journal
MENU ▼
Read by QxMD icon Read
search

Cancer Research

journal
https://www.readbyqxmd.com/read/27899382/a-metastatic-mouse-model-identifies-genes-that-regulate-neuroblastoma-metastasis
#1
Bo Kyung Alex Seong, Kelly E Fathers, Robin M Hallett, Christina K Yung, Lincoln D Stein, Samar Mouaaz, Lynn Kee, Cynthia Hawkins, Meredith S Irwin, David R Kaplan
Metastatic relapse is the major cause of death in pediatric neuroblastoma (NB), where there remains a lack of therapies to target this stage of disease. To understand the molecular mechanisms mediating NB metastasis, we developed a mouse model using intracardiac injection and in vivo selection to isolate malignant cell subpopulations with a higher propensity for metastasis to bone and the central nervous system. Gene expression profiling revealed primary and metastatic cells as two distinct cell populations defined by differential expression 412 genes and multiple pathways, including CADM1, SPHK1 and YAP/TAZ whose expression independently predicted survival...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27899381/castration-resistance-in-prostate-cancer-is-mediated-by-the-kinase-nek6
#2
Atish D Choudhury, Anna C Schinzel, Maura B Cotter, Rosina T Lis, Katherine Labella, Ying Jie Lock, Francesca Izzo, Isil Guney, Michaela Bowden, Yvonne Y Li, Jinal Patel, Emily Hartman, Steven A Carr, Monica Schenone, Jacob D Jaffe, Philip W Kantoff, Peter S Hammerman, William C Hahn
In prostate cancer, the development of castration resistance is pivotal in progression to aggressive disease. However, understanding of the pathways involved remains incomplete. In this study, we performed a high-throughput genetic screen to identify kinases that enable tumor formation by androgen-dependent prostate epithelial (LHSR-AR) cells under androgen-deprived conditions. In addition to the identification of known mediators of castration resistance, which served to validate the screen, we identified a mitotic-related serine/threonine kinase, NEK6, as a mediator of androgen-independent tumor growth...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27899380/crystal-structure-of-the-emerging-cancer-target-mthfd2-in-complex-with-a-substrate-based-inhibitor
#3
Robert Gustafsson, Ann-Sofie Jemth, Nina Gustafsson Sheppard, Katarina Färnegårdh, Olga Loseva, Elisée Wiita, Nadilly Bonagas, Leif Dahllund, Sabin Llona-Minguez, Maria Häggblad, Martin Henriksson, Yasmin Andersson, Evert Homan, Thomas Helleday, Pål Stenmark
To sustain their proliferation, cancer cells become dependent on one-carbon metabolism to support purine and thymidylate synthesis. Indeed, one of the most highly upregulated enzymes during neoplastic transformation is MTHFD2, a mitochondrial methylenetetrahydrofolate dehydrogenase and cyclohydrolase involved in one-carbon metabolism. Since MTHFD2 is expressed normally only during embryonic development, it offers a disease-selective therapeutic target for eradicating cancer cells while sparing healthy cells...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27899379/transcriptional-regulator-cnot3-defines-an-aggressive-colorectal-cancer-subtype
#4
Paloma Cejas, Alessia Cavazza, Chandri Yandava, Víctor Moreno, David Horst, Juan Moreno-Rubio, Emilio Burgos, Marta Mendiola, Len Taing, Ajay Goel, Jaime Feliu, Ramesh A Shivdasani
Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent and impact of these alterations are still being unraveled. Here we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers (CRC), as compared to corresponding benign precursor adenomas. Modification of certain CRC sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC)...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27895076/mesothelial-cells-create-a-novel-tissue-niche-that-facilitates-gastric-cancer-invasion
#5
Masamitsu Tanaka, Sei Kuriyama, Go Itoh, Daichi Maeda, Akiteru Goto, Yutaro Tamiya, Kazuyoshi Yanagihara, Masakazu Yashiro, Namiko Aiba
Peritoneal mesothelial cells (PMC) cover organ surfaces in the abdominal cavity. In this study, lineage tracing revealed that PMC guide cancer cell invasion in the gastric wall and in peritoneal metastatic lesions. Serosal PMC covering the stomach surface entered the gastric wall to create a novel niche that favored gastric cancer cell invasion. PMC infiltration was induced by incorporation of cancer cell-derived, Wnt3a-containing extracellular vesicles (EV). Infiltrated PMC in turn promoted subserosal invasion of cancer cells...
