bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1699: Impact of whole blood interferon gamma production for patient selection in vaccination with autologous formalin-fixed tumor vaccine
Authors: Sakamoto Naoyuki , Ishikawa Takeshi , Okayama Tetsuya , Yasuda Tomoyo , Doi Toshifumi , Tanigawa Mari , Naito Yuji , Itoh Yoshito , Yoshikawa Toshikazu 
Published: July 2017

Abstract
Introduction:
Immune checkpoint blockade by anti-CTLA-4 antibody and anti-PD-1 antibody led to clinical breakthrough for the treatment of patients with solid tumors. Moreover, recent reports have shown that neoantigens are important functional targets mediating response to immune checkpoint inhibitors. Therefore, sequential combination of personalized cancer vaccines and immune checkpoint blockade has emerged as a potential therapeutic strategy. However, existing drawbacks is that it is difficult to identify robust biomarkers for patient selection in vaccination with cancer vaccine. In this study, we examined whether the development of delayed-type hypersensitivity (DTH) response, measured after vaccination with autologous formalin-fixed tumor vaccine (AFTV), correlates to parameters of immune function such as whole blood cytokine levels and peripheral regulatory T cells (Treg) in patients with solid tumors.
Methods:
Subjects comprised 52 patients with solid malignancy. AFTV treatment consisted of 3 courses of vaccination performed at intervals of 2 weeks. DTH test was performed before and after vaccination. A positive DTH response was defined as a ≥ 10mm diameter erythema/induration. We evaluated whole blood cytokine production after phytohemagglutinin (PHA) stimulation using the bioplex array system. We also assessed the number of peripheral Tregs as well as routine hematological and biochemical parameters.
Results:
DTH positive patients and DTH negative patients did not differ with respect to the number of peripheral Tregs, leukocytes, lymphocytes or granulocyte/lymphocyte ratio. Whole blood IFN-γ production levels after phytohemagglutinin (PHA) stimulation at baseline in DTH positive patients were significantly higher than those in DTH negative patients (p=0.0397).
Conclusion:
These data indicate that whole blood IFN-γ production at baseline is likely to be useful to assess immunologic competence in vaccinated patients with AFTV. Consequently, clinical utility of whole blood IFN-γ production, as immunomonitoring method for patient selection in vaccination with cancer vaccine, is required to investigate in larger clinical studies in the future.
Citation Format: Naoyuki Sakamoto, Takeshi Ishikawa, Tetsuya Okayama, Tomoyo Yasuda, Toshifumi Doi, Mari Tanigawa, Yuji Naito, Yoshito Itoh, Toshikazu Yoshikawa. Impact of whole blood interferon gamma production for patient selection in vaccination with autologous formalin-fixed tumor vaccine [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 1699. doi:10.1158/1538-7445.AM2017-1699
Abstract 1710: Providing confidence around computational tissue analysis using heterogeneity assessments
Authors: Schnatwinkel Carsten , Rudmann Daniel , Aeffner Famke , Bajwa Jasmeet , Hutnick Natalie , Sharp Michael , Chu Gerry , Alvarez JD 
Published: July 2017

Abstract
Background: Though the techniques to interrogate the appearance of a biomarker in tissue sections have greatly advanced, there are limitations as to how representative an analysis of a tissue section is compared to the entire diseased tissue. Depending on the heterogeneous expression level of a biomarker, tissue sampling can result in different interpretations of the biomarker’s appearance, and hence could potentially lead to a false therapeutic intervention.
Hypothesis: Digital image analysis has demonstrated tremendous value in quantifying many features related to biomarker distribution and expression in biological tissues. The information can be collected for various indications and biomarkers and a phenotypic signature can be established that describes a biomarker representation across indications. Moreover, the assessment of new samples can be compared to the established phenotypic signature and a confidence score applied in support to the determined endpoint.
Approach: For a proof of concept, 6 prostate cancer samples were processed and a single section was collected after every 100microns. A total of 7 sections per sample were stained for the lymphocyte marker CD3, and the number of positive target cells were determined in the tumor and tumor microenvironment using tissue Image Analysis (tIA™). To assess how indicative the evaluation of a single tissue section would be for the entire tumor, the heterogeneity level was determined on the section level as well as by random grid analysis on each individual section. Both criteria were utilized to define an indication and biomarker specific confidence interval and heterogeneity score.
Conclusion: The combination of IHC and tIA is a powerful tool to convert complex data into meaningful interpretations. tIA is also a capable tool to catalogue valuable information about the biomarker’s expression pattern across different disease stages and hence could be used to evaluate how representative a single biomarker evaluation is in the grand scheme. Ultimately, we demonstrated a technique that can be applied to any biomarker and would assist in guiding therapeutic decisions.
Citation Format: Carsten Schnatwinkel, Daniel Rudmann, Famke Aeffner, Jasmeet Bajwa, Natalie Hutnick, Michael Sharp, Gerry Chu, JD Alvarez. Providing confidence around computational tissue analysis using heterogeneity assessments [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 1710. doi:10.1158/1538-7445.AM2017-1710
Abstract 1712: Detection of circulating tumor cells in stage IV non-small cell lung cancer
Authors: Shishido Stephanie N. , Bazhenova Lyudmila , Carlsson Anders , Hicks James , Kuhn Peter 
Published: July 2017

