bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia signaling during acute lung injury
Authors: Vohwinkel Christine U. , Hoegl Sandra , Eltzschig Holger K.
Published: May 2015

Acute lung injury (ALI) is an inflammatory lung disease that manifests itself in patients as acute respiratory distress syndrome and thereby contributes significantly to the morbidity and mortality of patients experiencing critical illness. Even though it may seem counterintuitive, as the lungs are typically well-oxygenated organs, hypoxia signaling pathways have recently been implicated in the resolution of ALI. For example, functional studies suggest that transcriptional responses under the control of the hypoxia-inducible factor (HIF) are critical in optimizing alveolar epithelial carbohydrate metabolism, and thereby dampen lung inflammation during ALI. In the present review we discuss functional roles of oxygenation, hypoxia and HIFs during ALI, mechanisms of how HIFs are stabilized during lung inflammation, and how HIFs can mediate lung protection during ALI.
miR-181a-5p Inhibits Cancer Cell Migration and Angiogenesis via Downregulation of Matrix Metalloproteinase-14
Authors: Li Yiyi , Kuscu Cem , Banach Anna , Zhang Qian , Pulkoski-Gross Ashleigh , Kim Deborah , Liu Jingxuan , Roth Eric , Li Ellen , Shroyer Kenneth R. , Denoya Paula I. , Zhu Xiaoxia , Chen Longhua , Cao Jian
Published: May 2015

Upregulation of matrix metalloproteinase MMP-14 (MT1-MMP) is associated with poor prognosis in cancer patients, but it is unclear how MMP-14 becomes elevated in tumors. Here, we show that miR-181a-5p is downregulated in aggressive human breast and colon cancers where its levels correlate inversely with MMP-14 expression. In clinical specimens, enhanced expression of MMP-14 was observed in cancer cells located at the invasive front of tumors where miR-181a-5p was downregulated relative to adjacent normal cells. Bioinformatics analyses defined a potential miR-181a-5p response element within the 3′-untranslated region of MMP-14 that was validated in reporter gene experiments. Ectopic miR-181a-5p reduced MMP-14 expression, whereas miR-181a-5p attenuation elevated MMP-14 expression. In support of a critical relationship between these two genes, miR-181a-5p–mediated reduction of MMP-14 levels was sufficient to decrease cancer cell migration, invasion, and activation of pro-MMP-2. Furthermore, this reduction in MMP-14 levels was sufficient to reduce in vivo invasion and angiogenesis in chick chorioallantoic membrane assays. Taken together, our results establish the regulation of MMP-14 in cancers by miR-181a-5p through a posttranscriptional mechanism, and they further suggest strategies to elevate miR-181a-5p to prevent cancer metastasis. Cancer Res; 75(13); 2674–85. ©2015 AACR.
Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti–PD-L1 Antibodies
Authors: Heskamp Sandra , Hobo Willemijn , Molkenboer-Kuenen Janneke D.M. , Olive Daniel , Oyen Wim J.G. , Dolstra Harry , Boerman Otto C.
Published: May 2015

Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive antitumor activity. Patients with tumors expressing PD-L1 are most likely to respond to this treatment. The aim of our study was to develop a noninvasive imaging technique to determine tumor PD-L1 expression in vivo. This could allow selection of patients that are most likely to benefit from anti–PD-1/PD-L1 treatment and to monitor PD-L1 expression during therapy. The monoclonal antibody PD-L1.3.1 was radiolabeled with Indium-111 (111In) and characterized using PD-L1–expressing MDA-MB-231 cells. Subsequently, the optimal antibody dose and time point for imaging was determined in mice with MDA-MB-231 xenografts. Finally, SPECT/CT imaging was performed in xenograft models with different PD-L1 expression levels and tumor sections were analyzed for PD-L1 expression using IHC. The optimal antibody dose of 111In-PD-L1.3.1 (Kd = 1 nmol/L) for SPECT/CT imaging was ≤1 μg. Highest tumor-to-normal tissue contrast was obtained at days 3 and 7 after injection. 111In-PD-L1.3.1 SPECT/CT showed efficient accumulation in high PD-L1–expressing tumors (MDA-MB-231 and SK-Br-3), whereas no specific uptake was observed in tumors with low or no detectable levels of PD-L1 (SUM149, BT474, and MCF-7). SPECT/CT and autoradiography showed a very heterogeneous distribution of 111In-PD-L1.3.1 within the tumor. In conclusion, this is the first study showing the feasibility of noninvasive in vivo imaging of PD-L1 expression in tumors. 111In-PD-L1.3.1 showed efficient and specific uptake in PD-L1 expressing xenografts. This technique may enable patient selection for PD-1 and PD-L1–targeted therapy. Cancer Res; 75(14); 2928–36. ©2015 AACR.
Macrophages Regulate the Systemic Response to DNA Damage by a Cell Nonautonomous Mechanism
Authors: Geiger-Maor Anat , Guedj Avital , Even-Ram Sharona , Smith Yoav , Galun Eithan , Rachmilewitz Jacob
Published: May 2015

