bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B93: Understanding cancer screening service utilization by Somali men in Minnesota
Authors: Sewali Barrett P. , Pratt Rebekah , Abdiwahab Ekland , Call Kathleen T. , Okuyemi Kolawole S.
Published: May 2015

Background: There is a growing recognition of the role of men in reproductive health of women, and the benefits of including men in public health programs addressing women's health. Involvement of men has important implications especially within the context that men act as social gatekeepers and as powerful family members who enforce cultural practices, often to the detriment of women's health. However, there is a dearth of information about the role of men in promoting cancer prevention especially within immigrant communities. Objective(s): The main objective of this qualitative study was to explore the potential role of Somali immigrant men in healthcare decisions that may involve promoting breast and cervical cancer screening in their communities. The secondary objective was to explore knowledge, attitudes, and beliefs about cancer prevention while examining factors associated with barriers and proposed solutions to increase cancer screening in this underserved community.

Methods: We formed a community-academic partnership and used a community based participatory research (CBPR) approach to conduct 20 key informant Interviews and 10 focus groups with Somali men. The Key Informant Interviews were audio-taped, transcribed verbatim and analyzed QSR Nvivo 10. Data were coded to identify main themes.

Results: Three quarters of the participants were 45 years and older with 85% (17) of them were married, and 55% (12) having attained a high school education or higher; 35% (7) of the participants had no healthcare insurance; 55% (11) attained high school graduate or higher level of education; 75% (15) of the participants have lived in Minnesota for more than 5 years. We identified three major themes; (i) Faith influencing the attitudes and beliefs towards cancer screening. (ii) The changing roles of men in a society that is known to be patriarchal. (iii) The migration effect on screening.

Conclusions: Given the low utilization of cancer screening services and the widening cancer screening disparity gap in the minority communities, involvement of men and religious leaders in cancer screening efforts for Somali communities is worth exploring for future interventions. With the diverse cultural and health seeking behaviors in immigrant communities, cancer screening programs must adapt to increase cancer screening rates.

Citation Format: Barrett P. Sewali, Rebekah Pratt, Ekland Abdiwahab, Kathleen T. Call, Kolawole S. Okuyemi. Understanding cancer screening service utilization by Somali men in Minnesota. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B93. doi:10.1158/1538-7755.DISP13-B93
Abstract C08: Cancer risk by air toxics in the Lowcountry: Examining the role of residential segregation and sociodemographic factors
Authors: Rice LaShanta , Burwell Kristen , Jiang Chengsheng , Zhang Hongmei , Samantapudi Ashok , Wilson Sacoby
Published: May 2015

Studies have demonstrated a relationship between segregation and level of education, occupational opportunities, and risk behaviors, yet a paucity of research has elucidated the association between residential segregation and health. We examined residential segregation by racial composition in census tracts in Metropolitan Charleston. The purpose of the study was to assess the impact of racial characteristics, socioeconomic factors, and various segregation and deprivation indices on estimated cancer risk by air toxics.

Segregation indices were used to measure the distribution of groups of people from different races within neighborhoods. Simple linear regression was conducted between segregation indices or sociodemographic variables and cancer risk controlling for urban-rural effects. The Townsend Index was used to measure socioeconomic status deprivation in the study area.

Cancer risk for all sources exceeded 28 ppl/million for half of the census tracts. Background (15.3) and on road (5.8) emission sources accounted for the greatest portion of exposure. There was no real pattern of correlation between race-based segregation (Dissimilarity Index) and cancer risk. However, for all source, area, and on road emissions, the higher the Diversity index, the higher the risk (r=0.13, p<0.01; r=0.14, p<0.01; r=0.11, p<0.05, respectively). Percent Black had the strongest association with cancer risk among the sociodemographic variables. The Townsend Index demonstrated statistically significant differences among quartiles for all emissions sources. Furthermore, a one unit increase in the Isolation Index increased cancer risk by 12.6 ppl/million, which is the highest among all segregation indices.

Our findings demonstrate residential segregation and socioeconomic deprivation may explain disparities in cancer risk in Metropolitan Charleston. Future studies should focus on elucidating the mechanisms by which segregation and neighborhood disadvantage perpetuate health inequalities.

Citation Format: LaShanta Rice, Kristen Burwell, Chengsheng Jiang, Hongmei Zhang, Ashok Samantapudi, Sacoby Wilson. Cancer risk by air toxics in the Lowcountry: Examining the role of residential segregation and sociodemographic factors. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C08. doi:10.1158/1538-7755.DISP13-C08
Abstract C25: Synthesis of N-substituted [benzoylamino]-5-ethyl-1,2,3,6-tetrahydropyridines as potential anticancer agents
Authors: Henderson Elizabeth , Ardley Tiffany
Published: May 2015

Prostate cancer (PC) is a cancer that forms in the tissues of the prostate which is a gland in the male reproductive system found below the bladder and in front of the rectum. PC is the second leading cause of cancer death in American men. African American men have a greater risk of developing PC and this cancer is more aggressive in this population. Cyclooxygenase-2 (COX-2) is an enzyme that has been found to be up-regulated in inflammation as well as some cancers including breast and some prostate cancers. Tetrahydropyridines (THPs) developed by our research group have been shown to be effective in inhibiting inflammation, the enzyme COX-2 and the growth of some breast cancer cells. Here we have synthesized a series of novel THP derivatives as potential prostate cancer agents. The novel N-[substituted benzoylamino]-5-ethyl-1,2,3,6-tetrahydropyridines were synthesized via sodium borohydride reduction of the corresponding N-[substituted phenylcarbonylimino]-3-ethyl pyridinium ylides. This project was supported by the National Center for Research Resources and the National Institute of Minority Health and Health Disparities of the National Institutes of Health through Grant Number 8 G12 MD007582-28 and 2 G12 RR003020.

