bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1756: Marijuana use and serum testosterone concentrations among U.S. males
Authors: McGlynn Katherine A. 
Published: July 2016

Abstract
Background: Testicular germ cell tumors (TGCT) of young men can be histologically divided into nonseminomas and seminomas. Although TGCTs are thought to be hormonally-related, very few risk factors have been identified. Recently, however, marijuana use has been linked to risk of nonseminoma, which has peak incidence at a younger age (25 years) than does seminoma (35 years). Whether marijuana may be related to nonseminoma via an effect on testosterone concentrations is unknown. Thus, an analysis of U.S. males was conducted, using data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) of the NCHS, CDC.
Methods: Data from 2409 males aged &gt;20 years were included in the analysis. Serum total testosterone (T) concentrations, determined using liquid chromatography-tandem mass spectrometry, were log transformed for statistical analyses. Marijuana use was categorized as: never, current (use on at least one day in prior 30 days) and past (no use within prior 30 days). Regular use was defined as use at least once a month for &gt; 1 year. Covariates included age, body mass index, race/ethnicity, cigarette smoking status and time of day of phlebotomy. Adjusted mean T concentrations were compared among marijuana use categories using weighted multiple linear regression analysis accounting for the complex sample design of NHANES. In addition to the overall analysis, models were stratified by age (20-30 years, &gt;30 years).
Results: Mean T concentration did not differ between never- and ever-users of marijuana (p = 0.62), but did differ between never-users and regular-users (2.56 ng/mL vs 2.59 ng/mL, p = 0.03) and between never-users and current-users (2.60 ng/mL, p = 0.007). In the analysis restricted to men &gt;30 years of age, significant differences in mean T concentration were evident among never-users and current-users (2.55 ng/mL vs 2.60 ng/mL, p = 0.003). Significant differences were also seen with increasing duration of use as mean T concentrations were higher among men who used marijuana regularly for &gt;5 years. In the analysis of men 20-30 years of age, no significant differences in mean T concentration by marijuana use were seen.
Conclusion: These results suggest that regular use and current use of marijuana are associated with higher T concentrations among U.S. men, particularly men &gt; 30 years of age. As nonseminomas are more common in younger men than in older men, the results may indicate that the association between marijuana use and nonseminoma is not due to an effect of marijuana on circulating T concentrations.
Citation Format: Katherine A. McGlynn. Marijuana use and serum testosterone concentrations among U.S. males. [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 1756.
Abstract 1757: Male pattern baldness and risk of incident skin cancer in a cohort of men
Authors: Li Wen-Qing , Cho Eunyoung , Han Jiali , Weinstock Martin , Qureshi Abrar 
Published: July 2016

Abstract
Background: Male pattern baldness (androgenic alopecia) has been associated with scalp skin cancer in case-control studies. A potential androgen basis of melanoma has been hypothesized and baldness has been associated with higher levels of androgens. We examined the association between male pattern baldness and risk of skin cancer, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) in a prospective cohort study.
Methods: We included 36,032 participants from the Health Professionals’ Follow-up Study. In 1992, participants reported their status of male-pattern baldness at age 45 years by choosing from five crown-view pictograms based on Norwood's classification. Diagnosis of skin cancers was reported in the self-reported questionnaires biennially and report on melanoma and SCC was pathologically confirmed. Cox proportional hazard models were used to compute the hazard ratios (HR) and 95% confidence intervals (CI).
Results: We identified 327 cases of melanoma, 1324 cases of SCC, and 8438 cases of BCC during the follow-up. Male-pattern baldness at age 45 was not associated with risk of incident melanoma, but was significantly associated with increased risk of both SCC and BCC. The multivariate-adjusted HR (95% CI) for the highest category of baldness (frontal plus severe vertex baldness) was 1.33 (1.06-1.68) for SCC (Ptrend = 0.001) and 1.23 (1.12-1.35) for BCC (Ptrend&lt;0.0001), compared with no baldness. Analyses by body sites of tumors found significant associations between frontal plus moderate to severe vertex baldness and risk of melanoma (HR = 1.83, 95% CI: 1.01-3.34) and SCC (HR = 1.30, 95% CI: 1.02-1.66) at head and neck. The associations were particularly stronger for scalp melanoma (HR = 7.15, 95% CI: 1.29-39.42) and scalp SCC (HR = 7.09, 95% CI: 3.84-13.08), but not for non-scalp head and neck sites.
Conclusion: Male pattern baldness was positively associated with increased risk of skin cancer. The associations may only exist for skin cancer at head and neck, particularly those occurring at scalp.
Citation Format: Wen-Qing Li, Eunyoung Cho, Jiali Han, Martin Weinstock, Abrar Qureshi. Male pattern baldness and risk of incident skin cancer in a cohort of men. [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 1757.
Abstract 1778: A comparison study of the disparities of cervical cancer excess mortality between Black and Caucasian women in Alabama and the US
Authors: Abdalla Ehsan M. 
Published: July 2016

