bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1704: High mobility group A1 chromatin remodeling protein expands the intestinal stem cell compartment and Paneth cell niche through Wnt/β-catenin signaling and Sox9
Authors: Xian Lingling , Huso Tait , Belton Amy , Huso David , Resar. Linda M. S. 
Published: July 2016

Abstract
The High Mobility Group A1 (HMGA1) gene is overexpressed in most poorly differentiated cancers and high levels portend adverse clinical outcomes, although the molecular mechanisms through which it functions are poorly understood. HMGA1 encodes the HMGA1a and HMGA1b chromatin remodeling proteins, which modulate gene expression by bending chromatin and orchestrating the assembly of transcription factor complexes to DNA. HMGA1 is highly expressed during embryogenesis, but silenced in adult, differentiated tissues. Postnatally, HMGA1 expression is maintained in adult stem cells, such as intestinal stem cells (ISCs); however, its role in this setting has been unknown. Here, we report that Hmga1 overexpression in ISCs of transgenic mice drives expansion in the ISC compartment leading to hyperproliferation, aberrant crypt formation, and polyposis. Surprisingly, Hmga1 transgenic mice also exhibit marked expansion in terminally differentiated Paneth cells, which comprise an epithelial cell niche for ISCs. To dissect the mechanisms mediating these phenotypes, we generated three-dimensional (3D) intestinal organoids with varied expression of Hmga1. Strikingly, silencing Hmga1 in wildtype crypt cells disrupts their ability to organize into functional 3D organoids with bud formation, while crypt cells expressing ectopic Hmga1 exhibit enhanced organoid formation with increased ISC number, proliferation, and bud development. Because Wnt/β-catenin signaling is central to ISC function, we determined whether Hmga1 modulates this pathway. β-catenin protein is increased in the crypts of the Hmga1 transgenic mice and organoids. Hmga1 amplifies Wnt/β-catenin signaling by inducing both genes that encode Wnt cell surface receptors and target genes downstream of Wnt/β-catenin. Hmga1 also directly up-regulates Sox9, which is required for terminal differentiation to Paneth cells. This is the first example of Hmga1 fostering terminal differentiation to establish a stem cell niche. In human intestinal epithelium, HMGA1 and SOX9 are highly correlated (P = 0.008), and both become up-regulated in carcinogenesis. These results reveal a novel role for Hmga1 in intestinal homeostasis by maintaining both the stem cell pool and epithelial niche compartment and suggest that deregulated Hmga1 perturbs this equilibrium during intestinal carcinogenesis.
Citation Format: Lingling Xian, Tait Huso, Amy Belton, David Huso, Linda M. S. Resar. High mobility group A1 chromatin remodeling protein expands the intestinal stem cell compartment and Paneth cell niche through Wnt/β-catenin signaling and Sox9. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1704.
Abstract 1720: Role of SENP1 in HBx-induced cell migration and stemness-related properties in hepatocellular carcinoma
Authors: Chang Te Sheng , Huang Yen-Hua 
Published: July 2016

Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer, and the third leading cause of cancer mortality worldwide. Surgical resection can be curative for early stage HCC, but the risk of tumor recurrence remains high. Tumor stemness properties have been linked to early recurrence of HBV-related HCC (HBV-HCC), which continues to be a great challenge in clinical practice. However, the progress in the strategy of individualized therapy against HBV-HCC is slow and disappointed. Here we demonstrate that HBx regulates the cell migration and cancer stemness properties of HCC cells through Sentrin-specific protease 1 (SENP1) modification. By a large cohort of HCC patients receiving curative heptectomy, we found that SENP1 expression level is highly associated with the gene expression levels of cell migration-related gene SNAIL/TWIST and pluripotency-related gene OCT4 particularly in HBV-HCC. Furthermore, SENP1 expression level is significantly associated with tumor metastasis as well as the early recurrence of HCC using Kaplan-Meier analysis. Further experiments using cell line model, we demonstrated that HBx overexpression not only increases the protein levels of SENP1 and pluripotent transcription factor OCT4, but also enhances cell migration in HepG2 cells. Inhibition of SENP1 significantly suppressed the HBx-induced cell migration and cancer stemness in vitro and in vivo. In summary, in this work, we demonstrate that SENP1 plays a critical role in HBx-induced cell migration- and cancer stemness-related properties in HBV-HCC. Findings in this study will facilitate the potential strategy targeting on SENP1 for individualized adjuvant therapy against HBV-HCC.
