bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3356: Characterization and enrichment of head and neck cancer stem cells suggests differences between HPV+ and HPV- subtypes of HNSCC cells
Authors: Chatterjee Anirban , Nickel Kwangok , Kimple Randall J. 
Published: July 2016

Abstract
Head and neck squamous cell carcinomas (HNSCC) are the sixth most prevalent type of malignancy worldwide. Despite recent advances in multidisciplinary treatments, the overall survival and quality of life of patients with advanced HNSCC have not improved considerably over the past decade. Recent reports have demonstrated that tumors contain a small subpopulation of cells called cancer stem-like cells (CSCs), which are responsible for tumor maintenance and metastasis. CSCs have the ability to self-renew and are responsible for tumorigenesis, progression, metastasis, and relapse after treatment. Recent studies demonstrate that even established HNSCC cell lines contain a definite sub-population of CSC providing us with the opportunity to discerning their roles in progression, treatment, and relapse of the disease.
In vitro Sphere Forming Assays (using ultra-low attachment plate and serum free media) were employed as the key method of CSC enrichment. qPCR analyses, aldehyde dehydrogenase (ALDH) activity, Side Population Phenotype assay (SPP) were used to confirm the results of the primary analyses. To confirm an in vivo CSC phenotype, xenograft tumor formation, through subcutaneous injection in immunocompromised mice was done.
In vitro sphere forming assay followed by subsequent passaging of the sphere enriched cells (SECs) have successfully demonstrated the existence and enrichment of a CSC sub-population in HNSCC cell lines. Findings suggest a differential existence of CSCs related to the HPV status of the cell. ALDH assay and SPP assay confirmed the results of sphere formation. qPCR analyses of the SECs have confirmed enrichment in several stemness marker genes (Oct-4, Sox2, Nanog, Bmi-1, cMyc, KLF4, Beta catenin etc.), also following the identical differential pattern. Various EMT markers genes (Vimentin, Fibronectin, E-cadherin, N-cadherin, Snail, Slug, Twist, ZO-1 etc.) were also assessed, portraying a significant level of expression in CSC populations. SECs subcutaneously injected in immunocompromised mice formed tumors with as few as 50 cells.
We have demonstrated that a definite subpopulation of CSCs exists in HNSCC cell lines. Significant differences were seen between the HPV+ and HPV- subtypes. Analyses of EMT marker genes and other molecular pathways in CSC confirm the differences between HPV+ and HPV- cells too following the similar pattern. In vivo tumor xenograft formation establishes the heightened tumorigenicity of CSCs/SECs.
Citation Format: Anirban Chatterjee, Kwangok Nickel, Randall J. Kimple. Characterization and enrichment of head and neck cancer stem cells suggests differences between HPV+ and HPV- subtypes of HNSCC cells. [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 3356.
Abstract 3389: Androgen deprivation therapy potentiates the efficacy of vascular targeted photodynamic therapy of prostate cancer xenografts
Authors: Kim Kwanghee , Watson Philip A. , Jebiwott Sylvia , Somma Alexander J. , La Rosa Stephen P. , Mehta Dipti , Murray Katie S. , Lilja Hans , Ulmert David , Scherz Avigdor , Coleman Jonathan 
Published: July 2016

