bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5253: LTβ receptor and NIK signaling activates the alternative NF-kB pathway in head and neck squamous cell carcinoma
Authors: Das Rita , Cheng Tsu-Fang , coupar Jamie , Saleh Anthony , Yang Xingping , Zhang jialing , Cornelius shaleeka , Van Waes Carter , Chen zhong 
Published: August 2015

Abstract
Head and neck squamous cell carcinomas (HNSCC) are highly inflammatory and preferentially metastasize to lymph nodes. NF-κB, a key target and regulator of inflammatory and cancer genes is constitutively activated in HNSCC, but the upstream regulation, especially for activation of alternative pathway involving LTβ/LTβR is not clear. We hypothesized that LTβ/LTβR mediated alternative NF-kB pathway signaling is an important mechanism for activation of downstream target genes, and promotion of malignant and metastatic phenotypes in HNSCC. In this study, we have found that LTβ and LTβR are overexpressed in subsets of HNSCC (UM-SCC) tissues and cell lines. In UM-SCC cell lines, LTβ mainly activated the alternative NF-kB pathway, enhancing nuclear translocation of RELB and NF-κB2/p52, in contrast to TNFα induced activation of classical NF-κB pathway. Knockdown of LTβR by Si RNA decreased LTβR mRNA by quantitative RT-PCR and protein expression by Western blots. Knockdown of LTβR decreased its target kinase NIK, and downstream NF-κB subunits RELB and NF-κB2/p52 protein expression. Knockdown of NIK protein decreased RELB and p52 protein expression, while LTβ treatment stabilized NIK, RELB and NF-κB2/p52 expression. LTB mediated NF-κB activity was examined by transient luciferase reporter assay or using stably transfected NF-κB reporter cell line through beta lactamase Fret Blazer activity. Knockdown of LTBR and NIK functionally decreased NF-κB reporter activity, while treatment of LTB partially restored the NF-κB reporter activity. Our data have shown that constitutive and LTβ induce activation of NIK and downstream NF-κB alternate pathway proteins, RELB and NF-kB2/p52 in HNSCC. LTβ and NIK activation of the alternative NF-κB pathway may contribute to the malignant phenotype and metastasis of HNSCC.
Citation Format: Rita Das, Tsu-Fang Cheng, Jamie coupar, Anthony Saleh, Xingping Yang, jialing Zhang, shaleeka Cornelius, Carter Van Waes, zhong Chen. LTβ receptor and NIK signaling activates the alternative NF-kB pathway in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5253. doi:10.1158/1538-7445.AM2015-5253
Abstract 5260: Mitochondrial DNA phylogenetic analysis for local recurrences and second primary tumors from patients with oral cavity squamous cell carcinoma
Authors: Lai Chih-Hsiung 
Published: August 2015

Abstract
Local recurrences (LRs) and second primary tumors (SPTs) are commonly observed in patients with oral squamous cell carcinoma (OSCC). A lower survival rate has been demonstrated in patients with LRs with respect to patients with SPTs. Therefore, the criteria for differentiating LRs and SPTs are indispensable for determining appropriate treatment. Currently, criteria based on histology, the distance and relapse time between new lesions and index primary tumor are generally used in clinical classification. In the genomic era, molecular classification based on the clonal relationship between the first and the second lesions may be more reliable than traditional clinical classification. The aim of the present study tried to establish a feasible molecular classification based on mitochondrial DNA (mtDNA) phylogenetic analysis. The study population consisted of 44 OSCC patients with multiple lesions for a total of 47 (19 LRs and 28 SPTs) paired lesions. The mtDNA analysis was performed by direct sequencing. The phylogenetic and molecular evolutionary analyses were conducted by using MEGA software version 6 and three common phylogenetic evolutionary methods (Maximun Likelihood (ML), Neighbor-Joining (NJ) and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) method) were applied. Preliminary analysis indicated that the prevalence of clonality for LRs and SPTs was 26.3% and 3.6%, respectively. A discrepancy between the clinical classification and mtDNA analysis was found in 15 paired tumors (31.9%) in which 14 paired lesions were classified as LRs based on clinical criteria, while mtDNA analysis suggested that they were nonclonal-related SPTs. Survival analysis indicated that there was no difference between patients with LRs and patients with SPTs based on clinical classification. On the other hand, patients with clonal second lesions had poorer overall survival than patients with nonclonal second lesions based on mtDNA analysis. In conclusion, our preliminary findings suggested that molecular clonality analysis could improve the accuracy in differentiating LRs from SPTs.
Citation Format: Chih-Hsiung Lai. Mitochondrial DNA phylogenetic analysis for local recurrences and second primary tumors from patients with oral cavity squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5260. doi:10.1158/1538-7445.AM2015-5260
Abstract 5262: Specific mtDNA variants and colorectal adenopolyps
Authors: Wallace LaShanale M. , Mehrabi Sharifeh , Yao Xuebiao , Aikhionbare Felix O. 
Published: August 2015

