bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A31: Intestinal resistance to celecoxib in Min/+ mice involves ECM changes and an expanded population of TGFβ-expressing myofibroblasts
Authors: Davids Jennifer , Carothers Adelaide , Damas Beatrice , Bertagnolli Monica 
Published: May 2012

Abstract
A31
The COX-2 inhibitor, celecoxib, inhibits prostaglandin E2 (PGE2) production and intestinal adenoma formation in mice and in humans. Previously, we showed that treatment of Min/+ mice with dietary celecoxib for 3 weeks reduced PGE2 and induced tumor regression, whereas treatment for 5 months resulted in increased PGE2 and tumor growth (Carothers et al. Cancer Res. 2006; 66: 6432-8). In the small intestine, cross-talk between epithelial and stromal cells occurs across the extracellular matrix (ECM). Heparan sulfate proteoglycans (HSPGs) within the ECM sequester and modulate the activities of growth factors and latent TGFβ ligands. TGFβ stimulates differentiation of fibroblasts into PGE2-producing myofibroblasts. These stromal cells play important roles in intestinal tumorigenesis and in the chemopreventive effect of nonsteroidal anti-inflammatory drugs. We tested the hypothesis that celecoxib resistance in the intestine of Min/+ mice involves ECM regulation of HSPGs and TGFβ signaling in epithelial and stromal cells. Using immunohistochemistry (IHC), we compared the non-tumor mucosa and adenomas of untreated Min/+ controls with Min/+ mice treated with celecoxib for 3 weeks and for 5 months. We performed IHC for the HSPG membrane protein syndecan-1, cytokines TGFβ1, 2, 3 (TGFβ), and the nuclear downstream TGFβ effector, Smad4. IHC was also performed to characterize subepithelial stromal cells using F4/80, a macrophage-specific marker, as well as α-smooth muscle actin (αSMA) and vimentin, myofibroblast-specific markers. In comparison to untreated Min/+ small intestine, celecoxib treatment for 3 weeks increased membrane-localized syndecan-1, TGFβ, and nuclear Smad4 in crypt and villus enterocytes. Under these conditions, few αSMA+ and vimentin+ myofibroblasts or F4/80+ macrophages were present in the pericryptal submucosa and lamina propria. Thus, brief treatment may sequester latent TGFβ and growth factors in the ECM, blocking their downstream signaling. A reciprocal effect was produced by 5 month treatment, in which there was markedly reduced expression of membrane-localized syndecan-1, TGFβ, and nuclear Smad4 in the crypt and villus enterocytes. There was also a dramatic increase in the number of myofibroblasts in the lamina propria and pericryptal submucosa (P&lt;.01). Thus, celecoxib resistance was associated with TGFβ-induced differentiation of fibroblasts into PGE2-producing myofibroblasts. These results suggest that the duration of celecoxib treatment affects the cross-talk between epithelial and stromal cells through the ECM, providing a novel mechanism for celecoxib resistance. Moreover, elevated numbers of myofibroblasts in the human colon may be predictive of chemoprevention failure.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A31.
Abstract A33: Superior efficacy of dietary 3,3’diindolylmethane (DIM) amongst several indoles to inhibit prostate cancer growth via induction of the p75NTR tumor suppressor protein
Authors: Khwaja Fatima , Posey Isadora , Song Xueqing , Wynne Shehla , Djakiew Daniel 
Published: May 2012

