journal
MENU ▼
Read by QxMD icon Read
search

Cancer Cell

journal
https://www.readbyqxmd.com/read/29290541/genomic-and-epigenomic-profiling-of-high-risk-intestinal-metaplasia-reveals-molecular-determinants-of-progression-to-gastric-cancer
#1
Kie Kyon Huang, Kalpana Ramnarayanan, Feng Zhu, Supriya Srivastava, Chang Xu, Angie Lay Keng Tan, Minghui Lee, Suting Tay, Kakoli Das, Manjie Xing, Aliya Fatehullah, Syed Muhammad Fahmy Alkaff, Tony Kiat Hon Lim, Jonathan Lee, Khek Yu Ho, Steven George Rozen, Bin Tean Teh, Nick Barker, Chung King Chia, Christopher Khor, Choon Jin Ooi, Kwong Ming Fock, Jimmy So, Wee Chian Lim, Khoon Lin Ling, Tiing Leong Ang, Andrew Wong, Jaideepraj Rao, Andrea Rajnakova, Lee Guan Lim, Wai Ming Yap, Ming Teh, Khay Guan Yeoh, Patrick Tan
Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We performed (epi)genomic profiling of 138 IMs from 148 cancer-free patients, recruited through a 10-year prospective study. Compared with GCs, IMs exhibit low mutational burdens, recurrent mutations in certain tumor suppressors (FBXW7) but not others (TP53, ARID1A), chromosome 8q amplification, and shortened telomeres. Sequencing identified more IM patients with active Helicobacter pylori infection compared with histopathology (11%-27%)...
December 26, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29275866/cooperative-epigenetic-remodeling-by-tet2-loss-and-nras-mutation-drives-myeloid-transformation-and-mek-inhibitor-sensitivity
#2
Hiroyoshi Kunimoto, Cem Meydan, Abbas Nazir, Justin Whitfield, Kaitlyn Shank, Franck Rapaport, Rebecca Maher, Elodie Pronier, Sara C Meyer, Francine E Garrett-Bakelman, Martin Tallman, Ari Melnick, Ross L Levine, Alan H Shih
Mutations in epigenetic modifiers and signaling factors often co-occur in myeloid malignancies, including TET2 and NRAS mutations. Concurrent Tet2 loss and NrasG12D expression in hematopoietic cells induced myeloid transformation, with a fully penetrant, lethal chronic myelomonocytic leukemia (CMML), which was serially transplantable. Tet2 loss and Nras mutation cooperatively led to decrease in negative regulators of mitogen-activated protein kinase (MAPK) activation, including Spry2, thereby causing synergistic activation of MAPK signaling by epigenetic silencing...
December 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29249692/%C3%AE-2-adrenergic-neurotrophin-feedforward-loop-promotes-pancreatic-cancer
#3
Bernhard W Renz, Ryota Takahashi, Takayuki Tanaka, Marina Macchini, Yoku Hayakawa, Zahra Dantes, H Carlo Maurer, Xiaowei Chen, Zhengyu Jiang, C Benedikt Westphalen, Matthias Ilmer, Giovanni Valenti, Sarajo K Mohanta, Andreas J R Habenicht, Moritz Middelhoff, Timothy Chu, Karan Nagar, Yagnesh Tailor, Riccardo Casadei, Mariacristina Di Marco, Axel Kleespies, Richard A Friedman, Helen Remotti, Maximilian Reichert, Daniel L Worthley, Jens Neumann, Jens Werner, Alina C Iuga, Kenneth P Olive, Timothy C Wang
Catecholamines stimulate epithelial proliferation, but the role of sympathetic nerve signaling in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. Catecholamines promoted ADRB2-dependent PDAC development, nerve growth factor (NGF) secretion, and pancreatic nerve density. Pancreatic Ngf overexpression accelerated tumor development in LSL-Kras+/G12D;Pdx1-Cre (KC) mice. ADRB2 blockade together with gemcitabine reduced NGF expression and nerve density, and increased survival of LSL-Kras+/G12D;LSL-Trp53+/R172H;Pdx1-Cre (KPC) mice...