Abstract
The clinical frequency of colorectal cancer occurrence increase in adenomas with a predominant villous histopathology: tubular (5%), tubulovillous (22%) and villous (40%). Adenoma may develop throughout the gastrointerestinal tract with coarse lobulations formed by branching tubular glands whose lumens open on the surface which are rare in most patient gastrointerestinal tract areas other than the colorectum. The adenoma-carcinoma sequence is clinically associated in patients with polyposis and ulcerative colitis since their predilection for developing carcinoma in adenomatous epithelium is greatly increased. This study focused on COX, ATPase, rRNA, Cytb and ND genes of the mitochondrial genome that have been associated as modifying risks of cancer. Using PCR-based sequence and High resolution restriction endonuclease, we investigated the potential role of mtDNA alterations in colorectal adenopolyps (Tubular, Tubulovillous, and Villous) and carcinoma. Fifty-eight primary tissues of colorectal adenopolyps, carcinoma and their matched normal controls were used in this study. Twenty-two variants were observed and most of these variants were germline and homoplasmic transitions. Unreported germline variants Cytb-A14782T (90%) and MT-ATPase 8 A9169C (75%) were associated with tubular adenomas. Also, MT-ATPase 6- variant T8994A (85%) was associated with tubulovillous adenomas. Moreover, in the highly conservative region of rRNA, variant T1738C was found in colorectal carcinoma only. Results suggest that some specific mtDNA variants may exert their effects on colorectal adenopolyps to gain a proliferative advantage in patients bearing CRC.
Citation Format: LaShanale M. Wallace, Sharifeh Mehrabi, Xuebiao Yao, Felix O. Aikhionbare. Specific mtDNA variants and colorectal adenopolyps. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5262. doi:10.1158/1538-7445.AM2015-5262
Abstract 5270: IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas
Authors: Olar Adriana , Wani Khalida , Diefes Kristin , Heathcock Lindsey , van Thuijl Hinke , Gilbert Mark , Armstrong Terri , Sulman Erik , Cahill Daniel , Reijneveld Jaap , Ylstra Bauke , Wesseling Pieter , Aldape Kenneth 
Published: August 2015

Abstract
Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II-III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and wild-type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR) = 1.21, 95% confidence interval (CI) = 0.91-1.61] compared to IDH-wild type tumors (HR = 1.74, 95% CI = 0.95-3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p&lt;0.01, HR = 4.41, 95% CI = 2.55-7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p = 0.471, HR = 1.10, 95% CI = 0.80-1.51), and could demonstrate a statistical interaction (p&lt;0.01) between IDH mutation and mitotic index. Patient age, an established prognostic factor in diffuse glioma, was associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II-III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II-II gliomas as independent entities.
Citation Format: Adriana Olar, Khalida Wani, Kristin Diefes, Lindsey Heathcock, Hinke van Thuijl, Mark Gilbert, Terri Armstrong, Erik Sulman, Daniel Cahill, Jaap Reijneveld, Bauke Ylstra, Pieter Wesseling, Kenneth Aldape. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5270. doi:10.1158/1538-7445.AM2015-5270
Abstract 5289: The role of the immune system in lymph node positive ER+ breast cancer
Authors: Cockburn Jessica G. , Gillgrass Amy , Bane Anita 
Published: August 2015

