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Cancer Research

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https://www.readbyqxmd.com/read/28330931/egfr-dependent-regulated-intramembrane-proteolysis-of-epcam-response
#1
LETTER
Ya-Ting Hsu, Pawel Osmulski, Yao Wang, Yi-Wen Huang, Lu Liu, Jianhua Ruan, Victor X Jin, Nameer B Kirma, Maria E Gaczynska, Tim Hui-Ming Huang
No abstract text is available yet for this article.
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28330930/egfr-dependent-regulated-intramembrane-proteolysis-of-epcam-letter
#2
LETTER
Olivier Gires
No abstract text is available yet for this article.
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28330929/the-role-of-pias-sumo-e3-ligases-in-cancer
#3
REVIEW
Andrea Rabellino, Cristina Andreani, Pier Paolo Scaglioni
SUMOylation modifies the interactome, localization, activity, and lifespan of its target proteins. This process regulates several cellular machineries, including transcription, DNA damage repair, cell-cycle progression, and apoptosis. Accordingly, SUMOylation is critical in maintaining cellular homeostasis, and its deregulation leads to the corruption of a plethora of cellular processes that contribute to disease states. Among the proteins involved in SUMOylation, the protein inhibitor of activated STAT (PIAS) E3-ligases were initially described as transcriptional coregulators...
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28330928/surgery-for-cancer-a-trigger-for-metastases
#4
REVIEW
Samer Tohme, Richard L Simmons, Allan Tsung
Surgery is a crucial intervention and provides a chance of cure for patients with cancer. The perioperative period is characterized by an increased risk for accelerated growth of micrometastatic disease and increased formation of new metastatic foci. The true impact for cancer patients remains unclear. This review summarizes the often fragmentary clinical and experimental evidence supporting the role of surgery and inflammation as potential triggers for disease recurrence. Surgery induces increased shedding of cancer cells into the circulation, suppresses antitumor immunity allowing circulating cells to survive, upregulates adhesion molecules in target organs, recruits immune cells capable of entrapping tumor cells, and induces changes in the target tissue and in the cancer cells themselves to enhance migration and invasion to establish at the target site...
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28330927/e3-ubiquitin-ligase-ubr5-drives-the-growth-and-metastasis-of-triple-negative-breast-cancer
#5
Liqiu Liao, Mei Song, Xin Li, Lili Tang, Tuo Zhang, Lixing Zhang, Yihang Pan, Lotfi Chouchane, Xiaojing Ma
Patients with triple negative breast cancers (TNBC) are at high risk for recurrence and metastasis at an early time despite standard treatment, underscoring the need for novel therapeutic modalities. Here we report for the first time a distinctive and profound role of the E3 ubiquitin ligase UBR5 in the growth and metastasis of TNBC. An analysis of primary TNBC specimen by whole exon sequencing revealed strong gene amplifications of UBR5 associated with the disease. UBR5 overexpression in TNBC tissues was confirmed at mRNA and protein levels...
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28314785/tumor-localized-secretion-of-soluble-pd1-enhances-oncolytic-virotherapy
#6
Mee Y Bartee, Katherine M Dunlap, Eric Bartee
Oncolytic virotherapy represents an attractive option for the treatment of a variety of aggressive or refractory tumors. While this therapy is effective at rapidly debulking directly injected tumor masses, achieving complete eradication of established disease has proven difficult. One method to overcome this challenge is to use oncolytic viruses to induce secondary anti-tumor immune responses. Unfortunately, while the initial induction of these immune responses is typically robust, their subsequent efficacy is often inhibited through a variety of immunoregulatory mechanisms, including the PD1/PDL1 T-cell checkpoint pathway...
