bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 1676: 15-Lipoxygenase-2 inhibits epithelial-to-mesenchymal transition (EMT) in metastatic prostate cancer
Authors: Alfardan Rana K. , Boral Debasish , Nie Daotai
Published: July 2016

Introduction

15-lipoxygenase-2 (15-LOX-2) is a lipid oxidizing enzyme which converts the unsaturated fatty acids (Arachidonic and linoleic acid) to bioactive lipids with anti-inflammatory properties. Abundantly expressed in normal prostate, 15-LOX-2 expression and activities were found reduced in prostate tumors. 15-LOX-2 has been suggested as functional tumor suppressor since restoration of its expression was found to reduce prostate tumor formation and growth and induce tumor dormancy. However, it is unknown how 15-LOX-2 modulates prostate tumor progression and metastasis.

Methods

Silico analyses of gene array data, Inducible Tet-on system to express 15-LOX-2 in PC3MM cells in an inducible manner, qPCR to check the expressions, western blot, wound healing assay, immunohistochemistry.

Result

Through in silico analyses of gene array data, we found 15-LOX-2 expression was markedly reduced in metastatic prostate tumors when compared to normal or primary prostate tumor tissues. To determine whether 15-LOX-2 can modulate metastatic potentials of prostate cancer, we used an Inducible Tet-on system to express 15-LOX-2 in PC3MM cells. Treatment with 750ng/ml of doxycycline led to induced expression of 15-LOX-2 in PC3MM cells. Restoration of 15-LOX-2 expression in PC3MM cells caused re-expression of several epithelial markers including claudin, desmocollin, desmoglein, Jam, EPCAM, β-Catenin molecules involved in the tight and desmosomal junctions. At mean time, 15-LOX-2 expression led to a decrease in the levels of mesenchymal markers, vitronectin and fibronectin, in PC3MM cells. Restoration of 15-LOX-2 expression in PC3MM cells reduced cell migration and reduced MMP2 and MMP3 expression.

Conclusion

Our data suggest that 15-LOX-2 is a barrier for prostate tumor cells to acquire metastatic potentials through inhibiting epithelial to mesenchymal transition.

Citation Format: Rana K. Alfardan, Debasish Boral, Daotai Nie. 15-Lipoxygenase-2 inhibits epithelial-to-mesenchymal transition (EMT) in metastatic prostate 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 1676.
Abstract 1685: Identification and characterization of EMT/MET signatures in circulating tumor cells isolated from patients with metastatic breast cancer using graphene oxide nano-chip
Authors: Kim Tae Hyun , Yoon Hyeun Joong , Nagrath Sunitha
Published: July 2016

Disseminated cancer cells identified in the circulatory system of cancer patients has implied to be the key drivers of tumor metastasis. These cells known as circulating tumor cells (CTCs) are emerging as an alternative to tissue biopsies to predict prognostic values, and to monitor evolving tumor heterogeneity through serial drug treatments. Recent technological advances have enabled the detection of CTCs in patient blood samples. However, the enumeration alone seems to be insufficient to obtain information that could benefit any clinical decisions. The limited sensitivity as well as the specificity of current approaches struggle from realizing the full promise of CTCs. We developed a sensitive microfluidic chip using functionalized graphene oxide (GO) nano-sheets to isolate CTCs with improved sensitivity and purity. Blood samples collected from metastatic breast cancer patients were processed through the chip within 6 hours of sampling and the CTCs were identified by the presence of cytokeratin with the absence of CD45 expression. EMT/MET signatures were characterized in the isolated CTCs to investigate its role by assessing gene expression profiles. Protein markers known to be up regulated during the EMT such as Vimentin and N-cadherin was examined along with HER2. mRNA expression

of EMT markers were studied simultaneously using a multiplex TaqMan-based qRT-PCR method and compared to healthy controls. CTCs were successfully detected in >95% of patients examined in this study. Cell-to-cell intrapatient heteroheneity was observed in the isolated CTCs. Markers of EMT/MET phenotypes including Vimentin, EpCAM, HER2, CDH1, CDH2 and cytokeratin in the CTC samples were differentially expressed. These studies demonstrate the feasibility of utilizing the GO nano-chip in CTC isolation and characterization from metastatic breast cancer patients. Given the high sensitivity and the reproducibility to measure protein/gene expression levels of CTC biomarkers, we envision that our GO nano-chip may provide potential tool for real-time monitoring of cancer patients on clinical trials.

