bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B120: Wnt expression and the association with autophage protein in pancreatic cancer
Authors: Lee Myung Ah , Park Jin Hee
Published: October 2015

Background: Aberrant wnt signaling pathway and contribution of autophagy have been documented in many types of human cancers. However, the association between and autophage-related protein has not been studied in pancreatic cancer. We analyzed the expression of wnt protein and autophage-related protein in pancreatic cancer to determine the association and its clinical significance.

Materials and Methods: From January 2001 to December 2009, paraffin embedded blocks from 74 patients undergone pancreatic resection for the treatment of pancreatic cancer were used in the present study. We performed immunohistochemical staining for wnt3, wnt5a, ß-catenin in wnt signaling pathway and Atg5, Ambra1, Beclin-1, LC3, Bif-1 in the fields of autophage related protein. We reviewed the clinicopathologic characteristics and analyzed the association between wnt signaling pathway and the autophage.

Results: In 74 patients, the expression rates of wnt protein were 68.9% for wnt3, 83.8% for wnt5a and 54.9% for ß-catenin. The wnt3 expression was more frequent in pancreatic head than in body or tail (p = 0.039) and ß-catenin was more commonly expressed in negative lymphatic invasion (p = 0.032). The wnt 3 expression is positively associated with ATG5 (p=0.004), Ambra1 (p=0.004), Beclin (p=0.022), and LC3 (p=0.002). The wnt5 expression also showed the correlation with ATG5 (p=0.01), Ambra1 (p=0.026), Beclin (p=0.012), and LC3 (p=0.003). There was no prognostic significance association between survival outcome and wnt expression.

Conclusion: In pancreatic cancer, wnt protein expression was very high, showing association with autophage-related protein. To determine the clinical significance of these protein expressions, we are currently ongoing further research.

Note: This abstract was not presented at the conference.

Citation Format: Myung Ah Lee, Jin Hee Park. Wnt expression and the association with autophage protein in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B120.
Abstract B16: Contributions of Ras and EZH2 in acinar to ductal metaplasia and ductal carcinoma in transgenic mouse pancreas
Authors: Ellis Jayne , Sandgren Eric P. , Grippo Paul J. , Figueiredo Marxa L.
Published: October 2015

Activating mutations of the ras protooncogene is the most frequent and an early genetic alteration associated with pancreatic cancer. To examine the link between mutant ras oncogenes and exocrine pancreatic cancer, and to develop mouse models of PanINs and also of lesions that progress to malignancy, we generated transgenic mice expressing either Kras or Hras in pancreas. The tetracycline transactivator system expression was targeted to the pancreatic acinar cells via the elastase promoter element. The transactivation target ras genes were placed under the control of the tetracycline-response element. Most double transgenic founder mice displayed perinatal pancreatic acinar cell hyperplasia and dysplasia. However, only adult mice expressing Hras displayed preinvasive pancreatic neoplastic lesions with ductal morphology. Therefore, these Kras and Hras models each represent useful models in which either the lesion histotype and agressiveness (Hras) or the initiating genetic alteration overlap with the human disease (Kras). More recently, we have developed and are characterizing the contributions of expressing enhancer of zeste 2 homolog (EZH2), a histone methyl transferase and key regulator of cell differentiation and tissue regeneration, in modifying aggressiveness of mutated ras genes in vivo. Our findings suggest that ras mutations are associated with development of early stage duct-like lesions in pancreas, which vary in severity depending on the mutated ras gene expressed and the stage of development and growth of pancreas tissue.

Citation Format: Jayne Ellis, Eric P. Sandgren, Paul J. Grippo, Marxa L. Figueiredo. Contributions of Ras and EZH2 in acinar to ductal metaplasia and ductal carcinoma in transgenic mouse pancreas. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B16.
Abstract B61: CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models
Authors: Zhu Yu , Brett Knolhoff , Melissa Meyer , Brian West , David Linehan , DeNardo David
Published: October 2015

The immune system is a promising therapeutic target that can be modulated to improve pancreatic ductal adenocarcinoma (PDAC) patient outcomes. Unfortunately, attempts to use immunotherapeutics as single agents have achieved very limited clinical benefits in PDAC. One major obstacle is the presence of an immunosuppressive tumor microenvironment. Critical drivers of this immunosuppressive microenvironment include tumor-associated macrophages, monocytic myeloid-derived suppressor cells, and immature granulocytes/granulocytic. In addition to instigating immune suppression, these tumor-infiltrating leukocytes can impart resistance to cytotoxic therapies and promote metastatic dissemination. As a consequence, high numbers of these myeloid cells are often associated with early metastatic relapse and poor survival in pancreatic cancer patients. Therefore, approaches that reprogram myeloid responses to potentiate antitumor immunity and/or bolster immunotherapy could hold significant therapeutic potential. In this report, we demonstrate that inhibition of colony stimulating factor 1 receptor (CSF1R) signaling functionally reprograms macrophage responses to enhance antigen presentation, thereby stimulating anti-tumor T cell responses. However, this immune reprograming also leads to the upregulation of T cell checkpoint molecules, including PDL1 and CTLA4, which significantly limits the potential of the CSF1R blockade to induce anti-tumor responses. While both programmed cell death protein 1 and CTLA4 antagonists show limited efficacy as single agents to restrain PDAC growth in a mouse model, the combination of these agents with CSF1R blockade achieves disease regression even in well-established tumors. These data suggest that reprograming myeloid responses through CSF1R blockade can improve the efficacy of checkpoint-based immunotherapeutics in pancreatic cancer.

