bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-24: C-terminal PTEN is essential for maintenance of genomic stability and tumor suppression
Authors: Shen Wen H. , Yin Yuxin P. 
Published: May 2015

Abstract
Tumor suppressor PTEN controls genomic stability and inhibits tumorigenesis. It is well established that the N-terminal phosphatase domain of PTEN dephosphorylates lipid PIP3 to PIP2, which antagonizes PI3K/AKT signaling. However, the C-terminal function of PTEN is much less defined. Here we describe a knock-in mouse model of a nonsense mutation that results in deletion of the entire Pten C-terminal region, referred to as PtenΔC. Mice heterozygous for PtenΔC develop multiple spontaneous tumors, including cancers of different origins and B cell lymphoma. We found that heterozygous deletion of the Pten C-terminal domain also causes genomic instability and common fragile site rearrangement. We found that Pten C terminal disruption induces p53 and its downstream targets, causing cell death by apoptosis. Simultaneous depletion of p53 promotes metastasis of thyroid cancer without influencing initiation of tumors, suggesting that p53 mainly suppresses tumor progression but not tumor initiation. This is the first evidence that PTEN and p53 plays distinct roles at different stages of tumor development. Our data highlight the essential role of the PTEN C-terminus in the maintenance of genomic stability and suppression of tumorigenesis. Finally, our work reveals a network of PTEN and p53 that controls cellular responses to environmental stresses.
Citation Format: Wen H. Shen, Yuxin P. Yin. C-terminal PTEN is essential for maintenance of genomic stability and tumor suppression. [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 LB-24. doi:10.1158/1538-7445.AM2014-LB-24
Abstract LB-246: Dietary strawberry phytochemical metabolism in saliva, urine, and genetic biomarkers in smokers and non-smokers
Authors: Ahn-Jarvis Jennifer H. , Clinton Steven K. , Riedl Kenneth M. , Sears Marta T. , Knobloch Thomas J. , Schwartz Steven J. , Weghorst Christopher M. , Vodovotz Yael 
Published: May 2015

Abstract
Background: Epidemiological studies implicate tobacco smoke and alcohol consumption are critical risk factors for oral cancer. Yet diets rich in strawberries have shown in rodent and cell studies to have significant protective effects which lower the risk of oral cancer. A fully-characterized strawberry confection was evaluated for safety and adherence in a 6-week, randomized, placebo-controlled, crossover trial involving smokers (n=12) and non-smokers (n=13).
Methods: Using HPLC with tandem mass spectroscopy, strawberry phytochemicals in strawberry powder, confection and saliva collected during a 30 minute timed intervention were fully characterized. Buccal tissue was evaluated using pre-validated TaqMan Gene Expression assays corresponding to known smoke-altered oral transcriptome biomarkers used for RT-qPCR analysis. UPLC with mass spectroscopy quantified ellagic acid metabolites (dimethyl-, isourolithin A, urolithin A, B, and C) in 24hr urine collections.
Results: Adherence strawberry confections intervention (equivalent to 2 cups of whole strawberries) in smoker (91%) and nonsmokers (99%) was excellent. Toxicities to strawberry intervention was limited to a grade I toxicity (NIH criteria). Significantly less ellagic acid and ellagitannins were observed in saliva compared to confection (p&lt;0.001). Anthocyanin profiles in saliva of smokers differed significantly than non-smokers. One biomarker, Ankyrin Repeat Domain 37 (ANKRD37), was found to be significantly down-regulated in smokers following strawberry confection intervention (p=0.0484). Significant increase (p&lt;0.001) in urolithin A (4.29 ± 1.16 nmol/24hr) and C (0.13 ± 0.03 nmol/24hr) was observed in all participants after strawberry intervention compared to anthocyanin-free diet or placebo intervention. Isourolithin A and urolithin B was observed in 29% and 24% of participants, respectively.
Conclusions: A fully characterized strawberry confection was utilized and significant changes in biomarkers of strawberry exposure from saliva, urine and genomic materials were observed. Both ellagitannin metabolites, urolithin A and C would be reliable biomarkers of strawberry exposure. Moreover, differences in ellagitannin metabolite profiles and in ANKRD37 between smokers and non-smokers warrant further studies.
Citation Format: Jennifer H. Ahn-Jarvis, Steven K. Clinton, Kenneth M. Riedl, Marta T. Sears, Thomas J. Knobloch, Steven J. Schwartz, Christopher M. Weghorst, Yael Vodovotz. Dietary strawberry phytochemical metabolism in saliva, urine, and genetic biomarkers in smokers and non-smokers. [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 LB-246. doi:10.1158/1538-7445.AM2014-LB-246
Abstract LB-248: Development of lipid-based transfection reagents for efficient expression of transgenes in hard-to-transfect cell types
Authors: Yin Dezhong , Wells Joy , Clinton James , Volpe Lysa-Anne , Grady Kevin , Curley Jeanmarie 
Published: May 2015