Citation Format: Elizabeth Henderson, Tiffany Ardley. Synthesis of N-substituted [benzoylamino]-5-ethyl-1,2,3,6-tetrahydropyridines as potential anticancer agents. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C25. doi:10.1158/1538-7755.DISP13-C25
Abstract C33: Cardiovascular health among black and white breast cancer patients initiating aromatase inhibitor therapy
Authors: Gallicchio Lisa , Calhoun Carla , Helzlsouer Kathy J.
Published: May 2015

Purpose: Breast cancer patients may have poor outcomes due to the toxic effects of breast cancer treatments in the presence of co-morbid conditions. Thus, it is hypothesized that racial disparities in breast cancer outcomes are, in part, related to a higher prevalence of certain co-morbid conditions prior to treatment among black compared to white women. As a first step to addressing this hypothesis, this analysis examined racial differences in cardiovascular health and co-morbid conditions among breast cancer survivors initiating aromatase inhibitor (AI) therapy.

Methods: Baseline data were analyzed from 49 white and 29 black women participating in an ongoing cohort study of the cardiovascular health of breast cancer patients over the first year of AI therapy. Prior to initiating AI therapy, women enrolling in the study completed a questionnaire and had a cardiovascular health evaluation that included a carotid intimal medial thickness (cIMT) ultrasound. Cardiovascular disease risk percentile was assigned using the cIMT data; category assignment was based on published age- and race-specific percentile risk categories from the Atherosclerosis Risk in Communities (ARIC) study.

Results: The white breast cancer patients were slightly older than their black counterparts (mean 62.5 years versus 61.5 years; p=0.6) and less likely to have had chemotherapy (32.6% versus 42.3%; p=0.4). After adjusting for age, the black breast cancer patients were more likely than their white counterparts to report having been diagnosed with hypertension (odds ratio (OR) 6.7; 95% confidence interval (CI) 2.0, 22.9) and diabetes (OR 2.5; 95% CI 0.6, 10.2). However, mean cIMT (mean 0.65 mm versus 0.64; p = 0.6) and the distribution of patients in the cardiovascular disease risk percentile categories did not differ significantly by race (p=0.6).

Conclusions: Black breast cancer survivors have a higher prevalence of cardiovascular co-morbid conditions compared to their white counterparts. The presence of these cardiovascular co-morbidities at diagnosis may affect treatment choices if continued follow-up demonstrates an adverse impact of estrogen deprivation therapy on cardiovascular outcomes. Enrollment into this study is currently ongoing. This research was supported by a Susan G. Komen for the Cure Health Disparities Career Catalyst grant.

Citation Format: Lisa Gallicchio, Carla Calhoun, Kathy J. Helzlsouer. Cardiovascular health among black and white breast cancer patients initiating aromatase inhibitor therapy. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C33. doi:10.1158/1538-7755.DISP13-C33
Abstract C40: Investigating histone deacetylase 3 expression in ovarian cancer cells
Authors: Huya-Kouadio Dembi O. , Khabele Dineo , Saskowski Jeanette L. , Wilson Andrew J.
Published: May 2015

Ovarian cancer is the leading cause of gynecologic death in the United States (1). Newer treatments are being developed to target specific proteins in order to inhibit cancer growth without affecting healthy cells. Histone deacetylase (HDAC) inhibitors have shown promise in this regard. HDAC3 inhibitors cause apoptosis, cell cycle arrest, inhibition of growth and angiogenesis with limited effects on healthy cells (2). Key functions of HDAC3 are the formation of DNA into heterochromatin and the regulation of proapoptotic genes (2). Khabele et al demonstrated that class I HDACs are overexpressed in ovarian cancers. Thus, if HDAC3 is linked to apoptosis, then treating ovarian cancer cell with chemotherapeutic drugs such as cisplatin should increase its translocation to the cytoplasm. We also believe that the overexpression of HDAC3 in ovarian cancer cells modulate the cells response to cisplatin. In order to support our hypothesis, ovarian cancer cells, SKOV3, were transfected with an HDAC3-Myc tagged constructs to allow visualization of HDAC3 in the cells. Before the immunofluorescence was performed, the transfected cells were characterized using Western blot and SRB cell viability assays to assure that their response to cisplatin did not differ from the parental cell line. Our results show that HDAC3 expression is decreased in ovarian cancer cells treated with cisplatin and that in the presence of cisplatin, there is an increase in HDAC3 translocation to the cytoplasm. Fractionation data for this research were omitted because the protocol needed to be optimized. Another limitation of this study is the limited knowledge on HDAC3 translocation mechanism to the cytoplasm. In conclusion, the downregulation and cytoplasmic translocation of HDAC3 are potential novel mechanism of apoptosis in ovarian cancer cell response to cisplatin .

