tbuckley/cabot-search huggingface dataset:
Abstract 825: TAPS: A bisulfite-free, base-resolution and quantitative sequencing method for cytosine modifications
Authors: Yibin Liu, Paulina Siejka, Gergana Velikova, Ying Bi, Marketa Tomkova, Benjamin Schuster-Boeckler, Chun-Xiao Song
Journal: Cancer Research (2019)

Abstract Aberrant DNA methylation changes are powerful prognostic and predictive biomarkers in cancer diagnosis and treatment. For decades bisulfite sequencing has been the gold standard for DNA methylation analysis. However, this method relies on harsh deamination reaction of unmodified cytosine to uracil which degrades the majority of DNA and generates sequencing libraries with low complexity. Those drawbacks limit the applications on low-input samples and lead to poor sequencing quality, low mapping rates, uneven genome coverage and increased sequencing cost. Here, we present a novel bisulfite-free and base-resolution sequencing method, TET Assisted Pyridine borane Sequencing (TAPS), for direct detection of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) without affecting unmodified cytosine. We utilised TET enzymes to readily oxidize 5mC and 5hmC to 5-carboxylcytosine (5caC), which was then converted to dihydrouracil by pyridine borane via a previously unknown reductive decarboxylation/deamination reaction. This non-destructive method enables high-throughput sequencing with nanoscale input materials (genomic DNA and cell-free DNA) and preserve DNA up to 10 kbs long which could allow long read sequencing. We demonstrated that TAPS could directly replace bisulfite sequencing with higher mapping rates, more even coverage and lower sequencing costs, and enable more comprehensive, cheaper and faster methylome analyses. This would be a revolutionary tool for epigenetic study and facilitate both academic research and clinical diagnostics. Citation Format: Yibin Liu, Paulina Siejka, Gergana Velikova, Ying Bi, Marketa Tomkova, Benjamin Schuster-Boeckler, Chun-Xiao Song. TAPS: A bisulfite-free, base-resolution and quantitative sequencing method for cytosine modifications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 825.
HIV Testing in 50 Local Jurisdictions Accounting for the Majority of New HIV Diagnoses and Seven States with Disproportionate Occurrence of HIV in Rural Areas, 2016–2017
Authors: Marc A. Pitasi, Kevin P. Delaney, John T. Brooks, Elizabeth A. DiNenno, Shacara D. Johnson, Joseph Prejean
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Since 2006, CDC has recommended universal screening for human immunodeficiency virus (HIV) infection at least once in health care settings and at least annual rescreening of persons at increased risk for infection (1,2), but data from national surveys and HIV surveillance demonstrate that these recommendations have not been fully implemented (3,4). The national Ending the HIV Epidemic initiative* is intended to reduce the number of new infections by 90% from 2020 to 2030. The initiative focuses first on 50 local jurisdictions (48 counties, the District of Columbia, and San Juan, Puerto Rico) where the majority of new diagnoses of HIV infection in 2016 and 2017 were concentrated and seven states with a disproportionate occurrence of HIV in rural areas relative to other states (i.e., states with at least 75 reported HIV diagnoses in rural areas that accounted for ≥10% of all diagnoses in the state).† This initial geographic focus will be followed by wider implementation of the initiative within the United States. An important goal of the initiative is the timely identification of all persons with HIV infection as soon as possible after infection (5). CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS)§ to assess the percentage of adults tested for HIV in the United States nationwide (38.9%), in the 50 local jurisdictions (46.9%), and in the seven states (35.5%). Testing percentages varied widely by jurisdiction but were suboptimal and generally low in jurisdictions with low rates of diagnosis of HIV infection. To achieve national goals and end the HIV epidemic in the United States, strategies must be tailored to meet local needs. Novel screening approaches might be needed to reach segments of the population that have never been tested for HIV.
Rejuvenated Photodynamic Therapy for Bacterial Infections
Authors: Qingyan Jia, Qing Song, Peng Li, Wei Huang
Journal: Advanced Healthcare Materials (2019)

