bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1845: Sensitivity of PC9 cells to erlotinib is affected by extracellular matrix
Authors: Onishko Halina M. , Zhao Jie , Jameson Katherine L. , Frick Peter L. , Tyson Darren R. , Quaranta Vito , Yankeelov Thomas E. , Rericha Erin C. 
Published: May 2015

Abstract
Tyrosine kinase inhibitors of epidermal growth factor receptor, such as erlotinib and gefinitib, have been effective in the initial treatment of non-small cell lung cancer. With time, however, initially responsive tumors almost invariably rebound and proliferate under therapy. Of general interest is the impact of tumor cell heterogeneity on rebound time. Previously, we isolated 89 single-cell derived discrete sublines (DS) from the commonly studied PC9 cell line by monitoring the distribution of cell fates (division, quiescence, and cell death) and the drug-induced proliferation (DIP) rate under erlotinib treatment. In this work we examine the role of the extracellular matrix (ECM) in determining proliferation behavior and the distribution of cell fates. Cells suspended in 3D matrices show increased sensitivity to erlotinb with the rate of cell death depending on the ECM composition. DS sublines that were highly resilient in 2D culture (i.e., positive DIP rate and &lt;10% cell death under treatment) asymptote to about 40% cell death in Matrigel after ten days in 1 µM erlotinb. Both the rate of cell death and the total percentage of the cell population that dies increased in collagen I and in collagen I coated hydrogel. At asymptotic levels, the cell population contained both dividing and quiescent cells. In contrast, DS sublines with negative DIP rates in 2D culture reached 90-99% cell death in each ECM considered. We conclude that the pathways conferring resilience in these cells are sensitive to ECM conditions. Intriguingly, we find that resilient DS sublines tend to have diversity in cluster morphologies in the matrices, suggesting a possible correlation between ECM engagement and/or adhesion and resilience. Molecular studies should clarify mechanistic relationships between ECM and sensitivity to targeted therapy, and whether such relationship may extend to clinical tumors.
Citation Format: Halina M. Onishko, Jie Zhao, Katherine L. Jameson, Peter L. Frick, Darren R. Tyson, Vito Quaranta, Thomas E. Yankeelov, Erin C. Rericha. Sensitivity of PC9 cells to erlotinib is affected by extracellular matrix. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1845. doi:10.1158/1538-7445.AM2014-1845
Abstract 1851: Colorectal adenomatous polyps and mitochondrial DNA variants
Authors: Aikhionbare Felix O. , Mehrabi Sharifeh , Cohen Shakeria , Yao Xuebiao , Iyamu Osatohamwen 
Published: May 2015

Abstract
Patients with adenomatous polyps have a threefold higher risk of colon cancer over the general population, which increases to sixfold if the polyps are multiple and with lower survival among African American population. Up to now, only 6% of CRC can be ascribed to mutations in particular genes. Moreover, the optimal management of patients with colorectal adenomatous polyps depends on the accuracy of appropriate staging strategies because patients with similar colorectal adenocarcinoma architecture display heterogeneity in the course and outcome of the disease. In this study, using high resolution restriction endonucleases and PCR-based sequencing, we have potentially identified some distinctive mitochondrial DNA restriction sites and sequence polymorphisms that distinguished variants among colorectal adenomatous polyps and between pre-cancer and carcinoma in the regions of ND, CYTO b, ATPase and COX genes. The distribution of some of the observed mtDNA sequence variants includes:0% (0/161) tubular, 1.2% (12/161) tubulovillous, 54% (87/161) villous, and 94.4% (152/161) cancer . The restriction analysis, using HINC II enzyme, identified a number of band shifts indicating site gains or losses in differentiating between colorectal adenomatous polyps and cancer. Results are the first study to systemic survey mitochondrial genome alterations on the pathology and clinical significance of colonic adenocarcinoma with villous architecture. This abstract was supported by NIH-NIGMS # GM099663.
Citation Format: Felix O. Aikhionbare, Sharifeh Mehrabi, Shakeria Cohen, Xuebiao Yao, Osatohamwen Iyamu. Colorectal adenomatous polyps and mitochondrial DNA variants. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1851. doi:10.1158/1538-7445.AM2014-1851
Abstract 1854: P16 immunoreactivity in endocervical tubo-endometrial metaplasia (TEM) and correlation with high risk HPV (HRHPV) status by chromogenic in-situ hybridization (HPV-CISH) and hybrid capture 2 assay
Authors: Talukdar Shobhana , Juan Gomez-Gelvez , Buekers Thomas E , Zhang Ziying 
Published: May 2015

