tbuckley/cabot-search huggingface dataset:
Abstract 2224: A panel of autoantibodies against multiple tumor-associated antigens in the early immunodiagnosis of lung cancer
Authors: Di Jiang, Tingting Wang, Lu Pei, Peng Wang, Hua Ye, Chunhua Song, Kaijuan Wang, Jianying Zhang, Liping Dai
Journal: Cancer Research (2019)

Abstract Lung cancer is the most common cancers worldwide and with very low 5-year survival rate due to lack of effective early diagnostic methods. In our previous study, nine autoantibodies against tumor-associated antigens (TAAs) were identified to be potential biomarkers in detection of lung cancer and this study aimed to find the optimal panel of TAAs to detect lung cancer in the early stage. Methods A total of 1,130 serum samples were included in this study, including patients with lung cancer, normal control and benign lung diseases patients. Autoantibodies against PSIP1,TOP2A,ACTR3,RPS6KA5,HMGB3,MMP12,GREM1,ZWINT and NUSAP1 were detected by enzyme-linked immunosorbent assay. Logistic regression models were generated from the training set and further validated in another independent set. We also evaluated the ability of the model to detecting benign lung diseases and early-stage lung cancer. Results Two greater models were selected. One model including 5 autoantibodies panel (GREM1,HMGB3,ZWINT,TOP2A and PSIP1) and another model including 3 autoantibodies panel (GREM1,HMGB3 and PSIP1). Finally, the panel of 3 autoantibodies showed high diagnostic accuracy with areas under the curve (AUC) of 0.711(95 % CI 0.674-0.746) in training cohort and 0.891(95% CI 0.845-0.927) in validation cohort, respectively. The AUC of the model of 3 autoantibodies panel was 0.948(95% CI 0.912-0.972) in discriminate lung cancer and benign pulmonary disease. This model could discriminate early-stage lung cancer patients from normal controls, with AUC of 0.686(95 % CI 0.633-0.735) in training cohort and AUC of 0.911(95 % CI 0.849-0.954) in validation cohort, and the overall AUC for early-stage lung cancer was 0.779(95 % CI 0.738-0.816) when the two cohorts were combined. Conclusions In summary, it would be more cost-effective and more efficient to use the model with 3 autoantibodies panel which has a high diagnostic performance for lung cancer detection, especially for early-stage lung cancer. And the model may apply a new help for the discrimination for benign pulmonary disease and lung cancer. Note: This abstract was not presented at the meeting. Citation Format: Di Jiang, Tingting Wang, Lu Pei, Peng Wang, Hua Ye, Chunhua Song, Kaijuan Wang, Jianying Zhang, Liping Dai. A panel of autoantibodies against multiple tumor-associated antigens in the early immunodiagnosis of lung cancer [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 2224.
Abstract 889: Biochemical and histopathological evaluation of Al2O3 nanomaterials in kidney of Wistar rats
Authors: Anita Patlolla, Paul Tchounwou
Journal: Cancer Research (2019)

Abstract The present study was investigated to evaluate the response of kidneys in Wistar rats following long term exposure to Al2O3 nanomaterials. To achieve this objective, Al2O3 of three different sizes (30nm, 40nm and bulk) was orally administered for 28 days to 9 groups of 10 Wistar rats each at the dose of 500, 1000 and 2000 mg/kg/rat. A tenth group of 10 rats received distilled water and served as control. After 28 days of exposure the animals were sacrificed and the serum was collected and tested for the activity levels of creatinine and urea following standard methods. Induction of oxidative stress was also investigated by assessing TBARS (MDA), Protein carbonyl, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities. A Histopathological evaluation was also performed to determine the extent of kidney damage. The results showed that both serum creatinine and serum urea levels increased significantly in the treated rats compared to control animals. The increase was found to be more in Al2O3-30nm followed by Al2O3-40nm and Al2O3-bulk treated rats in a dose-dependent manner. Further administration of Al2O3 significantly increased the activities of TBARS, protein carbonyl, catalase and decreased the activities of GSH and SOD in a dose dependent manner in the kidney of rats compared with control group. Histopathological evaluation showed significant morphological alterations in kidney tissue of treated rats in accordance with biochemical parameters. Taken together, the results of this study demonstrate that Al2O3 is nephrotoxic and its toxicity may be mediated through oxidative stress. Further, the results suggest that prolonged oral exposure to Al2O3 NMs has the potential to cause biochemical and histological alterations in kidney of rats at high concentration. Note: This abstract was not presented at the meeting. Citation Format: Anita Patlolla, Paul Tchounwou. Biochemical and histopathological evaluation of Al2O3 nanomaterials in kidney of Wistar rats [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 889.
Abstract 4498: O GlcNAcylation of SOX2 regulates its tumor initiation properties in pancreatic cancer
Authors: Nikita S. Sharma, Vineet K. Gupta, Patricia Dauer, Roey Hadad, Kousik K. kesh, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Journal: Cancer Research (2019)