Citation Format: Dembi O. Huya-Kouadio, Dineo Khabele, Jeanette L. Saskowski, Andrew J. Wilson. Investigating histone deacetylase 3 expression in ovarian cancer cells. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C40. doi:10.1158/1538-7755.DISP13-C40
Abstract C48: Racial-specific differences in breast cancer treatment
Authors: Barley Brittany N. , Horton Sara , Dunmore-Griffith Jacqueline , Ricks-Santi Luisel
Published: May 2015

Although the incidence of breast cancer (BCa) among Blacks is lower than Whites, health outcomes are dire, as the cancer is often diagnosed at a higher grade and more advanced stage. Additionally, in Blacks, BCa tends to be more aggressive, as triple negative breast cancer is more prevalent, is more lethal and less treatable than the cognate disease in Whites. In addition to the high prevalence of aggressive disease in Blacks, we hypothesized that recurrence and survival outcomes may also be due to treatment differences between populations. Therefore, the objective of this study was to determine if there were racial-specific treatment differences in BCa cases in Washington, DC (N=5932) between 2000 and 2010. Using chi-square and regression analysis, we demonstrate that after controlling for age, stage, grade, ER, PR, HER2, and BCa molecular subtype, no significant racial-specific differences in surgery or radiation were found. However, overall, Blacks and Hispanics were more likely to receive chemotherapy for BCa when compared to whites (OR for Blacks: 3.57, 95% CI: 1.66-8.33 and OR for Hispanics: 4.76, 95% CI: 1.33-0.16.67). Among those with Stage 3 and 4 BCa, Blacks and Hispanics were still more likely to receive chemotherapy (OR for Blacks: 1.93, 95% CI: 1.16-3.20 and OR for Hispanics: 3.95, 95% CI: 1.03-15.15). Differences in hormonal therapy were also found with Blacks and Hispanics being more likely to receive hormone therapy for ER and/or PR positive disease (OR for Blacks: 3.12, 95% CI: 1.27-7.69 and OR for Hispanics: 8.33, 95% CI: 2.27-33.33). Studies that identify driving factors behind these racial-related treatment differences are warranted.

Citation Format: Brittany N. Barley, Sara Horton, Jacqueline Dunmore-Griffith, Luisel Ricks-Santi. Racial-specific differences in breast cancer treatment. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C48. doi:10.1158/1538-7755.DISP13-C48
Abstract C59: Variable distribution of HIF-1α in human normal and carcinoma tissue, immortal cell lines, and effects of hyperoxia / hypoxia on HIF-1α deficient cells
Authors: Mazzio Elizabeth , Soliman Karam FA
Published: May 2015

Inadequate access to healthcare can lead to greater mortality rates from a delay in cancer diagnosis. It is believe that over time, the hypoxic microenvironment of solid tumors can elicit an elevation of HIF-1α, its translocation to the nucleus and targeted effects on the hypoxic response element (HRE) - initiating invasive metastasis. While this is a universally held supposition, “HIF-1α negative tumors” can also display aggressive pathology and poor clinical outcome. Given inconsistencies in the literature, we analyze public data sets for baseline HIF-1α gene expression amongst 329 human tissues (168 cancer, 161 normal) and NCI60 tumor cell lines. The data show little to no differences between a number of tumor and normal tissue samples, with some exceptions such as the case of bronchial epithelial tissue, exacerbated in respective cancer tissue. The data show extreme variation in HIF-1α across individuals with similar human cancers (below L.O.D. - 60% of GAPDH) with comparable patterns across tissue specific immortal cell lines (1% - 70% of GAPDH). Moreover, the effects of hyperoxia ∼91% O2, hypoxia ∼2.5% O2 versus normoxia ∼21% CO2/ 5% CO2/atm on a HIF-1α deficient malignant neuroblastoma cell line (N2a) were explored using Agilent genomic 4 x 44 k arrays. Hyperoxia evoked a rise in mRNA for 42 mitochondrial OXPHOS genes, DNA/base excision repair, protein synthesis, transcription, cytoskeletal proteins, G-protein signaling and ubiquitin-mediated proteolysis. On the other hand, hypoxia triggered primarily upregulation of chromatin remodeling events such as LDS's, histone-clusters H4k/d/j, Hist4h4, Hist2h3c1, Rara and REST co-repressor. In HIF-1α deficient tumor cells, a decline in O2 initiates epigenetic changes that parallel elevation of VEGF and ubiquitin proteolysis, albeit not related to HIF-1 α. Future research will be required to corroborate similar findings in other HIF-1α deficient models.

Citation Format: Elizabeth Mazzio, Karam FA Soliman. Variable distribution of HIF-1α in human normal and carcinoma tissue, immortal cell lines, and effects of hyperoxia / hypoxia on HIF-1α deficient cells. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C59. doi:10.1158/1538-7755.DISP13-C59
Abstract C70: ABCD3 expression in prostate and breast tumors
Authors: Reams R. Renee , Jones Jacqueline D. , Osborne Daniel , Wang Honghe , Yates Clayton C.
Published: May 2015

Background: In a previous study, we identified the ABCD3 gene as important in aggressive prostate tumors. The ABCD3 gene is a member of the ABC (ATP-Binding Cassette) family. The ABC gene family give instructions for making transporter proteins that carry many types of molecules, such as fats, sugars, protein building blocks (amino acids) and drugs, across cell membranes and is known to play a role in chemoresistance is some cancers.