Abstract The emergence of multidrug resistant bacterial strains has hastened the exploration of advanced microbicides and antibacterial techniques. Photodynamic antibacterial therapy (PDAT), an old‐fashioned technique, has been rejuvenated to combat “superbugs” and biofilm‐associated infections owing to its excellent characteristics of noninvasiveness and broad antibacterial spectrum. More importantly, bacteria are less likely to produce drug resistance to PDAT because it does not require specific targeting interaction between photosensitizers (PSs) and bacteria. This review mainly focuses on recent developments and future prospects of PDAT. The mechanisms of PDAT against bacteria and biofilms are briefly introduced. In addition to classical macrocyclic PSs, several innovative PSs, including non‐self‐quenching PSs, conjugated polymer–based PSs, and nano‐PSs, are summarized in detail. Numerous multifunctional PDAT systems such as in situ light‐activated PDAT, stimuli‐responsive PDAT, oxygen self‐enriching enhanced PDAT, and PDAT‐based multimodal therapy are highlighted to overcome the inherent defects of PDAT in vivo (e.g., limited penetration depth of light and hypoxic environment of infectious sites).
EGF-based cancer vaccine for advanced NSCLC: Results from a phase III trial.
Authors: Tania Crombet Ramos, Elia Neninger, Soraida Acosta, Rosa Mari­a Amador, Silvia Mendoza, Eduardo Rafael Santiesteban, Pedro Camilo Rodriguez, Beatriz Garcia, Xitlally Popa, Zaima Mazorra, Carmen Viada, Gisela Gonzalez, Agustin Lage
Journal: Journal of Clinical Oncology (2012)

2527 Background: The prognosis of patients with advanced non small cell lung cancer (NSCLC) remains dismal. Epidermal Growth Factor Receptor (EGFR) is overexpressed in epithelial tumors and its role in the development of NSCLC is widely proven. The EGF vaccine is a therapeutic cancer vaccine composed by recombinant Epidermal Growth Factor (EGF) conjugated to a carrier protein, P64K from Neisseria Meningitides and Montanide, as adjuvant. The vaccine is intended to induce antibodies against self EGF that would block EGF-EGFR interaction. Methods: A multicentric, randomized Phase III trial was designed to assess the efficacy, immunogenicity and safety of the EGF cancer vaccine in advanced NSCLC patients. Patients older than 18 years with histology or cytology proven NSCLC at stage IIIB and IV were enrolled in the trial. All patients received no less than 4 platinum-based cycles and achieved at least stable disease, before entering the trial. A low-dose of cyclophosphamide was administered 3 days before the first immunization. Then, patients received 4 quarterly immunizations followed by monthly re-immunizations. Control patients received best supportive care. Results: In total, 405 patients bearing stage IIIB/IV NSCLC were recruited in 21 sites. The vaccine was very well tolerated. The most frequent adverse events consisted in grade 1/2 injection site pain, fever, headache, vomiting and chills. The vaccine was immunogenic. Antibody titers against EGF significantly increased with vaccination and on the contrary, EGF concentration in sera showed a fast reduction after immunization. There was an inverse correlation between the anti-EGF antibody titers and the EGF concentration in sera. Baseline EGF concentration was a worse prognostic factor for the control patients and a predictive factor for vaccinated subjects. The overall survival was significantly better for vaccinated patients as compared to controls. There was a direct correlation between the antibody titers and survival. Conclusions: The EGF cancer vaccine was very well tolerated and significantly increased overall survival of the vaccinated patients. Baseline EGF concentration predicted survival benefit. The EGF vaccine is a new therapeutic option for advanced NSCLC patients.
Feasibility of next-generation sequencing of circulating tumor cells for predicting relapse after liver resection in metastatic colorectal cancer
Authors: K. Lam, J. Ko, A. Chan, H. Choi, W. Dai, K. Lau, S. Wu, T. So, T. Lam, C. Chiang, W. Chan, M. Chan, K. Chu, W. She, K. Ma, T. Cheung, T. Wong, K. Chok, C. Lam, V. Wong, V. Lee, M. Lung
Journal: Annals of Oncology (2019)
Years lost due to disability from skin diseases in China 1990–2017: findings from the Global Burden of Disease Study 2017
Authors: W. Dong, J. An, P. Geng, X. Zeng, Y. Chen, Z. Zhao, M. Zhou
Journal: British Journal of Dermatology (2019)

