bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B24: Evaluating an intervention to increase cancer knowledge in minority communities in South Carolina
Authors: Ford Marvella E. , Wahlquist Amy E. , Ridgeway Celina , Streets June , Mitchum Katherine A. , Harper Remus , Hamilton Ian , Etheredge Jim , Sweat Melanie A. , Garrett-Mayer Elizabeth
Published: May 2012

Objective: Cancer mortality rates for African Americans in South Carolina are among the highest in the nation. Lack of knowledge likely contributes to cancer disparities. To address this issue, we conducted a community based cancer education intervention to improve cancer knowledge among African American and other minority communities in South Carolina.

Methods: The study was conducted at eight different sites in six counties in South Carolina. The intervention consisted of a 3.5-hour evidence-based cancer education program in which a 3-hour component focused on general cancer knowledge and a 30-minute component focused on prostate cancer knowledge. Pre- and post-intervention surveys were administered immediately before and after the intervention was delivered at each site. The maximum score for the 31-item cancer knowledge instrument was 31. Prostate cancer knowledge was assessed using a 10-item instrument, with a maximum score of 10. Perceived self-efficacy in patient-physician communication about cancer was measured by a 5-item scale with a maximum score of 5. We hypothesized that the intervention would result in increases in general cancer knowledge, prostate cancer knowledge, and perceived self-efficacy in patient-physician interaction.

Results: The study sample consisted of 164 predominantly African American participants. One-hundred and twenty-five (78.6%) of the 159 participants who provided data on race were African American, 19 (12.0%) were Caucasian and 15 (9.4%) were Native American. The majority of the 160 participants who provided data on age were ages 50+ years (62.5%). The majority of the 154 participants who reported their income had an annual household income > = $40,000 (53.8%). The general cancer knowledge pre-test score had a mean of 26.2 with a standard deviation (SD) of 3.7 and a mean post-intervention increase of 2.04 points (p<0.01). The mean pre-test prostate cancer knowledge score was 7.3 (SD 2.0). The mean increase in prostate cancer knowledge was 0.48 points (p<0.01). Due to a ceiling effect, most sites showed little increase in perceived self-efficacy in patient-physician interaction (PEPPI). The exception was the Native American site, which had a larger increase in each PEPPI question from pre-test to post-test than the other sites.

Conclusions: General cancer knowledge scores and prostate cancer knowledge scores increased following the intervention. Future interventions could incorporate more intensive (i.e., repeated sessions) cancer education programs as well as an assessment of the impact of the interventions on the communication dynamics between patients and their health care providers.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B24.
Abstract B25: Feelings associated with research participation influence willingness to take part in epidemiological studies
Authors: Kiviniemi Marc T. , Erwin Deborah O. , Moysich Kirsten , Walker Charles , Davis Warren , Ciupak Greg , Clark-Hargrave Nikia , Congi Kim , Cohen Emily , Primus Alexandra , Posey Patrick , Hallman Elizabeth
Published: May 2012

Purpose: Cancer epidemiology research often involves members of the public as “healthy controls.” Encouraging broad participation in cancer research is a key concern, particularly for research involving members of the general public who may have lower motivation to take part. Most work of individuals' decisions about study participation has focused on expected utility constructs, examining the benefits participants see to participating and the barriers that make participation less likely. Little attention has been paid to emotional decision-making processes in this context. Such emotional processes (e.g., fear about procedures, anger about historical research misconduct) may guide decisions about participation. The purpose of this study was to examine the relation of cognitive and affective decision-making factors to individuals' participation in a epidemiologic study involving both questionnaire completion and blood collection.

Method: Participants (N=46) were community adults in Niagara Falls, NY who were taking part in an educational program about cancer-related research participation. Both prior to and following the educational program, we assessed participants' beliefs about the expected utility of participating in studies that involve questionnaire completion and studies that involve blood collection, the positive and negative feelings they associated with taking part in each type of study, and their willingness to take part in each type of study. Following the post-program questionnaire, participants were offered the opportunity to take part in an epidemiological study in which they could complete a questionnaire, provide a blood sample, or do both.

Results: Both willingness to participate in studies and actual participation was primarily predicted by the feelings individuals associated with research, for both blood draw studies and questionnaire studies, those with more negative feelings about participation were less like to report willingness to take part in the study; questionnaire willingness B=−1.21, p<.05; blood willingness B=−0.97, p<.05. For blood draw studies, affective associations also predicted actual participation; B=−1.15, p<.05.

Discussion: The feelings individuals have about research participation played a central role in determining participation. Both research to better understand determinants of research participation and interventions to increase participation should consider affective factors.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B25.
Abstract B27: Social representations of human papillomavirus (HPV) in Bogotá, Colombia: A qualitative study
Authors: Wiesner Carolina , Acosta Jesús , Díaz del Castillo Adriana , Tovar-Murillo Sandra L. , Salcedo-Fidalgo Hernando
Published: May 2012

Introduction: Identifying DNA of Human papillomavirus (HPV) among asymptomatic women has been proposed as a new screening method for cervical cancer control. Screening programs must be preceded by health education. Traditionally, health education is based on scientific information without considering any community cognitive processes. This paper studies HPV social representations constructed upon social interaction between men and women over 25 years of age, living in Bogotá, Colombia. The outcomes will be used as groundwork for an education strategy to promote HPV testing within a primary screening program.

