tbuckley/cabot-search huggingface dataset:
Abstract 2984: Plumbagin induces p53-dependent apoptosis via generation of reactive oxygen species in human cancer cells
Authors: Umasankar De, Amit Kundu, Eunbin Kim, Jonghwan Kwack, Hyungsik Kim
Journal: Cancer Research (2016)

Abstract Plumbagin [5-hydroxy-2-methyl-1,4-naphthaquinone], a major constituent derived from Drosera and Plumbago, displays antitumor activity both in vitro and animal models, but the molecular mechanisms of p53-mediated antitumor effects have not been clearly explored. The aim of this study is to determine the anticancer effects of plumbagin on MCF-7 (wild type p53) or Ishikawa (p53-mutant type) cells. We compared the cytotoxicity, cell cycle regulation, apoptotic cell death, and generation of intracellular reactive oxygen species (ROS) in these cancer cells. Plumbagin inhibits the growth of Ishikawa (endometrial cancer cells) and SKOV-3 cells, particularly MCF-7 cells. Plumbagin significantly increased the expression of p53 and reduced Murine Double Minute 2 (MDM2) in the MCF-7 cells. Plumbagin up-regulated the expression of p21(CIP1/WAF1) causing cell cycle arrest in the G2/M-phase by down-regulating cyclin B1 and Cdc2 in MCF-7 as well as Ishikawa cells. Plumbagin altered the ratio of Bax/Bcl-2 and cytochrome c released resulting apoptotic cell death in MCF-7 cells. Furthermore, plumbagin dramatically increased the intracellular ROS level, and pretreatment with the ROS scavenger, N-acetyl cysteine (NAC), protected against growth inhibition by plumbagin, suggesting that ROS play a pivotal role in the antitumor activity in MCF-7 cells. In mice bearing the MCF-7 cell xenografts, plumbagin significantly reduced the tumor growth and weight, without apparent side effects. In conclusion, plumbagin exerted anticancer activity in MCF-7 by generation of intracellular ROS that causes induction of apoptosis via Bcl-2/Bax pathways as well as cell cycle arrest. KEYWORDS: Plumbagin; breast cancer; apoptosis; p53, reactive oxygen species Citation Format: Umasankar De, Amit Kundu, Eunbin Kim, Jonghwan Kwack, Hyungsik Kim. Plumbagin induces p53-dependent apoptosis via generation of reactive oxygen species in human cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2984.
Abstract 185: Role of phosphorylation in Lmtk3 activation and its contribution in breast cancer progression
Authors: Giulia Lucchiari, Hua Zhang, Joao Nunes, Yichen Xu, Arnhild Grothey, Justin Stebbing, Georgios Giamas
Journal: Cancer Research (2016)

Abstract LMTK3 is an oncogenic receptor tyrosine kinase implicated in various types of cancer including breast, lung, gastric and colorectal. We have already demonstrated the contribution of LMTK3 in invasion, migration and transcriptional regulation as well as its involvement in endocrine resistance in breast cancer. Despite the significant progress in understanding the role of LMTK3 in human tumourogenesis, the signalling pathways implicated in LMTK3 regulation still remain to be elucidated. Protein phosphorylation play an essential role in regulating intracellular signal transduction pathways involving almost every aspect of cell activity. In silico phosphoproteomic analysis predicted several potential LMTK3 phosphorylation sites targeted by different kinases including Cyclin-dependent kinase 5 (CDK5), a cytoplasmic proline-directed serine/threonine kinase that is commonly overexpressed in many solid tumours. Interestingly, recent work performed by two different groups showed that CDK5 is a regulator of LMTK1 and LMTK2 in neuronal cells, resulting in axonal outgrowth and potentially influencing a number of neurophysiological processes. By performing a variety of molecular/cellular and biochemical experiments we confirmed the ability of CDK5 to phosphorylate LMTK3 in vitro and identified its exact phosphorylation sites. Moreover, we investigated the consequences of CDK5 phosphorylation on various LMTK3 processes, amongst which its stability, sub-cellular localization, its ability to interact with chromatin and others. In addition, the clinical correlation of CDK5 and LMTK3 expression in cell lines and patients’ samples were assessed. In aggregate, we describe a new cellular pathway encompassing CDK5 and LMTK3 that results in breast cancer tumour progression. Our data will be presented. Citation Format: Giulia Lucchiari, Hua Zhang, Joao Nunes, Yichen Xu, Arnhild Grothey, Justin Stebbing, Georgios Giamas. Role of phosphorylation in Lmtk3 activation and its contribution in breast cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 185.
Comprehensive molecular profiling of urothelial bladder cancer at the DNA, RNA, and protein levels: A TCGA project.
Authors: John N. Weinstein, Jaegil Kim, Chad J. Creighton, Rehan Akbani, Katherine A. Hoadley, William Y. Kim, Margaret B. Morgan, Toshinori Hinoue, Jonathan E. Rosenberg, Dean F. Bajorin, Donna E. Hansel, Hikmat Al-Ahmadie, Dmitry Gordenin, Joshua M. Stuart, Gordon Robertson, Raju Kucherlapati, Peter W. Laird, Gordon B. Mills, David J. Kwiatkowski, Seth P. Lerner
Journal: Journal of Clinical Oncology (2014)