decrease in the yearly mortality rate during the study period: coefficient per quarter, SE = À0Á0081 AE 0Á0033 (95% CI À0Á015 to À0Á0011), P = 0Á025 (Fig. 1).Multivariate analyses confirmed this decrease: coefficient per quarter, SE = À0Á0089 AE 0Á0032 (95% CI À0Á016 to À0Á0017), P = 0Á020.In this cohort study, we found a significant decrease in mortality over 20 years in both univariate and multivariate analysis that was not explained by a modification in patients' profiles, including their severity, except for those receiving ciclosporin.Indeed, 118 patients (33%) received ciclosporin, mainly from 2005.A prospective short trial performed from 2005 to 2007 in our dermatology department suggested a mild benefit of ciclosporin on mortality and healing. 6However, in a larger study using a propensity score methodology, including retrospectively all ciclosporin-treated patients at the same dermatology department from 2005 to 2016, the usefulness of ciclosporin could not be confirmed. 7Thus, we hypothesize that the decrease in mortality in our centre is due to improved supportive care rather than ciclosporin treatment. 1,8All of these measures were optimized by the creation of our reference centre in 2005 in the context of a national health policy for rare diseases, with implementation of a dedicated medical and paramedical team, a multidisciplinary approach to the acute phase and sequelae, teaching, and recently updated French guidelines. 8We included in the multivariate analysis most of the variables associated with mortality, including ciclosporin treatment.However, a limitation of the study is the retrospective design, including the failure to take into account some other confounding factors.
Abstract 1603: Valproic acid and hydralazine reverse increased mammary cancer risk and upregulate Cdkn2a/p16 in mice exposed to a high fat diet <i>in utero</i>
Authors: Leena A. Hilakivi-Clarke, Fabia de Oliveira Andrade, Nguyen Nguyen, Kerrie Bouker
Journal: Cancer Research (2019)

Abstract Maternal or paternal high fat (HF) diet that modifies the epigenome in germ cells and fetal somatic cells can program increased susceptibility to breast cancer among offspring. Resulting epigenetic changes include transgenerational upregulation of DNA methyltransferases (DNMTs). We studied here if this increased breast cancer risk can be reversed by treating HF offspring with a well-tolerated drug that inhibits DNA methyl transferase (DNMT; hydralazine), combined with a histone deacetylase (HDAC) inhibitor valproic acid (VPA). Adult C57BL/6NTac mouse offspring of dams fed either corn oil -based HF or control diet during pregnancy were treated with 5 g/kg/day VPA and 5 mg/kg/day hydralazine in drinking water, starting after mice received 7,12-dimethylbenz[a]anthracene (DMBA) to initiate mammary cancer. Treatment with VPA/hydralazine prevented the increase in mammary cancer risk associated with in utero HF diet exposure: it reduced mammary tumor multiplicity and lengthened tumor latency, compared with non-treated HF offspring. These drugs downregulated DNMT3a protein levels, and reversed down-regulation of Cdkn2a/p16 mRNA in the mammary tumors of HF offspring. p16 is a tumor suppressor that is often epigenetically silenced in human breast cancers. However, in control offspring not exposed to HF diet in utero, VPA/hydralazine increased mammary tumor incidence and burden. Further, this treatment upregulated genes involved in the unfolded protein response pathway in in utero control diet exposed animals that were already upregulated in non-VPA/hydralazine treated mammary tumors from in utero HF diet exposed animals, including HIF-1α, NFkB, PERK and SQSTM1 p62. Thus, VPA and hydralazine had opposing effects on breast cancer risk in HF and control offspring, suggesting the importance of individually tailoring breast cancer prevention strategies. Citation Format: Leena A. Hilakivi-Clarke, Fabia de Oliveira Andrade, Nguyen Nguyen, Kerrie Bouker. Valproic acid and hydralazine reverse increased mammary cancer risk and upregulate Cdkn2a/p16 in mice exposed to a high fat diet in utero [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1603.
Oral immunotherapy with antigenicity‐modified casein induces desensitization in cow’s milk allergy
Authors: Norio Kawamoto, Hideo Kaneko, Minako Kawamoto, Hidenori Ohnishi, Eiko Matsui, Takahide Teramoto, Zenichiro Kato, Toshiyuki Fukao, Hiroshi M. Ueno, Taku Nakano, Naomi Kondo
Journal: Allergy (2019)

