bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 325: Pediatric relapsed acute lymphoblastic leukemia patients display enrichment of the PI3K/mTOR pathway and respond to the dual PI3K/mTOR inhibitor PKI-587
Authors: Gazi Mohiuddin , Moharram Sausan A. , Marhäll Alissa , Shah Kinjal , Kazi Julhash U. 
Published: July 2017

Abstract
Although significant improvements have been observed in the treatment of acute lymphoblastic leukemia, there is a substantial subset of high-risk T-ALL patients with relatively poor prognosis. T-cell acute lymphoblastic leukemia (T-All) is a hematopoietic malignancy affecting lymphoblast of T-cell lineage which cause lots of hematopoietic cancer related deaths every year all over the world. The current overall cure rates of newly diagnosed childhood ALL are more than 80% in Europe, but approximately 20% of patients relapse due to treatment failure in childhood ALL. Like other leukemia types, alterations of PI3K/mTOR pathway are predominant in T-ALL which is also responsible for treatment failure and relapse. In this study, two different gene expression data sets of relapsed patients also displayed enrichment of the PI3K/mTOR pathway. Out of 88 different inhibitors targeting multiple components of this pathway, we observed that PKI-587 was the most selective to the T-ALL cell line CCRF-CEM. Thus, we characterized the activity of the novel dual PI3K/mTOR pathway inhibitor PKI-587 using CCRF-CEM and Molt3 cells. We observed that PKI-587 blocked proliferation, colony formation and induced apoptosis in the T-ALL cell lines and selectively abrogated PI3K/mTOR without affecting the MAPK signaling. In vivo PI3K/mTOR inhibition delayed tumor progression, and reduced tumor load in a NSG/SCID xenograft mouse model. Since no deceptive body weight decrease was noticed, our conclusion is that this dose is effective and well tolerated. The beneficial effects of PKI-587 on T-ALL cells that has been observed in this study both in vitro and in vivo warrant further investigation.
Citation Format: Mohiuddin Gazi, Sausan A. Moharram, Alissa Marhäll, Kinjal Shah, Julhash U. Kazi. Pediatric relapsed acute lymphoblastic leukemia patients display enrichment of the PI3K/mTOR pathway and respond to the dual PI3K/mTOR inhibitor PKI-587 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 325. doi:10.1158/1538-7445.AM2017-325
Abstract 3255: Circulating adipose stromal cells (CASCs) as a potential biomarker of response to weight loss interventions in obese women at high risk for breast cancer
Authors: Baker Hailey , Kreutzjans Amy L. , Nydegger Jennifer L. , Phillips Teresa L. , Hasting Richard C. , Dixon Dan A. , Kimler Bruce F. , Fabian Carol J. 
Published: July 2017

Abstract
Background Obesity is a modifiable risk factor for breast cancer in the United States. White adipose tissue is increased in obese (BMI ≥ 30 kg/m2) women, releasing estrogens and pro-inflammatory cytokines. Adipose stromal cells play a key role in releasing estrogens, while circulating adipose stromal cells (CASCs, characterized as CD34+CD31-CD45-) home to tumor sites and promote angiogenesis and vascularization. CASCs have been correlated with BMI in both cancer and non-cancer patients. However, BMI alone as a marker of adiposity has its limitations. We examined whether CASCs correlate with additional measures of adiposity in women who are at high risk for development of breast cancer.
Methods Women at high risk for development of breast cancer but without prior breast cancer were recruited for random periareolar fine needle aspiration (RPFNA), DEXA body composition, anthropomorphic assessment, and non-fasting venous blood collection. Mononuclear cells were isolated and the frequency of CD34brightCD31-CD45- cells was assessed by flow cytometry.
Results CASC frequency ranged from 0 to 0.018% (median 0.001%) for 13 non-obese and 20 obese women. There was no association between CASC frequency and BMI (range 19 - 46 kg/m2), either as a linear correlation or when dichotomized at a BMI of 30 kg/m2. However, there were tendencies for greater CASC frequencies in pre-menopausal women, women with greater waist circumference (p&lt;0.050), and women with visceral fat mass greater than 50%. With limited numbers, there was no apparent association of CASC frequency with cytology or proliferation (Ki-67) of benign breast epithelial cells acquired by RPFNA.
