bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2794: Urinary estrogen metabolites and prostate cancer risk: A case control analysis using healthy and biopsy controls
Authors: Kosti Ourania , Goldman Lenka , Bebu Ionut , Hsing Ann , Collins Sean , Dritschilo Anatoly , Lynch John , Xu Xia , Veenstra Timothy , Goldman Radoslav 
Published: February 2011

Abstract
Prostate gland is considered as an androgen-dependent organ, however it is now recognized that estrogens and their receptors are involved in the normal and abnormal growth of the prostate gland. The aim of this study was to evaluate urinary estrogens and estrogen metabolites (EMs) as a biomarker for prostate cancer risk and identify factors that affect EM levels in urine. Using a liquid chromatography-tandem mass spectrometry method, urinary concentration of 15 EMs was determined in 77 prostate cancer cases, 77 healthy controls and 37 subjects that underwent biopsy and confirmed to be cancer-free (biopsy controls). Multivariate Analysis of Variance (MANOVA) was used to identify the interactions among the EM levels and their association to case control status. Wilcoxon rank-sum test was used to compare urinary EM concentrations individually by case status. Results showed that the 3 groups were comparable when MANOVA testing was applied. Ranking of EM concentrations showed that the catechol estrogen 4-OHE1 was relatively more abundant in prostate cancer patients compared to participants without cancer. Univariate analysis showed a tendency for the metabolites with high estrogenic activity, namely16-KE2 and 17-epiE3 to be secreted in lower amounts among prostate cancer patients. Multivariate logistic regression analysis confirmed that having low 16-KE2 (based on median of healthy controls) increased risk of prostate cancer with an adjusted odds ratio (OR) of 1.97 (95% CI, 0.86-4.52). A significant trend of increasing risk with lower 16-KE2 levels was also observed (P-for-trend = 0.02), with OR for the highest quartile of 4.62 (95% CI =1.34-15.99) compared to the lowest quartile. To identify factors that affect EM levels, we performed analysis among the healthy controls; being a current smoker was associated with a significant increase in the 2-hydroxy products 2-OHE1 and 2-MeOE1 and a marginal increase in the 2-OHE1/16α-OHE1 ratio. Age, body Mass Index (BMI), presence of diabetes, family history of prostate cancer or presence of BPH did not affect estrogen levels in our population. Our study did not allow stratified analysis by race due to the small numbers of non-Caucasian subjects. To conclude, our findings encourage further investigation of urinary estrogens and EMs as biomarkers for prostate cancer risk assessment.
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 2794.
Abstract 2796: Circulating 25-hydroxyvitamin D and prostate cancer risk in a large male cohort
Authors: Albanes Demetrius , Weinstein Stephanie J. , Snyder Kirk , Yu Kai , Horst Ronald , Virtamo Jarmo 
Published: February 2011

Abstract
Vitamin D compounds have been shown to inhibit prostate tumorigenesis experimentally, but based on the small number of epidemiological studies conducted to date, the relation between vitamin D status and prostate cancer risk remains unclear. We investigated the association between 25-hydroxyvitamin D [25(OH)D] and prostate cancer in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of 50-69 year old Finnish men. To 1,000 cases diagnosed during up to 20 years of follow-up, we matched 1,000 controls on age (within 1 year) and baseline blood collection date (within 30 days). Serum samples were assayed for 25(OH)D using the DiaSorin LIAISON 25(OH)D method (intra-batch and inter-batch CVs, 10.5% and 12.3%), and conditional multivariate logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for the prostate cancer-25(OH)D association, conditioned on the matching factors and adjusted for body mass index, residence, benign prostatic hyperplasia, and the trial supplements. 25(OH)D concentrations were categorized according to quintiles based on control cut-points of &lt;18.6, −28.3, −39.7, &gt;53.3 nmol/L. ORs (95% CIs) for Q1-Q5 were 1.00 (reference), 1.39 (1.04-1.86), 1.54 (1.14-2.08), 1.20 (0.88-1.62), and 1.41 (1.03-1.93)(p-trend=0.06). These findings were similar for subgroups of age, season of blood draw, time from blood draw to diagnosis, body mass index, vitamin D intake, and disease stage. Analyses of 25(OH)D based on clinically-defined categories, season-adjusted (by regression residual method), and season-specific cut-points yielded similar results. Our findings suggest that men with lower serum 25(OH)D levels may be at lower risk of developing prostate cancer compared to men with higher levels.
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 2796.
Abstract 2905: Is obesity the cause for the increasing incidence of CRC in patients under 50 years of age and can an anti-adenoma antibody identify those at risk
Authors: Hwang Allen , Elkin Daniel , Kaplan David , Antaki Fadi , Rambus Mary Ann , Leavell Bonita , Naumoff Joann , Rodriguez Rebecca , Hatfield James , Xu Yi , Patel Pragnesh , Guirguis Tatwig , Lawson Michael , Tobi Martin 
Published: February 2011