Citation Format: Te Sheng Chang, Yen-Hua Huang. Role of SENP1 in HBx-induced cell migration and stemness-related properties in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1720.
Abstract 1730: Cancer stem cells might sustain stemness by the induction of autophagy in starvation stress
Authors: Masuda Go , Yashiro Masakazu , Kitayama Kishu , Miki Yuichiro , Kasashima Hiroaki , Morisaki Tamami , Fukuoka Tatsunari , Hasegawa Tsuyoshi , Ohira Masaichi , Hirakawa Kosei 
Published: July 2016

Abstract
Background: Cancer stem cells (CSCs), which have capacity for self-renewal and cancer cell supply, have been thought to be responsible for tumor initiation, distant metastasis, and chemoresistance. Side population (SP) cells extracted by the fluorescence-activated cell sorting technique using Hoechst 33342 are thought to be enriched for CSCs. Autophagy is an intracellular degradation system that is induced under stress, such as starvation. Although autophagy has been reported to be associated with tumor progression under various stresses, the significance of autophagy in CSCs has still remained to be unknown. The aim of this study is to clarify the role of autophagy of CSCs under starvation stress.
Materials and Methods: Two gastric cancer cell lines, OCUM-2MD3 and OCUM-12 were used. Two side population (SP) cell lines, OCUM-2MD3/SP and OCUM-12/SP were sorted by flow cytometry as CSC-rich cells from the parent OCUM-2MD3 and OCUM-12 cells, respectively. The effects of starvation stress, including low glucose, low amino acid, or low serum, on the stemness of CSCs were examined. The expression level of autophagy associated proteins, LC3A and LC3B, was evaluated by RT-PCR and western blotting. The effects of autophagy on the stemness and the proliferation of CSCs were examined by SP fraction and MTT assay. Chloroquine was used as an autophagy inhibitor.
Results: The percentages of SP cells were significantly higher in the OCUM-12/SP cells (10.2%) and OCUM-2MD3/SP cells (12.3%) than in their parent OCUM-12 cells (2.1%) and OCUM-2MD3 cells (1.2%). The expression level of LC3A and LC3B was high in both OCUM-2MD3/SP cells and OCUM-12/SP cells, in comparison to that in OCUM-2MD3 cells and OCUM-12 cells. Starvation stress increased the autophagy status of OCUM-2MD3/SP and OCUM-12/SP cells. Chloroquine significantly decreased the SP fraction and proliferation activity of OCUM-2MD3/SP cells and OCUM-12/SP cells.
Conclusion: Autophagy acts as a survival pathway in CSCs under starvation stress. CSCs might sustain stemness by the induction of autophagy in sarvation status. The autophagy inhibitor might be a promising therapy for CSCs.
Citation Format: Go Masuda, Masakazu Yashiro, Kishu Kitayama, Yuichiro Miki, Hiroaki Kasashima, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Masaichi Ohira, Kosei Hirakawa. Cancer stem cells might sustain stemness by the induction of autophagy in starvation stress. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1730.
Abstract 1732: The analysis of stem cell property and mesenchymal feature of anaplastic pancreatic cancer
Authors: Kimura Kenjiro , Miura Kotaro , Amano Ryosuke , Yamazoe Sadaaki , Kametani Naoki , Nishio Kohei , Ohira Masaichi , Hirakawa Kosei 
Published: July 2016

Abstract
Background: Anaplastic pancreatic cancer (APC) is the subtype of pancreatic ductal adenocarcinoma (PDAC). APC is poorer prognosis than ordinary PDAC. However, it is unclear what feature of APC is different from that of ordinary PDAC. Our previous studies suggested that the angiogenesis and the tolerance of hypoxia might related to the higher in vivo proliferation of APC than ordinary PDAC.