Conclusions This is the first study to investigate CASC frequency in a cohort of women at high-risk for development of breast cancer. Our results to date do not show an association between CASC frequency and obesity (BMI). However, associations with other indices of visceral fat suggest that evaluation of circulating adipose stromal cells could have value as a biomarker of response in clinical trials of obese breast cancer survivors and high risk women undergoing weight loss (especially fat mass) interventions.
Citation Format: Hailey Baker, Amy L. Kreutzjans, Jennifer L. Nydegger, Teresa L. Phillips, Richard C. Hasting, Dan A. Dixon, Bruce F. Kimler, Carol J. Fabian. Circulating adipose stromal cells (CASCs) as a potential biomarker of response to weight loss interventions in obese women at high risk for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3255. doi:10.1158/1538-7445.AM2017-3255
Abstract 3269: Impact of gender on survival of the patients with esophageal squamous cell carcinoma at a single institute in China
Authors: Lu Jian Liang , Lu Jian Liang , Xu Rui Ping , Li Bei , Wan Li Xin , Chen Ming Yao , Liu Chun Jiang , Han Zhan Qiang , Shen Fang Fang , Zhao Jian Bo , Guo Hai Zhou , Cao Wei , Fan Bing Yu , Wang Li Dong 
Published: July 2017

Abstract
Esophageal cancer (EC) has been well documented with predominant occurrence in male and with major histopathological type of esophageal squamous cell carcinoma (ESCC) in China. However, the influence by gender on ESCC survival is largely unknown in China. The present study was thus undertaken to elucidate the impact by gender on survival of Chinese patients with ESCC. A total of 17,969 ESCC patients was enrolled in this study, including 11,127 males with a mean age of 60.2±8.6 and 6842 females with a mean age of 61.0±8.4.All the patients were from ESCC database in Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University (1975 to 2015). Only the patients with T2–4N0–1M0–1 were enrolled in this study. Based on the diagnosed time, the patients were classified into two groups, group I (1996–2005, 6885/38.3%) and group II (2006–2015, 11084/61.7%). The followed–up was undertaken until October, 2016. Kaplan–Meier models were for describing the survival curves and Cox proportional hazards models were undertaken to observe the risk of death of male and female. The results demonstrated that the male patients had a poor survival than female (X2=58.17, P&lt;0.001). Furthermore, similar results were observed for the two different periods of 1996–2005 (X2=21.08, P&lt;0.001) and 2006–2015 (X2=34.67, P&lt;0.001). The present results indicate that gender is an independent survival factor for ESCC and the female patients with ESCC have a dramatic prolonged survival than male patients in China. [Supported by Doctoral Team Foundation of the First Affiliated Hospital of Zhengzhou University (2016-BSTDJJ-03), Natural Science Foundation of Henan
Province (20161110) and Correspondening author: Li Dong Wang, email:ldwang2007@126.com]
Note: This abstract was not presented at the meeting.