Abstract
A33
A comparison of the indoles etodolac, indomethacin, 5-methylindole-3-acetic acid, indole-3-carbinol, 3,3’diindolylmethane (DIM) and the related ketorolac molecule showed superior efficacy of DIM, a dietary indole, to induce expression of the p75NTR tumor suppressor and inhibit survival of the PC-3 prostate cancer cell line. Each indole that induced p75NTR expression exhibited the same rank-order for inhibition of prostate cell survival. Comparison of the activity of DIM, the most potent of the indoles, between several cell lines, showed that DIM induced p75NTR at low concentrations in prostate cells (PC-3 , DU-145), followed by bladder (T24), with breast (MCF-7) and fibroblast cells (3T3) being the least responsive to DIM. DIM induction of p75NTR levels in the various cell lines occurred in the same rank-order as inhibition of cell survival. Since the consumption of cruciferous vegetables has been reported to reduce the risk of prostate cancer through the release of indole-3-carbinol (I3C) which is subsequently metabolized in the acidic environment of the stomach to DIM, the superior activity of DIM to induce expression of the p75NTR tumor suppressor protein and inhibit cell survival suggests a mechanism of action for the anticancer activity of DIM in the prevention of prostate cancer. In order to demonstrate a cause and effect between DIM and p75NTR inhibition of survival, we used a dominant negative of p75NTR to rescue DIM induced loss of cell survival. In order to investigate the mechanism of action by which p75NTR transduces a biochemical signaling cascade leading to cell death of prostate cancer cells we utilized knockdown with p38 MAPK siRNA to rescue DIM induction of p75NTR thereby implicating p38 MAPK in DIM induction of cell death. Moreover, DIM treatment induced phosphorylation of p38 MAPK within one minute, suggesting the target of DIM is proximal to p38 MAPK. Hence, these results suggest that the anti-cancer activity of cruciferous vegetables may be mediated in part by DIM and that the mechanism of action occurs, in part, by activation of the p38 MAPK pathway leading to expression of the p75NTR death receptor with subsequent apoptosis of prostate cancer cells.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A33.
Abstract A38: Structure-activity relationship of closely-related flavonoids with possible chemopreventive qualities
Authors: Tsuji Petra , Stephenson Katherine , Wade Kristina , Liu Hua , Fahey Jed 
Published: May 2012

Abstract
A38
Dietary flavonoids are now widely presumed to have human health benefits, and increased intake is epidemiologically correlated with decreased risk of cardiovascular disease and cancer. The general mechanisms thought to be involved in chemoprevention through dietary compounds include the inhibition of the carcinogen-bioactivating phase I enzymes and/or induction of carcinogen-bioinactivating phase II enzymes. Methoxylated flavonoids have been shown to have chemopreventive activity in a number of in vitro assays, and we have selected 27 of them as the objects of this work. Furthermore, these flavonoids were analyzed to investigate possible structure-activity relationships for effective, non-toxic agents with chemopreventive potential.
The flavonoids are a structurally diverse class of low molecular weight polyphenolic benzo-c-pyrone derivatives. The basic structure is composed of two benzene rings (A and B) separated by an oxygen-containing heterocyclic ring. Substituent groups can attach on each of the molecule’s rings, with hydroxyl, methoxy groups or sugar moieties being present most frequently. Neither hydroxylation nor methoxylation solely on the B-ring had a strong inducing effect on the phase II enzyme NAD(P)H:quinone-reductase (NQO1) in murine hepatoma cells. However, flavonoids with a methoxy-group substitution at the 5-position of the A-ring were the most potent inducers of NQO1. Other flavonoids were equally potent inducers, but exhibited much higher toxicity in at least one of the cell lines tested. Certain methoxylated flavonoids that are found in dietary fruits and vegetables have significant potential for prevention of chemically-induced carcinogenesis and should be investigated further in animal models of cancer prevention.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A38.
Abstract A39: Dosage-dependent regulation of caspase 8 activation in LNCaP and DU-145 human prostate cancer cell lines by the Chinese medicinal herb scutellaria barbata.
Authors: Nguyen Dinh , Devadhason Rachel , Wong Brian 
Published: May 2012

