bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1862: Capsaicin mediated activation of JNK/FOXO/BIM causes apoptosis in pancreatic cancer cells
Authors: Pramanik Kartick C. , Srivastava Sanjay K. 
Published: August 2014

Abstract
Capsaicin, a homovanillic acid derivative (N-vanillyl-8-methyl-nonenamide) is an active component of chili pepper. We previously reported that capsaicin mediated generation of reactive oxygen species (ROS) causes apoptosis in pancreatic cancer cells. In the present study, we investigated the potential mechanism of capsaicin mediated apoptosis in pancreatic cancer cells. In a time and concentration dependent study, capsaicin treatment activated c-Jun N terminal kinase (JNK) in BxPC-3, AsPC-1 and L3.6PL pancreatic cancer cells. Further, capsaicin induced activation of JNK in turn activated FOXO1 by phosphorylating at Ser 256 and pro-apoptotic protein BIM at Ser 69. The expression of BIM also increased in response to capsaicin treatment. Capsaicin treatment also caused cleavage of caspase-9, caspase-3 and PARP resulting in apoptosis. Blocking capsaicin mediated activation of JNK by JNK-specific inhibitor SP600125 attenuated nuclear localization of FOXO-1, activation of BIM and abrogated capsaicin-induced apoptosis. To confirm the involvement of ROS in the activation of JNK, FOXO and Bim, cells were treated with antioxidants catalase and EUK (mimetic of catalase) prior to capsaicin treatment. Our results reveal that both the antioxidants blocked capsaicin mediated JNK/FOXO/BIM activation and protected the cells from apoptosis. Furthermore, silencing FOXO1 by siRNA blocked capsaicin-mediated activation of BIM and apoptosis. To further confirm the involvement of Bim in capsaicin-induced apoptosis, cells were transfected with BIM siRNA. Silencing Bim drastically reduced capsaicin-mediated cleavage of caspase-3 and PARP indicating the role of Bim in inducing apoptosis in our model. Taken together, our results suggest that ROS generated by capsaicin activates JNK and FOXO-1 which in turn activates BIM resulting in the cleavage of caspase-9/3 and PARP leading to apoptosis in pancreatic cancer cells. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute].
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1862. doi:10.1158/1538-7445.AM2011-1862
Abstract 1867: The natural product sulforaphane protects epidermal tissue from individuals at increased risk for melanoma from the effects of UV radiation
Authors: Cassidy Pamela B. , Quackenbush John , Campbell Jennifer , Moos Philip J. , Leachman Sancy A. 
Published: August 2014

Abstract
Our study focuses on the design and testing of melanoma-prevention strategies for use in high-risk populations. Individuals who have germline loss-of-function (LOF) mutations at the highly polymorphic MC1R locus are at 4-fold increased risk for melanoma. Much of this increase likely arises from the loss of MC1R-mediated upregulation of antioxidant, DNA repair, pigment synthesis and anti-apoptotic pathways that protect epidermal melanocytes from the mutagenic effects of UV radiation. We have found that the natural product sulforaphane (SF) protects normal human melanocytes in culture from UV-induced apoptosis and oxidative stress in the absence of MC1R stimulation by its ligand α-MSH. This led us to propose that SF might be useful for protecting the skin of human subjects with LOF MC1R mutations from the harmful effects of UV light. We have sequenced MC1R in volunteers both with and without the red hair phenotype that is typical for humans with LOF mutations. Sequencing was necessary in all volunteers because many individuals with heterozygous LOF mutations do not have the signature pigmentary phenotype, but are still at increased (2-fold) risk for melanoma. Shave biopsies were harvested from those with either wild-type MC1R or two LOF alleles. The epidermal tissues were treated ex vivo with UV and/or SF then analyzed histologically and by qPCR. We found that SF ameliorated many of the effects of UV radiation in tissues from donors with LOF MC1R. This study demonstrates the promise of SF as an agent for protection of human skin in individuals with high-risk MC1R genotypes from the harmful effects of UV radiation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1867. doi:10.1158/1538-7445.AM2011-1867
Abstract 1868: Sep15 knockout in mice provides protection against chemically-induced aberrant crypt formation
Authors: Tsuji Petra A. , Carlson Bradley A. , Yoo Min-Hyuk , Xu Xue-Ming , Naranjo-Suarez Salvador , Fomenko Dmitri , Gladyshev Vadim N. , Hatfield Dolph L. , Davis Cindy D. 
Published: August 2014