Abstract
Focal therapies for prostate cancer offer the possibility of less side effects than more aggressive interventions for organ-confined tumors. Vascular targeted photodynamic therapy (VTP) is being investigated in phase II and phase III clinical trials, and relies upon rapid, free radical-mediated destruction of tumor vasculature following photoactivation of a systemic prodrug. In a phase II trial, &gt;80% of patients did not have detectable cancer in prostate biopsies taken 6 months after VTP treatment. Although these early results are encouraging, VTP efficacy could potentially be improved upon by combining with other therapies. Using the LNCaP-AR prostate cancer model system, we employed microarrays and Gene Set Enrichment Analysis (GSEA) to identify potential druggable pathways active in tumors exposed to VTP. Three to six hours post-VTP, androgen responsive gene sets were enriched, suggesting that the androgen receptor (AR) may be a viable target in combination with VTP. We tested this hypothesis in mice bearing LNCaP-AR xenograft tumors by using the AR pathway inhibitors degarelix (to achieve pharmacological castration) or enzalutamide (AR antagonist), alone or in combination with VTP. Degarelix was administered as a single 0.5-1 mg dose 3 days prior to initiation of VTP, while enzalutamide was given daily for two weeks total both before and after VTP. Serum measurements of prostate specific antigen (PSA) were used as a readout of AR activity. Compared to either AR pathway inhibitor or VTP used alone, degarelix or enzalutamide in combination with VTP significantly inhibited tumor growth. A sharp decline in serum PSA confirmed AR inhibition. Combined degarelix plus VTP treated tumors displayed intense TUNEL staining 7 days post-treatment, supporting an increased apoptotic frequency underlying the effect on tumor inhibition. In prostate cancer treated with VTP, compensatory acute upregulation of pro-survival AR signaling may occur. These findings may warrant investigation of combination with androgen deprivation therapy in future clinical trials utilizing VTP for prostate cancer.
Citation Format: Kwanghee Kim, Philip A. Watson, Sylvia Jebiwott, Alexander J. Somma, Stephen P. La Rosa, Dipti Mehta, Katie S. Murray, Hans Lilja, David Ulmert, Avigdor Scherz, Jonathan Coleman. Androgen deprivation therapy potentiates the efficacy of vascular targeted photodynamic therapy of prostate cancer xenografts. [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 3389.
Abstract 3401: Impact of VEGF and VEGFR polymorphisms on neuroendocrine tumors of the gastro-entero-pancreatic system (GEPNETs) outcome
Authors: Berardi Rossana , Torniai Mariangela , Pagliaretta Silvia , Rinaldi Silvia , Morgese Francesca , Partelli Stefano , Caramanti Miriam , Onofri Azzurra , Polenta Vanessa , Pasquini Sonia , Falconi Massimo , Cascinu Stefano 
Published: July 2016

Abstract
Introduction: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are uncommon neoplasms including a wide range of anatomical, clinical, histological and molecular malignant entities. Improving our understanding of the molecular biology of GEP-NETs represents a key challenge in the treatment of these rare tumors. Therefore we aimed to analyze genotypes of VEGF-A, VEGFR2 and Flt4 in GEP-NETs and their potential correlation with the risk of these tumors and/or with the outcome.
Methods: The genomic DNA of 28 consecutive patients with GEP-NETs treated at our Institution was extracted from paraffinembedded tissue. We selected polymorphisms in the following genes: VEGF-A (rs2010963G&gt;C, rs699947A&gt;C), VEGFR-2 (rs2305948C&gt;T, rs1870377T&gt;A) and VEGFR-3 (rs307826T&gt;C, rs307821C&gt;A). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays.
Results: Median age was 58 (range 33-78) and M/F ratio was 1/1. Twenty-one out of the 28 patients had NETs of the pancreas. The allele frequency of VEGFR2 rs2305948C and of VEGFA rs2010963G showed a trend of lower frequency than in general population (82% vs. 92% and 60.3% vs. 68.8%, respectively, p&lt;0.001). The following factors significantly correlated with a poorer overall survival (p&lt;0.05): VEGFA rs699947C, VEGFA rs2010963A, VEGFR-2 rs1870377T/A, VEGFR-2 rs2305948C/T, VEGFR-3 rs307821C and VEGFR-3 rs307826T.
Conclusion: Our results suggest, for the first time, that inherited abnormalities in VEGF pathway influence the risk and aggressiveness of GEP-NETs. Within March 2016 final data about all the enrolled 64 patients will be also available. These results should be validated prospectively in order to optimize the diagnosis and treatment of these patients.
Citation Format: Rossana Berardi, Mariangela Torniai, Silvia Pagliaretta, Silvia Rinaldi, Francesca Morgese, Stefano Partelli, Miriam Caramanti, Azzurra Onofri, Vanessa Polenta, Sonia Pasquini, Massimo Falconi, Stefano Cascinu. Impact of VEGF and VEGFR polymorphisms on neuroendocrine tumors of the gastro-entero-pancreatic system (GEPNETs) outcome. [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 3401.
Abstract 3410: Downregulation of let 7a 5p predicts lymph node metastasis and prognosis in colorectal cancer: implications for chemotherapy
Authors: Cheng Ya-Wen , Liu Tsang-Pai , Wei Po-Li , Lee Huei 
Published: July 2016