Abstract
Background: The main purpose of this study was to assess the disparity of cervical cancer (CerCancer) mortality rates change through time between Black and Caucasian women residing in Alabama and the US.
Methods: The CerCancer behavioral risk factors and utilization of screening tests data were obtained from CDC's Behavioral Risk Factor Surveillance System (BRFSS) database. Baseline data and target objectives of utilization of CerCancer screening and mortality rates were obtained from Healthy People 2020. The CerCancer mortality rates data were obtained from the Surveillance, Epidemiology, and End Results (SEER). Mortality rates, percentage difference, percentage change and annual percentage change for trends were calculated and compared with the US baseline. Data were stratified by age, gender, race, and geography, using SEER*Stat version 8.4.1 in conjunction with Linear Trendlines analysis to model the racial changes of CerCancer mortality rates through time in Alabama and the US.
Results: Our results depicted in general, that although Blacks had higher CerCancer mortality rates at all times, a decreasing trend in CerCancer mortality rates was noted for both races. However, the degree of disparities in mortality rates fluctuated over time and differed by age. In Alabama, Blacks aged 65 years and older have not experienced significant decline in CerCancer mortality rates in recent years, despite a high screening rate compared to Whites. In contrast, between 2002 and 2012, Whites in Alabama and the US made a significant progress toward the Healthy People 2020 goal.
Conclusions: Conclusively in Alabama, a disparity still exists for the high CerCancer mortality rates in Blacks despite the higher rates of screening for CerCaner as would otherwise be expected. Additionally, the state has not yet achieved the Healthy People 2020 goal. Thus, although the gap in mortality rates in Alabama has narrowed, however the disparity remains, but if the dismal narrowing is sustained, it will reduce the racial disparities in CerCancer mortality though at a very slow rate. Therefore, Public health officials should monitor progress toward reduction and/or elimination of these disparities.
Citation Format: Ehsan M. Abdalla. A comparison study of the disparities of cervical cancer excess mortality between Black and Caucasian women in Alabama and the US. [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 1778.
Abstract 180: Identification and characterization of ATM substrates in mitosis
Authors: Boohaker Rebecca J. , Zeng Qinghua , Xu Bo 
Published: July 2016

Abstract
The Ataxia-Telangiectasia Mutated (ATM) Kinase, mutation of which is responsible for the autosomal recessive disorder Ataxia-Telangiectasia, is an essential element for cells to deal with DNA double-strand breaks. In the absence of DNA damage, it has also been recognized that ATM has a role in optimizing the spindle assembly checkpoint during mitosis. In the process, ATM is activated at a lower level (compared to the DNA damage response) which requires phosphorylation by the Aurora-B kinase. Known ATM targets in mitosis include kinetochore proteins Bub1 and Mad1. However, it has become clear that ATM-mediated phosphorylation in mitosis is distinct from that in the DNA damage response. Therefore, we performed an unbiased assay to identify ATM substrates in mitosis in order to study the functional significance of mitotic ATM activation. To achieve our goal, we utilized a stable isotope labeling by amino acid (SILAC) /Peptide IP with phosphor-specific SQ/TQ antibodies and mass spectrometry (MS). About 18 proteins were identified as substrates of mitotically activated ATM in the assay. We then conducted bioinformatic analyses for the identified proteins using PANTHER and Ingenuity programs. With many proteins having their known functions in mitosis, we found a much smaller number, but highly interconnected, pool of proteins in the ATM substrate list as compared to that of the DNA damage response. Among them, we validated several phosphorylation events using an in vitro kinase assay. Furthermore we present data to demonstrate the functional significance of ATM-mediated phosphorylation. Taken together, our data provide a comprehensive picture of how mitotically activated ATM signals to downstream targets to fine-tune the mitotic checkpoint.
Citation Format: Rebecca J. Boohaker, Qinghua Zeng, Bo Xu. Identification and characterization of ATM substrates in mitosis. [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 180.
Abstract 1803: Breast cancer cell lines with acquired resistance to selective ERα degraders (SERDs) are dependent on PI3K signaling
Authors: Ong Christy , Daemen Anneleen , Oeh Jason , Ingalla Ellen , Arrazate Alfonzo , Nanini Michelle , Sampath Deepak , Friedman Lori , O’Brien Thomas 
Published: July 2016

