bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3936: Identification and validation of the potential biomarker insulin-like growth factor binding protein acid-labile subunit for breast cancer in African American women
Authors: Tadi Uppala Padma P. , Garberoglio Carlos , Lum Sharon , Davis Willie , Leung Hon-Chiu Eastwood , Liebman Michael , Oda Keiji , Patel Utkarsh P. 
Published: July 2016

Abstract
Breast cancer is the most frequently diagnosed cancer in women, with an estimated 40, 730 breast cancer deaths in the US in 2015. African American (AA) women have a lower breast cancer incidence rate, but a higher breast cancer death rate, than non-Hispanic White women. Research indicates that breast tumor biology in AA women is different from that in Caucasian women. AA women are more likely to be diagnosed with breast cancer at an earlier age and with more aggressive form of the disease, characterized by higher grade and negative estrogen and progesterone receptor status. Because of the aggressive nature of these tumors and current lack of targeted therapies, identification of novel relevant protein markers is of great importance. The purpose of this study was to validate serum proteins that were previously identified by serum proteomic profiling in 22 serum samples by 2D-DIGE/MS analysis and a subset of samples by shotgun LC/MS technology. Methods and new data: The current study included serum samples from 15 African American breast cancer patients and 12 healthy controls. Patients were grouped into triple negative (TN), HER2 and Luminal A and B subtypes. Proteins of biological significance were validated using western blot analysis. For ceruloplasmin, and insulin-like growth factor binding protein acid-labile subunit (IGFBP-ALS), one-way ANOVA was used to compare mean density among the three groups. For Vitamin D Binding protein (VDB), a two-sample t-test was used to compare the density between the groups. Due to the small sample size, we have also conducted nonparametric tests. IGFBP-ALS was significantly lower in triple negative breast cancer patients (p = 0.016) and in HER2 (p = 0.025) subtypes. There was no significant difference in VDB protein in the luminal A and B subtypes (p = 0.98). Future efforts will focus on validating the identified panel of biomarkers to gain insight into their role(s) in the etiology of aggressive breast tumors. Funded by Susan G Komen for the Cure and SEED grant SPH.
Citation Format: Padma P. Tadi Uppala, Carlos Garberoglio, Sharon Lum, Willie Davis, Hon-Chiu Eastwood Leung, Michael Liebman, Keiji Oda, Utkarsh P. Patel. Identification and validation of the potential biomarker insulin-like growth factor binding protein acid-labile subunit for breast cancer in African American women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3936.
Abstract 3941: Novel biomarkers and multiplexed NGS to stratify FFPE NSCLC by tumor infiltrating lymphocytes and histopathology phenotypes
Authors: Mongan Ann , Rozenzhak Sophie , Bien Geoffrey , Chi David , Nishikawa Hiroyoshi , Hyland Fiona , Godsey Jim 
Published: July 2016

Abstract
There is increasing evidence supporting the association of tumor infiltrating lymphocytes (TIL) and drug sensitivity of solid tumors. In particular, primary and meta-analyses have reported a positive correlation between TIL level and outcome in advanced non-small cell lung cancer (NSCLC) treated with checkpoint inhibitors such as PD-1 and PD-L1. Recent trials with immunotherapies have started including TIL assessment in the study protocol in recognition of this metric as a predictive and prognostic biomarker. TIL levels are typically quantified by visual assessment of H&E-stained tumor sections. While this approach is generally accepted as the standard, there is an increased recognition that visual assessment of H&E-stained slides lacks precision and is relatively subjective (Salgado R, 2015; Schalper KA, 2015). Furthermore, as investigators are often also interested in measurements of additional biomarkers such as IFNg as well as the drug targets, a gene panel approach offers a convenient solution to objectively quantify expression levels of these informative markers. Here we report the discovery and verification of a unique gene expression signature that is capable of stratifying FFPE samples of NSCLC tumors by TIL levels and histopathology phenotypes (adenocarcinoma vs. squamous cell carcinoma). Gene expression was measured by an RNA Ion AmpliSeq Gene Expression research panel* containing 200 assays. Each research sample was measured with replicates at library generation step and sequencing step. Technical replicates were found to have &gt;0.99 correlation among each other. Assays on the panels were also found to be robust with respect to low input amount (1-10 ng RNA). *For Research Use Only. Not for use in diagnostic procedures.
Citation Format: Ann Mongan, Sophie Rozenzhak, Geoffrey Bien, David Chi, Hiroyoshi Nishikawa, Fiona Hyland, Jim Godsey. Novel biomarkers and multiplexed NGS to stratify FFPE NSCLC by tumor infiltrating lymphocytes and histopathology phenotypes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3941.
Abstract 3945: Antigen-specific immunity and regulation as predictive biomarkers for anti-tumor vaccination
Authors: Johnson Laura E. , Olson Brian M. , McNeel Douglas G. 
Published: July 2016