The DNA damage response (DDR) is a comprehensive and complex network of phosphorylation-mediated signaling pathways that originates endogenously from the DNA lesion and activates intrinsic DNA repair mechanisms. Here we describe a macrophage-dependent mechanism that regulates the response to DNA damage. We demonstrate that human monocytes, by releasing macrophage-derived HB-EGF, enhance DDR in neighboring cells suffering from DNA damage. Consequently, HB-EGF–treated cells exhibit higher double-strand break (DSB) rejoining and display lower levels of residual DSBs. Diethylnitrosamine (DEN) injection induce DSBs along with elevation in the number of macrophages and HB-EGF expression. Significantly, macrophage depletion or blocking HB-EGF activity results in higher levels of nonrepairable DSBs, suggesting that macrophages play a role in the resolution of DNA damage via HB-EGF. This study establishes that macrophages, acting through the activation of the EGFR cascade, constitute an important cell nonautonomous physiologic component of the DDR and points to a unique role played by immune cells in maintaining genome integrity. Cancer Res; 75(13); 2663–73. ©2015 AACR.
Classifying Cancers Based on T-cell Infiltration and PD-L1
Authors: Teng Michele W.L. , Ngiow Shin Foong , Ribas Antoni , Smyth Mark J.
Published: May 2015

Cancer immunotherapy may become a major treatment backbone in many cancers over the next decade. There are numerous immune cell types found in cancers and many components of an immune reaction to cancer. Thus, the tumor has many strategies to evade an immune response. It has been proposed that four different types of tumor microenvironment exist based on the presence or absence of tumor-infiltrating lymphocytes and programmed death-ligand 1 (PD-L1) expression. We review this stratification and the latest in a series of results that shed light on new approaches for rationally designing ideal combination cancer therapies based on tumor immunology. Cancer Res; 75(11); 2139–45. ©2015 AACR.
High Serum Transforming Growth Factor-β1 Levels Predict Outcome in Hepatocellular Carcinoma Patients Treated with Sorafenib
Authors: Lin Tzu-Hsuan , Shao Yu-Yun , Chan Soa-Yu , Huang Chung-Yi , Hsu Chih-Hung , Cheng Ann-Lii
Published: May 2015

Background: The TGF-β signaling pathway is crucial in the progression and metastasis of malignancies. We investigated whether the serum TGF-β1 level was related to the outcomes of patients treated with sorafenib for advanced hepatocellular carcinoma (HCC).

Experimental Design: We selected patients who had received sorafenib-containing regimens as first-line therapy for advanced HCC between 2007 and 2012. Serum TGF-β1 levels were measured and correlated with the treatment outcomes. The expression TGF-β1 and the sensitivity to sorafenib were examined in HCC cell lines.

Results:Ninety-one patients were included; 62 (68%) were hepatitis B virus surface antigen (+), and 11 (12%) were anti-hepatitis C virus (+). High (≥ median) pretreatment serum TGF-β1 levels (median 13.7 ng/mL; range, 3.0–41.8) were associated with high α-fetoprotein levels, but not with age, gender, or disease stage. Patients with high pretreatment serum TGF-β1 levels exhibited significantly shorter progression-free survival (median, 2.5 vs. 4.3 months; P = 0.022) and overall survival (median 5.6 vs. 11.6 months; P = 0.029) than did patients with low serum TGF-β1 levels. Compared with pretreatment levels, the serum TGF-β1 levels were significantly increased at disease progression (n = 29, P = 0.010). In preclinical models of HCC, higher TGF-β1 expression levels were associated with poorer sensitivity to sorafenib.

Conclusions: High pretreatment serum TGF-β1 levels were associated with poor prognoses, and increased serum TGF-β1 levels were associated with the disease progression of advanced HCC patients. TGF-β pathway may be explored as a therapeutic target for advanced HCC. Clin Cancer Res; 21(16); 3678–84. ©2015 AACR.
CCR 20th Anniversary Commentary: Expanding the Epigenetic Therapeutic Portfolio
Authors: Bates Susan E. , Robey Robert W. , Piekarz Richard L.
Published: May 2015

Epigenetic targets have emerged as an exciting area for drug discovery. The discovery that histone deacetylase (HDAC) inhibitors had marked anticancer activity in T-cell lymphoma gave impetus to the field. In a phase I study published in Clinical Cancer Research in March 2002, romidepsin (depsipeptide), a potent HDAC inhibitor, was found to be tolerable, with a side effect profile that was later understood to be characteristic of this class of agents. Evidence of activity in this key phase I trial provided momentum for the further study of epigenetic agents. Clin Cancer Res; 21(10); 2195–7. ©2015 AACR.

See related article by Sandor et al., Clin Cancer Res 2002;8(3) Mar 2002;718–28
CCR 20th Anniversary Commentary: Vorinostat—Gateway to Epigenetic Therapy
Authors: Kelly Wm. Kevin , Marks Paul , Richon Victoria M.
Published: May 2015

The study by Kelly and colleagues, published in the September 1, 2003, issue of Clinical Cancer Research, established the safety and biologic activity of the first-in-class histone deacetylase inhibitor, vorinostat, which was administered intravenously. Subsequent studies led to the development of oral vorinostat and the regulatory approval of vorinostat for cutaneous T-cell lymphomas, which opened the door for the next generation of inhibitors. Clin Cancer Res; 21(10); 2198–200. ©2015 AACR.