Citation Format: Yu Zhu, Knolhoff Brett, Meyer Melissa, West Brian, Linehan David, David DeNardo. CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B61.
Abstract B96: Non-viral gene therapy for pancreatic cancer, from preclinical models to phase II clinical trial
Authors: Buscail Louis , Bournet Barbara , Vernejoul Fabienne , Cambois Gilles , Lulka Hubert , Hanoun Naima , Meulle Aline , Vignolle-Vidoni Alix , Barbey Odile , Gross Fabian , Guimbaud Rosine , Ottal Philippe , Tiraby Gérard , Cordelier Pierre
Published: October 2015

To date, pancreatic adenocarcinoma (PDAC) can’t be diagnosed early. Consequently, a majority of patient (80%) display an advanced disease that results in a low resection rate leading to a dismal overall median survival of less than 6 months. We extensively demonstrated that delivering SSTR2, DCK and UMK genes using non-viral vectors strongly inhibit tumor progression and dissemination in relevant experimental models of PDAC. Consequently, we designed a GMP-grade gene therapy product, namely CYL-02, encoding for the above mentioned therapeutic proteins, delivered by a non-viral vector for the management of 24 patients diagnosed with advanced PDAC. In this phase I clinical trial, gene therapy was administered in dose-escalation in the tumors using endoscopic ultrasound. Patients received gemcitabine during this protocol. We demonstrate that the intratumoral injection of the gene therapy product is feasible, well tolerated and safe, and results in the presence and the expression of CYL-02 in the tumors. Consequently, tumor progression is inhibited during the course of the protocol. In patients with locally advanced PDAC at the time of diagnosis, tumor size and serum levels of CA 19-9 significantly decreased following gene therapy regardless of the previous lines of treatment and median progression free survival and median overall survival reaches 6.4 and 11.4 months respectively. In addition, we carried out several advanced proteomic and circulating miRNAs analyses to identify diagnostic biomarkers predictive and/or indicative of treatment response and follow-up, to select clinical trial participants and/or to tailor therapy for individual patient. We already identified several biomarkers of clinical interest using either CE-MS (capillary electrophoresis coupled with mass spectrometry) or high throughput q(RT)PCR for peptide and miRNA identification, respectively, to create a clear prescription path for gene therapy in forthcoming clinical trials. Based on these preliminary yet very encouraging results, we propose that patients may clinically benefit from this approach. Accordingly, we are now entering phase II clinical trial using CYL-02 gene therapy product in patients diagnosed with locally advanced PDAC.

Citation Format: Louis Buscail, Barbara Bournet, Fabienne Vernejoul, Gilles Cambois, Hubert Lulka, Naima Hanoun, Aline Meulle, Alix Vignolle-Vidoni, Odile Barbey, Fabian Gross, Rosine Guimbaud, Philippe Ottal, Gérard Tiraby, Pierre Cordelier. Non-viral gene therapy for pancreatic cancer, from preclinical models to phase II clinical trial. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B96.
Abstract B97: A phase II trial of low-dose multiagent chemotherapy with gemcitabine, taxotere, xeloda, and cisplatin (GTX-C) in subjects with metastatic pancreatic cancer
Authors: Le Dung , Laheru Daniel , Diaz Luis A.
Published: October 2015

Background: Triplet chemotherapy has been shown to delay the emergence of resistance and extend survival in patients with metastatic pancreatic adenocarcinoma. Four drug regimens, even at low doses, may further improve survival by simultaneously targeting multiple oncogenic pathways.

Methods: A phase II study of GTX-C (capecitabine 500 mg bid on days 1-14, and the combination of gemcitabine 500 mg/m2 (10 mg/m2/min), taxotere 20 mg/m2 and cisplatin 20 mg/m2 on days 4 and 11) was initiated in newly diagnosed untreated metastatic pancreatic cancer patients. The primary endpoint was progression-free survival rate at 6 months and designed such that the regimen would be considered active if the 6-month PFS rate was >75% and inactive if < 50%.