Abstract
Non-Small Cell Lung Cancer (NSCLC) is the most common cause of cancer related deaths in both men and women. Some lung cancer patients have a unique challenge of a tissue access due to tumor location or baseline lung disorders such as emphysema and chronic obstructive pulmonary disease (COPD). Liquid biopsy technologies can overcome tissue assess difficulties. However, as of today there are no commercially approved assays for CTC enumeration in lung cancer. Multiple non-commercial assays exist and some show correlation of CTC enumeration and changes in CTC counts on therapy with prognosis and response to therapy. Outside of absolute number of CTC there is little published data regarding prognostic significance of CTC morphologic heterogeneity in late stage NSCLC and its ability to predict treatment outcomes. Here we investigate CTC counts in 81 patients with stage IV NSCLC using a fluid phase biopsy and high definition (HD) diagnostic pathology imaging of all nucleated cells. HD-CTCs were detected in 51 (63%) patients at initiation of therapy with a median of 2.20 (range 0-509.20) and a mean of 26.21 HD-CTCs/mL (±15.64). There was no correlation between the absolute number of HD-CTCs at the time of initiation of new therapy and patient outcomes. A subset of 25 patients was further analyzed to determine the significance of HD-CTC kinetics, which may follow three distinct patterns: an increase in HD-CTCs with therapy, unchanged HD-CTCs numbers (stable), and a decline in HD-CTCs numbers. Patients that experienced an increasing, stable, or decreasing HD-CTC profile had an overall change of 118.40, 0.54, and 81.40 HD-CTCs/mL respectively during the first 3 months. The overall survival (OS) for increasing profiles was 31.08 months (±13.08, median 32.46, range 15.11-43.50), for stable profiles OS was 8.82 months (±3.57, median 7.23, range 3.91-19.75), and for decreasing profiles it was 15.30 months (±6.39, median 14.06, range 3.81-28.06) months. CTCs are identifiable in patients with stage IV NSCLC, but correlation of absolute HD-CTC counts with disease progression was not statistically significant. However, change in CTC counts were predictive of OS in patients with metastatic lung cancer receiving chemotherapy.
Citation Format: Stephanie N. Shishido, Lyudmila Bazhenova, Anders Carlsson, James Hicks, Peter Kuhn. Detection of circulating tumor cells in stage IV non-small cell lung 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 1712. doi:10.1158/1538-7445.AM2017-1712
Abstract 1714: Translating CTCs for clinical use: melanoma patient-derived CTCs evolution in xenografts
Authors: Vishnoi Monika , Liu Haowen N. , Boral Debasish , Yin Wei , Sprouse Marc L. , Thiery Jean P. , Glitza Isabella C. , Marchetti Dario 
Published: July 2017

