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Cancer Research

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https://www.readbyqxmd.com/read/28432052/genomic-instability-in-cancer-teetering-on-the-limit-of-tolerance
#1
REVIEW
Noemi Andor, Carlo C Maley, Hanlee P Ji
Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection, and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared with intermediate levels under this threshold...
April 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428283/regulatory-aspects-of-optical-methods-and-exogenous-targets-for-cancer-detection
#2
Willemieke S Tummers, Jason M Warram, Kiranya E Tipirneni, John Fengler, Paula Jacobs, Lalitha Shankar, Lori Henderson, Betsy Ballard, Brian W Pogue, Jamey P Weichert, Michael Bouvet, Jonathan Sorger, Christopher H Contag, John V Frangioni, Michael F Tweedle, James P Basilion, Sanjiv S Gambhir, Eben L Rosenthal
Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval. Because fluorescence-enhanced surgery requires a combination of both device and drug, each may be developed in conjunction, or separately, which are important considerations in the approval process...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428282/whither-radioimmunotherapy-to-be-or-not-to-be
#3
Damian J Green, Oliver W Press
Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B-cell lymphomas. Two "first-generation," directly radiolabeled anti-CD20 antibodies, (131)iodine-tositumomab and (90)yttrium-ibritumomab tiuxetan, were FDA-approved more than a decade ago but have been little utilized because of a variety of medical, financial, and logistic obstacles. Newer technologies employing multistep "pretargeting" methods, particularly those utilizing bispecific antibodies, have greatly enhanced the therapeutic efficacy of radioimmunotherapy and diminished its toxicities...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428281/role-of-cbx4-in-the-colorectal-carcinoma-metastasis-response
#4
LETTER
Xin Wang, Tiebang Kang
No abstract text is available yet for this article.
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428280/role-of-cbx4-in-the-colorectal-carcinoma-metastasis-letter
#5
LETTER
Valentina Sancisi, Alessia Ciarrocchi
No abstract text is available yet for this article.
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428279/interaction-between-tumor-cell-surface-receptor-rage-and-proteinase-3-mediates-prostate-cancer-metastasis-to-bone
#6
Mikhail G Kolonin, Anna Sergeeva, Daniela I Staquicini, Tracey L Smith, Christy A Tarleton, Jeffrey J Molldrem, Richard L Sidman, Serena Marchiò, Renata Pasqualini, Wadih Arap
Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428278/oncogenic-role-of-snd1-in-development-and-progression-of-hepatocellular-carcinoma
#7
Nidhi Jariwala, Devaraja Rajasekaran, Rachel G Mendoza, Xue-Ning Shen, Ayesha Siddiq, Maaged Akiel, Chadia L Robertson, Mark A Subler, Jolene Windle, Paul B Fisher, Arun J Sanyal, Devanand Sarkar
SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). In this study, we show that hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC with partial penetrance and exhibit more highly aggressive HCC induced by chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase in inflammatory markers and spheroid-generating tumor initiating cells (TIC). Mechanistic investigations defined roles for Akt and NF-kappaB signaling pathways in promoting TIC formation in Alb/SND1 mice...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#8
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428276/micellar-delivery-of-mir-34a-modulator-rubone-and-paclitaxel-in-resistant-prostate-cancer
#9
Di Wen, Yang Peng, Feng Lin, Rakesh K Singh, Ram I Mahato
Treatment of prostate cancer with paclitaxel (PTX) often fails due to development of chemoresistance caused by downregulation of the tumor suppressor gene miR-34a. In this study, we demonstrate that co-delivery of PTX and 2'-hydroxy-2,4,4',5,6'-pentamethoxychalcone (termed rubone) drives upregulation of miR-34a and chemosensitizes PTX-resistant prostate cancer cells, killing both cancer stem-like cells (CSCs) and bulk tumor cells. Rubone upregulated miR-34a and reversed its downstream target genes in DU145-TXR and PC3-TXR cells...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428275/epithelial-to-mesenchymal-transition-contributes-to-immunosuppression-in-breast-carcinomas
#10
Anushka Dongre, Mohammad Rashidian, Ferenc Reinhardt, Aaron Bagnato, Zuzana Keckesova, Hidde L Ploegh, Robert A Weinberg