Purpose: Little is known about role of ABCD3 in prostate cancer, hence in the present study we assessed the expression of ABCD3 in normal and malignant prostate tissue (without regard to racial ethnicity) and determined correlations between ABCD3 expression and clinicopathologic characteristics.

Methods: Clinically annotated duplicate core tissue high-density prostate adenocarcinoma tissue microarray of 92 cases of adenocarcinoma, 2 prostate transitional cell carcinoma, 12 prostate adjacent normal tissue and 8 normal prostate tissue were stained with a monoclonal antibody against ABCD3 and scored for percentage of visible staining.

Results: Increased ABCD3 expression correlated with increasing Gleason score (p=0.0094), age (p=0.0014) and pathology grade (p=0.0007). Interestingly, we also observed that ABCD3 expression was elevated to varying degrees in other types of cancers, breast (stage II a), brain, cervical, head and neck, kidney and pancreatic.

Conclusions: We postulate that ABCD3 may be a putative prognostic biomarker that discriminates between indolent and aggressive cancers, albeit ABCD3 function in cancer progression is still under investigation.

Citation Format: R. Renee Reams, Jacqueline D. Jones, Daniel Osborne, Honghe Wang, Clayton C. Yates, III. ABCD3 expression in prostate and breast tumors. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C70. doi:10.1158/1538-7755.DISP13-C70
Abstract PL01-03: Vitamin D deficiency and prostate cancer in men with African ancestry
Authors: Nonn Larisa
Published: May 2015

African-American men are disproportionally affected by prostate cancer in that African-American men are not only at increased risk of prostate cancer compared to American men of European descent, but also are at the highest risk of aggressive prostate cancer and death from prostate cancer. As well vitamin D3 deficiency is rampant in the African-American population. There is a biological component to this deficiency because sun-induced vitamin D3 synthesis in the skin is significantly reduced in melanin-rich pigmented skin. Consequently, about two thirds of African-American men are vitamin D3 deficient compared to about 20% of men of European descent. It is important to maintain a healthy vitamin D3 status because vitamin D3 deficiency increases the risk of prostate cancer mortality. Our group has examined vitamin D3 concentrations, metabolism and mediators in prostate tissue and cells of a racially diverse group of patients to discern differences in African-American men.

Citation Format: Larisa Nonn. Vitamin D deficiency and prostate cancer in men with African ancestry. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PL01-03. doi:10.1158/1538-7755.DISP13-PL01-03
Abstract PL02-03: Overcoming cultural and geographic barriers to participation in clinical trials among Native Hawaiians
Authors: Berenberg Jeffrey L.
Published: May 2015

The Native Hawaiian population of Hawaii has disproportionately high cancer incidence and mortality rates. Native Hawaiian women with breast cancer present at an advanced stage and have death rates that are 52 % above the state average. Prostate cancer among Native Hawaiian men is diagnosed at more advanced stage. Native Hawaiian participation in cancer clinical trials was historically low. Reasons for this were varied including access, health literacy, lack of primary and referring physician awareness/time constraints and cultural barriers. Since the establishment of the University of Hawaii Minority Based Clinical Oncology Program (UHMBCCOP) participation in cancer clinical trials has definitely increased. MBCCOP provided clinical trial promotion, increased access and clinical trial support for a group of hospital and office based oncologists across the islands of Oahu and Kauai have all contributed to the increase. Education programs in Hawaii by multiple organizations, in particular, Imi Hale, the Native Hawaiian Cancer Network Program have enhanced knowledge of cancer and clinical trials in the Native Hawaiian community. Imi Hale's emphasis has focused on community based patient training, patient navigation and referring physician cancer clinical trial training. In fact, a recent program was recently initiated in conjunction with Education Network to Advance Clinical Trials (ENNACT) and Queens Medical Center. Review of Native Hawaiian participation in both cancer prevention and treatment trials through the UHMBCCOP over the last 20 years shows a significant gender difference with more women participating in both prevention and treatment trials. The reasons for this are not well understood but are under investigation. In summary, increased focused access and community based education have improved Native Hawaiian participation in cancer clinical trials but challenges persist including gender disparities in enrollment onto clinical trials and lack of access outside of Oahu and Kauai islands.

Citation Format: Jeffrey L. Berenberg. Overcoming cultural and geographic barriers to participation in clinical trials among Native Hawaiians. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PL02-03. doi:10.1158/1538-7755.DISP13-PL02-03
Abstract SS02-02: A long walk from FGFR2 alternative splicing to cancer progression
Authors: Somarelli Jason A. , Somarelli Jason A. , Schaeffer Daneen , Schaeffer Daneen , Marengo Mathew S. , Marengo Mathew S. , Bepler Tristan , Bepler Tristan , Rouse Douglas , Buckley Anne F. , Epstein Jonathan I. , Armstrong Andrew J. , Garcia-Blanco Mariano A. , Garcia-Blanco Mariano A.
Published: May 2015

