bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2536: VEGF as a potential survival factor for keratinocytes following UV exposure in vivo
Authors: Nye Kelly E. , Lachey Monica K. , Parent Allison E. , Wilgus Traci A. 
Published: August 2012

Abstract
Non-melanoma skin cancer (NMSC) is the most prevalent type of cancer. These cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are primarily caused by chronic exposure to ultraviolet light (UV) from the sun. Vascular endothelial growth factor (VEGF) is produced by the skin in response to UV and is known to promote NMSC indirectly through the induction of angiogenesis. Evidence is emerging that VEGF can also promote skin carcinogenesis by directly affecting epidermal keratinocytes and tumor cells. In addition, epidermal keratinocytes express VEGFR-1 and proliferate and migrate directly in response to VEGF. In endothelial cells, VEGF functions as a potent survival factor by inhibiting apoptosis; however, it is not known if VEGF promotes survival in keratinocytes. Keratinocytes undergo apoptosis in response to UV exposure, a process that can be disrupted during carcinogenesis. Here, the role of VEGF and VEGFR-1 in keratinocyte and SCC-13 tumor cell survival after UV exposure was explored. Neutralizing VEGF or VEGFR-1 activity or adding VEGF did not affect UV-induced apoptosis, suggesting that VEGF-VEGFR-1 signaling is not important for keratinocyte or SCC-13 survival in vitro. The role of VEGFR-1 in keratinocyte survival was also examined in vivo. Mice with VEGFR-1-deficient keratinocytes (K14-Cre/VEGFR-1fl/fl) were generated and exposed to a single acute dose of UV light. Keratinocytes in the epidermis of K14-Cre/VEGFR-1fl/fl mice showed a significant increase in apoptosis 24 hours following UV exposure compared to K14-Cre/VEGFR-1+/+ controls. Future studies will investigate skin carcinogenesis in K14-Cre/VEGFR-1fl/fl mice chronically exposed to UV light. Overall, these results suggest that VEGFR-1 mediates the survival of keratinocytes exposed to acute UV in vivo and points to a mechanism by which VEGF could directly promote skin carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2536. doi:1538-7445.AM2012-2536
Abstract 2537: UVB irradiation induces nuclear translocation of TC-PTP in keratinocytes
Authors: Lee Young S. , Smith Liza Morales , Slaga Thomas J. , DiGiovanni John , Kim Dae J. 
Published: August 2012

Abstract
Ultraviolet B radiation (UVB) can cause DNA damage, induce gene mutations and modulate intracellular signal transduction contributing to the development of skin cancer. Signal transducer and activator of transcription 3 (Stat3) modulates various physiological functions, including apoptosis, cell cycle regulation, and tumor angiogenesis through regulation of gene expression, and its constitutive activation is associated with human epithelial cancers. Recent studies demonstrated that T-cell protein tyrosine phosphatase (TC-PTP) dephosphorylates activated Stat3 in keratinocytes after UVB irradiation. In the current work, we report that TC-PTP translocates from the cytosol to the nucleus and dephosphorylates Stat3 following UVB irradiation in keratinocytes. Western blot analysis showed that TC-PTP mainly localized in the cytoplasm of keratinocytes and translocated from cytoplasm to nucleus upon UVB irradiation. Immunofluorescence analysis of the exogenous expression of TC-PTP confirmed its nuclear translocation, and showed that nuclear translocation of TC-PTP occurs independently of its phosphatase activity. Nuclear translocation of TC-PTP was increased with increased dose of UVB exposure. Dephosphorylation of Stat3 by TC-PTP was enhanced after UVB irradiation of cultured keratinocytes with nuclear accumulation of TC-PTP. Knockdown of TC-PTP with siRNA suppressed dephoshorylation of Stat3 and enhanced cell viability in response to UVB irradiation. UVB irradiation also induced expression of 14-3-3α, a protein that has been shown to be involved in the transport of proteins. Further studies revealed that UVB-induced nuclear translocation of TC-PTP was effectively inhibited by knockdown of 14-3-3α, suggesting 14-3-3α is involved in nuclear import of TC-PTP. These results indicate that TC-PTP plays an important role as a regulator of Stat3 signaling in keratinocytes upon UVB irradiation. Nuclear translocation of TC-PTP is regulated by a 14-3-3α-dependent signaling pathway, resulting in the rapid dephosphorylation of activated Stat3 in the nucleus.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2537. doi:1538-7445.AM2012-2537
Abstract 2591: Caffeic acid phenethyl ester (CAPE) suppresses melanoma tumor growth by inhibiting AKT/XIAP pathway
Authors: Pramanik Kartick C. , Kudugunti Shashi , Moridani Majid , Srivastava Sanjay K. 
Published: August 2012