Results: Twenty-eight patients were enrolled. All patients were ECOG 0-1. Eighty-six percent of patients had evidence of liver metastases and 25% had biliary stents in place at time of study initiation. Median CA19-9 was 6,159 U/mL (37-154,323 U/mL). Median length of follow-up was 10.1 months. Grade 3/4 related adverse events included: nausea/vomiting (7%), transaminitis (10%), anemia (14%), thrombocytopenia (24%), and neutropenia (55%). However, febrile neutropenia occurred in only 3 patients (10%) and not until cycles 6, 14, and 15. PFS rate at 6 months was 74.2% (95% CI: 53.3% - 86.8%). The partial response (PR) rate was 50%, stable disease (SD) rate was 39% and the disease control rate (DCR) was 89%. CA19-9 declines of >80% occurred in 77% of patients with measurable levels. Estimated median PFS was 8.4 months (95% CI: 6.1-10.6 months) and OS was 12.9 months (95% CI: 10.0-NA months) as of 11/14/2013. Ten additional patients have been enrolled onto an expansion cohort in which the period off between cycles has been changed from 7 to 14 days.

Conclusions: GTX-C is highly active and well-tolerated in patients with metastatic pancreatic cancer and should be tested in a larger, comparative study. Clinical trial information: NCT01459614.

Citation Format: Dung Le, Daniel Laheru, Luis A. Diaz, Jr. A phase II trial of low-dose multiagent chemotherapy with gemcitabine, taxotere, xeloda, and cisplatin (GTX-C) in subjects with metastatic pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B97.
Abstract A06: Guided tours of a “Super Colon” increase knowledge and willingness to discuss colon cancer among residents of Appalachian Ohio
Authors: Fickle Darla K. , Randall Katherine E. , Jordan Audra L. , Torres Norma A. , Paskett Electra D.
Published: October 2015

Introduction: Due to the elevated colorectal cancer incidence and mortality rate in Appalachia Ohio, the “Blue Star Healthy Colon Initiative” was conducted to provide an interactive format to educate lay community members about colon cancer and colon cancer screening.

Methodology: The ‘Super Colon’ walk-through model was set up at two community events in Meigs County Ohio – an Appalachian county. At each event, participants were given tours of the Super Colon exhibit by nurses and public health professionals. Surveys on colon cancer knowledge, screening knowledge, testing intentions, and willingness to discuss colon cancer with others were collected from participants before and after tours. Information on age, colon cancer screening history, and insurance status of participants were also collected via survey before touring the Super Colon.

Data were analyzed with X2 tests to compare responses collected before touring the supercolon to responses collected after touring the supercolon.

Results: Over the two events, 227 pre-tour and 240 post-tour questionnaires were collected from respondents. The mean age of respondents was 57.0 years, 72.7% were at least fifty years of age, and 72.2% were female, 30.3% received Medicare, 19.2% received Medicaid, 9.2% had no health insurance, and 52.7% of respondents indicated that they had some form of private health insurance--including supplements to Medicare.

Of those respondents aged fifty years and older, 76.4% reported receiving encouragement from their doctor to screen for colon cancer, 74.7% reported undergoing a screening test, and 57.6% were up-to-date on colon cancer screening. After viewing the Super Colon, respondents showed improvement in colon cancer knowledge, specifically knowledge about colon polyps (p<0.001), colon cancer (p<0.001), colon cancer progression (p<0.001), colon cancer survival (p<0.001), and colon cancer screening tests (p<0.001).

After touring the Supercolon, respondents also reported greater willingness to discuss colon cancer with grandparents (p=0.004), relatives (p<0.001), peers (p<0.001), community members (p<0.001), and people at risk (p<0.001).

Discussion/Conclusions: Guided tours of the ‘Super Colon’ walk-through model appear to be effective educational and motivational tools in colon cancer screening promotion in underserved populations.

Citation Format: Darla K. Fickle, Katherine E. Randall, Audra L. Jordan, Norma A. Torres, Electra D. Paskett. Guided tours of a “Super Colon” increase knowledge and willingness to discuss colon cancer among residents of Appalachian Ohio. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A06.
Abstract A19: SHARE speaks: English, Japanese, Spanish, and cultures too
Authors: Walker Desiree
Published: October 2015

The poster will portray the many languages SHARE speaks both linguistically and culturally to meet the needs of underserved communities. The main focus will be on one of their latest special projects which is the Ambassador Program. It is a grassroots effort to reach medically underserved Latino/Hispanic and African American communities in New York City. Through educational presentations, trained survivors and other trained health advocates build public awareness and health empowerment regarding breast and ovarian cancers. The message is Be Informed, Empowered and Know Your Body! During outreach, women of African Ameican and Caribbean heritage frequently voiced they were looking for a support group with “people that look like me”. As a result of these comments, SHARE has begun to fill a void with the creation of a breast and ovarian cancers support group in the Harlem neighborhood of New York City.