Purpose: We tried to estimate the difference between APC and PDAC using SP cells which reflected cancer stem-like cell and drug resistance and western blotting of E-cadherin and vimentin which reflected epithelial-mesenchymal transition.
Materials and Methods: For SP cell analysis, OCUP-A1 and OCUP-A2 were used as APC cell lines and Panc-1 and MIAPaCa2 were used as ordinary PDAC cell lines. These cells were incubated in the medium including Hoechst 33342 with or without verapamil. Then, propidium iodide was added. And the analysis was performed using FACS Aria II. For western blotting, OCUP-A1 and OCUP-A2 were used as APC cell lines. And breast cancer cell line MCF-7 was used as control.
Results: The proportion of SP cells in all cells was as follows; OCUP-A1/ OCUP-A2/ Panc-1/ MIAPaCa2 = 1.8±0.28%/ 1.7±0.12%/ 1.1±0.20%/ 0.6±0.058%. The proportion of SP cells of OCUP-A1 and OCUP-A2 were similar to that of Panc-1. However the proportion of SP cells of OCUP-A1 and OCUP-A2 significantly larger than that of MIAPaCa2. In western blotting, the expression of vimentin was observed and the expression of E-cadherin was lost in OCUP-A1 and OCUP-A2. Inversely, the expression of E-cadherin was observed and the expression of E-cadherin was lost in MCF-7.
Discussion: It was reported that SP cells might contribute to tumorigenesis and drug resistance the same as cancer stem-like cell. Our current study suggested that larger proportion of SP cells in APC might induce higher malignancy of APC. Also, it was reported that mesenchymal feature might related to cancer stem cell properties. In this study, it was suggested that APC cell lines might have mesenchymal feature. However, it has been unclear whether mesenchymal feature of APC would affect the proportion of SP cells of APC from this study. So, we need to confirm the correlation with cancer stem sell property and mesenchymal feature of APC.
Conclusion: The large proportion of SP cells and the mesenchymal feature might contribute to higher malignant property of APC.
Citation Format: Kenjiro Kimura, Kotaro Miura, Ryosuke Amano, Sadaaki Yamazoe, Naoki Kametani, Kohei Nishio, Masaichi Ohira, Kosei Hirakawa. The analysis of stem cell property and mesenchymal feature of anaplastic pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1732.
Abstract 1736: Physical activity, sitting time and prostate cancer specific mortality: The Cancer Prevention Study II Nutrition Cohort
Authors: Wang Ying , Jacobs Eric J. , Gansler Ted , McCullough Marjorie L. , Stevens Victoria L. , Gapstur Susan M. , Patel Alpa V. 
Published: July 2016

Abstract
Objective: To investigate the associations of pre- and post-diagnostic recreational physical activity, and sitting time with prostate cancer specific mortality (PCSM) among men diagnosed with non-metastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort.
Methods: 10,067 men were diagnosed with non-metastatic prostate cancer between enrollment in 1992 or 1993 and June 2011, of whom 600 died of prostate cancer during follow-up through 2012. Multivariable-adjusted Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of self-reported pre-diagnostic and post-diagnostic physical activity and sitting time with PCSM.
Results: Compared with engaging in fewer than 3.5 metabolic equivalent (MET) hours per week of recreational physical activity, 17.5 or more MET hours (equivalent to 5 hours of walking) per week was associated with 30% lower risk of PCSM (HR: 0.70, 95% CI: 0.54-0.92) for pre-diagnostic, and with 34% lower risk (HR: 0.66, 95% CI: 0.46-0.93) for post-diagnostic recreational physical activity. Among men with walking as the only form of leisure time physical activity, walking 4 hours or more per week before diagnosis was associated with lower risk of PCSM (for 4-6 hours, HR: 0.65, 95% CI: 0.46-0.91; for 7+ hours, HR: 0.60, 95% CI: 0.41-0.88), while no statistically significant association was observed with walking after diagnosis. Sitting time was not associated with PCSM.