December 1, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29249691/dual-targeting-of-oncogenic-activation-and-inflammatory-signaling-increases-therapeutic-efficacy-in-myeloproliferative-neoplasms
#4
Maria Kleppe, Richard Koche, Lihua Zou, Peter van Galen, Corinne E Hill, Lauren Dong, Sofie De Groote, Efthymia Papalexi, Amritha V Hanasoge Somasundara, Keith Cordner, Matthew Keller, Noushin Farnoud, Juan Medina, Erin McGovern, Jaime Reyes, Justin Roberts, Matthew Witkins, Franck Rapaport, Julie Teruya-Feldstein, Jun Qi, Raajit Rampal, Bradley E Bernstein, James E Bradner, Ross L Levine
Genetic and functional studies underscore the central role of JAK/STAT signaling in myeloproliferative neoplasms (MPNs). However, the mechanisms that mediate transformation in MPNs are not fully delineated, and clinically utilized JAK inhibitors have limited ability to reduce disease burden or reverse myelofibrosis. Here we show that MPN progenitor cells are characterized by marked alterations in gene regulation through differential enhancer utilization, and identify nuclear factor κB (NF-κB) signaling as a key pathway activated in malignant and non-malignant cells in MPN...
December 1, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29198913/antibody-tumor-targeting-is-enhanced-by-cd27-agonists-through-myeloid-recruitment
#5
Anna H Turaj, Khiyam Hussain, Kerry L Cox, Matthew J J Rose-Zerilli, James Testa, Lekh N Dahal, H T Claude Chan, Sonya James, Vikki L Field, Matthew J Carter, Hyung J Kim, Jonathan J West, Lawrence J Thomas, Li-Zhen He, Tibor Keler, Peter W M Johnson, Aymen Al-Shamkhani, Stephen M Thirdborough, Stephen A Beers, Mark S Cragg, Martin J Glennie, Sean H Lim
Monoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T cell responses. Here, we examined the therapeutic potential of combining a direct tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs. Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple lymphoma models, including huCD27 transgenic mice using the anti-huCD27, varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing demonstrated that anti-CD27 stimulated CD8+ T and natural killer cells to release myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration and macrophage activation...
November 21, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29198914/glut3-addiction-is-a-druggable-vulnerability-for-a-molecularly-defined-subpopulation-of-glioblastoma
#6
Érika Cosset, Sten Ilmjärv, Valérie Dutoit, Kathryn Elliott, Tami von Schalscha, Maria F Camargo, Alexander Reiss, Toshiro Moroishi, Laetitia Seguin, German Gomez, Jung-Soon Moo, Olivier Preynat-Seauve, Karl-Heinz Krause, Hervé Chneiweiss, Jann N Sarkaria, Kun-Liang Guan, Pierre-Yves Dietrich, Sara M Weis, Paul S Mischel, David A Cheresh
While molecular subtypes of glioblastoma (GBM) are defined using gene expression and mutation profiles, we identify a unique subpopulation based on addiction to the high-affinity glucose transporter, Glut3. Although Glut3 is a known driver of a cancer stem cell phenotype, direct targeting is complicated by its expression in neurons. Using established GBM lines and patient-derived stem cells, we identify a subset of tumors within the "proneural" and "classical" subtypes that are addicted to aberrant signaling from integrin αvβ3, which activates a PAK4-YAP/TAZ signaling axis to enhance Glut3 expression...
November 17, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29153842/stress-activated-nrf2-mdm2-cascade-controls-neoplastic-progression-in-pancreas
#7
Jelena Todoric, Laura Antonucci, Giuseppe Di Caro, Ning Li, Xuefeng Wu, Nikki K Lytle, Debanjan Dhar, Sourav Banerjee, Johan B Fagman, Cecille D Browne, Atsushi Umemura, Mark A Valasek, Hannes Kessler, David Tarin, Michael Goggins, Tannishtha Reya, Maria Diaz-Meco, Jorge Moscat, Michael Karin
Despite expression of oncogenic KRAS, premalignant pancreatic intraepithelial neoplasia 1 (PanIN1) lesions rarely become fully malignant pancreatic ductal adenocarcinoma (PDAC). The molecular mechanisms through which established risk factors, such as chronic pancreatitis, acinar cell damage, and/or defective autophagy increase the likelihood of PDAC development are poorly understood. We show that accumulation of the autophagy substrate p62/SQSTM1 in stressed Kras(G12D) acinar cells is associated with PDAC development and maintenance of malignancy in human cells and mice...