March 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28314784/integrative-cancer-pharmacogenomics-to-infer-large-scale-drug-taxonomy
#7
Nehme El-Hachem, Deena M A Gendoo, Laleh Soltan Ghoraie, Zhaleh Safikhani, Petr Smirnov, Christina Chung, Kenan Deng, Alisa Fang, Erin Birkwood, Chantal Ho, Ruth Isserlin, Gary Bader, Anna Goldenberg, Benjamin Haibe-Kains
Identification of drug targets and mechanism of action (MoA) for new and uncharacterized anticancer drugs is important for optimization of treatment efficacy. Current MoA prediction largely relies on prior information including side effects, therapeutic indication, and chemo-informatics. Such information is not transferable or applicable for newly identified, previously uncharacterized small molecules. Therefore, a shift in the paradigm of MoA predictions is necessary towards development of unbiased approaches that can elucidate drug relationships and efficiently classify new compounds with basic input data...
March 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28302679/disrupting-androgen-receptor-signaling-induces-snail-mediated-epithelial-mesenchymal-plasticity-in-prostate-cancer
#8
Lu Miao, Lin Yang, Rui Li, Daniel Nava Rodrigues, Mateus Crespo, Jer-Tsong Hsieh, Wayne D Tilley, Johann S de Bono, Luke A Selth, Ganesh V Raj
Epithelial to mesenchymal plasticity (EMP) has been linked to metastasis, stemness, and drug resistance. In prostate cancer (PCa), EMP has been associated with both suppression and activation of androgen receptor (AR) signaling. Here we investigated the effect of the potent AR antagonist enzalutamide on EMP in multiple preclinical models of PCa and patient tissues. Enzalutamide treatment significantly enhanced the expression of EMP drivers (ZEB1, ZEB2, Snail, Twist, and FOXC2) and mesenchymal markers (N-cadherin, fibronectin, and vimentin) in PCa cells, enhanced PCa cell migration, and induced PCa transformation to a spindle, fibroblast-like morphology...
March 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28292977/the-host-microbiome-regulates-and-maintains-human-health-a-primer-and-perspective-for-non-microbiologists
#9
REVIEW
Sunil Thomas, Jacques Izard, Emily Walsh, Kristen Batich, Pakawat Chongsathidkiet, Gerard Clarke, David A Sela, Alexander J Muller, James M Mullin, Korin Albert, John P Gilligan, Katherine DiGuilio, Rima Dilbarova, Walker Alexander, George C Prendergast
Humans consider themselves discrete autonomous organisms, but recent research is rapidly strengthening the appreciation that associated microorganisms make essential contributions to human health and well being. Each person is inhabited and also surrounded by his/her own signature microbial cloud. A low diversity of microorganisms is associated with a plethora of diseases, including allergy, diabetes, obesity, arthritis, inflammatory bowel diseases, and even neuropsychiatric disorders. Thus, an interaction of microorganisms with the host immune system is required for a healthy body...
March 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28283655/cell-cycle-regulation-accounts-for-variability-in-ki-67-expression-levels
#10
Michal Sobecki, Karim Mrouj, Jacques Colinge, François Gerbe, Philippe Jay, Liliana Krasinska, Vjekoslav Dulic, Daniel Fisher
The cell proliferation antigen Ki-67 is widely used in cancer histopathology, but estimations of Ki-67 expression levels are inconsistent and understanding of its regulation is limited. Here we show that cell cycle regulation underlies variable Ki-67 expression in all situations analyzed, including non-transformed human cells, normal mouse intestinal epithelia and adenomas, human cancer cell lines with or without drug treatments, and human breast and colon cancers. In normal cells, Ki-67 was a late marker of cell cycle entry; Ki-67 mRNA oscillated with highest levels in G2 while protein levels increased throughout the cell cycle, peaking in mitosis...