Citation Format: Tae Hyun Kim, Hyeun Joong Yoon, Sunitha Nagrath. Identification and characterization of EMT/MET signatures in circulating tumor cells isolated from patients with metastatic breast cancer using graphene oxide nano-chip. [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 1685.
Abstract 1688: Mutation and gene expression analysis of circulating tumor cells (CTCs) enriched and retrieved by a sensitive microfluidic device
Authors: Wang Yixin
Published: July 2016

Molecular characterization of CTCs is hindered by low sensitivity and high level of background leukocytes of currently available CTC enrichment devices and assays. We have developed a novel technology to enrich and retrieve CTCs from blood samples using a microfluidic chip. The Celsee PREP100 device captures CTCs with high sensitivity and then allows the captured CTCs to be retrieved for subsequent molecular analysis. The Celsee PREP100 system uses the microfluidic chip which has approximately 56,320 capture chambers. Based on differences in cell size and deformability, each chamber ensures that small blood cells such as red blood cells and most leukocytes escape while larger CTCs are trapped and isolated in the chambers. In the work we used the Celsee PREP100 to capture breast and lung cancer cells spiked into normal donor blood samples, including SKBR3 and NCI-H1975. We were able to show that the device can capture 20 cells with high reproducibility. The captured CTCs were retrieved from the microfluidic chip and further purified with anti-CD45 magnetic beads. Our results suggest that the cell recovery rate of this back-flow procedure is greater than 80% and the level of remaining background leukocytes is very low (about 100 cells). Work in progress to extract DNA and RNA. The resulting DNA samples are subjected to mutation analysis of a panel of cancer markers by using PCR and sequencing. The resulting RNA samples are converted to cDNAs, and gene expression analysis of selected cancer markers are carried out by using RT-QPCR. Specific DNA mutations such as EGFR exon 21 (L585R) in NCI-H1975 and mRNA expression markers including CK-19, TTF1 are tested in the retrieved cells. The sensitive and easy-to-use Celsee PREP100 system represents a promising technology for CTC capturing and molecular characterization. Clinical blood samples from patients with metastatic cancer are being tested on the Celsee PREP100 device and the results will be discussed.

Citation Format: Yixin Wang. Mutation and gene expression analysis of circulating tumor cells (CTCs) enriched and retrieved by a sensitive microfluidic device. [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 1688.
Abstract 1696: Mitochondrial haplotype alters metastasis in a non-cell autonomous manner
Authors: Brinker Amanda E. , Vivian Carolyn J. , Welch Danny R.
Published: July 2016

Mitochondrial Nuclear Exchange (MNX) mice, created by transferring the nucleus from an oocyte from strain x into an enucleated oocyte of strain y, showed that mammary tumor formation and metastasis can be regulated by inherited mitochondrial polymorphisms (PMID26471915). Besides genetic (cell autonomous) changes observed, we asked whether mitochondrial polymorphisms in non-cancer compartments could exert effects on tumor formation or metastasis. Tumor cells were injected into syngeneic wild type mice and tumor growth and metastasis were compared to similarly injected cells into MNX mice sharing the same nuclear but different mtDNA backgrounds. Orthotopic tumor growth rates were equal for all of the cell lines tested. However, the ability to form experimental lung metastases following i.v. injection were dramatically altered. Compared to injections into wild-type, syngeneic mice, E0771 mammary carcinoma and B16-F10 melanoma cells (both syngeneic to C57BL/6J), formed significantly (P<0.01) more lung metastases in C57BL/6J-mtMNX(C3H/HeN) and K1735-M2 melanoma cells (syngeneic to C3H/HeN) formed significantly fewer lung metastases in C3H/HeNmtMNXC57BL/6J. These results have been replicated at least three times using >10 mice per experiment. Interestingly, C57BL/6J mitochondria confer resistance to metastasis in both cell autonomous and non-cell autonomous experiments. Basal metabolic differences comparing mouse embryonic fibroblasts isolated from wild-type and MNX mice are among mechanisms being explored. Together, our findings highlight the striking influences that mitochondrial haplotypes can exert on tumorigenicity and metastasis via both intrinsic and extrinsic mechanisms. Support: Susan G. Komen for the Cure (SAC11037), Natl Fndn Cancer Res, Steiner Family Fund for Metastasis Research, Kansas Bioscience Authority, CA134981, P30-CA168524