Abstract
The essential nutrient selenium appears to have cancer preventive properties that are partly mediated through selenoproteins. This study investigated the role of the 15 kDa selenoprotein (Sep15) in cancer by examining Sep15 knockout in mice. Weanling homozygous Sep15 knockout, heterozygote and wild type littermate controls (N=12/genotype) were given four weekly subcutaneous injections of the known colon carcinogen azoxymethane (10 mg/kg). Sep15 knockout mice developed significantly (p&lt;0.001) fewer aberrant crypt foci (ACF) than controls. Dietary selenium (0, 0.1 or 2.0 μg selenium/g diet) did not significantly affect ACF formation in Sep15 knockout mice. To investigate molecular targets affected by Sep15 knockout, gene expression patterns in colonic mucosal cells of knockout and wild type mice were compared with microarrays and Ingenuity Pathway Analysis. Quantitative PCR and western blot analysis revealed guanylate binding protein-1 (GBP1) mRNA and protein expression to be strongly upregulated in Sep15 knockout mice. Furthermore, serum analysis indicated significant differences in cytokine expression in Sep15 knockout mice. Our results suggest that Sep15 knockout mice are protected against chemically-induced ACF formation possibly through alterations in inflammatory pathways. Funded by NCI Intramural support, the Cancer Prevention Fellowship Program, NIH grants and the Division of Cancer Prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1868. doi:10.1158/1538-7445.AM2011-1868
Abstract 1874: Public health impact of occupational carcinogens exposure and lung cancer
Authors: De Matteis Sara , Consonni Dario , Lubin Jay H. , Wacholder Sholom , Tucker Margaret , Peters Susan , Vermeulen Roel C. H. , Kromhout Hans , Bertazzi Pier Alberto , Caporaso Neil , Pesatori Angela Cecilia , Landi Maria Teresa 
Published: August 2014

Abstract
Background. Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population.
Methods. We estimated lung cancer risk associated with occupational carcinogens using a new validated job-exposure matrix (JEM), in the Environment And Genetics in Lung cancer Etiology (EAGLE) study, a large (2100 cases and 2120 controls) population-based case-control study conducted in Lombardy, Italy, between 2002-2005. The JEM translated lifetime work-histories coded into standard job-titles into never, low, and high exposure levels for six known/suspected occupational lung carcinogens. We calculated odds ratios (OR) and 95% confidence intervals (CI) in men (1537 cases and 1617 controls), by multiple logistic regression, adjusted for potential confounders, e.g., tobacco smoking and co-exposure to JEM carcinogens. We estimated the Population Attributable Fraction (PAF) as impact measure.
Results. Exposure to asbestos (OR=1.76, 95%CI=1.42 to 2.18), crystalline silica (OR=1.31, 95%CI=1.00 to 1.71), or nickel-chromium (OR=1.18, 95%CI=0.90 to 1.53) was associated with increased risk even at low exposures, with positive trends for intensity and duration. We found an excess risk for exposure to polycyclic aromatic hydrocarbons only among highly exposed workers (OR=1.64, 95%CI=0.99 to 2.70). The PAFs for any exposure to asbestos, crystalline silica and nickel-chromium were 18.1%, 5.7%, and 7.0%, respectively, corresponding to ≈300-800 lung cancer cases/year.
Conclusion. These findings support the substantial role of selected occupational carcinogens on lung cancer burden, even in a low exposed general population. Health policy interventions are warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1874. doi:10.1158/1538-7445.AM2011-1874
Abstract 1875: Lung cancer risk among hairdressers in SYNERGY – pooled analysis from case-control studies in Europe and Canada with detailed smoking data
Authors: Olsson Ann C. , Guha Neela , Brüning Thomas , Pesch Beate , Kendzia Benjamin , Wichmann Heinz-Erich , Brüske Irene , Consonni Dario , Landi Maria Teresa , Caporaso Neil , Siemiatycki Jack , Gustavsson Per , Plato Nils , Merletti Franco , Mirabelli Dario , Richiardi Lorenzo , Ahrens Wolfgang , Pohlabeln Hermann , Jöckel Karl-Heinz , Zaridze David , Cassidy Adrian , Lissowska Jolanta , Szeszenia-Dabrowska Neonila , Stücker Isabelle , Benhamou Simone , Bencko Vladimir , Foretova Lenka , Janout Vladimir , Rudnai Peter , Fabianova Eleonora , Dumitru Rodica Stanescu , Forastiere Francesco , Bueno-de-Mesquita Bas , Gross Isabelle M. , Benhaim-Luzon Veronique , Peters Susan , Vermeulen Roel , Boffetta Paolo , Kromhout Hans , Straif Kurt 
Published: August 2014