March 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28283654/a-model-based-personalized-cancer-screening-strategy-for-detecting-early-stage-tumors-using-blood-borne-biomarkers
#11
Sharon Seiko Hori, Amelie M Lutz, Ramasamy Paulmurugan, Sanjiv S Gambhir
An effective cancer blood biomarker screening strategy must distinguish aggressive from non-aggressive tumors at an early, intervenable time. However, for blood-based strategies to be useful, the quality and quantiy of the biomarker shed into the blood and its relationship to tumor growth or progression must be validated. To study how blood biomarker levels correlate with early-stage viable tumor growth in an mouse model of human cancer, we monitored early tumor growth of engineered human ovarian cancer cells (A2780) implanted orthotopically into nude mice...
March 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28283653/antibody-drug-conjugates-bearing-pyrrolobenzodiazepine-or-tubulysin-payloads-are-immunomodulatory-and-synergize-with-multiple-immunotherapies
#12
Jonathan Rios-Doria, Jay Harper, Raymond Rothstein, Leslie Wetzel, Jon Chesebrough, Allison M Marrero, Cui Chen, Patrick Strout, Kathy Mulgrew, Kelly A McGlinchey, Ryan Fleming, Binyam Bezabeh, John Meekin, David Stewart, Maureen Kennedy, Philip Martin, Andrew Buchanan, Nazzareno Dimasi, Emil F Michelotti, Robert E Hollingsworth
Immunogenic cell death (ICD) is the process by which certain cytotoxic drugs induce apoptosis of tumor cells in a manner that stimulates the immune system. In this study, we investigated whether antibody-drug conjugates (ADC) conjugated with pyrrolobenzodiazepine dimer (PBD) or tubulysin payloads induce ICD, modulate the immune microenvironment, and could combine with IO drugs to enhance antitumor activity. We show that these payloads on their own induced an immune response that prevented the growth of tumors following subsequent tumor cell challenge...
March 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28283652/brca2-hypomorphic-missense-variants-confer-moderate-risks-of-breast-cancer
#13
Hermela Shimelis, Romy L S Mesman, Catharina Von Nicolai, Asa Ehlen, Lucia Guidugli, Charlotte Martin, Fabienne Mgr Calleja, Huong Meeks, Emily Hallberg, Jamie Hinton, Jenna Lilyquist, Chunling Hu, Cora M Aalfs, Kristiina Aittomaki, Irene L Andrulis, Hoda Anton-Culver, Volker Arndt, Matthias W Beckmann, Javier J Benitez, Natalia Bogdanova, Stig E Bojesen, Manjeet K Bolla, Anne-Lise Borresen-Dale, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Annegien Broeks, Barbara Brouwers, Thomas Bruning, Barbara Burwinkel, Jenny Chang-Claude, Georgia Chenevix-Trench, Ching-Yu Cheng, Ji-Yeob Choi, J Margriet Collée, Angela Cox, Simon S Cross, Kamila Czene, Hatef Darabi, Joe Dennis, Thilo Dork, Isabel Dos Santos Silva, Alison M Dunning, Peter A Fasching, Jonine D Figueroa, Henrik Flyger, Montserrat Garcia-Closas, Graham G Giles, Gord Glendon, Pascal Guenel, Christopher A Haiman, Per Hall, Ute Hamann, Mikael Hartman, Frans B L Hogervorst, Antoinette Hollestelle, John L Hopper, Hidemi Ito, Anna Jakubowska, Daehee Kang, Veli-Matti Kosma, Vessela Kristensen, Kah-Nyin Lai, Diether Lambrechts, Loic Le Marchand, Jingmei Li, Annika Lindblom, Artitaya Lophatananon, Jan Lubinski, Eva Machackova, Arto Mannermaa, Sara Margolin, Frederik Marme, Keitaro Matsuo, Hui Miao, Kyriaki Michailidou, Roger L Milne, Kenneth Muir, Susan L Neuhausen, Heli Nevanlinna, Janet E Olson, Curtis Olswold, Jan C Oosterwijk, Ana Osorio, Paolo Peterlongo, Julian Peto, Paul D P Pharoah, Katri Pylkäs, Paolo Radice, Muhammad U Rashid, Valerie Rhenius, Anja Rudolph, Suleeporn Sangrajrang, Elinor J Sawyer, Marjanka K Schmidt, Minouk J Schoemaker, Caroline M Seynaeve, Mitul Shah, Chen-Yang Shen, Martha J Shrubsole, Xiao-Ou Shu, Susan L Slager, Melissa C Southey, Daniel O Stram, Anthony J Swerdlow, Soo Hwang Teo, Ian Tomlinson, Diana Torres, Therese Truong, Christi J van Asperen, Lizet E van der Kolk, Qin Wang, Robert Winqvist, Anna H Wu, Jyh-Cherng Yu, Wei Zheng, Ying Zheng, Jennifer Leary, Logan C Walker, Lenka Foretova, Florentia Fostira, Kathleen Claes, Liliana Varesco, Setareh Moghadasi, Douglas F Easton, Amanda B Spurdle, Peter Devilee, Harry Vrieling, Alvaro N Monteiro, David E Goldgar, Aura Carreira, Maaike P G Vreeswijk, Fergus J Couch
Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls)...