SHARE's mission is to create and sustain a supportive network and community of women affected by breast or ovarian cancer. SHARE brings these women and their families and friends together with others who have experienced breast or ovarian cancer, and provides participants with the opportunity to receive and exchange information, support, strength and hope. SHARE's work focuses on empowerment, education and advocacy to bring better healthcare, an improved quality of life, and a cure for these diseases.

SHARE offers monthly educational programs on breast and ovarian cancers by medical professionals, researchers and health practitioners. LatinaSHARE is celebrating 20 yrs. of service to both the English and Spanish speaking Latino communities. They have breast and ovarian cancers helplines in English and Spanish. They offer breast and ovarian cancers support groups with some groups focused on women of African American and Caribbean, Japanese and Latino heritages.

Another one of SHARE's special projects is the Survivor Patient Navigators. It has two bilingual breast cancer survivors who work at Bellevue Hospital Breast Clinic and Mt. Sinai/St. Luke's Hospital Breast Clinic respectively. They help newly diagnosed patients especially Latina patients who only speak Spanish understand their diagnosis and empower them to be involved in their treatment decisions.

Citation Format: Desiree Walker. SHARE speaks: English, Japanese, Spanish, and cultures too. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A19.
Abstract A22: Using community-based participatory research to develop a culturally relevant resource for African American women affected by breast cancer
Authors: Bradley Patricia , Hanson Arin Ahlum , Guglielmino Janine Caplan , Henry Catherine Creme
Published: October 2015

Background: Research indicates that African-American women are more likely to die from breast cancer, be diagnosed at later stages and receive worse care than their white counterparts. In 1997, Living Beyond Breast Cancer (LBBC) wrote the booklet, Getting Connected: African-Americans Living Beyond Breast Cancer to address these issues. Changes over the last decade in breast cancer treatment, research on cancer disparities, and perceptions of breast cancer among African-Americans motivated LBBC to undertake a full revision of Getting Connected. In 2010 LBBC conducted a comprehensive, consumer-driven needs assessment engaging African-American women affected by breast cancer from across the country.

Methods/Approach: LBBC engaged stakeholders across the breast cancer continuum in the revision. The process included 1) Convening a national advisory committee of medical and advocacy experts to provide oversight 2) Holding five group interviews Philadelphia, Chicago and Little Rock with 44 African-American women diagnosed recently diagnosed with breast cancer 3) Interviewing eight key community informants who work closely with African-American survivors. Transcripts and notes were analyzed and salient themes were used to revise Getting Connected. The resource was redesigned using “plain language” principles and interactive elements were added.

Results: In October 2011, the second edition of Getting Connected was published. This 50 page, plain language, culturally relevant resource is designed to be used by African-American breast cancer survivors, their support network and their healthcare providers. This booklet promotes informed decision-making, while providing support, encouragement, and inspiration. Getting Connected addresses how one can live positively beyond breast cancer through the use of spirituality, developing and maintaining positive connections and reaching out to others.

Conclusions: Using a community-based participatory research process ensures that the resource is culturally relevant. This model can be replicated to produce resources for other populations. The personal and direct approach of Getting Connected makes this booklet a valuable resource for healthcare providers working with African-American women affected by breast cancer.

Citation Format: Patricia Bradley, Arin Ahlum Hanson, Janine Caplan Guglielmino, Catherine Creme Henry. Using community-based participatory research to develop a culturally relevant resource for African American women affected by breast cancer. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A22.
Abstract A44: Latino men enrolled in a clinical and health education collaborative for colorectal cancer screening
Authors: Mojica Cynthia M. , Liang Yuanyuan , Carmona Christina M.
Published: October 2015

Latino colorectal cancer screening rates are less than optimal (46.5% have been screened) compared to federal benchmarks (70.5%) and non-Hispanic Whites (60%). Latino men in particular have a 17% lower screening rate compared to non-Latino men.

This study used community health workers to recruit Latino men (ages > 50 who have never been screened for colorectal cancer) and offer educational sessions, navigation support, and no-cost stool blood tests and/or colonoscopies. The study partnered with three community-based organizations and a federally qualified health center.

To date, we have enrolled 262 eligible men (mean age: 57 + 5.3) who are uninsured (91%), employed (57%), and have an annual household income < $20,000 (77%). Most were born in Mexico (65%), speak Spanish (64%), and have < high school education (63%). Baseline analyses indicate at least 60% of men correctly identified starting age (> 50) and frequency (annual) for stool blood testing. However, 69% equated cancer with death and 35% felt no control over their chances of getting cancer. One hundred thirty two (50%) of enrolled men have received a colorectal cancer screening test. Of the remaining 130, 20 were lost-to-follow-up, refused further follow-up, or missed >3 appointments and the rest reported scheduling conflicts on clinic days. Preliminary analyses suggest that compared to men who have been screened, non-screened men have higher employment rates, are less likely to have seen a doctor in the past year, and exhibit no changes in knowledge/beliefs from baseline to follow-up.