Abstract
“Occupational exposure as a hairdresser or barber” was classified as probably carcinogenic to humans by the International Agency for Research on Cancer in volume 99 (2010). Small increases in lung cancer risk (20-40%) are found in most cohort studies but without adequate adjustment for smoking. Studies in Scandinavia and the USA show a higher prevalence of smokers among hairdressers than in the general population.
The SYNERGY project has pooled information on lifetime work histories (ISCO-68) and tobacco smoking from 13479 cases and 16350 controls, including 20% women, from 11 case-control studies in 12 European countries and Canada. The original studies were conducted between 1985 and 2005. Odds ratios (OR) for lung cancer and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusted for age, sex, study, cigarette pack-years and time since quitting smoking.
Less than 1% of the study population had ever worked as hairdresser or barber (0.89% of cases and 0.74% of controls). Hairdressers and barbers experienced a slight increase in lung cancer risk OR 1.16 (95%CI 0.90-1.49), which disappeared after adjusting for smoking OR 0.97 (95%CI 0.73-1.30). Results by duration of employment showed highest risks in hairdressers with short employment. Results were similar by gender, histology of lung cancer, and for women hairdressers. We observed a slight and non-significant increase in risk for male barbers, particularly in barbers with the longest employment and after adjustment for smoking.
We could not detect an association between having worked as hairdresser or barber and increased lung cancer risk overall after adjusting for smoking. However, among male barbers we observed an increasing risk with increasing duration, although non-significant, after adjusting for tobacco smoking. Final results will include several more studies, and thereby increase the precision of our effect estimates.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1875. doi:10.1158/1538-7445.AM2011-1875
Abstract 1925: Dietary patterns and the risk of colorectal adenomas: The Black Women's Health Study
Authors: Adams-Campbell Lucile L. , Makambi Kepher H. , Collins Tanya Agurs , Bright-Gbebry Mireille , Rosenberg Lynn , Palmer Julie R. 
Published: August 2014

Abstract
Background: Colorectal adenomas are benign lesions that may be precursors to colorectal cancer. No studies of African American women have investigated dietary patterns and the risk of colorectal adenomas. Objective: We examined data from the Black Women's Health Study (BWHS) to determine whether dietary patterns are associated with the risk of colorectal adenomas. Methods: This is a prospective cohort study of 59,000 participants followed biennially since 1995. During 155,414 person-years of follow-up from 1997 to 2007 among women who had had at least one screening colonoscopy, 620 incident cases of colorectal adenomas were identified. Using Cox regression models, we obtained incident rate ratios (IRR) for colorectal adenoma in relation to quintiles of each of two dietary patterns, adjusting for other colorectal adenoma risk factors. Results: Two dietary patterns, Western and prudent, were utilized to assess the association between dietary intake and adenoma risk. The highest quintile of prudent diet, relative to the lowest quintile, was significantly associated with 34% reduced colorectal adenoma risk overall (incidence rate ratio, IRR=0.66; 95% CI, 0.50-0.87; p for trend, &lt; 0.01). Higher scores on the Western pattern were associated with higher risk of colorectal adenoma (IRR = 1.42, 95% CI 1.09-1.85 for the highest quintile relative to the lowest; p trend, 0.01). Conclusion: Our findings suggest that African American women may be able to reduce their risk of developing colorectal adenomas by following a prudent dietary pattern and avoiding a more Western pattern.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1925. doi:10.1158/1538-7445.AM2011-1925
Abstract 1926: The changing incidence of primary central nervous system lymphoma (PCNSL) in the United States (US): A surveillance, epidemiology and end results (SEER) study
Authors: Tieu Christina , Cerhan James R. , O'Neill Brian Patrick 
Published: August 2014

