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https://www.readbyqxmd.com/read/27936464/refractory-testicular-germ-cell-tumors-are-highly-sensitive-to-the-second-generation-dna-methylation-inhibitor-guadecitabine
#1
Costantine Albany, Mary P Hever-Jardine, Katherine M von Herrmann, Christina Y Yim, Janice Tam, Joshua M Warzecha, Leah Shin, Sarah E Bock, Brian S Curran, Aneeq S Chaudhry, Fred Kim, George E Sandusky, Pietro Taverna, Sarah J Freemantle, Brock C Christensen, Lawrence H Einhorn, Michael J Spinella
Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936104/mechanical-loading-attenuates-radiation-induced-bone-loss-in-bone-marrow-transplanted-mice
#2
Peter M Govey, Yue Zhang, Henry J Donahue
Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown...
2016: PloS One
https://www.readbyqxmd.com/read/27935865/bronchial-airway-gene-expression-signatures-in-mouse-lung-squamous-cell-carcinoma-and-their-modulation-by-cancer-chemopreventive-agents
#3
Donghai Xiong, Jing Pan, Qi Zhang, Eva Szabo, Mark Steven Miller, Ronald A Lubet, Ming You, Yian Wang
Due to exposure to environmental toxicants, a "field cancerization" effect occurs in the lung resulting in the development of a field of initiated but morphologically normal appearing cells in the damaged epithelium of bronchial airways with dysregulated gene expression patterns. Using a mouse model of lung squamous cell carcinoma (SCC), we performed transcriptome sequencing (RNA-Seq) to profile bronchial airway gene expression and found activation of the PI3K and Myc signaling networks in cytologically normal bronchial airway epithelial cells of mice with preneopastic lung SCC lesions, which was reversed by treatment with the PI3K Inhibitor XL-147 and pioglitazone, respectively...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935860/t-lymphocyte-shp2-deficiency-triggers-anti-tumor-immunity-to-inhibit-colitis-associated-cancer-in-mice
#4
Wen Liu, Wenjie Guo, Lihong Shen, Zhen Chen, Qiong Luo, Xiaolin Luo, Gen-Sheng Feng, Yongqian Shu, Yanhong Gu, Qiang Xu, Yang Sun
Nonresolving inflammation is involved in the initiation and progression process of tumorigenesis. Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is known to inhibit acute inflammation but its role in chronic inflammation-associated cancer remains unclear. The role of SHP2 in T cells in dextran sulfate sodium (DSS)-induced colitis and azoxymethane-DSS-induced colitis-associated carcinogenesis was examined using SHP2CD4-/- conditional knockout mice. SHP2 deficiency in T cells aggravated colitis with increased level of pro-inflammatory cytokines including IFN-γ and IL-17A...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935748/atf4-targets-ret-for-degradation-and-is-a-candidate-tumor-suppressor-gene-in-medullary-thyroid-cancer
#5
Rozita Bagheri-Yarmand, Michelle D Williams, Elizabeth G Grubbs, Robert F Gagel
CONTEXT: Medullary thyroid cancer (MTC) is an aggressive tumor that harbors activating mutations of the RET proto-oncogene. We previously reported that RET inhibits transcriptional activity of ATF4, the master regulator of the stress response pathway, to prevent cell death. OBJECTIVE: We hypothesized that loss of function of ATF4 play a role in initiation of MTC. DESIGN: Targeted deletion of ATF4 in mice was used to assess ATF4 function in the thyroid gland...
December 9, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27935057/crosstalk-among-uv-induced-inflammatory-mediators-dna-damage-and-epigenetic-regulators-facilitates-suppression-of-the-immune-system
#6
Ram Prasad, Santosh K Katiyar
The suppression of the immune system by overexposure to ultraviolet (UV) radiation has been implicated in the initiation and progression of photocarcinogenesis. Numerous changes occur in the skin on UVB exposure, including the generation of inflammatory mediators, DNA damage, epigenetic modifications, and migration and functional alterations in the antigen-presenting dendritic cells. Although each of these alterations can elicit a cascade of events that have the potential to modulate immune sensitivity alone, there is emerging evidence that there is considerable crosstalk between these cascades...
