tbuckley/cabot-search huggingface dataset:
Abstract 229: Establishing reference intervals of human urine proteome for monitoring physiological and pathological changes
Authors: Wenchuan Leng, Xiaotian Ni, Changqing Sun, Anna Malovannaya, Yi Wang, Jun Qin
Journal: Cancer Research (2017)

Abstract Urine as a true non-invasive sampling source holds great potential for biomarker discovery. But the lack of method for profiling urine proteome in high throughput and systematic evaluation of variations in urine proteomes based on large number of population have been being the major obstacles for successfully finding new biomarkers from urine. Due to low throughput, only limited number of urine samples can be measured in discovery phase of biomarker studies, which make it hard to determine whether proteins differentially expressed between groups represent actual differences between control and disease states or just physiological variations among individuals. So, candidate biomarkers often fail in validation phase. Here, we report a streamlined workflow with capacity of measuring 8 urine proteomes per day per MS at the coverage of more than 1500 proteins. With this workflow, we systematically evaluated variations in 497 human urine proteomes from 167 apparently healthy donors, allowing us to evaluate day to day and inter-personal variation in human urine proteome. Then personal and pan-human reference intervals (RIs) of urine proteome were established based on this large-scale dataset. We demonstrated that RIs can be used to monitor physiological changes by detecting transient outlier proteins, such as trans-continental travel and common flu. And it was also found that if the underlying cause is physiological variation, outlier proteins will fall back to the normal range in the follow up measurement, as exemplified in the intercontinental travel case. Persistent outlier proteins may be indicative of non-physiological conditions. These results indicate that periodical measurements of a person’s urine proteome could establish a personal health archive that would be valuable for detecting future health issues. Furthermore, we proposed a complete novel strategy dependent on RIs-based algorithm for biomarker discovery and validation to screen for diseases, which were exemplified by analyzing 154 urine proteomes from patients with 7 types of cancers. The algorithm can distinguish normal people from cancer patients with specificity of 0.95 and sensitivity of 0.85. This study paves a way to use urine proteome for health monitoring and disease screening. Citation Format: Wenchuan Leng, Xiaotian Ni, Changqing Sun, Anna Malovannaya, Yi Wang, Jun Qin. Establishing reference intervals of human urine proteome for monitoring physiological and pathological changes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 229. doi:10.1158/1538-7445.AM2017-229
Abstract 3713: Higher numbers of cancer stem cells in the peripheral blood of children with B-ALL upon conventional chemotherapy
Authors: Mohamed L. Salem
Journal: Cancer Research (2017)

Abstract Background: Acute lymphocytic leukemia (ALL) is biologically and clinically considered as a heterogeneous neoplasm of lymphoid progenitor cells in the bone marrow (BM). 15- 20 % of children with ALL who achieve an initial remission, will show relapse. One potential mechanism behind this relapse could be the emergence of cancer stem cells (CSCs) which are considered the driving force of tumourigenesis due to their ability of self-renewal as well as the emergence of immune regulatory cells including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Treg). Aim: the main aim of this study was to analyze the numbers of CSCs and correlate these numbers with the numbers of blast cells, MDSCs and Treg cells in children with B-ALL before and after induction of chemotherapy. Materials and Methods: CSCs were defined as CD45dimCD19+CD10+CD34+CD38-, MDSCs were defined as Lin-HLA-DR-CD33+CD11b+ and Treg cells were defined as CD4+CD25+CD127-. The frequencies of these cells were analyzed in the peripheral blood of B-ALL patients before (n= 10) and after (n= 10) induction of chemotherapy using flow cytometry. Results: Significant increases in the numbers of CSCs were shown in B-ALL patients after induction of chemotherapy as compared to newly diagnosed patients (7.6± 8.3 vs. 2.7± 2.4, P&amp;lt;0.05). The numbers of CSCs in ALL patents before and after induction of chemotherapy inversely correlated with the numbers of the blast cells. Additionally, the numbers of MDSCs and Treg cells were higher and lower, respectively, in patients after induction of chemotherapy as compared to before chemotherapy. Conclusion: Our results indicate that chemotherapy of B-ALL patients results in emergence of high numbers of CSCs and MDSCs which might be contributing, respectively, to tumor relapse and creation of systemic immune suppression. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger population of B-ALL patients at different treatment stages. Note: This abstract was not presented at the meeting. Citation Format: Mohamed L. Salem. Higher numbers of cancer stem cells in the peripheral blood of children with B-ALL upon conventional chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3713. doi:10.1158/1538-7445.AM2017-3713
Abstract 4583: Heterogeneity in immune biomarker expression: Detailed analysis of a case with SCLC transformation after EGFR-TKI treatment
Authors: Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J. Rivard, Tetsuya Mitsudomi, Fred R. Hirsch
Journal: Cancer Research (2017)

