bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A53: Apoptosis initiated in colon cancer cells when treated with muscadine grape extract
Authors: Hannah Lane , Brown Vondina , Ranwala Damayanthi , Wargovich Michael 
Published: May 2012

Abstract
A53
Research suggests strong correlations between the inflammation process and colon cancer progression, making it an attractive target for anti-inflammatory drugs and compounds. Muscadines (Vitis rotundifolia), a grape species native to the Southeastern United States, are rich in polyphenols containing many biologically important flavonoids that may have potential anti-inflammatory and anti-oxidant properties. Current research has shown that the muscadine grape has a higher total phenolic and flavonoid content than commercially available red grapes. A hallmark of progressive colon cancers is disruption of different signaling pathways leading to increased proliferation and escape from apoptotic mechanisms. We hypothesize that extracts containing high levels of biologically important polyphenols from the muscadine pomace would induce cell cycle arrest and apoptosis in HT-29 and HT-15 colon cancer cell lines. Polyphenolic compounds were extracted from muscadine pomace using 80% methanol in 6N hydrochloric acid at 60ºC. Whole concentrated extract (WCE) was fractionized using an Oasis HLB column to yield three different muscadine fractions (MF). We compared the cytotoxic effects of both cell lines when treated with WCE versus three different muscadine fractions (MF-1, MF-2, and MF-3). Cell proliferation assays showed a decrease in viable cell proliferation in both cell lines treated with MF-3. Apoptosis was confirmed through the use of flow cytometry and we found evidence of G1 arrest in MF-3 treated cells. Immunoblots for apoptosis-related proteins suggest apoptotic activation of the caspase-3 pathway in treated cells compared to non-treated cells. We conclude that extracts of muscadine grape contain biologically active polyphenols that inhibit the growth of HT-29 and HT-15 colon cancer cells via an apoptotic pathway.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A53.
Abstract A55: A screening method for identifying potential angiogenesis inhibitors
Authors: Caldwell Kelli , Charlton Shirley , Krill Diane 
Published: May 2012

Abstract
A55

Objective
Plants produce chemical compounds to prevent encroachment by competitors. These turf wars that generate defense products in plants have potential medicinal value for humans. For example, compounds with anti-angiogenic properties are useful in combating cancer by preventing new blood vessel formation to support the tumor. The search for new angiogenesis inhibitors is ongoing, and utilizes a variety of time-intensive cell culture models. In this report we introduce a rapid, inexpensive method for screening potential anti-angiogenic compounds in a model system that stimulates the production of secondary defense chemicals in plants, thus increasing the potential yield of effective compounds.
Plant chemicals under investigation for anti-angiogenic activity include flavonoids, a broad group of compounds that are present in most photosynthesizing cells of plants. Flavonoids share a common phenyl-chromanone structure (C6-C3-C6), and include thousands of compounds, subdivided into 6 major categories; flavones, flavonols, isoflavones, flavanols, flavanones, and anthocyanins. Humans do not synthesize flavonoids, but derive an average of 1 gram per day in their diet. Their reported pharmacological properties include antioxidative, anti-inflammatory and antiproliferative properties.

Methods
In order to induce defense chemical production, we chose thyme and mint plants to combine because thyme was observed to inhibit the spread of mint, a highly invasive vascular plant. The thyme plants grown alone, as well as the mint alone, were analyzed as controls. The plant leaves and stems were extracted and the flavonoid products were analyzed by reverse phase HPLC. The flavonoids that appear in the thyme in the presence of mint, that are not present in the thyme plants grown alone, were considered induced by the presence of mint. The induced compounds were collected and tested in a vertical plate assay that measures root length as a quantitative assay for drug sensitivity. The compounds were applied to the vascular root tissue of mint seedlings 5-7 days after germination.

Results
Of eight Thymus vulgaris compounds that were induced by the presence of mint, 5 were tested by bioassay, and one was found to have an inhibitory effect. Known angiogenesis inhibitors, VEGF receptor tyrosine kinase and amelioride hydrochloride, significantly reduced root growth compared to the control. An HPLC-isolated compound b, which eluted at 15.2 minutes, reduced the growth of root vascular tissue compared to the control and vehicle control, and 50% as well as known angiogenesis inhibitors.

