bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3596: Short-term effect of nose-only cigarette smoke exposure on redox homeostasis and mitochondrial metabolism in mice.
Authors: Raza Haider , John Annie , Nemmar Abderrahim 
Published: August 2014

Abstract
The components of cigarette smoke have been implicated in the development of cancer as well as in cardiovascular diseases. We have previously reported oxidative stress in rat tissues induced by tobacco-specific toxins nicotine and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Recently, we have also shown increased oxidative stress and associated inflammatory responses in various tissues after exposure to cigarette smoke. In this study, we have further investigated the effects of nose-only cigarette smoke exposure on mitochondrial functions and glutathione-dependent redox metabolism in tissues of BALB/C mice. Liver, kidney, heart and lung tissues were analyzed for oxidative stress, glutathione (GSH) and cytochrome P450 dependent enzyme activities and mitochondrial functions after exposure to smoke generated by 9 cigarettes/day for 4 days. Control mice were exposed to air only. An increase in oxidative stress as observed by an increased production of reactive oxygen species (ROS) and altered GSH metabolism was apparent in all the tissues, but lung and heart appeared to be the main targets affected. Increased expression and activity of CYP450 1A1 and 1A2 were also observed in the tissues after exposure to cigarette smoke. Mitochondrial respiratory functions in the tissues, as observed by alterations in the activities of Complex I and IV enzymes, was also observed after exposure to cigarette smoke when compared with air only exposed mice. SDS-PAGE and Western blot results also indicate that alterations in the expression of enzyme proteins were in accordance with the changes in their catalytic functions. These results suggest that even short term exposure of cigarette smoke have adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking. (The study is supported by Terry Fox Cancer Research Funds and by the Research Committee Grants from College of Medicine and Health Sciences)
Citation Format: Haider Raza, Annie John, Abderrahim Nemmar. Short-term effect of nose-only cigarette smoke exposure on redox homeostasis and mitochondrial metabolism in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3596. doi:10.1158/1538-7445.AM2013-3596
Abstract 3621: Dietary zinc and prostate cancer: a case-control study in African Americans men.
Authors: Dabbous Firas , Al-alem Umaima , Springfield Sparkle , Mahmoud Abeer M. , Batai Ken , Shah Ebony , Ahaghotu Chiledum , Kittles Rick A. 
Published: August 2014

Abstract
Introduction: Prostate cancer is a solid malignancy that disproportionately affects men of African descent. Zinc, an essential dietary trace mineral, has been implicated in the pathogenesis of prostate cancer. Total zinc intake is lower in older African American men compared to European Americans (NHANES III). Despite the high prevalence of prostate cancer and decreased levels of zinc intake among African Americans, very little is known about the relationship between zinc intake and prostate cancer in this group. This is significant because dietary factors such as zinc intake are potentially modifiable risk factors. Here, we examine the association between self-reported zinc intake and prostate cancer in a hospital-based case-control study.
Methods: Newly diagnosed African American men with histologically confirmed prostate cancer (n=141) were recruited from an urban academic urology clinic in Washington, DC. Controls (n=109) were unaffected volunteers. Usual dietary intake was assessed at the time of recruitment (2000 to 2004) with the use of a food-frequency questionnaire. Two tailed T-Test was used to compare characteristic means between cases and controls. Unconditional logistic regression was used to calculate the unadjusted and adjusted odds ratio (OR) and 95% confidence intervals (95%CI).
Results: In this population, cases were older and had higher levels of PSA. Controls had higher zinc intake, with a mean of 13.23 mg/day (SD±13.9) versus 10.67 mg/day (SD±7.3) for cases. An increase of 1 mg/day of zinc decreased the odds of prostate cancer by 3% (OR=0.97 and 95% CI: 0.95-1.002). Controlling for age, body mass index (BMI), PSA and total food energy intake did not affect the observed association.
Conclusions: Overall, these results suggest that zinc intake may have slight protective effect on prostate cancer. These analyses should be repeated in large studies to confirm these findings.