November 7, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29153843/aberrant-activation-of-a-gastrointestinal-transcriptional-circuit-in-prostate-cancer-mediates-castration-resistance
#8
Shipra Shukla, Joanna Cyrta, Devan A Murphy, Edward G Walczak, Leili Ran, Praveen Agrawal, Yuanyuan Xie, Yuedan Chen, Shangqian Wang, Yu Zhan, Dan Li, Elissa W P Wong, Andrea Sboner, Himisha Beltran, Juan Miguel Mosquera, Jessica Sher, Zhen Cao, John Wongvipat, Richard P Koche, Anuradha Gopalan, Deyou Zheng, Mark A Rubin, Howard I Scher, Ping Chi, Yu Chen
Prostate cancer exhibits a lineage-specific dependence on androgen signaling. Castration resistance involves reactivation of androgen signaling or activation of alternative lineage programs to bypass androgen requirement. We describe an aberrant gastrointestinal-lineage transcriptome expressed in ∼5% of primary prostate cancer that is characterized by abbreviated response to androgen-deprivation therapy and in ∼30% of castration-resistant prostate cancer. This program is governed by a transcriptional circuit consisting of HNF4G and HNF1A...
November 3, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29316436/oncogenic-kras-regulates-amino-acid-homeostasis-and-asparagine-biosynthesis-via-atf4-and-alters-sensitivity-to-l-asparaginase
#9
Dana M Gwinn, Alex G Lee, Marcela Briones-Martin-Del-Campo, Crystal S Conn, David R Simpson, Anna I Scott, Anthony Le, Tina M Cowan, Davide Ruggero, E Alejandro Sweet-Cordero
KRAS is a regulator of the nutrient stress response in non-small-cell lung cancer (NSCLC). Induction of the ATF4 pathway during nutrient depletion requires AKT and NRF2 downstream of KRAS. The tumor suppressor KEAP1 strongly influences the outcome of activation of this pathway during nutrient stress; loss of KEAP1 in KRAS mutant cells leads to apoptosis. Through ATF4 regulation, KRAS alters amino acid uptake and asparagine biosynthesis. The ATF4 target asparagine synthetase (ASNS) contributes to apoptotic suppression, protein biosynthesis, and mTORC1 activation...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316435/molecular-predictors-of-gastric-neoplastic-progression
#10
Paul Lochhead, Emad M El-Omar
In this issue of Cancer Cell, Huang et al. describe comprehensive genetic and epigenetic profiling of gastric intestinal metaplasia lesions from a longitudinal cohort in which outcome data allowed for identification of potential markers of gastric neoplastic progression.
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316434/characterizing-the-killer-colorectal-carcinomas
#11
Stanley R Hamilton
In this issue of Cancer Cell, Yaeger et al. report mutations, copy number variations, and selected rearrangements from a large series of metastatic colorectal carcinomas and primaries that produced metastases. The results provide important insights into differences in anatomical site of origin, age at onset, etiologic factors, and therapeutic responses.
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316433/tim-3-regulates-cd103-dendritic-cell-function-and-response-to-chemotherapy-in-breast-cancer
#12
Álvaro de Mingo Pulido, Alycia Gardner, Shandi Hiebler, Hatem Soliman, Hope S Rugo, Matthew F Krummel, Lisa M Coussens, Brian Ruffell
Intratumoral CD103+ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103+ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8+ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316432/what-s-in-a-name-cell-fate-reprogramming-in-sarcomagenesis
#13
Kevin B Jones
Differentiation features in cancer cells are typically attributed to the cell of origin. In this issue of Cancer Cell, Drummond et al. demonstrate a transdifferentiation program apparent in rhabdomyosarcomas (cancers with skeletal muscle differentiation features) arising through cell fate reprogramming from a single oncogene activation in endothelial cell precursors.
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316431/bet-ing-on-dual-jak-bet-inhibition-as-a-therapeutic-strategy-for-myeloproliferative-neoplasms
#14
Qingfei Jiang, Catriona Jamieson
In this issue of Cancer Cell, Kleppe et al. describe a combination strategy designed to inhibit BET bromodomain and JAK/STAT signaling as a method for effectively inhibiting NF-κB and cytokine production in myeloproliferative neoplasms (MPNs). The results provide a strong rationale for clinical evaluation of dual BET/JAK inhibition in MPNs.