Conclusion
This report demonstrates that induced secondary defense chemicals produced by thyme plants include flavonoid compounds. Useful inhibitors may be identified with this rapid, sensitive, and inexpensive technique.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A55.
Abstract A56: Alterations in female reproductive organs of cyclic rats treated with aqueous extract of moringa oleifera lam: Indication of possible role in epithelial ovarian cancer
Authors: Bose Chinmoy 
Published: May 2012

Abstract
A56

Background
A hormonal etiology of epithelial ovarian cancer has long been suspected seeing its incidence menopausal age, and now the role of FSHR has also been demonstrated. Many ovarian cancer cell line express FSHR in them. In studies of the anticancer potential of plants used in folk medicine of Bengal, extracts of plants such as Oroxylum indicum, Moringa oleifera lam, Aegles marmelos could be considered as potential sources of anticancer compounds. Amongst them only Moringa oleifera lam has unique anticancer as well as hormonal property, which may or may not be attributable to isothiocyanate or glucosinolate that it contains. An animal experiment was planned to see effect of Moringa root extract in female reproductive system of mice.

Methods
5 adult female mice of swiss strain of 30 gm each 2-control, 3-treated kept on stock diet, pellet, having nutritional value of 7 days. An aqueous extract of the root was prepared according to a traditional method. In brief, 500 g of the root were placed in a container with 750 ml of water and boiled for 30 min. The preparation was left standing to cool and was then filtered. The filtrate, containing 66.7 mg root in 1 mL, was placed in small vials and kept in 4 degree C refrigerator until use. 1 ml of extract was used orally daily for 45 days.

Results
Attenuation/shrinkage of ovary and uterus was seen while mice tolerated the herb extract well. There was reversal to pre estrus phase of adult mice as was revealed by PAP smear from vagina. In histology there was absence of follicles in comparison to control ovary. There was lesser amount of fibrosis in treated ovary.

Conclusion
Isothiocyanate of Moringa may inhibit proliferation of ovarian granulosa and other cells as it induces apoptosis via caspase-9 and -3 pathways, a family of calcium-dependent cysteine proteases. It may also act by inhibiting ERK1/2 and Akt survival signaling while simultaneously activating pro-apoptotic p38 and JNK1/2. There are reports to show that Moringa induced decrease in cerebral dopamine and norepinephrine which may influence and lower NGF and FSHR through central mechanisms. There is strong possibilty of using this agent in epithelial ovarian cancer and, as such, a cell line experiment is urgently necessary.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A56.
Abstract A57: Lipid extract from the ostrich fern Matteucia struthiopteris displays potent anti-cancer effects in microtumors from human malignant cell lines via disruption of actin cytoskeleton
Authors: Crawford Sarah , Penarreta Rafaella , Diamond Deanna 
Published: May 2012

Abstract
A57
Previous studies from the Cancer Biology Research Laboratory identified primitive plants of moss, fern and lichen species with anti-cancer activities. Current research involves the extraction of a lipid-containing fraction from the ostrich fern, Matteucia struthiopteris, with 1,000-fold greater anti-cancer activity than whole plant aqueous homogenates in pre-clinical assays of microtumors prepared from several solid tumor malignancies, including drug-resistant glioblastoma multiforme. Confocal laser microscopy of phalloidin-stained tumor cells demonstrated that a primary effect of the plant extracts is the disruption of cortical actin cytoskeleton in the cell membrane. This represents a previously unrecognized therapeutic target for anti-cancer agents.
The targeted actin-cytoskeleton may also comprise a novel chemopreventive target. A novel biophysical model, proposed by Crawford, suggests that the active lipid fraction may affect cytoskeletal integrity as a consequence of the interaction of plant isoprenoids and dolichols on tumor membrane fluidity. Increased membrane fluidity may interfere with the dynamic assembly of actin cytoskeletal components essential to cell motility and focal adhesions essential for tumor viability and metastasis.
*Patent pending 2008
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A57.
Abstract A65: Identification of inflammation-associated plasma markers as response indicators in human colorectal cancer patients consuming freeze-dried black raspberries
Authors: Mentor-Marcel Roycelynn , Bobe Gerd , Sardo Christine , Wang Li-Shu , Albert Paul , Stoner Gary , Colburn Nancy 
Published: May 2012

