bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1244: Licofelone, a dual COX-LOX inhibitor prevents transitional cell carcinoma of urinary bladder in UPII-SV40T transgenic mice
Authors: Madka Venkateshwar , Mohammed Altaf , Li Qian , Zhang Yuting , Biddick Laura , Lightfoot Stanley , Wu Xue-Re , Kopelovich Levy , Steele Vernon , Rao Chinthallapally V. 
Published: May 2015

Abstract
Urinary bladder cancer is the sixth most commonly diagnosed cancer and significant proportion of the patients diagnosed with bladder cancer have high-grade tumors that are at potential risk for post-surgical recurrence and metastasis, where 5-year survival is very low. Hence it is important to identify and develop regimens that prevent urothelial tumorigenesis. Inflammatory pathways particularly, cyclooxygenase (COX-2) and lipoxygenase (5-LOX) mediated metabolites are known to play important role in bladder tumor progression. Consistent with that epidemiological and clinical observations suggest that use of anti-inflammatory agents is associated with reduced risk for bladder cancer. Here we determined the chemopreventive efficacy of a Licofelone, a dual COX-LOX inhibitor, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC). Six-week old transgenic UPII-SV40T mice (n=30/group) were fed control (AIN-76A) or experimental diets containing 150 or 300 ppm licofelone for 34 weeks. At 40 weeks of age, all mice were euthanized; urinary bladders were collected to determine urothelial tumor weights and histopathological grading. Results suggest that bladders of the control diet fed transgenic mice weighed 3-5 fold more than that of the wild type mice. However, treatment of transgenic mice with licofelone led to a significant, dose dependent inhibition of the urothelial tumor weights (65.2 - 82.7%, p&lt;0.0001 in males; 35.0 - 49.0%, p&lt;0.0001 in females) compared to the control group. Importantly, mice fed licofelone diet significantly reduced development of invasive tumors. Urothelial tumor progression to invasive TCC was inhibited in both male (up to 50%; p&lt;0.01) and females mice (up to 46%; p&lt;0.003). Molecular analysis of urothelial tumors by immuno-histochemisty, qPCR and/or western immunoblotting for the expression of various markers that effect tumor growth and progression showed an increase in apoptosis (p53, p21, Bax, Caspase3, Annexin V) with a decrease in proliferation and angiogenesis (PCNA, COX2, 5LOX, mPGES2, VEGF) in the licofelone diet fed mice tumors. These results suggest that licofelone can serve as potential chemopreventive for bladder TCC. (Supported in part by NCI-CN53300)
Citation Format: Venkateshwar Madka, Altaf Mohammed, Qian Li, Yuting Zhang, Laura Biddick, Stanley Lightfoot, Xue-Re Wu, Levy Kopelovich, Vernon Steele, Chinthallapally V. Rao. Licofelone, a dual COX-LOX inhibitor prevents transitional cell carcinoma of urinary bladder in UPII-SV40T transgenic mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1244. doi:10.1158/1538-7445.AM2014-1244
Abstract 1252: 6-c-(e-phenylethenyl)-naringenin suppresses colorectal cancer growth by inhibiting cyclooxygenase-1
Authors: Li Haitao , Zhu Feng , Chen Hanyong , Cheng Ka Wing , Zykova Tatyana , Oi Naomi , Lubet Ronald A. , Bode Ann M. , Wang Mingfu , Dong Zigang 
Published: May 2015