December 9, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27934896/transient-appearance-of-circulating-tumor-dna-associated-with-de-novo-treatment
#7
Kikuya Kato, Junji Uchida, Yoji Kukita, Toru Kumagai, Kazumi Nishino, Takako Inoue, Madoka Kimura, Fumio Imamura
The limitation of circulating tumor DNA (ctDNA) is its inability to detect cancer cell subpopulations with few or no dying cells. Lung cancer patients subjected to the EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment were prospectively collected, and ctDNA levels represented by the activating and T790M mutations were measured. The first data set (21 patients) consisting of samples collected in the period from before initiation of EGFR-TKI to at least 2 weeks after initiation: the ctDNA dynamics generally exhibited a rapid decrease and/or a transient increase...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27934311/a-switch-on-nir-probe-for-specific-detection-of-hg-2-ion-in-aqueous-medium-and-in-mitochondria
#8
Hridesh Agarwalla, Pankaj S Mahajan, Debashis Sahu, Nandaraj Taye, Bishwajit Ganguly, Santosh B Mhaske, Samit Chattopadhyay, Amitava Das
A new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based probe molecule (L) is synthesized for specific binding to Hg(2+) ion in physiological condition with an associated luminescence ON response in the near-IR region of the spectrum. Appropriate functionalization in the 5-position of each of two pyrrole moieties with styryl functionality in a BODIPY core helped us in achieving the extended conjugation and a facile intramolecular charge transfer transition with a narrow energy gap for frontier orbitals...
November 21, 2016: Inorganic Chemistry
https://www.readbyqxmd.com/read/27934110/molecular-imaging-biosensor-monitors-p53-sumoylation-in-cells-and-living-mice
#9
Thillai V Sekar, Kira Foygel, Rammohan Devulapally, Vineet Kumar, Sanjay Malhotra, Tarik F Massoud, Ramasamy Paulmurugan
Small molecule mediated stabilization of p53 tumor suppressor protein through sumoylation is a promising new strategy for improving cancer chemotherapy. A molecular tool that monitors p53 sumoylation status and expedites screening for drugs that enhance p53 sumoylation would be beneficial. We report a molecularly engineered reporter fragment complementation biosensor based on optical imaging of Firefly luciferase (FLuc), to quantitatively image p53 sumoylation and desumoylation in cells and living mice. We initially characterized this biosensor by successfully imaging sumoylation of several target proteins, achieving significant FLuc complementation for ERα (p < 0...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27933405/current-challenges-of-metastatic-breast-cancer
#10
Bora Lim, Gabriel N Hortobagyi
Metastasis is one of the most characteristic yet problematic behaviors of cancer cells. Stage IV breast cancer accounts for a large portion of breast cancer-related morbidity and mortality. Despite early detection and improvement in survival owing to advancements in biomedical research and overall improvement of the health system, 6-10% of patients present with stage IV disease in the developed world, with a higher incidence noted elsewhere. Despite advances in biomedical research into cancer, up to 70-80% of patients with stage IV breast cancer die of cancer in 5 years, a disproportionally higher mortality compared with non-metastatic breast cancer...