Abstract
A65

Background
Inflammatory cytokines have been reported as biomarkers of colorectal adenoma risk in humans, however, little is known of biomarkers of response to interventions that may be useful as preventive or therapeutic agents for colorectal cancer. Freeze-dried black raspberries given to colorectal cancer patients were previously shown to be efficacious in altering cellular parameters associated with colorectal tumor development (i.e. apoptosis, cell proliferation, angiogenesis). We hypothesized that berry-induced changes in these cellular responses would be associated with changes in plasma levels of inflammatory cytokines that may serve as measures of efficacy of a 2-4 week dietary intervention of berries in colorectal cancer patients.

Methods
26 patients who had not received prior therapy consumed a slurry of black raspberries (20g in 100 ml drinking water) 3 times a day for 2-4 weeks. Plasma was collected before and after berry treatment and was analyzed for 9 inflammation-associated proteins.

Results
2 of 9 inflammation-associated plasma proteins were increased (i.e. IL-1β, GM-CSF) with berry treatment. Whether these diet-induced plasma changes correlate with changes in apoptosis, cell proliferation, and angiogenesis is being determined.

Conclusion
In summary, IL-1β and GM-CSF emerged as plasma proteins that were increased in colorectal cancer patients upon berry treatment. Changes in a subset of inflammation-associated plasma proteins may serve as response indicators to berry treatment under efficacious conditions and thus may be useful as a short term assay to monitor response to berry-based interventions for treatment of colorectal cancer.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A65.
Abstract A71: Molecular trail for the action of a metal-based drug in HPV positive cervical cancer cells
Authors: Srinivas Priya , Nair Rakesh , Kurup Maliyeckal Ramakrishna Panicker , Kuriakose Mini 
Published: May 2012

Abstract
A71
Cervical cancer is one of the most prevalent female cancers in world. The treatment for cervical cancer includes chemotherapy. Most potential standard chemotherapeutic agents have side effects. A need-based approach for developing new anti cancer agents from metal compounds with fewer side effects will have enormous implications. Opportunities exist to exploit metal-based drugs in the discovery and development of pharmaceuticals against cancers. Vanadium is a transition metal widely distributed in the environment, which is also a dietary micronutrient. The antidiabetic and anticancer activities of the oxovanadium complexes are recently known. In this study, human cervical cancer cell line SiHa, which is HPV16 - positive has been employed to determine the anticarcinogenic property of two oxovanadium complexes, OVK 49 and OVK 89. Among these OVK 49 proved to be more effective than OVK 89. Both complexes inhibited the growth of SiHa cells in a concentration and time dependent manner. Treatment of cells with oxovanadium complexes caused loss of mitochondrial membrane potential (ΔΨm) and morphological changes characteristic of apoptosis, such as the nuclear condensation. Moreover oxovanadium complex induced apoptosis, which involved release of mitochondrial cytochrome c and activation of caspase 8 and 9. The molecular mechanism behind the apoptotic induction due to these oxovanadium complexes is well established in this study. The E6 oncoprotein of human papillomaviruses has the potential to funtionally antagonize p53. Here it has also been investigated whether this reflects the regulation of p53 expression in HPV positive cervical cells. It has also been found that p21 was efficiently induced and HPV E6, E7 p53 and GADD45 were decreased by OVK 49 and 89 in SiHa cells. These results suggests that inspite of the presence of E6 protein HPV 16 positive cervical cancer cell lines are capable of responding efficiently to DNA damage provoked by metal based drug treatment through a p53 dependent pathway.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A71.
Abstract A75: DNA repair genotypes associated with benign breast disease in women at high breast cancer risk
Authors: Jorgensen Timothy , Helzlsouer Kathy , Hoffman Sandra , Hoffman-Bolton Judith , Crum Rosa , Visvanathan Kala 
Published: May 2012

Abstract
A75

Background
Benign breast disease (BBD) is a risk factor for breast cancer and may have a heritable component. Little is known about genetic factors associated with BBD risk. Deficient DNA repair has been implicated in the etiology of breast cancer. Since DNA repair occurs early in the breast carcinogenesis pathway, it is logical that polymorphic forms of DNA repair genes may alter BBD risk. No prior studies have reported on the association between DNA repair variants and BBD.

