tbuckley/cabot-search huggingface dataset:
Abstract 985: Downregulation of long noncoding RNA TINCR promotes invasion and metastasis and predicts poor prognosis in tongue squamous cell carcinoma
Authors: Zehang Zhuang, Cheng Wang, Nan Xie, Yue Wu, Jinsong Hou, Xiqiang Liu, Hongzhang Huang
Journal: Cancer Research (2016)

Abstract Background and aim: Recently long non-coding RNAs (lncRNAs) have emerged as new gene regulators involving in a number of developmental and tumorigenic processes. However, few lncRNAs have been well characterized in tongue squamous cell carcinoma (TSCC). The aim of this study is to determine whether lncRNAs play a role in TSCC progression. Methods: The expression profiles of lncRNAs and protein-coding genes in TSCC tissues and paired adjacent non-tumor tissues from 10 patients were compared by using lncRNA microarrays. TSCC-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Levels of these differentially expressed lncRNAs were verified in TSCC tissues (n = 45) using Quantitative real-time PCR (qRT-PCR) and further confirmed in another patient cohort (n = 103) by in situ hybridization (ISH). The effects of lncRNA on tumor cell invasion and migration were assessed by silencing or overexpressing the lncRNA in vitro. Results: A total of 815 lncRNAs and 1783 protein-coding genes were differentially expressed between TSCC tissues and paired adjacent non-tumor tissues. WGCNA showed that one of the co-expression networks was significantly enriched for biological process that was relevant to epithelial cell differentiation, among which, TINCR was significantly down-regulated. Both PCR and ISH analyses validated that the down-regulation of TINCR in tumor tissues compared with controls. The expression level of TINCR was associated with tumor size, differentiation, cervical lymph node metastasis status, clinical stage and outcomes in patients with TSCC.Patients with TINCR low expression had a reduced overall survival. COX regression analysis showed that TINCR can be served as an independent prognostic factor for patients with TSCC. More, ectopic transfection of TINCR dramatically suppressed cell invasion and migration in vitro. On the contrary, knockdown of TINCR led to p63 upregulation, and enhanced cell invasion and migration. Conclusion: Our study suggests that downregulation of TINCR plays a role in TSCC progression, at least partially, by regulating epithelial differentiation-associated genes. Citation Format: Zehang Zhuang, Cheng Wang, Nan Xie, Yue Wu, Jinsong Hou, Xiqiang Liu, Hongzhang Huang. Downregulation of long noncoding RNA TINCR promotes invasion and metastasis and predicts poor prognosis in tongue squamous cell carcinoma. [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 985.
Abstract 3188: Targeted semiconductor sequencing of 409 cancer-related genes for somatic mutations and copy number variations in multiple myeloma
Authors: Hiroshi Ikeda, Yasushi Sasaki, Kazuya Ishiguro, Tadao Ishida, Yuka Aoki, Takashi Tokino
Journal: Cancer Research (2016)

Abstract Background: 2016's NCCN guideline recommended that induction therapy used conventional chemotherapy such as proteasome inhibitors and Imids in MM. Overall survival is improving by these Novel agents. However, we don't know how to choose these new agents. In the future, we can use next generation sequencer as a tool of drug choosing system. So we reviewed newly diagnosed 11 patients with MM who had received novel agents in our institution.The comprehensive analysis of genetic alterations in tumor by next generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients. Method: DNA was extracted from magnetic bead-enriched bone marrow CD138-positive malignant plasma cells from 11 cases of MM, and CD138-negative cells were used as matched non-tumor cells. Forty nanograms of DNA were used for multiplex PCR amplification with an Ion Ampliseq Comprehensive Cancer Panel that offers targeted coverage of all exons in 409 tumor suppressor genes and oncogenes frequently cited and frequently mutated in human cancers. (covered regions: 95.4% of total). We sequenced 15,992 regions which obtained more than 1.5 megabases of target sequence. Result: Each sample underwent on average 8.3 million sequencing reads after quality filtering. The mean read depths were 539x, and &amp;gt;95% of targeted bases were represented by at least 20 reads. The average number of non-synonymous mutations detected per patient was 5.8 (range 0-11). We also detected copy number variations in which segments of the genome can be duplicated or deleted from sequencing data. We found several genetic alterations that may have been associated with the poor prognosis and poor response to chemotherapy of MM patients. Pathway assessment has shown that somatic aberrations within MM genomes are mainly involved in several important pathways, including cell cycle regulation, RTK-MAPK-PI3K and NF-kB. Conclusion: We performed targeted next-generation sequencing for rapid (2 days), standardized, and cost-effective gene analysis of malignant plasma cells from patients with MM. We can use targeted next-generation sequencing as tool of drug choosing system. Citation Format: Hiroshi Ikeda, Yasushi Sasaki, Kazuya Ishiguro, Tadao Ishida, Yuka Aoki, Takashi Tokino. Targeted semiconductor sequencing of 409 cancer-related genes for somatic mutations and copy number variations in multiple myeloma. [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 3188.
Abstract 921: Pericellular-interactions promote malignant progression of glioblastoma via novel NOTCH-1/HIF-1α pathway
Authors: Eunsoo Kim, Jungwhoi Lee, Seung-Wook Ryu, Chulhee Choi, Kyungsun Choi
Journal: Cancer Research (2016)