Abstract
Introduction. Up to now PCNSL incidence in the US was presumed to be increasing in all age groups independent of changes in nosology, new diagnostic techniques, and HIV infection. The intent of our study was, firstly, to extend our prior study of PCNSL incidence in the US (Olson et al, Cancer 2002;95:1504-10) with an additional decade of SEER data; and, secondly, to determine time trends during the HAART era in the US.
Methods. PCNSL age-adjusted incidence rates from 1973-2007 were obtained from the nine SEER registries used in the Olson et al. study. Similarly, the same exclusion criteria were used to remove PCNSL most likely associated with HIV (never married males and females; persons of unknown marital status; all cases reported in the San Francisco registry). To assess the accuracy of the criteria in removing HIV associated cases, incidence rates of Kaposi sarcoma (KS) were assessed with and without the use of the same exclusion criteria.
Results. The incidence of PCNSL in the general population decreased from 1995 to 2000. Following this decrease, the incidence stabilized and is now beginning to increase in the last 5 years. Stratifying the incidence rate by age group and employing the exclusion criteria, PCNSL incidence has remained stable in the 20-64 year old population, but has steadily increased in the 65+ population. Removing the exclusion criteria did not alter the data for the 65+ population but demonstrated a sharp drop in incidence after 1996 for the 20-64 year old population. Applying the same HIV exclusion criteria the incidence of KS resulted in no appreciable change in incidence rates over the same time frame.
Conclusion. The incidence rate of PCNSL is increasing. This increase is driven by a continued increase in incidence among the 65+ population while the incidence for those aged 20-64 has stabilized during the same time frame. An effect of HAART on PCNSL incidence in the US is suggested by the decline in the incidence among the 20-64 year old population without the HIV exclusion criteria.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1926. doi:10.1158/1538-7445.AM2011-1926
Abstract 1930: Trends of invasive and in-situ melanoma diagnosis in the U.S
Authors: Han Jiali , Wei Erin , Qureshi Abrar A. 
Published: August 2014

Abstract
Melanoma, accounts for about 4% of skin cancer cases, but is associated with 79% of skin cancer deaths. The number of new cases of melanoma in the US is rising dramatically. The incidence of in-situ melanoma is increasing at a more rapid rate than for melanoma overall. This may be due to better awareness, improved screening techniques and access to dermatologists that result in early diagnosis of melanoma. There is also concern that over the last few years, pathologists have had a lower threshold to diagnose in-situ melanoma due to medico-legal reasons. However, the lesions that are being called in-situ melanoma are most certainly severely dysplastic (atypical) nevi that are considered melanoma precursor lesions. The distinction is important to make an accurate diagnosis when providing medical care to a patient.
We investigated the trend of diagnosis and melanoma invasive versus in situ in three national prospective cohorts of women and men: Nurses’ Health Study I (1976-2008, age at enrollment 30-55), Nurses’ Health Study II (1989-2007, age at enrollment 25-42), and Health Professionals Follow-up Study (1986-2008, age at enrollment 40-75). We accrued 940 invasive and 424 in situ cases in NHS I, 447 invasive and 326 in situ cases in NHS II, and 310 invasive and 153 in situ cases in HPFS. In each cycle of 2-year follow-up, the incidence rate of melanoma steadily increased, and the increased incidence rate of in-situ melanoma was substantially greater than invasive melanoma. These trends were similar in all three cohorts. The ratio of invasive and in-situ melanoma in each cycle 2-year follow-up decreased more than 5 folds over the follow-up period in the NHS I and II. The decrease was not apparent in HPFS.
In this study, we found that in-situ melanoma incidence has continued to rise in the US in the last few decades, especially among women where the rate of in-situ melanoma increased more sharply compared to invasive melanoma incidence.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1930. doi:10.1158/1538-7445.AM2011-1930
Abstract 1932: Bortezomib sensitizes malignant human glioma cells to histone deacetylase inhibitors depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation and Mcl-1 cleavage
Authors: Premkumar Daniel R. , Jane Esther P. , Agostino Naomi R. , Pollack Ian F. 
Published: August 2014