Methods: It is a qualitative study based upon symbolic interaccionism. Inter individual communication is precisely the ground where a framework of references is constructed and social representations emerge. Focus group selection was planned using a theoretical population sample. Twelve focus groups were held with 124 men and women from diverse educational status. Information source analysis and graphic analysis of significants were performed.

Results: Social representation of HPV involves a series of figurative nuclei that arose from associated meanings linked to scientific information. While women focused on symbols associated to contagion; men focused on its venereal character. Negative feelings were expressed particularly among women with a history of one sexual partner. Figurative nuclei also included long-term uncertainty, need or urgent treatment and feelings of imminent death that are associated to cancer and chronic sexually transmitted infections. The social representation burden of HPV impeded many participants from clearly understanding written information about HPV transmission, clearance and cancer risk.

Conclusion: HPV social representations are built into a whole framework of values, which must be deconstructed to allow women full participation in HPV screening programs and to prevent psychosocial adverse effects. Delivering scientific information may not be enough for achieving this purpose. Shared decision making is a communication strategy that must be promoted for anticipatory discussion on HPV-DNA testing to be able to deconstruct different values and meanings particularly its association with promiscuity and venereal diseases.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B27.
Abstract B3: Effect of consuming pistachios on the intake and serum levels of γ-tocopherol
Authors: Hernandez Ladia M. , Forman Michele R. , Radcliffe John D.
Published: May 2012

Pistachios are one of the best dietary sources of gamma-tocopherol (γ-T), a form of vitamin E that may help to protect against certain forms of cancer, such as lung among high risk groups like smokers. We investigated the effect of the incorporation of pistachios (at a level of 68 g per day) on the intakes and serum cholesterol-adjusted γ-T (micromole/millimole) using a six-week randomized, controlled, clinical trial design, having a two-week preintervention period and a four-week intervention period. Participants (n = 36) were healthy males and females, randomized to either the control group or the intervention group. Intakes were calculated using the Nutrition Data System for Research Version 2007. Diet diaries and weights of returned pistachios were reviewed to assess consumption. Weekly compliance for pistachio consumption ranged between 88-93%. No statistically significant treatment differences were observed for BMI, total energy or percent energy from protein. On the pistachio diet (PD), statistically significant increases were seen for percent energy from fat at weeks 3 and 4 and weeks 5 and 6 compared to weeks 1 and 2. Additionally, on the PD, a statistically significant increase for percent energy from fat was seen at weeks 5 and 6 compared to the control diet (CD). On the PD, statistically significant decreases were seen for percent energy from carbohydrate at weeks 3 and 4, and weeks 5 and 6 compared to weeks 1 and 2. Additionally, on the PD, a statistically significant decrease for percent energy from carbohydrate was seen at weeks 5 and 6 compared to the CD. On the PD, statistically significant increases were seen in energy-adjusted dietary γ-T at weeks 3 and 4 compared to weeks 1 and 2 (mean difference of 26%; p < 0.001), weeks 5 and 6 compared to weeks 1 and 2 (mean difference of 27%; p < 0.001). Additionally, statistically significant increases in energy-adjusted dietary γ-T were seen at weeks 3 and 4 on the PD compared to the CD (mean difference of 21%; p < 0.001) and at weeks 5 and 6 on the PD compared to the CD (mean difference of 24%; p < 0.001). On the PD, a statistically significant increase was observed for post intervention cholesterol-adjusted serum γ-T (mean difference of 26%; p < 0.001) compared to pre-intervention value. For the intervention group, a Pearson correlation was calculated for the change in energy-adjusted γ-T intake between weeks 1 and 2 and weeks 5 and 6 and the change in cholesterol-adjusted serum γ-T pre- and post intervention (r =.373; p =.025). Thus, consumption of pistachios can lead to an increase in serum levels of γ-T. Pistachios could be incorporated into dietary strategies designed to reduce the risk of lung cancer.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B3.
Abstract B30: Patient navigation for cervical cancer in Kentucky: Baseline results
Authors: White Carol , Dignan Mark , Slone Stacey , Gomez Maria , Jones Kate
Published: May 2012

Background: Although morbidity and mortality rates are low compared to other types of cancer, cervical cancer remains a high priority for the following reasons: 1) invasive cervical cancer is a disease that could be prevented in nearly all cases, with greater use of the Pap test; 2) the Pap test is a well-established, low cost, widely available screening test that should present minimal barriers to its use; and 3) despite our ability to prevent and treat cervical cancer, the burden of cervical cancer morbidity and mortality continues to be higher among low-income women with limited education, many of whom reside in rural areas. Despite public health recommendations for cervical cancer screening and follow-up of abnormal Pap test results, adherence is still low among rural Appalachian women in Kentucky. In response to this concern, the University of Kentucky Prevention Research Center is implementing a National Cancer Institute-funded project that is integrating patient navigators (PN) in cervical cancer screening programs in several rural health departments.

Goal: To reduce the disproportionate burden of cervical cancer experienced by rural Appalachian women in Kentucky.

Objectives: To: 1) improve our understanding of the barriers to follow-up; 2) recruit, train, and utilize lay health workers as PNs in cervical cancer screening programs; 3) increase the proportion of women who adhere to recommended follow-up; and 4) evaluate the efficacy of the intervention.