Abstract
Estrogen positive (ER+) breast cancer accounts for the majority of all breast cancers and is primarily treated with endocrine therapy. However, even though current endocrine treatments are effective, a subset of patients inevitably become resistant to these treatments. The novel oral SERD, GDC-0810/ARN-810, is currently in Phase II clinical trials in ER+ breast cancer patients. GDC-0810 induces ERα degradation in ER+ MCF7 and T47D cells and inhibits cell proliferation. Moreover, it is also efficacious in ER+ tumor models in vivo, including in MCF7-ESR1 Y537S xenografts and in WHIM20 ESR1 mutant Y537S PDX tumors. Given that little is known about resistance mechanisms to SERDs, our aim was to understand what mechanisms may underlie resistance after continuous exposure.
We generated cell lines resistant to GDC-0810 and show that all of these lines were also cross-resistant to fulvestrant and tamoxifen. We determined that cells with acquired-resistance were more sensitive than parental cells to inhibitors of the PI3K/AKT signaling pathway. Additionally, in some resistant clones, ERα protein expression was lost, but this loss was transient and could be regained after long-term growth in the absence of SERDs. A range of approaches are being undertaken to explore the underlying mechanisms driving acquired-resistance to SERDs. These preclinical studies may inform future clinical combinations.
Citation Format: Christy Ong, Anneleen Daemen, Jason Oeh, Ellen Ingalla, Alfonzo Arrazate, Michelle Nanini, Deepak Sampath, Lori Friedman, Thomas O’Brien. Breast cancer cell lines with acquired resistance to selective ERα degraders (SERDs) are dependent on PI3K signaling. [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 1803.
Abstract 185: Role of phosphorylation in Lmtk3 activation and its contribution in breast cancer progression
Authors: Lucchiari Giulia , Zhang Hua , Nunes Joao , Xu Yichen , Grothey Arnhild , Stebbing Justin , Giamas Georgios 
Published: July 2016

Abstract
LMTK3 is an oncogenic receptor tyrosine kinase implicated in various types of cancer including breast, lung, gastric and colorectal. We have already demonstrated the contribution of LMTK3 in invasion, migration and transcriptional regulation as well as its involvement in endocrine resistance in breast cancer. Despite the significant progress in understanding the role of LMTK3 in human tumourogenesis, the signalling pathways implicated in LMTK3 regulation still remain to be elucidated.
Protein phosphorylation play an essential role in regulating intracellular signal transduction pathways involving almost every aspect of cell activity. In silico phosphoproteomic analysis predicted several potential LMTK3 phosphorylation sites targeted by different kinases including Cyclin-dependent kinase 5 (CDK5), a cytoplasmic proline-directed serine/threonine kinase that is commonly overexpressed in many solid tumours. Interestingly, recent work performed by two different groups showed that CDK5 is a regulator of LMTK1 and LMTK2 in neuronal cells, resulting in axonal outgrowth and potentially influencing a number of neurophysiological processes.
By performing a variety of molecular/cellular and biochemical experiments we confirmed the ability of CDK5 to phosphorylate LMTK3 in vitro and identified its exact phosphorylation sites. Moreover, we investigated the consequences of CDK5 phosphorylation on various LMTK3 processes, amongst which its stability, sub-cellular localization, its ability to interact with chromatin and others. In addition, the clinical correlation of CDK5 and LMTK3 expression in cell lines and patients’ samples were assessed. In aggregate, we describe a new cellular pathway encompassing CDK5 and LMTK3 that results in breast cancer tumour progression.
Our data will be presented.
Citation Format: Giulia Lucchiari, Hua Zhang, Joao Nunes, Yichen Xu, Arnhild Grothey, Justin Stebbing, Georgios Giamas. Role of phosphorylation in Lmtk3 activation and its contribution in breast cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 185.
Abstract 1850: Transcription factor E2F3 up-regulates the expression of Gadd45b gene in the mouse liver
Authors: Kim Jung-Hwan , Gonzalez Frank J. 
Published: July 2016