November 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879272/quantification-of-pathway-crosstalk-reveals-novel-synergistic-drug-combinations-for-breast-cancer
#6
Samira Jaeger, Ana Igea, Rodrigo Arroyo, Victor Alcalde, Begoña Canovas, Modesto Orozco, Angel R Nebreda, Patrick Aloy
Combinatorial therapeutic approaches are an imperative to improve cancer treatment, since it is critical to impede compensatory signaling mechanisms that can engender drug resistance to individual targeted drugs. Currently approved drug combinations result largely from empirical clinical experience and cover only a small fraction of a vast therapeutic space. Here we present a computational network biology approach, based on pathway crosstalk inhibition, to discover new synergistic drug combinations for breast cancer treatment...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879271/vitamin-d3-prevents-calcium-induced-progression-of-early-stage-prostate-tumors-by-counteracting-trpc6-and-calcium-sensing-receptor-upregulation
#7
Sophie Bernichtein, Natascha Pigat, Nicolas Barry Delongchamps, Florence Boutillon, Virginie Verkarre, Philippe Camparo, Edouard Reyes-Gomez, Arnaud Méjean, Stephane Marie Oudard, Eve M Lepicard, Melanie Viltard, Jean-Claude Souberbielle, Gerard Friedlander, Thierry Capiod, Vincent Goffin
Active surveillance has emerged as an alternative to immediate treatment for men with low-risk prostate cancer. Accordingly, identification of environmental factors that faciliate progression to more aggressive stages is critical for disease prevention. Although calcium-enriched diets have been speculated to increase prostate cancer risk, their impact on early-stage tumors remains unexplored. In this study, we addressed this issue with a large interventional animal study. Mouse models of fully penetrant and slowly-evolving prostate tumorigenesis showed that a high calcium diet dramatically accelerated the progression of prostate intraepithelial neoplasia, by promoting cell proliferation, micro-invasion, tissue inflammation and expression of acknowledged prostate cancer markers...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879270/breast-cancer-resistance-to-antiestrogens-is-enhanced-by-increased-er-degradation-and-erbb2-expression
#8
Tomohiro Shibata, Kosuke Watari, Hiroto Izumi, Akihiko Kawahara, Satoshi Hattori, Chihiro Fukumitsu, Yuichi Murakami, Ryuji Takahashi, Uhi Toh, Ken-Ichi Ito, Shigehiro Ohdo, Maki Tanaka, Masayoshi Kage, Michihiko Kuwano, Mayumi Ono
Endocrine therapies effectively improve the outcomes of patients with estrogen receptor (ER)-positive breast cancer. However, the emergence of drug-resistant tumors creates a core clinical challenge. In breast cancer cells rendered resistant to the antiestrogen fulvestrant, we defined causative mechanistic roles for the transcription factor YBX1 and the levels of ER and the ERBB2 receptor. Enforced expression of YBX1 in parental cells conferred resistance against tamoxifen and fulvestrant in vitro and in vivo...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879269/basophils-promote-tumor-rejection-via-chemotaxis-and-infiltration-of-cd8-t-cells
#9
Ibrahim M Sektioglu, Rafael Carretero, Nadja Bulbuc, Tobias Bald, Thomas Tüting, Alexander Y Rudensky, Günter J Hämmerling
Elevated numbers of regulatory T-cells (Tregs) in patient tumors are known to inhibit efficient anti-tumor T-cell responses. To study the mechanisms controlling tumor rejection, we assessed different mouse models for Treg depletion. In Foxp3DTR knock-in mice, about 99% Treg depletion was achieved, resulting in complete rejection of transplanted HCmel12 melanomas in a CD8+ T cell-dependent way. In contrast, about 90% Treg depletion obtained in BAC transgenic Foxp3.LuciDTR4 mice failed to induce complete rejection of HCmel12 melanomas, demonstrating that residual Tregs were able to control CD8+ T cell responses against the tumor...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879268/transcriptional-selectivity-of-epigenetic-therapy-in-cancer
#10
Takahiro Sato, Matteo Cesaroni, Woonbok Chung, Shoghag Panjarian, Anthony Tran, Jozef Madzo, Yasuyuki Okamoto, Hanghang Zhang, Xiaowei Chen, Jaroslav Jelinek, Jean-Pierre J Issa
A central challenge in the development of epigenetic cancer therapy is the ability to direct selectivity in modulating gene expression for disease-selective efficacy. To address this issue, we characterized by RNA-seq, DNA methylation and ChIP-seq analyses the epigenetic response of a set of colon, breast and leukemia cancer cell lines to small molecule inhibitors against DNA methyltransferases (DAC), histone deacetylases (Depsi), histone demethylases (KDM1A inhibitor S2101), and histone methylases (EHMT2 inhibitor UNC0638 and EZH2 inhibitor GSK343)...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879267/pifithrin-%C3%A2%C2%B5-prevents-cisplatin-induced-chemobrain-by-preserving-neuronal-mitochondrial-function