Abstract
The incidence of melanoma is constantly on the rise indicating that current available therapies are not very effective. Moreover, melanoma is highly metastatic and resistant to chemotherapeutic drugs. Our previous studies have demonstrated that caffeic acid phenethyl ester (CAPE) suppress the growth of melanoma cells and induce ROS generation. However, the exact mechanism of the growth suppressive effects of CAPE was not clear. Here we determined the potential mechanism of CAPE against melanoma in vitro and in vivo. In a concentration and time-dependent study, CAPE treatment suppressed the activating phosphorylation of PI3K at Tyr-458, PDK1 at Ser-241, mTOR at Ser-2448 and AKT at Ser-473 in B16F0 and SK-MEL-28 melanoma cells. Furthermore, the expression of XIAP, survivin and BCl2 were down-regulated by CAPE treatment in both the cell lines. Significant apoptosis was observed in both the cell lines by CAPE treatment as indicated by cleavage of caspase-3 and PARP. AKT kinase activity was inhibited by CAPE in a concentration-dependent manner. Since Akt regulates XIAP, their interaction was examined by immunoprecipitation studies. Our results show that CAPE treatment decreased the interaction of AKT with XIAP. To establish the involvement of Akt in the apoptosis-inducing effects of CAPE, cells were transfected with Akt. Our results reveal that AKT over-expression attenuated the decrease in XIAP and significantly blocked CAPE-mediated apoptosis. Similarly, over-expression of XIAP further decreased CAPE-induced apoptosis. To confirm the involvement of ROS in the inhibition of AKT/XIAP pathway, cells were treated with antioxidant NAC prior to CAPE treatment. Our results indicate that NAC blocked CAPE mediated AKT/XIAP inhibition and protected the cells from apoptosis. In addition, oral administration of 10mg/kg/day CAPE substantially suppressed the growth of B16F0 tumor xenografts in C57BL/6 mice. Tumors from CAPE treated mice showed reduced phosphorylation of PI3K, AKT, mTOR and protein level of XIAP and enhanced the cleavage of caspase-3 and PARP. Taken together, our results suggest that CAPE suppresses AKT/XIAP pathway leading to apoptosis in melanoma tumor cells in vitro and in vivo. [Supported in part by R01 grant CA129038 (to S.K.S) awarded by the National Cancer Institute].
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2591. doi:1538-7445.AM2012-2591
Abstract 2592: Vitamin E forms and 13′-carboxychromanol, a long-chain metabolite of α-tocopherol, induce cell death by interrupting de novo sphingolipid synthesis in human cancer cells
Authors: Jang Yumi , Rao Xiayu , Jiang Qing 
Published: August 2012

Abstract
Studies have shown that vitamin E forms including gamma-tocopherol (≥T), delta-tocopherol (≥T) and especially gamma-tocotrienol (≥TE), a major form of vitamin E in palm oil, exhibited potent anticancer activities in various types of cancer cells. 13′-carboxychromanol (13′-COOH), a long-chain metabolite of αT, has recently been shown to have anti-inflammatory activities and appears to induce apoptosis in certain type of cancer cells. However, the molecular mechanisms of the anticancer effects are not understood. In the current study, we found that 13′-COOH inhibited the growth and induced death of human colon and pancreatic cancer cells in a time- and dose-dependent manner. In these activities, 13′-COOH was more potent than αTE, which is much stronger than αT and αT. Since we have previously shown that αTE and αT induce prostate cancer cell death by modulation of sphingolipid metabolism, we investigated whether αTE and 13′-COOH have effects on sphingolipids using liquid chromatography tandem mass spectrometry. Treatment of HCT116 cells with αTE or 13′-COOH significantly increased dihydroceramides and dihydrosphingosine, two sphingoid bases in de novo synthesis pathway of sphingolipids. In contrast, sphingomyelins and ceramides remained largely unchanged after treatment. This accumulation of intracellular dihydroceramides and no apparent change of sphingomyelins suggest potential inhibition of dihydroceramide desaturase (DEGS) enzyme by these compounds. Consistently, we found that αTE inhibited the DEGS activity in a time- and dose-dependent manner in an in situ assay, while it did not have any effect on DEGS expression. These results indicate that αTE and 13′-COOH interrupt de novo synthesis of sphingolipids, which play a role in regulating cell death.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2592. doi:1538-7445.AM2012-2592
Abstract 2603: Subtype-specific ovarian cancer risk associated with SNPs in IL1A
Authors: Charbonneau Bridget , White Kristin L. , Schildkraut Joellen M. , Palmieri Rachel T. , Iversen Ed , Berchuck Andrew , Vierkant Robert A. , Rider David N. , Cicek Mine S. , Sutphen Rebecca , Birrer Michael J. , Pharoah Paul P.D. , Song Honglin , Tyrer Jonathan , Gayther Simon A. , Ramus Susan J. , Wentzensen Nicolas , Yang Hannah P. , Garcia-Closas Montserrat , Phelan Catherine M. , Cunningham Julie M. , Fridley Brooke L. , Sellers Thomas A. , Goode Ellen L. 
Published: August 2012