4509 Background: Urothelial carcinoma (UC) is a major cause of mortality with no approved molecularly targeted agents or good treatment options beyond cisplatin-based chemotherapy. Methods: For The Cancer Genome Atlas (TCGA), we profiled muscle-invasive UCs for mutations, DNA copy number variants (CNVs), mRNA and microRNA expression, protein expression and phosphorylation, DNA methylation, transcript splicing, gene fusion, viral integration, pathway perturbation, clinical correlates, and histopathology. The finding here are based on the first 131 tumors, but >250 more are being processed as of 1/2014. Results: Whole-exome sequencing revealed 29 recurrently mutated genes. Potential therapeutic targets included altered PIK3CA, ERBB2, FGFR3, TSC1, and ERBB3, plus mutated chromatin-regulating genes MLL, MLL2, MLL3, CREBBP, CHD7, SRCAP, ARID1A, KDM6A (UTX), and EP300. There were 27 focal CNVs, including CDKN2A deletion in 47%. Low-pass whole-genome sequencing identified 3 tumors with FGFR3-TACC3 fusions. Viral DNA was found in 6% (CMV, HHV6B, HPV16, BK polyoma), and viral transcripts were identified in 4% (CMV, BK polyoma, HPV16). mRNA-seq showed 4 tumor clusters: (I) papillary morphology, FGFR3 dysregulation. (I and II) high HER2 (ERBB2), estrogen receptor beta signaling signature (like Luminal A breast cancer). (III) similar to basal-like breast and squamous cell head and neck. Integrated analyses confirmed changes in cell cycle regulation (93%), kinase and PI3-K signaling (72%), and epigenetic regulation (histone-modifiers: 89%; SWI/SNF nucleosome remodeling complex: 64%). Recurrent defects in PI3-kinase/AKT/mTOR (42%) and RTK/RAS (44%) pathways may be actionable. Conclusions: This study and others identify druggable targets in UC. FGFR3 is activated by mutation, gene fusion, and overexpression, suggesting trials of FGFR3 inhibitors. PI3-kinase/mTOR/AKT/TSC1 pathway defects are frequent, and mutations in TSC1 suggest trial of mTOR inhibitors. ERBB2 amplifications and activating mutations suggest agents such as trastuzumab, trastuzumab-DM1, lapatinib, and neratinib. The mutations in epigenetic regulatory genes suggest potential for chromatin modifying agents.
Abstract 3504: Arginylated BiP/oxidized DJ-1 complex mediates crosstalk between the endoplasmic reticulum and mitochondria
Authors: Dae-Hee Lee.
Journal: Cancer Research (2016)

Abstract In cell death induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), although much is known about signal pathways involving external signals through cell surface receptors or internal signals through mitochondrial dysfunction, little is known about signal pathways activated by endoplasmic reticulum (ER) stress during TRAIL treatment. Here, we report that TRAIL-induced caspase activation is a prerequisite for TRAIL-induced ER stress response. During TRAIL treatment, ER chaperon BiP dissociates from ER stress sensors such as PERK and IRE1α and the activation of the PERK-eIF2α-ATF4-CHOP apoptotic signal transduction pathway occurs. Meanwhile ER-stress induces BiP release to the cytosol and ATE1-encoded Arg-tRNA transferase arginylates BiP. TRAIL also induces loss of ΔΨm and redox sensor DJ-1 detects mitochondria-derived ROS. Oxidized DJ-1 binds to arginylated BiP (R-BiP) in the cytosol. DJ-1 binding activity was abrogated in C106A and C53A but not C46A mutant. R-BiP/oxidized DJ-1 complex may mediate crosstalk between the ER and mitochondria. Key words: TRAIL; endoplasmic reticulum; apoptosis; colorectal cancer Citation Format: Dae-Hee Lee. Arginylated BiP/oxidized DJ-1 complex mediates crosstalk between the endoplasmic reticulum and mitochondria. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3504.
When and how to update systematic reviews: consensus and checklist
Authors: Paul Garner, Sally Hopewell, Jackie Chandler, Harriet MacLehose, Holger J Schünemann, Elie A Akl, Joseph Beyene, Stephanie Chang, Rachel Churchill, Karin Dearness, Gordon Guyatt, Carol Lefebvre, Beth Liles, Rachel Marshall, Laura Martínez García, Chris Mavergames, Mona Nasser, Amir Qaseem, Margaret Sampson, Karla Soares-Weiser, Yemisi Takwoingi, Lehana Thabane, Marialena Trivella, Peter Tugwell, Emma Welsh, Ed C Wilson
Journal: BMJ (2016)