Abstract Background: Pancreatic Cancer is an extremely aggressive disease with a bad outcome owing to its late detection, high rate of metastasis and self-renewal post-surgical and chemotherapeutic intervention. In cancer the balance between differentiation and self-renewal is tightly regulated by SOX2. Over expression of SOX2, as in pancreatic cancer, can tilt the balance towards self-renewal and thus increase the population of these undifferentiated “stem cells”. Methods: A CRISPR based OGT knockout kit was purchased from Origene and a knockout cell line was generated with S2VP10 cells. For the tumor initiation studies OGTi (OGT knockout cells) were implanted subcutaneously at a limiting dilution from 500,000 cells to 500 cells. Site directed mutagenesis was performed using theQuick-change Lightning from Agilent. Results: In the current study we show for the first time that SOX2 undergoes a type of post translational modification known as O GlcNAcylation. We also show for the first time that in humans this modification happens at Serine 246 and mutating this particular site via a side directed mutagenesis leads to a loss of O GlcNAcylation of SOX2.O GlcNAc modification of SOX2 further leads to its activation which then leads to its stabilization in the nucleus. A CRISPR-OGT knockout in pancreatic cancer cell line S2VP10 resulted in a delayed tumor initiation. We further showed that mutation of this site (S246A) prevents the modification of Sox2 and its downstream activity. Our study also demonstrated that targeting OGT in vivo with a small molecule inhibitor OSMI, results in decreased tumor burden, delayed tumor progression and a decreased expression of SOX2 in pancreatic cancer cells. Conclusion: Our study highlights for the first time that the O-GlcNAc transferase dependent SOX2 glycosylation has a profound effect on the transcriptional activity of SOX2 and is instrumental in determining self-renewal in pancreatic cancer which can be targeted therapeutically. Citation Format: Nikita S. Sharma, Vineet K. Gupta, Patricia Dauer, Roey Hadad, Kousik K. kesh, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee. O GlcNAcylation of SOX2 regulates its tumor initiation properties in pancreatic cancer [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 4498.
A compendium of promoter-centered long-range chromatin interactions in the human genome
Authors: Inkyung Jung, Anthony Schmitt, Yarui Diao, Andrew J. Lee, Tristin Liu, Dongchan Yang, Catherine Tan, Junghyun Eom, Marilynn Chan, Sora Chee, Zachary Chiang, Changyoun Kim, Eliezer Masliah, Cathy L. Barr, Bin Li, Samantha Kuan, Dongsup Kim, Bing Ren
Journal: Nature Genetics (2019)
Characteristics of US Counties With High Opioid Overdose Mortality and Low Capacity to Deliver Medications for Opioid Use Disorder
Authors: Rebecca L. Haffajee, Lewei Allison Lin, Amy S. B. Bohnert, Jason E. Goldstick
Journal: JAMA Network Open (2019)

Opioid overdose deaths in the United States continue to increase, reflecting a growing need to treat those with opioid use disorder (OUD). Little is known about counties with high rates of opioid overdose mortality but low availability of OUD treatment.
Abstract 1258: Pooled-analysis of response markers in cancer cell lines treated with tumor treating fields
Authors: Gitit Lavi Shahaf, Moshe Giladi, Rosa S. Schneiderman, Karnit Gotlieb, Einav Zeevi, Yaara Porat, Mijal Munster, Uri Weinberg, Eilon D. Kirson, Yoram Palti
Journal: Cancer Research (2019)