Abstract
We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, PAP-specific proliferating and IFNγ-producing T cells developed in some patients, and persistent Th1-type immunity was associated with an increase in PSA doubling time. In the current study, we sought to determine if one or more measures of antigen-specific or antigen non-specific immunity present prior to treatment was associated with subsequent immune response as a possible predictive biomarker. Specifically, patients who had developed PAP-specific, IFNγ-secreting immune responses, detectable at least twice over one year after immunization, were defined as immune “responders”. The frequency of peripheral T cell and B cell lymphocytes, natural killer cells, monocytes, dendritic cells, myeloid derived suppressor cells, and regulatory T cells did not differ between the immune responder and non-responder groups. PAP-specific immune responses, detected as cytokine secretion following antigen stimulation of peripheral blood mononuclear cells in vitro, were detected in many patients pre-immunization. PAP-specific expression of granzyme B, IFNγ, and IL-6 was not significantly different between immune responding (n = 7) and non-responding patients (n = 23), however non-responder patients tended to have higher PAP-specific IL-10 production (p = 0.09). Using a trans vivo delayed-type hypersensitivity (DTH) assay to assess for antigen-specific immune regulation, responder patients tended to have preexisting PAP-specific bystander regulatory responses that suppressed DTH to a recall antigen, a response previously demonstrated to be IL-35-mediated (p = 0.049). While the number of patients analyzed was low, these results suggest that different measures of antigen-specific regulation might help predict outcome from vaccination. These will be prospectively evaluated in an ongoing randomized, placebo-controlled, phase II trial evaluating this vaccine (NCT01341652).
Citation Format: Laura E. Johnson, Brian M. Olson, Douglas G. McNeel. Antigen-specific immunity and regulation as predictive biomarkers for anti-tumor vaccination. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3945.
Abstract 3948: Lysosomal acid phosphatase 2 is an unfavorable prognostic factor associated with better survival in colorectal cancer patients receiving chemotherapy
Authors: Chen. Chi-Long 
Published: July 2016

Abstract
Colorectal cancer (CRC) is one of leading malignancies worldwide. The therapeutic modality for advanced CRC including stage III and IV, is operation following by chemotherapy. For stage II CRC, surgery is the main therapeutic modality but the usage of adjuvant chemotherapy is still controversial and there is no reliable indicator for their purpose. In this study, we found that the expression of lysosomal acid phosphatase 2 (ACP2) in the tumor tissue of CRC was elevated and was correlated with poor outcome in stage II CRC patients, especially. In addition, in CRC patients with high ACP2 expression tended to have more sensitive for 5-FU treatment in our cohort. In CRC of stage II patients, multivariate Cox proportion hazard model analysis revealed that ACP2 expression and T stage are independent prognostic factor for overall survival (HR: 3.274, CI: 1.413-7.586, p = 0.006; HR: 3.742, CI: 1.058-13.233, p = 0.041). Our data indicated that high expression of ACP2 was a negative prognosticator and could predict 5-FU chemotherapy response in stage II CRC. Moreover, we used HCT116 cells transfected with ACP2 lentivirus to create stable shACP2-HCT116 clone. Our results showed knockdown ACP2 could induce chemoresistance and more mesenchymal-like phenotype of CRC cell line. Therefor, targeting ACP2 might be a novel chemotherapy factor and might a new strategy in stage II CRC patients.
Citation Format: Chi-Long Chen. Lysosomal acid phosphatase 2 is an unfavorable prognostic factor associated with better survival in colorectal cancer patients receiving chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3948.
Abstract 3953: Highly accurate genetic profiling of circulating tumor cells using a label-free inertial microfluidic approach coupled with droplet PCR-based next-generation sequencing
Authors: Lee Yi Fang , Consugar Mark , Helzer Kimberly , Tan Mei Hui , Emrick Lori , Bhagat Ali Asgar 
Published: July 2016