See related article by Kelly et al., Clin Cancer Res 2003;9(10) September 1, 2003;3578–88
Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors
Authors: Patnaik Amita , Kang S. Peter , Rasco Drew , Papadopoulos Kyriakos P. , Elassaiss-Schaap Jeroen , Beeram Muralidhar , Drengler Ronald , Chen Cong , Smith Lon , Espino Guillermo , Gergich Kevin , Delgado Liliana , Daud Adil , Lindia Jill A. , Li Xiaoyun Nicole , Pierce Robert H. , Yearley Jennifer H. , Wu Dianna , Laterza Omar , Lehnert Manfred , Iannone Robert , Tolcher Anthony W.
Published: May 2015

Purpose: This phase I study evaluated the safety, maximum tolerated dose, antitumor activity, and pharmacokinetics and pharmacodynamics of pembrolizumab in patients with advanced solid tumors.

Experimental Design: In a 3 + 3 dose escalation study, 10 patients received pembrolizumab 1, 3, or 10 mg/kg intravenously every 2 weeks until progression or intolerable toxicity. Seven additional patients received 10 mg/kg every 2 weeks. Thirteen patients participated in a 3-week intrapatient dose escalation (dose range, 0.005–10 mg/kg) followed by 2 or 10 mg/kg every 3 weeks. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Results: No dose-limiting toxicities were observed. Maximum administered dose was 10 mg/kg every 2 weeks. One patient with melanoma and one with Merkel cell carcinoma experienced complete responses of 57 and 56+ weeks' duration, respectively. Three patients with melanoma experienced partial responses. Fifteen patients with various malignancies experienced stable disease. One patient died of cryptococcal infection 92 days after pembrolizumab discontinuation, following prolonged corticosteroid use for grade 2 gastritis considered drug related. Pembrolizumab exhibited pharmacokinetic characteristics typical of humanized monoclonal antibodies. Maximum serum target engagement was reached with trough levels of doses greater than or equal to 1 mg/kg every 3 weeks. Mechanism-based translational models with a focus on intratumor exposure prediction suggested robust clinical activity would be observed at doses ≥2 mg/kg every 3 weeks.

Conclusions: Pembrolizumab was well tolerated and associated with durable antitumor activity in multiple solid tumors. The lowest dose with full potential for antitumor activity was 2 mg/kg every 3 weeks. Clin Cancer Res; 21(19); 4286–93. ©2015 AACR.

See related commentary by van Elsas et al., p. 4251
Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects
Authors: Carniti Cristiana , Gimondi Silvia , Vendramin Antonio , Recordati Camilla , Confalonieri Davide , Bermema Anisa , Corradini Paolo , Mariotti Jacopo
Published: May 2015

Purpose: Immune-mediated graft-versus-tumor (GVT) effects can occur after allogeneic hematopoietic stem cell transplantation (HSCT), but GVT is tightly linked to its main complication, graft-versus-host disease (GVHD). Strategies aimed at modulating GVHD, while maintaining the GVT effect, are needed to improve the cure rate of transplant. Given the emerging role of Janus-activated kinase (JAK) signaling in lymphoproliferative and myeloproliferative diseases and its established function at dictating T-cell differentiation, we postulated that JAKs might be potential therapeutic targets through a pharmacologic approach.

Experimental Design: We examined the effect of JAK1/JAK2 modulation by ruxolitinib in a mouse model of fully MHC mismatched bone marrow transplant comprising in vivo tumor inoculation.

Results: JAK1/JAK2 inhibition by ruxolitinib improved both overall survival (P = 0.03) and acute GVHD pathologic score at target organs (P ≤ 0.001) of treated mice. In addition, treatment with ruxolitinib was associated with a preserved GVT effect, as evidenced by reduction of tumor burden (P = 0.001) and increase of survival time (P = 0.01). JAK1/JAK2 inhibition did not impair the in vivo acquisition of donor T-cell alloreactivity; this observation may account, at least in part, to the preserved GVT effect. Rather, JAK1/JAK2 inhibition of GVHD was associated with the modulation of chemokine receptor expression, which may have been one factor in the reduced infiltration of donor T cells in GVHD target organs.

Conclusions: These data provide further evidence that JAK inhibition represents a new and potentially clinically relevant approach to GVHD prevention. Clin Cancer Res; 21(16); 3740–9. ©2015 AACR.
Immune Checkpoint Modulation for Non–Small Cell Lung Cancer
Authors: Soria Jean-Charles , Marabelle Aurélien , Brahmer Julie R. , Gettinger Scott
Published: May 2015

Therapies targeting immune checkpoints have recently shown encouraging activity in patients with heavily pretreated advanced non–small cell lung cancer (NSCLC), independently of NSCLC histology or mutational status, with low toxicity profiles when used as monotherapy. Objective response rates of approximately 20% have been reported in patients with advanced NSCLC treated with antagonist antibodies targeting the immune checkpoint, programmed death 1 (PD-1) on activated T cells, or its primary ligand, programmed death ligand 1 (PD-L1) expressed within the tumor microenvironment. Response rates appear to be higher in patients with tumor PD-L1 expression documented by immunohistochemistry, although responses have been appreciated in patients with reportedly PD-L1–negative tumor specimens. Antibodies directed against cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), another immunosuppressive T-cell signaling molecule, are also being evaluated in clinical trials, with one randomized phase II trial demonstrating improved immune-related progression-free survival in lung cancer patients when added to standard chemotherapy. Additional clinical trials are combining anti–CTLA-4 antibodies with either anti–PD-1 or anti–PD-L1 antibodies. Combinations of other immune checkpoint antagonists or agonist antibodies with anti–PD-1 or anti–PD-L1 antibodies are also being pursued. Clin Cancer Res; 21(10); 2256–62. ©2015 AACR.