Citation Format: Firas Dabbous, Umaima Al-alem, Sparkle Springfield, Abeer M. Mahmoud, Ken Batai, Ebony Shah, Chiledum Ahaghotu, Rick A. Kittles. Dietary zinc and prostate cancer: a case-control study in African Americans men. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3621. doi:10.1158/1538-7445.AM2013-3621
Abstract 3640: Age-related DNA methylation in normal breast tissues.
Authors: Johnson Kevin C. , Jensen Amanda K. , Murphy Megan A. , Koestler Devin C. , Christensen Brock C. 
Published: August 2014

Abstract
Age-related DNA methylation in normal breast tissues
It is well established that age is a key risk factor for breast cancer, with increasing incidence associated with older age. Epigenetic mechanisms, such as DNA methylation alterations, may contribute to age-related increases in breast cancer risk. Altered patterns of DNA methylation can modify the regulation of gene expression or expression potential, and DNA methylation alterations are frequently observed in the early stages of breast tumorigenesis. However, genome-wide interindividual variation in normal breast DNA methylation has not been well characterized for its relation with age and other key breast cancer risk factors. To investigate the relationship between age and DNA methylation in normal breast tissues, we first performed a meta-analysis using two independent data sets GSE32393 (n=23) and GSE31979 (n=15), from the Gene Expression Omnibus (GEO) database. For each of the considered datasets, genome-wide DNA methylation was assessed using the Illumina Infinium HumanMethylation27 Beadchip, which profiles the methylation status of ∼27,000 CpG loci, associated with &gt;14,000 genes. Associations between DNA methylation and age were examined by fitting a series of linear regression models to arcsine square root transformed average beta values for all CpG loci in both data sets. Between these data sets, 204 CpG loci were significantly and consistently associated (P &lt; 0.05) with subject age. Relative to the distribution of CpG loci on the array, we observed a significant enrichment of age-related DNA methylation patterns at CpG loci residing in CpG islands (P = 8.7e-6). Further, compared to non-island CpGs, loci in CpG islands were significantly more likely to exhibit increased age-related methylation (P = 0.008). To validate observed age-related DNA methylation, we performed bisulfite pyrosequencing of selected CpGs in an independent set of normal breast tissues (n=20) obtained through the National Disease Research Interchange. Our findings demonstrate consistent age-related methylation changes in normal breast tissue that may represent early events contributing to breast carcinogenesis and additional investigation for enrichment of local sequence and bioinformatic features near CpGs with age-related methylation is ongoing. This work contributes to the understanding of epigenetic mechanisms by which age serves as a major risk factor in the development of breast cancer.
Citation Format: Kevin C. Johnson, Amanda K. Jensen, Megan A. Murphy, Devin C. Koestler, Brock C. Christensen. Age-related DNA methylation in normal breast tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3640. doi:10.1158/1538-7445.AM2013-3640
Abstract 3676: Selective modulation of CHOP/GADD153 in prostate cancer cells by alpha-mangostin promotes cell death.
Authors: Li Gongbo , Petiwala Sakina , Pierce Dana , Johnson Jeremy 
Published: August 2014

Abstract
Background: It is well-established that during endoplasmic reticulum (ER) stress cells utilize several cell signal pathways collectively named “unfolded protein reaction (UPR)” to re-establish homeostasis and promote cell survival. The upregulation of UPR proteins to an extent is thought to be a growth advantage for cancer cells. However, chronic ER stress or prolonged UPR will lead to apoptosis. Alpha-mangostin, a xanthone from mangosteen fruit, has been reported to effectively induce prostate cancer cell apoptosis in vitro and suppress xenograft tumor growth. Thus, we investigated the alteration of ER stress-related proteins in mangosteen fruit extract (MFE)- or α-Mangostin-treated prostate cancer cells as well as its correlation with apoptosis.
Methods: Two human prostate cancer cell lines, 22Rv1 and LNCaP, and a prostate epithelial cell line were treated with MFE or α-mangostin. Flow cytometry, MTT and BrdU were used to evaluate cell apoptosis, viability and proliferation. Western blot and fluorescent microscopy were used to detect proteins involved in apoptosis or ER stress. We also evaluated the anti-cancer activity of MFE and α-mangostin in nude mice inoculated with 22Rv1 cells. In addition, pharmacokinetics data of α-mangostin was collected on wild type C57BL6 mice for toxicity concern.