Abstract
As pathways of the immune system play an important role in multiple malignancies, we assessed the association between single-nucleotide polymorphisms (SNPs) in inflammation-related genes and risk of ovarian cancer in a multi-site case-control study. Using a custom array, we genotyped 930 epithelial ovarian cancer cases and 1,037 controls for SNPs in ALOX12, ALOX15, ALOX5, CCL11, CCL2, CCL3, CCR3, CRP, CXCL16, IL10, IL15RA, IL18, IL1A, IL1B, IL1RN, IL4R, IL6, IL6R, IL7R, IL8RA, IL8RB, IL9, NOS3, PTGS1, PTGS2, TLR2, and TNF. After analysis by logistic regression, SNPs with p&lt;0.10 were evaluated in an independent data set of 3,143 cases and 2,102 controls from the Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI) collaboration. Combined analysis revealed association with interleukin 1, alpha (IL1A) SNPs (rs17561 and rs4848300, r2=0.990, p=0.005) which varied by histological subtype (heterogeneity p=0.03). For example, IL1A rs17561, which results in a missense change in amino acid at position 114 and correlates with multiple inflammatory phenotypes, was inversely associated with risk of clear cell, mucinous, and endometrioid subtypes, but not with the serous subtype (Table 1). Additional data on IL1A rs17561 in an even larger collection of ovarian cancer cases and controls are pending and will be analyzed soon. We also found that genotype at rs1864414 in ALOX5 (arachidonate 5-lipoxygenase) was associated with decreased risk combined across subtypes (OR 0.86, 95% CI 0.78-0.95; p=0.002). Thus, inherited variation in IL1A and ALOX5 appears to have a role in ovarian cancer risk, though it is limited to rarer subtypes for IL1A. These data add to existing literature on the importance of inflammation in tumorigenesis and growing evidence of subtype-specific traits in ovarian cancer and may provide important clues on prevention.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2603. doi:1538-7445.AM2012-2603
Abstract 2604: Transforming growth factor beta signaling pathway variants and breast cancer risk: results from the Shanghai Breast Cancer Genetics Study
Authors: Ma Xiangyu , Beeghly-Fadiel Alicia , Cai Qiuyin , Lu Wei , Gao Yu-Tang , Long Jirong , Zhang Ben , Shi Jiajun , Zheng Ying , Shu Xiao-Ou , Zheng Wei 
Published: August 2012

Abstract
The transforming growth factor beta (TGF-β) signaling pathway is critical for several important cellular functions, and plays dual roles in the carcinogenic process. We systematically evaluated associations of common variants in TGF-β signaling pathway genes with breast cancer risk using a multi-staged, population-based, case-control study among Chinese women. In Stage I, 341 single nucleotide polymorphisms (SNPs) with MAFs ≤ 0.05 across 11 genes were evaluated among 2,926 cases and 2,380 controls. In Stage II, 20 SNPs with promising associations were evaluated among an additional 1,890 cases and 2,000 controls. Six SNPs from the TGFB2, TGFBR1, TGFBR2 and TGFBR3 genes were found to have consistent and significant associations in combined analyses with breast cancer risk in combined analyses of Stage I and Stage II data. One variant, TGFBR2 rs1078985, had not only consistent, but also highly significant associations with breast cancer risk in both study stages, as well as promising results from in silico analysis, and so was further evaluated. Results from additional genotyping in Stage III (2,475 cases and 2,343 controls) were also consistent; compared with the major allele homozygotes (GG) of rs1078985, reduced breast cancer risks were associated with AA(OR=0.75, 95%CI=0.60-0.94) and AG (OR=0.89, 95%CI=0.82-0.96) genotypes (Ptrend =0.0003). These data support a role for common genetic variation in TGF-β signaling pathway genes, specifically for a variant in TGFBR2, in breast cancer susceptibility.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2604. doi:1538-7445.AM2012-2604
Abstract 2605: Apolipoprotein E polymorphisms, plasma cholesterol, and prostate cancer
Authors: Shui Irene M. , Platz Elizabeth A. , Stampfer Meir , Mucci Lorelei A. , Giovannucci Edward 
Published: August 2012