Abstract Low intensity, intermediate frequency alternating electric fields (TTFields) exert an inhibitory effect on numerous cancer cell lines with some variability in the response. The goal of the present study is to compare characteristics of cell lines based on their response pattern to TTFields and to identify response markers. Forty-five different human cancerous cell lines were treated for 72 hours with TTFields at optimal cell-specific frequency at the same nominal intensity (1.7 V/cm). Cytotoxicity and clonogenic potential were determined. Functional analysis of differentially expressed genes and mutations associated with response to TTFields was performed based on the Cancer Cell Line Encyclopedia (CCLE) database. Sensitivity to TTFields was compared with pharmacological profiling (CCLE). The cytotoxic response to TTFields was found to be distributed around an average of 50% with (ranging between 14% and 86% reductions in cell counts). The clonogenic effect varied between no effect and 88% reduction in the number of colonies. Increased sensitivity to: Lapatinib, PHA-665752 and PLX-4720 was common in the group of cell lines which were more highly responsive to TTFields. Functional analysis of cell line gene expression and mutation data revealed enriched pathways related to DNA damage repair response, cell migration, hypoxia signaling and oxidative stress. This analysis of cancerous cell line response to TTFields define the optimal frequency to be applied for each cell line and demonstrates the broad effectiveness of TTFields in cells. The role of the specific mutations associated with TTFields response should be further explored in additional studies. Pharmacological profiling may offer a rational for combining specific agents with TTFields. Citation Format: Gitit Lavi Shahaf, Moshe Giladi, Rosa S. Schneiderman, Karnit Gotlieb, Einav Zeevi, Yaara Porat, Mijal Munster, Uri Weinberg, Eilon D. Kirson, Yoram Palti. Pooled-analysis of response markers in cancer cell lines treated with tumor treating fields [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 1258.
Abstract 1304: Aryl hydrocarbon receptor ligands 5F 203 and 3,3'-Diindolylmethane disrupt mammospheres derived from MCF-7 cells and induce tumor suppressor miR125b-2 expression
Authors: Eileen Brantley, Nicole Mavingire, Jonathan Wooten, Petreena Campbell
Journal: Cancer Research (2019)

Abstract While anti-estrogen tamoxifen (Tam) effectively treats many patients with estrogen receptor positive (ER+) tumors, up to 40% experience relapse following resistance. Breast cancer stem cells (CSCs) within tumors greatly contribute to tamoxifen resistance (TamR) and exhibit unique molecular signatures that drive metastasis and promote relapse. Tumor suppressor miRNAs aid in suppressing breast cancer progression. We have previously shown that aryl hydrocarbon receptor (AhR)-ligand Aminoflavone disrupts the formation of spheres and inhibits the expression of putative stemness marker α6-integrin and α6-integrin-src-Akt signaling. We hypothesize that two AhR ligands, 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) and 3,3'-Diindolylmethane (DIM), exhibit anticancer properties in MCF-7 breast cancer cells by targeting the CSC population in an AhR-dependent fashion. We found that DIM and 5F 203 disrupted mammospheres derived from MCF-7 cells but demonstrated a reduced capacity to do so in mammospheres derived from AHR100 cells (MCF-7 variants that are AhR-unresponsive). Wound healing and colony forming assays respectively revealed that 5F 203 and DIM also decreased cell migration and cell proliferation in MCF-7 cells and to a much lesser extent in AhR100 cells. 5F 203 and DIM induced miR125b-2 expression and suppressed the expression of stemness-regulating genes such as α6-integrin, a predicted miR125b-2 target. The reduction in stemness-gene expression in MCF-7 cells was attenuated following pretreatment with AhR antagonist CH223191. These data suggest that AhR ligands such as DIM and 5F 203 confer their anticancer actions including those against breast CSCs in an AhR-dependent manner. Our data is expected to provide a rationale for the development of anticancer AhR ligands designed to combat ER+ breast cancer and decrease the risk of relapse. Citation Format: Eileen Brantley, Nicole Mavingire, Jonathan Wooten, Petreena Campbell. Aryl hydrocarbon receptor ligands 5F 203 and 3,3'-Diindolylmethane disrupt mammospheres derived from MCF-7 cells and induce tumor suppressor miR125b-2 expression [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 1304.
Dietary Supplements for Brain Health—Reply
Authors: Joanna Hellmuth, Gil D. Rabinovici, Bruce L. Miller
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 608: Examining H. pylori core genes for epidemiological typing
Authors: Guoqin Yu
Journal: Cancer Research (2019)