Abstract
Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors therefore COX-1 is now being reconsidered as a target for chemoprevention. Our aim was to examine whether selective COX-1 inhibition could delay or prevent cancer development and clarify the underlying mechanisms. Data clearly showed that COX-1 was required for maintenance of malignant characteristics of colon cancer cells or tumor promoter(s)-induced transformation of pre-neoplastic cells. We also successfully applied a ligand docking computational method to identify a novel selective COX-1 inhibitor, 6-C-(E-phenylethenyl)-naringenin (designated herein as 6CEPN). 6CEPN could bind to COX-1 and specifically inhibit its activity both in vitro and ex vivo. In colorectal cancer cells, it suppressed anchorage-independent growth by inhibiting COX-1 activity. 6CEPN also effectively suppressed tumor growth in a 28-day colon cancer xenograft model without any obvious systemic toxicity. Taken together, COX-1 plays a critical role in human colorectal carcinogenesis, and the specific COX-1 inhibitor merits further investigation as a potential preventive agent against colorectal cancer.
Keywords: colon cancer; natural product; cyclooxygenases; signal transduction
Note: This abstract was not presented at the meeting.
Citation Format: Haitao Li, Feng Zhu, Hanyong Chen, Ka Wing Cheng, Tatyana Zykova, Naomi Oi, Ronald A. Lubet, Ann M. Bode, Mingfu Wang, Zigang Dong. 6-c-(e-phenylethenyl)-naringenin suppresses colorectal cancer growth by inhibiting cyclooxygenase-1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1252. doi:10.1158/1538-7445.AM2014-1252
Abstract 1277: The association between seasonality, vitamin D and calcium intake and mammographic density in Norwegian postmenopausal women
Authors: Ellingjord-Dale Merete , Silva Isabel dos Santos , Grotmol Tom , Sakhi Amrit Kaur , Qureshi Samera , Hofvind Solveig , Markussen Marianne Skov , Couto Elisabeth , Andersen Lene Frost , Ursin Giske , Ursin Giske 
Published: May 2015

Abstract
Background:
Mammographic density (MD) is one of the strongest known breast cancer risk factors. The role of vitamin D in breast cancer etiology is unclear. The evidence of an association between Vitamin D and MD is limited and inconsistent, as is the seasonal variation of MD. We evaluated the association between MD and season/month the mammogram was obtained, as well as vitamin D intake, energy and calcium intake in a population of women from Norway, a country with limited sunlight exposure for a large part of the year.
Methods:
We studied 2662 postmenopausal women aged 50-69 who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004 or 2006/07. Women completed risk factor and food frequency questionnaires (FFQ). Vitamin D and calcium intake was assessed with and without taking supplements into consideration. Month of mammogram was recorded from the mammogram. MD was assessed using a computer assisted method (Madena, University of Southern California). We used linear regression to determine the association between month of mammogram and MD, as well as vitamin D and calcium intake (assessed from the FFQ) and MD, adjusting for age, education, body mass index (BMI), parity and postmenopausal estrogen and progestin therapy. We also examined the association between vitamin D, calcium and MD by season (month) the mammogram was obtained.
Results:
Age, BMI and parity were inversely associated with MD, while education and postmenopausal estrogen and progestin therapy were positively associated\ with MD. There was no association between quartiles of vitamin D or calcium intake and MD, regardless of whether the nutrients were estimated with our without supplements. We found no association between season (month) and MD. There was no evidence for an inverse association between vitamin D intake and MD when women were stratified by the month the mammogram was obtained.
Conclusion:
Our results provide no support for a protective effect of dietary vitamin D intake against increased MD. We found no evidence that season or month the mammogram was obtained, was associated with MD.
Citation Format: Merete Ellingjord-Dale, Isabel dos Santos Silva, Tom Grotmol, Amrit Kaur Sakhi, Samera Qureshi, Solveig Hofvind, Marianne Skov Markussen, Elisabeth Couto, Lene Frost Andersen, Giske Ursin, Giske Ursin. The association between seasonality, vitamin D and calcium intake and mammographic density in Norwegian postmenopausal women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1277. doi:10.1158/1538-7445.AM2014-1277
Abstract 1287: Mutations in the CBL gene among breast cancer patients in an Asian clinic-based population
Authors: Wong Edward , Yap Yoon Sim , Cheng Ying Ying , Chua Delia , Hong Lewis Zuocheng , Burkholder William F. , Ho Gay Hui , Tan Min Han , Ang Peter , Lee Ann S.G. 
Published: May 2015