Results: MFE increased apoptosis, decreased viability and inhibited proliferation in prostate cancer cell lines. Both MFE and α-mangostin significantly upregulated the expression of ER stress proteins, such as PERK, CHOP and IRE1α. Both MFE and α-mangostin also effectively suppressed tumor growth in a xenograft tumor model without affecting body weight. Interestingly, CHOP knockdown enhanced apoptosis in α-mangostin-treated prostate cancer cells; both MFE and α-mangostin decreased PERK expression and did not induce ER stress in prostate epithelial cells (PrECs) from prostate cancer patients.
Conclusions: Both MFE and α-mangostin selectively promote ER stress in prostate cancer cells and inhibit prostate cancer cell growth in a xenograft mouse model without observable toxicity, suggesting further research is needed to evaluate its potential as an anti-cancer agent.
Citation Format: Gongbo Li, Sakina Petiwala, Dana Pierce, Jeremy Johnson. Selective modulation of CHOP/GADD153 in prostate cancer cells by alpha-mangostin promotes cell death. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3676. doi:10.1158/1538-7445.AM2013-3676
Abstract 368: Detection of circulating tumor cells in peripheral blood of renal cell carcinoma patients is correlated with survival.
Authors: Goebel Steffen , Bluemke Karen , Bilkenroth Udo , Meye Axel , Fuessel Susanne , Lautenschlaeger Christine , Melchior Andres , Heynemann Hans , Fornara Paolo , Taubert Helge 
Published: August 2014

Abstract
Purpose:
The aim of this study was to evaluate the clinical relevance of the presence of disseminated tumor cells in peripheral blood [so called circulating tumor cells (CTCs)] for renal cell carcinoma (RCC) patients after a median follow-up time of 81 months.
Methods:
233 peripheral blood samples from 154 RCC patients were investigated for the presence of disseminated tumor cells (DTCs) by autoMACS technique and immunocytochemical (ICC) staining of cytokeratin. The frequency of CTCs was analyzed statistically for correlation with relevant clinical data.
Results:
Two kinds of tumor cells were detected: Those with expression of cytokeratin 8/18 (CK+), but also cells without a detectable CK+ expression, which we called large blue stained cells (Bl+) with a tumor-like morphology. We hypotesized, that the latter cells could be “sleeping” tumor cells.
After following the CD45 autoMACS depletion protocol, we identified CTCs in 96 out of 233 peripheral blood samples (41%), which originated from 81 out of 154 (53%) RCC patients.
An update to follow up the RCC patients was conducted in 2012. Besides a significant correlation between the detection of CTCs before and after primary tumor resection a significant association with prognosis was found (p &lt; 0.002; Chi-squared test). RCC patients with CK+ CTCs in their peripheral blood had a 5 times risk of tumor-related death compared to patients without these cells. In a Kaplan-Meier-Analysis these results were confirmed (p &lt; 0.001).
Patients with large blue stained cells (Bl+) also had a shorter survival time.
Conclusion:
In summary, for RCC patients, the presence of CTCs was associated with a poor overall survival and significantly correlated with an increased risk of tumor-related death. It is important to evaluate CK+ tumor cells to determine the role of CTCs in tumor behavior and disease progression. Detection of CK+ CTCs in peripheral blood is a significant and independent prognostic factor for renal cell carcinoma patients.
Citation Format: Steffen Goebel, Karen Bluemke, Udo Bilkenroth, Axel Meye, Susanne Fuessel, Christine Lautenschlaeger, Andres Melchior, Hans Heynemann, Paolo Fornara, Helge Taubert. Detection of circulating tumor cells in peripheral blood of renal cell carcinoma patients is correlated with survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 368. doi:10.1158/1538-7445.AM2013-368
Abstract 3684: Differential mechanisms of green tea polyphenols-induced apoptosis in human prostate cancer cells: Role of p53.