Updating of systematic reviews is generally more efficient than starting all over again when new evidence emerges, but to date there has been no clear guidance on how to do this. This guidance helps authors of systematic reviews, commissioners, and editors decide when to update a systematic review, and then how to go about updating the review.
Abstract 2869: FLASH-dependent post-translational regulation of the EMT activator ZEB1
Authors: Camille Abshire, Ana Maria Dragoi
Journal: Cancer Research (2016)

Abstract Understanding the mechanisms of metastasis initiation and tumor persistence despite aggressive treatments is paramount to developing new viable therapeutic targets. Critical to tumor progression is initiation of epithelial-to-mesenchymal transition (EMT), a cellular process characterized by loss of E-cadherin, a critical cell-cell adhesion molecule, gain of migratory properties and chemoresistance. Transcriptional repression of E-cadherin and other genes responsible for maintaining the epithelial phenotype by ZEB1/ZEB2 family is one of the most significant events occurring at the interface between non-metastatic/metastatic cancer and chemo-sensitive/chemo-resistant cancer. Using a novel interdisciplinary high-throughput screen methodology we uncovered novel regulators of E-cadherin. Caspase 8 - associated protein 2 (CASP8AP2 or FLASH) a protein involved in apoptosis and transcriptional control was identified through this screen and we discovered that FLASH depletion resulted in increased E-cadherin levels at the plasma membrane through loss of ZEB1 expression. Subsequent examination of ZEB1 protein expression revealed that ZEB1 is rapidly degraded in FLASH-depleted cells. This process is blocked by proteasome inhibitors suggesting that post-translational modifications (PTMs) and in particular ubiquitination of ZEB1 is responsible for its fast turnover and decreased protein expression in the absence of FLASH. Indeed, ubiquitinated ZEB1 was detected in FLASH-depleted cells in the presence of proteasome inhibitors. Although ZEB1 is degraded through the ubiquitin pathway, its rapid turnover in the absence of FLASH suggests that protective mechanisms are in place to delay and/or prevent this process. Even more, we determined that the atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 is involved in ZEB1 degradation in the absence of FLASH and is upregulated in cells depleted for FLASH. Altogether our data suggests that FLASH can stabilizes ZEB1 indirectly by transcriptional repression of the ubiquitin ligase responsible for its degradation and directly by binding to ZEB1 and masking the recognition site of the ubiquitin ligase. Even more, absence of FLASH reprograms the cells into a more epithelial-like phenotype which is less invasive and is resistant to TGFβ-induced loss of E-cadherin. Not only is FLASH-dependent post-translational regulation of ZEB1 novel, but is also conserved in multiple cells lines from various tissues, making this mechanism an original therapeutic target for cancer metastasis. Citation Format: Camille Abshire, Ana Maria Dragoi. FLASH-dependent post-translational regulation of the EMT activator ZEB1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2869.
Abstract 2879: PIGU modulates radioactive iodine uptake in differentiated thyroid cancers
Authors: MORAN AMIT, shorook Na’ara, Tomer Charas, Ziv gil.
Journal: Cancer Research (2016)

