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https://www.readbyqxmd.com/read/28885696/survivorship-care-planning-in-skin-cancer-an-unbiased-statistical-approach-to-identifying-patterns-of-care-plan-use
#1
Joseph L Benci, Andy J Minn, Carolyn C Vachani, Christina Bach, Karen Arnold-Korzeniowski, Margaret K Hampshire, James M Metz, Christine E Hill-Kayser
BACKGROUND: Nearly 1 in 5 Americans will develop skin cancer, and as a result, survivors of skin cancer compose one of the largest groups of cancer survivors. Survivorship care plans (SCPs) are an important tool for improving patient outcomes and provide critical information to both survivors and health care professionals. Recent efforts have been made to expand SCP utilization; however, which patients currently receive SCPs is poorly understood. METHODS: This study used 596 individuals with a diagnosis of melanoma (n = 391) or nonmelanoma skin cancer (n = 205) who had used an Internet-based SCP tool from May 2010 to December 2016 to model the patient and provider characteristics that determine SCP utilization...
September 8, 2017: Cancer
https://www.readbyqxmd.com/read/28759889/mitotic-progression-following-dna-damage-enables-pattern-recognition-within-micronuclei
#2
Shane M Harding, Joseph L Benci, Jerome Irianto, Dennis E Discher, Andy J Minn, Roger A Greenberg
Inflammatory gene expression following genotoxic cancer therapy is well documented, yet the events underlying its induction remain poorly understood. Inflammatory cytokines modify the tumour microenvironment by recruiting immune cells and are critical for both local and systemic (abscopal) tumour responses to radiotherapy. A poorly understood feature of these responses is the delayed onset (days), in contrast to the acute DNA-damage responses that occur in minutes to hours. Such dichotomous kinetics implicate additional rate-limiting steps that are essential for DNA-damage-induced inflammation...
August 24, 2017: Nature
https://www.readbyqxmd.com/read/28709002/exosome-rna-unshielding-couples-stromal-activation-to-pattern-recognition-receptor-signaling-in-cancer
#3
Barzin Y Nabet, Yu Qiu, Jacob E Shabason, Tony J Wu, Taewon Yoon, Brian C Kim, Joseph L Benci, Angela M DeMichele, Julia Tchou, Joseph Marcotrigiano, Andy J Minn
Interactions between stromal fibroblasts and cancer cells generate signals for cancer progression, therapy resistance, and inflammatory responses. Although endogenous RNAs acting as damage-associated molecular patterns (DAMPs) for pattern recognition receptors (PRRs) may represent one such signal, these RNAs must remain unrecognized under non-pathological conditions. We show that triggering of stromal NOTCH-MYC by breast cancer cells results in a POL3-driven increase in RN7SL1, an endogenous RNA normally shielded by RNA binding proteins SRP9/14...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28689661/nuclear-acetyl-coa-production-by-acly-promotes-homologous-recombination
#4
Sharanya Sivanand, Seth Rhoades, Qinqin Jiang, Joyce V Lee, Joseph Benci, Jingwen Zhang, Salina Yuan, Isabella Viney, Steven Zhao, Alessandro Carrer, Michael J Bennett, Andy J Minn, Aalim M Weljie, Roger A Greenberg, Kathryn E Wellen
While maintaining the integrity of the genome and sustaining bioenergetics are both fundamental functions of the cell, potential crosstalk between metabolic and DNA repair pathways is poorly understood. Since histone acetylation plays important roles in DNA repair and is sensitive to the availability of acetyl coenzyme A (acetyl-CoA), we investigated a role for metabolic regulation of histone acetylation during the DNA damage response. In this study, we report that nuclear ATP-citrate lyase (ACLY) is phosphorylated at S455 downstream of ataxia telangiectasia mutated (ATM) and AKT following DNA damage...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28577836/radiation-and-immune-checkpoint-blockade-from-bench-to-clinic
#5
REVIEW
Jacob E Shabason, Andy J Minn
Immune escape of malignant cells is an important hallmark of cancer, necessary for tumor formation and progression. Accordingly, in recent years, therapies that enhance the immune system have had remarkable success in treating a myriad of malignancies. Particularly successful has been immune checkpoint blockade (ICB), which is a therapy that targets T-cell inhibitory receptors, or immune checkpoints. Despite these encouraging clinical results, most patients do not respond to such agents. Therefore, determining methods to better target and enhance the therapeutic efficacy of ICB is of paramount importance...
July 2017: Seminars in Radiation Oncology
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#6
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27573852/assessing-intratumor-heterogeneity-and-tracking-longitudinal-and-spatial-clonal-evolutionary-history-by-next-generation-sequencing
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
2013: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/23811687/tap73-enhances-the-pentose-phosphate-pathway-and-supports-cell-proliferation
#20
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
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