Previously, our group developed fluorescence-based alternative splicing reporters of epithelial plasticity to visualize phenotypic transitions in real time in vivo (Oltean et al., 2008; Oltean et al., 2006; Somarelli et al., 2013). We reasoned that our mesenchymal-epithelial transition (MET) reporters could be extremely useful to test the hypothesis that MET is a modulator of metastatic colonization in undifferentiated, sarcomatoid-like cancers. Along these lines, we generated a lineage-tracing reporter based on combined transcription and alternative splicing regulatory elements to measure the frequency of MET-like events during tumor growth and metastasis in the post-EMT Dunning rat AT3 model of prostate cancer. In a parallel set of experiments, we also used the combinatorial control strategy to drive a suicide reporter that kills cells undergoing MET to test the hypothesis that MET is required for metastatic colonization in undifferentiated, mesenchymal-like cancers. The combinatorial use of both transcription and alternative splicing regulation provided exquisite cell-type discrimination in the expression of enzymes, such as the Cre recombinase and Diphtheria A (DipA) toxin. Using the lineage tracing reporter system, we were able to quantify, for the first time, overall frequencies of MET during primary tumor and metastatic growth. Remarkably, we observed that the frequency of MET within primary tumors and metastatic nodules was not significantly different, with very low rates of MET taking place during the growth of tumors and metastases. Moreover, targeted killing of cells undergoing MET did not reduce the number of macrometastatic colonies in the lungs. This work demonstrates the ability of tumors to metastasize efficiently without the need for MET, and we suggest that this may be similar to the behavior of highly aggressive prostate carcinosarcomas or undifferentiated carcinomas. Using this system we will describe new experiments that will address differential behavior in different types of prostate cancer.

Citation Format: Jason A. Somarelli, Jason A. Somarelli, Daneen Schaeffer, Daneen Schaeffer, Mathew S. Marengo, Mathew S. Marengo, Tristan Bepler, Tristan Bepler, Douglas Rouse, Anne F. Buckley, Jonathan I. Epstein, Andrew J. Armstrong, Mariano A. Garcia-Blanco, Mariano A. Garcia-Blanco. A long walk from FGFR2 alternative splicing to cancer progression. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr SS02-02. doi:10.1158/1538-7755.DISP13-SS02-02
Adenovirus Improves the Efficacy of Adoptive T-cell Therapy by Recruiting Immune Cells to and Promoting Their Activity at the Tumor
Authors: Tähtinen Siri , Grönberg-Vähä-Koskela Susanna , Lumen Dave , Merisalo-Soikkeli Maiju , Siurala Mikko , Airaksinen Anu J. , Vähä-Koskela Markus , Hemminki Akseli
Published: May 2015

Despite the rapid progress in the development of novel adoptive T-cell therapies, the clinical benefits in treatment of established tumors have remained modest. Several immune evasion mechanisms hinder T-cell entry into tumors and their activity within the tumor. Of note, oncolytic adenoviruses are intrinsically immunogenic due to inherent pathogen-associated molecular patterns. Here, we studied the capacity of adenovirus to overcome resistance of chicken ovalbumin-expressing B16.OVA murine melanoma tumors to adoptive ovalbumin-specific CD8+ T-cell (OT-I) therapy. Following intraperitoneal transfer of polyclonally activated OT-I lymphocytes, control of tumor growth was superior in mice given intratumoral adenovirus compared with control mice, even in the absence of oncolytic virus replication. Preexisting antiviral immunity against serotype 5 did not hinder the therapeutic efficacy of the combination treatment. Intratumoral adenovirus injection was associated with an increase in proinflammatory cytokines, CD45+ leukocytes, CD8+ lymphocytes, and F4/80+ macrophages, suggesting enhanced tumor immunogenicity. The proinflammatory effects of adenovirus on the tumor microenvironment led to expression of costimulatory signals on CD11c+ antigen-presenting cells and subsequent activation of T cells, thus breaking the tumor-induced peripheral tolerance. An increased number of CD8+ T cells specific for endogenous tumor antigens TRP-2 and gp100 was detected in combination-treated mice, indicating epitope spreading. Moreover, the majority of virus/T-cell–treated mice rejected the challenge of parental B16.F10 tumors, suggesting that systemic antitumor immunity was induced. In summary, we provide proof-of-mechanism data on combining adoptive T-cell therapy and adenovirotherapy for the treatment of cancer. Cancer Immunol Res; 3(8); 915–25. ©2015 AACR.
Reduction of Mitochondria–Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury
Authors: He Xi , Bi Xue-yuan , Lu Xing-zhu , Zhao Ming , Yu Xiao-jiang , Sun Lei , Xu Man , Wier W. Gil , Zang Wei-jin
Published: May 2015

Objective—

We explored the role of endoplasmic reticulum (ER)–mitochondria Ca
2+
cross talk involving voltage-dependent anion channel-1 (VDAC1)/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 in endothelial cells during hypoxia/reoxygenation (H/R), and investigated the protective effects of acetylcholine.

Approach and Results—

Acetylcholine treatment during reoxygenation prevented intracellular and mitochondrial Ca
2+
increases and alleviated ER Ca
2+
depletion during H/R in human umbilical vein endothelial cells. Consequently, acetylcholine enhanced mitochondrial membrane potential and inhibited proapoptotic cascades, thereby reducing cell death and preserving endothelial ultrastructure. This effect was likely mediated by the type-3 muscarinic acetylcholine receptor and the phosphatidylinositol 3-kinase/Akt pathway. In addition, interactions among members of the VDAC1/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex were increased after H/R and were associated with mitochondrial Ca
2+
overload and cell death. Inhibition of the partner of the Ca
2+
channeling complex (VDAC1 siRNA) or a reduction in ER–mitochondria tethering (mitofusin 2 siRNA) prevented the increased protein interaction within the complex and reduced mitochondrial Ca
2+
accumulation and subsequent endothelial cell death after H/R. Intriguingly, acetylcholine could modulate ER–mitochondria Ca
2+
cross talk by inhibiting the VDAC1/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 expression. Phosphatidylinositol 3-kinase siRNA diminished acetylcholine-mediated inhibition of mitochondrial Ca
2+
overload and VDAC1/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex formation induced by H/R.