Abstract
CRC incidence in patients &lt;50 years of age has increased by 17% in the last decade predominantly rectal cancer in Whites (Siegel et al, 2009). This age group is rarely screened. We determined the rectal binding Adnab-9 antibody in patients &lt;50 years and a &gt;50 year control at high clinical CRC risk of cancer. Methods: Adnab-9 is an adenoma-carcinoma sequence marker. We performed Adnab-9 immunohistocemistry on colonoscopic rectal biopsies. Results: Our study found that of 25 patients age &lt;50 years, 48% had rectal binding of Adnab-9 versus 21.8% in 220 patients ≥50yrs (p&lt;0.01) and with BMI was confirmed as an independent risk factor by multivariate analysis. Demographics are summarized (Table) and significant differences were seen for gender, ASA intake and BMI, however female gender was equally distributed 58.3 in the positive and 61.5% in the negative group. Hematochezia tended (p=0.23) to associate with positive rectal binding (50 versus 23%) and the colonoscopic finding was more likely to reveal adenomatous tissue in the positive group (58.3 versus 23.1%, p=0.11). Older patients were significantly more likely to take ASA which may have reduced the polyp number in this group and they also have an decreased BMI (p&lt;0.02). In the entire group Adnab-9 positivity correlated with BMI as a continuous variable (U=0.03; p&lt;0.01). Conclusions: Adnab-9 is an independent CRC risk marker in patients &lt;50 years of age suggesting that they are more prone to development of neoplasia. The mechanism appears to be that of an adenoma-carcinoma sequence. ASA may be a factor but was not an independent mitigating marker in this study. BMI is also greater in the younger group and may be the underlying cause of the observed increase in neoplasia in the young. Adnab-9 staining of sigmoidoscopic rectal biopsies may be a convenient way of identifying a high-risk population of patients &lt;50 years of age for CRC surveillance in this population hithertofore not afforded screening.Parameter (n)Patients &lt;50 (25)Patients &gt;50 (220)Age(mean+st.deviation[SD])44.8 (5.4)62.4 (9.3)% Non-Hispanic Whites4041.4% Female Gender60 (OR 11.0, CI 4.4-27.2; p&lt;0.0001)10.9Any NSAID/Statin/ASA(%)30.4/44/41.18/4.6 (less ASA-p&lt;0.02)37.6/46.6/30.5Symptom %/BMI(SD)60/31.6(6.1) (BMI p&lt;0.02)*42.9/28.7(5.4)
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 2905.
Abstract 2909: ApoFLIP: A bioactive peptide that restarts the apoptotic machinery in cancer cells
Authors: Jin Taiguang , Kurakin Alexei , Song Keli , Wang Jun-Xia , Santos Tanya , Khosravi-Far Roya 
Published: February 2011