Abstract Radioactive iodine (RAI) treatment has a significant role in the management of differentiated thyroid carcinoma after surgical treatment. Although there is significant variability between patients, in response to RAI treatment, the mechanism responsible for this phenomenon is unknown. PIGU is an endoplasmic reticulum protein and a component of the GPIT complex, which plays a crucial role in post-translational modification of proteins such as sodium iodide symporter (NIS). Immunohistochemical analysis revealed significantly lower expression of PIGU in papillary carcinomas compared to matched normal thyroid tissue (P&amp;lt;0.001). To study the role of PIGU in RAI uptake of differentiated thyroid cancer, we stably expressed PIGU and mock plasmid in the papillary cancer cell line (K1-PIGU and K1, respectively). Immunofluorescence analysis showed a significant increase in perinuclear expression of PIGU in the K1-PIGU cancer cells compared to controls. Similarly, flow cytometry analysis showed a significant increase in membranous expression of NIS in PIGU transfected cancer cells compared to controls. There were no significant differences in proliferation, invasion or motility between K1-PIGU and K1 cell lines. PIGU expression significantly increased I125 uptake compared to controls both in vitro (1.13 and 1030 ppm, respectively, p&amp;lt; .001) and in vivo (153 and 1.2×105 ppm, respectively, p&amp;lt; .001). Mitogen-activated protein kinase inhibition showed clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine. To address the mechanism underlying PIGU down regulation in RAI resistant tumors, we treated K1 and KI-PIGU cells with U0126 MEK inhibitor. This inhibition resulted in a significant increase in PIGU expression and I125 uptake in vitro. Taken together, our results revealed a pivotal role for PIGU in RAI sensitivity of thyroid cancer cells, by modulation of NIS expression. Citation Format: MORAN AMIT, shorook Na’ara, Tomer Charas, Ziv gil. PIGU modulates radioactive iodine uptake in differentiated thyroid cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2879.
Incidence of febrile neutropenia with docetaxel plus cyclophosphamide in a university-based breast oncology clinic.
Authors: A. Soni, A. Brufsky, R. C. Jankowitz, P. Rastogi, V. G. Vogel, S. Puhalla
Journal: Journal of Clinical Oncology (2011)

9061 Background: ASCO guidelines indicate that an incidence of febrile neutropenia (FN) greater than 20 percent justifies the use of prophylactic granulocyte colony stimulating factor (G-CSF) after a particular chemotherapy regimen. Docetaxel plus cyclophosphamide (TC) is a commonly used chemotherapeutic regimen for patients with early stage breast cancer, and an FN incidence of 5 percent has been reported by Jones, et al with this regimen. In clinical practice, the incidence of FN with TC may be higher than previously reported, and we sought to determine the incidence of febrile neutropenia in our outpatient clinic. Methods: We conducted a retrospective review of paper and electronic records for 130 patients with early-stage breast cancer who received at least one standard dose cycle of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) at a university-based practice between November 2007 and August 2010. Fever was defined as a temperature > 101 degrees Fahrenheit or clinician-defined fever, and neutropenia was defined as an absolute neutrophil count < 500 (grade 4 neutropenia). Chi-squared analysis was used for categorical data. Results: One hundred of 130 patients studied did not receive primary prophylactic G-CSF. The incidence of febrile neutropenia was found to be 23 percent amongst these 100 patients who received at least one cycle of TC without prophylactic G-CSF versus 3 percent of the 30 patients who received G-CSF starting cycle one (p = 0.015). Seventy-six of the 100 patients not receiving cycle one G-CSF experienced grade 4 neutropenia. The average length of hospitalization for those with FN was 3.14 days. Incidence of FN was not significantly affected by age, and this data is summarized in the table below (p = 0.658). Conclusions: The incidence of FN in the current study is higher than expected based on initial reports with the TC regimen. This warrants investigation in larger cohorts to determine whether primary prophylactic G-CSF should be considered to limit this morbidity for patients receiving TC. FN [n (%)] No FN [n (%)] Total Age ≤ 50 6 (18%) 28 (82%) 34 Age 51-64 14 (26%) 40 (74%) 54 Age ≥ 65 3 (25%) 9 (75%) 12 Total 23 (23%) 77 (77%) 100
Intensive Insulin Therapy.
Journal: Annals of Internal Medicine (1984)