See all articles in this CCR Focus section, “Progress in Lung Cancer.”
Abstract A25: Evaluation of the food environment in rural towns in eastern Washington
Authors: Ko Linda K. , Perry Cynthia , Mariscal Norma , Rodriguez Edgar , Duggan Catherine , Kratz Mario , Thompson Beti
Published: May 2015

Introduction: Hispanics are at increased risk for obesity, which places them at increased risk for a variety of health conditions, including cancer. Risk factors for both obesity and cancer include limited access to healthy affordable foods. This problem is especially prevalent in low-income communities such as rural towns. This study assessed the availability of healthful foods and food environment scores in two rural towns with large percentages of Hispanic residents in Eastern Washington State.

Experimental Procedures: Store inventories were collected in 14 food stores (3 grocery and 11 convenience stores) from July-August 2013 using the Nutrition Environment Measures Survey. We recorded data on availability of a variety of fresh fruits, vegetables, whole grain bread, lean ground beef, low-fat hot dogs, baked or low-fat chips, and low sugar cereal. Food environment scores were generated for stores, which consisted of a composite score of availability of healthy food, quality, and price.

Results: Convenience stores comprised 79% of food stores. Availability of specific healthful items differed between grocery and convenience stores with all the grocery stores (100%) selling at least 1 fresh fruit compared to 27% of the convenience stores. More grocery stores also had fresh vegetables (100% vs. 18%), whole grain bread (100% vs. 36%), lean ground beef (100% vs. 9%), low-fat hot dogs (100% vs. 9%), baked or low-fat chips (67% vs. 0%), and low sugar cereal (67% vs. 18%). Grocery stores, however, were slightly less likely to be stocked with 100% fruit juice (67% vs. 73%), while more stocked with diet soda (100% vs. 91%) than convenience stores. Out of a possible maximum food environment score of 62, grocery stores scored 29 while convenience stores scored 3.64.

Conclusions: Convenience stores make up a large proportion of available food sources in rural towns and have limited stocks of healthful foods. The low food environment scores of both grocery and convenience stores are indication that stores have room for improvements. Increasing the variety of healthy food offerings in food stores could be the first step in improving the food environment in rural towns.

Citation Format: Linda K. Ko, Cynthia Perry, Norma Mariscal, Edgar Rodriguez, Catherine Duggan, Mario Kratz, Beti Thompson. Evaluation of the food environment in rural towns in eastern Washington. [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 A25. doi:10.1158/1538-7755.DISP13-A25
Abstract A30: Using the principles of community-based participatory research to build an office of health equity within a nationally designated cancer institute
Authors: Barrett Nadine Josann , Worthy Valarie , Boyce-Manon Xiomara , Reyes Rebecca , Banks Lamisha , Patierno Steve , Chu Claire
Published: May 2015

Across the nation academic health centers, including cancer centers are establishing offices or departments focused specifically on health disparities and health equity. This movement is critical to ensure health disparities research and its dissemination, becomes an ongoing theme in the fabric of an institution. Offices or departments of this nature can often be shaped and defined based on initial funder priorities and may miss the opportunity to engage authentically with the community in the initial stages of its development. Limited practical research is available to describe the development, implementation, and initial outcomes of a new Office of Health Equity built within a NCI designated cancer institute. Using CBPR methodology, this project conducted assessments reaching over 121 diverse community members, faith leaders, cancer survivors, and caregivers from Latino, Asian, African American and medically underserved communities. Community partnerships were developed to conduct group sessions designed to describe community attitudes on cancer, clinical trials and research participation. Participants provided recommendations to collaboratively overcome barriers to accessing cancer information and care, clinical trials education and participation, and reduce cancer health disparities. Findings are reported back to the community and a full research platform and strategic plan has been developed and currently implemented with the community, survivors and practitioners. Practical methods of authentic community engagement are utilized to improve outreach and access to cancer services, clinical trials education and minority participation, ensure cancer survivors have a seamless journey throughout the cancer continuum, and to enhance cancer disparities research.