#11
Gabriel S Chiu, Magdalena A Maj, Sahar Rizvi, Robert Dantzer, Elisabeth G Vichaya, Geoffroy Laumet, Annemieke Kavelaars, Cobi J Heijnen
Cognitive impairment termed chemobrain is a common neurotoxicity associated with chemotherapy treatment, affecting an estimated 78% of patients. Prompted by the hypothesis that neuronal mitochondrial dysfunction underlies chemotherapy-induced cognitive impairment (CICI), we explored the efficacy of administering the small molecule pifithrin (PFT)-µ, an inhibitor of mitochondrial p53 accumulation, in preventing CICI. Male C57BL/6J mice injected with cisplatin +/- PFT-µ for two 5-day cycles were assessed for cognitive function using novel object/place recognition and alternation in a Y-maze...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879266/threshold-analysis-and-biodistribution-of-fluorescently-labeled-bevacizumab-in-human-breast-cancer
#12
Maximillian Koch, Johannes S de Jong, Jürgen Glatz, Panagiotis Symvoulidis, Laetitia E Lamberts, Arthur Adams, Mariëtte E G Kranendonk, Anton G T Terwisscha van Scheltinga, Michaela Aichler, Liesbeth Jansen, Jakob de Vries, Marjolijn N Lub-de Hooge, Carolina P Schröder, Annelies Jorritsma-Smit, Matthijs D Linssen, Esther de Boer, Bert van der Vegt, Wouter B Nagengast, Sjoerd G Elias, Sabrina Oliveira, Arjen Witkamp, Willem P Th M Mali, Elsken van der Wall, Beatriz P Garcia-Allende, Paul J Van Diest, Elisabeth G de Vries, Axel Walch, Gooitzen M van Dam, Vasilis Ntziachristos
In vivo tumor labeling with fluorescent agents may assist endoscopic and surgical guidance for cancer therapy as well as create opportunities to directly observe cancer biology in patients. However, malignant and non-malignant tissues are usually distinguished on fluorescence images by applying empirically determined fluorescence intensity thresholds. Here we report the development of fSTREAM, a set of analytic methods designed to streamline the analysis of surgically excised breast tissues by collecting and statistically processing hybrid multi-scale fluorescence, color, and histology readouts toward precision fluorescence imaging...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879265/il-6-signaling-in-peripheral-blood-t-cells-predicts-clinical-outcome-in-breast-cancer
#13
Lei Wang, Andrea K Miyahira, Diana Simons, Xuyang Lu, Andrew Chang, Carrie Wang, Maria Suni, Vernon C Maino, Frederick M Dirbas, John H Yim, James Waisman, Peter P Lee
Interleukin-6 (IL-6) is a pleiotropic cytokine with both pro- and anti-inflammatory properties which acts directly on cancer cells to promote their survival and proliferation. Elevated serum IL-6 levels negatively correlate with survival of cancer patients, which is generally attributed to the direct effects of IL-6 on cancer cells. How IL-6 modulates the host immune response in cancer patients is unclear. Here we show the IL-6 signaling response in peripheral blood T cells is impaired in breast cancer (BC) patients and is associated with blunted Th17 differentiation...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879264/differential-regulation-of-the-melanoma-proteome-by-eif4a1-and-eif4e
#14
Cailin E Joyce, Adrienne G Yanez, Akihiro Mori, Akinori Yoda, Johanna S Carroll, Carl D Novina
Small molecules and antisense oligonucleotides that inhibit the translation initiation factors eIF4A1 and eIF4E have been explored as broad-based therapeutic agents for cancer treatment, based on the frequent upregulation of these two subunits of the eIF4F cap-binding complex in many cancer cells. Here we provide support for these therapeutic approaches with mechanistic studies of eIF4F-driven tumor progression in a preclinical model of melanoma. Silencing eIF4A1 or eIF4E decreases melanoma proliferation and invasion...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27872098/systematic-drug-screening-identifies-tractable-targeted-combination-therapies-in-triple-negative-breast-cancer
#15
Vikram B Wali, Casey G Langdon, Matthew A Held, James T Platt, Gauri A Patwardhan, Anton Safonov, Bilge Aktas, Lajos Pusztai, David F Stern, Christos Hatzis
Triple-negative breast cancer (TNBC) remains an aggressive disease without effective targeted therapies. In this study, we addressed this challenge by testing 128 FDA-approved or investigational drugs as either single agents or in 768 pairwise drug combinations in TNBC cell lines to identify synergistic combinations tractable to clinical translation. Medium-throughput results were scrutinized and extensively analyzed for sensitivity patterns, synergy, anticancer activity and validation in low-throughput experiments...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27872097/menin-and-daxx-interact-to-control-neuroendocrine-tumors-via-epigenetic-regulation-of-membrane-metallo-endopeptidase