Abstract
How to balance high efficiency of transgene expression with low cytotoxicity is a central concern for cell biology. Developing lipid-based transfection reagents that have those attributes and can be conveniently used for multiple cell types is critical for studies in cancer biology and cell biology. To address these concerns, ATCC has developed two lipid-based transfection reagents, GeneXPlus and TransfeX™ that provide a powerful tool for efficiently transfecting a broad spectrum of cell types including continuous cancer cell lines, stem cells, immortalized cells, and primary cells with little or no cytotoxicity. For recognized hard-to-transfect cancer cell lines, like THP-1, SH-SY5Y, and Raw 264.7 cells, we have achieved over 30% GFP expression without obvious cytotoxicity by using the GeneXPlus and an EF1α-GFP vector. TransfeX™ has been found to be highly suitable for the transfection of stem cells, immortalized cell lines, and many types of primary cells such as mammary, renal and bronchial epithelial cells, dermal microvascular endothelial cells, and human dermal fibroblasts. We have developed optimized transfection protocols for the TransfeX™ transfection reagent for different cell types and achieved over 50% transfection efficiency and low cytotoxicity. ATCC will provide data showing the broad spectrum of cell types successfully transfected with either GeneXPlus or TransfeX™.
Citation Format: Dezhong Yin, Joy Wells, James Clinton, Lysa-Anne Volpe, Kevin Grady, Jeanmarie Curley. Development of lipid-based transfection reagents for efficient expression of transgenes in hard-to-transfect cell types. [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 LB-248. doi:10.1158/1538-7445.AM2014-LB-248
Abstract LB-25: CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting p53-dependent signaling pathway
Authors: Huang Qichao , Li Jibin , Xing Jinliang 
Published: May 2015

Abstract
Background & Aims: Cancer cells exhibit the reprogrammed metabolism characterized by high level of glycolysis even in the presence of oxygen. Aerobic glycolysis, known as the Warburg effect, supplys cancer cells with the substrates required for biomass generation. To date, several intracellular signaling mediators have been identified in metabolic regulation of cancer cells. However, it remains largely ambiguous how molecules on cell surface are involved in regulation of cancer metabolism. Methods: In the current study, we established several HCC cell lines differing in their CD147 (a typical transmembrane glycoprotein) expression status by zinc-finger nuclease and RNAi techniques. Then, we systematically investigated the role of CD147 in the regulation of Warburg effect in HCC cells and explored the underlying mechanism. Results: We found that CD147 significantly contributed to the reprogramming of glucose metabolism in HCC cells through a p53-dependent way. CD147 facilitated the cell surface expression of MCT1 and lactate export, which led to the activation of PI3K/Akt/MDM2 pathway and thus increased p53 degradation. The gain/loss-of-function studies demonstrated that while CD147 promoted glycolysis mediated by p53-dependent up-regulation of GLUT1 and activation of PFKL; it inhibited mitochondrial biogenesis and functions mediated by p53-dependent down-regulation of PGC1α, TFAM and P53R2. Additionally, proliferation of HCC cells was suppressed by blocking CD147 and/or MCT1 which resulted in down-regulation of glucose metabolism. Conclusions: we demonstrate that CD147 is a crucial regulator of glucose metabolism.
Citation Format: Qichao Huang, Jibin Li, Jinliang Xing. CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting p53-dependent signaling pathway. [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 LB-25. doi:10.1158/1538-7445.AM2014-LB-25
Abstract LB-252: Matrix metalloproteinase-2 dysregulate anti-tumor immunity
Authors: Godefroy Emmanuelle , Gallois Anne , Idoyaga Juliana , Jotereau Francine , Bhardwaj Nina 
Published: May 2015