Abstract
INTRODUCTION
Although mutations in BRCA1 and BRCA2 are associated with familial hereditary breast and ovarian cancer, mutations are only found in 20 to 25% of these patients. This suggests that additional genes may be mutated. The Casitas B-lineage lymphoma (CBL) gene encodes a RING finger E3 ubiquitin ligase. Recent studies have shown that mutations in the CBL gene occurs in human acute myeloid leukemia and lung cancers. The relationship of the CBL gene with breast cancer, however, is not well characterized. The aim of this study was to identify mutations in the CBL gene in Asian patients with familial or early-onset breast cancer.
METHODS
All patients (n=75) were accrued at the risk assessment clinic at the National Cancer Centre Singapore, and presented with a family history of breast and/or ovarian cancer or early-onset breast cancer. Screening for mutations in the BRCA1 and BRCA2 genes was performed using Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). Next generation sequencing was done using the Agilent SureSelect target-enrichment technology on the Illumina MiSeq platform, followed by validation using Sanger sequencing.
RESULTS
Two mis-sense variants in the CBL gene were identified. They are CBL c. 560C&gt;T (p. A187V) and c. 1858C&gt;T (p.L620F) occurring in 2/75 (3%) and 8/75 (11%) of the patients, respectively. Both mis-sense mutations were predicted to be damaging using Polyphen-2 and SIFT. The p.A187V alteration was predicted to interrupt the N-terminal tyrosine kinase binding domain (TKB) that is important for ligand-induced ubiquitination of receptor tyrosine kinases (RTKs). The CBL c. 1858C&gt;T variant has previously been reported in the NCBI database (rs2227988). Three individuals, who carried this mutation, had early-onset breast cancer. In addition, the p.L620F alteration within the proline-rich region, may disrupt the interactions of binding partners to the c-CBL protein, which are required to recruit c-CBL to RTKs. All patients, except one, with germline CBL mutations were negative for BRCA1 and BRCA2 mutations.
CONCLUSION
This preliminary study has identified damaging CBL mutations in an Asian population with breast cancer and warrants further investigations in other breast cancer populations.
Citation Format: Edward Wong, Yoon Sim Yap, Ying Ying Cheng, Delia Chua, Lewis Zuocheng Hong, William F. Burkholder, Gay Hui Ho, Min Han Tan, Peter Ang, Ann S.G. Lee. Mutations in the CBL gene among breast cancer patients in an Asian clinic-based population. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1287. doi:10.1158/1538-7445.AM2014-1287
Abstract 1292: Identification of BRCA1 and BRCA2 founder mutations in population isolates from Colombia
Authors: Tuazon Anna Marie D. , Ramírez Carolina , Bohorquez Mabel , Prieto Rodrigo , Castro Jorge , Mateus Gilbert , Velez Alejandro , Echeverry Magdalena , Carvajal-Carmona Luis G. 
Published: May 2015

Abstract
Breast cancer (BC) is the most common malignancy in women. Germline mutations in breast cancer risk genes, such as BRCA1 and BRCA2, account for a large portion of hereditary breast cancer families. The contribution of mutations in breast cancer susceptibility genes has been poorly investigated in minority populations, such as in Hispanics from South America. While mutations in BRCA1 and BRCA2 display a heterogeneous mutation spectrum, specific mutations often occur in population isolates. Using the KASP genotyping technology, we screened 476 unselected Colombian breast cancer patients for three common BRCA1 and one BRCA2 founder mutations in the Hispanic population. The BRCA2 c.2806_2809delAAAC founder mutation was identified in 3 of the 476 BC cases (0.6%). Strikingly, 24 out of 476 cases (5.0%) harbored the BRCA1 founder mutation c.3331_3334delCAAG, which has also been reported in Southern European populations, including Spain and Portugal. The clinical data and family history of these patients have highlighted a distinct geographic region from where these cases originate. This finding potentially represents one of the most remarkable founder effects reported in human populations. To date the arrival of the BRCA1 c.3331_3334delCAAG mutation to Colombia, we are completing haplotype analysis of the patients and their families, along with BC cases from Spain and Portugal that harbor the same mutation. Interestingly, haplotype analyses of our BC cases have revealed a haplotype larger than 3.5 cM. In the future, we aim to perform haplotype analysis of family members of the mutation carriers and BC cases from Portugal and Spain to further study the haplotype around this BRCA1 mutation, which will allow us to date the origin of the mutation. By understanding the prevalence of mutations in known breast cancer risk genes in minority populations, cancer disparities can be better addressed and breast cancer screening can be improved. Furthermore, the ability to identify such strong founder effects highlights an advantage of using this Colombian population isolate in facilitating the identification of novel BC risk genes.
Citation Format: Anna Marie D. Tuazon, Carolina Ramírez, Mabel Bohorquez, Rodrigo Prieto, Jorge Castro, Gilbert Mateus, Alejandro Velez, Magdalena Echeverry, Luis G. Carvajal-Carmona. Identification of BRCA1 and BRCA2 founder mutations in population isolates from Colombia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1292. doi:10.1158/1538-7445.AM2014-1292
Abstract 13: Color-coded imaging of vessel anastomosis in vivo using RFP and CFP transgenic mice
Authors: Uehara Fuminari , Tome Yasunori , Maehara Hiroki , Tanaka Kazuhiro , Kanaya Fuminori , Miwa Shinji , Hiroshima Yukihiko , Yano Shuya , Yamamoto Mako , Matsumoto Yasunori , Hoffman Robert M. 
Published: May 2015