Abstract
Background
Several studies have shown that endocervical TEM can intensively over express p16 and involve more than 50% of the cells. It could be speculated that TEM may be a precursor lesion of cervical glandular intraepithelial neoplasm. The aim of this study is to evaluate endocervical TEM p16 overexpression pattern and further investigate its potential driven mechanisms by correlating with HRHPV status.
Method
Our search included cervical biopsy, LEEP, conization with TEM diagnosis from January 2005-May 2013. Only cases with concurrent Pap smear with HRHPV testing were selected. HRHPV detected in liquid based cytology is by Hybrid Capture 2 Assay. Surgical specimens containing concurrent squamous dysplasia were excluded due to potential confounding by HRHPV positivity in dysplastic squamous epithelium. P16 stain was performed and graded as negative, focal+ (&lt;50% cytoplasmic and nuclear stain) and diffuse+ (&gt;50% cytoplasmic and nuclear stain). HRHPV data was collected from Pap reports. HPV-CISH assays will be performed for all cased with positive HRHPV detected in liquid based cytology.
Result:
Our search generated 159 cases with TEM. Only 81 cases had concurrent Pap smear with HRHPV testing. 48 cases were excluded due to squamous dysplasia. A total of 33 patients with an age range of 20-59 were available for the study. Twenty nine out of 33 had negative HRHPV in liquid based cytology; in which, p16 stain results as: 8/29 negative, 14/29 focally +. 7/29 diffusely +. Four out of 33 had positive HRHPV detected in liquid based cytology; in which, p16 stain results as: 1/4 negative, 3/4 diffusely +. HPV-CISH assays were performed in all 4 cases and they were negative.
Conclusions
P16 overexpression in TEM can be intense and involve more than 50% of the cells but the pattern is heterogenous and positivity never involves 100% of the cells. Neither HPV-CISH nor Hybrid Capture 2 Assay detects HRHPV in TEM. P16 overexpression in TEM is most likely HRHPV-independent mechanisms.
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Note: This abstract was not presented at the meeting.
Citation Format: Shobhana Talukdar, Gomez-Gelvez Juan, Thomas E Buekers, Ziying Zhang. P16 immunoreactivity in endocervical tubo-endometrial metaplasia (TEM) and correlation with high risk HPV (HRHPV) status by chromogenic in-situ hybridization (HPV-CISH) and hybrid capture 2 assay. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1854. doi:10.1158/1538-7445.AM2014-1854
Abstract 1857: Prognostic biomarker for SNP (-617C-A) in ARE-like loci of the NRF2 gene in lung adenocarcinoma
Authors: Okano Yasuko , Ichikawa Yasushi , Miyagi Yohei , Kondo Keiichi , Natsumeda Yutaka 
Published: May 2015

Abstract
Purpose: We here report that SNP (c.-617C&gt;A; rs6721961) in the ARE-like region of NRF2 gene is associated with Japanese non-smoking female patients with adenocarcinoma and their overall survival.
Experimental Design: We prepared genomic DNA samples from 387 Japanese patients with primary lung cancer and detected a SNP (-617C&gt;A) in NRF2 gene by the rapid genetic testing method we developed in this study. We analyzed the association between the SNP in the NRF2 gene and overall survival.
Results:Patients harboring wild-type -617C/C, -617C/A, and -617A/A alleles numbered 216 (55.8%), 147 (38.0%), and 24 (6.2%), respectively. Multivariate logistic regression models revealed that SNP homozygote (-617A/A) was significantly related to gender. Its frequency was four-fold higher in female patients than in males (10.8% female vs 2.7% male) and was associated with female non-smokers with adenocarcinoma. Interestingly, lung cancer patients carrying the SNP homozygous alleles (-617A/A) and the 309T (WT) allele in the MDM2 gene exhibited remarkable survival over 1,700 days after surgical operation (log-rank p=0.021). Conclusion: SNP homozygous (-617 A/A) alleles in the NRF2 gene are associated with female non-smokers with adenocarcinoma and regarded as a prognostic biomarker for assessing overall survival of patients with lung adenocarcinoma.
Citation Format: Yasuko Okano, Yasushi Ichikawa, Yohei Miyagi, Keiichi Kondo, Yutaka Natsumeda. Prognostic biomarker for SNP (-617C-A) in ARE-like loci of the NRF2 gene in lung adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1857. doi:10.1158/1538-7445.AM2014-1857
Abstract 1861: S100P is a potential biomarker in distinguishing mucinous from non-mucinous pancreatic cysts and predicting invasive adenocarcinoma
Authors: Mi Wenyi , Diehl David L. , Shi Jianhi , Blansfield Joseph , Hunsinger Marie , Yang Wannian , Lin Fan 
Published: May 2015