Method: Intervention activities are as follows: 1) nurse case managers refer patients with abnormal pap tests to PNs in selected local health departments in Big Sandy, Lake Cumberland, and Kentucky River Area Development Districts; 2) PNs enroll patients in the study; 3) study participants complete a baseline interview; 4) PNs provide navigation services including outreach, education, and support; 5) PNs conduct follow-up interviews; and 6) PNs document follow-up recommendations, barriers, patient needs, and specific actions taken to ensure adherence to follow-up recommendations.

Evaluation: To assess the efficacy of the intervention, outcome data will be collected from health department records in intervention and control counties.

Findings: The total number of referrals to date is 600. Among the referrals: 82 (14%) were ineligible (patient less than 18 years, refused services, dropped by health department for non-compliance, or lost to follow-up); 379 (63%) were offered enrollment; and enrollment is pending for 139 (23%). Among those offered enrollment, 297 (78%) agreed to participate in the study. Additional preliminary findings will be presented including reason for referral, characteristics of women enrolled, patient needs, adherence to follow-up, etc.

Conclusions: The program creates a unique opportunity to support rural cervical cancer screening programs, ensuring women obtain their recommended follow-up care through the support of PNs.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B30.
Abstract B33: Reducing the ethnic/minority cancer burden in communities in S.E. Michigan utilizing a community-based participatory process
Authors: Dykes Vicky A. , Akhtar Adil , Berry Stanley , Jaiyesimi Ishamael , Douglas-Nikitin Vonda , Rivers Aeisha , Shetty Sugandh , Vicini Frank A. , Fakhouri Monty
Published: May 2012

Purpose: We reviewed the impact of a community based participatory process (CBPP) addressing cancer education, prevention, and screening in five major ethnic/minority populations in Southeastern Michigan to determine their impact on personal health related decisions.

Materials and Methods: From 2003 to 2009, 2,988 community members participated in CBPP conducted by Beaumont Cancer Institute in collaboration with the Arab American and Chaldean Council, Michigan Association of Physicians from India, North American Indian Association, American Indian Health and Family Services, Mexican Consulate, Multicultural La Famila, National Cancer Institute, and American Cancer Society. The study population consisted of 1,253 (42%) individuals completing a post-cancer forum survey and/or obtaining some type of cancer screenings: 747 (59.6%) from African American, 425 (33.9%) from Arab American/Chaldean, 14 (1.1%) from Native American, 35 (2.8%) from South East Asian and 32 (2.6%) from Hispanic/Latino communities. Data were collected on behavioral intent and knowledge including: (1) forum content, (2) participants' cancer screening history, (3) symposium logistics (4) educational materials and (5) participation in subsequent cancer screening tests.

Results: After attending at least one cancer forum, 426 (34%) of 1,253 respondents (14.3 % of all attendees) underwent some type of cancer screening: 146 women (11.7%) underwent a screening mammogram, 94 (7.5%) a pap smear and 97 (7.7%) men underwent a screening PSA. A total of 89 (7.1%) had other forms of cancer screenings.

Conclusions: Results from this study suggest that CBPP's around a perceived and/or serious disease negatively affecting a target population can positively impact their personal health related decisions.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B33.
Abstract B39: Prostaglandin E2 induces human enhancer of filamentation 1 to promote the cell motility of colorectal carcinoma cells
Authors: Xia Dianren , Wang Dingzhi , Menter David G. , DuBois Raymond N.
Published: May 2012

PGE2 promotes cell motility during colorectal carcinogenesis. The mechanism by which PGE2 signaling regulates cell motility is not completely understood. Here, we demonstrated that PGE2 treatment induces HEF1 expression that links with cell motility in colorectal cancer cells. PGE2 rapidly stimulated HEF1 expression in colorectal cancer cells. Both PGE2 treatment and HEF1 overexpression activated Rac 1 and resulted in similar effects on cell spreading. Moreover, knockdown of HEF1 using shRNA suppressed PGE2-driven cell spreading. PKA activator forskolin induced HEF1 expression and cell spreading in a similar manner as PGE2. Inhibition of PKA activity by H-89 attenuated HEF1 expression induced by PGE2. Furthermore, PKA knockdown by siRNA blocked the HEF1 expression and cell spreading induced by PGE2. These data suggest that PGE2 induces HEF1 expression to promote cell motility through a PKA-involved pathway.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B39.
Abstract B42: Modulation of integrin-mediated cell adhesion by ADAM15 disintegrin-like domain
Authors: Lee Hee Doo , Park Michael Y. , Jeon Ok-Hee , Kim Doo-Sik
Published: May 2012

Integrin-mediated cell adhesion on extracellular matrix works essentially on numerous physiological processes such as cell adhesion, migration and angiogenesis. As integrin ανβ3 and integrin α5β1 are the representative receptors for cell adhesion and due to their important function in cancer biology, the antagonists targeting the integrins has been sought for long. Lately, the interactions between ADAM (A Disintegrin And Metalloprotenase) 15, the only member in ADAM family with Arg-Gly-Asp (RGD) motif, and the ανβ3 and α5β1 intergins was observed. For that, we experimented on the cellular function of recombinant ADAM15-derived disintegrin-like domain containing Asp-Typ-Lys-Arg-Gly-Asp (rNWKRGD) in integrin-mediated cell adhesion. The binding affinity of HUVEC, COS-1, MCF-7 and MDAH 2274 cells to various extracellular matrix proteins were increased by the disintegrin-like domain in a dose-dependent manner, and the presence of inhibitory integrin α5β1 antibody thoroughly abrogated the rNWKRGD-stimulated binding. By mutagenic analysis, it was founded that RGD motif is essential for the binding. In comparison, saxatilin, RGD disintegrin from snake venom, inhibited binding of cells to ECM proteins. Through flow cytometric analysis, we confirmed that β1 integrin on the cell surface was activated by rNWKGRD. All these results indicated that the activation of integrin α5β1 mediates the rNWKRGD-stimulated cell adhesion. Therefore rNWKRGD could function as the potential activator of cell migration and proliferation. Although disintegrin is known as inhibitor of cell migration and proliferation, it is possible that ADAM15 disintegrin domain could have a regulatory role in integrin function such as angiogenesis and invasion of cancer cells. (This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (No. 2009-0081759), KIST grant, and the Brain Korea 21 (BK21).)