Citation Format: Amanda E. Brinker, Carolyn J. Vivian, Danny R. Welch. Mitochondrial haplotype alters metastasis in a non-cell autonomous manner. [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 1696.
Abstract 17: Metabolic analysis of IDH mutant gliomas in Drosophila
Authors: Brown Michaela , Buccetti Jenna , Tipping Marla
Published: July 2016

Metabolic reprogramming is a common hallmark shared by nearly all proliferating cancer cells and has emerged as an exciting new direction in cancer research. Many signaling pathways have been implicated in mechanisms leading to the shift of metabolic programs in tumors, but more recently a small number of metabolic enzymes have also been identified in this process. Genes encoding the metabolic enzymes Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) were found to be mutated in up to 70% of low-grade and medium grade gliomas, and in 15-20% of adult acute leukemia samples. These findings were the first to link the IDH gene to tumorigenesis. IDH1 and IDH2 function to irreversibly catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). Although these are important metabolic enzymes, little is known about the metabolic impact harboring mutant IDH protein has on cells. Our goal is to model the IDH mutant phenotype in Drosophila glial cells for further characterization of both metabolic status, and IDH enzymatic activity. To this end, we have generated Drosophila cell lines and transformant flies that express the most commonly identified IDH mutations under control of the UAS-Gal4 system. We have also investigated the metabolic flux of Drosophila cell lines expressing IDH mutant protein, and loss of IDH function, and glycolytic enzyme expression analysis. Currently, we are investigating the metabolic flux analysis (MFA) using labeled metabolites as well as comparing the protein interactions of the wild type to the mutant IDH cells. The results of these investigations will identify potential new targets for the treatment of aggressive gliomas at the level of cellular metabolism.

Citation Format: Michaela Brown, Jenna Buccetti, Marla Tipping. Metabolic analysis of IDH mutant gliomas in Drosophila. [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 17.
Abstract 1701: CCR6 associates with colon cancer metastasis
Authors: Kapur Neeraj , Mir Hina , Clark Clarence E. , Krishnamurti Uma , Beech Derrick J. , Lillard James W. , Singh Shailesh
Published: July 2016

Despite established benefits of screening, colon cancer remains a leading cause of cancer death in the U.S. Majority of colon cancer deaths result from metastasis. Effective treatments are not available for advanced disease because molecular mechanisms of initiation and progression of this disease are yet to be defined. Chemokine-chemokine receptor interaction plays an important role in cancer progression. In this study, using colon cancer tissue microarray, we have shown that expression of CCR6 was significantly higher in advanced colon cancer (p<0.0001) with distant and regional lymph node metastasis as compared to non-metastatic and adjacent normal tissues. Expression of CCR6 was further confirmed in cell lines derived from Dukes's type C and type D colon cancer patients using flow cytometric analysis. Like tissues, CCR6 expression was significantly (p<0.0001) higher in colon cancer cell lines compared to normal colon epithelial cells. Furthermore, colon cancer cells showed higher migratory potential toward chemotactic gradient of its only known natural ligand, CCL20. Cell proliferation was also inhibited in presence of CCL20. Significant decrease in E-cadherin, increased expression of vimentin, β-catenin, N-cadherin, α-SMA, SNAIL and ZEB1 was observed following CCL20 treatment. These results suggest the importance of CCR6-CCL20 axis in the etiopathogenesis of colon cancer and highlight its potential as therapeutic target.

Citation Format: Neeraj Kapur, Hina Mir, Clarence E. Clark, Uma Krishnamurti, Derrick J. Beech, James W. Lillard, Shailesh Singh. CCR6 associates with colon cancer metastasis. [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 1701.
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

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

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

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

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

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

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 (<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

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 <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 >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 >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

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.
Abstract 1767: Racial/ethnic disparities of obesity in a breast clinic population: Consideration for weight loss program in improving clinical outcomes
Authors: Puyana Barcha Carolina , Lee Eunkyung , Takita Cristiane , Wright Jean L. , Zhao Wei , Reis Isildinha M. , Hu Jennifer J.
Published: July 2016

Introduction: Accumulating evidence suggest that obesity is associated with breast cancer diagnosis, recurrence, and mortality. Obese subjects with genetic predisposition may need more aggressive weight loss management, such as bariatric surgery. Therefore, the primary aim of this study was to assess the racial/ethnic disparities in obesity and the prevalence of breast cancer study participants who may be eligible for bariatric surgery.