Abstract
A39
Scutellaria barbata (SB) (known in traditional Chinese medicine as Ban-Zhi-Lian) is a perennial herb. It has been used to treat appendicitis, hepatitis, pulmonary abscess, and several cancers. LNCaP cells are derived from a human prostate cancer cell line with mutated androgen receptors (AR) while DU-145 is a classical human prostate cell line without androgen receptors. Our previous data indicated that SB activated apoptosis in LNCaP cells via caspases 3, 8, and 9. Histopathological data revealed that the herb had the ability to delay tumor progression and development in TRAMP mice. Recent Western blot data from LNCaP cells undergoing treatment with SB showed increased expression of Akt protein while decreased phosphorylation of Akt in the cells. In this study, we compared the effect of AR-dependence on the herb's apoptosis activation through caspase 8 on these two different cell lines. The two cell lines were incubated with distilled water as a control group and 100 µL and 200µL of SB as experimental groups for 2 and 8 hours separately. A specific carboxyfluorescein (FAM) labeled peptide fluoromethyl ketone (FMK) caspase inhibitor (FAM-Peptide-FMK) was used to label caspase 8- activated cells. Caspase positive (+) cells appeared green whereas necrotic cells were stained red with propidium iodide and observed under a fluorescent microscope. Pictures were taken and the activation/necrosis ratio (A/N ratio) was analyzed using ImageJ software (developed by the National Institutes of Health). Significant induction of caspase 8 by SB was observed in androgen receptor positive LNCaP cells. In both 2 and 8 hour incubation, SB activated more caspase 8 in LNCaP cells than in DU-145 cells treated at 100 µL and 200 µL concentrations ( A/NLNCaP &gt; A/NDU-145 ). In addition, DU-145 exhibited significant dosage-dependent induction of caspase 8 by SB, while dosage-dependence was not observed in LNCaP cells (A/N100µL = A/N200µL). These data indicate that SB might activate apoptosis through an up-stream androgen receptor pathway, thus suggesting a plausible mechanism for this herb’s activation of the apoptotic pathway in prostate cancer cells.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A39.
Abstract A4: Antagonistic effects of sulphated polysaccharides from Turbinaria conoides (J. Agardh) on tumor cell migration and angiogenesis
Authors: Delma Caroline , Ramalingam Karthikeyan , Pandian Vijayabaskar , Baskar Albert , Savarimuthu Ignacimuthu , Thangavelu Balasubramanian , Somasundaram Somasundaram 
Published: May 2012

Abstract
A4
Seaweeds are considered to be a rich source of biologically active substances like antioxidants, anti-viral, anti-inflammatory and anticoagulant agents. There are some evidences that seaweeds contain compounds with a relatively high antioxidant and antiproliferative activity. Seaweeds are low in fats but contain vitamins and bioactive compounds, like terpenoids and sulfated polysaccharides. Sulphated polysaccharides from brown algae are found to exhibit diverse biological activities like anticoagulant, antihyperlipidemic, antiviral, antioxidant, antitumor, antimetastatic and antiangiogenic activities. In this study, the antiproliferative, antiinvasive and antiangiogenic properties of sulphated polysaccharides from brown seaweed, Turbinaria conoides against colon carcinoma cell line COLO 320DM were investigated. Crude sulphated polysaccharide was extracted from T. conoides, collected from Mandapam coast, South east coast of India. The antiproliferative activity of the seaweed polysaccahrides on COLO 320DM was evaluated by MTT assay and DNA fragmentation studies. The inhibitory potential on the migration of this invasive cell line was assessed by wound healing assay. The effect of sulphated polysaccharides against angiogenesis was investigated by chorio allantoic membrane (CAM) assay in chick embryo. It was observed that sulphated polysaccharides from T. conoides inhibited the proliferation of COLO 320DM cells at a concentration of 1mg/ml by 40% at 24 hours. DNA fragmentation as evidenced by ladder formation in agarose gel indicates that the antiproliferative activity of seaweed polysaccharides is due to the induction of apoptosis. The migration of the carcinoma cell line was effectively inhibited by the seaweed extract. The antiinvasive property increased with increasing concentrations. However, the activity was more or less similar at 24 and 48 hours. In the CAM assay, it was found that sulphated polysaccharides from the brown seaweed inhibited vasculogenesis in a developing chick embryo. These results clearly indicate that sulphated polysaccharides from brown algae are potential molecular leads for antimetastatic drug development.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A4.
Abstract A40: The enhancement of p53 stability via the inhibition of JNK-modulated ubiquitination with the activation of redox factor 1 (Ref-1) in response to non-genotoxic antioxidant selenomethionine (semet)
Authors: Jung Hwa Jin , Lee Ju Han , Jeong Seok Won , Kwon Jee Young , Park Jee Yeon , Kim Hye Lim , Lee Young Ju , Chang Sung-Goo , Seo Young Rok 
Published: May 2012