Citation Format: Nadine Josann Barrett, Valarie Worthy, Xiomara Boyce-Manon, Rebecca Reyes, Lamisha Banks, Steve Patierno, Claire Chu. Using the principles of community-based participatory research to build an office of health equity within a nationally designated cancer institute. [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 A30. doi:10.1158/1538-7755.DISP13-A30
Abstract A35: Barriers faced and enablers used by community health workers in 3 underserved communities on cervical cancer screening among Haitian, Hispanic, and African American women
Authors: Rodriguez Brendaly , McCann Shelia , Carrasquillo Olveen , Kobetz Erin , Amofah Anthony , Koru-Sengul Tulay
Published: May 2015

As trusted members of their communities, community health workers (CHWs) have the potential to link hard-to-reach underserved populations with appropriate health care. As part of a National Cancer Institute (NCI)-funded initiative, we are examining the effectiveness of CHWs at increasing cervical cancer screening among minority women. CHWs are placed at one of three federally qualified health centers (FQHCs)/FHQC-look alike and obtain additional input from project specific Community Advisory Boards (CABs) in each community. Using a mixed methods approach consisting of quantitative recruitment data as well as key informant interviews we have identified several barriers and enablers for outreach, recruitment and retention of participants in our project. CHW characteristics facilitating study participant recruitment and retention include: personality, prior field experience, language, cultural congruence, degree of familiarity with community, ability to connect with their CAB members and degree of interaction with existing resources at their respective FQHCs (programmatic, structural, environmental and personnel). Ongoing CWH training and quality control were also important enablers of achieving our recruitment targets. Study participant characteristics such as cultural norms/beliefs, immigration status, health insurance, and economic factors (ability to meet clinic co-payments) were frequently cited as barriers. Structural/organizational characteristics of each FQHCs such as how health services are delivered, paperwork requirements, accessibility of location and tight linkages with local health departments also served as enablers and/or barriers. Lessons learned from our CHW led cervical cancer screening study can be applied to many distinct community based programs aimed at improving health care in underserved communities.

Note: This abstract was withdrawn after the Proceedings was printed and was not presented at the conference.

Citation Format: Brendaly Rodriguez, Shelia McCann, Olveen Carrasquillo, Erin Kobetz, Anthony Amofah, Tulay Koru-Sengul. Barriers faced and enablers used by community health workers in 3 underserved communities on cervical cancer screening among Haitian, Hispanic, and African American women. [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 A35. doi:10.1158/1538-7755.DISP13-A35
Abstract A42: Adherence to cancer screening tests among Appalachian women
Authors: Paskett Electra D. , Young Gregory , Pennell Michael , Katz Mira L. , Reiter Paul L.
Published: May 2015

Purpose. Appalachian populations suffer from higher rates of cancer incidence and mortality than non-Appalachian populations. Research has documented disparities in the receipt of recent cancer screening tests for each test individually (ie, mammography (MA), Pap Test (PT) and colonoscopy, flexible sigmoidoscopy or FOBT (CRC)), however, no study has documented disparities in the receipt of multiple screening tests in this population.

Methods. As part of a larger study on community-based participatory research strategies to reach Appalachian community members about the need for CRC screening, we surveyed 644 women aged 51-75 who completed a phone survey after being randomly selected from commercially available lists for 12 Appalachian Ohio counties. The survey included questions about the receipt of PT (within last year), MA (within the last year), and CRC (last year for FOBT, last 5 years for FS and last 10 years for colonoscopy). The frequencies of each test, as well as the total number of tests reported (0,1,2,3), were calculated. Analysis of factors associated with being in guidelines by test and by number of tests was also conducted.

Results. About 2/3 of the women (67%) had not had a recent PT, 46% had not had a recent MA, and 46% were not within guidelines for CRC. Only 19% of the women were within guidelines for all 3 tests, with 27% reporting not being within guidelines for any of the 3 tests. Predictors of adherence to the screening tests will be presented.

Conclusions. Many women in Appalachia Ohio have not received recent cancer screening tests. The PT appears to be the most underused, which may explain the higher cervical cancer mortality rates in this region of the country. A quarter of the women were not adherent to any of the 3 tests, which suggests that interventions should focus on improving multiple screening behaviors to reduce high cancer rates in this underserved population.

Citation Format: Electra D. Paskett, Gregory Young, Michael Pennell, Mira L. Katz, Paul L. Reiter. Adherence to cancer screening tests among Appalachian women. [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 A42. doi:10.1158/1538-7755.DISP13-A42
Abstract A45: HPV awareness prevents positive infections
Authors: Kenya Sonjia , Fatil Marie , Koru-Sengul Tulay , Kobetz Erin , Carrasquillo Olveen
Published: May 2015

Background: Haitian Immigrant women, the largest growing Black ethnic group in Miami, experience the highest rates of cervical cancer and account for one of the largest populations diagnosed with HIV/AIDS in South Florida.

Objective: Using community-based participatory research methods, we examined HPV/cervical cancer knowledge and intervention preferences among HIV positive Haitian women. This data was used to develop and pilot test a culture-specific educational intervention among HIV positive and sexually active HIV negative Haitian women in Miami, Florida. The pilot study was conducted in two phases.

Methods:

Phase 1: Qualitative, August 2011: Three focus groups with 21 HIV-positive Haitian women living in Miami, Florida were completed in Haitian Kreyol, digitally recorded, and later interpreted and transcribed into English. The first focus group assessed HPV Knowledge; the second session explored HPV considerations specific to HIV positive women, and the third focus group discussed HPV Screening and intervention preferences.

Phase 2: Quantitative, July 2012 – Nov 2012: Using feedback from the focus groups, a flip-chart with educational illustrations was developed. Five small group (3-10 participants) HPV/Cervical Cancer education sessions led by a community health worker were conducted with 25 sexually active Haitian women (8 HIV + and 13 HIV –). Surveys assessing HPV/Cervical Cancer knowledge, screening behaviors, and research participation were administered at baseline and 3 months post-study.