Abstract
Estrogen receptor (ER) positive breast cancer (BC) accounts for 70% of BC diagnoses and is associated with a good outcome when treated with conventional therapies, including tamoxifen. However, there remains a sub-population of patients who undergo relapse within 10 years of diagnosis and do not respond well to standard therapies. While lymph node (LN) status is an important indicator of poor prognosis, additional information is needed to more accurately predict patients who will or will not relapse. Previous genomic studies from our lab have shown that immune response is an important feature of LN+ BCs that do not relapse. In addition, other studies have also examined the role of the immune system in ER+ BC, but due to varying study designs, it is unclear how immune response pertains to ER+ BC relapse. The goal of this project is to characterize immune response in ER+ BC by measuring levels of immune markers using immunohistochemistry (IHC) and RNA expression levels and comparing those to tumour characteristics. We have developed a cohort of retrospective ER+ BC patients with tumour samples available through the Hamilton Health Science tumour bank. Patients were selected for eligibility based on ER status, early stage disease, and having long term clinical follow-up. Clinical charts for each patient were reviewed and pathological, treatment, and outcome data were abstracted. Tumour blocks were obtained and sections stained for haematoxylin and eosin were marked for tumour boarders then used to construct Tissue microarrays (TMA) for IHC assays and RNA is to be extracted from each tumour block. 318 patient samples have been obtained that meet eligibility requirements. Among those, 163 are LN- and 110 are LN+, and the remainder have unknown LN status. Primary endpoint for this study is the development of distant metastasis. Roughly 10% of LN- patients developed distant metastasis within 10 years and roughly 20% of LN+ patients developed distant metastasis. In total, 14% of patients came to endpoint during the study period. TMAs were stained for pathological markers, including ER, PR, HER2, and Ki67 as well as immune markers such as CD8 and CD20. RNA expression levels for each of these were also determined and both were compared with clinical outcome. Here we present a retrospective cohort of ER+ BC patients with 10 years of clinical follow-up data that can be used for IHC and RNA analysis. Further, we have examined the association between immune response and prognosis in lymph node positive ER+ BC patients.
Citation Format: Jessica G. Cockburn, Amy Gillgrass, Anita Bane. The role of the immune system in lymph node positive ER+ breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5289. doi:10.1158/1538-7445.AM2015-5289
Abstract 529: Phosphorylation of Thr165 within the activation loop of Nek3 kinase is necessary for its pro-migratory function in breast cancer cells
Authors: Harrington Katherine M. , Clevenger Charles V. 
Published: August 2015

Abstract
The polypeptide hormone prolactin (PRL) is increasingly recognized as contributing to the development and progression of human breast cancer. Activation of the prolactin receptor (PRLr) by PRL contributes to the growth, survival and motility of human breast cancer cells. The PRL/PRLr complex activates multiple signaling pathways, including the serine/threonine kinase, Nek3 (NIMA-related kinase 3). PRL acts as a chemoattractant for breast cancer cells, accompanied by reorganization of the cytoskeleton. However, the molecular mechanisms by which PRLr signaling contributes to the invasive breast cancer cellular phenotype is not fully understood. Nek3 [NIMA (never in mitosis gene a)-related kinase 3] is a member of the serine/threonine (S/T) Nek protein kinases. Data from our laboratory suggests that Nek3 may contribute to breast cancer pathogenesis through regulation of cell migration/invasion, apoptosis, and cytoskeletal reorganization. Therefore, targeting Nek3 in breast cancer cells represents a novel therapeutic approach to potentially improve the treatment of breast cancer. We previously demonstrated that PRL/PRLr-signaling activates Nek3, however the molecular mechanisms of Nek3 kinase activation remain to be elucidated. Therefore, to better understand the mechanism of PRL-dependent regulation of Nek3 kinase activity, we focused on determining whether Nek3 activity is regulated by phosphorylation and to identify the potential sites(s) of autophosphorylation. Through site-directed mutagenesis of Nek3 residues in the activation segment, we identified threonine residue 165 (Thr165), as a major site that regulates the catalytic activity of Nek3. In addition to being autophosphorylated in vitro, Nek3 Thr165 was also phosphorylated in response to the PRL-MEK-ERK1/2 signaling pathway in PRL-stimulated breast cancer cells. We show here that phosphorylation at Thr165 Nek3 plays an important regulatory role in cell migration and adhesion, steps that are critical in the invasive process leading to tumor metastasis. In order to test this, we expressed wild-type Nek3 and a nonphosphorylatable Nek3 mutant (T165V) in the breast cancer cell lines T47D and MCF7. We found that expression of T165V Nek3 resulted in a significant decrease in cell adhesion to the basement membrane matrix, Matrigel, while additionally inhibiting cell motility in a wound healing assay. Ongoing studies are further examining the role of Nek3 in regulating focal adhesion dynamics and cytoskeletal remodeling.
Citation Format: Katherine M. Harrington, Charles V. Clevenger. Phosphorylation of Thr165 within the activation loop of Nek3 kinase is necessary for its pro-migratory function in breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 529. doi:10.1158/1538-7445.AM2015-529
Abstract 5292: Determination of the receptor for advanced glycation end-products in breast cancer patients previous chemotherapy
Authors: Guadarrama-Orozco Jorge A. , Ruiz-García Erika B. , Maldonado-Martinez Hector A. , Barron-Rodríguez Lilia P. , Mainero-Ratchelous Fernando , Astudillo-delaVega Horacio 
Published: August 2015