Conclusion: Higher recreational physical activity levels before and after diagnosis may improve prognosis in men diagnosed with non-metastatic prostate cancer. These results additional support that prostate cancer survivors should adhere to physical activity guidelines and that physicians should promote adopting a physically active lifestyle to prostate cancer survivors.
Citation Format: Ying Wang, Eric J. Jacobs, Ted Gansler, Marjorie L. McCullough, Victoria L. Stevens, Susan M. Gapstur, Alpa V. Patel. Physical activity, sitting time and prostate cancer specific mortality: The Cancer Prevention Study II Nutrition Cohort. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1736.
Abstract 1737: Reproductive and hormonal factors in relation to lung cancer among Nepali women
Authors: Vohra Sanah N. , Sapkota Amir , Lee Mei-Ling T. , Hashibe Mia , Siwakoti Bhola , Pun Chin B. , Dallal Cher M. 
Published: July 2016

Abstract
Of the 1.8 million global incident lung cancer cases estimated in 2012, approximately 58% occurred in less developed regions (LDRs). Studies conducted in more developed regions suggest potential gender differences in lung cancer risk, whereby women may be more susceptible to the carcinogenic effects of tobacco. However, studies of reproductive and hormonal factors and lung cancer among women have been inconsistent and to date, no prior study has assessed these relationships among Nepali women. Using data from a hospital-based case-control study conducted in B. P. Koirala Memorial Cancer Hospital (Nepal, 2009-2012), relationships between reproductive and hormonal factors and lung cancer were examined among women aged 23-85 years. Lung cancer cases (n = 268) were frequency-matched to controls (n = 226), on the basis of age (±5 years), ethnicity and residential area. Controls were selected from visitors of non-lung cancer patients within the same hospital. Participants completed an interviewer-administered questionnaire and provided detailed information on demographics, medical history, smoking history, and reproductive and hormonal factors. The main exposures in this analysis included menopausal status, age at menarche, age at menopause, menstrual duration, gravidity, and age at first live-birth. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Final models include adjustment for key confounders including age and smoking status. Among postmenopausal women, those with a younger age at menopause (&lt;45years; 45-49years) had an increased odds of lung cancer compared to those with an older (≥50years, referent) age at menopause (OR = 2.14, 95%CI = 1.09, 4.17; OR = 1.93, 95%CI = 1.07, 3.51, respectively), after adjusting for age and cumulative active smoking (CAS). No statistically significant associations were observed with the other exposures examined. Ongoing analyses include stratification by key factors including CAS years. Further research is needed to corroborate and expand on these findings in order to better understand hormonal risk factors for lung cancer among Nepali women.
Citation Format: Sanah N. Vohra, Amir Sapkota, Mei-Ling T. Lee, Mia Hashibe, Bhola Siwakoti, Chin B. Pun, Cher M. Dallal. Reproductive and hormonal factors in relation to lung cancer among Nepali women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1737.
Abstract 1755: Weight change, prostate cancer-specific mortality, and biochemical recurrence in a prospective cohort study of U.S. men
Authors: Dickerman Barbra , Ahearn Thomas , Giovannucci Edward , Mucci Lorelei , Wilson Kathryn 
Published: July 2016

Abstract
Obesity is associated with an increased risk of fatal prostate cancer. However, the relevant timing of obesity for risk has not been established, and the impact of weight change on prognosis has been understudied.
We prospectively investigated the association between weight change and obesity with prostate cancer outcomes among 5,173 men diagnosed with prostate cancer (clinical TNM-stage &lt;T3b) from 1986 to 2012 in the Health Professionals Follow-up Study. Men were followed for biochemical recurrence, development of distant metastasis, and mortality until 2014. Cox proportional hazards models were used to estimate hazard ratios for change in weight from age 21 to diagnosis and in the 4 years prior to diagnosis, adjusting for potential confounding by lifestyle and clinical factors. Because weight, weight change, and mortality are strongly associated with smoking, we conducted the analysis among all prostate cancer patients and among never smokers only (N = 2,554).