macology of Primary Nociceptive Neuron. The chapter entitled Control of Cancer Pain With Analgesics Acting in the Central Nervous System is useful in principle, but most of the drugs described are not available in the United States. The chapter on the use of epidural opiates is a current and timely review of a useful technique. The chapter on the use of psychotropic drugs is one of the best reviews of this topic that I have read. Several chapters address the topics of regional nerve blocks and neurolytic therapy. The role of specific antineoplastic chemotherapy and radiation therapy in the management of cancer pain is not overlooked, nor is the role of surgical management. In summary, this book is exceedingly well written, carefully edited, and brief (only 238 pages), and it is a thorough review of the characteristics and the management of pain in the patient with cancer. It should be suggested reading for all oncologists and trainees in oncology and is appropriate reading for nurses in this field as well. Anyone who deals with patients who have cancer wi l l find Pain in the Cancer Patient a useful reference source.
Advances in Cosmetic Dermatology. Neil S.Saddick, NilsKrueger, eds. Publisher: McGraw Hill Medical, 2014; 126 pp. ISBN: 978-0-323-26389-4 (E-ISBN: 978-0-323-26389-4). Price £62.99 (Ebook £75.59).
Authors: S. Rai
Journal: British Journal of Dermatology (2016)
Abstract 4449: TET1 inhibits gastric cancer metastasis by demethylation and re-expression of PTEN
Authors: Bingya Liu, Yao-fei Pei, Jian-fang Li, Liping Su, Ran Tao, Min Yan, Zhang-gang Zhu
Journal: Cancer Research (2016)

Abstract TET1 is a member of ten eleven translocation enzymes, which can convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), eventually to promote CpG islands demethylation of specific gene.. In this study, we found that TET1 expression and 5-hmC content were low in tumor tissues compared to its adjacent non-tumor tissues of gastric cancer. Cell proliferation, migration and invasion were enhanced when TET1 knocked down in gastric cancer cell in vitro and in vivo, while it was suppressed when TET1 over-expressed. We also found that PTENis one of the target genes of TET1. TET1 directly binds to the promoter region of PTEN, activates its transcription through demethylating its CpG islands. Knockdown of TET1 results in hypermethylation of PTEN promoter and low expression of PTEN. PTEN knockdown activates AKT and FAK pathway, which are suppressed by PTEN. The activation of PTEN downstream AKT and FAK facilitates tumor migration, invasion and accelerates cell growth. In conclution, we found a novel mechanism that TET1 suppresses tumor cell growth, migration and invasion through conversion PTEN promoter CpG island methylation to demehylation and then re-expression PTEN. Citation Format: Bingya Liu, Yao-fei Pei, Jian-fang Li, Liping Su, Ran Tao, Min Yan, Zhang-gang Zhu. TET1 inhibits gastric cancer metastasis by demethylation and re-expression of PTEN. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4449.
Adipocytes and Neutrophils Give a Helping Hand to Pancreatic Cancers
Authors: Vincenzo Bronte, Giampaolo Tortora
Journal: Cancer Discovery (2016)

Abstract Summary: Obesity-induced inflammation can build up a confined microenvironment in pancreatic adenocarcinoma that is associated with increased desmoplasia, neutrophil recruitment, reduced delivery of chemotherapeutic drugs, and immune evasion. Targeting molecular pathways empowering this circuit might represent a necessary measure to reach clinical efficacy for combination therapies in patients with excess body weight. Cancer Discov; 6(8); 821–3. ©2016 AACR. See related article by Incio et al., p. 852.
Abstract 711: The essential role of NKX6.3 in gastric cancer cell migration and invasion through targeting of Wnt/â-catenin and Rho-GTPase signaling pathways
Authors: Jung Hwan Yoon, Won Suk Choi, Won Sang Park
Journal: Cancer Research (2016)

Abstract Despite ongoing research and recent progress, the prognosis for patients with advanced gastric cancer remains poor. Wnt/â-catenin and Rho-GTPase signaling pathways are known to play essential roles in malignant transformation and progression of various tumours, including gastric cancer. Here, we identify that NKX6 transcription factor, locus 3 (NKX6.3) binds directly to specific promoter regions of Wnt/â-catenin and Rho-GTPase pathway-related genes, resulting in inhibition of cancer cell migration and invasion. Additionally, we find that the expression level of NKX6.3 is involved in regulation of gastric cancer progression and expression of Wnt/â-catenin and Rho-GTPase pathway-related genes in clinical samples. These results suggest that NKX6.3 prevents EMT and cell migration, implying that NKX6.3 inactivation might be one of the key mechanisms of gastric cancer cell invasion and metastasis and might serve as a potential candidate for targeted gastric cancer therapy. Citation Format: Jung Hwan Yoon, Won Suk Choi, Won Sang Park. The essential role of NKX6.3 in gastric cancer cell migration and invasion through targeting of Wnt/â-catenin and Rho-GTPase signaling pathways. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 711.