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B42.
Abstract B45: Identification of chromosome aberration of oral squamous cell carcinoma patients in southern India
Authors: Manikantan Pappuswamy , Balachandar Vellingiri , Sasikala Keshavarao , Mohanadevi S. , Lakshmankumar Balasubramanium , Velmurugan Palanivel , Prabudhas K.
Published: May 2012

Oral squamous cell carcinoma (OSCC) is the most frequent cancer and constitutes a major health problem in India, representing the leading cause of death. The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation, inversion and mosaic in OSCC patients of South India. Genetic factors play an important role in the etiology of OSCC. Totally 300 oral sumucosa fibrosis symptoms patients were chosen from various hospitals from southern india by advent screening like Toluidine blue staining and brush biopsy. Finally 103 severely affected OSCC patients were selected. 5ml of peripheral blood samples were taken from affected patients. Equal numbers of normal healthy control subjects were chosen after signing a consent form. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by spectral karyotyping (SKY) technique. In the present investigation, major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. Results showed frequent CA in chromosomes 3p, 3q, 8p, 7p, 9p, 11q, 17p, 19q and X. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P<0.05). In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the centromere in OSCC tumorigenesis, interesting chromosomal regions which may harbor susceptibility genes. Identification of chromosome alterations may be helpful in understanding the molecular basis of the disease in a better manner.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B45.
Abstract B46: Celecoxib induces autophagy and apoptosis in human colorectal cancer cells: Strategies to enhance cell death
Authors: Huang Shengbing , Sinicrope Frank A.
Published: May 2012

Purpose: Celecoxib has been shown to induce cell death in conjunction with its chemopreventive effects. However, the mechanisms by which celecoxib induces cell death are incompletely understood. We determined whether celecoxib can induce autophagy, a process of cell destruction whereby cytoplasmic proteins and organelles are sequestered in vacuoles and delivered to lysosomes for degradation and recycling. Both apoptosis and autophagy have been shown to be negatively regulated by pro-survival Bcl-2 proteins, and the small molecule Bcl-2/Bcl-xL antagonist (ABT-737), can enhance both processes. Since autophagy can be pro-survival or pro-death depending upon the cellular context, we determined whether autophagy inhibition can drive colon cancer cells into apoptosis.

Methods: HCT116 (wild-type and Bax−/−), HT29, SW480 colorectal cancer cell lines were treated with celecoxib (0–120 µM) and/or ABT-737 (Abbott; 0–5 µM) in the presence or absence of a pan caspase inhibitor, z-VAD-fmk. Cell viability was determined using the MTS assay and apoptosis was analyzed by Annexin V FITC labeling. Immunoblotting was used to analyze caspase cleavage and LC3 conversion. GFP-LC3B cellular localization was determined by confocol microscopy. Autophagic flux was determined by LC3 immunoblotting in the presence of the lysosome inhibitor, bafilomycin A1. Knockdown of Bcl-xL, Vps34 or Atg8/LC3B were achieved by lentiviral shRNA or siRNA.

Results: Celecoxib was shown to induce apoptosis that was attenuated by ectopic Bcl-2 or Bax knockout. ABT-737 synergistically enhanced celecoxib-induced apoptosis as shown by caspase cleavage and Annexin V labeling. Celecoxib also induced autophagy, as shown by conversion of the autophagosome-associated protein light chain 3 (LC3) from a cytosolic (LC3I) to a membrane-bound (LC3II) form as shown by immunoblotting, and a punctate fluorescence pattern of ectopic GFP-LC3 protein. Celecoxib-induced conversion of LC3 that was due to autophagy induction, as shown using the lysosome inhibitor, Bafilomycin A1 that produced an accumulation of LC3II. Furthermore, ABT-737 enhanced LC3 conversion by celecoxib. Autophagy inhibition was achieved using 3-methyladenine (3-MA), wortmannin or knockdown of Vps34 or Atg8/LC3B using siRNA. Inhibition of autophagy enhanced apoptosis as shown by caspase cleavage and Bid truncation in cells treated with celecoxib plus ABT-737. Furthermore, the addition of 3-MA to celecoxib plus ABT-737 produced a 5-fold increase in apoptosis that was associated with caspase cleavage and cytochrome c release.