The Epithelial-to-mesenchymal transition (EMT) is a cell-biological program that confers mesenchymal traits on carcinoma cells and drives their metastatic dissemination. It is, unclear, however, whether activation of EMT in carcinoma cells can change their susceptibility to immune attack. We demonstrate here that mammary tumor cells arising from more epithelial carcinoma cell lines expressed high levels of MHC-I, low levels of PD-L1 and contained within their stroma CD8+ T cells and M1 (anti-tumor) macrophages...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428274/egfr-mediates-responses-to-small-molecule-drugs-targeting-oncogenic-fusion-kinases
#11
Aria Vaishnavi, Laura Schubert, Uwe Rix, Lindsay A Marek, Anh T Le, Stephen Keysar, Magdalena J Glogowska, Matthew A Smith, Severine L Kako, Natalia J Sumi, Kurtis D Davies, Kathryn E Ware, Marileila Varella-Garcia, Eric B Haura, Antonio Jimeno, Lynn E Heasley, Dara L Aisner, Robert C Doebele
Oncogenic kinase fusions of ALK, ROS1, RET and NTRK1 act as drivers in human lung and other cancers. Residual tumor burden following treatment of ALK or ROS1+ lung cancer patients with oncogene-targeted therapy ultimately enables the emergence of drug-resistant clones, limiting the long-term effectiveness of these therapies. To determine the signaling mechanisms underlying incomplete tumor cell killing in oncogene-addicted cancer cells, we investigated the role of EGFR signaling in drug-naive cancer cells harboring these oncogene fusions...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428273/assessing-prostate-cancer-aggressiveness-with-hyperpolarized-dual-agent-3d-dynamic-imaging-of-metabolism-and-perfusion
#12
Hsin-Yu Chen, Peder E Z Larson, Robert A Bok, Cornelius von Morze, Renuka Sriram, Romelyn Delos Santos, Justin Delos Santos, Jeremy W Gordon, Naeim Bahrami, Marcus Ferrone, John Kurhanewicz, Daniel B Vigneron
New magnetic resonance (MR) molecular imaging techniques offer the potential for non-invasive, simultaneous quantification of metabolic and perfusion parameters in tumors. This study applied a 3D dynamic dual-agent hyperpolarized (13)C magnetic resonance spectroscopic imaging (MRSI) approach with (13)C-pyruvate and (13)C-urea to investigate differences in perfusion and metabolism between low and high grade tumors in the TRAMP transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1 relaxation and RF excitation and modeled to provide quantitative measures of pyruvate to lactate flux (kPL) and urea perfusion (urea AUC) that correlated with TRAMP tumor histologic grade...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428271/master-transcriptional-regulators-in-cancer-discovery-via-reverse-engineering-approaches-and-subsequent-validation
#13
REVIEW
Bruce Moran, Arman Rahman, Katja Palonen, Fiona T Lanigan, William M Gallagher
Reverse engineering of transcriptional networks using gene expression data enables identification of genes that underpin the development and progression of different cancers. Methods to this end have been available for over a decade and, with a critical mass of transcriptomic data in the oncology arena having been reached, they are ever more applicable. Extensive and complex networks can be distilled into a small set of key master transcriptional regulators (MTR), genes that are very highly connected and have been shown to be involved in processes of known importance in disease...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28416491/locoregional-effects-of-microbiota-in-a-preclinical-model-of-colon-carcinogenesis
#14
Sarah Tomkovich, Ye Yang, Kathryn Winglee, Josee Gauthier, Marcus Mühlbauer, Xiaolun Sun, Mansour Mohamadzadeh, Xiuli Liu, Patricia Martin, Gary P Wang, Eric Oswald, Anthony A Fodor, Christian Jobin
Inflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF) ApcMin/+ and ApcMin/+;Il10-/- mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found colon tumorigenesis significantly correlated with inflammation in SPF housed ApcMin/+;Il10-/-, but not ApcMin/+ mice. In contrast, small intestinal neoplasia development significantly correlated with age in both ApcMin/+;Il10-/- and ApcMin/+ mice...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28416490/preclinical-characterization-of-bet-family-bromodomain-inhibitor-abbv-075-suggests-combination-therapeutic-strategies
#15
Mai H Bui, Xiaoyu Lin, Daniel H Albert, Leiming Li, Lloyd T Lam, Emily J Faivre, Scott Warder, Xiaoli Huang, Denise Wilcox, Cherrie K Donawho, George S Sheppard, Le Wang, Steve Fidanze, John K Pratt, Dachun Liu, Lisa Hasvold, Tamar Uziel, Xin Lu, Fred Kohlhapp, Guowei Fang, Steven W Elmore, Saul H Rosenberg, Keith F McDaniel, Warren M Kati, Yu Shen
ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered Phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models representing a variety of hematological malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) cells...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28416489/nrf2-induction-supporting-breast-cancer-cell-survival-is-enabled-by-oxidative-stress-induced-dpp3-keap1-interaction
#16
Kevin Lu, Allen L Alcivar, Jianglin Ma, Tzeh K Foo, Susan Zwyea, Amar Mahdi, Yanying Huo, Thomas W Kensler, Michael L Gatza, Bing Xia
NRF2 is a transcription factor serving as a master regulator of the expression of many genes involved in cellular responses to oxidative and other stresses. In the absence of stress, NRF2 is constantly synthesized but maintained at low levels as it is targeted by KEAP1 for ubiquitination and proteasome-mediated degradation. NRF2 binds KEAP1 mainly through a conserved "ETGE" motif that has also been found in several other proteins, such as DPP3, which has been shown to bind KEAP1 and enhance NRF2 function upon overexpression...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28416488/activation-of-notch-signaling-by-tenascin-c-promotes-growth-of-human-brain-tumor-initiating-cells
#17
Susobhan Sarkar, Reza Mirzaei, Franz J Zemp, Wei Wu, Donna L Senger, Stephen M Robbins, V Wee Yong
Elevated NOTCH signaling is implicated in tumorigenesis. The brain tumor- initiating cells (BTICs) present in malignant glioma exhibit elevated NOTCH activity but the mechanism of this activation is unknown. Here, we provide evidence that tenascin-C (TNC), an extracellular matrix protein prominent in malignant glioma, increases NOTCH activity in BTICs to promote their growth. We demonstrate the proximal localization of TNC and BTICs in human glioblastoma specimens, and in the brains of mice implanted with human BTIC intracranial xenografts...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28416487/metabolic-markers-and-statistical-prediction-of-serous-ovarian-cancer-aggressiveness-by-ambient-ionization-mass-spectrometry-imaging
#18
Marta Sans, Kshipra M Gharpure, Robert Tibshirani, Jialing Zhang, Li Liang, Jinsong Liu, Jonathan H Young, Robert Dood, Anil K Sood, Livia Eberlin
Ovarian high-grade serous carcinoma (HGSC) results in the highest mortality among gynecological cancers, developing rapidly and aggressively. Dissimilarly, serous borderline ovarian tumors (BOT) can progress into low-grade serous carcinomas and have relatively indolent clinical behavior. The underlying biological differences between HGSC and BOT call for accurate diagnostic methodologies and tailored treatment options, and identification of molecular markers of aggressiveness could provide valuable biochemical insights and improve disease management...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28416486/a-squalene-based-nanomedicine-for-oral-treatment-of-colon-cancer
#19
Larissa Kotelevets, Eric Chastre, Joachim Caron, Julie Mougin, Gerard Bastian, Alain Pineau, Francine Walker, Therese Lehy, Didier Desmaele, Patrick Couvreur
Nanotechnology offers many possibilities to improve drug treatments, including with regard to drug pharmacology. The current study reports a simple approach to improve cisplatin efficacy in the treatment of colon cancer through the creation of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ-CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited at least 10-fold greater cytotoxic potency compared to uncomplexed cisplatin, reflecting an enhancement in intracellular accumulation and DNA platination...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28416485/targeting-autocrine-ccl5-ccr5-axis-reprograms-immunosuppressive-myeloid-cells-and-reinvigorates-antitumor-immunity
#20
Yi Ban, Junhua Mai, Xin Li, Marisa Mitchell-Flack, Tuo Zhang, Lixing Zhang, Lotfi Chouchane, Mauro Ferrari, Haifa Shen, Xiaojing Ma
The tumor-promoting potential of CCL5 has been proposed but remains poorly understood. We demonstrate here that an autocrine CCL5-CCR5 axis is a major regulator of immunosuppressive myeloid cells (IMC) of both monocytic and granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation of granulocytic myeloid-derived suppressor cells and tumor-associated macrophages. In parallel, enhanced maturation of intratumoral neutrophils and macrophages occurred in spite of tumor-derived CCL5. The refractory nature of ccl5-null myeloid precursors to tumor-derived CCL5 was attributable to their persistent lack of membrane-bound CCR5...
April 17, 2017: Cancer Research
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