Abstract
Growth arrest and DNA damage-inducible beta (GADD45b) plays an important role in many intracellular events, such as cell survival- and cell death-related signaling. In normal condition, Gadd45b is suppressed by the negative regulator, such as STAT3, however, when it induced by the PPARa agonist, Wy-14,643. Thus, we investigated the positive regulator of Gadd45b. Based on the Gadd45b-reporter assay, we assumed that E2Fs could regulate the Gadd45b. As results, E2F3 mRNA was induced only in the liver of Wy-14,643-treated mice. In addition, deletion of E2Fs consensus sequence in the Gadd45b reporter gene showed significant decrease of luciferase activity. Furthermore, overexpression of E2F3 significantly increased the Gadd45b-luciferase activity and this was inhibited by the siE2F3 in the Hepa1c1c7 cells. Taken together, E2F3 may play a pivotal role in the Gadd45b induction as a positive regulator.
Citation Format: Jung-Hwan Kim, Frank J. Gonzalez. Transcription factor E2F3 up-regulates the expression of Gadd45b gene in the mouse liver. [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 1850.
Abstract 1868: Glycodelin-producing endometrial adenocarcinoma cells are resistant to TGFβ
Authors: Hautala Laura , Koistinen Hannu 
Published: July 2016

Abstract
Glycodelin is a secreted glycoprotein belonging to lipocalin protein family. It is expressed mainly in reproductive and glandular tissues. Glycodlin is involved in the regulation of reproductive and immune systems and it drives epithelial differentiation. In endometrium, the expression of glycodelin is abundant in secretory phase of the menstrual cycle, while in proliferative phase it is not expressed. Most studies agree that glycodelin is not expressed in endometrial cancer. To study the effects of glycodelin in endometrial cancer cells, we have made stable glycodelin-producing HEC-1B endometrial adenocarcinoma cells. Previously, we have shown that glycodelin differentiated HEC-1B cells towards less malignant phenotype and the cells formed significantly smaller tumors in preclinical xenograft mice. In addition, glycodelin-producing cells were resistant to phorbol ester-stimulated migration and phenotypic differentiation, which was mediated by repressed activation of PKCδ. Here we studied the effect of TGFβ on glycodelin-induced differentiation of the HEC-1B cells.
Glycodelin-producing and control cells were plated on Matrigel and grown with or without TGFβ. The media was changed every second day and the cells were monitored up to one week. For Western blot analysis the cells were grown on Matrigel and TGFβ was added for 0-2h, after which the cells were detached from Matrigel and lysed.
TGFβ induced control cells to form net-like structures, similar to those found after phorbol ester exposure. However, the glycodelin-producing cells remained unresponsive. PKCδ siRNA and PKCδ inhibitor Rottlerin inhibited the effects of TGFβ. Western blot analysis showed equal phosphorylation levels of SMAD2 in glycodelin-transfected and control cells. In contrast, PKCδ and ERK1/2 were differently phosphorylated, indicating the involvement of MAPK-pathway in the TGFβ-induced changes of the control cells.
Endometrial cancer is the most common cancer of the female reproductive tract in developed countries. However, the molecular mechanisms affecting the pathogenesis of the disease are still poorly understood. It has been suggested that TGFβ is involved in carcinogenesis of endometrial cancer. Therefore, our results showing that glycodelin-producing HEC-1B endometrial adenocarcinoma cells are resistant to the effects of TGFβ, due to the repressed PKCδ phosphorylation, may be important to understand the pathogenic mechanisms of endometrial cancer.
Citation Format: Laura Hautala, Hannu Koistinen. Glycodelin-producing endometrial adenocarcinoma cells are resistant to TGFβ. [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 1868.
Abstract 1869: Dislodgement of K-Ras from plasma membranes, induction of apoptosis and tumor regression by PCAIs, a novel class of polyisoprenylated small molecules
Authors: AMISSAH FELIX , NTANTIE ELIZABETH , POKU ROSEMARY A. , NKEMBO AUGUSTINE T. , SALAKO OLUFISAYO O. , FLORES-ROZAS HERNAN , LAMANGO NAZARIUS S. 
Published: July 2016