Conclusions: Celecoxib induces both apoptosis and autophagy that can both be potentiated by ABT-737. Inhibition of autophagy was shown to potently drive cells into apoptosis, suggesting a novel therapeutic strategy against colon cancer cells.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B46.
Abstract B52: MicroRNAs and SEL1L gene regulation in human pancreatic ductal adenocarcinoma
Authors: Liu Qian , Chen Jinyun , Amos Chris , Killary Ann , Sen Subrata , Frazier Marsha
Published: May 2012

Pancreas-specific tumor suppressor gene SEL1L is downregulated at both the mRNA and protein levels in a significant proportion of human pancreatic ductal adenocarcinoma (PDAC) cases. We sought to use statistical methods to determine if one or more aberrantly upregulated microRNAs (miRNA) are responsible for the repression of SEL1L, which would help elucidate the role of specific miRNAs in PDAC.

Based on published microRNAs microarray data and miRNA targets prediction resource, we initially identified seven miRNAs for our study which were reported to be upregulated in PDAC and potentially target SEL1L. Using real-time PCR, we quantitatively assessed the expression levels of SEL1L mRNA and these miRNAs in 42 pairs of PDAC samples and matched normal adjacent tissues. Fisher's Exact Test and Kruskal-Wallis Test were applied to evaluate the correlation between SEL1L and the miRNAs.

Our results showed that the expression of SEL1L mRNA inversely correlates with the expression of 3 miRNAs (P < 0.0001, P < 0.0001 and P = 0.002, respectively). As the number of these overexpressed miRNAs increase from 0 to 3, we observed progressively increasing downregulation of SEL1L (P − trend = 0.001).

Our findings suggest that the 3 miRNAs work cooperatively to repress SEL1L mRNA expression. These specific miRNAs may serve as useful biomarkers for PDAC.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B52.
Abstract B56: Regulation of immune-related genes by integrin signaling affects the cancer cell proliferation and invasion
Authors: Park Michael Y. , Lee Hee Doo , Jeon Ok-Hee , Kim Doo-Sik
Published: May 2012

Cytokines have been implicated in tumor proliferation and metastasis. Saxatillin, snake venom-derived disintegrin, is known to suppress tumor progression in vivo and in vitro but its correlation with cytokine's functions has not been known yet. We have investigated the role of immune-related genes in cancer cell proliferation and metastasis in human ovarian cancer cell (MDAH 2774). We demonstrate that saxatilin, an integrin antagonist, mitigated MDAH 2774 proliferation and invasion by reducing the level of TNF- induced matrix metalloproteinase-9 (MMP-9) and IL-8 expression in a dose-dependent manner. And Immunoblot assay of nuclear extracts of the cancer cells implicated that signal transducer and activator of transcription (STAT) is related in integrin signaling pathway. We also observed the activity of human glioma cell-invasion mediated by IL-8, as examined by a Boyden chamber assay, involved the mechanism of enhancing the actin stress fiber formation. IL-8 increased the phosphorylation of focal adhesion kinase (FAK), known to be the site of integrin clustering and nuclear translocation of STAT. We have shown here that interleukin-8 promotes the cancer proliferation and that mRNA levels of immune-related genes are regulated by disintegrin in human ovarian cancer cell line. These results demonstrate immune-related genes as a mediator of metastasis and proliferation and disintegrin would contribute in slowing of cancer development by regulating integrin signaling. (This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea Government (No.2009-0081759), KIST grant, and the Brain Korea 21 (BK21) program.)

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B56.
Abstract B58: Gene expression study on a highly aggressive canine transmissible venereal tumor of a NOD/SCID mice model
Authors: Chu Reamin , Lei Hang-Rong , Lin Cheng-Se , Lin Cheng-Se , Lee Chien-Yueh , Yeh Lih-Seng , Chang Shih-Chieh
Published: May 2012

We have set up a xenograft NOD/SCID mice model bearing canine transmissible venereal tumor (CTVT) (designated as MCTVT). In addition to the similarity of the tumor cells between CTVT and MCTVT, the insertion of the specific gene fragment in the 5′ end of c-myc characteristic for a CTVT cell was also confirmed in MCTVT. However, as inoculating back to dogs, the MCTVT showed a much more aggressive growth and much higher metastatic frequency than a common CTVT. The goal of this research was to explore the gene expression differences between CTVT and MCTVT, and tried to delineate the mechanisms of their growth pattern differences. The differential gene expressions between the 2 tumors were studied using Affymetrix. Studied by hierarchical analysis and filtering the differential expressed genes by 2-fold method, we have found 105 genes significantly up-regulated and 37 down-regulated in MCTVT comparing to CTVT. Many of these genes were previously published to be involved in the areas such as malignant candidate genes, important biological processes, tumor development and immune modulation. We then used Real-Time RT-PCR to study the top 30 up-regulated genes. Three genes (APOC1, MMP1 and KMO) were further confirmed that were significantly up-regulated in MCTVT. The three genes were then tested in 22 spontaneous canine mammary gland tumors (CMGT) using Real-Time RT-PCR, the results indicated that two out of the three up-regulated genes discriminated malignant from benign CMGT and their gene expression was significantly higher in grades 4 and 5 malignant CMGT than those from lower grade tumors. We are currently studying the activities of KMO in association with the tumor cell growth. This study presented the novel candidate gene (KMO) that might associate with the malignant growth of tumor cells and has potential to be used as a biological marker to differentiate degrees of malignancy.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B58.
Abstract B59: Induction of TXNIP in response to metabolic changes associated with loss of p53
Authors: Wheatley Karrie , Nogueira Leticia , Perkins Susan N. , Hursting Stephen D.
Published: May 2012