December 8, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27933313/genetic-engineering-of-chimeric-antigen-receptors-using-lamprey-derived-variable-lymphocyte-receptors
#11
Robert Moot, Sunil S Raikar, Lauren Fleischer, Melissa Querrey, Daniel E Tylawsky, Hirotomo Nakahara, Christopher B Doering, H Trent Spencer
Chimeric antigen receptors (CARs) are used to redirect effector cell specificity to selected cell surface antigens. Using CARs, antitumor activity can be initiated in patients with no prior tumor specific immunity. Although CARs have shown promising clinical results, the technology remains limited by the availability of specific cognate cell target antigens. To increase the repertoire of targetable tumor cell antigens we utilized the immune system of the sea lamprey to generate directed variable lymphocyte receptors (VLRs)...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933304/preclinical-validation-lv-il-12-transduction-of-patient-leukemia-cells-for-immunotherapy-of-aml
#12
Ju Huang, Yuanfeng Liu, Bryan C Au, Dwayne L Barber, Andrea Arruda, Axel Schambach, Michael Rothe, Mark D Minden, Christopher J Paige, Jeffrey A Medin
Interleukin-12 (IL-12) is a potent cytokine that may be harnessed to treat cancer. To date, nearly 100 IL-12-based clinical trials have been initiated worldwide. Yet systemic administration of IL-12 is toxic. Different strategies are being developed to reduce such toxicities by restricting IL-12 distribution. Our previous studies employed lentivector-mediated expression of murine IL-12 in tumor cells and demonstrated effective protection in both mouse leukemia and solid tumor challenge models. In this study, we carried out preclinical validation studies using a novel lentivector to engineer expression of human IL-12 in acute myeloid leukemia blast cells isolated from 21 patients...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27932399/novel-hybrid-phenotype-revealed-in-small-cell-lung-cancer-by-a-transcription-factor-network-model-that-can-explain-tumor-heterogeneity
#13
Akshata R Udyavar, David J Wooten, Megan D Hoeksema, Mukesh Bansal, Andrea Califano, Lourdes Estrada, Santiago Schnell, Jonathan M Irish, Pierre P Massion, Vito Quaranta
Small cell lung cancer (SCLC) is a devastating disease due to its propensity for early invasion and refractory relapse after initial treatment response. Although these aggressive traits have been associated with phenotypic heterogeneity, our understanding of this association remains incomplete. To fill this knowledge gap, we inferred a set of 33 transcription factors (TF) associated with gene signatures of the known neuroendocrine/epithelial (NE) and non-neuroendocrine/mesenchymal-like (ML) SCLC phenotypes...
December 8, 2016: Cancer Research
https://www.readbyqxmd.com/read/27932068/rovalpituzumab-tesirine-a-dll3-targeted-antibody-drug-conjugate-in-recurrent-small-cell-lung-cancer-a-first-in-human-first-in-class-open-label-phase-1-study
#14
Charles M Rudin, M Catherine Pietanza, Todd M Bauer, Neal Ready, Daniel Morgensztern, Bonnie S Glisson, Lauren A Byers, Melissa L Johnson, Howard A Burris, Francisco Robert, Tae H Han, Sheila Bheddah, Noah Theiss, Sky Watson, Deepan Mathur, Bharathi Vennapusa, Hany Zayed, Satwant Lally, Donald K Strickland, Ramaswamy Govindan, Scott J Dylla, Stanford L Peng, David R Spigel
BACKGROUND: Rovalpituzumab tesirine is a first-in-class antibody-drug conjugate directed against delta-like protein 3 (DLL3), a novel target identified in tumour-initiating cells and expressed in more than 80% of patients with small-cell lung cancer. We aimed to assess the safety and activity of rovalpituzumab tesirine in patients who progressed after one or more previous regimen. METHODS: We conducted a phase 1 open-label study at ten cancer centres in the USA...
December 2, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27930920/indoleamine-2-3-dioxygenase-regulates-t-cell-activity-through-vav1-rac-pathway
#15
Runmei Li, Hui Li, Qian Sun, Liang Liu, Chen Zhang, Xiubao Ren
The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in tumor resistance. A previous study determined that IDO inhibits Vav1 mRNA expression and the activation of Vav1 and its downstream targets in T cells in the guanine exchange factor (GEF)-independent pathway. The current study aims to determine whether IDO induces T-cell immunosuppression through Vav1/Rac signaling pathway, which is a GEF-dependent pathway. The correlation between Vav1 mRNA expressions in T cells of tumor infiltrating lymphocytes and the levels of IDO expression in lung cancer tissues from lung cancer patients was detected...