Authors: Gupta Karishma , Thakur Vijay S. , Bhaskaran Natarajan , Nawab Akbar , Babcook Melissa A. , Jackson Mark W. , Gupta Sanjay 
Published: August 2014

Abstract
Tumor suppressor gene p53 is frequently inactivated in a variety of human cancers including prostate cancer and is associated with therapeutic resistance. We have previously demonstrated that green tea polyphenols (GTP) induces apoptosis in prostate cancer cells irrespective of p53 status (Carcinogenesis 33:377-84, 2012). However, the molecular mechanisms underlying these observations are not properly understood. In the present study we investigated the mechanisms of GTP-induced apoptosis in human prostate cancer cells with and without functional p53. Human prostate cancer LNCaP cells were stably transfected with short hairpin-53 (LNCaPshp53) and control vector (LNCaPshV), exposed to GTP in dose and time dependent manner. GTP exposure induced p53 stabilization and activation of downstream targets p21/waf1 and Bax in dose-dependent manner specifically in LNCaPshV cells. However, GTP-induced FAS upregulation through the activation of c-jun N-terminal kinase resulting in FADD phosphorylation, caspase-8 activation and truncation of BID leading to apoptosis was common in both LNCaPshV and LNCaPshp53 cells. In parallel, treatment of cells with GTP resulted in inhibition of survival pathway, mediated by Akt deactivation and loss of BAD phosphorylation more prominently in LNCaPshp53 cells. These distinct routes of cell death converged to a common pathway leading to loss of mitochondrial transmembrane potential, cytochrome c release and activation of terminal caspases resulting in PARP cleavage. GTP-induced apoptosis was attenuated with JNK inhibitor, SP600125 in both cell lines; whereas PI3K-Akt inhibitor, LY294002 resulted in increased cell death in LNCaPshp53 cells, establishing the role of two distinct pathways of GTP-mediated apoptosis. Furthermore, GTP exposure resulted in the inhibition of class I HDAC protein, accumulation of acetylated histone H3 in total cellular chromatin resulting in increased accessibility to bind with the promoter sequences of p21/waf1 and Bax irrespective of p53 status of cells, consistent with the effects elicited by HDAC inhibitor, trichostatin A. These results demonstrate that GTP induces prostate cancer cell death by two distinct mechanisms irrespective of p53 status, thus identifying for the first time through defined molecular targets for their chemopreventive and/or therapeutic actions.
Citation Format: Karishma Gupta, Vijay S. Thakur, Natarajan Bhaskaran, Akbar Nawab, Melissa A. Babcook, Mark W. Jackson, Sanjay Gupta. Differential mechanisms of green tea polyphenols-induced apoptosis in human prostate cancer cells: Role of p53. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3684. doi:10.1158/1538-7445.AM2013-3684
Abstract 3699: Chemoprevention of skin cancer by benzophenone sunscreen agents in mice.
Authors: Kapadia Govind J. , Rao G Subba , Takasaki Midori , Iida Akira , Suzuki Nobutaka , Konoshima Takao , Tokuda Harukuni 
Published: August 2014

Abstract
Our recent study demonstrated the skin cancer chemoprevention potential of commonly used benzophenone sunscreen agents using the Epstein-Barr virus early antigen in vitro assay (Int. J. Cosmet. Sci. 2012: doi:10.1111/ics.12015). We now report the in vivo anti-tumor activity of two of the benzophenone sunscreens tested positive in the above in vitro assay, octabenzone (UV-1) and dioxybenzone (UV-2), in the two-stage mouse skin carcinogenesis test model utilizing (±)-(E)-4-methyl-2-[-(E)-hydroxyamino]-5-nitro-6-methoxy-3-hexanamide (NOR-1) as inducer and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) as promoter. Studies were conducted in pathogen-free, female hairless mice of HOS-HR-1 strain, 15 animals per control and test groups. Tumor was induced by a single dose of NOR-1 (390 nmol in 100 μl of acetone). One week later, TPA (1.7 nmol in 100 μl of acetone) was applied to skin twice weekly for 20 weeks as a tumor promoter. The test compounds, 0.0025% of UV-1 or UV-2 were administered to the animals through drinking water ad libitum, starting 1 week prior to tumor initiation and stopping 1 week after tumor initiation. All animals were examined weekly for the development of skin papillomas and the following were recorded: the week papillomas appeared, number of mice bearing papillomas and number of papillomas per mouse. In both UV-1 and UV-2 treated mice, 2-week delay in tumor appearance and significant inhibition of tumor incidence (50% and 60%, respectively) and burden (papilloma inhibition/mouse, 50% and 70%, respectively) were observed when compared to the positive control group. Also, treatment with both benzophenone sunscreens produced marked reduction in the average number of tumors formed per mouse (5 and 3 papillomas/mouse for UV-1 and UV-2, respectively compared to 10 papillomas in positive control group) at the end of the 20-week experimental period. These in vivo results in mice further affirm the skin cancer chemoprevention potential of benzophenone sunscreen use in humans.