Results: Three month follow up data was collected on 21 of the 25 women who participated in Phase 2 of the study. Participants' mean age was 52+8yrs, 71% lived in US > 5 years, and 71% were uninsured. At post study, the percent of women answering > 4/6 questions correct increased from 10% to 28% and the number of women who heard of HPV increased from 48% to 81%. All (100%) of participants were willing to participate in a research study.

Conclusions: An intensive one time small group educational intervention was associated with small improvements in cervical cancer / HPV knowledge at 3 months. Our findings show strong support for increased clinical research targeting low SES Haitian women.

Citation Format: Sonjia Kenya, Marie Fatil, Tulay Koru-Sengul, Erin Kobetz, Olveen Carrasquillo. HPV awareness prevents positive infections. [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 A45. doi:10.1158/1538-7755.DISP13-A45
Abstract A74: Community engagement approach to address contributors to cancer health disparities in Worcester, MA
Authors: Jesus-Monge Wilfredo Eugenio De , Jesus-Monge Vivianna Margarita De
Published: May 2015

Introduction: Community engagement is the process of working collaboratively with groups of people, considering that approaches for their health improvement must account for their concerns. Cancer health disparities are adverse differences in cancer incidence, prevalence, mortality, survivorship, and burden or related health conditions that exist among specific population groups in the US. Low socioeconomic status (SES) is a factor that contributes to the observed cancer health disparities among racial, ethnic, and underserved groups. SES is most often based on a person's income, education level, and other factors, such as native language and household composition. The objectives of this poster are: 1) to compare the racial / ethnic composition and SES factors in Worcester, Massachusetts (MA) with MA state and US, 2) to compare SES factors by racial / ethnic groups in Worcester, MA, and 3) to discuss how community engagement research can address the contributors to cancer health disparities.

Methods: Racial/ethnic composition and SES factors were collected from the US Census Bureau.

Results: The percentage of Hispanics, non-Hispanic (NH) Blacks, and NH Asians was higher in Worcester, MA population than in MA state in 2010. In addition, the percentage of families and people whose income is below the poverty level is higher in Worcester, MA than in MA state and US. Finally, the percentage of the population of Worcester, MA that has single-parent family households, non-family householders living alone, or speaks at home a language other than English is higher than in MA state and US.

Conclusion: Community engagement research is necessary to tackle the SES factors that can contribute to cancer health disparities in Worcester, MA.

Funding: National Institutes of Health, National Cancer Institute Research Supplement to Promote Diversity in Health-related Research (PI Brian C. Lewis, PhD, University of Massachusetts Medical School, Worcester, MA).

Citation Format: Wilfredo Eugenio De Jesus-Monge, Vivianna Margarita De Jesus-Monge. Community engagement approach to address contributors to cancer health disparities in Worcester, MA. [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 A74. doi:10.1158/1538-7755.DISP13-A74
Abstract A78: Factors associated with screening mammography in Asian Americans: Test of the Andersen's Behavioral Model of Health Services Use
Authors: Do ThuyQuynh Ngoc , Peek M. Kristen
Published: May 2015

Despite its effectiveness as a preventive measure, minority women are less likely to obtain screening mammograms. Although numerous studies have examined factors associated with mammography utilization and women's adherence to mammography screening guidelines, less attention has been directed to mammography adherence among Asian Americans and how nativity influences adherence. Asian Americans may be one of the fastest growing racial/ethnic groups in the United States, but remains one of the most poorly understood minorities in terms of screening mammography adherence. Using an adapted Andersen's Behavioral Model of Health Services Use and data from the California Health Interview Survey (2001-2009), this study sought to determine the relationship between predisposing, enabling, and need factors on mammography adherence among Asian Americans and to determine if it varied by nativity. The sample included 8,353 Asian Americans with 80.2% foreign-born. A multivariate logistic regression models were used to explore the association between enabling, predisposing, and need factors to screening mammography. The factors associated with screening mammography varied by nativity. Among U.S.-born Asian females, mammography adherence was associated with current smokers, prior cancer prevention health service use, Asians over the age of 65 years old, household size, speaking English very good or well and being uninsured. Among foreign-born Asian females, mammography adherence is associated with being overweight, sedentary, prior cancer prevention health service use, age (50-64 years old), household size, marital status, health insurance, and having one or more chronic conditions. Understanding the factors that impact mammography adherence may inform intervention strategies.

Citation Format: ThuyQuynh Ngoc Do, M. Kristen Peek. Factors associated with screening mammography in Asian Americans: Test of the Andersen's Behavioral Model of Health Services Use. [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 A78. doi:10.1158/1538-7755.DISP13-A78
Abstract A90: Changes in lung cancer rate over four years in a tobacco producing state: Examining the effect of race and gender
Authors: Husaini Baqar A. , Cain Van , Novotny Mehhan , Samad Zaheed , Levine Robert
Published: May 2015

Objective: According to a recent CDC report, lung cancer rates have declined in several states during 19975-2005. Tennessee, being a tobacco producing State, has received a large settlement from the tobacco industry and engaged in quit smoking program since 2006. Effective October 2007, the state also banned smoking in public places. However, the effect of this ban and smoking cessation program on lung cancer rates remains unknown. This presentation examines whether the lung cancer rates have changed over four years (2005-2008), and whether they vary by race and gender.

