bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2880: Spices suppress oxidative stress during DMBA induced skin carcinogenesis in mice, mimicking human non-melanoma skin cancer
Authors: Das Ila , Acharya Asha , Sengupta Archana , Das Shukta , Bhattacharya Sudin , Saha Tapas 
Published: February 2011

Abstract
Background: Cancer chemoprevention is the use of natural, synthetic or biologic substances to reverse, suppress, or prevent the development of cancer. Spices like cinnamon, cardamom and cumin are the naturally occurring phytoproducts that display an active cancer preventive strategy to inhibit, delay or reverse the human carcinogenesis.
Aims and Objectives: Our aim of this study is to decipher the chemopreventive effect of aqueous infusion of the spices as a diet on DMBA induced skin carcinogenesis, which mimics UV radiation mediated non melanoma skin cancer that has high mortality rate if not diagnosed early.
Research Design and Methodology: Female Swiss Albino Mice have been divided into 5 groups in each case. Normal control (NC) and DMBA treated control (CC) mice received acetone and DMBA/croton oil on it's dorsally shaven skin for eight weeks, respectively. Aqueous suspensions of the spices were orally administered to three groups of mice either before or after or both before and after DMBA applications on the shaved skin during the entire study period. Treated skins were excised after harvesting the mice and H & E staining, immunohistochemistry assays for lipid peroxides, antioxidation enzymes activities, immunoblotting, cell proliferation and apoptosis were performed.
Results: All the spices demonstrate inhibition of the skin papillomagenesis. The best chemopreventive actions of these spices were observed when the spice treatments were performed both before and after the induction of skin carcinogenesis by DMBA. An up-regulation of the phase II detoxification enzymes and induction of non-protein thiol antioxidants were observed in mice treated with the spices. Additionally, cumin and cardamom demonstrate downregulation of COX-2 expression, inhibit cell proliferation and block p53-induced apoptosis. Cardamom stimulates NRF2 and inhibits NF-κB transcription factors to demonstrate its beneficial action against skin carcinogenesis.
Conclusion: Spices inhibit DMBA induced skin carcinoma in mice when treated early and it is believed to be due, at least in part, to the induction of cellular defense systems. We are in a process of identifying unique chemical components of these spices to maximize the benefits.
References:
1. Das, I., and Saha, T.; Nutrition. (2009); 25(4):459-471.
2. Das, I., Das, S. and Saha, T.; Acta Histochem. (2009); (In Press)
3. Das, I., Rana, T., Sengupta, A., and Saha, T.; J. Biol. Chem. 2009; (In Revision)
4. Acharya, A, Das, I., Chandhok, D., and Saha, T.; Oxidative Stress and Cellular Longevity; 2009; (In Press)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2880.
Abstract 2882: Penta-O-galloyl-beta-D-glucose induces DNA replicative S arrest and G1 arrest independent of p21Cip1, p27Kip1 and p53 in human breast cancer cells and is orally active against breast cancer xenograft
Authors: Chai Yubo , Lee Hyo-Jeong , Shaik Ahmad , NKhata Katai , Xing Chengguo , Kim Sung-Hoon , Lü Junxuan 
Published: February 2011

Abstract
Natural herbal compounds with novel actions different from existing breast cancer targeting modalities are attractive for improving treatment and prevention efficacy and safety. We have recently shown that penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG), a naturally occurring gallotannin polyphenol compound, induced S-phase arrest in prostate cancer cells through inhibiting DNA replicative synthesis, in addition to the induction of G1 arrest and cell deaths at higher levels of exposure. We and others have shown that PGG through i.p. injection exerts a strong in vivo growth suppression of human prostate cancer xenograft models in athymic nude mice. We hypothesize that the novel DNA replication targeting action and the cellular arrest and death effects of PGG are applicable to breast cancer cells and PGG could be a novel agent for treatment or prevention of breast cancer, especially those without proven drugable targets such as triple-negative breast cancer.
In cell culture studies, exposure to serum achievable level of PGG induced rapid S arrest in p53-wild type ER-dependent MCF-7 breast cancer cells and in p53-mutant ER-/PR- and Her2-negative (triple-negative) MDA-MB-231 breast cancer cells as indicated by the lack of BrdU incorporation into S-phase cells. Higher levels of PGG induced more caspase-mediated apoptosis in MCF-7 than in MDA-MB-231 cells. In addition to S-arrest, PGG induced G1 arrest in both cell lines. Contrary to a study by others with questionable design, we have found no induction of CDK inhibitory proteins p21Cip1 and p27Kip1 with G1 arrest. PGG treatment led to decreased cyclin D1 in both cell lines and over-expressing cyclin D1 abolished G1 arrest and hastened S arrest. In serum-starvation synchronized MCF-7 cells, we observed a close association of down-regulation of cyclin D1 and de-phosphorylation of Rb by PGG shortly before G1-S transition stimulated by serum. Though PGG inhibited estrogen-stimulated cell growth in MCF-7 cells, it had little effect on estrogen receptor-alpha level. To test the in vivo efficacy of PGG, we treated female athymic mice inoculated with MDA-MB-231 xenograft with 10 mg/kg body weight by daily gavage and compared with weekly paclitaxel treatment at the same dosage. Oral administration of PGG led to a better growth inhibitory efficacy than the taxane drug. Together, our in vitro and in vivo data support PGG as a potential chemopreventve or treatment agent for breast cancer with novel targeting actions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2882.
Abstract 2888: Vitamin D inhibits obesity-induced endometrial carcinogenesis in Pten+/− mice
Authors: Yu Wei , Maxwell Larry G. , Cline Mark , Berrigan David , Rodriguez Gustavo , Warri Anni , Hilakivi-Clarke Leena 
Published: February 2011