Abstract
Although mutation-induced dysregulation of Ras signaling constitutes the biochemical change that drives some of the most difficult-to-manage cancers, directly targeting the constitutively active mutant Ras GTPases has not resulted in clinically useful drugs. Therefore, modulating Ras activity for targeted treatment of cancer remains an urgent healthcare need. In the current study, we investigated a novel class of compounds, the polyisoprenylated cysteinyl amide inhibitors (PCAIs), for their anticancer molecular mechanisms using the NSCLC cell panel with K-Ras and/or other mutant genes. Treatment of the lung cancer cells with PCAIs, NSL-RD-035, NSL-BA-036, NSL-BA-040, NSL-BA-055 and NSL-BA-040 resulted in concentration-dependent cell death in both K-Ras mutant (A549 and NCI-H1573), N-Ras mutant (NCI-H1299) and other (NCI-H661, NCI-H460, NCI-H1975, NCI-H1563) NSCLC cells. The PCAIs at sub- to low micromolar 1.0 -10 μM concentrations induced the degeneration of 3D spheroid cultures, inhibited, clonogenic cell growth, and induced marked apoptosis and cell cycle arrest, together with a significant increase in active caspase 3 (p&lt;0.001). NSL-BA-040 at 5 μM prominently dislodged YFP-tagged K-Ras, but not H-Ras and N-Ras from the plasma membranes of transfected A549 and NCI-H661 cells. NSL-RD-035 attenuated the tumor growth of A549 cells in xenografted athymic mice in vivo. Taken together, PCAIs likely suppress NSCLC cell growth by disrupting growth signaling through the dislodgement of K-Ras the plasma membrane.
Citation Format: FELIX AMISSAH, ELIZABETH NTANTIE, ROSEMARY A. POKU, AUGUSTINE T. NKEMBO, OLUFISAYO O. SALAKO, HERNAN FLORES-ROZAS, NAZARIUS S. LAMANGO. Dislodgement of K-Ras from plasma membranes, induction of apoptosis and tumor regression by PCAIs, a novel class of polyisoprenylated small molecules. [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 1869.
Abstract 1874: Oncogenic EGFR signaling inhibits the Spred1-NF1 interaction to sustain constitutive Ras signaling
Authors: Markegard Evan , Mercado Ellen L. , Galeas Jacqueline , Trinidad Marena I. , Urisman Anatoly , McCormick. Frank 
Published: July 2016

Abstract
Spred proteins negatively regulate Ras/MAPK signaling following mitogen stimulation. Inhibition of Ras primary occurs through Spreds ability to bind and localize NF1, a RasGAP and major tumor suppressor, to the plasma membrane. Loss-of-function Spred1 and NF1 mutations occur across multiple cancer types including melanoma, non-small cell lung carcinoma, stomach carcinoma, and uterine carcinosarcoma. Here we demonstrate that oncogenic EGFR signaling disrupts Spred1-NF1 binding. Mass spectrometry was performed on cells overexpressing EGFRL858R to identify potential phosphorylation sites on Spred1 and NF1 that could disrupt Spred1-NF1 binding by steric hindrance. A serine phosphorylation site on Spred1 was identified in which a phosphomimetic and phosphodeficient mutant decreased or increased Spred1-NF1 binding, respectively. Therefore, phosphorylation of Spred1 at this site by a serine kinase downstream of oncogenic EGFR may disrupt Spred1-NF1 binding. Our findings provide one potential mechanism by which oncogenic EGFR signaling disrupts negative feedback to allow for constitutive Ras signaling. Furthermore, this work may elucidate a novel kinase therapeutic target for restoring NF1 mediated inhibition of Ras.
Citation Format: Evan Markegard, Ellen L. Mercado, Jacqueline Galeas, Marena I. Trinidad, Anatoly Urisman, Frank McCormick. Oncogenic EGFR signaling inhibits the Spred1-NF1 interaction to sustain constitutive Ras signaling. [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 1874.