Abstract
Background: Circulating tumor cells (CTCs) could provide significant insights into cancer metastatic events and potentially even inform clinical decisions. However, the scarcity of CTCs, compounded by the abundance of circulating white blood cells, poses a major technical challenge in the isolation, yield and downstream molecular analysis. Moreover, next-generation sequencing (NGS) of CTCs has been challenged by low CTC purity and nucleic acid yields commonly derived from existing technologies. Here, we present a label-free microfluidic approach that utilizes curvilinear microchannel geometry for high purity CTC enrichment from 7.5 ml whole blood.
Methods: We showed high purity isolation of CTCs using a label-free inertial focusing microfluidics platform, ClearCell® FX. The lung cancer cell line, NCI-H1975, with known EGFR, CDKN2A and TP53 mutations, were spiked into 7.5ml healthy donor peripheral blood samples at varying concentrations (50, 100, 200 cells). DNA was extracted using the QIAamp Micro kit. The Thunderbolts Cancer Panel droplet digital PCR NGS library preparation method was used to enrich 230 loci in 50 known cancer genes from the isolated CTC gDNA. The libraries were sequenced on a MiSeq system.
Results: The CTCs were sufficiently enriched with an average recovery of 45.8% and purities ranging from 1% - 70%. All libraries were successfully generated and sequenced with ≥1400× mean coverage, even with as little as 2 ng of starting material. Known EGFR, CDKN2A and TP53 mutations in H1975 were successfully detected in all the samples (n = 9), with a significant variant frequency that correlates with CTC purity levels.
Conclusion: We have demonstrated a highly accurate and sensitive workflow utilizing a combination of inertial focusing and digital droplet microfluidics to detect low numbers of rare CTCs and interrogate their molecular profiles from as little as 10 cells/mL frequency. This workflow has the potential for further development and adoption as a liquid biopsy approach for non-invasive genomic profiling of metastatic cancers.
Citation Format: Yi Fang Lee, Mark Consugar, Kimberly Helzer, Mei Hui Tan, Lori Emrick, Ali Asgar Bhagat. Highly accurate genetic profiling of circulating tumor cells using a label-free inertial microfluidic approach coupled with droplet PCR-based next-generation sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3953.
Abstract 398: Real-life example of biobanking: results of the PATH Biobank
Authors: Anzeneder Tobias , Ohlms Ulla , Bodenmüller Heinz 
Published: July 2016