Abstract
Glioblastomas are invasive tumors with poor prognosis despite current therapies. Unfortunately, individual targeted therapies have failed to offer long-term survival benefit. Histone deacetylase inhibitors (HDACIs) represent a class of agents that can modulate gene expression to reduce tumor growth. Suberoylanalide hydroxamic acid (SAHA, vorinostat) and LBH-589 are inhibitors of several members of the HDAC family, and we and others have noted some antiglioma activity, although insufficient to warrant use as single-agent therapy. Proteasome inhibitors represent a promising class of anticancer agents, already in clinical use, as bortezomib (PS-341/Velcade) has been approved for the treatment of multiple myeloma with inactivation of NF-κB signaling pathway. We have recently demonstrated that bortezomib exhibited potent anti-glioma activity and dramatically sensitized highly resistant glioma cells to TRAIL cytotoxicity, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. These studies showed that bortezomib enhanced vorinostat and LBH-589-induced apoptosis in malignant glioma cells. Although vorinostat or LBH-589 treatment alone did not induce apoptosis in glioma cells, efficacy was enhanced by addition of bortezomib, which promoted activation of proapoptotic mitochondrial injury, generation of ROS, and inhibition of the prosurvival NF-κB signaling pathway. Our results also revealed that cotreatment with bortezomib and vorinostat enhanced apoptosis by increasing Mcl-1, Noxa cleavage and other pro-apoptotic protein expression. The significantly enhanced antitumor activity that results from the combination of bortezomib and HDACIs offers promise as a novel treatment for glioma patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1932. doi:10.1158/1538-7445.AM2011-1932
Abstract 1938: Raf/MEK/ERK-mediated differential regulation of androgen receptor levels in prostate cancer cells
Authors: Hong Seung-Keun 
Published: August 2014

Abstract
Androgen receptor (AR), a member of the nuclear receptor superfamily, controls the growth regulatory and differentiation pathways in prostate epithelial cells, and its altered signaling is a pivotal event in the carcinogenesis of prostate epithelium. Previous studies show that basal Raf/MEK/extracellular signal-regulated kinase (ERK) activity is required for androgen-induced AR expression or for maintaining its levels in cells. However, loss of AR expression is correlated with upregulated Raf/MEK/ERK activity in certain contexts of PCa biology, including androgen withdrawal-induced PCa differentiation. Indeed, we found a strong correlation between AR downregulation and ERK1/2 phosphorylation in LNCaP cells cultured under a hormone-depleted condition and in the neuroendocrine derivates of LNCaP that were generated by prolonged culture under such condition. In this in vitro model, we investigated the role of Raf/MEK/ERK pathway in regulating AR expression. Sustained activation of the Raf/MEK/ERK pathway, mediated by an inducible Raf, was sufficient to induce AR downregulation at mRNA and protein levels in LNCaP. Interestingly, when the intensity of Raf induction was serially decreased to levels under a certain threshold, activation of the Raf/MEK/ERK pathway no longer downregulated but rather upregulated AR levels in cells. Our study therefore suggests that the Raf/MEK/ERK pathway can regulate AR levels in PCa cells in opposing contexts depending upon its different signaling intensity. We also found that sustained Raf/MEK/ERK activation can induce downregulation of full length AR as well as hormone binding domain-deficient AR isoforms in CWR22Rv1 cells, which are known to more potently stimulate PCa cell growth. Further investigation of the mechanisms underlying Raf/MEK/ERK-mediated AR downregulation may lead to a novel means to control AR levels in PCa cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1938. doi:10.1158/1538-7445.AM2011-1938