bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3800: Antiproliferative effect of fingolimod (FTY720) in human prostate cancer cells: Insights to estrogen metabolism in situ
Authors: Allam Rasha M. , Mosli Hisham A. , Khalifa Amany E. , Nofal Salwa M. , Sharaf Ola A. , Abdel-Naim Ashraf B. , Al-Abd Ahmed M. 
Published: May 2015

Abstract
Sphingokinase-1/sphingosine-1-phosphate pathway contributes significantly to progression of different types of cancer which has been recently reported to influence estrogen level in breast cancer cells. Current evidence suggests that estrogen (E2) and its metabolites, especially catechol metabolites, are playing a key role in the proliferation and carcinogenesis of the prostate glands. FTY720 is Sphingokinase-1inhibitorwhich possess anticancer properties in various tumor cell types. The aim of this study is to investigate the chemotherapeutic effect of FTYY720 against prostate cancer cells with emphasis on estrogenic microenvironment in-situ. The IC50 of FTY720 in DU145 cell line was4.2±1.4µg/ml. The concentration of estrogen and its metabolites were assayed in the media over DU145 cells using liquid chromatography tandem mass (LC/MS) technique. FTY720 treatment resulted in a dramatic decrease in estradiol (E2) and estrone (E1) levels compared to control untreated cells (2652.76±115.62 vs. 725.69±1.28 and 283.36±4.18vs. 150.32±8.96ng/g, respectively); however, it had no significant effect on the concentration of Estriol(E3). In terms of catechol estrogens, 4-hydroxyEstradiol (4-OHE2) and 2-hydroxy Estradiol (2-OHE2) formation was significantly decreased after treatment withFTY720 compared to control cells (25.42±2.40 vs. 7.45±0.82 and 485.93±3.10 vs. 477.42±4.24 ng/g), respectively. FTY720 had no significant effect on formation of 16α-hydroxyEstrone (16 α-OHE1). On the other hand, treatment with FTY720 significantly increased the concentration of 2-methoxyestrone (2-MOHE1) and 2-methoxyestradiol (2-MOHE2) compared to control cells (5.45±0.12 vs. 29.94±2.97 and165.62±5.67 vs. 269.97±15.85), respectively..The expression of catechol estrogen synthesizing enzymes (CYP19, CYP1A1 and CYP1B1) was significantly decreased within prostate cancer cells after treatment with FTY720 compared to untreated counterpart. On the other hand, the expression level of catechol estrogen degrading enzyme (COMT) was significantly decreased. Cell cycle analysis of DU145 cells showed arrest at G1 phase with significant decrease in the G2-M population due to treatment with FTY720. In conclusion, FTY720 induced anti proliferative effect in prostate cancer cells might be attributed partly to its influence on estrogen metabolism in-situ.
Citation Format: Rasha M. Allam, Hisham A. Mosli, Amany E. Khalifa, Salwa M. Nofal, Ola A. Sharaf, Ashraf B. Abdel-Naim, Ahmed M. Al-Abd. Antiproliferative effect of fingolimod (FTY720) in human prostate cancer cells: Insights to estrogen metabolism in situ. [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 3800. doi:10.1158/1538-7445.AM2014-3800
Abstract 3814: FAK inhibition targets nucleostemin, a nucleolar protein, impacting breast cancer spheroid growth and tumor progression
Authors: Tancioni Isabelle , Uryu Sean , Miller Nichol L. G. , Lawson Christine , Jean Christine , Chen Xiao Lei , Schlaepfer David D. 
Published: May 2015

