bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 749: Novel ALK specific mRNA in situ hybridization assay for non-small cell lung carcinoma
Authors: Hirai Noriko , Sasaki Takaaki , Ohsaki Yoshinobu 
Published: July 2017

Abstract
A recent technical advance in the mRNA in situ hybridization (mRNA-ISH) assay provides simultaneous signal amplification and background suppression with a unique probe design to achieve single molecule visualization. We assessed the utility of the mRNA-ISH assay as a diagnostic tool to detect anaplastic lymphoma receptor tyrosine kinase (ALK) mRNA in non-small cell lung carcinoma. We compared the mRNA-ISH assay with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The study included 279 surgically resected lung adenocarcinomas and 44 transbronchial biopsied (TBB) adenocarcinomas. mRNA-ISH was conducted using the RNAscope 2.0 system which includes pre-designed detection probes for the tyrosine kinase domain of ALK mRNA. IHC was conducted on all of the 323 samples using ALK-specific antibodies. mRNA-ISH was performed on 279 surgical samples and 6 TBB samples. Break-apart FISH was used to assess cases that were mRNA-ISH or IHC positive. ALK protein expression was detected in 11/279 (3.9%) specimens. ALK mRNA was also detected by mRNA-ISH in these cases, and 9 of the 11 specimens (81%), were also positive by ALK FISH. Using the IHC results as a reference, the sensitivity and specificity of mRNA-ISH was 100%. In the TBB cohort, ALK protein expression was observed in 3/44 (6.8%) of specimens, in which ALK mRNA expression was also detected. ALK mRNA-ISH data were highly correlated with the IHC data, and ALK mRNA-ISH was able to identify every FISH-positive sample. We conclude that mRNA-ISH could play an alternative or complementary role in ALK genetic diagnosis in NSCLC.
Citation Format: Noriko Hirai, Takaaki Sasaki, Yoshinobu Ohsaki. Novel ALK specific mRNA in situ hybridization assay for non-small cell lung carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 749. doi:10.1158/1538-7445.AM2017-749
Abstract 751: Characterization of STAT3 activation in human prostate cancer
Authors: Velasco Marco A. De , Hatanaka Yuji , Kura Yurie , Ando Naomi , Sakai Kazuko , Sugimoto Koichi , Nozawa Masahiro , Yoshimura Kazuhiro , Yoshikawa Kazuhiro , Nishio Kazuto , Uemura Hirotsugu 
Published: July 2017

Abstract
Signal transducers and activators of transcription (STATs) were initially associated with cytokine signal transduction pathways but are now also recognized as key modulators of key survival processes in in various cancers. Activation of STAT3 occurs by the binding of various cytokines to its receptors leading to the activation of the JAK/ STAT3 signaling pathway. Interleukin-6 (IL-6) has been implicated in regulating growth of various malignant tumors. Activated IL-6 has also been shown to be elevated in the sera from patients with metastatic prostate cancer, and persistent activation of STAT3 is a common feature. To better characterize the potential role of JAK/STAT3 as a therapeutic target for advanced prostate cancer, we examined expression patterns of activated STAT3 in 111 cases of localized prostate cancer from patients who underwent radical prostatectomy. Association studies were conducted with clinicopathological characteristics and biochemical recurrence. We also analyzed the expression of IL-6/KAK/STAT3 genes from RNA-sequencing data form the Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data set and its association to long-term outcomes. Immunohistochemical analysis revealed that 11.7%, 42.3% and 45.9% of patients had high, moderate or low/negative expression of phosphorylated-STAT3 (Tyr705). Cancerous glands tended to have higher STAT3 expression compared to paired normal adjacent tissue, P=0.088. No correlations were observed between STAT3 expression and clinicopathological parameters. Patients with moderate-high p-STAT3 expression tended to experience shorter times to biochemical recurrence (median time, 15 months) compared to patients with low/negative STAT3 activity, (median time to recurrence not reached, P=0.064). Cluster analysis suggested a trend for decreased disease-free survival for patients with high IL-6/KAK/STAT3 gene expression signature. Our data suggests an association between STAT3 signaling and prostate cancer recurrence and provides clinical evidence to support JAK/STAT3 as a potential therapeutic target for patients with advanced prostate cancer.
Citation Format: Marco A. De Velasco, Yuji Hatanaka, Yurie Kura, Naomi Ando, Kazuko Sakai, Koichi Sugimoto, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura. Characterization of STAT3 activation in human prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 751. doi:10.1158/1538-7445.AM2017-751
Abstract 753: Human epidermal growth receptor-2 immunohistochemistry in gastric cancer
Authors: Duduyemi Babatunde M. , Afihene Mary Y. , Asiamah Emmanuel A. 
Published: July 2017