Abstract
Introduction. Our previous publications demonstrated that S100P was a highly sensitive biomarker in identifying pancreatic mucinous neoplasms (PMNs) and invasive ductal adenocarcinomas (ADCs) on both cytological and surgical specimens. When working on pancreatic cystic lesions, there are two important undertakings: 1) distinguishing mucinous neoplasms from non-mucinous cysts and 2) predicting the presence of invasive adenocarcinomas. In this study, we investigated the potential utility of S100P for these purposes.
Design. Thirty pancreatic cystic fluid samples obtained by EUS-FNA biopsy were retrieved from Geisinger Biospecimen Bank. Diagnosis was based on definitive cytological diagnosis in all cases and additional surgical pathology confirmation in 11 cases. These 30 samples included 7 benign cysts in Group 1, 14 PMNs in Group 2, and 9 ADCs in Group 3. The S100P protein level of each sample was quantitatively measured by enzyme-linked immunoassay (ELISA) (CircuLex S100P ELISA kit, MBL International Corporation) according to the vendor's protocol.
Results. The results are summarized in Table 1. Marked elevation of S100P was seen in 6 of 9 ADCs (2129.81 + 1834.34 ng/ml), in contrast to the moderate increase in Group 2 (666.67 + 1439.91 ng/ml) and the minimal increase in Group 1 (22.27 + 18.62 ng/ml). Using 50 ng/ml as a cutoff value to differentiate a PMN/ADC (Group 2 and Group 3) from a benign cyst (Group 1), the sensitivity, specificity, positive predictive value and negative predictive value for identifying a PMN/ADC were 60.9%, 100%, 100%, and 43.8%, respectively.
Conclusion. These preliminary data suggest that S100P is a useful biomarker in identifying invasive adenocarcinomas and in distinguishing mucinous neoplasms from non-mucinous cysts. Caution should be taken since some ADCs may show only mildly increased S100P levels, similar to some PMNs and non-mucinous cysts. Additional study in a large series of cases is needed to substantiate the current findings.
Table 1.Summary of S100P protein level (ng/ml) in 30 pancreatic cysts by ELISACase #Benign CystsMucinous NeoplasmsAdenocarcinomas12.515.4812.6722.596.6413.2135.0410.8544.07428.0918.371849.20530.6219.802162.98643.2929.402831.67743.75120.483076.958137.954441.439158.684736.0810221.7711285.6012290.78133385.19144628.37
Citation Format: Wenyi Mi, David L. Diehl, Jianhi Shi, Joseph Blansfield, Marie Hunsinger, Wannian Yang, Fan Lin. S100P is a potential biomarker in distinguishing mucinous from non-mucinous pancreatic cysts and predicting invasive adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1861. doi:10.1158/1538-7445.AM2014-1861
Abstract 1869: Using Nanoparticle Tracking Analysis (NTA) to characterize cellular microvesicles
Authors: Capracotta Sonja , Carnell Pauline , Malloy Andrew , Hole Patrick , Carr Bob 
Published: May 2015