Methods: In three clinic-based studies conducted at University of Miami during 2008 to 2015, we evaluated 462 healthy controls and 975 breast cancer patients. Genotyping data of two obesity-related genes (FTO and MC4R) were also evaluated. Race/ethnicity and obesity-related comorbidities were self- reported. Body Mass Index (BMI) was calculated as kg/m2. The classification of BMI was: (1) < 18.5, underweight; (2) 18.5-24.9, normal weight; (3) 25.0-29.9, overweight; (4) 30.0-34.9, class I obesity; (5) 35.0-39.9, class II obesity; and (6) ≥ 40.0, class III obesity. The NIH eligibility for bariatric surgery was for class II obese subjects with obesity-related comorbidities and class III obese subjects.

Results: The study consists of 70.0% Hispanic whites (HW), 21.7% black or African American (AA), and 6.4% non-Hispanic whites (NHW). Mean and SD of age was 54.1± 9.9 years and mean BMI was 29.0±6.1 kg/m2. Overall, about 11.1% of study participants met criteria for bariatric surgery and there were significant racial/ethnic disparities (19.7% AA, 8.5% HW, 8.8% NHW, and 17.2% others; p<0.0001). Subgroup analysis observed increased BMI at follow up (29.60 vs. 29.16 kg/m2, p = 0.00229). Women with the AA risk genotype of rs1121980 (FTO gene) had 3.6-fold higher risk of obesity class II or III compared to those with the GG genotype (p = 0.00393).

Conclusion: In addition to cancer risk, obesity is a major risk factor for cancer treatment-related side effects and worse survival. Our results suggest that at least 11% of breast cancer patients may be eligible for bariatric surgery. Considering some other beneficial effects of bariatric surgery on physical quality of life, metabolic syndrome, diabetes, and microbiome, future studies will consider weight loss and bariatric surgery programs in breast cancer patients, particularly in underserved minorities with higher obesity rate and worse survival.

Citation Format: Carolina Puyana Barcha, Eunkyung Lee, Cristiane Takita, Jean L. Wright, Wei Zhao, Isildinha M. Reis, Jennifer J. Hu. Racial/ethnic disparities of obesity in a breast clinic population: Consideration for weight loss program in improving clinical outcomes. [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 1767.
Abstract 1768: Racial/ethnic differences in endometrioid endometrial cancer survival among cases identified through the National Cancer Database
Authors: Beckmeyer-Borowko Anna B. , Peterson Caryn E. , Brewer Katherine C. , Otoo Mary O. , Davis Faith G. , Hoskins Kent F. , Joslin Charlotte E.
Published: July 2016

OBJECTIVES: Past research suggests that at the local level, Non-Hispanic whites (NHW) have better survival when diagnosed with endometrioid endometrial cancer (EEC) than non-Hispanic blacks (NHB), Hispanics, and American Indians; however, little is known about survival differences at a national level and among other minorities. This study examined whether racial and ethnic differences in 5-year survival are present in U.S. women (NHW, NHB, Hispanics, non-Hispanic Asians (NHA), non-Hispanic Pacific Islanders/Hawaiians (NHPI), non-Hispanic American Indians/Aleutians or Eskimos (NHAI/AN) and non-Hispanics Others (NHO).

METHODS: EEC cases from the National Cancer Database were analyzed to evaluate racial/ethnic differences in 5-year survival among women diagnosed with EEC between 1998 and 2007. Chi-Square test was used to examine whether differences in demographic, clinical, institutional, and treatment variables varied by race/ethnicity. Multivariable Cox proportional hazard regression models were fit to estimate the adjusted hazard ratio (HR) and 95% confidence interval (95% CI) between race/ethnicity and survival.

RESULTS: A total of 178,310 women were diagnosed with EEC between 1998 and 2007. Of these; 74.8% were NHW, 8.3% were NHB, 13.9% were Hispanic, 1.8% were NHA, 0.2% were NHPI, 0.2% were NHAI/AN and 0.8% were NHO. Adjusting for covariates, NHB (HR = 1.29; 95%CI 1.24-1.34) and NHPI (HR = 1.59; 95%CI 1.50-1.67) had poorer survival than NHW. Yet results show that NHA (HR = 0.83; 95%CI 0.74-0.92) and NHO (HR = 0.81; 95%CI 0.69-0.94) had a better survival when compared to NHW. No survival differences were detected between Hispanics, NHAI/AN and NHW.