Abstract
The cellular factors inhibiting apoptosis are often employed by cancer cells to resist therapy. c-FLIP is an endogenous inhibitor of apoptosis upregulated in many drug resistant tumors. Herein, we show that a peptide derived from c-FLIP is a potent inducer of apoptosis in both in vitro and in vivo cancer models. Mechanistic studies suggest that the apoptogenic peptide of c-FLIP (ApoFLIP) removes the inhibition of pro-apoptotic signaling at the level of activated death receptors by competing c-FLIPL off receptor complexes and clearing the way for activation of the caspase cascade. At the same time, ApoFLIP impairs the pro-survival signaling along the PI3K/Akt pathway by blocking the interaction between the p85 subunit of PI3K and c-FLIPL. The selectivity and apoptogenic potency of ApoFLIP in killing cancer cells suggests that simultaneous targeting of two or more hallmark features of cancer may prove to be a winning therapeutic strategy.
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 2909.
Abstract 2910: Mono- or double-site phosphorylation distinctly regulates the proapoptotic function of Bax
Authors: Wang Qinhong , Wang Ton , Gao Fengqin , Sun Shi-Yong , Khuri Fadlo R. , Curran Walter J. , Deng Xingming 
Published: February 2011

Abstract
Bax is the major multidomain proapoptotic molecule that is required for apoptosis. It has been reported that phosphorylation of Bax at serine(S) 163 or S184 activates or inactivates its proapoptotic function, respectively. To uncover the mechanisms by which phosphorylation at these two sites regulate the proapoptotic function of Bax, a series of serine (S)→ alanine/glutamate (A/E) mutants, including S163A, S184A, S163E, S184E, S163E/S184A (EA), S163A/S184E (AE), S163A/S184A (AA) and S163E/S184E (EE), were created to mimic or abrogate, respectively, either single or double-site phosphorylation. The compound Bax mutants (i.e. EA and AE) can flesh out the functional contribution of individual phosphorylation site(s). WT and each of these Bax mutants were overexpressed in Bax−/− MEF or human lung cancer H157 cells and the proapoptotic activities were compared. Intriguingly, expression of any of Bax mutants containing the mutation S→A at S184 (i.e. S184A, EA or AA) represents more potent proapoptotic activity as compared to WT Bax in association with conformational change, mitochondrial localization/insertion and prolonged half-life. In contrast, all Bax mutants containing the mutation S→E at S184 (i.e. S184E, AE or EE) have decreased protein stability and less apoptotic activity without conformational change and mitochondrial localization/insertion. Unexpectedly, mutation either S→A or S→E at S163 site does not significantly affect the proapoptotic activity of Bax. These findings indicate that S184 but not S163 is the major phosphorylation site for functional regulation of Bax's activity. Thus, manipulation of the phosphorylation status at S184 may represent a novel strategy for treatment of cancers that express Bax.
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 2910.
Abstract 2913: Autophagy resulting from specific ablation of the proapoptotic function of cytochrome c
Authors: Li Hua , Wang Peng , Yu Jian , Zhang Lin 
Published: February 2011

Abstract
Apoptosis and autophagy are two evolutionarily conserved and sometimes mutually exclusive cell death regulatory mechanisms. The balance and cross talk between these two processes determine cell fate and have an important role in therapeutic response to anticancer agents. It has been shown that apoptosis can cross talk with autophagy through the actions of the Bcl-2 family proteins. For example, Bcl-2 inhibits autophagy by interacting with Beclin-1, the master regulator of autophagy. However, the underlying mechanisms by which apoptosis and autophagy regulate each other remain unclear. In this study, we investigated whether cytochrome c (cyto c), a critical regulator of the mitochondrial apoptotic pathway, is involved in regulating autophagy. A cyto c mutant (K72A) that retains its normal electron transfer function but fails to bind to Apaf-1 was knocked into HCT116 colorectal cancer cells by homologous recombination. Although the mutant cyto c can still be released from the mitochondria into the cytosol in response to apoptosis induction, caspase activation and other execution steps of apoptosis were inhibited. Remarkably, a significant increase in autophagy was observed in the cyto c-knockin cells, as indicated by formation of GFP-LC3 puncta and increased conversion of LC3-I into LC3-II. Furthermore, knockdown of Beclin-1 by siRNA suppressed autophagy in the cyto c-knockin cells. These results indicate that the execution steps of apoptosis downstream of cytochrome c release, including formation of apoptosome and activation of caspases, can inhibit autophagy. Autophagy can be unleashed when apoptosis is initiated, but fails to be executed.
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 2913.
Abstract 2936: In situ antitumor immunotherapy with pharmacological blockade of MFG-E8 and chemotherapy against solid and hematological tumors
Authors: Jinushi Masahisa , Tahara Hideaki , Koyasu Shigeo , Dranoff Glenn 
Published: February 2011