Abstract
Cellular microvesicles (100 nm-1µm) are shed into the circulation from many different cell types including; platelets, erythrocytes and endothelial cells. They have major potential as novel biomarkers as they have been shown to be implicated in a multitude of pathological conditions. However, developments in this area are constrained by limitations in the technology available for their measurement.
Nanoparticle Tracking Analysis (NTA) (NanoSight Ltd, Amesbury) offers the potential to both enumerate and speciate (through fluorescent markers) these microparticles in a rapid manner. In this method a laser beam passes through a suspension at a low angle. The particles scatter light which is collected onto a CCD (or sCMOS) camera by a microscope-type configuration. Particles between 10-2000 nm are tracked individually and their diffusion coefficient, and therefore size, calculated directly from their speed.
Therefore, this characterization method gives a direct measurement of the concentration and size distribution of the particles in the field of view. If the particles are fluorescently labelled, then the concentration and size distribution are those of the labelled particles only, allowing a proportion of labelled particles to be calculated. However, this requires a combination of aspects to be identified and optimised during the process. This talk will look at some of the challenges and considerations that need to be taken during the protocol development and measurement.
It will also review the application of the technique in this field, compare and contrast it to other applicable technologies such as various forms of electron microscopy (EM) and to flow cytometry.
Citation Format: Sonja Capracotta, Pauline Carnell, Andrew Malloy, Patrick Hole, Bob Carr. Using Nanoparticle Tracking Analysis (NTA) to characterize cellular microvesicles. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1869. doi:10.1158/1538-7445.AM2014-1869
Abstract 1879: Dual function HDAC and PI3K inhibitor, CUDC-907 affects cancer cells and the tumor microenvironment in hematological malignancies
Authors: Ma Anna W. , Atoyan Ruzanna , Younes Anas , Flinn Ian W. , Oki Yasuhiro , Copeland Amanda , Berdeja Jesus G. , Laliberte Robert , Viner Jaye , Samson Maria Elena S. , Dellarocca Steven , Yi Ling , Borek Mylissa , Zifcak Brian , Xu Guangxin , Wang Jing 
Published: May 2015

Abstract
Histone deacetylases (HDACs) and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway are promising therapeutic targets in hematologic cancers and evidence of synergistic anti-cancer activity has recently emerged. CUDC-907, a small molecule drug candidate that is designed to target HDACs and PI3Ks in a single chemical entity, is currently in Phase 1 clinical testing for the treatment of patients with lymphoma or multiple myeloma. Preclinically, CUDC-907 has been shown to inhibit activation of PI3K/AKT, JAK/STAT and MAPK pathways in hematologic cancer cell lines such as Hodgkin's lymphoma, diffuse large B-cell lymphoma, and multiple myeloma. In this study, we report that in the setting of hematological malignancies, CUDC-907 targets not only the cancer cells but also the tumor microenvironment. Cytotoxicity against primary CLL cells was independent of the protective effects provided by stromal cells when primary CLL cells were co-cultured with nurse-like cells. CUDC-907 was shown in vitro to impair cytokine and chemokine production by immune cells in the tumor microenvironment and by Hodgkin's lymphoma cells. The ongoing first-in-human Phase 1 clinical study of CUDC-907 has yielded preliminary evidence of anti-cancer activity and impact on the tumor microenvironment as measured by cytokine and chemokine levels (e.g., thymus and activation regulated chemokine [TARC]). Ongoing analyses are probing the potential utility of selected cytokine and chemokine as predictive markers of CUDC-907 activity.
Citation Format: Anna W. Ma, Ruzanna Atoyan, Anas Younes, Ian W. Flinn, Yasuhiro Oki, Amanda Copeland, Jesus G. Berdeja, Robert Laliberte, Jaye Viner, Maria Elena S. Samson, Steven Dellarocca, Ling Yi, Mylissa Borek, Brian Zifcak, Guangxin Xu, Jing Wang. Dual function HDAC and PI3K inhibitor, CUDC-907 affects cancer cells and the tumor microenvironment in hematological malignancies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1879. doi:10.1158/1538-7445.AM2014-1879
Abstract 1880: Pathologic response pattern of breast cancer after neoadjuvant chemotherapy: its correlation with molecular subtypes
Authors: Song In-Hye , Lee Hee Jin , Gong Gyungyub 
Published: May 2015