Abstract Malignant tumors generally develop hypoxic condition in the core region of tumor mass, which induces stabilization of hypoxia inducible factor-1 alpha (HIF-1α) by preventing proteasome-dependent degradation. HIF-1α has been shown to regulate various oncogenes for malignant progression of many types of tumors including glioblastoma multiforme (GBM). In the present study, we showed that cell-to-cell interactions at high density can induce malignant transformation of tumor cells by activation of HIF-1α even under normoxic condition. To delineate the biological effect of cell culture density, we maintained cancer cells in different density. Four types of GBM cell lines (U251-MG, LN215-MG, U373-MG, and CRT-MG) were used to examine the oncogenic phenotypes of cancer cells cultured in different densities. Cells cultured in a high-density condition showed higher rate of proliferation and migration activity and higher resistance to temozolomide, an anti-cancer drug commonly used for GBM treatment. We found that the pericellular interactions stimulate the cleavage of notch-1 intracellular domain (NICD), and the cleaved NICD protects the HIF-1α from hydroxylation and subsequent proteasomal degradation, resulting in nuclear translocation of HIF-1α. Collectively, we suggest that the cell-cell interactions in high-density culture conditions induce NICD-mediated HIF-1α activation, which leads to malignant phenotypic changes. Therefore, treatment of gamma-secretase inhibitor (GSI), which can block NOTCH-1 signaling pathway, in combination with TMZ could be a promising therapeutic strategy in TMZ-resistant tumor cells. This research was supported by a grant of the Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea (grant number : HI14C0042) Citation Format: Eunsoo Kim, Jungwhoi Lee, Seung-Wook Ryu, Chulhee Choi, Kyungsun Choi. Pericellular-interactions promote malignant progression of glioblastoma via novel NOTCH-1/HIF-1α pathway. [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 921.
Meta-analysis: Self-monitoring in non-insulin-treated type 2 diabetes improved HbA 1c by 0.25%
Authors: A Farmer
Journal: Annals of Internal Medicine (2012)

Question Does self-monitoring of blood glucose improve glycemic control in patients with type 2 diabetes who are not treated with insulin? Review scope Included studies compared self-monitoring of blood glucose with no self-monitoring in patients with non-insulin-treated type 2 diabetes, included ≥ 80 patients, and had ≥ 6 months of followup. Primary outcome was HbA                         1c level; secondary outcomes were blood pressure and serum cholesterol level. Review methods MEDLINE and EMBASE/Excerpta Medica (Apr 2009 to Jun 2010), the reference list of a systematic review that included studies from January 2000 to April 2009, reference lists of other reviews, conference proceedings, and a current controlled trials register were searched for randomized controlled trials (RCTs). Authors of included studies were contacted for individual patient data. 6 RCTs (n = 2552, mean age 60 y, 54% men) met inclusion criteria. 3 RCTs described randomization, and all had allocation concealment and blinded outcome assessors. Loss to follow-up ranged from 2% to 31% (mean 15%). Analysis was by intention-to-treat. Main results Meta-analysis of individual patient data showed that self-monitoring blood glucose reduced HbA                         1c levels at 3, 6, and 12 months compared with no self-monitoring (Table). Mean pooled reduction in HbA                         1c was 9.6 mmol/mol (0.88%) in the intervention group and 7.5 mmol/mol (0.69%) in the usual care group. Groups did not differ for blood pressure or total cholesterol (Table). Results were similar across patients with different levels of HbA                         1c at baseline (P = 0.3), including those with HbA                         1c > 64 mmol/mol (> 8%). Conclusion Self-monitoring of blood glucose in patients with non-insulintreated type 2 diabetes reduces HbA                         1c by 0.25% at 6 months compared with no self-monitoring. © 2012 American College of Physicians.
Abstract 4983: Aminoflavone acts as an immunomodulator of tumor growth in a breast cancer mouse model
Authors: Mariana Alejandra Callero, Cristina Elisa Rodriguez, Aldana Sólimo, Elisa Bal de Kier Joffé, Andrea Loaiza Pérez.
Journal: Cancer Research (2016)