Conclusions—

Our data suggest that ER–mitochondria interplay plays an important role in reperfusion injury in the endothelium and may be a novel molecular target for endothelial protection. Acetylcholine attenuates both intracellular and mitochondrial Ca
2+
overload and protects endothelial cells from H/R injury, presumably by disrupting the ER–mitochondria interaction.
Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National Collegiate Athletic Association Athletes
Authors: Harmon Kimberly G. , Asif Irfan M. , Maleszewski Joseph J. , Owens David S. , Prutkin Jordan M. , Salerno Jack C. , Zigman Monica L. , Ellenbogen Rachel , Rao Ashwin L. , Ackerman Michael J. , Drezner Jonathan A.
Published: May 2015

Background—

The incidence and cause of sudden cardiac death (SCD) in athletes is debated with hypertrophic cardiomyopathy often reported as the most common cause.

Methods and Results—

A database of all National Collegiate Athletic Association deaths (2003–2013) was developed. Additional information and autopsy reports were obtained when possible. Cause of death was adjudicated by an expert panel. There were 4 242 519 athlete-years (AY) and 514 total student athlete deaths. Accidents were the most common cause of death (257, 50%, 1:16 508 AY) followed by medical causes (147, 29%, 1:28 861 AY). The most common medical cause of death was SCD (79, 15%, 1:53 703 AY). Males were at higher risk than females 1:37 790 AY versus 1:121 593 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9–5.5;
P
<0.00001), and black athletes were at higher risk than white athletes 1:21491 AY versus 1:68 354 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9–5.2;
P
<0.00001). The incidence of SCD in Division 1 male basketball athletes was 1:5200 AY. The most common findings at autopsy were autopsy-negative sudden unexplained death in 16 (25%), and definitive evidence for hypertrophic cardiomyopathy was seen in 5 (8%). Media reports identified more deaths in higher divisions (87%, 61%, and 44%), whereas the percentages from the internal database did not vary (87%, 83%, and 89%). Insurance claims identified only 11% of SCDs.

Conclusions—

The rate of SCD in National Collegiate Athletic Association athletes is high, with males, black athletes, and basketball players at substantially higher risk. The most common finding at autopsy is autopsy-negative sudden unexplained death. Media reports are more likely to capture high-profile deaths, and insurance claims are not a reliable method for case identification.
Measuring Spatial Presence: Introducing and Validating the Pictorial Presence SAM
Authors: Weibel David , Schmutz Jan , Pahud Olivier , Wissmath Bartholomäus
Published: May 2015

The aim of the present study was to develop a pictorial presence scale using self-assessment-manikins (SAM). The instrument assesses presence sub-dimensions (self-location and possible actions) as well as presence determinants (attention allocation, spatial situation model, higher cognitive involvement, and suspension of disbelief). To qualitatively validate the scale, think-aloud protocols and interviews (n = 12) were conducted. The results reveal that the SAM items are quickly filled out as well as easily, intuitively, and unambiguously understood. Furthermore, the instrument's validity and sensitivity was quantitatively examined in a two-factorial design (n = 317). Factors were medium (written story, audio book, video, and computer game) and distraction (non-distraction vs. distraction). Factor analyses reveal that the SAM presence dimensions and determinants closely correspond to those of the MEC Spatial Presence Questionnaire, which was used as a comparison measure. The findings of the qualitative and quantitative validation procedures show that the Pictorial Presence SAM successfully assesses spatial presence. In contrast to the verbal questionnaire data (MEC), the significant distraction–effect suggests that the new scale is even more sensitive. This points out that the scale can be a useful alternative to existing verbal presence self-report measures.
Taxonomic revision and distribution of Erigeron acris s. l. (Asteraceae) in Poland
Authors: Pliszko Artur
Published: May 2015

The species Erigeron acris L. s. l. is revised in Poland. Three subspecies are recognized (E. acris subsp. acris, E. acris subsp. droebachiensis (O.F. Müll.) Arcang., and E. acris subsp. serotinus (Weihe) Greuter), a diagnostic key is provided, syntypes of two synonyms are discovered. Cauline leaves, capitula, and achenes are studied under scanning electron microscope. The updated distribution of the subspecies in Poland are presented using the ATPOL cartogram method. The distribution and hybridization are discussed.
Four new species of Tanycarpa (Hymenoptera, Braconidae, Alysiinae) from the Palaearctic Region and new records of species from China
Authors: YAO JUNLI , KULA ROBERT R. , WHARTON ROBERT A.
Published: May 2015