Although the study has steadily enrolled and educated men (with support from spouses) on colorectal cancer risk factors, screening guidelines, and the benefits of early detection, our findings are consistent with other studies that find low colorectal cancer screening rates among Latino men. Future research is needed to better understand screening behavior and explore effective methods of increasing screening behavior in Latino men.

Citation Format: Cynthia M. Mojica, Yuanyuan Liang, Christina M. Carmona. Latino men enrolled in a clinical and health education collaborative for colorectal cancer screening. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A44.
Abstract A55: Racial differences in cultural values for cancer prevention and control: Fact or fiction
Authors: Jefferson Melanie , Riley Jodie , Rice Lashanta , Hughes-Halbert Chanita
Published: October 2015

Background: Attention to cultural beliefs and values is a critical component of culturally competent cancer care for prevention, treatment, and control among all individuals. Yet, culturally tailored interventions have only been developed for racial and ethnic minorities. This is because cultural beliefs and values for cancer behavioral outcomes have only been ascribed to and evaluated in racial and ethnic groups.

Objective: The purpose of this study was to evaluate racial and ethnic differences in cultural beliefs and values related to religiosity, collectivism, individualism, and past and present temporal orientation for cancer prevention and control (CPC) in a national random sample of African Americans, whites, and Hispanic adults (n=1699). Respondents completed the Multi-Dimensional Cultural Values Assessment Tool (MCVAT) to assess cultural beliefs and values for CPC.

Results: There were significant racial/ethnic differences only in religious beliefs and values for CPC. Compared to whites, African Americans (Coefficient=3.75, p=0.001) and Hispanic (Coefficient=2.42, p=0.001) reported significantly greater religiosity. In addition, religious values were higher among respondents who were female (Coefficient=1.10, p=0.01), those who were high school graduates or had less education (Coefficient=-1.87, p=0.001), and respondents who had incomes less than $50,000 (Coefficient=-2.23, p=0.001). Education had a similar association with collectivist values (Coefficient=-1.01, p=0.01), but only the comparison of Hispanics versus whites had a significant association with these values (oefficient=0.76, p=0.04), individualistic values for CPC (Coefficient=1.04, p=0.001), and past (OR=1.85, 95% CI=1.28, 2.68, p=0.001) and present temporal orientation (OR=1.72, 95% CI=1.21, 2.44, p=0.003).

Conclusions: With the exception of religiosity, there are few differences in cultural beliefs and values for CPC between African Americans, whites, and Hispanics. Endorsement of cultural beliefs and values should not be assumed based on racial and ethnic group membership. Rather, cultural beliefs and values for CPC should be evaluated individually among patients and at-risk groups to provide culturally competent cancer care.

Citation Format: Melanie Jefferson, Jodie Riley, Lashanta Rice, Chanita Hughes-Halbert. Racial differences in cultural values for cancer prevention and control: Fact or fiction. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A55.
Abstract A75: Excess of proximal microsatellite-stable colorectal cancer in African Americans from a multiethnic study
Authors: Xicola Rosa ,   The Chicago Colorectal Cancer Consortium, Kupfer Sonia , Braunschweig Carol , Ellis Nathan , Llor Xavier
Published: October 2015

Background: African Americans (AAs) have the highest incidence of colorectal cancer (CRC) compared to other US populations and more proximal CRCs. The objective is to elucidate the basis of these cancer disparities.

Methods: 566 AA and 328 Non-Hispanic White (NHW) CRCs were ascertained in five Chicago hospitals. Clinical and exposure data were collected. Microsatellite instability and BRAF (V600E) and KRAS mutations were tested. Statistical significance of categorical variables was tested by Fisher's exact test or logistic regression and age by Mann-Whitney U test.

Results: Over a ten-year period, the median age at diagnosis significantly decreased for both AAs (68 to 61; P<0.01) and NHWs (64.5 to 62; P=0.04); more AA patients were diagnosed before age 50 than NHWs (22% vs 15%; P=0.01). AAs had more proximal CRC than NHWs (49.5% vs. 33.7%; P<0.01), but overall frequencies of microsatellite instability, BRAF and KRAS mutations were not different nor were they different by location in the colon. Proximal CRCs often presented with lymphocytic infiltrate (P<0.01) and were diagnosed at older ages (P=0.02). Smoking, drinking, and obesity were less common in this group, but results were not statistically significant.

Conclusions: Patients with CRC have gotten progressively younger. The excess of CRC in AAs predominantly consists of more proximal, microsatellite stable tumors, commonly presenting lymphocytic infiltrate and less often associated with toxic exposures or a higher BMI. Younger AAs had more distal CRCs than older ones. These data suggest two different mechanisms driving younger age and proximal location of CRCs in AAs.