Abstract
Background. Colorectal cancer guidelines recommend adjuvant chemotherapy is based on the number of lymph nodes metastasis. Let-7a-5p is a microRNA which could inhibits migration, invasion and epithelial-mesenchymal transition by targeting HMGA2. The aim of this study was to investigate the role of let-7a-5p in clinical impact of colorectal cancer (CRC).
Methods. One hundred ninety-two CRC patients were enrolled. The expression of let-7a-5p and HMGA2 in serums and tumor tissues were analyzed by real-time PCR and immunohistochemistry. Univariate (Kaplan-Meier) analysis was used to analyze primary outcomes included 5-year overall survival and tumor recurrence.
Results. The expression of let-7a-5p in tumor tissues was significantly negative correlated with tumor size, stage, and lymph node metastasis in CRC patients (p = 0.024 for tumor size, p = &lt;0.0001 for stage, and p&lt;0.0001 for lymph node metastasis). There was a negative correlation between levels of let-7a-5p and the HMGA2 gene (p &lt;0.0001), especially in CRC patients with wildtype APC gene. Patients with let-7a-5p low / HMGA2 high had poorer overall survival (OS) and disease-free survival (DFS) rates than those with let-7a-5p high / HMGA2 high, let-7a-5p high / HMGA2 low, and let-7a-5p low /HMGA2 low groups. In addition, the expression levels of let-7a-5p in PBMCs were positive correlated with in tumor tissues of CRC patients.
Conclusion. We suggest that down-regulation of let-7a-5p in PBMCs and tumor tissues patients could be used to predicts lymph node metastasis and prognosis impact on chemotherapy of colorectal cancer
Citation Format: Ya-Wen Cheng, Tsang-Pai Liu, Po-Li Wei, Huei Lee. Downregulation of let 7a 5p predicts lymph node metastasis and prognosis in colorectal cancer: implications for chemotherapy. [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 3410.
Abstract 342: BGB-283, a slow-off inhibitor of RAF dimers, differentiates from vemurafenib in MAPK signaling inhibition
Authors: Liu Ye , Yuan Xi , Tang Zhiyu , Wang Lai , Luo Lusong , Wei Min 
Published: July 2016

Abstract
Dysregulations of the mitogen-activated protein kinase (MAPK) signaling through abnormal expression or activating mutations of key signaling molecules, including RAS and RAF, have been identified in a wide range of cancers. Targeting these signaling molecules in the pathway represents a promising strategy to target dysregulated MAPK signaling. BGB-283 is a novel pan-RAF inhibitor and currently under clinical development to treat BRAF and KRAS/NRAS mutated tumors. In this study, we show that BGB-283 inhibits WT B-RAF dimer much more potently than vemurafenib at millimolar ATP concentration that is representative of the cellular ATP level, although BGB-283 and vemurafenib display similar inhibitory activity at the Km ATP concentration. BGB-283 has very slow off-rate and the dissociation half-life (t1/2) on WT B-RAF enzyme is well above 24 hrs. In comparison, vemurafenib has much faster off rates with t1/2 in the range of minutes. The crystal structure of BGB-283/B-RAF protein complex shows the benzimidazole and trifluoro group of BGB-283 binds significantly deeper into pocket formed by α-C helix and activation loop than vemurafenib. BGB-283 exhibits time-dependent inhibition both in biochemical assay and in B-RAF or K-RAS mutated cells. BGB-283 potently inhibits the p-ERK signaling in splicing isoform p61B-RAF(V600E) cells which were reported to be resistant to vemurafenib through a dimer mechanism. In vivo, BGB-283 significantly suppressed the tumor growth in A375-p61B-RAF(V600E) melanoma xenograft model. In addition, BGB-283 inhibits vemurafenib induced p-ERK activation and selumetinib induced p-MEK feedback activation in K-RAS mutated cancer cells. In both cases, activation is reported to be mediated by RAF dimers. Taken together, we propose that BGB-283 is a novel, slow-off RAF dimer inhibitor that targets the MAPK signaling differently from the first generation BRAF inhibitor vemurafenib. This feature of BGB-283 may help to address the drug resistance issues in BRAF mutated tumors and further expand its utility as mono- or combination therapy into RAS mutated patient populations.
Citation Format: Ye Liu, Xi Yuan, Zhiyu Tang, Lai Wang, Lusong Luo, Min Wei. BGB-283, a slow-off inhibitor of RAF dimers, differentiates from vemurafenib in MAPK signaling inhibition. [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 342.
Abstract 3426: Recurrent breast cancer risk and physical activity
Authors: Lehman Teresa A. , Modali Ramakrishna V. , Ratnasinghe Luke D. 
Published: July 2016