Abstract
Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that controls cell proliferation and survival downstream of integrin-matrix receptors. However, under deprivation of anchorage, FAK translocates to the nucleus. The nucleolus, a non-membrane structure within the nucleus, is important in the control of ribosome biogenesis, regulates the sequestration of nuclear proteins, and increased nucleolar size is a marker of aggressive tumors. Nucleostemin, a nucleolar-localized protein, acts to modulate cell cycle progression and anchorage-independent cell growth. Although many drugs have low efficacy on tumor cells cultured in suspension, nanomolar small molecule FAK inhibitor (PF-271 or PND-1186) addition can prevent anchorage-independent growth of tumor cells as spheroids through mechanism(s) that remain unresolved. Here, we show that pharmacological FAK inhibitor (FAK-I) treatment or kinase-dead (KD) FAK re-expression analyses reduced breast cancer (MDA-MB-231 and 4T1-L) anchorage-independent cell growth with a G0/G1 cell cycle block. This was associated with a specific decrease in nucleostemin protein levels. As FAK-KD forms a complex with nucleostemin, and proteasome inhibitor treatment increased nucleostemin levels in FAK-KD cells, FAK-KD may function as a scaffold to facilitate nucleostemin degradation. In orthotopic breast cancer mouse tumor models, oral FAK-I administration or FAK-KD expression resulted in smaller tumors, decreased Ki67 positive cells, and lower levels of tumor-associated nucleostemin. Ongoing experiments are focused on understanding the molecular mechanisms of FAK nucleolar localization and the regulation of nucleostemin protein levels. Our results point to a novel function of FAK in nucleolar function, spheroid growth, and breast cancer progression.
Supported by NIH CA102310 and Susan G. Komen for the Cure (KG111237).
Citation Format: Isabelle Tancioni, Sean Uryu, Nichol L. G. Miller, Christine Lawson, Christine Jean, Xiao Lei Chen, David D. Schlaepfer. FAK inhibition targets nucleostemin, a nucleolar protein, impacting breast cancer spheroid growth and tumor progression. [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 3814. doi:10.1158/1538-7445.AM2014-3814
Abstract 3818: Tumor budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma
Authors: Kubo Naoshi , Ohira Masaichi , Sakurai Katsunobu , Toyokawa Takahiro , Tanaka Hiroaki , Muguruma Kazuya , Yashiro Masakazu , Maeda Kiyoshi , Onoda Naoyoshi , Hirakawa Kosei 
Published: May 2015

Abstract
Background The endoscopic treatment has been increasingly used for T1 esophageal squamous cell carcinoma (ESCC). However, this therapy is sometimes incomplete if the depth of the T1 primary tumor reaches the muscularis mucosae (MM) or submucosal layer (SM) because these tumors have relatively high incidences of lymph node metastasis. However, no previous report on the predictive factor of nodal metastasis determined by evaluating primary tumor specimens of patients with ESCC is available.
Patients and Methods A total of 55 patients with T1 ESCC invading as deep as the submucosal layer who underwent curative esophagectomy were examined. We investigated the significance of the immunohistochemical stainings of VEGF-C and E-cadherin in the primary tumor and tumor budding for prediction of nodal metastasis.
Results Metastasis to the regional lymph nodes was observed in 26 cases (47.3%) in this setting. VEGF-C expression and reduced E-cadherin expression in the primary tumor was observed in 32 (58.1%) and 38 cases (69.1%), respectively. High-grade tumor budding was observed in 29 cases (52.7%). E-cadherin expression and tumor budding were closely correlated with nodal metastasis (p = 0.039 and &lt;0.01 respectively), whereas VEGF-C expression tended to correlate with lymph node metastasis (p = 0.055). In addition, high-grade tumor budding was significantly correlated (p &lt; 0.01) with reduced E-cadherin expression. The accuracies of tumor budding and E-cadherin expression for nodal metastasis were 67.3% and 65.4% respectively, which were comparable with those of lymphatic involvement (63%). Tumor budding (p &lt; 0.01), but not E-cadherin and VEGF-C expression, was significantly correlated with poor survival.
Conclusion After the endoscopic treatment, additional therapy, such as surgery or chemoradiotherapy, may be required if reduced E-cadherin expression and high-grade tumor budding are observed in the primary tumor specimen.
Citation Format: Naoshi Kubo, Masaichi Ohira, Katsunobu Sakurai, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Masakazu Yashiro, Kiyoshi Maeda, Naoyoshi Onoda, Kosei Hirakawa. Tumor budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma. [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 3818. doi:10.1158/1538-7445.AM2014-3818
Abstract 3837: Innovative rapid gene methylation analysis of surgical margin tissues in head and neck cancer
Authors: Hayashi Masamichi , Guerrero-Preston Rafael , Kahn Zubair , Li Xiufeng , Ahn Julie , Goldsmith Marla , Michailidi Christina , Koch Wayne 
Published: May 2015