March 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28280038/pancreatic-cancer-progression-relies-upon-mutant-p53-induced-oncogenic-signaling-mediated-by-nop14
#14
Yongxing Du, Ziwen Liu, Lei You, Pengjiao Hou, Xiaoxia Ren, Tao Jiao, Wenjing Zhao, Zongze Li, Hong Shu, Changzheng Liu, Yu-Pei Zhao
Mutant p53 (mutp53) proteins promote tumor invasion and metastasis in pancreatic ductal adenocarcinoma (PDAC). However, the mechanism underlying sustained activation of mutp53 oncogenic signaling is currently unclear. In this study, we report that NOP14 nucleolar protein (NOP14) expression is upregulated in PDAC tumors and metastatic tissue specimens. NOP14 overexpression promoted cell motility, whereas NOP14 inhibition decreased invasive capacity of PDAC cells. In vivo invasion assays conducted on established subcutaneously, orthotopically, and intravenously injected tumor mouse models also indicated NOP14 as a promoter of PDAC metastasis...
March 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28280037/local-activation-of-p53-in-the-tumor-microenvironment-overcomes-immune-suppression-and-enhances-antitumor-immunity
#15
Gang Guo, Miao Yu, Wei Xiao, Esteban Celis, Yan Cui
Mutations in tumor suppressor p53 remain a vital mechanism of tumor escape from apoptosis and senescence. Emerging evidence suggests that p53 dysfunction also fuels inflammation and supports tumor immune evasion, thereby serving as an immunological driver of tumorigenesis. Therefore, targeting p53 in the tumor microenvironment (TME) also represents an immunologically desirable strategy for reversing immunosuppression and enhancing antitumor immunity. Using a pharmacological p53 activator nutlin-3a, we show that local p53 activation in TME comprising overt tumor infiltrating leukocytes (TILeus) induces systemic antitumor immunity and tumor regression, but not in TME with scarce TILeus, such as B16 melanoma...