December 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27930437/case-of-metastatic-urothelial-carcinoma-of-the-retina-and-vitreous
#16
Katherine E Whalen, Ralph C Eagle, Tamara R Vrabec
PURPOSE: To report a rare case of vitreo-retinal metastasis from urothelial carcinoma of the bladder. METHODS: Case report. RESULTS: A 55-year-old man with a history of bladder cancer developed atypical vitritis and a white fundus mass. Intravenous fluorescein angiography demonstrated connection between the retinal and tumor vasculature consistent with a retinal malignancy. Cytologic analysis of the vitreous sample revealed large, atypical cells with pleomorphic nuclei, mucin vacuoles, and rare mitotic figures...
December 7, 2016: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/27930094/cancer-stem-cell-hypothesis-for-therapeutic-innovation-in-clinical-oncology-taking-the-root-out-not-chopping-the-leaf
#17
Kevin Dzobo, Dimakatso Alice Senthebane, Arielle Rowe, Nicholas Ekow Thomford, Lamech M Mwapagha, Nasir Al-Awwad, Collet Dandara, M Iqbal Parker
Clinical oncology is in need of therapeutic innovation. New hypotheses and concepts for translation of basic research to novel diagnostics and therapeutics are called for. In this context, the cancer stem cell (CSC) hypothesis rests on the premise that tumors comprise tumor cells and a subset of tumor-initiating cells, CSCs, in a quiescent state characterized by slow cell cycling and expression of specific stem cell surface markers with the capability to maintain a tumor in vivo. The CSCs have unlimited self-renewal abilities and propagate tumors through division into asymmetric daughter cells...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27929600/risk-of-thyroid-malignancy-following-an-index-head-and-neck-squamous-cell-carcinoma-a-population-based-study
#18
Jason Y Chan, Zhen Gooi, Wojciech K Mydlarz, Nishant Agrawal
To evaluate the incidence of a subsequent primary thyroid malignancy in patients with an index head and neck squamous cell carcinoma (HNSCC), we analyzed the National Cancer Institute's Surveillance, Epidemiology, and End Results database to identify a cohort of patients who had been diagnosed with a primary HNSCC from 1973 through 2004. The study population was made up of 60,323 patients of all ages, roughly three-quarters of whom were male. A total of 60 patients (0.1%) developed a subsequent thyroid malignancy-not a statistically significant finding...
December 2016: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/27926864/low-cd38-identifies-progenitor-like-inflammation-associated-luminal-cells-that-can-initiate-human-prostate-cancer-and-predict-poor-outcome
#19
Xian Liu, Tristan R Grogan, Haley Hieronymus, Takao Hashimoto, Jack Mottahedeh, Donghui Cheng, Lijun Zhang, Kevin Huang, Tanya Stoyanova, Jung Wook Park, Ruzanna O Shkhyan, Behdokht Nowroozizadeh, Matthew B Rettig, Charles L Sawyers, David Elashoff, Steve Horvath, Jiaoti Huang, Owen N Witte, Andrew S Goldstein
Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38(lo) luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38(lo) luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926494/p38-and-jnk-pathways-control-e-selectin-dependent-extravasation-of-colon-cancer-cells-by-modulating-mir-31-transcription
#20
Liang Zhong, Bryan Simoneau, Jacques Huot, Martin J Simard
Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to vascular endothelial cells. It requires the interaction between adhesion receptors such as E-selectin present on endothelial cells and their ligands on cancer cells. Notably, E-selectin influences the metastatic potential of breast, bladder, gastric, pancreatic, and colorectal carcinoma as well as of leukemia and lymphoma. Here, we show that E-selectin expression induced by the pro-inflammatory cytokine IL-1β is directly and negatively regulated by miR-31...
December 2, 2016: Oncotarget
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