Citation Format: Rosa Xicola, The Chicago Colorectal Cancer Consortium, Sonia Kupfer, Carol Braunschweig, Nathan Ellis, Xavier Llor. Excess of proximal microsatellite-stable colorectal cancer in African Americans from a multiethnic study. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A75.
Abstract A84: Rural residence and late staging at breast cancer diagnosis
Authors: Lycan Thomas W. , Isom Scott , Lawrence Julia
Published: October 2015

Rural residing residents in the United States are medically under-served which may contribute to the late stage presentation of breast cancer, a major determinant of prognosis in breast cancer. We sought to determine if women from more rural residing communities presented to an academic medical center with later stage cancers than those women who live in more urbanized areas. We also determined if the cancers from the two communities were biologically similar by comparing the distribution of estrogen receptors (ER + vs. ER-). From the cancer registry at Wake Forest Baptist Medical Center we identified newly diagnosed female breast cancer cases between 1999-2013 (N = 3,372) who lived in the Piedmont and Appalachian Mountain regions of North Carolina and Virginia. These cases were characterized by urban-rural status at diagnosis to the level of ZIP code. Using both a linear model and a Cochran-Armitage trend test , women from rural areas presented with a more advanced clinical stage (stage 3 incidence 17.8% vs 15.6%, p 0.051). This trend remained roughly significant when we controlled for age at diagnosis (p 0.04), ER status (0.05), insurance status (0.06), and healthcare access (p 0.06). However, the difference became insignificant when we controlled for local poverty (p 0.12) and unemployment (p 0.13) levels within the individual ZIP-defined communities. Overall, we did not find large differences in the stage of presentation between urban and rural residing women. However, the trend that was found could be largely accounted for by measures of local poverty and unemployment, suggesting that communities may be identified for tailored educational or outreach efforts.

Citation Format: Thomas W. Lycan, Jr., Scott Isom, Julia Lawrence. Rural residence and late staging at breast cancer diagnosis. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A84.
Abstract A90: Predictors of inpatient mortality, charges, and length of stay among the very old with colon cancer in the United States
Authors: Nuño Tomas , Skrepnek Grant
Published: October 2015

Objective: The purpose of this study was to assess economic and clinical outcomes associated with inpatient colon cancer cases among persons 85 years and older in the U.S. from 2001-2010. We hypothesize that colon cancer is associated with higher inpatient charges and worse outcomes among those with infections compared to those without infections.

Methods: This retrospective cohort analysis utilized nationally-representative hospital discharge data from the Healthcare Cost and Utilization Project. Cases 85+ years of age with any diagnosis of colon cancer were included. Generalized linear models were used to assess outcomes of mortality, charges, and length of stay controlling for Elixhauser and predominant comorbidities, patient demographics, payer, year, and hospital characteristics.

Results: Of all adult colon cancer cases (n=1,846,363), 12.5% (n=230,133) occurred in persons 85+ years, averaging 88.7±3.2 years, 5.0±8.1 days for length of stay, and $55,485±67,938 in charges. Among the 9.5% (n=21,851) of inpatient mortality cases, predominant comorbidities included fluid and electrolyte disorders (60.7%), cardiac dysrhythmias (40.2%), heart failure (36.8%), distant metastases (33.5%), respiratory failure (31.8%), anemia (30.1%), surgical complications (28.8%), hypertension (28.3%), coronary atherosclerosis (25.7%), intestinal obstruction (25.6%), renal failure (25.3%), and sepsis (24.5%). Results of the multivariate binomial regression indicated that significantly increased odds of mortality (p<0.05) were particularly associated with comorbidities of heart failure, fluid and electrolyte disorders, paralysis, renal failure, wasting syndrome, respiratory failure, cardiac dysrhythmias, intestinal obstruction, sepsis, and metastases to the bone, liver and other digestive organs. Increased charges and lengths of stay were also associated with several clinical conditions, including various pulmonary diseases, surgical complications, end organ failure, sepsis, metastases, and other comorbidities (p<0.05).

Conclusions: Colon cancer has a large burden of illness among older persons. Continued research that seeks to risk stratify these cases based on comorbid conditions and complications should improve both clinical and economic outcomes in this vulnerable population.

Citation Format: Tomas Nuño, Grant Skrepnek. Predictors of inpatient mortality, charges, and length of stay among the very old with colon cancer in the United States. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A90.
Abstract A95: Overall endometrial cancer survival among non-Hispanic white and Hispanic women: A trend analysis of SEER reported cases 1992-2010
Authors: Rodriguez Ana M. , Do ThuyQuynh Ngoc
Published: October 2015

Objective: To compare demographic and tumor characteristics, treatment, and overall and cancer-specific survival of non-Hispanic White and Hispanic women with endometrial cancer.

Background: Hispanics are one of the fastest growing minority groups in the U.S. Limited research has looked at age distribution, disease presentation, and outcome of endometrial cancer among ethnic minority women.