March 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28249908/kinome-wide-rna-interference-screen-reveals-a-role-for-pdk1-in-acquired-resistance-to-cdk4-6-inhibition-in-er-positive-breast-cancer
#16
Valerie M Jansen, Neil E Bhola, Joshua A Bauer, Luigi Formisano, Kyung-Min Lee, Katherine E Hutchinson, Agnieszka K Witkiewicz, Preston D Moore, Monica Valeria Estrada, Violeta Sanchez, Paula G Ericsson, Melinda Sanders, Paula R Pohlmann, Michael J Pishvaian, David A Riddle, Wenyi Wei, Teresa C Dugger, Erik Knudsen, Carlos L Arteaga
To discover mechanisms of resistance to CDK4/6 inhibitors, we used a kinome-wide siRNA screen to identify kinases that, when downregulated, promote sensitivity to ribociclib. We identified 3-phosphoinositide dependent protein kinase 1 (PDK1) as the top siRNA that sensitized ER+ MCF-7 cells to ribociclib. Pharmacological inhibition of PDK1 with GSK2334470 in combination with ribociclib or palbociclib, synergistically inhibited proliferation and increased apoptosis in a panel of ER+ breast cancer cell lines. Ribociclib-resistant MCF-7, T47D and HCC1428 cells, selected after chronic drug exposure, displayed increased levels of PDK1, P-RSK2, P-AKT and P-S6 compared to parental drug-sensitive cells...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28249907/hdac-inhibitor-panobinostat-engages-host-innate-immune-defenses-to-promote-the-tumoricidal-effects-of-trastuzumab-in-her2-tumors
#17
Mikolaj Medon, Eva Vidacs, Stephin J Vervoort, Jason Li, Misty R Jenkins, Kelly M Ramsbottom, Joseph A Trapani, Mark J Smyth, Phillip K Darcy, Peter W Atadja, Michael A Henderson, Ricky W Johnstone, Nicole M Haynes
Histone deacetylase inhibitors (HDACi) may engage host immunity as one basis for their antitumor effects. Herein we demonstrate an application of this concept using the HDACi panobinostat to augment the antitumor efficacy of trastuzumab (anti-HER2) therapy, through both tumor cell autonomous and non-autonomous mechanisms. In HER2+ tumors that are inherently sensitive to the cytostatic effects of trastuzumab, co-treatment with panobinostat abrogated AKT signaling and triggered tumor regression in mice that lacked innate and/or adaptive immune effector cells...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28249906/nr4a3-suppresses-lymphomagenesis-through-induction-of-pro-apoptotic-genes
#18
Alexander Ja Deutsch, Beate Rinner, Martin Pichler, Katharina Troppan, Katrin Pansy, Marco Bischof, Karoline Fechter, Stefan Hatzl, Julia Feichtinger, Kerstin Wenzl, Marie-Therese Frisch, Verena Stiegelbauer, Andreas Prokesch, Anne Margrethe Krogsdam, Heinz Sill, Gerhard G Thallinger, Hildegard T Greinix, Chenguang Wang, Christine Beham-Schmid, Peter Neumeister
Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared to vector control and uninduced cells which formed massive tumors...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28249905/intrinsic-subtypes-and-gene-expression-profiles-in-primary-and-metastatic-breast-cancer
#19
Juan Miguel Cejalvo, Eduardo Martínez de Dueñas, Patricia Galvan, Susana García-Recio, Octavio Burgués Gasión, Laia Paré, Silvia Antolin, Rossella Martinello, Isabel Blancas, Barbara Adamo, Angel Guerrero-Zotano, Montserrat Muñoz, Paolo Nuciforo, María Vidal, Ramón M Pérez, José Ignacio Chacón López-Muñiz, Rosalía Caballero, Vicente Peg, Eva Carrasco, Federico Rojo, Charles M Perou, Javier Cortes, Vincenzo Adamo, Joan Albanell, Roger R Gomis, Ana Lluch, Aleix Prat
Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and Chi-square tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors and 55...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28249904/nr1d1-recruitment-to-sites-of-dna-damage-inhibits-repair-and-is-associated-with-chemosensitivity-of-breast-cancer
#20
Na-Lee Ka, Tae-Young Na, Hyelin Na, Min-Ho Lee, Han-Su Park, Sewon Hwang, Il-Yong Kim, Je Kyung Seong, Mi-Ock Lee
DNA repair capacity is critical for survival of cancer cells upon therapeutic DNA damage and thus is an important determinant of susceptibility to chemotherapy in cancer patients. In this study, we identified a novel function of nuclear receptor NR1D1 in DNA repair, which enhanced chemosensitivity in breast cancer cells. NR1D1 inhibited both non-homologous end joining and homologous recombination double strand breaks (DSB) repair, and delayed the clearance of γH2AX DNA repair foci that formed after treatment of doxorubicin...
March 1, 2017: Cancer Research
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