Citation Format: Jian Liang Lu, Jian Liang Lu, Rui Ping Xu, Bei Li, Li Xin Wan, Ming Yao Chen, Chun Jiang Liu, Zhan Qiang Han, Fang Fang Shen, Jian Bo Zhao, Hai Zhou Guo, Wei Cao, Bing Yu Fan, Li Dong Wang. Impact of gender on survival of the patients with esophageal squamous cell carcinoma at a single institute in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3269. doi:10.1158/1538-7445.AM2017-3269
Abstract 327: EpCAM/EpEX regulate tumor progression through EGFR signaling in colon cancer cells
Authors: Liang Kang-Hao , Lai Jun-Kai , Kuan I-I , Tso Hsien-Cheng , Wu Han-Chung 
Published: July 2017

Abstract
Epithelial cell adhesion molecule (EpCAM) is highly expressed in advanced epithelial cancers and tumor-initiated cells (TICs), but its roles in cancer progression remain to be elucidated. Here, we showed that the extracellular domain of EpCAM (EpEX) could bind to EGFR through EGF-like domain I, and subsequently activated its downstream molecules, ERK1/2 and Akt. EGFR inhibitor and knockdown of EGFR by shRNA ablated EpEX-induced ERK1/2 phosphorylation. Regulated intramembrane proteolysis (RIP) of EpCAM was induced similarly by EpEX and EGF through EGFR-dependent activation of ERK pathway. MEK inhibitor, U0126, could abolish ADAM17 and PS2 phosphorylation induced by EpEX. EpAb2-6, an anti-EpEX neutralizing monoclonal antibody, inhibits EpEX-activated EGFR-PI3K-AKT pathway in detached colon cancer cells. Moreover, intracellular domain of EpCAM (EpICD), the product of RIP-induced cleavage of EpCAM, is necessary for nuclear accumulation of β-catenin, and their target gene expressions in vitro and in mouse xenograft models. We also found that an increase of nuclear EpICD observed in CRCs predicted metastasis and poor prognosis in CRC patients. Finally, in animal model studies, EpAb2-6 therapy exhibited an enhanced antitumor effect and markedly extended the survival time of mice with human colorectal cancer in metastatic and orthotopic models. These results demonstrate that EpEX works as a growth factor in activating EGFR-mediated signaling, and as a potential target for treatment of colon cancer. This research was supported by grants from Academia Sinica and Ministry of Science and Technology [MOST 104-0210-01-09-02,MOST 105-0210-01-13-01], and the National Science Council (NSC103-2321-B-001-064), Taiwan (to H-C Wu).
Citation Format: Kang-Hao Liang, Jun-Kai Lai, I-I Kuan, Hsien-Cheng Tso, Han-Chung Wu. EpCAM/EpEX regulate tumor progression through EGFR signaling in colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 327. doi:10.1158/1538-7445.AM2017-327
Abstract 3276: Impact of the different treatments on the survival of advanced esophageal squamous cell carcinoma
Authors: Cheng Rang , Zhou Fu You , Wang Neng Chao , Wang Ran , Wang Wei Peng , Wang Xian Zeng , Yue Wen Bin , Zhou Jian Wei , Miao Zhan Hui , Ding Guang Cheng , Bu De Chao , Wang Li Dong 
Published: July 2017

Abstract
Esophageal squamous cell carcinoma (ESCC) remains one of the leading cause of cancer-related death in China. Moreover, more than 90% of the ESCC patients have been in the advanced stage when diagnosed, the 5-year survival is very poor even though the medical techniques have been improved in the past decades. Although the accumulated evidences have suggested the crucial role of genetic changes in esophageal carcinogenesis, the target therapy based on these genetic changes is largely in the very beginning, and radical esophagectomy and radiochemotherapy remain the chief choice for ESCC treatment at present. The present study was thus designed to evaluate the efficacy of the present treatment methods in China to provide more information for optimal choice in advanced ESCC treatment. The enrolled 20,712 ESCC patients in this study were from the ESCC database in Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University. Of the patients, there were 12,818 males with a mean age of 59.59±8.2 and 7,894 females with a mean age of 60.34±8.3. All the 20,712 patients were confirmed by histopathology as ESCC at II to IV stage (advanced stage) and classified into three groups based on the treatment methods: radical esophagectomy (R0) alone (17,577, 84.8%), R0 plus radiochemotherapy (2,510, 12.1%) and radiochemotherapy alone (625, 3.1%). The followed-up was undertaken until 2016. The SPSS21.0 software and Kaplan-Meier survival analysis and Log Rank test were used to evaluate the efficiency of different treatments. The results demonstrated that the overall median survival time for the three groups was 5.81 years, 4.82 years and 2.85 years, respectively (P&lt;0.001). Moreover, compared with surgery alone, R0 plus radiochemotherapy did not prolong survival of the advanced patients. Obviously, much efforts, especially combined with genetic application are much desirable to improve the survival for the advanced ESCC patients. [Supported by National High-Tech Research and Development Program of China (SQ2015AA0202183), Project for Characteristic and Advantage Discipline of Henan Province (20151208) and Correspondence to: Li Dong Wang, Email: ldwang2007@126.com]
Note: This abstract was not presented at the meeting.