Methods: We used public use data from the SEER registry between 1992 and 2010. Inclusion criteria included non-Hispanic and Hispanic women who were diagnosed with endometrial cancer after 1992; not missing age, the first course of treatment, lymphadenectomy or lymph node status; and not diagnosed by autopsy or death certificate

Results: A total of 83,904 non-Hispanic and Hispanic patients were analyzed. Factors predictive of overall survival included being U.S.-born Hispanic, year of diagnosis, age at diagnosis, being single or other marital status, stage, histology-based risk, grade, extent of lymphadenectomy, and the first course of treatment. Factors predictive of cancer-specific survival included year of diagnosis, age at diagnosis, marital status, stage, other histology-based risk, grade, extent of lymphadenectomy, and the first course of treatment.

Conclusions: U.S.-born Hispanic women with endometrial cancer exhibited significantly poorer overall survival compared to non-Hispanic white women even after controlling for confounding variables. There was no difference in overall survival or cancer-specific survival between U.S.-born and foreign-born Hispanics compared to non-Hispanic Whites.

Citation Format: Ana M. Rodriguez, ThuyQuynh Ngoc Do. Overall endometrial cancer survival among non-Hispanic white and Hispanic women: A trend analysis of SEER reported cases 1992-2010. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A95.
Abstract A96: African Americans and colorectal cancer: Using multilevel analysis to understand the influence of neighborhood and individual level factors on screening behavior
Authors: Garza Mary A. , Assini Luciana C. , Villacis Gabriella , Ford Jean G.
Published: October 2015

Background: Early detection of colorectal cancer (CRC) effectively prevents premature deaths. However, racial disparities in CRC persist due to underutilization of cancer screening, which is associated with late stage diagnosis and higher mortality rates among African Americans. It is well documented that “…individual behavior both influences and is influenced by the social and physical environment…” Interventions that incorporate the environmental context of the individual behavior are more associated with increasing CRC screening. Methods: Using a community-engaged approach we recruited 230 African American adults aged 50 to 74 years to complete a psychosocial survey. Participants were recruited from a variety of venues, including churches, barbershops, community centers and public housing complexes in the Washington, DC Metropolitan Area. The survey instrument included valid standardized scales designed to assess 1) knowledge of cancer, 2) risk perception, 3) neighborhood perceptions, 4) social support, 5) behavioral risk factors, 6) religiousness and 7) trust in research. Results: Participants were women (80%), married (39%) and low income (34%). Preliminary analysis demonstrated that participants who were midlife (< 60 years of age), unmarried, unemployed and reported no medical home were less likely to be screened for CRC (p<0.01). Additionally, subscale measures for neighborhood perceptions, “social cohesion” (p<0.04) and CRC knowledge were also significantly associated with receiving a CRC screening (p<0.001). Additional analyses (multilevel modeling) are underway, using census data. Conclusions: Understanding the combined effects of individual and neighborhood factors may contribute to the development of scientifically sound and culturally relevant interventions to increase CRC screening among African Americans.

Citation Format: Mary A. Garza, Luciana C. Assini, Gabriella Villacis, Jean G. Ford. African Americans and colorectal cancer: Using multilevel analysis to understand the influence of neighborhood and individual level factors on screening behavior. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A96.
Abstract B50: Elucidating the roles of Kaiso in the metastasis of triple-negative breast cancer cells
Authors: Bassey Blessing I. , Crawford-Brown Catherine , Hallet Robin , Daniel Juliet
Published: October 2015

The triple negative breast cancer (TNBC) subtype represent a subset of breast tumours that lack expression of the estrogen-receptor, progesterone-receptor and human epidermal growth factor receptor-2. Interestingly, TNBC is more prevalent in young women of African ancestry (WAA) than other ethnicities, and WAA have a high mortality despite a low BC incidence compared to Caucasian women. This high mortality rate is attributed to the highly aggressive and metastatic nature of triple-negative tumors and limited treatment options or targeted-therapies. The metastatic nature of TNBC suggests a deregulation of the epithelial-to-mesenchymal (EMT) pathway that is often implicated in tumor progression. During EMT, cells downregulate the tumor suppressor and cell adhesion protein E-cadherin and re-express mesenchymal proteins such as N-cadherin and vimentin, which endow the cells with increased motility. During the course of our characterization of the unique transcription factor Kaiso that was implicated as a potential regulator of E-cadherin, we found that increased nuclear expression of Kaiso is significantly correlated with basal/TNBCs. However, little is known about the role of Kaiso in EMT or TNBC metastasis. Thus, the goal of our research is to elucidate the function of Kaiso in TNBC metastasis. To gain insight into Kaiso's role in TNBC metastasis we generated stable Kaiso-depleted TNBC cells (MDA-MB-231) using a Kaiso specific shRNA. Stable Kaiso-depleted cells were then analyzed for the gene expression profile of key EMT markers and for their migratory and invasive capacities in vitro using wound healing and Matrigel invasion assays. We found that Kaiso is highly expressed at both the transcript and protein level in breast tumor cells and tissues. Kaiso-depletion reduced the migratory and invasive capacities of TNBC cells, and induced the down-regulation of potent E-cadherin regulators including Slug and ZEB1 at both the transcript and protein levels. Interestingly, we observed that Kaiso-depletion also resulted in the downregulation of TGFβR1 and TGFβR2; key effectors of the TGFβ signaling pathway. Since TGFβ signaling is a potent inducer of EMT in late stage breast cancer via up-regulation of Snail and/or Slug and ZEB1/2, our results suggests that Kaiso may be promoting TNBC metastasis via the TGFβ signaling pathway. Kaiso's expression might thus be a useful biomarker for TNBC prognosis.