Abstract
Background: Several ways to assess pathologic response of breast cancer after neoadjuvant chemotherapy (NAC) are currently used, including Miller-Payne system and residual cancer burden. However, the relationship between pathologic response pattern and molecular subtype of breast cancer is unclear. Methods: We investigated the pathologic response pattern of breast cancer after NAC in each molecular subtype. Female breast cancer patients who received NAC and subsequent breast operation were retrospectively analyzed. The NAC regimen used for breast cancer was primarily anthracycline and taxane-based, depending on the axillary lymph node involvement. We evaluated the molecular subtypes by immunohistochemistry, pretreatment tumor sizes by MRI, absolute invasive tumor cellularities in pretreatment biopsy and operation specimens, pathologic complete response (pCR) rates, posttreatment pathologic tumor sizes, overall residual tumor cellularities, and grades for Miller-Payne system. Results: A total of 119 patients (age: 45.2 ± 9.5 yr) were enrolled. Sixty-six cases were hormone receptor positive (ER or PR positive), 18 cases were HER2 positive (ER and PR negative), and 35 cases were triple negative. There were no significant differences in pretreatment tumor size by MRI and absolute cellularity in biopsy between three groups. After NAC, hormone receptor positive tumors showed the lowest pCR rate (18.2 %) while triple negative tumors showed the highest pCR rate (45.7 %, p=0.013). In patients with residual carcinoma, hormone receptor positive tumors showed the largest ypT size (p=0.016), the least reduction of tumor size (p=0.001), and the least absolute invasive tumor cellularity (p=0.006). Overall residual tumor cellularity and Miller-Payne grade were not significantly different between three groups (p=0.4 and p=0.703, respectively). Conclusion: These results suggest that each molecular subtype of breast cancer shows characteristic pathologic response patterns following NAC.
Citation Format: In-Hye Song, Hee Jin Lee, Gyungyub Gong. Pathologic response pattern of breast cancer after neoadjuvant chemotherapy: its correlation with molecular subtypes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1880. doi:10.1158/1538-7445.AM2014-1880
Abstract 1887: Global gene expression analysis of tamoxifen-resistant breast cancer cell lines identified a gene signature predictive of clinical outcome of breast cancer patients treated with endocrine therapy
Authors: Roro Daniel Elias , Vever Henriette , Lykkesfeldt Anne , Ditzel Henrik 
Published: May 2015

Abstract
Objective: Altered gene expression associated with endocrine resistance in breast cancer cell lines may have potential prognostic/predictive values in patients with ER+ breast cancer receiving endocrine therapy. In this study, we investigated mRNA expression profiles associated with the tamoxifen-resistant phenotype using a panel of isogenic MCF-7-based breast cancer cell lines to elucidate the endocrine resistance mechanism and assess whether the pattern of gene expression predicted clinical outcome in breast cancer patients treated with endocrine therapy.
Method: Gene array was performed on a panel of clinically-relevant tamoxifen-resistant breast cancer cell lines (TamR) and their tamoxifen-sensitive parental cell line. Genes that showed significant alteration in expression (FDR 0.01) in TamRs vs parental cell lines were evaluated for their potential to stratify tamoxifen-treated breast cancer patients based on outcome using published gene expression data sets.
Results: Using a testing set consisting of microarray data from 163 ER+ primary breast cancer patients treated with tamoxifen we identified 20 genes among those that showed significant altered expression in TamR that could stratify patients according to clinical outcome. . The potential of this 20-gene signature to stratify patients was further confirmed in 2 independent data sets consisting of ER+ tamoxifen-treated breast cancer patients with a sensitivity and specificity 53% and 79% respectively in the first cohort (N=153), and sensitivity and specificity of 37% and 91% respectively in the second cohort (N=201). Evaluation of relapse-free survival of tamoxifen-treated patients classified by the signature as having bad or good outcomes showed significant differences in time-to-relapse, with median disease-free survival times of 5.1 vs 8.9 years in the first cohort (N=153, p=0.03) and 4.2 vs 7.7 years in the second (N=201, p=0.006).
Conclusions: The expression pattern of the 20-gene signature identified in this study appears to have a strong potential as a biomarker of clinical outcome of endocrine-treated breast cancer patients.
Citation Format: Daniel Elias Roro, Henriette Vever, Anne Lykkesfeldt, Henrik Ditzel. Global gene expression analysis of tamoxifen-resistant breast cancer cell lines identified a gene signature predictive of clinical outcome of breast cancer patients treated with endocrine therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1887. doi:10.1158/1538-7445.AM2014-1887