Among all patients, weight gain from age 21 to the time of diagnosis was associated with risk of lethal prostate cancer (distant metastases or prostate cancer death). Compared to those with stable weight (±10 lbs) from age 21 to diagnosis, those who gained &gt;30 lbs had a 1.44-fold higher risk of lethal cancer (95% CI 1.03-2.01, p-trend = 0.06, adjusting for lifestyle factors, stage, grade, PSA at diagnosis, and weight at age 21). Among never smokers, this association was stronger (HR 2.19, 95% CI 1.31-3.68, p-trend = 0.005). Weight gain in the 4 years preceding diagnosis was suggestively, but not significantly, associated with lethal cancer among never smokers (HR for &gt;5 lbs gain vs stable weight [±5 lbs] 1.48, 95% CI, 0.96, 2.28). No significant associations were found between weight change and biochemical recurrence.
Our findings suggest a positive association between adult weight gain and risk of lethal prostate cancer. Metabolic changes associated with weight gain may promote prostate cancer progression.
Citation Format: Barbra Dickerman, Thomas Ahearn, Edward Giovannucci, Lorelei Mucci, Kathryn Wilson. Weight change, prostate cancer-specific mortality, and biochemical recurrence in a prospective cohort study of U.S. men. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1755.
Abstract 1766: An evaluation of the post-stroke cancer risk among post-menopausal women: The Women's Health Initiative
Authors: Sealy-Jefferson Shawnita , Cote Michele L. , Beebe-Dimmer Jennifer , Chlebowski Rowan , Rexrode Kathryn , Simon Michael 
Published: July 2016

Abstract
Links between cancer history and incident stroke have been established, such that 15% of cancer patients experience a stroke at some point during their clinical course. However, we do not know whether stroke history is associated with cancer risk, especially for those cancers with overlapping risk factors with stroke. To address this, we used data from the observational and clinical trial of the Women's Health Initiative (n = 145,075), to test whether stroke history was associated with cancer risk and tumor type, and whether variation in cancer risk and tumor type exist by race/ethnicity. Time to incident cancer (in months) was estimated with bivariate and multivariate adjusted cox proportional hazards models, accounting for competing risks, comparing women with incident or prevalent stroke to women without stroke at baseline or at any point during follow-up, and models were stratified by race/ethnicity. Women with a stroke history, compared to those without, had significant differences in the following baseline characteristics: age, body mass index, smoking status, hormone replacement therapy usage, hypertension, hypercholesterolemia and diabetes, and differences were consistent among race/ethnic groups. In unadjusted and adjusted competing risk models of the overall sample, lower cancer risk was observed for women who had a prior stroke, compared to those with no stroke history (adjusted HR: 0.81; 95% CI: 0.75, 0.88). In race-stratified models, Non-Hispanic White (NHW) women experienced significantly lower risk of cancer following stroke, compared to those with no stroke history (adjusted HR: 0.81; 95% Confidence Interval: 0.74-0.89), and the magnitude of the association was similar, although not significant, for African American (AA) and ‘Other’ racial/ethnic groups. The associations with stroke were stronger for African American women with invasive breast (p = 0.02), lung (p = 0.04), and ‘other’ (p = 0.001) cancers, compared to NHW women. The results of the current study suggest that overall, women have lower cancer risk post-stroke, but that AA women, compared to their NHW counterparts, have higher risk of certain types of cancers after stroke. Future studies should investigate the mechanisms underlying the lower cancer risk among all stroke survivors, as well as examine why AA women develop certain tumors more often than NHW women.
Citation Format: Shawnita Sealy-Jefferson, Michele L. Cote, Jennifer Beebe-Dimmer, Rowan Chlebowski, Kathryn Rexrode, Michael Simon. An evaluation of the post-stroke cancer risk among post-menopausal women: The Women's Health Initiative. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1766.