Abstract
We previously report the development of a color-coded imaging model that can visualize the anastomosis between blood vessels of red fluorescent protein (RFP)-expressing vessels in Gelfoam® previously vascularized in RFP transgenic mice and blood vessels of nestin-driven green fluorescent protein (ND-GFP) mice that express GFP in nascent vessels (Anticancer Res. 33: 3041-3046, 2013). In the present study, fourteen days after transplantation into RFP transgenic nude mice, the Gelfoam® was removed and re-transplanted into the subcutis on the flank of cyan fluorescent protein (CFP) transgenic mice. Skin flaps were made and anastomosis between the CFP-expressing vessels and RFP blood vessels in the Gelfoam® was imaged 14 and 21 days after re-transplantation. The results presented in this and our previous report suggest a new paradigm of visualizing blood vessel anastomosis and its implications for tumor angiogenesis.
Citation Format: Fuminari Uehara, Yasunori Tome, Hiroki Maehara, Kazuhiro Tanaka, Fuminori Kanaya, Shinji Miwa, Yukihiko Hiroshima, Shuya Yano, Mako Yamamoto, Yasunori Matsumoto, Robert M. Hoffman. Color-coded imaging of vessel anastomosis in vivo using RFP and CFP transgenic mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 13. doi:10.1158/1538-7445.AM2014-13
Abstract 1304: Cyclin D:Cdk4/6 activates RB by mono-phosphorylation during early G1 phase
Authors: Dowdy Steven F. , Kaulich Manuel 
Published: May 2015

Abstract
The retinoblastoma tumor suppressor protein (Rb) functions to transcriptionally regulate multiple critical cellular activities, including early G1 phase, the DNA damage response, cell cycle exit and differentiation, but is infrequently mutated or deleted in cancer. To account for the lack of Rb mutations, a large body of work over the last 20+ years has led to a widely accepted model of G1 cell cycle progression that proposes cyclin D:Cdk4/6 complexes partially inactivate Rb during early G1 phase by progressive multi-phosphorylation, termed hypo-phosphorylation, on 15 Cdk sites resulting in release of E2F transcription factors that drive cells across the late G1 phase checkpoint and ultimately undergo cellular division. Surprisingly given the importance of G1 cell cycle progression in cancer, the core tenet of the model, namely cyclin D:Cdk4/6 inactivation of Rb by progressive multi-phosphorylation, remains largely unproven biochemically. Consequently, it remains entirely unknown if hypo-phosphorylated Rb contains one, two, three, five, seven or more phosphates, at what phosphate number hypo-phosphorylated Rb releases E2F transcription factors, what the phosphorylation kinetics are and what the biologically active form(s) of Rb during early G1 phase is. Here using highly synchronized normal and tumor cells combined with two-dimensional isoelectric focusing (2D IEF) to quantify the number of phosphates on Rb, we find no evidence to support the 20 year old notion that cyclin D:Cdk4/6 complexes progressively hypo-phosphorylate Rb. In contrast, we discovered that cyclin D:Cdk4/6 complexes exclusively mono-phosphorylates Rb throughout early G1 phase, and generates fourteen independent mono-phosphorylated Rb isoforms. Cells undergoing a DNA damage response activate cyclin D:Cdk4/6 complexes to generate mono-phosphorylated Rb that regulated global transcription, whereas non-phosphorylatable Rb remained non-functional. These observations fundamentally change our understanding of G1 cell cycle progression and show that mono-phosphorylated Rb, generated by cyclin D:Cdk4/6 complexes, is the functionally active isoform of Rb in early G1 phase.
Citation Format: Steven F. Dowdy, Manuel Kaulich. Cyclin D:Cdk4/6 activates RB by mono-phosphorylation during early G1 phase. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1304. doi:10.1158/1538-7445.AM2014-1304
Abstract 1310: Increased cytoplasmic CDC25A phosphatase in cutaneous squamous cell carcinoma leads to 14-3-3 relocalization and suppression of apoptosis
Authors: Almatouq Jenan , Ho Kristen , Hansen Laura A. 
Published: May 2015