Citation Format: Govind J. Kapadia, G Subba Rao, Midori Takasaki, Akira Iida, Nobutaka Suzuki, Takao Konoshima, Harukuni Tokuda. Chemoprevention of skin cancer by benzophenone sunscreen agents in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3699. doi:10.1158/1538-7445.AM2013-3699
Abstract 3707: Early stage inhibition of murine mammary carcinogenesis by ultraviolet radiation.
Authors: Makarova Anastasia M. , Wang Grace , Wang Lynn , Wang Joy , Khaimskiy Yefim , Epstein Ervin H. 
Published: August 2014

Abstract
Epidemiological studies of geographical variations in breast cancer mortality rates have found increased death rates at higher latitudes in USA and other countries 1. This breast cancer latitudinal gradient is hypothesized to be mediated by ultraviolet radiation (UVR) - produced vitamin D3. We first have tested this latitudinal hypotheses using the well-described C3(1)/Tag transgenic murine mammary carcinogenesis model2. We have found that UVR significantly prolongs palpable tumor - free survival (135±23 vs.118±18 days) and reduces the tumor burden and multiplicity (2.9±1.6 vs. 7.2±2.3 tumors), but does not alter the time between the appearance of the first palpable tumor and death in Tag female mice. Therefore we have focused on the effects of UVR on earlier stage carcinogenesis. Tag transgenic female mice have a time-dependent increase in the incidence of ductal carcinoma in situ (DCIS) - like incidence. Thus, Tag mice develop ductal epithelial atypia in 50% of mice at age 8 wks, with progression to intraepithelial neoplasia (resembling human DCIS) in 70-90% of mice (in at least one gland) at 10-13 wks, and DCIS-like changes and early invasion in 100% of mice at age 14-15 wks. We compared weekly the similarity of histological changes between the pairs of mammary glands and found no significant gland site-to-gland site variations. UVR treatment, 350mJ/cm2 thrice weekly from age 6 wks to 15 wks, reduced both the percentage of DCIS-bearing mice (65, 60, 51, 32 and 20% reduction at week 8, 9, 11, 13 and 14) and the percentage of DCIS-bearing glands in each animal (82, 55, 66, 20 and 19% reduction at week 9, 11, 13, 14 and 15). The mechanism of the UVR-mediated prevention of the murine mammary carcinogenesis is unclear but there is evidence favoring a Hedgehog (HH) signaling-dependent mechanism, since D3 is a potent inhibitor of the HH signaling pathway, which is upregulated in many cancers including breast cancer3-5. Consistent with this idea we found that UVR reduces DCIS-like changes in Ptch+/- mice. Taken together our results support our hypothesis that inhibition of early stage mammary carcinogenesis by UVR-produced vitamin D3 underlies the latitudinal gradient. 1. Garland, F. C. et all. Prev Med 1990, 19, 614-22. 2. Green, J. E. et all. Oncogene 2000, 19, 1020-7. 3. Bijlsma, M. F. et all. PLoS Biol 2006, 4, e232. 4. Moraes, R. C. et all. Development 2009, 136, 1423-32. 5. Lewis, M. T. et all. Development 1999, 126, 5181-93.
Citation Format: Anastasia M. Makarova, Grace Wang, Lynn Wang, Joy Wang, Yefim Khaimskiy, Ervin H. Epstein. Early stage inhibition of murine mammary carcinogenesis by ultraviolet radiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3707. doi:10.1158/1538-7445.AM2013-3707