Abstract
Introduction: Gastric cancer is the second most common GI cancers and third leading cause of cancer-related deaths worldwide. In Ghana, gastric cancer contributes significantly to cancer morbidity and mortality. The recent development on the benefit of targeted therapy in the management of gastric cancer using HER-2 monoclonal antibody in combination with chemotherapy has greatly improved the overall survival of patients. This study therefore aims at determining the frequency of Her-2 over-expression in gastric carcinomas in Kumasi, Ghana and comparing with other prognostic factors.
Methodology: Demographic data and histological diagnosis were retrieved from the surgical day book of the Department of Pathology, Komfo Anokye Teaching Hospital, Kumasi. The slides were retrieved and reviewed to confirm diagnosis, grading and classification of gastric cancer. Immunohistochemistry was done with anti-HER-2 antibody to confirm HER-2 over-expression. The data was analysed with SPSS version 17. Results: Of the 99 cases of gastric cancer seen over the 8 year period, there were 57 males and 42 females, adenocarcinoma (91), GIST (5) and Non Hodgskin Lymphoma (3). The age range of the study population was 8-90 years with modal age group in the 6th decade. There were more biopsies (63) than resections (36). Of the adenocarcinomas, 45 were poorly differentiated, 38 moderately differentiated and 8 well differentiated. Diffuse type is most common with 47 cases followed by intestinal 41cases and mixed type 3 cases. Three of the 4 patients under the age of 30 years had lymphoma. HER-2 over-expression was seen in 14 out of the 47 tested and all were intestinal type.
Conclusion: HER -2 over-expression was seen a small cohort of our patients with gastric cancer especially those with intestinal type.
Citation Format: Babatunde M. Duduyemi, Mary Y. Afihene, Emmanuel A. Asiamah. Human epidermal growth receptor-2 immunohistochemistry in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 753. doi:10.1158/1538-7445.AM2017-753
Abstract 759: Highly-sensitive detection of EGFR mutation in non-small cell lung cancer using mutant-enrichment method
Authors: Chien Hung-Chi 
Published: July 2017

Abstract
Detection of mutations in EGFR in non-small cell lung cancer is important for the clinical decision-making process of molecularly targeted therapies, including Iressa®, Tarceva®, and Tagrisso®. In this study we developed an assay allowing the detection of EGFR gene mutations being conducted in the routine diagnostic procedure and its analytic and clinical performance were evaluated using different types of specimens. The EGFR mutation assay in this study allows for detecting EGFR exon 19 deletion (Del), exon 20 insertion (Ins), and mutation in T790M, L858R, S768I and L861Q of rare amounts in a normal genetic background. Enhancement of detection sensitivity was achieved with the developed mutant enrichment method which combines mutation-specific primers and 3'-phosphorylation oligonucleotides as blockers for inhibiting wild-type gene from DNA amplification. Analytic performance for each mutant was assessed using the control plasmids containing the mutant genes of known amounts as well as the genomic DNA extracted from mutant cell lines and Horizon FFPE samples. The assay performance were also evaluated using clinical samples in parallel with the FDA-approval companion diagnostic product therascreen® EGFR RGQ PCR Kit . The sensitivity of the assay evaluated using control plasmids for Del, T790M , L858R, S768I, L861Q mutation and Ins was 5%, 0.5%, 1%, 0.5%, 0.1% and 0.5% respectively, and was 1%, 0.5%, 0.5%, 0.5%, 0.1% and 0.5% respectively when applying on HDx reference standards. Diagnostic results for the 116 clinical samples for identifying mutations of del, T790M, L858R, S768I, L861Q and Ins was 92.2%, 100%, 99.1%, 100%, 97.4% and 100% respectively concordance with the therascreen® EGFR RGQ PCR Kit, including 17 cases of multiple mutations. The overall diagnostic results for all mutations evaluated with PPA (positive percent agreement), NPA (negative percentage agreement) and OPA (overall percentage agreement) were 83.3%, 98.2% and 90.5%, respectively. The three samples firstly diagnostic as false positive were retested and confirmed to be Exon 19 del by DNA sequencing. The assay demonstrated good sensitivity when compared with commercial product. More clinical studies are being performed to establish relationship between drug efficacy and different mutation combinations.
Citation Format: Hung-Chi Chien. Highly-sensitive detection of EGFR mutation in non-small cell lung cancer using mutant-enrichment method [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 759. doi:10.1158/1538-7445.AM2017-759
Abstract 763: Analytical validation of Ki67/CD8 duplex IHC assay using computational tissue analysis (cTATM)
Authors: Kearney Staci J. , Black Joshua C. , Landis Benjamin J. , Koegler Sally , Hirsch Brooke , Gianani Roberto 
Published: July 2017