Abstract
Objectives: A growing body of epidemiologic and experimental evidence suggests that vitamin D may lower the risk of a number of epithelial malignancies. In this study, we sought to determine whether vitamin D exposure reverses endometrial carcinogenesis in an animal model, and further whether it modifies the enhanced risk of endometrial carcinoma associated with obesity. Methods: When 4 weeks of age, Pten+/− and wildtype (WT) mice were each divided into four treatment groups and fed an AIN93G based diet containing either (1) 18% energy from fat (control diet), (2) 18% fat and 25K IU of VD3/kg diet (VD3 supplemented control diet), (3) 58% fat to induce obesity (obesity inducing diet, OID), and (4) 58% fat and 25K IU of VD3/kg diet (VD3 supplemented OID). Mice were kept on these diets until they were sacrificed at 28 weeks of age. Results: Dietary VD3 exposure did it cause any apparent toxicity. VD3 increased the expression of 25-hydroxylase (25-OHase, an enzyme converting VD3 to 25(OH)D3) in the endometrium of WT (p&lt;0.027) and Pten+/− mice (p&lt;0.025). Further, it increased vitamin D receptor (VDR) levels (p&lt;0.006) in the obese Pten+/− mice. Although VD3 did not affect endometrial cancer risk, it inhibited obesity-induced increase in endometrial cancer. Specifically, OID increased focal glandular hyperplasia with atypia and malignant lesions from 58% in the control diet fed Pten+/− mice to 78%. Dietary VD3 supplementation decreased the incidence of endometrial pathology in Pten+/− mice fed OID to 25% (p&lt;0.001). Estrogen receptor (ER)-α mRNA levels were significantly higher (p&lt;0.014) and progesterone receptor (PR) protein levels in the luminal epithelium were significantly lower (p&lt;0.04) in the endometrium of control diet fed Pten+/− mice than in the WT mice, but the expression of ER-α, ER-β or PR mRNA, or epithelial or stromal protein expression were not affected by the dietary exposures. Conclusions: Our data obtained in Pten+/− mice confirm the known association between increased body weight and endometrial cancer risk. Dietary exposure to VD3 inhibited the carcinogenic effect of obesity on the endometrium; the mechanism mediating this protective effect was not linked to changes in the expression of ER-α, ER-β or PR.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2888.
Abstract 2888A: Prevention of MAPK pathway by Brazilian medicinal plant, Tabebuia avellanedae, on peroxynitrite induced carcinogenesis
Authors: Tokuda Harukuni , Kaneko Masafumi , Yamashita Mituaki , Suzuki Nobutaka , Iida Akira 
Published: February 2011