Citation Format: Blessing I. Bassey, Catherine Crawford-Brown, Robin Hallet, Juliet Daniel. Elucidating the roles of Kaiso in the metastasis of triple-negative breast cancer cells. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B50.
Abstract B54: SR-B1 directed nanoparticles in targeted therapy for the treatment of metastatic triple-negative breast cancer
Authors: Johnson Rebecca , Lacko Andras
Published: October 2015

This study endeavors to fill a void in the treatment of metastatic triple negative breast cancer (TNBC) with the use of scavenger receptor class B type 1 (SR-B1) targeted reconstituted high-density lipoprotein (rHDL) nanoparticles. Though new therapies are being evaluated in clinical trials, TNBC remains an incurable disease. Accordingly, the 5-year survival rate for women with metastatic TNBC is less than 30%. The overall goal of this study is to evaluate the efficacy of Lapatinib (an EGFR inhibitor) and Valrubicin (a topoisomerase II inhibitor) encapsulated rHDL nanoparticles in the treatment of metastatic TNBC. Selective uptake of anticancer agents delivered by rHDL nanoparticles via the SR-B1 is being evaluated using H3 cholesterol ester labeled rHDL nanoparticles in the presence and absence of a chemical inhibitor of SR-B1. Anti-proliferative effects of Lapatinib and Valrubicin encapsulated nanoparticles were evaluated using CCK-8 kits. The findings from these studies revealed that the rHDL encapsulated forms of Lapatinib and Valrubicin had enhanced efficacy when used in combination than the free drugs. In particular, rHDL encapsulated Lapatinib had a 55% increase in efficacy in MDA-MB-231 cell line over the un-encapsulated form as a single agent. The ultimate goal of these studies is to assess the impact of rHDL encapsulated Lapatinib and Valrubicin, alone or in combination against TNBC. One of the major barriers to successful cancer chemotherapy is the development of multidrug resistance (MDR) by malignant tumors. rHDL nanoparticles provide a cytosolic drug delivery mechanism for malignant cells and will likely help to overcome drug resistance by TNBC tumors. In addition, the tumor selective delivery of the drug payload via the rHDL nanoparticles is anticipated to reduce or eliminate off target toxicity to normal tissues upon clinical application.

Citation Format: Rebecca Johnson, Andras Lacko. SR-B1 directed nanoparticles in targeted therapy for the treatment of metastatic triple-negative breast cancer. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B54.
Abstract B70: Perception of contraceptive use among black people infected with prostate cancer in high risk urban poor population in Africa
Authors: Odor King Odor
Published: October 2015

Prostate cancer is a growing public health challenge in Africa, the pandemic affects every individual including healthy person especially the black people. To combat sexually transmitted infections among prostate cancer infected black people, contraceptive-use is effective measure to interrupt any transmission. However, perception of black people about contraceptive usefulness has been limited to research. This study therefore examined prostate cancer among black population in Africa

The study was cross-sectional in design. A multi-stage-stratified-random-sampling technique were adopted to select 400 adults aged 25years and above in Nigeria. A pre-tested questionnaire developed from results of 10 focus-group-discussions (FGD) was used to collect information. FGD and questionnaire data were analyzed thematically and descriptively using chi-square statistics respectively.

Twenty-five percent of the participants who were sexually active, one year preceding the study had multiple premarital-sex. Among the subgroup that had multiple premarital-sex, only few (6.8%) used a contraception in the episode. More males (5.3%) than females (1.5%) used contraception in last premarital-sex (p<0.5). Non-contraceptive use was due to confidence in traditional herbs perceived to prevent prostate cancer. Similarly, FGD participants were unanimous in their opinion visiting tradomedicine dealers and the believe (10.3%) herbs/concussion-use could prevent prostate cancer.

Risky sexual engagement among black people could be a distortion to prostate cancer reduction, because safe sex practices among this population was unimportant based on perception. In order to mitigate prostate cancer in Africa, information on safe-sex practices among young people are needed to address this misconception.

Note: This abstract was not presented at the conference.

Citation Format: King Odor Odor. Perception of contraceptive use among black people infected with prostate cancer in high risk urban poor population in Africa. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B70.