Citation Format: Rang Cheng, Fu You Zhou, Neng Chao Wang, Ran Wang, Wei Peng Wang, Xian Zeng Wang, Wen Bin Yue, Jian Wei Zhou, Zhan Hui Miao, Guang Cheng Ding, De Chao Bu, Li Dong Wang. Impact of the different treatments on the survival of advanced esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3276. doi:10.1158/1538-7445.AM2017-3276
Abstract 328: PARP inhibitors suppress growth of EGFR-mutant cancers by targeting nuclear PKM2
Authors: Li Nan , Lin Steven H. 
Published: July 2017

Abstract
Poly(ADP-robose) polymerase-1 (PARP1) or ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1) is the most abundant and the best understood member of the 17 PARP family proteins. PARP1 binds to both single strand breaks (SSBs) and double-strand breaks (DSBs) and participates in the recognition, excision and repair of DNA damage. The most extensively studied role of PARP1 is its involvement in base excision repair (BER) and PARP inhibition induced-trapping of PARP1 during BER. Moreover, suppression of PARP1/2 leads to synthetic lethality in BRCA1/2-defecient tumors, indicating that PARP1-dependent BER and BRCA-dependent homologous repair pathway have overlapping and redundant functions in DNA repair. Recent studies have also pointed to a broader utility of PARP inhibitors beyond hereditary BRCA-deficient cancers. Pyruvate kinase isoform M2 (PKM2) is a glycolysis enzyme that converts phosphoenolpyruvate (PEP) into pyruvate. Up-regulation of PKM2 has been shown recently to be an important feature of tumorigenesis. In tumor cells, PKM2 forms a dimmer that is catalytically inactive as a glycolysis enzyme, but provides advantage for tumor progression due to Warburg effect. In this report, we demonstrated that poly-ADP-ribose (PAR) is required for nuclear retention and nuclear function of PKM2. PKM2 translocates into nucleus and binds to PAR upon EGF stimulation. PARP inhibition, or the PKM2-C/A mutant, which abolishes the PKM2/PAR interaction, suppresses the nuclear function of PKM2. In addition, PARP inhibition also diminishes the nuclear PKM2-dependent glycolysis and tumor growth. Moreover, we showed that nuclear localization of PKM2 correlates with PAR expression in EGFR-mutant human lung cancer tissues. Interestingly, PARP inhibition leads to growth suppression of some EGFR-mutant lung cancer cells, which are resistant to EGFR inhibitor. These data together support an unexpected function of PARP inhibition in tumor suppression and indicate that nuclear PKM2 may serve as a promising biomarker for the further development of PARP inhibitor-based therapies.
Note: This abstract was not presented at the meeting.
Citation Format: Nan Li, Steven H. Lin. PARP inhibitors suppress growth of EGFR-mutant cancers by targeting nuclear PKM2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 328. doi:10.1158/1538-7445.AM2017-328
Abstract 3288: Effects of concomitant metformin and statins on overall survival of pancreatic cancer patients: results from SEER-Medicare data analyses
Authors: E Jian-Yu , Lu Shou-En , Lin Yong , Graber Judith M. , Rotter David , Zhang Lanjing , Petersen Gloria M. , Demissie Kitaw , Lu-Yao Grace , Tan Xiang-Lin 
Published: July 2017

Abstract
Purpose: Growing mechanistic and epidemiologic evidence suggests that both metformin and statins have anti-cancer effects and are associated with reduced pancreatic cancer mortality. However, the joint effect of combination statin/metformin on pancreatic cancer mortality is unknown. By applying a robust analytic approach, we aim to examine the association between metformin and/or statin use and overall survival in a large cohort of patients with primary pancreatic adenocarcinoma (PDAC). Patients and Methods: 12,572 elderly patients with primary PDAC diagnosed between 2008 and 2012 were identified by using the Surveillance, Epidemiology, and End Results (SEER), and the detailed information on metformin and statin use was extracted from Medicare Part D. A Cox proportional hazard model with time-varying covariate adjusted for the propensity score was applied to assess the association of metformin and /or statin use with overall survival while controlling for potential confounders. Results: Of total 12,572 PDAC patients (median age = 76 years), 11,526 (91.77%) patients died before the study ended with a median follow-up of 3.8 months (interquartile range: 1.4-10.1). By the time-varying covariate analysis, statin use was significantly associated with an improved overall survival [Hazard ratio (HR), 0.938; 95% confidence interval (CI), 0.898 to 0.979], and more pronounced in post-diagnosis statin users (HR, 0.693; 95% CI, 0.555 to 0.864). However, metformin use was not significantly associated with overall survival (HR, 1.011; 95% CI, 0.939 to 1.091), neither in pre-diagnosis users (HR, 1.015; 95% CI, 0.970 to 1.061) nor in post-diagnosis users (HR, 0.990; 95% CI, 0.866 to 1.131). Additionally, no superior beneficial effect was observed for dual users (HR, 0.998; 95% CI, 0.947 to 1.053). Conclusions: Exposures to statin, not metformin, was significantly associated with reduced overall mortality of PDAC, indicating potential benefits of statin use on improving survival among PDAC patients. Further prospective validation is required to confirm these findings.