The understanding of the function of p53 has expanded beyond its role as a master cell cycle regulator. Recent findings connect p53 to cellular metabolism in that it suppresses anaerobic metabolism, the preferred mode of ATP production of most transformed cells. Interestingly, the p53-inducible genes that modulate metabolism also alter production or scavenging of reactive oxygen species (ROS). To better understand the metabolic changes that occur in response to p53-deficiency, we compared the expression of genes related to oxidative stress in the mammary fat pad of p53 +/+ and p53 +/− female mice. From a qPCR array that measured the expression of 85 genes, thioredoxin-interacting protein (TXNIP) levels were markedly increased in the p53 +/− mice compared to p53 +/+ mice (n = 3/group). This gene is of particular interest because TXNIP expression is increased by glucose flux and binds reduced thioredoxin, resulting in accumulation of ROS which has been shown to activate p53. To validate this finding, qPCR was performed (n=6/group) and TXNIP mRNA expression was increased 2.6 ± 0.2 fold (p < 0.001) in the mammary fat pad of p53 +/− mice compared to p53 +/+ mice. Importantly, the p53 +/− mice exhibited significantly lower fasting glucose levels than 53 +/+ mice (104.2 ± 7.0 versus 128.5 ± 3.1 mg/dL, p <0.01). We hypothesized that induction of TXNIP is in response to metabolic changes occurring with loss of p53. Using siRNA to knockdown p53, we tested this hypothesis and found that TXNIP mRNA expression increased 2.4 ± 0.3 fold (p < 0.01) 72 hours after p53 knockdown compared to control cells receiving scrambled siRNA. Furthermore, this increase was preceded by a spike in glucose consumption and lactate production. From these data, we conclude that TXNIP, in the absence of p53, is responding to changes in cellular metabolism. Current experiments are aimed at determining the effect of TXNIP induction in MCF7 cells on proliferation and glucose metabolism.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B59.
Abstract B60: HPP1-mediated tumor suppression and interferon signaling
Authors: Hernandez Jonathan M. , Elahi Abul , Shibata David
Published: May 2012

Interferon resistance is common to the majority of cancer cell lines and primary tumors, and confers increased tumorigenicity and evasion of immune surveillance. HPP1, a recently characterized tumor suppressor gene associated with STAT1 signaling, is silenced in the majority of colorectal neoplasms. We have sought to determine if HPP1's tumor suppressive effects are mediated by interferon-associated pathways and whether HPP1 is capable of restoring sensitivity to interferon. We have overexpressed HPP1 in the HCT 116 colorectal cancer cell line and, by microarray analysis, have demonstrated that ectopic expression of HPP1 resulted in a dramatic upregulation of STAT1 as well as a number of associated interferon-inducible genes. We have previously shown that downregulation of STAT1 by siRNA in HPP1 transfectants results in a restoration of growth potential. Given that STAT1 homodimers bind specifically to promoter GAS (gamma activating sites) sites causing transcriptional upregulation of target genes, we transfected luciferase GAS reporter (pLucGAS) and control plasmids into HPP1 and control transfectants. Overexpression of HPP1 was associated with a significant increase in GAS site binding (p=0.007), suggesting that HPP1 mediates tumor suppression via its association with Type II-like (gamma) interferon pathways. To investigate the importance of Type II-like pathways, we treated HCT 116 cells, with and without overexpression of HPP1, with increasing doses of interferon gamma. Induction of activated STAT1 (phosphoSTAT1), was demonstrable in HPP1-overexpressing transfectants with a progressive rise concordant with interferon dose escalation. Interferon gamma was unable to induce any augmentation of activated STAT1 in controls. Despite progressive induction of phosphoSTAT1, no significant alterations in proliferation, apoptosis or cell cycle distribution were observed with interferon gamma treatment of HPP1 transfectants. We conclude that activated STAT1 and Type II-like interferon-associated pathways are important in mediating the tumor suppressive effects of HPP1. The lack of additional anti-proliferative effects of interferon on HPP1 transfectants may be due to saturation of the pathway. However, further investigation of the role of other STAT1-associated mechanisms in HPP1 tumor suppression, such as the Type I-like interferon (alpha) pathway is warranted.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B60.
Abstract B66: Aggressiveness of MMTV-Wnt-1 mammary tumors corresponds with enrichment of a CD44+/CD24− putative cancer stem cell population
Authors: Smith Sarah M. , Chiao Lucia J. , Salcido Crystal D. , Varticovski Lyuba , Hursting Stephen D.
Published: May 2012

