimulated, genes are significantly enriched for predicted binding sites of Myc-regulated miRNAs, primarily those comprising the Myc-activated miR-17~92 cluster. Notably, gene set enrichment analysis demonstrates that miR-17∼92 is a major regulator of B-cell receptor (BCR) pathway components. Many of them are immunoreceptor tyrosine inhibitory motif (ITIM)-containing proteins, and ITIM proteins CD22 and FCGR2B were found to be direct targets of miR-17∼92...
December 19, 2013: Blood
https://www.readbyqxmd.com/read/23982961/triple-negative-breast-cancer-initiating-cell-subsets-differ-in-functional-and-molecular-characteristics-and-in-%C3%AE-secretase-inhibitor-drug-responses
#13
Diana J Azzam, Dekuang Zhao, Jun Sun, Andy J Minn, Prathibha Ranganathan, Katherine Drews-Elger, Xiaoqing Han, Manuel Picon-Ruiz, Candace A Gilbert, Seth A Wander, Anthony J Capobianco, Dorraya El-Ashry, Joyce M Slingerland
Increasing evidence suggests that stem-like cells mediate cancer therapy resistance and metastasis. Breast tumour-initiating stem cells (T-ISC) are known to be enriched in CD44(+) CD24(neg/low) cells. Here, we identify two T-ISC subsets within this population in triple negative breast cancer (TNBC) lines and dissociated primary breast cancer cultures: CD44(+) CD24(low+) subpopulation generates CD44(+) CD24(neg) progeny with reduced sphere formation and tumourigenicity. CD44(+) CD24(low+) populations contain subsets of ALDH1(+) and ESA(+) cells, yield more frequent spheres and/or T-ISC in limiting dilution assays, preferentially express metastatic gene signatures and show greater motility, invasion and, in the MDA-MB-231 model, metastatic potential...
October 2013: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/23811687/tap73-enhances-the-pentose-phosphate-pathway-and-supports-cell-proliferation
#14
Wenjing Du, Peng Jiang, Anthony Mancuso, Aaron Stonestrom, Michael D Brewer, Andy J Minn, Tak W Mak, Mian Wu, Xiaolu Yang
TAp73 is a structural homologue of the pre-eminent tumour suppressor p53. However, unlike p53, TAp73 is rarely mutated, and instead is frequently overexpressed in human tumours. It remains unclear whether TAp73 affords an advantage to tumour cells and if so, what the underlying mechanism is. Here we show that TAp73 supports the proliferation of human and mouse tumour cells. TAp73 activates the expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP)...
August 2013: Nature Cell Biology
https://www.readbyqxmd.com/read/23430223/pi3k-mtor-inhibition-can-impair-tumor-invasion-and-metastasis-in-vivo-despite-a-lack-of-antiproliferative-action-in-vitro-implications-for-targeted-therapy
#15
Seth A Wander, Dekuang Zhao, Alexandra H Besser, Feng Hong, Jianqin Wei, Tan A Ince, Clara Milikowski, Nanette H Bishopric, Andy J Minn, Chad J Creighton, Joyce M Slingerland
Oncogenic PI3K/mTOR activation is frequently observed in human cancers and activates cell motility via p27 phosphorylations at T157 and T198. Here we explored the potential for a novel PI3K/mTOR inhibitor to inhibit tumor invasion and metastasis. An MDA-MB-231 breast cancer line variant, MDA-MB-231-1833, with high metastatic bone tropism, was treated with a novel catalytic PI3K/mTOR inhibitor, PF-04691502, at nM doses that did not impair proliferation. Effects on tumor cell motility, invasion, p27 phosphorylation, localization, and bone metastatic outgrowth were assayed...
April 2013: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/23249750/targeting-of-tgf%C3%AE-signature-and-its-essential-component-ctgf-by-mir-18-correlates-with-improved-survival-in-glioblastoma
#16
Jamie L Fox, Michael Dews, Andy J Minn, Andrei Thomas-Tikhonenko
The miR-17∼92 cluster is thought to be an oncogene, yet its expression is low in glioblastoma multiforme (GBM) cell lines. This could allow unfettered expression of miR-17∼92 target genes such as connective tissue growth factor (CTGF; or CCN2), which is known to contribute to GBM pathogenesis. Indeed, microRNA-18a (but not other miR-17∼92 members) has a functional site in the CTGF 3' UTR, and its forced reexpression sharply reduces CTGF protein and mRNA levels. Interestingly, it also reduces the levels of CTGF primary transcript...