Abstract
The conventional anticancer strategies, such as chemotherapy and radiotherapy, induce the tumor cell death, which would theoretically become the source of tumor antigens to be recognized in situ by the immune system. However, most of the cytotoxic therapies rarely induce the immunological responses potent enough to cause obvious tumor destruction in the actual clinical settings. This discrepancy might be caused by the tumor evasion systems, which restrain the induction of host immune responses. Thus, the therapeutic efficacy of various anticancer agents could be improved if the novel strategies are found to reverse molecular machineries of tumor-mediated immune evasion.
Milk-fat globule EGF-8 (MFG-E8) has been known to maintain tissue homeostasis in multiple aspects; regulating the phagocytosis of apoptotic cells, breast tissue morphogenesis, intestinal epithelium homeostasis and angiogenesis. Here we have shown that the therapeutic interference of MFG-E8 synergistically potentiates antitumor activities of various cytotoxic and target therapies, and radiotherapy, against various murine tumors. These antitumor activities relied on the induction of the potent and specific antitumor immune responses in situ. The MFG-E8 blockade triggered infiltration and activation of dendritic cells at the tumor sites, where apoptotic cells were made available with cytotoxic treatments, resulting in the potent antitumor effector T cell activation and inhibition of Foxp3+Treg cell function. Furthermore, the administration of anti-MFG-E8 antibodies switches the receptor for MFG-E8-mediated tumor cell ingestion from integrins αvβ3 to activating FcγRI/III receptors in dendritic cell recognition of tumor cells, augmenting dendritic cell-mediated cross-priming of tumor-specific T cells.
These findings demonstrated that the blockade of MFG-E8, one of the key negative regulators to restrain immune responses against the dying cells, would be a novel strategy to improve durable antitumor responses by various anticancer therapeutic agents.
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 2936.
Abstract 2967: The p53 target gene TRIM22 colocalizes with the centrosome independently of cell cycle phase
Authors: Petersson Jessica , Lönnbro Per , Herr Anna-Maria , Mörgelin Matthias , Gullberg Urban , Drott Kristina 
Published: February 2011

Abstract
TRIM22 (Staf50) is an interferon (IFN)-inducible protein as well as a p53 target gene. The specific molecular function of TRIM22 is largely unknown, but TRIM22 is suggested to play a role in viral defense by restriction of viral replication. Furthermore, TRIM22 may function as an ubiquitin E3 ligase, targeting proteins for degradation. TRIM22 is highly expressed in lymphoid tissues as well as in peripheral blood leukocytes and in the ovary and lung. TRIM22 belongs to the TRIM family of proteins, named based on a characteristic tripartite-motif (TRIM), including a RING-finger, one or two B-boxes and a coiled-coil domain. The TRIM family consists of more than 70 proteins, implicated in diverse biological processes such as apoptosis, cell proliferation, viral defense and ubiquitylation. Several TRIM family members are involved in cancer. Interestingly, TRIM proteins have been suggested to identify specific cell compartments by means of multimerization. There have previously been conflicting reports regarding the subcellular localization of exogenous TRIM22. Utilizing immunoflourescence and subcellular fractionation, we show here that endogenous TRIM22 is localized to both nucleus and cytosol in the human osteosarcoma cell line U2OS. Furthermore, the same localization pattern is present in human peripheral blood mononuclear cells (PBMCs), an environment more relevant to its physiological function. Moreover, we demonstrate a colocalization of TRIM22 with the centrosomes in U2OS cells as well as in PBMCs, and show that this colocalization is independent of cell cycle phase, utilizing the centrosome markers gamma-tubulin, aurora A and pericentrin. The centrosomal localization was confirmed with electronic microscopy, suggesting TRIM22 to be localized in the pericentriolar material (PCM) and not at any specific site at the centrioles. Additionally, the colocalization with centrosomes appears to be independent on the microtubule network as shown by the microtubuli destabilizing agent nocodazole. Centrosomes are essential organelles, vital for mitosis and organization of the microtubule network as well as providing sites for viral replication, viral assembly and protein degradation. Our data suggest that centrosomal TRIM22 may have important functions in these processes. However, further studies are required to confirm this notion.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 2967.
Abstract 2986: Melanocytes are deficient in repair of oxidative DNA damage and UVC induced photoproducts
Authors: Wang Hsiang-Tsui 
Published: February 2011