Abstract
Circulating tumor cells (CTCs) are known to disseminate from primary/metastatic tumors, survive in the circulation, and develop competency to colonize distant organs. Dissecting CTC heterogeneity is therefore crucial to provide improve prognostic and diagnostic tools (concept of “liquid biopsy”). However, the clinical significance of CTC heterogeneity is still unknown. We hypothesized that melanoma patient blood-derived, lineage-negative cells (CD45-/CD34-/CD73-/CD90-/CD105-) contain melanoma cell subpopulations (Melan A+, S100+, CD146+ and NG2+ CTCs) that evolve in vivo and achieve metastatic potency when reaching an organ-specific niche. We enriched Lin-negative cells from peripheral blood of melanoma patients clinically diagnosed with or without brain metastasis (MBM) by multi-parametric flow cytometry; and analyzed CTC heterogeneity in xenografts by longitudinal capturing and interrogation at the single-cell level (DEPArrayTM platform). First, we evaluated the presence of melanoma CTC subpopulations in Lin-negative cells and developed Lin-negative murine xenograft models. Human-cell derived melanoma metastasis in xenografts confirmed that CTCs require metastasis-potentiating factors present in the Lin-negative population. Second, we performed multi-parametric flow cytometry to isolate human-derived HLA+/Melan A+/- CTCs/DTCs population from murine blood and bone marrow at T0, Tmid and Tend phases of metastasis. We interrogated the differential levels of CTCs/DTCs in HLA+/Melan A+ cell population and established their neoplastic identity by genetic profiling and the expression of melanoma markers at single-cell level. Third, we dissected longitudinal transcriptional signatures of CTCs vs DTCs in association with MBM onset. We assessed the comprehensive EMT scores of CTCs and DTCs transcriptomics and identified the pathways associated with CTC/DTCs dynamic functional states depending upon melanoma progression. Collectively, this study provide important insights to identify novel EMT-related biomarkers of MBM progression. Further elucidation of these CTC biomarkers and properties may provide novel therapeutic strategies that can be clinically useful in melanoma patients which are yet to develop MBM.
Citation Format: Monika Vishnoi, Haowen N. Liu, Debasish Boral, Wei Yin, Marc L. Sprouse, Jean P. Thiery, Isabella C. Glitza, Dario Marchetti. Translating CTCs for clinical use: melanoma patient-derived CTCs evolution in xenografts [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 1714. doi:10.1158/1538-7445.AM2017-1714
Abstract 1720: Circulating tumor cell (CTC) enrichment and DNA mutation detection by sequencing
Authors: Kou Ruqin , Zhao Eric , Leung Conrad , Gogoi Priya , Chow Will , Wang Yixin 
Published: July 2017

Abstract
Molecular analysis of circulating tumor cells (CTCs) is hindered by low sensitivity and high level of background leukocytes of currently available CTC enrichment technologies. The Celsee PREP100 device captures CTCs with high sensitivity and allows the captured CTCs to be retrieved for molecular analysis. To evaluate the potential of utilizing PREP100 in CTC molecular analysis, we first prepared mock samples using cultured prostate cancer cells PC3 and LnCAP and analyzed captured cells by PCR amplicon sequencing. Using Celsee PREP100, we were able to recover the average of 79% (ranging from 40% to 100%) of 110 - 1,100 PC3 cells and 60 - 1,500 LnCAP cells and detect p.K139fs*3 deletion in PC3 cells and T877A mutation in LnCAP cells. In addition, we also spiked in the two cell lines into normal donor blood samples and analyzed the captured cells by PCR amplicon sequencing. Preliminary experiments showed that 40% of 250 spiked PC3 cells and 74% of 50 spiked LnCAP cells were captured. Further, we were able to detect p.K139fs*3 deletion in the retrieved 50 - 1,000 spiked PC3 cells. Our results illustrate that Celsee PREP100 system represents a promising technology for capturing and molecular characterization of CTCs.
Citation Format: Ruqin Kou, Eric Zhao, Conrad Leung, Priya Gogoi, Will Chow, Yixin Wang. Circulating tumor cell (CTC) enrichment and DNA mutation detection by sequencing [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 1720. doi:10.1158/1538-7445.AM2017-1720
Abstract 1737: ALK rearrangement analysis in circulating tumor cells of lung cancer patients
Authors: Jeon Min Kyung , Kim Young Hun , Hwang Eunjoo , Lee Hye Seon , Uh Ji-hyun , Kim Myoung Shin , Park JooKyung , Jeon Byung Hee , Lee Se-Hoon 
Published: July 2017