Abstract
Chromogenic multiplex immunohistochemistry (IHC) assays enable investigation of the spatial relationships between tumor and immune cells, which is thought to be important for understanding and predicting therapeutic response. Development and analytical validation of multiplex IHC assays enables the use of such assays to simultaneously investigate multiple biomarkers as predictors of clinical response. In this study, we analytically validated a chromogenic duplex IHC assay that quantifies Ki67 and CD8 in formalin-fixed, paraffin-embedded non-small cell lung cancer tissues. Five performance criteria were selected and evaluated based on Clinical Laboratory Standards Institute guidelines: reportable range, analytical sensitivity, analytical specificity, accuracy, and precision. Similar to analytical validation studies for monoplex IHC assays, this study utilized a reference method and multiple days of staining. The percentage of cells positive for Ki67 nuclear staining and/or CD8 membrane staining were quantified using our computational Tissue Analysis (cTATM) platform. Performance of the Ki67/CD8 chromogenic duplex IHC assay was considered acceptable for the five criteria evaluated. Once the performance of the assay was established, additional exploratory cTA-based endpoints were examined, including the quantification of each biomarker in the tumor compartment and the tumor microenvironment, and analysis of the spatial arrangement of immune cells relative to tumor cells. In conclusion, Flagship’s cTA platform allows for more consistent quantification of individual analytes on dual-stained tissue sections, enabling investigation of complex biological questions that cannot be achieved with traditional tissue-based manual endpoints.
Citation Format: Staci J. Kearney, Joshua C. Black, Benjamin J. Landis, Sally Koegler, Brooke Hirsch, Roberto Gianani. Analytical validation of Ki67/CD8 duplex IHC assay using computational tissue analysis (cTATM) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 763. doi:10.1158/1538-7445.AM2017-763
Abstract 765: Prognostic impact of Philadelphia chromosome in elderly acute lymphoblastic leukemia patients ineligible for hematopoietic stem cell transplantation
Authors: Byun Ja Min 
Published: July 2017

Abstract
Elderly acute lymphoblastic leukemia (ALL) patients are often unfit for neither dose-intensive chemotherapy nor stem cell transplantation, thus their clinical outcomes have been dismal. The increased incidence of BCR-ABL translocation with increasing age also contributed to poor prognosis but, it was our conjecture that the introduction of potent tyrosine kinase inhibitors (TKI) targeting ABL, BCR-ABL translocation might not deliver negative prognostic impact in elderly ALL. Considering that many elderly Ph- ALL patients do not tolerate cytotoxic chemotherapy required for effective tumor control, we supposed that efficacy of ABL TKIs and their combination strategy with low dose cytotoxic chemotherapy would result in better survival for elderly Ph+ ALL compared to their Ph- counterparts.
This study was a multicenter longitudinal cohort study of elderly de novo ALL (≥ 60 years) recruited from 11 hospitals in Korea from January 2005 to December 2015. We considered Ph+ if it was positive in at least one of three techniques: conventional cytogenetics, fluorescence in situ hybridization, or quantitative real-time polymerase chain reaction (qRT-PCR).
Among the 96 patients enrolled, there were 50 Ph- ALL patients (52.1%) and 46 Ph+ ALL patients (47.9%). There were no differences between the 2 groups regarding age, sex distribution, performance status, and induction regimens. For treatment outcomes evaluation, the 5 Ph+ ALL patients not receiving TKI were eliminated and 41 Ph+ ALL patients treated with TKI were compared with 50 Ph- ALL patients (Table). Complete remission (CR) was attained in 27 (54.0%) of patients in the Ph- group versus 35 (85.4%) in the Ph+ group (P=0.001). The median RFS was significantly longer in the Ph+ group (3.1 months for Ph- vs. 8.9 months for Ph+, P=0.017). Induction death and induction failure occurred significantly more often in the Ph- group. The median OS was 6.3 months for Ph- group versus 10.3 months for Ph+ group (P=0.033).
In conclusion, using real world data, this study reports the possible favorable impact of Ph+ in TKI-era for elderly patients.
Citation Format: Ja Min Byun. Prognostic impact of Philadelphia chromosome in elderly acute lymphoblastic leukemia patients ineligible for hematopoietic stem cell transplantation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 765. doi:10.1158/1538-7445.AM2017-765
Abstract 766: Comorbidities limiting recruitment of non-small cell lung cancer (NSCLC) patients in early phase trials
Authors: Duma Narjust , Wang Yucai , Mansfield Aaron 
Published: July 2017