Methods
We examined the association between a panel of DNA repair genotypes and BBD in a sub-cohort of women within CLUE II, a population based cohort study in Washington County, Maryland. The women were followed from 1989 to 2003 with biennial questionnaires from 1996 onwards eliciting information on many health outcomes, including physician diagnosis of BBD and breast biopsies. 3,212 women reporting no prior diagnosis of BBD at baseline were genotyped for non-synonymous SNPs in 8 DNA repair genes (ERCC2, ERCC4, ERCC5, RAD23B, XPC, XRCC1, XRCC2, and XRCC4) that had previously been implicated in cancer risk. BBD-free survival time was fitted to age-adjusted Cox proportional hazards model and analyzed by DNA repair genotype.

Results
Carriers of the variant alleles of XRCC1 codon 194 and ERCC4 codon 415 were significantly more likely to be diagnosed with BBD than non-carriers -- hazard ratios (HR) = 1.36, 95%CI 1.06-1.74 and 1.39, 95%CI 1.09-1.76, respectively. The association between the ERCC4 variant and BBD was even greater among women with a positive family history of breast cancer. In this subgroup, the variant ERCC4 allele was associated with a 2.7 fold increase in breast cancer risk (HR = 2.63, 95% CI 1.52-4.66, p interaction = 0.02).

Conclusion
Variant ERCC4 and XRCC1 genotypes are significantly associated with a diagnosis of BBD in this population, particularly in women with a family history of breast cancer. These same genes have also been implicated in the risk of breast cancer in other studies. Taken together, these studies support the notion that these two DNA repair genes may have a common role in the etiology of both BBD and breast cancer.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A75.
Abstract A78: Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut
Authors: Lee Kyoung-Mu , Dalsu Baris , Zhang Yawei , Hosgood H. Dean , Yeager Meredith , Zahm Shelia , Wang Sophia , Purdue Mark , Chanock Stephen , Zheng Tongzhang , Qing Lan 
Published: May 2012

Abstract
A78

Background
Increased risk of multiple myeloma has been observed among those who have a family history, suggesting a genetic component in multiple myeloma development. Also, a number of studies have shown that changes in immuoregulatory role of T cells may contribute to the development of multiple myeloma.

Objective
In light of the relationship between immune system dysregulation and multiple myeloma risk, we investigated whether genetic variation in 153 immune function genes are associated with multiple myeloma susceptibility in a population-based case-control study conducted among White Connecticut women.

Methods
Tagging single-nucleotide polymorphisms (SNPs; N=876) were selected using a pairwise linkage-disequilibrium based algorithm. Odds ratios (ORs) and 95% confidence intervals (CIs) for SNP genotypes were estimated using unconditional logistic regression. Tests of association for gene regions were conducted using the minP test. We applied the false discovery rate (FDR) method to the minP test results as a means of controlling for multiple comparisons. Haplotype analyses among subjects were performed using the haplo.stat statistical package in the R program. Haplotype frequencies were estimated from genotype data using the expectation-maximization algorithm while at the same time excluding those with frequencies less than 1%, and were evaluated by the global score test.

Results
Six out of 75 gene regions were significantly (P&lt;0.05) associated with multiple myeloma using the MinP test. However, only the PTMS-LAG3-CD4-GPR162-LEPREL gene region remained noteworthy after adjustment for multiple tests using the FDR method (minP=0.0018; noteworthy at a level of FDR control of 0.14). In this region, a total of six SNPs in two genes (CD4 and LAG3) were significantly associated with risk (Ptrend&lt;0.05), with the strongest association observed for rs11064392 (ORAG/GG=2.53, 95% CI=1.59-4.02; Ptrend=0.0001). Haplotype analyses also supported an association with rs11064392.

Conclusion
Our findings suggest that genetic variation in CD4 may influence susceptibility to multiple myeloma.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A78.
Abstract A79: Hormonal factors and breast cancer risk in nulliparous women
Authors: Schonfeld Sara , Pfeiffer Ruth , Lacey James , Hartge Patricia , Doody Michele , Greenlee Robert , Park Yikyung , Schairer Catherine , Schatzkin Arthur , Sigurdson Alice , Visvanathan Kala 
Published: May 2012

Abstract
A79

Background
Nulliparous women are a growing population in the U.S. that is known to be at elevated risk for breast cancer. A term pregnancy is believed to exert a protective effect on the ductal structures in the breast through terminal differentiation. It is biologically plausible that limited ductal maturation in nulliparous women renders the breast more susceptible to the effects of hormonal factors.