CONCLUSIONS: Results identify racial/ethnic differences in 5-year survival among women diagnosed with EEC cancer in the U.S. between 1998 and 2007. NHA and NHO had a better and NHB and NHPI had a poorer survival when compared to NHW.

Citation Format: Anna B. Beckmeyer-Borowko, Caryn E. Peterson, Katherine C. Brewer, Mary O. Otoo, Faith G. Davis, Kent F. Hoskins, Charlotte E. Joslin. Racial/ethnic differences in endometrioid endometrial cancer survival among cases identified through the National Cancer Database. [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 1768.
Abstract 177: Src family kinase Fyn promotes the neuroendocrine phenotype and visceral metastasis in advanced prostate cancer
Authors: Cavassani Karen , Gururajan Murali , Sievert Margarit , Duan Peng , Freeman Michael , Chu Gina Chia-Yi , Bhowmick Neil , Chung Leland , Posadas Edward
Published: July 2016

FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of visceral metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PCa cells lines treated with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients.

Citation Format: Karen Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael Freeman, Gina Chia-Yi Chu, Neil Bhowmick, Leland Chung, Edward Posadas. Src family kinase Fyn promotes the neuroendocrine phenotype and visceral metastasis in advanced prostate 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 177.
Abstract 1785: Sociodemographic correlates of knowledge and risk perception of HPV and HPV-associated oropharyngeal cancer
Authors: Chen Betty Y. , Osazuwa-Peters Nosayaba , Adjei Boakeye Eric , Clancy Jennifer , Su Jonathan , Vallot Patrice , Beck Geoffrey , Walker Ronald J. , Varvares Mark A.
Published: July 2016

Purpose

To analyze how key sociodemographic variables correlate with risk perception and knowledge of HPV-associated oropharyngeal cancer in the community.

Methods

A cross-sectional study was conducted at a drag racing event on September 12-13, 2015 in Madison, Illinois. The independent variables were sociodemographic factors including age, gender, race, income level, education level, drinking history, smoking history, and number of sexual partners. The outcome variables were HPV risk perception and knowledge of HPV-associated oropharyngeal cancer, both derived from combining questionnaire items to form knowledge and perception scores. Multivariable linear regression analysis assessed the predictors of risk perception and knowledge of HPV-associated oropharyngeal cancer.

Results

Final sample population was 301. Mean risk perception score was 2.16 ± 1.37 out of 6, and mean knowledge score was 5.65 ± 4.63 out of 15. In multivariable linear regression, race and education were significant predictors of HPV risk perception. Compared to Caucasians, African Americans had a lower perceived risk of developing oropharyngeal cancer (β = -0.35; 95% CI: -0.69 - -0.02). Participants with ≤ high school diploma had a lower perceived risk of developing oropharyngeal cancer compared to those with ≥ college degree (β = -0.60; 95% CI: -1.05 - -0.15). Age, gender, race and education were significant predictors of HPV-associated oropharyngeal cancer knowledge in multivariable analysis. For every one year increase in age, HPV-associated oropharyngeal cancer knowledge decreased by 5%. Men had lower HPV-associated oropharyngeal cancer knowledge (β = -1.30; 95% CI: -2.35 - -0.26) as were African Americans compared to Caucasians (β = -1.30; 95% CI: -2.36 - -0.25). Participants with ≤ high school diploma had lower HPV-associated oropharyngeal cancer knowledge compared to those with ≥ college degree (β = -3.33; 95% CI: -4.75 - -1.91).

Conclusions

Age and gender were independent predictors of knowledge of HPV-associated oropharyngeal cancer, while race and education predict both knowledge and risk perception of HPV-associated oropharyngeal cancer. The sociodemographic correlates demonstrated in our study should inform future interventions targeted at increasing knowledge of HPV-associated oropharyngeal cancer in the community.

Citation Format: Betty Y. Chen, Nosayaba Osazuwa-Peters, Eric Adjei Boakeye, Jennifer Clancy, Jonathan Su, Patrice Vallot, Geoffrey Beck, Ronald J. Walker, Mark A. Varvares. Sociodemographic correlates of knowledge and risk perception of HPV and HPV-associated oropharyngeal 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 1785.