Abstract
The evaluation of ALK rearrangement in non-small-cell lung cancer (NSCLC) is a significant tool when considering chemotherapy. It is not always possible to perform a tumor biopsy in patients. We suggest isolation and culturing of circulating tumor cells (CTCs) as an alternative tool to a tumor biopsy for the diagnosis of ALK rearrangement. From 22 patients with NSCLC harboring ALK rearrangement, blood samples were collected and divided into two parts: one for immunofluorescence staining of CTC marker and the other for culturing of CTCs. Both samples were processed by size-based filtration, and Cultured CTCs were analyzed for EML4-ALK translocation by fluorescence in situ hybridization (FISH) using Vysis ALK break apart FISH probe kit. CTC culturing was successful in 18 of 22 cases (81.8%). Among 18 cases of successful CTC cultures, 13 cases showed ALK rearrangement positivity (72.2%). Therefore, we suggest that the CTCs can be used as an alternative method to tissue biopsy for diagnosing ALK rearrangement. In addition, this method may have clinical applications including serial blood sampling for the development of personalized cancer therapy based on individual genomic information.
Citation Format: Min Kyung Jeon, Young Hun Kim, Eunjoo Hwang, Hye Seon Lee, Ji-hyun Uh, Myoung Shin Kim, JooKyung Park, Byung Hee Jeon, Se-Hoon Lee. ALK rearrangement analysis in circulating tumor cells of lung cancer patients [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 1737. doi:10.1158/1538-7445.AM2017-1737
Abstract 1762: Keratin 17 identifies prognostic subtypes of pancreatic ductal adenocarcinoma
Authors: Escobar-Hoyos Luisa F. , Leiton Cindy , Vanner Elizabeth , Roa-Pena Lucia , Li Jinyu , Powers Scott , Akalin Ali , Bandovic Jela , Bailey Peter , Chang David , Moffitt Richard , Yeh Jen Jen , Biankin Andrew , Shroyer Kenneth 
Published: July 2017

Abstract
Recent RNA sequencing (RNASeq) studies from Bailey et al., 2016, Moffitt et al., 2015 and Collisson et al., 2011 reported that mRNA expression from bulk tumor defines molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) that are highly correlated with patient survival. These studies independently identified Keratin 17 (K17) mRNA overexpression as one of over 20 upregulated transcripts that define the RNA signature of the most lethal PDACs. Studies in our lab determined that neither K17 gene missense mutations nor copy-number alterations explain the upregulation of K17 mRNA expression by malignant cells. In addition, we found that K17 expression, measured at the protein level by immunohistochemistry or at the level of mRNA by RNASeq, is sufficient to stratify patients by short- vs long- term survival at baseline after resection. These retrospective survival analyses were performed in four independent patient cohorts using a uniform threshold to define low- vs high- K17 patients (total n= 558). High-K17 cases were twice as likely to die from this disease compared to stage-matched low-K17 cases (P values &lt; 0.05). Furthermore, we determined that K17 expression is associated with outcome after Gemcitabine treatment using the Bailey et al., 2016 patient cohort (n= 94). This is the first study to show that the expression of a single gene, K17, can accurately subtype PDAC at initial diagnosis. In conclusion, K17 was identified as a robust and independent, clinically relevant, prognostic and predictive biomarker to stratify clinical outcome at the time of initial diagnosis and to potentially inform clinical decisions regarding chemotherapeutic intervention.
Citation Format: Luisa F. Escobar-Hoyos, Cindy Leiton, Elizabeth Vanner, Lucia Roa-Pena, Jinyu Li, Scott Powers, Ali Akalin, Jela Bandovic, Peter Bailey, David Chang, Richard Moffitt, Jen Jen Yeh, Andrew Biankin, Kenneth Shroyer. Keratin 17 identifies prognostic subtypes of pancreatic ductal adenocarcinoma [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 1762. doi:10.1158/1538-7445.AM2017-1762
Abstract 1763: A novel RNA in situ hybridization approach highly sensitive for detection of Merkel cell polyomavirus
Authors: Wang Lisha , Harms Paul W. , Palanisamy Nallasivam , Carskadon Shannon , Cao Xuhong , Siddiqui Javed , Patel Rajiv M. , Zelenka-Wang Sylvia , Johnson Timothy M. , Durham Alison , Su Fengyun , Shukla Sudhanshu , Mehra Rohit , Chinnaiyan Arul M. 
Published: July 2017