Abstract
Introduction: Physical activity reduces the risk of breast cancer. However, the potential role of physical activity in recurrence of breast cancer is not well established. The aim of our study is to examine the association between physical activity and risk of recurrent breast cancer. Methods: Data was obtained from the Global Epidemiological Study (GES). The GES is an IRB approved multinational biorepository and database to assess cancer and other disease risk factors and biomarkers. In-person interviews of all subjects provided demographics, family-history and other disease related information including age, BMI, diet and physical activity. For statistical analyses, t-tests were used for continuous variables and chi-square tests for categorical variables. The association between recurrent breast cancer and physical activity was assessed using logistic regression in univariate and multivariate analyses. Results: From a total of 2435 breast cancer subjects 215 had recurrent breast cancer. The average age of subjects without recurrence was 55.62 years and those with breast cancer recurrence was 58.35 years. In univariate analysis, subjects in the highest tertile of physical activity were 39% less likely to have recurrent breast cancer compared to those who reported no physical activity [Odds Ratio: 0.61, 95% Confidence Interval: 0.40-0.93]. In multivariate analysis, subjects in the highest tertile of physical activity were 45% less likely to have recurrent breast cancer compared to those who reported no physical activity [Odds Ratio: 0.55, 95% Confidence Interval: 0.34-0.89] after adjusting for age, BMI and cancer-stage. A statistically significant dose-response for physical-activity and reduced risk of recurrent breast cancer was observed with a P-value for trend of 0.05. Conclusion: Our study suggests that physical activity reduces the risk of recurrence of breast cancer. Further studies with larger sample size are needed to confirm our findings.
Citation Format: Teresa A. Lehman, Ramakrishna V. Modali, Luke D. Ratnasinghe. Recurrent breast cancer risk and physical activity. [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 3426.
Abstract 3448: ERG-negative index tumor status combined with obesity predict prostate cancer progression in Caucasian American prostate cancer patients
Authors: Cullen Jennifer , Young Denise , Chen Yongmei , Degon Michael S. , Baptiste Wagner , Farrell James S. , Sedarsky Jason S. , Kuo Huai-Ching , Kagan Jacob , Srivastava Sudhir , Rosner Inger L. , Petrovics Gyorgy , Dobi Albert , McLeod David G. , Srivastava Shiv , Sesterhenn Isabell A. 
Published: July 2016

Abstract
Introduction: and Objectives: A significantly lower prevalence of ERG oncoprotein has been reported for African American (AA) compared to Caucasian American (CA) prostate cancer (PCa) patients. This difference has been observed when examining prostate cancer (PCa) index tumors as well as for comparisons of non-index tumor foci. To evaluate the potential of ERG status in predicting disease progression, this study examined a large cohort of AA and CA PCa patients within a racially diverse, equal access, military health care center.
Methods: Representative sections of whole mounted prostatectomy specimens from AA (n = 373) and CA (n = 684) patients were evaluated for ERG oncoprotein status by immunohistochemistry. Demographic, clinical, and pathologic patient features, including body mass index, were compared across ERG status (positive vs. negative). Time to event regression analysis was used to model ERG status as a putative predictor of biochemical recurrence (BCR) and distant metastasis.
Results: A significantly lower prevalence of ERG positivity was noted in both index and non-index tumors of AA patients as compared to CA patients. Among CA patients only, ERG-negative index tumors were associated with greater odds of developing BCR and metastasis. Similarly, among CA patients only, having an ERG negative index tumor and being obese at time of prostatectomy was strongly associated with developing biochemical recurrence and metastasis.
Conclusions: These provocative data warrant further investigation of the combined roles between race, obesity, and ERG status on PCa progression. Despite a robust sample size of AA men, the absence of statistically significant associations between ERG and obesity status on disease progression among AA patients could be attributed to insufficient statistical power.
Source of Funding: This research was supported by the National Cancer Institute R01CA162383 grant to SS, by the Center for Prostate Disease Research and by the EDRN/NCI ACN12011-001 to GP, AD, IAS, DGM and SS.
Citation Format: Jennifer Cullen, Denise Young, Yongmei Chen, Michael S. Degon, Wagner Baptiste, James S. Farrell, Jason S. Sedarsky, Huai-Ching Kuo, Jacob Kagan, Sudhir Srivastava, Inger L. Rosner, Gyorgy Petrovics, Albert Dobi, David G. McLeod, Shiv Srivastava, Isabell A. Sesterhenn. ERG-negative index tumor status combined with obesity predict prostate cancer progression in Caucasian American prostate cancer patients. [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 3448.
Abstract 3460: Breast and ovarian cancer prevention: is it time for population screening for BRCA mutations
Authors: Campbell Ian G. , Thompson Ella , Mitchell Gillian , Trainer Alison , Young Mary-Anne , James Paul 
Published: July 2016