Methods
We assessed the association between hormonal and other factors and breast cancer risk by parity among postmenopausal women. Data were combined from four prospective cohort studies [The Breast Cancer Detection Demonstration Project Follow-up Study, the NIH-AARP Diet and Health Study, The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, and The United States Radiologic Technologist Study]. Each dataset was analyzed using multivariable Cox Proportional Hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) separately for nulliparous and parous women for known risk factors. Study-specific results were combined using a meta-analytic random effects model.

Results
A total of 1,611 breast cancers were reported among 32,636 nulliparous women and 8,284 breast cancers among 207,763 parous women. The meta-analytic HRs for the one of the strongest risk factors, current use of menopausal hormone therapy for ≥5 years, were 1.46 (95% CI: 1.10-1.82) and 1.50 (95% CI: 1.42-1.59) for nulliparous and parous women, respectively. Patterns of risk were similar for nulliparous and parous women for other factors including ages at menarche and last menstrual period, body mass index, family history of breast cancer, and benign breast disease. Some study-specific variability was detected.

Conclusions
Similar associations between hormonal risk factors and breast cancer were observed for nulliparous and parous women. However, given their elevated baseline risk, these risk factors are likely to contribute to a greater absolute risk of breast cancer among nulliparous women.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A79.
Abstract A9: Expression of insulin-like growth factor II and of the type 1 receptor gene in esophageal adenocarcinoma
Authors: Zhao Ronghua , Geyer Ron , Decoteau John , Casson Alan 
Published: May 2012

Abstract
A9

Aim
To explore potential biological mechanisms underlying the association between obesity and esophageal malignancy, we studied the expression of insulin-like growth factor-II (IGF-II) and of the type 1 receptor (IGF-IR) gene in a well characterized series of patients with primary esophageal adenocarcinoma (EADC) and matched histologically normal esophageal epithelia (NE).

Patients and Methods
Banked esophageal tissues (EADC and matched NE, obtained with informed consent) were available from a consecutive series of 52 patients who underwent esophageal resection without preoperative chemoradiation therapy. Following extraction of RNA, expression of IGF-II and IGF-IR mRNA was determined using reverse transcription and real time polymerase chain reaction (RT-PCR). The 2-ΔΔCT (Livak) method was used to quantitate tissue expression of IGF-II and IGF-IR mRNA, which was correlated with measured body mass index (BMI), clinicopathological findings, and outcome.

Results
As expected, significant correlations between tumor stage, differentiation and survival were found for the 49 male and 3 female patients in this series, who ranged in age from 36 to 85 years (median: 60.5 years). A significant association was seen between BMI and IGF-II mRNA expression in NE tissues (rs=0.26, p=0.075). Significantly higher IGF-II mRNA expression was seen in EADC tumors (median 6.45, 95%CI 7.00-13.46) compared to matched NE tissues (median 1.32, 95%CI 1.37-4.31, p&lt;0.01), particularly in poorly differentiated tumors. On multivariate analysis, IGF-II expression was an independent predictor of disease-free survival (p=0.02) and overall survival (p=0.03). Expression levels of IGF-II mRNA correlated significantly with IGF-IR in both EADC (rs=0.47, p&lt;0.01) and NE (rs=0.46, p&lt;0.01). Furthermore, IGF-IR mRNA expression was found to be significantly higher in EADC (median 1.57; 95%CI 1.47-3.86) compared with matched NE (median 0.57; 95%CI 0.50-0.85) (p&lt;0.01), but only in patients with the A variant of the common IGF-IR G3174A polymorphism, which has recently been shown to modulate the obesity risk for EADC.

Conclusions
These studies further implicate perturbations of the IGF axis in the molecular pathogenesis of human EADC, and suggest a plausible mechanistic basis to explain the association between obesity and risk for malignancy. The significant association between IGF-II expression and survival suggests that IGF-II may be a clinically relevant biomarker for prognosis, or molecular target for novel anti-cancer therapies.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A9.