Abstract
Background: Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin. Merkel cell polyomavirus (MCPyV) plays an oncogenic role in the majority of MCC tumors. Detection of MCPyV in MCC tumors has diagnostic utility, and potentially prognostic and therapeutic implications. We investigated whether RNAscope, a novel RNA in situ hybridization (ISH) method for detection of RNA transcripts in tissues at the single-cell/single-molecule level, is useful for MCPyV detection.
Methods: We applied an RNAscope probe targeting MCPyV T antigen transcripts on tissue microarrays (TMAs) and full tissue sections encompassing 91 MCC tumors from 75 patients, 14 carcinomas of other types, and various normal tissues. qPCR and immunohistochemistry (IHC) for MCPyV were performed on 58 and 88 cases, respectively. qPCR was also performed on 18 cases of normal skin to establish background levels of MCPyV in non-tumor tissues.
Results: RNA-ISH demonstrated the presence of MCPyV in 46.2% (42/91) of cases. A total of 58 samples had data from all the three detection modalities (qPCR, RNA-ISH and IHC). RNA-ISH demonstrated 100% concordance with qPCR results, whereas IHC had a slightly lower concordance (96.6%). RNA-ISH demonstrated higher agreement than IHC among TMA cores from the same case, and between TMA cores and matched full tissue sections. Of samples with background inflammatory cells, 5 of 37 (15.6%) showed moderate nonspecific staining of lymphocytes by IHC, whereas RNA-ISH lacked background.
Conclusions: RNA-ISH is comparably sensitive to qPCR for detection of MCPyV, and allows for correlation with tissue morphology. Our findings support RNA-ISH as a highly effective method for MCPyV detection in tumors.
Citation Format: Lisha Wang, Paul W. Harms, Nallasivam Palanisamy, Shannon Carskadon, Xuhong Cao, Javed Siddiqui, Rajiv M. Patel, Sylvia Zelenka-Wang, Timothy M. Johnson, Alison Durham, Fengyun Su, Sudhanshu Shukla, Rohit Mehra, Arul M. Chinnaiyan. A novel RNA in situ hybridization approach highly sensitive for detection of Merkel cell polyomavirus [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 1763. doi:10.1158/1538-7445.AM2017-1763
Abstract 1769: The clinical outcome of stage I lung adenocarcinoma patients with or without activating EGFR mutation
Authors: Fang Yueh-Fu 
Published: July 2017

Abstract
Purpose: Advanced stage lung adenocarcinoma patients with activating EGFR mutation have better survival result after EGFR tyrosine kinase inhibitor developed. The prevalence of EGFR mutation is high in Asian lung adenocarcinoma patients. The difference of clinical outcome of stage I lung adenocarcinoma patients with or without activating EGFR mutation was unclear. Our aim of study is to evaluate the clinical outcome between wild and mutated stage I lung adenocarcinoma.
Patients and Methods: We had 343 Stage I lung adenocarcinoma patients who received surgical resection from January 2010 to April 2014. The preliminary data of EGFR mutation in 167 patients was done. Sanger method of direct PCR, scorpion & ARMS method or ABI allele specific TagMan PCR were used to check the EGFR mutation status of these patients’ samples. The selection of these methods was depended on purity of tumor samples.
Results: There were 93 stage IA patients and 74 stage IB patients. Sixty-four (69%) patients had activating EGFR mutations in stage IA patients, and fifty (68%) patients had activating EGFR mutations in stage IB patients. The survival of stage IA and IB were similar in patients with or without EGFR mutations. The patients without mutated EGFR had better progression free survival in IA and IB patients, especially in the IB patients, although the significance did not be reached in small preliminary sample size.
Conclusion: The survival was similar in stage IA or IB lung adenocarcinoma with or without EGFR mutations. Patient without EGFR mutation had better progression free survival although there was no statistical significance between patients with or without EGFR mutations. We will collect more patients’ data for analysis.
Citation Format: Yueh-Fu Fang. The clinical outcome of stage I lung adenocarcinoma patients with or without activating EGFR mutation [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 1769. doi:10.1158/1538-7445.AM2017-1769