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316430/tumor-evolution-of-glioma-intrinsic-gene-expression-subtypes-associates-with-immunological-changes-in-the-microenvironment
#15
Qianghu Wang, Baoli Hu, Xin Hu, Hoon Kim, Massimo Squatrito, Lisa Scarpace, Ana C deCarvalho, Sali Lyu, Pengping Li, Yan Li, Floris Barthel, Hee Jin Cho, Yu-Hsi Lin, Nikunj Satani, Emmanuel Martinez-Ledesma, Siyuan Zheng, Edward Chang, Charles-Etienne Gabriel Sauvé, Adriana Olar, Zheng D Lan, Gaetano Finocchiaro, Joanna J Phillips, Mitchel S Berger, Konrad R Gabrusiewicz, Guocan Wang, Eskil Eskilsson, Jian Hu, Tom Mikkelsen, Ronald A DePinho, Florian Muller, Amy B Heimberger, Erik P Sulman, Do-Hyun Nam, Roel G W Verhaak
No abstract text is available yet for this article.
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316429/integrative-analysis-identifies-four-molecular-and-clinical-subsets-in-uveal-melanoma
#16
A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman
No abstract text is available yet for this article.
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316428/arid1a-has-context-dependent-oncogenic-and-tumor-suppressor-functions-in-liver-cancer
#17
Xuxu Sun, Sam C Wang, Yonglong Wei, Xin Luo, Yuemeng Jia, Lin Li, Purva Gopal, Min Zhu, Ibrahim Nassour, Jen-Chieh Chuang, Thomas Maples, Cemre Celen, Liem H Nguyen, Linwei Wu, Shunjun Fu, Weiping Li, Lijian Hui, Feng Tian, Yuan Ji, Shuyuan Zhang, Mahsa Sorouri, Tae Hyun Hwang, Lynda Letzig, Laura James, Zixi Wang, Adam C Yopp, Amit G Singal, Hao Zhu
No abstract text is available yet for this article.
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316427/a-tfiid-saga-perturbation-that-targets-myb-and-suppresses-acute-myeloid-leukemia
#18
Yali Xu, Joseph P Milazzo, Tim D D Somerville, Yusuke Tarumoto, Yu-Han Huang, Elizabeth L Ostrander, John E Wilkinson, Grant A Challen, Christopher R Vakoc
Targeting of general coactivators is an emerging strategy to interfere with oncogenic transcription factors (TFs). However, coactivator perturbations often lead to pleiotropic effects by influencing numerous TFs. Here we identify TAF12, a subunit of TFIID and SAGA coactivator complexes, as a selective requirement for acute myeloid leukemia (AML) progression. We trace this dependency to a direct interaction between the TAF12/TAF4 histone-fold heterodimer and the transactivation domain of MYB, a TF with established roles in leukemogenesis...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316426/clinical-sequencing-defines-the-genomic-landscape-of-metastatic-colorectal-cancer
#19
Rona Yaeger, Walid K Chatila, Marla D Lipsyc, Jaclyn F Hechtman, Andrea Cercek, Francisco Sanchez-Vega, Gowtham Jayakumaran, Sumit Middha, Ahmet Zehir, Mark T A Donoghue, Daoqi You, Agnes Viale, Nancy Kemeny, Neil H Segal, Zsofia K Stadler, Anna M Varghese, Ritika Kundra, Jianjiong Gao, Aijazuddin Syed, David M Hyman, Efsevia Vakiani, Neal Rosen, Barry S Taylor, Marc Ladanyi, Michael F Berger, David B Solit, Jinru Shia, Leonard Saltz, Nikolaus Schultz
Metastatic colorectal cancers (mCRCs) are clinically heterogeneous, but the genomic basis of this variability remains poorly understood. We performed prospective targeted sequencing of 1,134 CRCs. We identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, increasing oncogenic WNT pathway alterations to 96% of CRCs. Right-sided primary site in microsatellite stable mCRC was associated with shorter survival, older age at diagnosis, increased mutations, and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43, and SMAD4 compared with left-sided primaries...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29316425/hedgehog-pathway-drives-fusion-negative-rhabdomyosarcoma-initiated-from-non-myogenic-endothelial-progenitors
#20
Catherine J Drummond, Jason A Hanna, Matthew R Garcia, Daniel J Devine, Alana J Heyrana, David Finkelstein, Jerold E Rehg, Mark E Hatley
Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma that histologically resembles embryonic skeletal muscle. RMS occurs throughout the body and an exclusively myogenic origin does not account for RMS occurring in sites devoid of skeletal muscle. We previously described an RMS model activating a conditional constitutively active Smoothened mutant (SmoM2) with aP2-Cre. Using genetic fate mapping, we show SmoM2 expression in Cre-expressing endothelial progenitors results in myogenic transdifferentiation and RMS...
January 8, 2018: Cancer Cell
journal
journal
39886
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"