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Abstract 2771: Identification of novel genes associated with metastasis from TCGA transcriptomic data
Authors: Takahiko Koyama, Laxmi Parida
Journal: Cancer Research (2019)

Abstract Introduction: Many cancer patients suffer from metastasis in bone, brain, liver and lung. However, understanding of metastasis in molecular level is quite limited. To improve survival rate and quality of life, preventing metastasis is crucial. In this study, we analyzed transcriptomic data with tumor node metastasis (TNM) classification from The Cancer Genome Atlas (TCGA) to identify genes associated with metastasis. Method: TCGA samples in 20 solid tumor types with both transcriptome and TNM annotation data are used. To obtain the best cut point separating cohorts of high and low gene expression, Hothorn and Lausen’s method is used. A contingency table is created with expression separated by the the cut point and presence of staging T, N, M for each gene. Association between the staging category and the gene was calculated with Fisher’s exact test. Results: In total, 13,220 distinct genes including miRNAs are associated with either lymph node or distant metastasis for some cancer types with a loose criteria of p-value &amp;lt; 1.0e-3. Among them, we identified 1,357 genes with p-value &amp;lt; 1.0e-8. ADAMTS12, AURKB, BUB1, C17orf53, CCNA2, CEP55, EPR1, KIF4A, KIF11, KRT80, MELK, MKI67, NCAPG, NEIL3, PBK, PLK1, RRM2, TPX2, miR139, miR30a, miR375, and miR379 appear most commonly in lymph node metastasis for many cancer types. Likewise, NOP56, PKD1L2, miR150, miR365, miR9, miR149, miR210, miR425, miR675, and miR937 are most commonly associated genes in distant metastasis. Many of these genes have been already reported in association with metastasis. Conclusions: This study created comprehensive list of metastasis associated genes for the 20 solid tumors in TCGA. They would be useful as diagnostic and prognostic biomarkers; however, we found therapeutically relevant genes such as PLK1, AURKB, MET, MELK, CDK1, BUB1, and PBK. Some adhesion molecules associated with a particular cancer type might explain its organ destination preference. Among distant metastatic miRNAs discovered, metastasis promoting miRNAs in high abundance might be engaged in homing as exosomal miRNAs by reprogramming destination niche in favor of migrating tumor cells. Further work to reveal metastasis mechanism and to discover some pharmaceutical agents to prevent metastasis will be conducted. Citation Format: Takahiko Koyama, Laxmi Parida. Identification of novel genes associated with metastasis from TCGA transcriptomic data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2771.
Abstract 3582: Circular RNA circPLEHM3 acts as the sponge of microRNA-9 to suppress ovarian carcinoma progression
Authors: Lei Zhang, Pengyuan Liu, Bingjian Lu, Weiguo Lu, Yan Lu
Journal: Cancer Research (2019)

Abstract Circular RNAs(circRNAs) are a class of stable and widespread endogenous noncoding RNA. CircRNAs have been reported to play essential roles in cancer biology, and have potential as biomarkers and therapeutic targets for cancer intervention. Here, we screened the expression profiles of human circRNAs in 27 ovarian cancer and 26 normal ovary tissues, and found circPLEKHM3 (hsa_circ_0001095) was significant down-regulated in ovarian cancer tissues. Patients with lower circPLEKHM3 expression tended to have poorer prognosis. Functionally, circPLEKHM3 overexpression inhibited cell growth, migration and epithelial-mesenchymal transition (EMT) in vitro and in vivo, but its knockdown reversed these effects. Further analyses showed that circPLEKHM3 sponges miR-9 to regulate the expression of BRCA1, DNAJB6 and KLF4, and inactivates the AKT1 expression. In addition, AKT inhibitor MK-2206 blocked the tumor-promoting effect of circPLEKHM3 knockdown, and potentiated taxol induced growth inhibition of ovarian cancer cells. Taken together, our findings demonstrated that circPLEKHM3 functions as a tumor suppressor in ovarian cancer cells by targeting the miR- 9/BRCA1/DNAJB6 /KLF4/AKT1 axis and may provide a prognostic biomarker and therapeutic target in ovarian cancer. Note: This abstract was not presented at the meeting. Citation Format: Lei Zhang, Pengyuan Liu, Bingjian Lu, Weiguo Lu, Yan Lu. Circular RNA circPLEHM3 acts as the sponge of microRNA-9 to suppress ovarian carcinoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3582.
Colorectal cancer characteristics and outcomes in patients less than age 50: A comparison of an urban university hospital with the NCI SEER database.
Authors: Edith P. Mitchell, Allan Topham, Pramila R. Anne, Scott Goldstein, Gerald Isenberg, Fran Guiles, Juan Palazzo
Journal: Journal of Clinical Oncology (2012)