Abstract
Non-melanoma skin cancer, the most common cancer in the United States, frequently results from chronic exposure to ultraviolet (UV) irradiation. UV-induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin-dependent kinase activators, the Cell Division Cycle 25 (CDC25) phosphatases, which are over-expressed and, thus, deregulate cell cycle control in many human cancers. To investigate a role for CDC25 in skin cancer, CDC25 levels were examined in both UV-induced mouse tumors and human skin cancer. CDC25A and CDC25C protein and transcripts were increased in benign and malignant skin tumors from UV-exposed v-rasHa transgenic Tg.AC mice. CDC25B protein but not transcripts was increased in mouse skin tumors compared to normal skin. Similarly, CDC25A and CDC25C but not CDC25B were elevated in human squamous cell carcinoma (SCC) and in the premalignant precursors actinic keratosis and Bowen's disease when compared to skin. While CDC25A was localized primarily to nuclei in normal epidermis, both the premalignant precursors and SCC exhibited strong cytoplasmic CDC25A localization. To determine whether increased CDC25A stimulates proliferation in skin SCC, CDC25A levels were modulated by siRNA-targeting or forced expression in cultured SCC cells, but no difference in proliferation resulted. Because cytoplasmic CDC25A can bind to the apoptotic regulator 14-3-3, we hypothesized that the increase in cytoplasmic CDC25A may suppress apoptosis. Forced over-expression of CDC25A in SCC cells suppressed cell death, whereas CDC25A silencing increased apoptotic cell death. Phosphorylation of CDC25A at serine178, a docking site for 14-3-3 proteins, was elevated in the cytoplasmic compartment of SCCs, and cytoplasmic 14-3-3ϵ was increased in cutaneous SCC.Mutation of the nuclear export sequence on CDC25A relocalized both CDC25A and 14-3-3ϵ to the nucleus, while mutation of 14-3-3 binding sites on CDC25A led to a decrease in 14-3-3ϵ levels. Furthermore, silencing of 14-3-3ϵ increased cell death by 60%. Taken together, these data suggest that increased cytoplasmic CDC25A in cutaneous SCC may suppress apoptotic cell death through its interaction with 14-3-3ϵ.
Citation Format: Jenan Almatouq, Kristen Ho, Laura A. Hansen. Increased cytoplasmic CDC25A phosphatase in cutaneous squamous cell carcinoma leads to 14-3-3 relocalization and suppression of apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1310. doi:10.1158/1538-7445.AM2014-1310
Abstract 1318: Mps1 is modified by sumoylation during the cell cycle
Authors: Restuccia Agnese , Yang Feikun , Yixin Yao , Dai Wei 
Published: May 2015

Abstract
Mps1 is a dual specificity protein kinase with crucial roles in regulating the spindle assembly checkpoint and chromosome microtubule attachment. Molecular mechanisms that regulate Mps1 levels and its activity during mitosis remain unclear. Given that sumoylation plays an important role in mitotic progression, we investigated if Mps1 could be modified by SUMO conjugation. Endogenous sumoylated Mps1 was detected by nickel affinity pull-down from HeLa cells that constitutively expressed His6-SUMO1 or His6-SUMO2. When HEK293T cells transfected with a plasmid construct expressing Myc-Mps1, along with plasmids expressing His-SUMO-1 and FLAG-UBC9, were analyzed sumoylated Mps1 was also detected in both asynchronized and mitotic cell populations. Expression of wild-type FLAG-SENP1 completely abrogated sumoylated Mps1 compared with cells transfected with enzymatically defective FLAG-SENP1, confirming that Mps1 is modified by sumoylation. We also identified potential lysine residues of Mps1 that were sumoylated by the mutagenesis approach. Our study reveals that Mps1 is modified via sumoylation and that future experiments will be centered on understanding the biological function of this modification during the cell cycle.
Citation Format: Agnese Restuccia, Feikun Yang, Yao Yixin, Wei Dai. Mps1 is modified by sumoylation during the cell cycle. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1318. doi:10.1158/1538-7445.AM2014-1318