Abstract H. pylori is the major causative risk factor of a serious of diseases including gastric cancer. It is highly diverse. Conventional method of typing H. pylori has been based on seven MLST loci, which however are not sufficient to distinguish closely-related strains. High diverse core genes that are present in all H. pylori strains are potential good candidates for investigating genomic variation within closely-related strains, therefore improving our understanding of H. pylori -related disease epidemiology. In this study, we investigated the variation of the H. pylori genome, especially its core genes. We downloaded 80 H. pylori whole genome from National Center for Biotechnology Information (NCBI), and identified core genes (99% &amp;lt;= strains &amp;lt;= 100%: 840 genes), Soft core genes (95% &amp;lt;= strains &amp;lt; 99%: 185), Shell genes (15% &amp;lt;= strains &amp;lt; 95%: 933), Cloud genes (0% &amp;lt;= strains &amp;lt; 15%: 2313). Compared with other gene groups, we found that core genes have higher proportion of polymorphic sites, similar level of nucleotide diversity per site, higher recombination events per site, and lower number of gaps per site. In addition, core genes evolve slower than other gene groups with lower Tajima’s D value and nonsynonymous to synonymous ratio. Among the core and soft-core genes, we found that majority have low genetic diversity while a few showed higher diversity. We evaluated these high diverse core genes further in terms of their evolution, function and potential to serve as candidates to distinguish closely related H. pylori strains. Note: This abstract was not presented at the meeting. Citation Format: Guoqin Yu. Examining H. pylori core genes for epidemiological typing [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 608.
Abstract 1407: Histone marks interplay at LIFR enhancer determines the response to HDAC inhibitors in breast cancer
Authors: Xiaomin Wang, Jun Xu, Jian Ding, Meiyu Geng, Min Huang
Journal: Cancer Research (2019)

Abstract The dynamic crosstalk of epigenetic modifications is believed to impose a strong impact on epigenetically-targeted therapies, such as histone deacetylase (HDAC) inhibitors, but current understanding in this regard is extremely limited.Our previous work has revealed that the transcriptional feedback activation of leukemia inhibitory factor receptor (LIFR) limits the response to HDAC inhibitors in breast cancer. However, LIFR transcriptional response appears highly heterogeneous in breast cancer and the reason behind is unclear. This study takes LIFR as a representative to dissect how histone marks interplay determines the transcriptional outcome of epigenetically-targeted therapies. We herein discover that the H3K27 methylation specifically at LIFR enhancer restricts the H3K27 acetylation upon HDAC inhibition and prevents the upregulation of LIFR. The intrinsic level of H3K27 methylation at LIFR enhancer stratifies the responsive subset to HDAC-targeted therapies in a panel of patient-derived breast cancer models. This study provides strong evidence showing how existing histone marks and their specific localization together determine the transcriptional output and the outcome of epigenetically-targeted therapies, highlighting the significance of histone marks crosstalk in epigenetic therapeutics. Note: This abstract was not presented at the meeting. Citation Format: Xiaomin Wang, Jun Xu, Jian Ding, Meiyu Geng, Min Huang. Histone marks interplay at LIFR enhancer determines the response to HDAC inhibitors in breast cancer [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 1407.
Aerobic Plus Resistance Exercise in Obese Older Adults Improves Muscle Protein Synthesis and Preserves Myocellular Quality Despite Weight Loss
Authors: Georgia Colleluori, Lina Aguirre, Uma Phadnis, Kenneth Fowler, Reina Armamento-Villareal, Zheng Sun, Lorenzo Brunetti, Jun Hyoung Park, Benny Abraham Kaipparettu, Nagireddy Putluri, Vimlin Auetumrongsawat, Kevin Yarasheski, Clifford Qualls, Dennis T. Villareal
Journal: Cell Metabolism (2019)
Abstract 3901: Nonclinical safety evaluation of CA102N, a hyaluronic acid (HA) and nimesulide (Nim) conjugate, for colorectal cancer treatment
Authors: Eskouhie Tchaparian, Louis Lin, Elin Hsu, Ivy Chen, Albert Wu
Journal: Cancer Research (2019)