Abstract
Background: To secure negative surgical margins is the primary goal of surgical cancer treatment. However, tumor recurrence sometimes occurs even with histologically negative surgical margins. In order to detect submicroscopic residual cancerous cells intra-operatively, a time saving molecular biological approach is required.
Methods: We established an innovative rapid Quantitative methylation PCR (QMSP) assay, which consists of remarkably time-minimized DNA extraction, bisulfite treatment and QMSP quantification. In order to assess the feasibility of completing the rapid assay during a surgical procedure, 10 serial specimens of primary head and neck cancers were evaluated by both rapid QMSP and conventional QMSP.
Results: The DNA product quality of the most time saving procedure was as good as that of a conventional procedure. In the QMSP assay, target gene methylation and reference gene methylation were equally detected by both rapid and conventional methods. Finally, two frequently methylated genes in head and neck cancers, homeobox A9 (HOXA9) and endothelin receptor type B (EDNRB) were analyzed in 10 head and neck tumors, margin tissues and normal tissues. Relative QMSP values of rapid and conventional QMSP were quite similar in almost all tumors, margins and normal tissues. The average total time for the rapid QMSP procedure was less than 3 hours. Although postoperative follow-up periods are less than a year, local tumor recurrence occurred in one case whose margin tissue was QMSP positive.
Conclusion: This innovative rapid QMSP yields acceptable levels of methylation detection and can be completed during the operative window. The procedure promises to become a useful clinical tool, if the methylated surgical margins are revealed to correlate with the local tumor recurrence in a larger cohort.
Citation Format: Masamichi Hayashi, Rafael Guerrero-Preston, Zubair Kahn, Xiufeng Li, Julie Ahn, Marla Goldsmith, Christina Michailidi, Wayne Koch. Innovative rapid gene methylation analysis of surgical margin tissues in head and neck 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 3837. doi:10.1158/1538-7445.AM2014-3837
Abstract 3839: Oxidative damage in predicting early adverse skin reactions from adjuvant radiotherapy in a tri-racial/ethnic breast cancer population
Authors: Nelson Omar L. , Takita Cristiane , Wright Jean , Lee Eunkyung , Hu Jennifer J. 
Published: May 2015

Abstract
Adjuvant radiotherapy (RT) following breast conservation surgery has significantly improved survival. However, may patients develop adverse skin reactions, pain, breast edema and poor cosmetic results that impact quality of life. Inter-individual variability in the development of RT-induced adverse reactions in normal tissue is well-documented for both acute and late effects. Therefore, we evaluated the first 161 patients in an ongoing prospective study of conservatively managed breast cancer patients using the NCI CTCAE v3.0 criteria. We recorded patient characteristics, smoking history, body mass index (BMI), and treatments. We pilot tested urinary 8-hydroxydeoxyguanosine (8-OHdG) as an oxidative damage marker in predicting RT-induced skin toxicity. Women younger than 50 years of age had a significantly (p=0.016) higher post-RT skin toxicity (grade 2); higher proportion of African Americans have grade 3 skin (p=0.008) compared to other races; and obesity (BMI&gt;30) was associated with worse skin toxicity. In multivariate analysis, women with a higher pre-RT 8-OHdG had a significantly higher risk of worse skin toxicity at week 3 (OR=11.77; 95C%CI=1.21-114.45; p=0.034). Obesity (BMI&gt;30) was associated with worse skin toxicity at the end of RT (OR=2.27; 95C%CI=1.14-4.50; p=0.019). This is the first study evaluating oxidative damage in RT-induced skin toxicity. We reported significant racial/ethnic differences in urinary 8-OHdG levels and a significant association between pre-RT 8-OHdG and worse skin toxicity at week 3. If confirmed in our larger ongoing study of 1,255 patients, our study will lead to effective treatment strategies and improve quality of life of breast cancer patients undergoing RT.
Citation Format: Omar L. Nelson, Cristiane Takita, Jean Wright, Eunkyung Lee, Jennifer J. Hu. Oxidative damage in predicting early adverse skin reactions from adjuvant radiotherapy in a tri-racial/ethnic breast cancer 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 3839. doi:10.1158/1538-7445.AM2014-3839
Abstract 3844: Venous thromboembolism in patients with pancreatic cancer
Authors: Yoon Seug Yun , Lee Namsu , Kim Sook-Ja , Cheong Hee-Jeong , Kim Kyoung Ha , Won Jong-Ho , Park Hee Sook 
Published: May 2015