Abstract
A40
p53 has been known to play an important role as an tumor suppressor gene for the maintaining of genome stability. In the field of cancer prevention study, p53 has been issued to clarify the mechanism of activation under the non-genotoxic cancer preventive agents containing antioxidant selenium. In previous our study, p53 has been reported to be the function of transcriptional activation activated without the genotoxicity through the redox modulation in response to selenomethionine (SeMet). In this study, we investigated that the mechanism of p53 protein stabilization enhanced by SeMet. Our data showed that the ubiquitinated p53 was decreased in the cells exhibiting the downregulation of JNK which is one of E3-ubiquitin ligases compared with in mock-treated cells suggesting that the JNK-modulated p53 ubiquitination might be inhibited by SeMet. To define the mechanism of the enhanced p53 stability in the presence of SeMet, redox factor 1 (Ref-1) which has been documented as one of the factors modulating the redox status in response to antioxidants was downregulated using siRNA. Our data showed the first time that the interaction of JNK and p53 was increased in Ref-1 siRNA-treated cells in the presence of SeMet implicating that the Ref-1 activated by SeMet might be involved in the inhibition of JNK-mediated p53 ubiquitination. Our study suggested that the enhancement of p53 stabilization in response to SeMet might provide an important clue for the cancer prevention.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A40.
Abstract A44: Carnosol, a dietary diterpene functions as a dual AR and ER-alpha antagonist in prostate cancer.
Authors: Johnson Jeremy , Syed Deeba , Heren Chenelle , Siddiqui Imtiaz , Mukhtar Hasan 
Published: May 2012

Abstract
A44
Emerging evidence suggest that androgens may not be the only hormone responsible for the etiology of prostate cancer (PCa). Recent data has suggested that estrogens may be another important piece to the PCa puzzle. For example the use of the Selective Estrogen Receptor Modulator (SERM) toremifene in HG-PIN patients for one year resulted in a 21% reduction in the conversion of HG-PIN to PCa after one year of treatment. It is well established that race correlates with the levels of androgens with African Americans having the highest, followed by Caucasians and lowest in Japanese males. A similar trend has been observed in regard to serum estrogen levels and it is noteworthy that with age estrogen levels remain constant while androgens levels decrease. Given that experimental animal models suggest that both estrogens and androgens are necessary for PCa development it may be a reasonable approach to simultaneously disrupt both androgen and estrogen signaling in PCa. Several SERMs that include tamoxifen, toremifine, and fulvestrant have been evaluated for their ability to also target the AR and function as a dual AR and ER antagonist, however, experiments have suggested these effects are saturable and in some instances SERMs exert AR agonist properties. In our quest to find a dual AR and ER antagonist present in dietary substances that humans consume we found that the dietary diterpene Carnosol displays growth inhibitory properties in the hormone sensitive prostate (LNCaP and CWR22Rv1) and breast (MCF7 and AU565) cancer cell lines. Given the structural similarity between Carnosol to dihydrotestosterone and estradiol we hypothesized that it may interact with both the androgen and estrogen receptor alpha (ER-α). Using a TR-FRET cell free biochemical assay we found that Carnosol can interact with both AR and ER-alpha with similar potencies. Next, we evaluated the antagonist and agonist properties of Carnosol using a functional assay where the AR and ER-alpha ligand binding domains are expressed as a fusion protein in HEK293 cells. We observed that Carnosol exhibits antagonist properties that are dose responsive and even more interestingly, regardless of dose, did not exert agonist properties. In LNCaP, CWR22Rv1, and MCF7 cells Carnosol was found to disrupt both androgen and estrogen signaling in a dose and time dependent manner. Our finding that Carnosol displays the ability to disrupt both androgen and estrogen signaling simultaneously suggesting that Carnosol may be developed or chemically modified through more rigorous structure activity relationship studies of other such chemical entities for a new class of investigational agents - a dual AR/ER modulator.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A44.
Abstract A46: Ablack raspberry extract inhibits the proliferation of cervical cancer cells partially through proapoptotic effects
Authors: Zhang Zhaoxia , Seamon Leigh , Knobloch Thomas , Stoner Gary , Cohn David , O'Malley David , Paskett Electra , Fowler Jeffrey , Weghorst Christopher 
Published: May 2012