Abstract
Germline mutations in BRCA1 and BRCA2 confer high lifetime risk of breast and ovarian cancer but importantly these risks are not irreversible. Identification of asymptomatic carriers could significantly reduce the incidence of these diseases. The traditional model of familial breast and ovarian cancer practice involves ascertaining high-risk individuals based on family history. In general, the family is first identified because one member develops cancer and because of high-risk indicators, is referred to a Familial Cancer Centre. However, more than 50% of women who carry a BRCA1/2 mutation may not have a family history of cancer in a close relative. Momentum toward genetic screening of the asymptomatic population is growing but there remain some significant unknowns. For example it is unclear what is the true frequency of actionable mutations in the general western population and the extent to which the public would accept such screening, particularly for those individuals identified with an actionable mutation in the absence of an overt family history. As a first step toward population based BRCA gene screening, we are sequencing the entire coding region of 18 known and proposed HBOC genes in 4,000 cancer-free Australian women recruited from the lifepool study (www.lifepool.org), which is a cohort of women attending the Australian population, based mammographic screening program. To date, data from 1,997 women has identified 17 with actionable mutations in BRCA1 (4 mutations), BRCA2 (9 mutations) or PALB2 (4 mutations). All 17 women subsequently accepted an invitation to attend a Familial Cancer Centre and then proceeded to formal clinical genetic testing. In addition 4 women had pathogenic mutations in BRIP1. Our unique pilot data directly demonstrates a population carrier frequency of ∼1% for pathogenic mutations in these recognized high risk breast and/or ovarian cancer genes and that such testing is well accepted by the screened population.
Citation Format: Ian G. Campbell, Ella Thompson, Gillian Mitchell, Alison Trainer, Mary-Anne Young, Paul James. Breast and ovarian cancer prevention: is it time for population screening for BRCA mutations. [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 3460.
Abstract 3471: Perceived role of family for Hispanic/Latino lung cancer patients: A qualitative study
Authors: Motta-Moss Ana , Alago William , Lin Lorna , Akhuetie Jane 
Published: July 2016

Abstract
Healthcare decisions are not made by the patients alone, but rather the result of collaborative efforts between healthcare professionals and, more importantly, family members who become significant because of the various roles they perform throughout the process. The purpose of this study was to examine the role of family in the care of Hispanic/Latinos patients with lung cancer. Inconsistent expectations of the role of family affect how patients view family support throughout the diagnosis and treatment process. Therefore, it is important to examine what patients perceive to be an appropriate role for family members that assist in their healthcare. Twenty-four patients self-identified as Hispanic/Latino and treated at Memorial Sloan Kettering Cancer Center (MSKCC) for lung cancer stage I-IV participated in semi-structured face-to-face interviews. The four major themes of the role of family identified in this study include: general support, navigation of healthcare system, communications, and lack of family support. It is important to understand that family roles change as the patients’ needs change over the course of the disease. Nonetheless, identifying the various forms of support provided by family is essential to understanding the benefits of family presence in the diagnosis and treatment of lung cancer, particularly among Latinos.
Citation Format: Ana Motta-Moss, William Alago, Lorna Lin, Jane Akhuetie. Perceived role of family for Hispanic/Latino lung cancer patients: A qualitative study. [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 3471.