Abstract
Introduction: Since 2002, PATH Foundation has kept a biobank collecting high-quality fresh frozen breast cancer specimens adhering to uniform SOPs at seven certified breast cancer centres in Germany. Research groups from academia and industry can obtain samples after application and review. PATH Biobank is a not-for-profit organisation and asks for a cost recovery fee in exchange for sample allocation to sustainably finance the expenses it incurs.
Material and methods: The PATH Biobank consists of a centralized database and a decentralized bio repository. The samples are collected and stored at seven institutes for pathology at certified German breast cancer centres. Tumour tissue, along with normal (benign) adjacent tissue and blood serum aliquots are processed, labelled and stored according to uniform SOPs. Informed consent to biobanking and the use of the samples and data for research is obtained from the donors individually during pre-operation discussions.
Results: Since 2004, more than 8,600 breast cancer patients have given their informed consent to the storage and analysis of their tissue and blood serum for research purposes. Breast cancer tissue samples from 59% of donors could be stored due to size of the surgically removed tissue specimen. In addition, normal adjacent tissue is available from 62% of donors and blood serum aliquots can be derived from 92% of patients.
Using the annotating data, 96% of donors can be classified into the intrinsic molecular breast cancer subtypes in accordance with the St. Gallen Criteria. In 2008, PATH Biobank started to support research groups by providing breast cancer samples and data as well as informing the public about the projects on-line. In 2015 three co operations resulted in scientific publications.
One landmark collaborations started in 2012 and has been studying the frequency and background of defined mutations in breast cancer. A number of 701 tissue samples have been used for this study. All samples were subject to quality testing, only 11% failed due to less than 5% tumour content. Tumour content depended on clinical conditions and staging (ranging from 34% failure in samples derived from neo adjuvantly treated patients to 2% in cases with staging UICC IV). Additional results concerning the quality of samples from PATH Biobank will be presented.
Conclusions: For breast cancer research and biomarker studies, PATH Biobank can be a valuable resource.
Citation Format: Tobias Anzeneder, Ulla Ohlms, Heinz Bodenmüller. Real-life example of biobanking: results of the PATH Biobank. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 398.
Abstract 3984: Novel t(X;21)(q26;q22) detected in a case of acute unclassifiable leukemia by application of anchored multiplex PCR-based next-generation sequencing
Authors: Johnson Laura , Wang Helen , Trifilo Katelyn , Kudlow Brian , Pappenhausen Peter R. , Hussaini Mohammad 
Published: July 2016

Abstract
In this study, we demonstrate real-time clinical application of novel anchored multiplex PCR (AMP) technology in hematologic disease. A 78-year-old man with a history of hairy cell leukemia treated with Cladribine (2013) and bladder cancer (2014) developed dyspnea in August 2015. Work up revealed bicytopenia and leukocytosis. Outside bone marrow biopsy was read as B lymphoblastic leukemia/lymphoma. Rebiopsy was performed at our NCI-designated cancer center with extensive work up resulted in reclassification as acute unclassifiable leukemia (rare) with deferral to molecular diagnostics for guidance regarding classification. MLL, BCR-ABL, and MDS FISH panel were negative. Next generation sequencing (NGS) interrogating more than 400 genes showed FLT3-ITD, truncation of RUNX1 exon 6, ASXL1 p.G646Wfs*12, MLL p.V297L, and EZH2 p.V674M and p.C443Y mutations. The molecular profile favored therapy-related AML. Interestingly, cytogenetics revealed 46,Y,t(X;21)(q26;q22)[20]. FISH confirmed RUNX1 rearrangement but the partner was unknown. The t(X;21)(q26;q22) appears to be novel. However, the rare t(3;21)(q26.2;q22) has been cited to segregate with therapy-related MDS/AML. Subsequent aberrant activation of RUNX1 and MECOM is postulated to be pivotal in pathogenesis. Therefore, it is of great interest to determine the translocation partner associated with RUNX1 in our case. This type of analysis is not easily amenable to either Sanger or conventional NGS approaches. Fortuitously, with the recent advent of AMP technology (Archer FusionPlex) novel fusion detection has become possible. AMP was key in the characterization of this sample and promotes discovery of novel fusions by targeting one (known) of the two genes involved in a translocation event. Application of this cutting edge technology lead to the discovery of the novel fusion RUNX1-G6PD in this case. The identity of the novel fusion partners was supported by the breakpoints originally observed by the karyotype analysis. G6PD has been previously reported to be upregulated in acute leukemia. This discovery raises the possibility convergent pathogenic pathways and carries potential biological, diagnostic, and therapeutic implications.
Citation Format: Laura Johnson, Helen Wang, Katelyn Trifilo, Brian Kudlow, Peter R. Pappenhausen, Mohammad Hussaini. Novel t(X;21)(q26;q22) detected in a case of acute unclassifiable leukemia by application of anchored multiplex PCR-based next-generation sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3984.
Abstract 3988: Detection of novel t(12;17)(p12;p13) in treatment-refractory/relapsed acute myeloid leukemia by anchored multiplex PCR(AMP)-based next-generation sequencing
Authors: Johnson Laura , Trifilo Katelyn , Wang Helen , Kudlow Brian , Padron Eric , Pappenhausen Peter R. , Hussaini Mohammad 
Published: July 2016