Methods: We extracted relevant data pertaining to primary diagnosis of lung cancer (adenocarcinoma, ICD-9 codes of 160-165) and demographics from Tennessee Hospital Discharge Data system (HDDS) for 2005-2008. Data for each year pertained to 3,500 patients, mostly white (79%) and males (56.8%) with an average age of 66 years. To examine the effect of race and gender on cancer rate, we computed lung cancer prevalence rates per CDC procedures for age-adjusted rates (per 100,000 hospitalized patient population standardized to 2000 Census).

Results: Our analyses show that the overall rates of lung cancer increased during four years by 26.3% (from 61.6/100K in 2005 to 77.8/100K in 2008). The increase was larger for blacks than whites (66.0% vs. 42.2%, p<.001). In general, in each year, rates were higher for blacks than whites (48.2 vs. 46.2 in 2005, 57.9 vs. 54.5 in 2006, 71.1 vs. 64.9 in 2007, and 80.0 vs. 65.7 in 2008). Similarly in each year, rates were higher for males than females (75.5 vs. 50.6 in 2005, 75.2 vs. 48.1 in 2006, 92.1 vs. 62.1 in 2007, and 93.8 vs. 65.3 in 2008). Further analyses revealed that (i) higher black rates were largely driven by higher rates among black males, and (ii) rates increased linearly from ages 45 through 74 years, and this was true for both black and white patients (both males and females). After age 84, rates dropped dramatically reflecting increasing mortality.

Conclusion: Lung cancer rates have increased for both blacks and males. However, it is too early to tell if smoking cessation programs, banning asbestos use and smoking in public places will produce the desired decline in lung cancer rates. The results at present point to the need for more population-based intensive smoking cessation programs in Tennessee to lower lung cancer rates.

Citation Format: Baqar A. Husaini, Van Cain, Mehhan Novotny, Zaheed Samad, Robert Levine. Changes in lung cancer rate over four years in a tobacco producing state: Examining the effect of race and gender. [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 A90. doi:10.1158/1538-7755.DISP13-A90
Abstract B15: Development and validation of an areca (betel) nut usage measurement tool for Micronesia
Authors: Paulino Yvette C. , Novotny Rachel , Katz Alan , Wilkens Lynne , Hurwitz Eric
Published: May 2015

Roughly 10% of the world's population chews areca nut, known as betel nut for the Piper betle leaf often chewed with the nut. It is the fourth most widely used addictive substance after nicotine, ethanol, and caffeine. Capturing the wide variability in chewing patterns among Micronesian ethnic subgroups is important, as it may lead to differing betel nut-oral cancer associations. A Betel Nut Measurement Tool (BENUT) was developed in 2007-2009 with Micronesian ethnic subgroups living in Guam. Subsequently, eighty-two betel nut chewers (42 males; 40 females) participated in the validation of BENUT against four weekly betel nut recalls. Concordance between the instruments was measured with Cohen's kappa. Areca nut comparisons were made on variety (red/white); maturity (unripe/ripe); and the addition of the Piper betle leaf, slaked lime, and tobacco (yes/no). Correlations were used for frequency measures (never, sometimes, usually, always) of ingestion and of adding the aforementioned ingredients. The BENUT was effective in measuring most variables with correlations of 0.60-0.93. The lowest correlations were: Piper betle leaf addition (0.10; 95% CL=-0.05-0.47 in males), Piper betle leaf frequency (0.25; 95% CL=0.09-0.41 in males), and slaked lime frequency (0.05; 95% CL=-0.05-0.14 in males and 0.12; 95% CL=0.04-0.19 in females). Occasional users of the Piper betle leaf among men and of the slaked lime among men and women tended to underestimate their use on the questionnaire. The BENUT is a valid instrument, and with modifications to the frequency of Piper betle leaf/slaked lime questions, can be used in epidemiologic studies in the region.

Citation Format: Yvette C. Paulino, Rachel Novotny, Alan Katz, Lynne Wilkens, Eric Hurwitz. Development and validation of an areca (betel) nut usage measurement tool for Micronesia. [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 B15. doi:10.1158/1538-7755.DISP13-B15
Abstract B24: Differential profiles of methylation in African American and Caucasian men diagnosed with prostate cancer
Authors: Koochekpour Shahriar , Zabaleta Jovanny
Published: May 2015

Background. Prostate cancer (PCa) is the most common non-skin cancer in men. Risk factors include age, African race, and family history. Methylation has been associated with gene regulation and prostate cancer development. Here we compared the global methylation profiles in normal and malignant tissues of African American (AA) and Caucasian patients with PCa.

Methods. DNA was extracted, treated with sodium bisulfite and hybridized to chips interrogating the status of more than 27,000 CpG sites in 14,000 genes. The β value (methylation fraction) was compared separately between normal and malignant tissues from AA and Caucasians to identify those CpG with at least 2-fold change (tumor/normal). The genes containing those differentially methylated CpG were analyzed in MetaCore to find cellular processes associated with either AA or Caucasians, or both.