Abstract
A46
Cervical carcinoma, the second most common female cancer worldwide, is the seventh leading cause of cancer death in women. Although pap smears to screen abnormal cervical cytology have helped reduce mortality rates, it remains a challenge to manage preinvasive and invasive cervical lesions. The long latency of cervical cancer allows preventive and therapeutic interventions before progressing onto invasive disease. Thus, phytochemical-based cancer chemoprevention and the role of bioactive food components have attracted significant interest in current cancer-fighting interventions. We have previously shown that lyophilized black raspberries (LBR, Rubus occidentalis) inhibit the cell proliferation of human oral squamous cell carcinoma cells in vitro as well as oral tumorigenesis in vivo. Given the similar epidemiologic basis of oral and cervical cancers, we evaluated whether an LBR extract had anti-proliferative effects in cervical cancer cells in vitro and began to elucidate the possible regulatory molecular mechanisms. We found that LBR inhibited the proliferation of three human cervical cancer cell lines, HeLa (HPV16−/HPV18+) SiHa (HPV16+/HPV18−) and C-33A (HPV18−/HPV16−), in a dose-dependent manner (at 25, 50, 100 or 200µg/ml for 1, 3 and 5 days, respectively) to a maximum of 44%, 53% and 45% respectively (P&lt;0.005). While exogenous hydrogen peroxide (H2O2, 100µM), a common reactive oxygen species (ROS) intermediate and inhibitor of cell growth, inhibited C-33A proliferation, HeLa and SiHa cells were not significantly affected. The anti-proliferative effects of either LBR or LBR+catalase were similar in all cell lines as shown by WST1 (tetrazolium salt cleavage) and crystal violet assays, which supporting the hypothesis that decreased proliferation is specific to LBR bioactive components and independent in vitro peroxide generation. Flow cytometric analysis of propidium iodide and Annexin V staining showed that LBR induced apoptotic markers in all three cells lines, and did not change cell cycle progression. LBR treatment induced hypercondensation and volume contracted nuclei in Hela cells as demonstrated by fluorescence microscopy analysis of Hoechst 33342 staining. In conclusion, an extract of lyophilized black raspberries demonstrated significant anti-proliferative and pro-apoptotic activities in human cervical cancer cells in vitro. Therefore, black raspberries and their bioactive components may represent promising candidates for the phytochemical-based chemoprevention of cervical cancer and warrant further investigation.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A46.
Abstract A51: Chemopreventive effects of Brazilian herb oral feeding on UVB induced photocarcinogenesis
Authors: Tokuda Harukuni , Kaneko Masafumi , Yamashita Mitsuaki , Iiida Akira 
Published: May 2012

Abstract
A51
Ultraviolet(UV) light is the most common cause of skin
cancer in humans and it is very acute problem in our life
style during living. Several effects of UVB(290-320 nm) are thought to contribute to skin carcinogenesis and generation of free radicals and related oxidants produced by UVB exposure.Tabebuia avellanedae (Bignoniaceae)(TA), which is native in South America from Brazil to northern Argentina, is well known in traditionalfolk medicne used for the treatment of various disease during five hundred years. The inner bark of this plant produced in Brazil is distributed in Asia and Japan as a healthy purpose herb tea. Previously, we reported that extract essense of TA(TA ess.) and including naphthoquinones type compounds, NQ801, inhibited TPA-induced in vitro assay for chemopreventive potency and also inhibited TPA-induced in vivo assay on two-stage mouse skin test. We have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with UVB irradiation and promoted with 1.7 nmol of TPA in SENCAR mice. These tumor -free mice, which had a high risk of developing skin tumors, using these experimental systems, were then treated drinking with TA ess. Oral feeding of 0.0025 % of TA ess., two weeks before and after tumor initiation resulted in a significant reduction in tumor incidence (40 %) accompanied by an extension(&gt; 20 %) of the tumor latency and also decrease papilloma multiplicity. These results provide a basis for further development of TA ess. against sunlight-induced skin cancer in humans.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A51.