Abstract Introduction: The expression status of immune markers are of current research interest due to their potential roles as predictive biomarkers for immunotherapy in cancers. Currently there is little information on how the microenvironment of tumors and/or therapy-inducible histological transformation may affect the expression of these immune markers. Methods: A 76-year-old never-smoking female with epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma (AC) acquired resistance to gefitinib. After her death, autopsy revealed small-cell lung cancer (SCLC) transformation and EGFR T790M secondary mutation as mutually exclusive resistance mechanisms. Two liver metastases (SCLC vs. AC with T790M) and two lymph node metastases (SCLC vs. AC with T790M) were analyzed to compare the expression status of immune markers by immunohistochemistry (IHC) and an immune-oncology gene expression panel (HTG EdgeSeq Immuno-Oncology Assay). Results: IHC analysis revealed that PD-L1 was expressed in 5% of tumor cells with AC histology (T790M) but not in tumor cells with SCLC transformation (Table 1). The liver metastasis with SCLC transformation showed negative stromal PD-L1 expression and scant tumor infiltrating lymphocytes, while the other lesions demonstrated stromal PD-L1 staining and infiltration of CD8-positive T cells. PD-1 was positive in lymphocytes from lymph node metastases, but not in those from liver metastases. Data generated using an IO panel indicated higher expression of galectin 9 and higher level of T cell stimulatory checkpoints in lesions with SCLC transformation. Bioinformatic analysis also demonstrated lower expression of type I interferon regulated genes in lesions with SCLC transformation. Conclusion: These data highlight the heterogeneity of expression of immune markers depending on the metastatic sites and histological transformation, and indicate that a biopsy from one lesion may not be representative of immune marker status for all lesions. Summary of immune marker IHC staining in all specimensSpecimensPD-L1 (tumor)PD-L1 (stroma)TILsCD8 (T cells)PD-1 (T cells)Liver metastasis (AC / T790M)5%5%+++negativeLiver metastasis (SCLC)negativenegativescantn.a.n.a.Lymph node metastasis (AC / T790M)5%5%++++Lymph node metastasis (SCLC)negative10%++++ Citation Format: Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J. Rivard, Tetsuya Mitsudomi, Fred R. Hirsch. Heterogeneity in immune biomarker expression: Detailed analysis of a case with SCLC transformation after EGFR-TKI treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4583. doi:10.1158/1538-7445.AM2017-4583
Abstract 5710: <i>PGRMC1</i> is a biomarker for breast cancer cell proliferation and early relapse
Authors: Elizabeth S. McDonald, Dhruv K. Pant, Tien-chi Pan, David A. Mankoff, Robert H. Mach, Lewis A. Chodosh
Journal: Cancer Research (2017)

Abstract Background: Breast cancers may recur following a long latency period, implying a dormant or quiescent phase, however little is known about the biology of cellular quiescence and few markers exist for this clinically important state. The purpose of this study was to investigate whether progesterone receptor membrane component family 1 (PGRMC1), which is expressed in both proliferating and quiescent tumor cells, is a prognostic biomarker in human breast cancer and to define its expression in breast cancer subtypes. Methods: Seventeen publicly available data sets were combined to analyze PGRMC1 expression in 4,463 invasive breast cancers as a function of established molecular and phenotypic markers, estimates of cellular proliferation, and recurrence-free survival data. A gene expression signature-based assay was utilized to estimate cellular proliferation. Association between gene expression and relapse-free survival was assessed using Cox proportional hazards regression while controlling for the effect of proliferation. Results: PGRMC1 expression was analyzed stratified by immunohistochemical and molecular subtype, tumor grade and size and compared with a known triple negative breast cancer biomarker, BCL11a. PGRMC1 and BCL11a each exhibited a robust positive correlation of comparable magnitude with proliferation across all breast cancer subtypes (r=0.27, p=6.5x10-17 and r=0.29, 1.7x10-41, respectively), and PGRMC1 was strongly associated with proliferation within the basal subtype (r=0.42, p=2.4x10-37 PGRMC1 versus 0.31, p=1.1x10-8 BCL11a). PGRMC1 expression was associated with a higher risk of early breast cancer recurrence (HR=1.25, 95% CI [1.12,1.39], p=6.4x10-5) and this association was dependent upon its association with proliferation. Conclusions: PGRMC1 is a breast cancer proliferation biomarker. Further study of the function of this protein is warranted. Citation Format: Elizabeth S. McDonald, Dhruv K. Pant, Tien-chi Pan, David A. Mankoff, Robert H. Mach, Lewis A. Chodosh. PGRMC1 is a biomarker for breast cancer cell proliferation and early relapse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5710. doi:10.1158/1538-7445.AM2017-5710
Abstract 5573: A high-affinity Optide (optimized peptide) inhibitor of the Hippo pathway’s YAP-TEAD interaction
Authors: Zachary R. Crook, Philip Bradley, Gregory Sevilla, Della Friend, Chris King, Andrew Mhyre, Roland Strong, David Baker, James M. Olson
Journal: Cancer Research (2017)