Abstract
The present study was carried out to examine the chemopreventive activity of natural Brazilian medicinal plant, Tabebuia avellanedae ext. and its components on peroxynitrite(PN) induced carcinogenesis. Tabebuia avellanedae,(TA) which is a plant that has been used for herbal medicine in South America and from Brazil to northern Argentina, is well known in traditional folk 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 as a herb tea and healthy purpose. On the fundamental findings, this substance was observed the inhibitory effects against chemical carcinogenesis induced tumor initiating and promoting activity using two-stage mouse skin model.
In the course of these studies, female SENCAR mouse
(6 weeks of age) were treated topically with single dose of PN solution, followed by TPA twice a weekly for 20 weeks. Tumor incidences were 100% with 6 to 7 paillomas per mouse at end of experiment as positive control group. TA powder were orally fed with drinking water for only 2 weeks, before and after initiation and following promoting treatment with drinking water only, as test compounds. In our observations, TA and its components treated group cause about 60-70 % reduction in the average number of tumors per mouse after 20 weeks of experiment, respectively. Topical administration of TA and its components had much influence against PN induced expression stage. We postulate that these data suggeste possible role of a regulatory mechanism of chemopreventive activity in PN induced carcinogenesis. Employing Western blot analysis studies, we found that H-Ras, MEK-2 and p38 levels observed the effects against PN induced activation, and more detail Western blot analysis indicated a active decrease in p38 expression in the skin after TA treatment. Summary of our findings, we suggest that one target of TA and its component effects in mouse skin is the modulation or regulation of the MAPK signaling.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2888A.
Abstract 2896: Effects of Calcium and Vitamin D Supplementation on the Inflammation Marker Cyclooxygenase-2 (COX-2) in Normal Colon Mucosa: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Chen Vincent , Bostick Roberd M. 
Published: February 2011

Abstract
To investigate whether calcium and vitamin D reduce the expression of the inflammation marker COX-2 in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial (n=92) of 2.0 g elemental calcium daily and vitamin D3 800 IU/day, alone and in combination, versus placebo over 6 months. COX-2 expression and colorectal crypt distribution in biopsies of normal-appearing colorectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. COX-2 expression along the entire crypt increased by 4% (p=0.73) in the calcium group and decreased by 3% (p=0.86) and 4% (p=0.73) in the vitamin D3 and joint calcium and vitamin D3 supplementation groups, respectively, relative to the placebo group. The distribution of COX-2 in the colorectal crypts overall or in various regions of the crypt (proliferative zone, differentiation zone, and area closest to contact with colon lumen contents) did not substantially change over follow-up. Our findings did not support the hypothesis that calcium and/or vitamin D3 supplementation can substantially decrease COX-2 expression in the normal appearing colorectal mucosa of sporadic adenoma patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2896.
Abstract 2898: Prognostic value of postoperative alpha-fetoprotein level on recurrence after curative resection for hepatocellular carcinoma
Authors: Nobuoka Daisuke , Kato Yuichiro , Gotohda Naoto , Takahashi Shinichiro , Konishi Masaru , Kinoshita Taira , Nakatsura Tetsuya 
Published: February 2011

Abstract
Background: The high incidence of recurrence after curative resection is a major challenge in hepatocellular carcinoma (HCC) treatment. Although serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) are well known as tumor markers of HCC, the clinical usefulness for early detection of HCC recurrence remains controversial. In this retrospective study, we evaluated the clinical value of AFP and DCP levels in predicting HCC recurrence after curative resection, with a focus on the time course as surveillance tools.
Methods: A total of 165 consecutive HCC patients who had undergone curative hepatectomy at the National Cancer Center Hospital East from 2005 to 2007 and whose serum AFP and DCP had been measured before and after hepatectomy were included in this study. The minimum postoperative levels within a 4-month period were used for analysis. In this study, the cut-off levels for AFP and DCP were set to 10 ng/ml and 40 mAU/ml, respectively.
Results: Until the end of follow-up, tumor recurrence was identified in 114 patients (69.1%). Among the patients with a positive level of AFP before operation, the number of patients whose AFP level did not change from positive to negative after operation in the group with recurrence exceeded that in the group without recurrence (48/60, 80.0% vs. 4/23, 17.4%), and the difference was significant (P &lt; 0.001). In contrast, there was no significant difference between two groups in DCP (14/72, 19.4% vs. 2/29, 6.9%; P=0.118). Minimum postoperative AFP level was found to be a significant independent risk factor for recurrence by univariate and multivariate analysis (P &lt; 0.001). There was no statistically significant correlation between AFP level and grade of hepatitis activity (P = 0.599).
Conclusions: Postoperative AFP level is a useful predictor of recurrence after curative hepatectomy. A positive level of AFP after operation might suggest a site of residual viable cancer. The need for effective adjuvant therapy and close follow-up is suggested in patients with a positive postoperative AFP level.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2898.
Abstract 2908: Promyelocytic leukemia-retinoic acid receptor α forms complexes with Fas and FLIP and impairs Fas-mediated apoptosis
Authors: Tao Rong-Hua , Berkova Zuzana , Wise Jillian , Daniluk Urszula , Samaniego Felipe 
Published: February 2011