Abstract
Background: Early phase trials (EPCT) provide significant value by evaluating the possible benefits of new agents. The eligibility criteria in EPCT are usually rigorous and may exclude many patients (pts) commonly seen in clinical practice. Our objective was to identify the most common comorbidities excluded in EPCT for NSCLC.
Methods: ClinicalTrials.gov was queried on August 1st of 2016. 299 interventional drug trials were extracted from 2010 to 2016. We studied the trial characteristics including: experimental therapy, location, funding and eligibility criteria. Exclusion of CNS metastasis was treated as a binary variable (strict exclusion vs. allowed). Logistic regressions were used for statistical analysis.
Results: Of the 299 trials, 164 (55%) were phase II, 81 (27%) phase I and 54 (18%) phase Ib/II. 164 (55%) were conducted in the United States (US), 45 (15%) in Asia, 39 (13%) in Europe and 51 (17%) were international. 171 (57%) trials were funded by the industry, 54 (18%) by government agencies and 74 (25%) were investigator initiated. Survival was an end-point in 97 (32%) trials. 70 (23%) trials required a repeat lung biopsy. 54 (18%) trials excluded pts &gt;75 years of age. 99 (33%) trials required creatinine levels &lt;1.5 mg/dl, 132 (44%) liver enzymes &lt;2.5 and total bilirubin &lt;1.5 of the upper limit of normal. 88 (29%) trials required Hgb&gt;9 g/dl and 141 (47%) excluded pts with platelets &lt;100,000/dl. In terms of comorbidities, 84 (28%) trials excluded pts with atrial fibrillation, 94 (31%) with any anticoagulation therapy and 120 (40%) HIV positive pts. CNS involvement was a significant exclusion factor, 123 (41%) trials excluded pts with CNS metastasis. On univariate analysis, the odds of CNS metastasis exclusion were significantly higher in immunotherapy trials (OR 1.72, 95%CI 1.2-2.4, p&lt;0.01) and lower in European trials (OR 0.76, 95%CI 0.6-0.9, p&lt;0.005). In multivariate analysis, US based trials had higher odds of exclusion of CNS metastasis (OR: 3.2, 95%CI 1.4-7.5, p&lt;0.05).
Conclusions: Many of the EPCTs excluded pts with advanced age, cytopenias and other common comorbidities, eliminating the possibility of many of our aging pts from participation. Regarding CNS disease, our analysis suggests the type of agent and location may influence the trial design about CNS metastasis inclusion. Investigators should review whether sufficient justification exists for every exclusion criterion before their incorporation in future trial protocols.
Citation Format: Narjust Duma, Yucai Wang, Aaron Mansfield. Comorbidities limiting recruitment of non-small cell lung cancer (NSCLC) patients in early phase trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 766. doi:10.1158/1538-7445.AM2017-766
Abstract 768: The utility of a breast cancer registry for improved cancer management in developing countries
Authors: McGarity DeAnna , Epps Brandon , Maynor Alexis , Anderson Tania , Alema-Mensah Ernest , Fray Delroy , Aung Maung , Holden Kisha , Lillard James , Rivers Brian , Beech Derrick 
Published: July 2017