Abstract
The receptor for advanced glycation end-products (RAGE) is a newly recognized factor regulating cancer cell invasion and metastasis. RAGE has recently been recognized as a cancer-associated protein responsible for cancer progression and metastasis in gastrointestinal and epithelial cancers. The aim was to examine the role of RAGE in breast cancer previous to chemotherapy treatment.
Methods: A retrospective study in surgical specimens obtained from 68 consecutive patients who underwent surgery for stage II-III breast cancer at the Oncology Hospital at National Medical Center SXXI, between 2008 and 2009. RAGE expression was examined by immunohistochemistry (IHQ) and PCR in 68 patients with stage II or III breast cancer previous chemotherapy treatment. RAGE expression was compared with clinicopathological parameters including clinical stage, invasive depth, nodal metastasis, disease recurrence and disease-free survival. The positive expression rate of RAGE was defined as 50% or more of stain in IHQ.
Results: In all 68 samples no RAGE membrane expression was found significantly. Just one specimen was 50% positive in tumor IHQ and no clinicopathological correlation was found. In PCR the results were more significant. Our findings shows suggestive no evidence for the presence of RAGE in membrane, but possibly RAGE gene expression could had relationship in the progression of breast cancer in stages II and III.
Citation Format: Jorge A. Guadarrama-Orozco, Erika B. Ruiz-García, Hector A. Maldonado-Martinez, Lilia P. Barron-Rodríguez, Fernando Mainero-Ratchelous, Horacio Astudillo-delaVega. Determination of the receptor for advanced glycation end-products in breast cancer patients previous chemotherapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5292. doi:10.1158/1538-7445.AM2015-5292
Abstract 5295: Latent class longitudinal modeling of CTCs in ER+ metastatic breast cancer patients
Authors: Hyslop Terry , Li Xuechan , Duan Rui , Giuliano Mario , Giordano Antonio , Orloff Marlana , Rui Hallgeir , Reuben James M. , Cristofanilli Massimo 
Published: August 2015

Abstract
The baseline and longitudinal monitoring of circulating tumor cells (CTCs) demonstrated strong prognostic and predictive value in patients with metastatic breast cancer (MBC) irrespective of tumor subtype but particularly in ER+ disease. Utilizing a cohort of ER+ MBC patients, with longitudinal assessments of CTCs, we applied a novel statistical model to identify subgroups of CTC patterns that inform patient prognosis.
This is a retrospective analysis of 516 patients with MBC who had CTCs serially enumerated as part of their disease evaluation and monitoring. Two-hundred and six patients with ER+ disease and at least 3 CTC measures were identified and constitute the cohort for this analysis. Peripheral blood samples (7.5 ml) collected within 30 days before starting any systemic treatment were drawn into CellSave tubes and processed within 72 hours of collection. The standardized US Food and Drug Administration-cleared CellSearch System was used to isolate and count CTCs. Two-stage models, consisting of patterns of trajectories of CTCs in stage 1, defined via a latent class zero-inflated Poisson model, followed by a probability weighted Cox model of survival outcomes were employed. Both overall survival (OS) and progression free survival (PFS) were considered separately. Model selection was based on Akaike Information Criteria (AIC).
Three classes of CTC trajectories are identified (always low = L, 70.3%, controlled moderate = M, 20.9%, high uncontrolled = H, 8.7%) with significant differential OS (AHR M vs L 5.32, p&lt;0.001, H vs L 10.41, p&lt;0.001, H vs M 1.96, p = 0.039) and PFS (AHR M vs L 2.05, p&lt;0.001, H vs L 4.24, p&lt;0.001, H vs M 2.06, p = 0.015) in multivariable modeling adjusting for bone metastases (Y vs. N), number of metastatic sites, and Her2 status.
In summary, longitudinal monitoring of CTCs in patients with ER+ MBC can provide additional prognostic stratification and predictive value compared to standard baseline assessment and could potentially assist in better therapy selection and specific efficacy monitoring.
Citation Format: Terry Hyslop, Xuechan Li, Rui Duan, Mario Giuliano, Antonio Giordano, Marlana Orloff, Hallgeir Rui, James M. Reuben, Massimo Cristofanilli. Latent class longitudinal modeling of CTCs in ER+ metastatic breast cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5295. doi:10.1158/1538-7445.AM2015-5295