Abstract Aminoflavone (AFP464, NSC 710464), an antitumor agent which recently entered phase II clinical trials, acts against estrogen-positive breast cancer (ER+). AFP464, which has a unique mechanism of action by activating aryl hydrocarbon receptor (AhR) signaling pathway, decreased tumor growth rate in an estrogen dependent, tamoxifen-sensitive mammary cancer murine model (M05) syngeneic in BALB/c developed in our animal facility. Considering that AhR has recently emerged as a physiological regulator of the innate and adaptive immune responses, it is our aim to investigate whether AFP464 modulates the immune response in our mouse model. Cytometric analyses of splenic cells obtained from AFP464-treated and control animals, at three different times after treatment (13, 21 and 41 days), revealed that MDSCs were lower in animals treated with AFP464 than in the vehicle control group. On the contrary (On the other hand) no differences in macrophages, NK, CD8+ T, and CD4+ T cells were observed between these two groups. We also found a diminished quantity of MDSCs in the inflammatory infiltrate, isolated from tumors treated with AFP464. According to these results, we also observed a higher cytotoxic activity of splenic cells from the AFP464-treated group compared with the control one (13 days: 1,50 ± 0,12 vs 0,74 ± 0,18; 21 days: 2,4 ± 0,3 vs 1,16 ± 0,2; 41 days: 2,97 ± 0,2. vs 1,07 ± 0,2 p &amp;lt; 0,05). After an adoptive transfer of splenic cells to mice bearing M05 tumors, we observed that tumors were significantly smaller in mice that received splenic cells from AFP464-treated mice compared with controls (p &amp;lt; 0,05). Finally, we also investigated the effects of AFP464 on metalloproteinase, arginase and iNOS activities in peritoneal macrophages. We found a time-dependent modulation: at 13 day after treatment AFP464 induces an anti-tumor M1 profile, which was gradually reverted to a pro-tumoral M2 profile, at 41 days after treatment. These data suggest that AFP464 modulates the immune response in order to collaborate with its anti-tumor activity and places the immune system as a novel target for this anti-cancer agent to strengthen the rationale for its inclusion in breast cancer treatment regimens. Citation Format: Mariana Alejandra Callero, Cristina Elisa Rodriguez, Aldana Sólimo, Elisa Bal de Kier Joffé, Andrea Loaiza Pérez. Aminoflavone acts as an immunomodulator of tumor growth in a breast cancer mouse model. [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 4983.
Abstract 2221: HHLA2, a novel member of the B7 family of inhibitory ligands, is highly expressed in osteosarcoma
Authors: Pratistha Koirala, Michael Roth, Jonathan Gill, Jordan Chinai, Michelle Ewart, Sajida Piperdi, David Geller, Bang Hoang, Yekaterina Fatakhova, Maya Ghorpade, Xingxing Zang, Richard Gorlick
Journal: Cancer Research (2016)