Citation Format: Jian-Yu E, Shou-En Lu, Yong Lin, Judith M. Graber, David Rotter, Lanjing Zhang, Gloria M. Petersen, Kitaw Demissie, Grace Lu-Yao, Xiang-Lin Tan. Effects of concomitant metformin and statins on overall survival of pancreatic cancer patients: results from SEER-Medicare data analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3288. doi:10.1158/1538-7445.AM2017-3288
Abstract 3290: Cancer mortality by antiarrhythmic drug use in a population-based cohort of Finnish men
Authors: Kaapu Kalle J. , Murtola Teemu , Talala Kirsi , Taari Kimmo , Tammela Teuvo , Auvinen Anssi 
Published: July 2017

Abstract
Introduction: In-vitro studies have suggested that antiarrhythmic drug digoxin might restrain the growth of cancer cells by inhibiting Na+/K+-ATPase. A non-selective beta-blocker sotalol has similar effect on K+-channels. We evaluated the association between cancer mortality and digoxin, sotalol and general antiarrhythmic drug use in a retrospective cohort study.
Materials and methods: The study population consists of 78,615 men originally identified for the Finnish Randomized Study for Screening of Prostate Cancer. Men were 55-69 years old at baseline. Prevalent prostate cancer cases were excluded; no exclusions were made based on other cancer types. Information on antiarrhythmic drug purchases was collected from the national prescription database. We used Cox regression method to analyze the overall cancer mortality and individually mortality from the most common causes of cancer death.
Results: A total of 8,064 men (10.3%) had used antiarrhythmic drugs. Of these 5,668 had used digoxin and 2,540 had used sotalol. During the median follow-up of 16.9 years after baseline 26,790 (34.1%) men died, of these 8,225 (30.7% of deaths) due to cancer. Overall cancer mortality was elevated among antiarrhythmic drug users compared to non-users (HR 1.25, 95% CI 1.12-1.40). Similar results were observed for digoxin (HR 1.44, 95% CI 1.26-1.63) but not for sotalol (HR 0.92, 95% CI 0.68-1.24). Furthermore, the antiarrhythmic drug use was associated with elevated risk of lung-cancer death (HR 1.76 95% CI 1.46-2.14). However, the risk associations disappeared in long-term use. When we restricted the analysis to cancer cases only, no differences were observed in survival after the cancer diagnosis for any cancer type.
Conclusion: Cancer mortality was elevated among users of antiarrhythmic drugs compared to non-users. This association is probably due to the differences between users and non-users as it was related to short-term use, and disappeared in long-term use. Use of digoxin or sotalol was not associated with improved cancer-specific survival.
Citation Format: Kalle J. Kaapu, Teemu Murtola, Kirsi Talala, Kimmo Taari, Teuvo Tammela, Anssi Auvinen. Cancer mortality by antiarrhythmic drug use in a population-based cohort of Finnish men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3290. doi:10.1158/1538-7445.AM2017-3290