3621 Background: Cancer of the colon and rectum is the third most commonly occurring cancer, as well as the third leading cause of cancer deaths in American men and women. Colorectal cancer in younger patients is believed to have worse pathological features and prognosis than in older patients. The objective of this study was to assess pathological features and outcomes of CRC in patients less than age 50 using an institutional sample and comparing to the Surveillance, Epidemiology and End Results (SEER) database. Methods: Included in the study were a total of 4595 cases from the Tumor Registry at Thomas Jefferson University Hospital (TJUH) over a twenty year period from 1988 through 2007 and 290,338 cases from the Surveillance, Epidemiology and End Results (SEER) database from 1988 through 2004. Patients less than age 50 were compared to those age 50 and older. Results: Patients under age 50 with CRC presented with more advanced stage tumors in both data sets (&lt;0.0001) , and had more poorly differentiated tumors than older patients (P TJUH =0.02754; P SEER &lt;0.0001). Patients under 50 also had more mucinous/signet ring cell tumors with 12 percent to 8.1 percent in the TJUH data (p=0.002916) and 13.2 percent to 10.3 percent in the SEER data (p&lt;0.0001), with younger males having the highest prevalence in both data sets. Younger patients had fewer proximal tumors than patients 50 and over, and a higher proportion of rectal tumors (p&lt;0.001). Patients under age 50 were more likely to have positive nodes at all stages (P SEER &lt;0.0001) relative to 50 and over, as well as more likely to develop peritoneal metastases (P TJUH =0.3507),, but less likely to have lung metastases P TJUH =0.05249) than older pts. Despite their poor pathologic features, patients under age 50 had better than or equal survival to those 50 and older. Conclusions: Colorectal cancer patients under age 50 presented with worse histological characteristics and metastasized much sooner, yet the younger patients had better than or equal survival to those ages 50 and older. Ongoing studies will assess differences in treatment and molecular features between younger and older colorectal cancer patients.
Abstract 4439: MLN4924, a protein neddylation inhibitor, elicits antitumor effect via suppression of angiogenesis
Authors: Kuan-Lin Kuo, Shao-Ping Yang, Shih-Ming Liao, Yeong-Shiau Pu, Kuo-How Huang
Journal: Cancer Research (2019)

Abstract In the process of tumorigenesis, angiogenesis provide oxygen and nutrients for tumor progression. Anti-angiogenesis has become a promising target of cancer therapy. Cullin-RING ligases (CRLs) are a cullin scaffold RING-finger domain containing E3 and are involved in the ubiquitination of specific substrates which regulate important biological processes. The holoenzyme E3 activity of CRLs is controlled by NEDD8. A novel NEDD8-activating enzyme inhibitor, MLN4924, is reported to block the neddylation of cullins and elicits antitumor effect. MLN4924 has been reported to be assoiciated with antiangiogenesis. In this study, we aim to investigate the role of anti-angiogensis in the antitumor effect of MLN4924. Our results showed that MLN4924 induces the cell cycle arrest, apoptosis and suppresses the cell viability and migration in human umbilical vein endothelial cells (HUVECs). Moreover, MLN4924 inhibits angiogenesis in Matrigel plug assay in vivo and tube-formation assay in vitro. Anti-angiogesis was involved in the antitumor effect on human urothelial carcinoma cells (T24) and colon cancer cells in vivo xenograft model. MLN4924 suppressed the VEGF-mediated VEGFR2 downstream activation. Note: This abstract was not presented at the meeting. Citation Format: Kuan-Lin Kuo, Shao-Ping Yang, Shih-Ming Liao, Yeong-Shiau Pu, Kuo-How Huang. MLN4924, a protein neddylation inhibitor, elicits antitumor effect via suppression of angiogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4439.