Results. Two hundred fifteen (215) CpG sites were associated with AA, 42 CpG sites were found exclusively in Caucasians, and 47 were found in both ethnic groups. Pathway and network analyses showed that the most prominent cellular processes associated with the genes harboring those significant CpG sites in AA are involved in tissue remodeling / wound repair (p=2.98 x 10-5) and neurogenesis (1.068 x 10-5), while neurotransmission (p=0.006) and regulation of proliferation (p=0.0004) were the most prominent in Caucasians. Calcium signaling and platelet aggregation were the most prominent common processes to both ethnic groups.

Conclusion. Divergent pathways may exist in PCA in AA and Caucasians suggesting different targets for treatment

Citation Format: Shahriar Koochekpour, Jovanny Zabaleta. Differential profiles of methylation in African American and Caucasian men diagnosed with prostate cancer. [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 B24. doi:10.1158/1538-7755.DISP13-B24
Abstract B28: Racial/ethnic differences in prostate-specific antigen levels among U.S. men with metabolic syndrome: Results from NHANES 2001-2006
Authors: Advani Shailesh M. , Lopez David S.
Published: May 2015

Objective: Effect of the interplay between metabolic syndrome and race/ethnicity on prostate specific antigen (PSA) remains unclear. Different definitions of metabolic syndrome (National Cholesterol Education Program [ATP III], International Diabetes Federation [IDF] and World Health Organization [WHO]) may influence PSA disparities. Prevalence of these definitions varies by race/ethnicity. Little is known whether the degree to which serum PSA levels differ is dependent upon the metabolic syndrome definition used, and whether these associations vary by race and ethnicity.

Methods: We measured serum PSA (ng/mL) in 3528 adult men >40 years from the National Health and Nutrition Examination Survey (NHANES) 2001-2006. Metabolic syndrome was defined with ATP III, IDF, and WHO criteria. Racial/ethnic groups included non-Hispanic blacks (NHB's), non-Hispanic whites (NHW's) and Mexican-Americans (MA's). We computed adjusted geometric mean PSA by definition of metabolic syndrome and race/ethnicity. Univariate and multivariate regression analysis were performed.

Results: Univariate analysis was used to calculate age adjusted geometric mean PSA. Multivariable analysis were adjusted for age, smoking, moderate and vigorous physical activity and plasma-volume. Multivariable analyses showed men classified with ATP III and WHO metabolic syndrome had lower PSA concentrations than those without it (P=0.01 and P=0.03, respectively). Stratifying these associations by race and ethnicity showed that NHW's classified with ATP III and WHO definitions had lower PSA concentrations than those without it (P<0.01 and P=0.04, respectively). Similarly, MA's classified with WHO metabolic syndrome had lower PSA concentration than those without it (P=0.02). No significant differences were detected in PSA levels among NHB's with and without metabolic syndrome.

Conclusion: Different criteria for defining metabolic syndrome and its stratification by race and ethnicity had an inverse effect on PSA concentrations among MA and NHW. Our findings highlight the implications when investigating the interplay of different anthropometric measurements and metabolic factors with PSA levels by race and ethnicity.

Citation Format: Shailesh M. Advani, David S. Lopez. Racial/ethnic differences in prostate-specific antigen levels among U.S. men with metabolic syndrome: Results from NHANES 2001-2006. [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 B28. doi:10.1158/1538-7755.DISP13-B28
Abstract B40: Injectable multifunctional biodegradable polymeric microspheres for localized drug delivery in breast cancer treatment
Authors: Obayemi John David , Soboyejo Winston Oluwole , Odusanya Olushola S. , Anuku Nicolas , Uhrich Kathryn E. , Yue Wei
Published: May 2015

The conventional methods for the treatment of breast cancer include: bulk systematic surgery, chemotherapy and radiotherapy. These have been associated with high cost and severe side effects. However, the incremental improvements in breast cancer therapy are far from addressing the challenges associated with the cost and side effects of breast cancer treatment. There is, therefore, the need to develop localized drug delivery systems that mitigate these side effects. This research explores the synthesis and physicochemical characterization of injectable multi-functional biodegradable polymer-based microparticles with sizes of the order of ∼ 1-10 μm. These are loaded with a biosynthesized cancer drug (prodigiosin) that is obtained from the bacteria Serratia marcescens, for controlled drug release. By integrating therapeutic agents, these multi-functional and porous particles can serve as reservoirs for localized drug delivery. The prodigiosin was encapsulated using a double emulsion solvent evaporation technique in the presence of poly (DL-lactide-co-glycolide) (PLGA) and poly (vinyl alcohol) (PVA) emulsifier, which are all approved by WHO and FDA as implant materials for use in medicine and pharmacy. The dependence of the particle size and morphology, and the in-vitro release of the drug used were elucidated using a combination of scanning electron microscopy (SEM), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) and UV-visible spectrophotometry. The drug loading efficiency and the encapsulation efficiency were also shown to be ∼ 1 % and 82 % respectively. The implications of the results are discussed for the potential development of injectable multi-functional polymeric microparticles for the targeting and localized drug delivery of drugs for the treatment of breast cancer.

Citation Format: John David Obayemi, Winston Oluwole Soboyejo, Olushola S. Odusanya, Nicolas Anuku, Kathryn E. Uhrich, Wei Yue. Injectable multifunctional biodegradable polymeric microspheres for localized drug delivery 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 B40. doi:10.1158/1538-7755.DISP13-B40