Abstract
Background:
Venous thromboembolism (VTE) is a critical complication of malignant disease. Pancreatic cancer is one of the cancers most commonly associated VTE. In general, the VTE incidence rate of Asians is lower than that of Caucasians. In 2007, a Korean study reported that only four cases of VTE (5.3%) occurred in Seventy five patients with advanced pancreatic adenocarcinoma. We evaluated VTE incidence in pancreatic cancer and characteristics of pancreatic cancer patients with VTE.
Method:
We retrospectively reviewed the medical records of patients with histopathologically proven pancreatic cancer from January 2006 to December 2012 at Soonchunhyang university hospital. We detected VTE through CT (chest CT, pulmonary embolism CT) and low extremity ultrasoundgraphy.
Results
Five hundred and fourteen patients with pancreatic adenocarcinoma were enrolled. (M: F, 300:214, localized: locally advanced: metastatic=31:230:253, mean age: 66.7 years). Ninety six of 514 patients (18.6%, symptomatic: aymptomatic=38:58, PE: DVT: PE+DVT: visceral thrombosis=20:19:19:38) were diagnosed as VTE. At the time of DVT diagnosis, cancer status of 50 patients cancer was progression, and that of 15 was stable. Thirty one patients were diagnosed with the pancreatic cancer and VTE, at the same time. They all had metastatic lesions. Fifty VTE patients were treated with antithrombotic therapy. Ninety three of 96 patients died, and three of them have probability that cause of death was VTE. The others died of pancreatic cancer progression. From pancreatic cancer diagnosis to VTE diagnosis, the period is 1.7month. (95%CI 1.1-2.3 month). Median overall survival (OS) was not significantly different between pancreatic cancer with VTE or without VTE. OS was significantly longer VTE patients after pancreatic cancer diagnosis than VTE patients with pancreatic cancer at the same time (10.73m vs. 1.7, p=0.00).
Conclusion
The incidence of VTE (18.6%) in Soonchunhyang university hospital with pancreatic cancer was not lower than that in western groups.
Citation Format: Seug Yun Yoon, Namsu Lee, Sook-Ja Kim, Hee-Jeong Cheong, Kyoung Ha Kim, Jong-Ho Won, Hee Sook Park. Venous thromboembolism in patients with pancreatic 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 3844. doi:10.1158/1538-7445.AM2014-3844
Abstract 3851: Molecular profiling of aggressive breast cancer in a unique patient population from Kenya
Authors: Torrorey Rispah , Kerper Maggie , Hartland Emilia , Shi Zonggao , Prosperi Jenifer , Badve Sunil , Stack Sharon , Mining Simeon , Littlepage Laurie 
Published: May 2015

Abstract
Breast cancer rates of incidence and mortality vary significantly between different nations and racial groups. African nations have the highest breast cancer mortality rates in the world, even though the incidence rates are below those of many other nations. In Kenya, breast cancer tumors are often highly aggressive at presentation and occur at a significantly earlier age (as early as the teens and 20s), relative to North American women. In the United States, non-Hispanic white women have the highest incidence of breast cancer, but African-American women have the highest mortality. These striking racial disparities are due not only to inequities in screening and treatment but also to variations in the rates of aggressive breast cancer. Differences in disease progression suggest that aggressive breast cancer tumors may harbor components of a unique molecular signature that result in racial disparities. We aim to identify drivers of poor prognosis breast cancer growth by identifying molecular signatures with high prognostic value from tumor samples of patients with aggressive disease. We hypothesize that changes in the DNA, RNA, and post-translational protein regulation contribute to aggressive disease. To characterize the tumors from this patient population, we used samples from &gt;100 Kenyan breast tumor tissue samples. We stained tissue microarray sections for clinical breast cancer markers including lymphocyte markers. Using DNA and RNA that we isolated from these patient-derived breast tumors, we are characterizing these tumors by analyzing them for gene expression, genome sequencing, proteomics, and pathology analysis coupled with bioinformatics to develop signatures of aggressive breast cancer growth and metastasis. Our data will be foundational in understanding how aggressive, lethal breast tumors of Kenyan breast cancer patients differ from less aggressive tumors and will enhance our ability to diagnose and eliminate outcome disparities in breast cancer patients.
Citation Format: Rispah Torrorey, Maggie Kerper, Emilia Hartland, Zonggao Shi, Jenifer Prosperi, Sunil Badve, Sharon Stack, Simeon Mining, Laurie Littlepage. Molecular profiling of aggressive breast cancer in a unique patient population from Kenya. [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 3851. doi:10.1158/1538-7445.AM2014-3851
Abstract 3856: Progesterone generates breast cancer stem cells through nuclear receptor-independent mechanisms in irradiated human mammary cell lines
Authors: Vares Guillaume , Cui Xing , Wang Bing , Nakajima Tetsuo , Nenoi Mitsuru 
Published: May 2015