Abstract
Fas plays a critical role in cell proliferation and in the selective killing of autoreactive lymphocytes and abnormal cells, including infected cells. To explain the common expression of Fas and the resistance to the Fas-induced apoptosis observed in some normal and cancer cells, we have screened cells for potential regulators of the Fas death receptor. By using mass spectroscopy analysis of Fas-associated proteins, we identified peptides derived from promyelocytic leukemia (PML).
PML enhances pro-apoptotic signaling, while the promyelocytic leukemia-retinoic acid receptor α (PMLRARα) activates pro-survival pathways. Given these opposing functions, we tested whether PMLRARα, which typically operates in a dominant-negative manner, blocks Fas-mediated apoptosis.
Co-immunoprecipitation analysis demonstrated that PMLRARα interacts with Fas in acute promyelocytic leukemia (APL)-derived NB4 cells, U937-PR9 cells and in APL primary cells. The binding of PMLRARα to Fas was mapped to the B-box domain of PMLRARα. Flow cytometry analysis of propidium iodide-stained and Annexin-V-stained cells challenged with Fas ligand (FasL) or agonistic anti-Fas antibody (CH-11) indicated that the presence of PMLRARα was associated with blocked Fas-mediated apoptosis at early and late stages. The knockdown of PMLRARα with shRNA sensitized the NB4 cells to Fas-mediated apoptosis. Expression of PMLRARα in U937-PR9 cells prevented Fas-mediated cleavage of procaspase-8 and also prevented procaspase-8 from binding to the Fas complex upon stimulation with the agonistic anti-Fas antibody (CH-11). Further analysis indicated that PMLRARα bound to FLIPL/S and forms a complex with Fas associated with suppression of Fas signaling.
These data suggest that cancer-specific inhibitors of Fas such as PMLRARα block Fas-mediated apoptosis and thus can contribute to cancer development and resistance to therapy. Our results may provide an explanation for the long-known role of PMLRARα and PML in the regulation of Fas signaling, which we have shown to occur by direct regulation. We have identified an attractive potential target to the regulation of apoptosis at the PMLRARα-Fas and PML-Fas interfaces. By neutralizing the effect of death receptor inhibitors such as PMLRARα and other potential inhibitors, we can improve on the success of the many chemotherapeutic treatments that depend on activation of death receptors for effective elimination of cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2908.
Abstract 2915: p53 isoforms Δ133p53 and p53β are endogenous regulators of replicative cellular senescence
Authors: Fujita Kaori , Mondal Abdul M. , Horikawa Izumi , Nguyen Giang H. , Kumamoto Kensuke , Sohn Jane J. , Bowman Elise D. , Mathe Mathe A. , Schetter Aaron J. , Pine Sharon R. , Ji Helen , Vojtesek Borivoj , Bourdon Jean-Christophe , Lane David P. , Harris Curtis C. 
Published: February 2011

Abstract
The finite proliferative potential of normal human cells leads to replicative cellular senescence, which is a critical barrier to tumor progression in vivo. The p53 signaling pathway plays central roles in the regulation of cellular senescence. Humans, as well as Drosophila and zebrafish, have p53 isoforms; however, their regulation and function are poorly understood. We here examine the expression profiles of two human p53 isoforms, p53β (lacking the C-terminal oligomerization domain due to an alternative mRNA splicing) and Δ133p53 (lacking the N-terminal transactivation and proline-rich domains due to the transcription from an alternative promoter in intron 4), during in vitro and in vivo cellular senescence and their biological activities in regulating cellular senescence. Induced p53β and diminished Δ133p53 were associated with replicative senescence, but not oncogene-induced senescence, in normal human fibroblasts. The replicatively senescent fibroblasts also expressed increased levels of miR-34a, a p53-induced microRNA, the antisense inhibition of which delayed the onset of replicative senescence. The siRNA-mediated knockdown of endogenous Δ133p53 induced cellular senescence, which was attributed to the regulation of p21WAF1 and other p53 transcriptional target genes. In overexpression experiments, while p53β cooperated with full-length p53 to accelerate cellular senescence, Δ133p53 repressed miR-34a expression and extended cellular replicative lifespan, providing a functional connection of this microRNA to the p53 isoform-mediated regulation of senescence. The senescence-associated signature of p53 isoform expression (i.e., elevated p53β and reduced Δ133p53) was observed in vivo in colon adenomas with senescent phenotypes. The decreased p53β and increased Δ133p53 expression found in colon carcinomas might signal an escape from the senescence barrier during the progression from premalignant to malignant tumors in vivo. This study shows that natural p53 isoforms constitute an endogenous regulatory mechanism for p53-mediated replicative senescence and may open up a new p53-based, senescence-mediated strategy to manipulate carcinogenesis and aging. The molecular details of the senescence-associated Δ133p53 repression and p53β induction are currently under investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2915.