Abstract
Background: Men who use cholesterol-lowering statin drugs and those with lower cholesterol levels may have a decreased risk of aggressive prostate cancer (PCa), providing support for further investigation of cholesterol metabolism in the etiology of PCa. Apolipoprotein E (APOE) plays an important role in cholesterol metabolism and may also affect tumor growth and angiogenesis. Compared to the APOE wild-type isoform (e3e3), the e4 allele has been associated with elevated cholesterol and the e2 allele with lower cholesterol. Our study aimed to determine if APOE polymorphisms were associated with PCa risk, especially aggressive disease, and whether this association varied by plasma total cholesterol level. Methods: We included 1193 total PCa cases and 1244 controls nested in the prospective Health Professionals Follow-up Study (1993-2004). APOE status was characterized by genotyping two SNPs (rs429358 and rs7412). Total plasma cholesterol was measured enzymatically. We calculated odds ratios and 95% confidence intervals for PCa risk (overall, high grade, and advanced stage/lethal) using unconditional logistic regression comparing e2 and e4 carriers to men homozygous for e3. Results: APOE genotype prevalence in controls was: e3e3 (0.60), e2e3 (0.14), e2e2 (0.007), e3e4 (0.22), e4e4 (0.016); those with e2e4 (0.027) were excluded from the analysis. APOE genotype was significantly associated with total plasma cholesterol: e2 carriers had significantly lower mean and standard deviation (188.5+/−34.7 mg/dL) compared to the e3e3 men (200.4+/−35.4 mg/dL) or the e4 carriers (201.2+/−36.3 mg/dL). However, we saw no significant associations with PCa by APOE genotype for total, advanced stage/lethal, or high-grade PCa (Table). There was no significant effect modification by plasma total cholesterol. Conclusions: In this large prospective cohort study we did not observe an association between APOE genotype and PCa. Future analyses will assess whether associations are modified by statin use.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2605. doi:1538-7445.AM2012-2605
Abstract 2608: Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer
Authors: Pujana Miguel Angel , Maxwell Christopher A. ,   Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
Published: August 2012

Abstract
Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio (wHR) = 1.09 (95% CI 1.02-1.16), ptrend = 0.017; and n = 3,965, wHR = 1.04 (95% CI 0.94-1.16), ptrend = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2608. doi:1538-7445.AM2012-2608
Abstract 2609: Addition of ER and PTEN, but not cytokeratins, aids identification for BRCA1 carriers in Malaysian breast cancer patients
Authors: Phuah Sze-Yee , Looi Lai Meng , Rhodes Anthony , Dean Sarah , Taib Nur Aishah Mohd , Yip Cheng Har , Teo Soo-Hwang 
Published: August 2012

Abstract
Background: Given that BRCA1 carriers are more likely to develop triple negative breast cancers (TNBC) and that current risk assessment models underestimate BRCA carriers in Asian populations, we have sought to determine the prevalence of BRCA mutations amongst TNBC patients and whether addition of pathological features improves the sensitivity of the Manchester scoring method of BRCA risk assessment. Methods: A total of 399 patients from the Malaysian Breast Cancer Genetic Study were fully analysed for BRCA1 and BRCA2 mutations, including 101 patients with TNBC. Pathological features, including estrogen receptor (ER) and PTEN status were assessed and included in a modified Manchester scoring method. Results: Our study in an Asian series of triple negative breast cancer patients has demonstrated that 22% [22/101] of patients have germline mutations in BRCA1 [18/101] and BRCA2 [4/101]. We find that amongst patients who were diagnosed with breast cancer aged 36-50 but with no family history of breast or ovarian cancer, the prevalence of BRCA mutations was similar amongst those who developed triple negative breast cancer (7%) and non-TNBC (7%). By contrast, in two other groups of patients (a) those who were diagnosed with breast cancer β35 years old with no family history of these cancers, and (b) those with family history of breast cancer, the prevalence of mutations was higher in those with TNBC compared to those with non-TNBC [29% and 11%; p=0.07; and 40% and 14%; p=0.001 respectively]. Furthermore, we find that incorporation of estrogen-receptor status improves the sensitivity of the Manchester Scoring method [38% to 62%] and in particular, incorporation of the status of PTEN, further improves sensitivity [43% to 100%]. Conclusion: We find that TNBC is an important criteria for highlighting patients who may benefit from genetic testing, but that this may be most useful for individuals with early onset breast cancer (≥35 years old) or with family history of cancers. Furthermore, addition of ER and PTEN status improves the sensitivity of the Manchester scoring method and may be particularly important in the Asian context when family history is often inaccurately reported.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2609. doi:1538-7445.AM2012-2609