Abstract
Background: Cancer cells, including melanoma, can be highly resistant to traditional treatments such as chemotherapy and radiotherapy. As a result, a lot of effort has been put into developing immune therapies to treat cancer patients. The main barrier to design effective immunotherapies is the immunosuppression induced by the tumor. Matrix metalloproteinase-2 (MMP-2) is over-expressed in most cancers including melanoma, and its expression is associated with increased dissemination and poorer survival/prognosis. Here, we not only uncovered an immunosuppressive role of MMP-2 in inducing ineffective/detrimental TH2 immune responses, but also the underlying mechanisms.
Methods: Human dendritic cells (DCs) were cultured in the presence of MMP-2 and/or various TLR agonists. DCs responses were monitored using immunostaining, ELISA or cytometric bead array methods. Autologous CD4+ T cells were stimulated using these conditioned tumor-associated antigen (TAA)-pulsed DCs. TAA-specific CD4+ T cells were cloned and characterized using mainly the same techniques as for DCs.
Results: Here we showed that MMP-2-conditioned human DCs primed naïve CD4+ T cells to differentiate into an inflammatory TH2 phenotype, i.e. mainly secreting TNFα, IL-4 and IL-13 and expressing GATA3. Accordingly, we detected MMP-2-specific CD4+ T cells displaying the same inflammatory TH2 profile in tumor-infiltrating lymphocytes from melanoma patients. Patients displaying such responses tended to have a poorer survival outcome. We revealed the underlying mechanisms for these T cell skewing: on the one hand, MMP-2 was found to degrade the type-I IFN receptor IFNAR1, thereby preventing STAT1 phosphorylation, which is necessary for IL-12 production. On the other hand, MMP-2 triggers the Toll-like receptor (TLR)-2 on DCs, which leads to NF-κB activation and OX40L expression. Both lack of IL-12 and over-expression of OX40L were found responsible for skewing T cell responses towards a detrimental TH2 phenotype.
Conclusions: MMP-2, therefore, acts as an endogenous TH2 “conditioner” and may underlie the prevalence of detrimental TH2 responses in cancer. Our findings also described the responsible MMP-2-dependent mechanisms, which open the way to novel therapeutic strategies and/or targets to skew anti-tumor CD4+ T cell responses towards a more efficient anti-tumor TH1 phenotype to treat cancer patients.
Citation Format: Emmanuelle Godefroy, Anne Gallois, Juliana Idoyaga, Francine Jotereau, Nina Bhardwaj. Matrix metalloproteinase-2 dysregulate anti-tumor immunity. [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 LB-252. doi:10.1158/1538-7445.AM2014-LB-252
Abstract LB-26: Androgen receptor splice variant AR3 promotes prostate cancer via modulating expression of autocrine/paracrine factors
Authors: Qiu Yun , Sun Feng , Yang Xi 
Published: May 2015