Abstract Purpose: Over the past four decades there have been minimal improvements in outcomes for patients with osteosarcoma (OS). New targets and novel therapies are needed to improve outcomes for these patients. In this study, we sought to evaluate the prevalence and prognostic utility of the immune checkpoint inhibitor HHLA2 in OS. Experimental Design: HHLA2 expression was evaluated in two cohorts of OS patients using a tumor microarray (TMA) (n = 62) and whole slides (n = 48). HHLA2 expression was assessed in primary tumor specimens and metastatic disease, and correlated with the presence of tumor infiltrating lymphocytes (TILs), and event free survival. Results: HHLA2 was expressed in 68% of OS tumors in the TMA and in 54% in the second cohort. HHLA2 was expressed in almost all metastatic disease specimens and was more prevalent than in primary specimens without known metastases (93% vs 53%, p = 0.02). TILs were present in 75% of all osteosarcoma specimens. Patients whose tumors were ≥25% or ≥50% HHLA2 positive had significantly worse five-year event-free-survival (33% vs 64%, p = 0.03 and 14% vs 59%, p = 0.02). Conclusions: HHLA2 is expressed in the majority of OS tumors, is associated with metastatic disease, and is associated with poorer survival. Further studies are needed assessing the effect of HHLA2 expression on the function of the immune microenvironment, as well as assessing the feasibility and utility of targeting HHLA2 in OS. Citation Format: Pratistha Koirala, Michael Roth, Jonathan Gill, Jordan Chinai, Michelle Ewart, Sajida Piperdi, David Geller, Bang Hoang, Yekaterina Fatakhova, Maya Ghorpade, Xingxing Zang, Richard Gorlick. HHLA2, a novel member of the B7 family of inhibitory ligands, is highly expressed in osteosarcoma. [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 2221.
Abstract 3214: A fully human anti-TIM3 antibody with co-stimulatory activity
Authors: J Dixon Gray, Irina Krapf, Heyue Zhou, Gunnar Kaufmann
Journal: Cancer Research (2016)

Abstract Targeting immune checkpoint molecules has been demonstrated to have significant benefit to patients with cancer. One such molecule is TIM3 whose expression is associated with a phenomenon referred to as T cell exhaustion. While it has been suggested that ligation of TIM3 provides a negative signal to the T cell, there is no obvious inhibitory signaling motif associated with the molecule. We have developed a fully human antibody to TIM3 which demonstrates potent co-stimulatory activity. T cells stimulated with anti-CD3 plus either anti-CD28 or anti-TIM3 show comparable levels of cell activation. Similar to co-stimulation with anti-CD28, the anti-TIM3 antibody promotes expression of CD25, interferon gamma, Tbet and granzyme B, amongst others. Thus, anti-TIM3 co-stimulation promotes T cells with a pro-inflammitory phenotype. With TIM3 being associated with exhausted T cells, co-stimulation with this antibody would be expected to specifically re-activate these exhausted T cells at the tumor site. Moreover, since some NK cells constitutively express TIM3, it would be expected that this antibody would activate these cells as well. Altogether, we have identified a novel anti-TIM3 antibody that is capable of targeting T cells at the tumor site and activating them. Citation Format: J Dixon Gray, Irina Krapf, Heyue Zhou, Gunnar Kaufmann. A fully human anti-TIM3 antibody with co-stimulatory activity. [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 3214.
Feasibililty of Azacitidine As Bridge to Allogeneic Stem Cell Transplantation in Patients with Higher-Risk MDS or Low-Blast Count AML: Results of the BMT-AZA Multicenter Prospective Study
Authors: Maria Teresa Voso, Giuseppe Leone, Alfonso Piciocchi, Luana Fianchi, Paolo Di Bartolomeo, Anna Candoni, Marianna Criscuolo, Arianna Masciulli, Elisa Cerqui, Alfredo Molteni, Carlo Finelli, Matteo Parma, Flavia Rivellini, Nicola Cascavilla, Francesco Spina, Agostino Cortelezzi, Flavia Salvi, Mauro Montanari, Emilio Paolo Alessandrino, Alessandro Rambaldi, Simona Sica
Journal: Blood (2015)
Treatment of Primary CNS Lymphoma in the Elderly, a Multicenter Retrospective Analysis
Authors: Jacoline E.C. Bromberg, Jeanette Doorduyn, Macha Schuurmans, Philip Poortmans, Martin J.B. Taphoorn, Tatjana Seute, Adriaan W. Dekker, Roelien H. Enting, Gustaaf van Imhoff, Yvette van Norden, Martin van den Bent
Journal: Blood (2008)
SPECIAL FOCUS : SURVEILLANCE FOR REPRODUCTIVE HEALTH
Authors: Hani K. Atrash, Ruth Ann Dunn, Alice Frye, Tatiana E. Goldner, Robert L. Heuser, Lisa M. Koonin, Herschel W. Lawson, James S. Marks, Leo Morris, Allyn K. Nakashima, Merrell Ramick, Gregg C. Sylvester, Jack C. Smith, Sandra Smith, Alison M. Spitz, Lilo T. Strauss, Stephanie J. Ventura, Linda A. Webster, Phyllis A. Wingo, Zhisen Xia
Journal: MMWR Morbidity and Mortality Weekly Report (1997)
Addition of apatorsen, an inhibitor of Hsp27, to first-line gemcitabine/carboplatin in advanced squamous cell lung cancer: Design of the Cedar study.
Authors: Peter Schmid, Dakshinmoorthy Muthukumar, Fiona Helen Blackhall, Jason Francis Lester, Sarah Khan, Marianne Illsley, Joss Adams, Angel Garcia-Alonso, Carey MacDonald-Smith, Siow Ming Lee, Cindy Jacobs, Gary William Middleton, Christine James, Kelly Mousa, Shah-Jalal Sarker, Louise Lim
Journal: Journal of Clinical Oncology (2015)