Abstract The HIPPO pathway plays a critical role in contact inhibition, a pathway that is commonly dysregulated in many human cancers (including liver, colon, ovarian, and lung). The signaling pathway culminates in the intranuclear interaction of the transcriptional co-activator YAP and the transcription factor TEAD. This is representative of a number of cancer driving pathways that have proven nearly impossible to drug, as they are mediated by intracellular protein-protein interactions. High throughput screening campaigns with small molecule libraries have failed to provide specific, high affinity binders capable of disrupting larger protein-protein interfaces (such as YAP-TEAD), while at the same time, antibodies cannot penetrate the cell membrane to access cytosolic and nuclear targets. Optides are small disulfide-knotted peptides (knottins) that are large enough to interfere with protein-protein interactions, but small enough to access compartments beyond the reach of antibodies. Examples include the calcines, activators of sarcoplasmic reticulum ryanodine receptors, and BLZ-100, a knottin-fluorophore conjugate that is capable of accumulating in a wide range of tumor types. Using the computational design software Rosetta, we created a library of Optides designed to interact with TEAD in locations that overlap YAP binding. Mammalian surface display screening against soluble TEAD yielded a candidate (Hit1) that binds TEAD with nanomolar affinity and inhibits YAP binding. Affinity maturation, using site saturation mutagenesis, produced an improved sub-nanomolar variant (IV1) with potent YAP inhibition. This variant was also found to be highly resistant to reduction and proteolysis, crucial for a disulfide-knotted peptide with a cytosolic target in the proteinase-rich tumor milieu. With this highly potent YAP inhibitor, efforts are now focused on cell penetration and biodistribution with the long-term goal of advancing a clinical development candidate. Citation Format: Zachary R. Crook, Philip Bradley, Gregory Sevilla, Della Friend, Chris King, Andrew Mhyre, Roland Strong, David Baker, James M. Olson. A high-affinity Optide (optimized peptide) inhibitor of the Hippo pathway’s YAP-TEAD interaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5573. doi:10.1158/1538-7445.AM2017-5573
Effect of Two AZO Compounds When Added to the Diet of Mice
Authors: Andervont, Howard B., White, Julius, Edwards, Jesse E.
Journal: JNCI Journal of the National Cancer Institute (1944)