Abstract CA102N is a conjugate of the biological polymer hyaluronic acid (HA) and Nimesulide (Nim), a cyclooxygenase-2 (COX-2) inhibitor that represents a promising new approach to addressing cancer treatment. Similar to an antibody-drug conjugate or a pro-drug, CA102N enhances the efficacy of Nim through targeting and binding of HA to CD44 receptors highly expressed in solid tumors. Pharmacological (in vitro and in vivo) studies indicated that CA102N exhibits apoptotic and tumor growth inhibitory activities against colorectal cancer. The MOA of CA102N was demonstrated to be related to apoptosis and disruption of the PI3K/Akt/mTOR pathway in addition to inhibition of the COX-2/PGE2 related pathways. Safety of CA102N was assessed in acute dose range finding and repeat-dose intravenous toxicity studies in rats and beagle dogs. Three dose levels including the Maximum Tolerated Dose (MTD) from DRF study, a middle dose and a low dose equivalent to the proposed clinical dose were administered twice weekly (BID). A 28-day recovery group was also included in the rat study. Overall CA102N was well tolerated in both species. CA102N did not induce any significant effects on the CNS, the cardiovascular and respiratory systems in animal models. Some changes in hematological parameters were observed only in rats at the highest dose (Std 10: ≥ 600 mg/kg/day ), however, most of these observations were reversible. No hERG inhibition (in vitro) was observed suggesting the risk of QT prolongation with CA102N is low. The Highest Non-Severely Toxic Dose (HNSTD) of CA102N in the dog was determined to be 280 mg/kg/day (7.24 mg/kg in Nim equivalents ) and the rat NOAEL was 400 mg/kg/day (10.16 mg/kg in Nim equivalents ). These doses are 2.3 times (rat) and 5.6 times (dog) of nimesulide dose to be evaluated (up to 0.72 mg/kg of nimesulide) in the proposed phase 1 study. On the basis of the mechanism of action and the nonclinical safety profiles, toxicity associated risks to patients appear to be low at the proposed clinical dose levels. A Phase I study of CA102N in patients with locally advanced or metastatic colorectal cancer is ongoing. Citation Format: Eskouhie Tchaparian, Louis Lin, Elin Hsu, Ivy Chen, Albert Wu. Nonclinical safety evaluation of CA102N, a hyaluronic acid (HA) and nimesulide (Nim) conjugate, for colorectal cancer treatment [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 3901.
Abstract 392: Impacto of Nifedipine on Polymorphonuclear Cells in Wounds
Authors: Augusto Brasileiro, Dinaldo C Oliveira, Danielle Oliveira, Jessica Amorim, Marina Rocha, Bruno Medeiros, Lais Dantas, Maria Isabel Gadelha, Vitor Nunes
Journal: Circulation Research (2017)

Introduction: Skin wounds are a problem and many occur due to vascular diseases. There is a need for drugs (low cost) that can heal wounds. We aimed to evaluate if the use of nifedipine in wounds is associated with recruitment of polymorphonuclear cells higher than placebo. Hypothesis: Nifedipine stimulates the recruitment of polymorphonuclear in wounds. Methods: We performed 32 wounds in pigs and locally applied placebo or nifedipine (1%, 10% or 20%). Wounds were evaluated macro and microscopically at 6 different moments. A logistic longitudinal model of mixed effects was applied. For this purpose, the response to moderate or marked polymorphonuclear cells was considered as a dependend variable, with the comparison groups (placebo, nifedipine 1%, 10% and 20%) as the explanatory variable. Based on the placebo group, the OR was estimated with its respective confidence interval for the nifedipine groups at the different doses. Value of p &lt;0.05 was considered significant. This study was approved by the animal research ethics committee. Results: The table below shows the proportion of polymorphonuclear cells among the comparison groups over the 6 analyzed moments. Conclusions: Wounds treated with nifedipine had higher recruitment of polymorphonuclear, regardless of the concentration used. This drug has potential for recruitment of this type of cell and may have a beneficial effect on healing.