TPS8111 Background: Outcomes remain poor in patients with non-small cell lung cancer (NSCLC) of squamous origin. There are few established therapeutic targets, and benefits of chemotherapy are frequently short-lived, with rapid development of treatment resistance. More effective therapies are urgently required. Substantial preclinical data demonstrates that heat shock protein 27 (Hsp27) affects numerous pathways implicated in cancer progression and treatment resistance. Approximately 70-98% of squamous-cell tumours express Hsp27. Apatorsen (OGX-427) is a second generation antisense oligonucleotide that effectively down-regulates Hsp27 in vitro and in vivo; clinical studies are evaluating apatorsen in lung, bladder, prostate, and pancreatic cancers. Methods: The phase 2, UK, investigator led, randomized, open-label trial Cedar trial was initiated in July 2014. Eligible patients have confirmed Stage IIIB/IV squamous cell lung cancer and no prior chemotherapy for advanced disease, with ECOG score of 0-2 and adequate bone marrow, renal, and liver function; patients with known EGFR mutation or ALK rearrangements are excluded. Planned enrollment is 140 patients; randomization (1:1) is stratified by stage and performance status. Patients receive 21-day cycles of gemcitabine (1250 mg/m2) and carboplatin (AUC5) or gemcitabine/carboplatin plus apatorsen (600 mg IV/wk, preceded by 3 doses during a 9-day loading period) for up to 6 cycles. Tumor evaluation occurs q6 wks. Patients randomized to apatorsen may continue weekly single agent maintenance until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. The primary efficacy measure is progression-free survival. Secondary efficacy measures include objective response (OR), change in tumour size at 12 wks, clinical benefit rate, duration of OR/clinical benefit, overall survival, and proportion without PD at 12 and 24 wks. Efficacy analyses are intent-to-treat. Adverse events and laboratory results are assessed, and interim safety analyses are planned. Pre-specified subset analyses will characterize the relevance of Hsp27 expression in tumour and blood samples. Clinical trial information: 16622.
Abstract 3437: Cancer and all-cause mortality among white and blue collar workers in middle-aged and elderly chinese women in a prospective cohort study
Authors: Bu-Tian Ji.
Journal: Cancer Research (2016)

Abstract Inequalities in health and mortality between white and blue collar workers have been well documented in western countries, particularly among men. Studies regarding occupation related mortality disparities in Asian populations including Chinese are limited. We included 74,941 40-70 years old Chinese women from the Shanghai Women's Health Study (SWHS) in an analysis of occupation and mortality. An in-person interview was conducted at enrolment to obtain lifetime job history as well as lifestyle and other potential risk factors for each participant. Each job title was coded in three digits according to the Chinese National Standard Occupation and Industry Codes Manual, and the categories of white and blue collar work were defined based on this coding. The information on mortality was provided by annual linkage to the Shanghai Vital Statistics Registry. Cox regression models were applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and cause-specific mortality. In comparison with lifetime white collar workers, lifetime blue collar workers had 18% excess in all cause-mortality (HR = 1.18, 95% CI = 1.04-1.34) and 12% excess in cancer deaths (HR = 1.12, 95% CI = 0.93-1.35) after adjustment for lifestyle and other potential risk factors. A significantly increased risk was also associated with mortality from diabetes (HR = 1.89, 95% CI = 1.06-3.37). There were no statistically significant differences in mortality between white and blue collar workers for other causes of death including circulatory, respiratory, gastrointestinal or other diseases among this population. Our study provides suggestive evidence that blue collar workers may have a higher risk of total cancer mortality compared to white collar workers among women in Shanghai. Citation Format: Bu-Tian Ji. Cancer and all-cause mortality among white and blue collar workers in middle-aged and elderly chinese women in a prospective cohort study. [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 3437.