Abstract
Melanomas occur mainly in sunlight-exposed skin, xeroderma pigmentosum complementation (XP) patients, defective in nucleotide excision repair function, have 1000-fold higher incidence of melanoma. These findings indicate that sunlight induced “bulky” photoproducts are responsible for melanomagenesis. On the other hand, sunlight also induces a high level of reactive oxygen species (ROS) in melanoctes (MC), oxidative DNA damage (ODD) therefore may contribute to melanomagenesis and that the XP protein may participate in ODD repair. To address these questions we determined: 1) the effect of melanin on UVA (320-400 nm) irradiation induced ODD and UV photoproducts using formamidopyrimidine glycosylase (Fpg) and UvrABC incision assays, 2) the repair capacity for ODD and UV-induced photoproducts in MC and XPA cells using host cell reactivation and in vitro DNA repair synthesis assays. We found: 1) UVA irradiation-inducing a significantly higher amount of Fpg sensitive ODD in MC than in normal human skin fibroblasts (NHSF). In contrast, UVA irradiation induces an insignificant amount of UvrABC sensitive sites in either of these two types of cells. 2) Compared to NHSF, MC have a reduced repair capacity for ODD and photoproducts. 3) H2O2 modified DNA induces a higher mutation frequency in MC than in NHSF. 4) XPA cells are deficient in ODD repair and ODD induces a higher mutation frequency in XPA cells than in NHSF. Based on these results, we propose: 1) UVA is a major etiological agent for melanomagenesis and the mechanism is through melanin sensitizes UVA in induction of ODD and reduced repair capacity in MC; 2) the reduced repair capacity for ODD contributes to the high melanoma incidence in XPA 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 2986.
Abstract 2991: Glucose deprivation induces Chk1 degradation through the ubiquitin-proteasome pathway and defective checkpoint response to replication blocks
Authors: Kim Ae Jeong , Kim Hyun-Ju , Jee Hye Jin , Bae Yoe-Sik , Yun Jeanho 
Published: February 2011

Abstract
Chk1 is a key regulator for DNA replication checkpoint and preservation of genomic integrity. Previous studies showed that reduction of Chk1 function leads to defect in checkpoint response and closely associated to tumorigenesis. Here, we found that Chk1 protein is rapidly degraded upon glucose deprivation while its mRNA level is not changed. The glucose deprivation-induced Chk1 degradation is observed in various cancer cell lines as well as human normal fibroblast therefore appears to be a universal phenomenon in mammalian cells. Specific proteasome inhibitor blocks glucose deprivation-induced degradation of Chk1, and the ubiquitination of Chk1 is induced, indicating that the proteasome-ubiquitin pathway mediates the degradation of Chk1. Glucose deprivation-induced Chk1 degradation was not affected by AMPK inhibitor compound C or antioxidant NAC and GSH treatment. Instead, we found that Chk1 phosphorylation at Ser317 and Ser345 site were important step for degradation of Chk1 in response to glucose deprivation. In glucose deprivation condition, cells showed defective checkpoint response to replication stresses, camptothecin (CPT) and hydroxyurea (HU) treatment. Taken together, our results suggest that Chk1 function is suppressed through the ubiquitin-mediated proteolysis in glucose deprivation condition and thereby results in inactivation of proper checkpoint function. Glucose deprivation-induced Chk1 degradation could cause defect in maintaining DNA integrity and may contribute to tumor development in tumor microenvironment.
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 2991.