Four new species of Tanycarpa (Hymenoptera, Braconidae, Alysiinae), T. gymnonotum Yao sp. n., T. similis Yao sp. n., T. areolata Yao sp. n., and T. lineata Yao sp. n., are described from the Palaearctic Region of China, and T. chors Belokobylskij is newly recorded from China. Significant range extensions are given for T. bicolor (Nees von Esenbeck), T. gracilicornis (Nees von Esenbeck), and T. mitis Stelfox. A key to the Palaearctic species of Tanycarpa is provided.
To systematics of the mite genus Hoplocheylus (Acariformes: Tarsocheylidae)
Authors: KHAUSTOV ALEXANDER A.
Published: May 2015

A new species of the genus Hoplocheylus Atyeo and Baker, 1964 (Acariformes: Heterostigmatina: Tarsocheylidae), H. magnificus sp. nov. is described from the nest of the ant Formica rufa Linnaeus (Hymenoptera: Formicidae) from Kurgan Province, Western Siberia, Russia. A poorly-known species Hoplocheylus sogdianicus Barilo and Sharipov, 1987 is redescribed from the holotype. A key to species of the genus Hoplocheylus is provided.
Two new high altitude genera of Camiarini (Coleoptera: Leiodidae: Camiarinae) from Australia and New Zealand
Authors: Seago Ainsley E. , Leschen Richard A. B. , Newton Alfred F.
Published: May 2015

Two new leiodid genera and species, Camisolus ptinoides gen. nov., sp. nov. and Camiarodes nunni gen. nov., sp. nov. are described from southeastern Australia and New Zealand, respectively. Each new species is placed within its own genus on the basis of morphological uniqueness within Camiarini (Camiarinae) based on the presence of an enlarged maxillary palpomere 4 and metanepisternum with a lateral, tongue-like process that overlaps the elytron in repose. A key to the described genera is provided for world Camiarini. The tribe, new to Australia, is otherwise known only from New Zealand (six genera including one new) and southern South America (one genus). Both new genera are found exclusively in high altitude areas.
The presence of species of Pseudochironomus Malloch 1915 (Diptera: Chironomidae) in watercourses of Chaco Serrano Ecoregion (Argentina, South America)
Authors: PAGGI ANALÍA C. , GARAY GRETEL N. RODRIGUEZ
Published: May 2015

Male imagos of Pseudochironomus viridis (Kieffer) are redescribed, the immature stages are described and figured for the first time. During this study, larva and pupal exuviae associated to P. richardsoni (Malloch) were recorded for the first time for South America. The specimens were collected from a stream and a river in the Pampasic Hills System in the Chaco Serrano ecoregion of Argentina.
Redescription of Argyresthia mirabiella Toll, 1947 (Lepidoptera: Argyresthiidae)
Authors: Baraniak Edward , Walczak Urszula
Published: May 2015

Moths of the family Argyresthiidae are widely distributed globally, as they include a few cosmopolitan species (Dugdale et al. 1999). So far the family has not been the subject of any monograph, and the systematic position of many species is unclear (Agassiz 1996). This applies also to Argyresthia mirabiella (Toll, 1947). Its type specimen with the microscopic slide of the female genitalia is deposited in the collection of S. Toll, at the Institute of Systematics and Animal Evolution, Polish Academy of Sciences (Krakow, Poland). Toll’s (1947) description of this species is limited to a few lines of text. The female genitalia are described in a few sentences concerning the antrum, ductus bursae, and signum. The drawing is schematic and greatly simplified. That brief description of A. mirabiella does not allow its proper identification. Here we provide a more detailed re-description and illustrations based on a re-examination of the type.
The Use of CloudSat Data to Evaluate Retrievals of Total Ice Content in Precipitating Cloud Systems from Ground-Based Operational Radar Measurements
Authors: Matrosov Sergey Y.
Published: May 2015

An approach is described to retrieve the total amount of ice in a vertical atmospheric column in precipitating clouds observed by the operational Weather Surveillance Radar-1988 Doppler (WSR-88D) systems. This amount expressed as ice water path (IWP) is retrieved using measurements obtained during standard WSR-88D scanning procedures performed when observing precipitation. WSR-88D-based IWP estimates are evaluated using dedicated cloud microphysical retrievals available from the CloudSat and auxiliary spaceborne measurements. The evaluation is performed using measurements obtained in extensive predominantly stratiform precipitation systems containing both ice hydrometeors aloft and rain near the ground. The analysis is based on retrievals of IWP from satellite and the ground-based KWGX and KSHV WSR-88D that are closely collocated in time and space. The comparison results indicate a relatively high correlation between satellite and WSR-88D IWP retrievals, with corresponding correlation coefficients of around 0.7. The mean relative differences between spaceborne and ground-based estimates are around 50%–60%, which is on the order of IWP retrieval uncertainties and is comparable to the differences among various operational CloudSat IWP products. The analysis performed in this study suggests that the quantitative information on ice content of precipitation systems can generally be obtained from operational WSR-88D measurements, when they perform routine scans to observe precipitation. The limitations of WSR-88D IWP estimates due to radar beam tilt restrictions and the overshooting effects due to Earth’s sphericity are discussed.
The Melting Arctic and Midlatitude Weather Patterns: Are They Connected?*
Authors: Overland James , Francis Jennifer A. , Hall Richard , Hanna Edward , Kim Seong-Joong , Vihma Timo
Published: May 2015