Abstract
Deregulation of androgen receptor (AR) splice variants have been implicated to play a role in prostate cancer development and progression. To understand their functions in prostate, we established a transgenic mouse model (AR3Tg) with targeted expression of the constitutively active and androgen-independent AR splice variant AR3 (a.k.a. AR-V7) in prostate epithelium. We found that over-expression of AR3 modulates expression of a number of tumor-promoting autocrine/ paracrine growth factors (including Tgfβ2 and Igf1) and expands prostatic progenitor cell population, leading to development of prostatic intraepithelial neoplasia. In addition, we showed that some epithelial-mesenchymal-transition (EMT) associated genes are upregulated in AR3Tg prostates, suggesting that AR3 may antagonize AR activity and halt differentiation process driven by AR and androgen. This notion is supported by our observations that the number of ck5+/ck8+ intermediate cells is increased in AR3Tg prostates after castration, and expression of AR3 transgene in these intermediate cells compromises prostate epithelium regeneration upon androgen replacement. Our results demonstrate that AR3 is a driver of prostate cancer, at least in part, through modulating multiple tumor-promoting autocrine/paracrine factors.
Citation Format: Yun Qiu, Feng Sun, Xi Yang. Androgen receptor splice variant AR3 promotes prostate cancer via modulating expression of autocrine/paracrine factors. [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 LB-26. doi:10.1158/1538-7445.AM2014-LB-26
Abstract LB-277: Irregular menstruation predicts increased risk of subsequent ovarian cancer death in a prospective cohort, The Child Health and Development Studies
Authors: Cohn Barbara A. , Cirillo Piera M. , Wang Erica T. , Cedars Marcelle I. 
Published: May 2015

Abstract
Background. Early detection of ovarian cancer has proved elusive, resulting in poor survival. This is the first prospective study to link a common reproductive condition to risk. Polycystic ovarian syndrome (PCOS) is an endocrine disorder, characterized by irregular menstrual cycles with long-term health consequences. Although some women with PCOS are infertile, the majority achieve pregnancy. It has been suggested that women with less frequent ovulation are protected, however, previous reports are inconsistent. Here we examine whether irregular cycling is associated with subsequent ovarian cancer death in a large prospective pregnancy cohort, The Child Health and Development Studies.
Methods. Subjects were 14,403 pregnant women recruited from the Kaiser Permanente Health Plan in 1959-1967 and followed for over 50 years. Menstrual irregularity, cycles &gt;35 days or anovulation, was a proxy for PCOS, identified from medical record and self-report, at a median age of 26 years in 13% of women. Linkage to California Vital Statistics and National Death Index records identified 64 ovarian cancer deaths diagnosed at a median age of 69 years.
Results. Contrary to expectations, women with irregular cycles had a two-fold greater risk of ovarian cancer (Hazard Ratio=2.4; 95% Confidence Interval=1.3,4.5), independent of age, race, parity, and weight. This association was specific to cancer of the ovary - no association was observed for breast or uterine cancer - and it increased over the follow-up period (p=0.08 for time-dependence).
Conclusions. This is the first large prospective study of irregular cycles as an early marker of ovarian cancer. If confirmed, women with irregular cycles could be targeted for screening. This finding offers a strategy to search for antecedent ovarian cancer biomarkers, creating the opportunity for new early detection strategies.
Citation Format: Barbara A. Cohn, Piera M. Cirillo, Erica T. Wang, Marcelle I. Cedars. Irregular menstruation predicts increased risk of subsequent ovarian cancer death in a prospective cohort, The Child Health and Development Studies. [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 LB-277. doi:10.1158/1538-7445.AM2014-LB-277
Abstract LB-281: Coffee intake reduces hepatocellular carcinoma risk: The Multiethnic Cohort
Authors: Setiawan Veronica Wendy , Wilkens Lynne R. , Hernandez Brenda Y. , Marchand Loic L. , Henderson Brian E. 
Published: May 2015