February 2013: RNA
https://www.readbyqxmd.com/read/22659842/identification-of-novel-metastasis-suppressor-signaling-pathways-for-breast-cancer
#17
REVIEW
Andy J Minn, Elena Bevilacqua, Jieun Yun, Marsha Rich Rosner
Cancer lethality is mainly caused by metastasis. Therefore, understanding the nature of the genes involved in this process has become a priority. Given the heterogeneity of mutations in cancer cells, considerable focus has been directed toward characterizing metastasis genes in the context of relevant signaling pathways rather than treating genes as independent and equal entities. One signaling cascade implicated in the regulation of cell growth, invasion and metastasis is the MAP kinase pathway. Raf kinase inhibitory protein (RKIP) functions as an inhibitor of the MAP kinase pathway and is a metastasis suppressor in different cancer models...
July 1, 2012: Cell Cycle
https://www.readbyqxmd.com/read/21873975/signalling-pathway-for-rkip-and-let-7-regulates-and-predicts-metastatic-breast-cancer
#18
Jieun Yun, Casey A Frankenberger, Wen-Liang Kuo, Mirjam C Boelens, Eva M Eves, Nancy Cheng, Han Liang, Wen-Hsiung Li, Hemant Ishwaran, Andy J Minn, Marsha Rich Rosner
Tumour metastasis suppressors are inhibitors of metastasis but their mechanisms of action are generally not understood. We previously showed that the suppressor Raf kinase inhibitory protein (RKIP) inhibits breast tumour metastasis in part via let-7. Here, we demonstrate an integrated approach combining statistical analysis of breast tumour gene expression data and experimental validation to extend the signalling pathway for RKIP. We show that RKIP inhibits let-7 targets (HMGA2, BACH1) that in turn upregulate bone metastasis genes (MMP1, OPN, CXCR4)...
November 2, 2011: EMBO Journal
https://www.readbyqxmd.com/read/21423468/arriving-safely-and-avoiding-a-puncture-use-of-a-radi-pressurewire-to-cross-an-ats-prosthetic-aortic-valve-for-direct-measurement-of-left-ventricular-pressure
#19
Mohammed Aziz Moharram, Andy S Yong, Vincent Khoury, Harry C Lowe
The direct measurement of left ventricular pressure in the presence of a mechanical aortic valve is a technical challenge for the interventional cardiologist. Direct recording, which is rarely performed, becomes necessary when other imaging methods have failed to evaluate prosthetic valve stenosis or restrictive physiology. Left ventricular pressure has typically been measured after transseptal or direct left ventricular apical puncture.In recent years, investigators have used the 0.014-in coronary Radi PressureWire™ (St...
2011: Texas Heart Institute Journal
https://www.readbyqxmd.com/read/21382866/supported-community-exercise-in-people-with-long-term-neurological-conditions-a-phase-ii-randomized-controlled-trial
#20
RANDOMIZED CONTROLLED TRIAL
Charlotte Elsworth, Charlotte Winward, Cath Sackley, Charmaine Meek, Jane Freebody, Patrick Esser, Hooshang Izadi, Andy Soundy, Karen Barker, David Hilton-Jones, Catherine Minns Lowe, Sandra Paget, Martin Tims, Richard Parnell, Smitaa Patel, Derick Wade, Helen Dawes
OBJECTIVE: Adults with long-term neurological conditions have low levels of participation in physical activities and report many barriers to participation in exercise. This study examines the feasibility and safety of supporting community exercise for people with long-term neurological conditions using a physical activity support system. DESIGN: A phase II randomized controlled trial using computer-generated block randomization, allocation concealment and single blind outcome assessment...
July 2011: Clinical Rehabilitation
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