MMTV-Wnt-1 transgenic mice develop heterogeneous mammary tumors that accurately recapitulate human basal-like breast cancer. Additionally, targeted alterations in the Wnt signaling pathway in mammary epithelial cells preferentially induce mammary cancers from progenitor cells. Therefore, we hypothesized that MMTV-Wnt-1 mammary tumors harbor cells with cancer stem cell characteristics. To test this hypothesis, we characterized (in vitro and in vivo) two newly generated, clonal mammary epithelial cell lines (WA4 and WG4) from a MMTV-Wnt-1 transgenic mouse tumor. The cell lines were analyzed using flow cytometry for CD44 and CD24 cell surface markers (a CD44+/CD24− profile is indicative of putative human and murine mammary cancer stem cells), mammosphere formation (low density seeding on non-adherent plates in stem-cell media), in vitro scratch assay (to measure wound healing), and by an in vitro Matrigel invasion chamber assay (to quantitate cell invasion). Finally, unsorted WA4 and WG4 cell lines were transplanted into syngeneic mammary fat pads of C57BL/6 mice (1×10^7 cells/mouse; n=5/cell line), and tumor burden was assessed after 3 weeks. Flow cytometric analysis demonstrated that the percentage of CD44+/CD24− cells was 62.2% in the WA4 line and 2.4% in the WG4 line. Serum starvation enriched the WA4 line for CD44+/CD24− cells (from 62.2% to 82.0%), without altering the composition of the WG4 line. Approximately 30% of unsorted WA4 cells, but <1% of unsorted WG4 cells, formed mammospheres. Additionally, the WA4 line showed increases in wound healing by scratch assay and significant increases in invasion (226-fold increase versus WG4 cells after 30 hours). In vivo, the WA4 cell line was associated with larger, more aggressive tumors on average (+SD) than the WG4 line (2.09 +/−0.68 g and 0.03 +/−0.02 g, respectively, p<0.0001). WA4 tumors were characterized by increased cellular proliferation, microvascular proliferation, and a basal appearance lacking ductal structures. In conclusion, MMTV-Wnt-1 transgenic mouse mammary tumors harbor a CD44+/CD24− putative cancer stem cell population, and an increased percentage of this population corresponds with a more aggressive tumor phenotype.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B66.
Abstract B67: Influence of black cohosh and its isolated triterpenes on tamoxifen-induced endometrial cell proliferation
Authors: Dietz Birgit M. , Hagos Ghenet K. , Yao Ping , Lantvit Daniel D. , Chen Shao-Nong , Goedecke Tanja , Farnsworth Norman R. , Pauli Guido F. , Bolton Judy L.
Published: May 2012

The selective estrogen modulator tamoxifen has been proven efficacious in the treatment and prevention of breast cancer. However, tamoxifen treatment leads to consequences of estrogen deprivation including inducing menopausal hot flashes. In addition, tamoxifen causes enhanced endometrial cell proliferation resulting in an increased endometrial cancer risk. The latter effect is thought to be due to pro-estrogenic effects specific to the endometrium. The botanical dietary supplement black cohosh (Cimicifuga racemosa) is frequently used for the alleviation of hot flashes in this high-risk population. Black cohosh extracts contain antioxidative, antiproliferative, anti-inflammatory, and detoxification enzyme inducing compounds. We therefore analyzed whether a standardized black cohosh extract or its isolated compounds prevent tamoxifen induced endometrial cell proliferation. First, we analyzed the influence of black cohosh on the proliferation in the Ishikawa endometrial cancer cell line with and without tamoxifen. At concentrations of 30 µg/mL black cohosh significantly decreased endometrial cell proliferation as measured by the SRB assay in the presence as well as in the absence of tamoxifen. Assaying various black cohosh fractions and isolated compounds revealed that a small sub-fraction of the triterpenes contained within black cohosh were responsible for the observed activity. Both, the extract and its sub-fraction, induced G1 cell cycle arrest. Next, we analyzed the influence of black cohosh extract on tamoxifen induced endometrial cell proliferation in an immature rat model. The results demonstrated that black cohosh extract did not influence tamoxifen's uterotrophic activity in vivo suggesting that the concentrations achieved in vivo with commonly used black cohosh doses are too low for this effect. Further analysis is ongoing to explore the potential of the isolated active compounds in preventing tamoxifen enhanced endometrial cancer risk.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B67.
Abstract B68: Pomegranate extract inhibits growth and viability of human pancreatic cancer cells in vitro
Authors: Nair Vidhya R. , Dai Zhaoli , Khan Maruf , Ciolino Henry P.
Published: May 2012

Pancreatic cancer is highly resistant to chemotherapeutic agents, and therefore new therapeutic and chemopreventive agents are needed. In the present study we examined the effect of pomegranate extract (PE) on human pancreatic cancer cells in vitro. We studied two human pancreatic cell lines, the aggressive AsPC line derived from pancreatic adenocarcinoma, and the slow growing PANC-1 cell line derived from pancreatic epitheloid cell carcinoma. PE inhibits proliferation in both the cell lines in a concentration-dependent manner, with an IC50 of 100 (both cell lines) µg per ml of culture medium. PE caused a concentration-dependent cell cycle arrest in G2/M in AsPC cells. Higher concentrations of PE were cytotoxic to both cell lines, with an IC50 of 250 (AsPC) and 150 (PANC-1) µg per ml of culture medium. There was a concentration-dependent increase in caspase-3 activity in both cell lines, suggesting that PE induces apoptosis. These results are the first demonstration of an inhibitory effect of PE on human pancreatic cancer cells, and suggest that PE holds promise for further development as a chemopreventive and chemotherapeutic agent against pancreatic cancer.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B68.
Abstract B70: Berberine, a putative bioactive compound from traditional herbal plant, induces apoptosis in MCF-7 breast cancer cells through p53 activation and mitochondrion-dependent pathway
Authors: Jeevitha Patil , Kim Jinhee , Kumar Pratap , Jayaprakasha G. K.
Published: May 2012