Abstract
Background: Coffee consumption has been suggested to reduce hepatocellular carcinoma (HCC) risk in epidemiological studies. Yet, data from prospective studies in US populations are nonexistent. Here we evaluated the association between coffee intake and HCC incidence in multiethnic US populations.
Methods: We conducted a prospective analysis of 179,890 African-American, Native Hawaiian, Japanese-American, Latino and white men and women who were recruited into the Multiethnic Cohort Study between 1993 and 1996. Participants reported their coffee consumption and other dietary and lifestyle factors at baseline and were followed up to 18 years for HCC incidence. Serologic testing for hepatitis B (HBV) and C (HCV) infection was performed on a subset of cohort participants (152 HCC cases and 460 non-cases). Hazard rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using Cox regression adjusting for sex, ethnicity, education, alcohol intake, smoking status, body mass index (BMI), and history of diabetes mellitus.
Results: During a median follow-up period of 16.6 years, 498 participants had developed HCC. High levels of regular coffee consumption were associated with reduced risk of HCC (P for trend &lt;0.0001). Compared to non-drinkers/low consumers (up to six cups per week) of coffee, individuals who consumed one to three cups of coffee per day had a 29% reduction in risk of HCC (RR=0.71; 95% CI: 0.60, 0.86) and those who had four or more cups of coffee per day had a 42% reduction in risk of HCC (RR=0.58; 95% CI: 0.36, 0.92). The inverse relationships between coffee and HCC were similar regardless of the participants’ ethnicity, sex, BMI, smoking status, alcohol intake, or diabetes status. Within a subset of cohort participants with available HBV and HCV serologic data, coffee consumption was not associated with infection status (P=0.63).
Conclusions: These results suggest that an increased coffee consumption may reduce the risk of developing HCC in multiethnic US populations.
Citation Format: Veronica Wendy Setiawan, Lynne R. Wilkens, Brenda Y. Hernandez, Loic Le Marchand, Brian E. Henderson. Coffee intake reduces hepatocellular carcinoma risk: The Multiethnic Cohort. [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 LB-281. doi:10.1158/1538-7445.AM2014-LB-281
Abstract LB-286: Aspirin and nonsteroidal anti-inflammatory drug use and the risk of upper aerodigestive tract cancer
Authors: Macfarlane Tatiana V. , Lefevre Karen , Watson Margaret C. 
Published: May 2015

Abstract
Introduction: Aspirin and other NSAIDs are widely used as analgesic and preventative agents. Data on the chemopreventative role of these drugs on the risk of the upper aerodigestive tract (UADT) cancer are insufficient and mostly refer to oesophageal cancer.
Aim: To investigate the effect of aspirin and other NSAIDs use on the risk of UADT cancers. Specific objectives were to investigate risk by cancer sub-site, duration of use and type of NSAIDs.
Methods: A nested case-control study using the Primary Care Clinical Informatics Unit (PCCIU) database. Conditional logistic regression was used for data analysis.
Results: There were 2,392 cases of UADT diagnosed between 1996 and 2010 and 7,165 age, gender and medical practice matched controls from 131 general medical practices. Mean age of cases was 66 years (SD 12), and most cases were males (63%). Aspirin was prescribed in a quarter of cases and controls, COX-2 inhibitors were prescribed in 4% of cases and 5% of controls and other NSAIDs were prescribed in 33% of cases and 36% of controls. Aspirin prescription was associated with non-significant reduced risk of cancer of UADT (OR 0.9 95% CI 0.8, 1.0), head and neck (HN) cancer (OR 0.9, 95% CI 0.7, 1.1) or the oesophagus (OR 0.8, 0.7, 1.0). Similar results were found for COX-2 prescription. Prescription of other NSAIDs was associated with significantly reduced risk of cancer of UADT (adjusted OR 0.8, 95% CI 0.7, 0.9), HN (adjusted OR 0.8, 95% CI 0.7, 0.9) and the oesophagus (OR 0.8, 0.7, 0.9). Significant risk reduction occurred with an increased number of aspirin prescriptions (OR 0.8, 95% CI 0.6, 0.9) for over 29 prescriptions compared to “never” aspirin prescription (test for trend P&lt;0.001).
Conclusion: There is evidence of a decreased risk of UADT cancer associated with ever being prescribed an NSAID (non-COX-2) as well as with increased number of aspirin prescriptions.
Citation Format: Tatiana V. Macfarlane, Karen Lefevre, Margaret C. Watson. Aspirin and nonsteroidal anti-inflammatory drug use and the risk of upper aerodigestive tract cancer. [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 LB-286. doi:10.1158/1538-7445.AM2014-LB-286