Abstract
Background
Breast cancer is one of the leading causes of cancer related deaths in the island nation of Jamaica, West Indies. Cancer and other non-communicable diseases have increased in many developing nations in the Caribbean as well as Central and South America. The health systems of these developing countries continue to provide care to patients with limited resources. The use of a breast cancer registry can assist in care coordination of these patients and allow targeted screening and treatment programs in under-resourced environments.
Methods
In collaboration with the Western Regional Health Authority, a breast cancer registry database was developed in RedCap to provide a comprehensive analysis of breast cancer in under resourced environment. 53 patients from Atlanta were compared to 78 patients from Jamaica These patients were entered into the breast cancer registry from June 1, 2014 to March 31, 2015 by the attending physician and de-identified. Demographics, tumor related factors, treatment, survival and health behavior information was collected by the attending physician. The findings were then analyzed using Statistical Analysis System (SAS) and Data Analysis and Statistical Analysis (STATA): Fisher Exact test, chi-square and multiple regressions.
Results
The median of patient ages were 61 years old (range 38 - 81 years) for the U.S. patients and 53 years old (range 26 - 84 years old) for Jamaican women. For the U.S. patients, 84% were Black, 4% White, and 12.24% were Latin or Asian. The majority of the patients were diagnosed with stage 1 invasive ductal breast cancer. In contrast, the majority of the Jamaican patients were diagnosed with late-stage breast cancer. Utilizing the data from the breast cancer registry, we were able to identify parishes (counties) with disproportionately high rates of late-staged cancer at the time of diagnosis.
Conclusion
The use of a disease specific registry can improve care coordination and identify actionable target areas for enhanced screening and treatment. It is our hope to frequent review the dashboards associated with the registry data by providers, medical centers and health systems. This will optimize care coordination and allow timely improvements in cancer diagnosis and management in developing countries.
Citation Format: DeAnna McGarity, Brandon Epps, Alexis Maynor, Tania Anderson, Ernest Alema-Mensah, Delroy Fray, Maung Aung, Kisha Holden, James Lillard, Brian Rivers, Derrick Beech. The utility of a breast cancer registry for improved cancer management in developing countries [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 768. doi:10.1158/1538-7445.AM2017-768
Abstract 775: Identification of activated signal transduction pathways and molecules in the HMGB-1 induced angiogenesis
Authors: Kwon Yujin , Shin Sujin , Kim Won Kyu , Kim Hoguen 
Published: July 2017

Abstract
High-mobility group box-1 (HMGB-1) is a highly conserved protein playing various roles both in the nucleus and cytosol and known to be expressed in almost all types of mammalian cells. Secreted HMGB-1 has been most intensively studied and reported as an immune cell derived cytokine regulating systemic inflammation, signal transduction, and activation of endothelial cells (EC). Especially, HMGB-1 over-expression is now considered as a hallmark in cancers based on its involvement in cell proliferation, inflammatory microenvironment, invasion, metastasis, and sustained angiogenesis. Numerous studies have shown that secreted HMGB-1 directly or indirectly promotes angiogenesis by activation of ECs. However, mechanisms of HMGB-1 mediated angiogenesis have not yet been fully understood, especially, in terms of genomic changes caused by HMGB-1 treatment. Moreover, differences between vascular endothelial growth factor (VEGF) mediated and HMGB-1 mediated angiogenesis have not been studied.
To explore the roles of HMGB-1 in angiogenesis, we first confirmed whether HMGB-1 treatment renders ECs angiogenic by evaluating proliferation, migration, wound-healing, and tubule formation of ECs after HMGB-1 treatment. In addition, we performed gene expression microarray to clarify how HMGB-1 treatment induced EC activation at various time points and subsequent angiogenic features according to time-dependent gene expression changes.
We show that HMGB-1 treatment induces proangiogenic features to ECs such as stimulation of tubule formation, promotion of proliferation, and accelerated wound healing. By analysis of microarray data, we found that VEGF and HMGB-1 commonly promoted the activation of MAPK, cell proliferation, and wound healing pathways which directly regulate angiogenesis. On the other hand, axon guidance, gap junction, P53 signaling, cell cycle, and cell differentiation pathways were specifically up-regulated by HMGB-1. Taken together, HMGB-1 leads to angiogenesis via upregulation of both angiogenic and nonangiogenic genes.
Citation Format: Yujin Kwon, Sujin Shin, Won Kyu Kim, Hoguen Kim. Identification of activated signal transduction pathways and molecules in the HMGB-1 induced angiogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 775. doi:10.1158/1538-7445.AM2017-775