#16
Zijie Feng, Lei Wang, Yanmei Sun, Zongzhe Jiang, John Domsic, Chiying An, Bowen Xing, Jingjing Tian, Xiuheng Liu, David C Metz, Xiaolu Yang, Ronen Marmorstein, Xiaosong Ma, Xianxin Hua
Neuroendocrine tumors (NETs) often harbor loss-of-function mutations in the MEN1 gene that encodes the protein menin as well as in the Daxx gene. Both menin and Daxx interact with several partners to regulate cellular processes and gene expression. Here, we show that menin directly interacts with Daxx to suppress proliferation of NET cells partly by inhibiting a common target gene, membrane metallo-endopeptidase (Mme). Menin and Daxx are required for each other to enhance histone H3 lysine9 trimethylation (H3K9me3) at Mme promoter, partly through SUV39H1...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27872096/polyi-c-and-cpg-synergize-with-anti-erbb2-mab-for-treatment-of-breast-tumors-resistant-to-immune-checkpoint-inhibitors
#17
Roxanne Charlebois, Bertrand Allard, David Allard, Laurence Buisseret, Martin Turcotte, Sandra Pommey, Pavel Chrobak, John Stagg
Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs such as trastuzumab. In the clinic, breast tumors poorly infiltrated with immune cells are more resistant to trastuzumab and patients have a worse prognosis. Because type I and II interferons (IFNs) are critical to the immune-mediated activity of anti-ErbB2 mAb, we investigated the effect of combining polyI:C and CpG with trastuzumab-like therapy in immunocompetent mouse models of ErbB2+ breast cancer. We demonstrated that in situ delivery of polyI:C and CpG combined to systemic anti-ErbB2 mAb triggered a potent inflammatory response in breast tumors able to induce long lasting CD8+ T cell-dependent anti-tumor immunity...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27872095/t-cells-redirected-to-a-minor-histocompatibility-antigen-instruct-intratumoral-tnf-%C3%AE-expression-and-empower-adoptive-cell-therapy-for-solid-tumors
#18
Teresa Manzo, Tabea Sturmheit, Veronica Basso, Elisabetta Petrozziello, Rodrigo Hess Michelini, Michela Riba, Massimo Freschi, Angela R Elia, Matteo Grioni, Flavio Curnis, Maria Pia Protti, Ton N Schumacher, Reno Debets, Melody A Swartz, Angelo Corti, Matteo Bellone, Anna Mondino
Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such effects could be reproduced in autologous settings by TCR-gene engineered lymphocytes. We report that T cells redirected either to a broadly expressed Y-encoded minor H antigen or to a tumor-associated antigen, although poorly effective if individually transferred, when simultaneously administered enabled acute autochthonous tumor debulking and resulted in durable clinical remission...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27872094/mif-induced-stromal-pkc%C3%AE-il8-is-essential-in-human-acute-myeloid-leukemia
#19
Amina Abdul-Aziz, Manar Shafat, Tarang Mehta, Federica Di Palma, Matthew Lawes, Stuart A Rushworth, Kristian Bowles
Acute myeloid leukemia (AML) cells exhibit a high level of spontaneous apoptosis when cultured in vitro but have a prolonged survival time in vivo, indicating that tissue microenvironment plays a critical role in promoting AML cell survival. In vitro studies have shown that bone marrow-mesenchymal stromal cells (BM-MSC) protect AML blasts from spontaneous and chemotherapy-induced apoptosis. Here we report a novel interaction between AML blasts and BM-MSC which benefits AML proliferation and survival. We initially examined the cytokine profile in cultured human AML compared to AML cultured with BM-MSC and found that macrophage-migration inhibitory factor (MIF) was highly expressed by primary AML, and that interleukin-8 (IL-8) was increased in AML/BM-MSC co-cultures...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27872093/a-novel-platinum-ii-based-bifunctional-adc-linker-benchmarked-using-89zr-desferal-and-auristatin-f-conjugated-trastuzumab
#20
Niels J Sijbrandi, Eugen Merkul, Joey A Muns, Dennis Cj Waalboer, Kevin Adamzek, Marije Bolijn, Veronica Montserrat, Govert W Somsen, Rob Haselberg, Paul Jgm Steverink, Hendrik-Jan Houthoff, Guus A M S van Dongen
Greater control is desirable in the stochastic conjugation technology used to synthesize antibody-drug conjugates (ADCs). We have shown recently that a fluorescent dye can be stably conjugated to a monoclonal antibody (mAb) using a bifunctional platinum(II) linker. Here we describe the general applicability of this novel linker technology for the preparation of stable and efficacious ADCs. The ethylenediamineplatinum(II) moiety, herein called Lx®, was coordinated to Desferal® (DFO) or auristatin F (AF) to provide storable "semi-final" products, which were directly conjugated to unmodified mAbs...
November 21, 2016: Cancer Research
journal
journal
20068
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"