Journal Article Effect of Two AZO Compounds When Added to the Diet of Mice Get access Howard B. Andervont, Howard B. Andervont principal biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Julius White, Julius White senior biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Jesse E. Edwards Jesse E. Edwards research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 6, June 1944, Pages 583–586, https://doi.org/10.1093/jnci/4.6.583 Published: 01 June 1944
SAT0409 Importance of ultrasonography for the detection of peripheral enthesitis in spondyloarthritis
Authors: L Mani, K Baccouche, S Hmila, M Bouhoula, B Safaa, Z Alaya, N El Amri, H Zeglaoui, E Bouajina
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Peripheral enthesitis has been repeatedly described like the primary lesion in all forms of spondyloarthritis (SpA), and it may occur at any enthesis in SpA, though it is most common in the entheses of the lower limbs. Ultrasonography (US) has proved to be a highly sensitive and noninvasive tool, to assess the presence of enthesitis <h3>Objectives</h3> To estimate the prevalence and the US abnormalities of enthesitis in patients with SpA, compared to a control group. <h3>Methods</h3> We have consecutively included 40 patients with established SpA, including 30 patients with ankylosing spondylitis (AS), 8 patients with psoriatic arthritis (RP) and two patients with arthritis-associated with Crohn9s disease. Control populations consisted of 20 patients with mechanical low back pain (MBP). Ultrasound (US) in B mode and power Doppler (PD) was performed at Achille tendon (AT) and plantar fascia (PF). <h3>Results</h3> The study sample included 40 control patients (4 male- 16 female) with a mean (SD) age of 51.05 (11.45) years (range 32–73) and mean duration of disease 8.40 (range 5–81) years. SpA subtypes were: ankylosing spondylitis 30; psoriatic arthritis 8; arthritis-associated inflammatory bowel disease (AIBD) 2. 47.5% of entheses were tender at clinical examination. Axial form was found in 36 cases (90%) and peripheral form in 4 cases (10%). In SpA patients, a total of 109/160 (68.12%) of the entheseal sites were abnormal compared with 27/80 (33.75%) in controls, which was statistically significantly fewer than in the SpA group for AT (p=0.000) and PF (p=0.023). Abnormal vascularization in the cortical bone insertion was found in 47 cases (29.375%) versus 4 cases in control group with a significant correlation. We also found a significant correlation for decreased echogenicity and bone erosions. No major variation in the proportion of abnormal entheses identified by US examination was observed between different forms of SpA. US abnormalities were not correlated to the duration of the disease in patients with SpA, and there was no significant difference between US findings and either ESR, CRP, BASDAI score or BASFI score. We also, found no significant correlation between entheseal US abnormalities and the anti-TNF medications used among the SpA patients. <h3>Conclusions</h3> Ultrasonography can be useful for detecting subclinical enthesitis in SpA patient and the enthesis US score can be useful for improving the diagnostic of SpA. <h3>References</h3> Balint PV, Kane D, Wilson H. Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy. Ann Rheum Dis 2002;61:905–10. D9Agostino MA, Said-Nahal R, Hacquard-Bouder C. Assessment of peripheral enthesitis in the spondyloarthropathies by ultrasonography combined with power Doppler: a cross-sectional study. Arthritis Rheum 2003;48:523–33. <h3>Disclosure of Interest</h3> None declared
Abstract 2306: Sleep duration and risk of fatal prostate cancer in CPS-I and CPS-II
Authors: Susan M. Gapstur, Victoria L. Stevens, Brian D. Carter, Ying Wang, Eric J. Jacobs
Journal: Cancer Research (2017)

Abstract There is growing evidence that factors associated with circadian rhythm disruption may be associated with prostate cancer risk. In a previous analysis focusing on shift-work in the Cancer Prevention Study (CPS)-II that included only employed men, we observed an association between short sleep duration and higher risk of prostate cancer death that was limited to the first eight years of follow-up of the cohort. To corroborate and expand on these results, we examined the association between sleep duration and death from prostate cancer in a combined analysis of men in CPS-II and men enrolled in an earlier cohort study, CPS-I, regardless of employment status. After excluding men with uninterpretable sleep information, prevalent cancer and prevalent prostate disease at baseline, the analysis included 407,649 men from CPS-I followed from 1950 through 1972, and 416,040 men from CPS-II followed from 1982 through 2012. During follow-up, 1,546 men in CPS-I and 8,704 men in CPS-II died of prostate cancer. Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) and estimates were meta-analyzed using a fixed-effects model because the design and population of CPS-I and CPS-II were similar. Among men aged 65 years and younger, short sleep duration was associated with higher risk of death from prostate cancer during the first eight years of follow-up; compared to 7 hours/night, the RRs (95% CIs) for 3-5, and 6 hours/night were 1.61 (1.10-2.37), and 1.25 (0.99-1.58), respectively. Among men older than age 65 years, the corresponding RRs (95% CIs) were 0.97 (0.68, 1.38), and 1.02 (0.82, 1.27), respectively. There was no association between sleep duration and fatal prostate cancer during later follow-up. These findings support evidence that factors related to circadian rhythms may increase fatal prostate cancer risk. The observed association between short sleep duration and higher risk of fatal prostate cancer only during the first 8-years of follow-up suggests that short sleep duration could affect later stages of prostate carcinogenesis. Reasons for lack of an association in older men are unclear but may include the marked decline in nocturnal melatonin levels with age, which could reduce the relative biologic impact of melatonin inhibition by sleep-deprivation. Citation Format: Susan M. Gapstur, Victoria L. Stevens, Brian D. Carter, Ying Wang, Eric J. Jacobs. Sleep duration and risk of fatal prostate cancer in CPS-I and CPS-II [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2306. doi:10.1158/1538-7445.AM2017-2306
Direct and rapid encoding of numerosity in the visual stream
Authors: Joonkoo Park, Nick K DeWind, Elizabeth M Brannon
Journal: Behavioral and Brain Sciences (2017)

The target article dismisses all prior work purporting to demonstrate that number is a conceptual primitive. Here, we take issue with their misrepresentation of our recent line of work on numerosity perception, which demonstrates rapid and direct encoding of numerosity and undermines the thesis of the target article that "continuous magnitudes are more automatic and basic than numerosities" (sect. 1, para. 2).