Abstract
Epidemiological evidence has shown the existence of increased breast cancer risk following chest radiation exposure. There is strong evidence that steroid hormones influence radiosensitivity and breast cancer risk. Tumors may be initiated by a small subpopulation of cancer stem cells (CSCs). In order to evaluate whether the modulation of radiation-induced breast cancer risk by steroid hormones could involve CSCs, we measured the proportion of ALDH+ and CD44+/CD24- CSCs in irradiated breast cancer cell lines after progesterone and estrogen treatment. Progesterone stimulated the expansion of the CSC compartment both in progesterone receptor (PR)-positive breast cancer cells and in PR-negative normal cells. In MCF10A normal epithelial PR-negative cells, progesterone-treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the down-regulation of miR-22 and miR-29c expression), which resulted in increased proportions of radiation-resistant tumor-initiating CSCs. Therefore progesterone might influence radiation-induced breast cancer risk by generating tumor-initiating breast CSCs through nuclear PR-independent mechanisms (such as membrane progesterone receptors - mPRs).
Citation Format: Guillaume Vares, Xing Cui, Bing Wang, Tetsuo Nakajima, Mitsuru Nenoi. Progesterone generates breast cancer stem cells through nuclear receptor-independent mechanisms in irradiated human mammary cell lines. [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 3856. doi:10.1158/1538-7445.AM2014-3856
Abstract 3858: Implications of the downregulation of stemness/reprogramming factor expression by ibuprofen and biguanides
Authors: Grenlin Laura , Tran Tuan-Anh , Lomahan Sarah , Ikegaki Naohiko , Tang Xao X. 
Published: May 2015

Abstract
Cancer stem cells (CSCs) are thought to have the capacity to renew indefinitely, to initiate tumor formation, and to give rise to multiple non-tumorigenic progenies via asymmetric cell division. As a result of this phenotypic drift, an established tumor would consist of a mixture of CSC and non-CSC. Based on the current view, the CSC population is likely responsible for distant metastases, drug resistance and recurrence. However, the process by which this cell population is generated in a tumor mass has continued to be unclear. Based on our previous study (PNAS Vol. 110: 6097-6102, 2013), this process may involve nuclear reprogramming, namely the elevated expression of stemness/reprogramming factors (SOX2, OCT4, NANOG, LIN28, KLF4, MYC/MYCN, and those with equivalent functions). If so, it is conceivable that destabilization of these proteins would prevent or substantially slow down the generation of CSC compartment(s) within a tumor mass. Recently, we have reported that anti-inflammatory Ibuprofen and anti-diabetic biguanides destabilize MYC and MYCN in neuroblastoma cells. In this study, we have investigated the effects of Ibuprofen and Phenformin on stemness phenotypes of cancer cells (i.e., the expression of stemness factors) using the teratocarcinoma cell line NT2. NT2 cells were chosen as the experimental system because unlike many other cancer cell lines, they retain the expression of stemness/reprogramming factors. Furthermore, they express both MYC and MYCN proteins. Our data showed that high-dose/short-term treatment of NT2 cells with Phenformin and Ibuprofen significantly down-regulated the expression of MYC/MYCN, OCT4, SOX2, and NANOG. Moreover, the anti-stemness effect of Ibuprofen in the low-dose/long-term treatment was also evident (0.15 mM at Day 7 of the drug-treatment or 0.15 mM and 0.25 mM at Day 4). Experiments are underway to address the similar effect of low-dose/long-term treatment of Metformin and Phenformin in NT2 cells. We are also investigating a change in global gene expression in the drugs-treated NT2 cells, with the emphasis on stem cell-related genes and pathways. Results of these studies will help us better understand how these common drugs (anti-inflammation and diabetes medications) can be used in anti-cancer therapeutics, and more importantly, in cancer prevention, which is the key to eradication of this disease.
Citation Format: Laura Grenlin, Tuan-Anh Tran, Sarah Lomahan, Naohiko Ikegaki, Xao X. Tang. Implications of the downregulation of stemness/reprogramming factor expression by ibuprofen and biguanides. [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 3858. doi:10.1158/1538-7445.AM2014-3858