The potential of recent Arctic changes to influence hemispheric weather is a complex and controversial topic with considerable uncertainty, as time series of potential linkages are short (<10 yr) and understanding involves the relative contribution of direct forcing by Arctic changes on a chaotic climatic system. A way forward is through further investigation of atmospheric dynamic mechanisms. During several exceptionally warm Arctic winters since 2007, sea ice loss in the Barents and Kara Seas initiated eastward-propagating wave trains of high and low pressure. Anomalous high pressure east of the Ural Mountains advected Arctic air over central and eastern Asia, resulting in persistent cold spells. Blocking near Greenland related to low-level temperature anomalies led to northerly flow into eastern North America, inducing persistent cold periods. Potential Arctic connections in Europe are less clear. Variability in the North Pacific can reinforce downstream Arctic changes, and Arctic amplification can accentuate the impact of Pacific variability. The authors emphasize multiple linkage mechanisms that are regional, episodic, and based on amplification of existing jet stream wave patterns, which are the result of a combination of internal variability, lower-tropospheric temperature anomalies, and midlatitude teleconnections. The quantitative impact of Arctic change on midlatitude weather may not be resolved within the foreseeable future, yet new studies of the changing Arctic and subarctic low-frequency dynamics, together with additional Arctic observations, can contribute to improved skill in extended-range forecasts, as planned by the WMO Polar Prediction Project (PPP).
An Evaluation of Advanced Dvorak Technique–Derived Tropical Cyclone Intensity Estimates during Extratropical Transition Using Synthetic Satellite Imagery
Authors: Manion Alexander , Evans Clark , Olander Timothy L. , Velden Christopher S. , Grasso Lewis D.
Published: May 2015

It is known that both Dvorak technique and advanced Dvorak technique–derived intensity estimates for tropical cyclones during extratropical transition are less reliable because the empirical relationships between cloud patterns and cyclone intensity underlying each technique are primarily tropical in nature and thus less robust during extratropical transition. However, as direct observations of cyclone intensity during extratropical transition are rare, the precise extent to which such remotely sensed intensity estimates are in error is uncertain. To address this uncertainty and provide insight into how advanced Dvorak technique–derived intensity estimates during extratropical transition may be improved, the advanced Dvorak technique is applied to synthetic satellite imagery derived from 25 numerical simulations of Atlantic basin tropical cyclones—five cases, five microphysical parameterizations—during extratropical transition. From this, an internally consistent evaluation between model-derived and advanced Dvorak technique–derived cyclone intensity estimates is conducted. Intensity estimate error and bias peak at the beginning of extratropical transition and decline thereafter for maximum sustained surface wind. On average, synthetic advanced Dvorak technique–derived estimates of maximum sustained surface wind asymptote toward or remain near their weakest-possible values after extratropical transition begins. Minimum sea level pressure estimates exhibit minimal bias, although this result is sensitive to microphysical parameterization. Such sensitivity to microphysical parameterization, particularly with respect to cloud radiative properties, suggests that only qualitative insight regarding advanced Dvorak technique–derived intensity estimate error during extratropical transition may be obtained utilizing synthetic satellite imagery. Implications toward developing improved intensity estimates during extratropical transition are discussed.
Interleukin-6 in cerebrospinal fluid as a biomarker of acute meningitis
Authors: García-Hernández Pablo , Prieto Belén , Martínez-Morillo Eduardo , Rodríguez Verónica , Álvarez Francisco V
Published: May 2015

Background

Microbiological culture of cerebrospinal fluid is the gold standard to differentiate between aseptic and bacterial meningitis, but this method has low sensitivity. A fast and reliable new marker would be of interest in clinical practice.

Objective

Interleukin-6, secreted by T cells in response to meningeal pathogens and quickly delivered into cerebrospinal fluid, was evaluated as a marker of acute meningitis.

Design and Methods

A total of 150 cerebrospinal fluid samples were analysed by an electrochemiluminescence method, selected according to patient diagnosis: (a) bacterial meningitis confirmed by positive culture ( n = 26); (b) bacterial meningitis with negative culture or not performed ( n = 15); (c) viral meningitis confirmed by polymerase chain reaction or immunoglobulin G determination ( n = 23); (d) viral meningitis with polymerase chain reaction negative or not performed ( n = 42); and (e) controls ( n = 44).

Results

Cerebrospinal fluid interleukin-6 concentration showed significant differences between all pathologic groups and the control group ( P < 0.001). As a diagnostic tool for bacterial meningitis, interleukin-6 showed an area under the curve of 0.937 (95% confidence intervals: 0.895–0.978), significantly higher than those of classical biomarkers. An interleukin-6 cutoff of 1418 pg/mL showed 95.5% sensitivity and 77.5% specificity, whereas a value of 15,060 pg/mL showed 63.6% sensitivity and 96.7% specificity, for diagnosis of bacterial meningitis.

Conclusion

Interleukin-6 measured by electrochemiluminescence method is a promising marker for early differentiation between aseptic and bacterial meningitis. More studies are needed to validate clinical implications for future practice in an emergency laboratory.
ISO standards for pathology – a step too far?
Authors: Burnett David
Published: May 2015

The International Standard, ISO 15189 which specifies requirements for quality and competence in medical laboratories was written by medical laboratory professionals. Since its first publication in 2003, it has raised awareness of the importance of medical laboratories with governments throughout the world and provided a tool with which laboratories may develop their quality management systems and assess their own competence. This paper examines the use of the Standard in the context of self-assessment, accreditation and regulation of medical laboratories.