Plant bioactive compounds found in many plant species have been used in Chinese, Unani, and Indian ayurvedic medicine. Accumulative evidences in both in vitro and in vivo studies using berberine seem to play anti-cancer and anti-inflammatory roles in different cancer cells. Previous research suggested berberine to exhibit potential anticancer activities in the various cancer cell lines. In the present study, we have isolated a putative compound from Phellodendron amurense using methanol and purified by chromatographic techniques. The structure of the isolated compound was identified as berberine by 2D NMR and mass spectral data. The isolated berberine was tested against MCF-7 breast cancer cell line and the MCF-12f normal breast epithelial cell line for 24, 48 and 72h at various concentrations (0, 12.5, 25, 50, 100, and 200µM). Using the MTT cell viability assay, berberine has demonstrated a significant cytotoxic effect on the MCF-7 cell line (p <0.05) in a time and concentration dependent manner. However, the same alkaloid did not show an effect on the proliferation of the MCF-12f normal cells. The induction of apoptosis or debilitation of cancer cells without causing excessive damage to normal cells by any natural putative compound is a key target for identifying methods of cancer prevention and therapy. Based on these results, MCF-7 cells treated with 25µM berberine for 48 and 72h were used for further studies to illustrate a time dependent induction of apoptosis with flow cytometry and agarose gel electrophoresis to identify visible DNA fragmentation. Western blotting with treated cells revealed that berberine induces apoptosis in MCF-7 cells through a mitochondrion-dependent pathway by increasing levels of pro-apoptotic protein, Bax, cytoplasmic cytochrome c, caspase-9 activity and cleavage of PARP while decreasing levels of anti-apoptotic protein, Bcl-2. Immunoblotting also suggests that p53 plays a pro-apoptotic role in berberine treated cells. We conclude that berberine inhibits the proliferation of MCF-7 breast cancer cells through an apoptotic pathway which may serve as a potential compound for cancer prevention or therapy. Further studies are needed to elucidate specific mechanism of action of this putative compound in breast cancer cells.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B70.
Abstract B71: Phellodendron bioactive molecule (PBM): A potential natural agent for prevention of colon cancer
Authors: Chidambara Murthy Kotamballi N. , Kumar Addanki Pratap , Jayaprakasha G. K. , Patil Bhimanagouda S.
Published: May 2012

PBM is a yellow colored compound isolated from extracts of Phellodendron species. In the current study, PBM was subjected to understand the effect on colon cancer using human cancer cell lines. The activity was studied using three cancer cells having different degree if malignancy induction namely, SW-480, HT-29 and Caco-2 cells. The colon fibroblast (112CoN) cells, which are non cancerous were used to understand the toxicity of compound. The cell viability assay of PBM demonstrated both dose and time dependent activity in all the cells. This naturally occurring compound was found be effective after 24 h of treatment (IC50 value at 12 h was more than 75 µM) showing minimum IC50 against SW-480, which was 24, 16 and 5 µM at 24, 48 and 72 h, respectively. The IC50 was in the range of 42–50 µM for HT-29 cells and 18–53 µM for Caco-2 cells. Furthermore, the toxicity to normal cell was not significant indicating the non-toxicity compound at 100 µM in the model. Treatment at 10 µM has shown induction of aneuploidy (35±2% of cells) in SW-480 cells and treatment at 25 and 10 µM has increased accumulation of cells in G0/G1 phase. Protein expression results suggest that, PBM is capable of inhibiting cancer through inducing caspases dependant apoptosis in case of SW-480 cells. The inhibition was also found to be through inhibiting inflammatory proteins. Both the apoptosis and anti-inflammatory activity were higher at 48 and 72 h of treatment. Result of the current study provides an evidence for inhibition of colon cancer by PBM through multiple targets such as cell cycle arrest, apoptosis and inhibition of inflammation. In summary, PBM may be an ideal compound to be considered for in vivo studies to explore its application in colon cancer prevention. This project is based upon work supported by the USDA-CSREES # 2009-34402-19831 “Designing Foods for Health” through the Vegetable and Fruit Improvement Center.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B71.
Abstract B74: Phenethyl isothiocyanate and 4-phenylbutyl isothiocyanate inhibit the proliferation and viability of human renal carcinoma cells in vitro
Authors: Khan Maruf , Ciolino Henry
Published: May 2012

Epidemiological studies have demonstrated a protective association between dietary intake of cruciferous vegetables and the incidence of renal cell carcinoma. Isothiocyanates (ITCs) are a class of sulfur-containing phytochemicals found uniquely and abundantly in cruciferous vegetables (broccoli, cauliflower, brussel sprouts, etc). We hypothesize that the inhibition of renal carcinoma cell growth and viability by ITCs underlies the protective effect of cruciferous vegetables on renal cell carcinoma. To test this hypothesis, we examined the effects of two ITCs: the naturally-occurring phenethyl ITC (PEITC) and the synthetic 4-phenylbutyl ITC (PBITC) on the Caki-1 human renal carcinoma cell line. Both PEITC and PBITC inhibited the proliferation of Caki-1 cells in a concentration-dependent manner. Cell cycle analysis revealed that PEITC and PBITC caused an arrest in the G2/M phase. Additionally, higher concentrations of PEITC and PBITC were cytotoxic to Caki-1 cells (IC50 of 7.0 and 4.8 µM, respectively). PEITC and PBITC induced caspase-3/7 activity in a concentration- and time-dependent manner, indicating that the ITCs induce apoptosis in the cells. These results indicate that PEITC and PBITC may be efficacious against renal cell carcinoma and suggest that the preventive effect of diets rich in cruciferous vegetables is due to their ITC content.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B74.