Abstract
Gene fusions are an important class of mutations and have been shown to drive many genetic diseases. While several technologies can be used to detect fusions, anchored multiplex PCR (AMP) next generation sequencing (NGS)-based detection offers the advantages of novel fusion detection and the ability to multiplex multitudinous genes. Here we report application of this technology in the evaluation of a 56-year-old man diagnosed with AML (2013). He was treated initially with Vidaza and later with CLAG-M induction (2014) with complete response and consolidation CLA (2015). He relapsed (4/2015) and was reinduced with 7+3 (Ida). He relapsed again and was reinduced with FCT but bone marrow biopsy showed persistent disease (75% blasts). Karyotype showed 46, XY, t(12;17)(p12;p13)[20]. It was postulated that ETV6 oncogene was involved based on 12p13 locus. The partner gene was unknown in this patient with multiply relapsed/refractory disease. AMP technology (Archer FusionPlex) confirmed involvement of the expected ETV6. However, more importantly, employing this technology lead to the discovery of a novel fusion partner, HIC1. The identity of the novel fusion partners was supported by the breakpoints originally observed by karyotype analysis. AMP promotes discovery of novel fusions by targeting one (known) of two genes involved in the fusion event. HIC1 regulates cellular growth and serves as a tumor suppressor gene. Inactivation of HIC1 has been associated with aggressive disease and poor survival in other cancer types. Interestingly, in vitro restoration of gene function by 5-aza-dC resulted in decreased cell proliferation and tumor aggressiveness in pancreatic cancer and head and neck squamous cell carcinoma suggesting the prospect of a therapeutic target. This discovery provides new insight into a possible leukemogenic pathway in AML and potential for targeted therapy.
Citation Format: Laura Johnson, Katelyn Trifilo, Helen Wang, Brian Kudlow, Eric Padron, Peter R. Pappenhausen, Mohammad Hussaini. Detection of novel t(12;17)(p12;p13) in treatment-refractory/relapsed acute myeloid leukemia by anchored multiplex PCR(AMP)-based next-generation sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3988.
Abstract 3997: The impact of PD-L1 expression in patients with metastatic GEP-NETs
Authors: Kim Seung T. , Lee Won 
Published: July 2016

Abstract
Programmed death-ligand 1 (PD-L1), which is expressed on many cancer cells, interacts with PD1 expressed on the surface of T cells, inhibiting the T cells and blocking the antitumor immune response. Expression of PD-L1 in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been studied. We investigated the impact of PD-L1 expression in 32 patients with metastatic GEP-NET.
The expression of PD-L1 was evaluated using an anti-PD-L1 immunohistochemistry (IHC) antibody optimized for staining of formalin-fixed paraffin-embedded (FFPE) tissue samples. The correlation between PD-L1 and clinicopathological data including survival and response to systemic treatments was analyzed.
Primary sites were 24 foregut-derived GEP-NETs, including stomach (n = 1), duodenum (n = 2), biliary tract (n = 7), and pancreas (n = 14), and 8 hindgut-derived GEP-NETs of the distal colon and rectum. Among the 32 patients with metastatic GEP-NET analyzed in this study, 7 (21.9%) had expression of PD-L1 in tumor tissues. Expression of PD-L1 was significantly associated with high-grade WHO classification (grade 3) (p = 0.008) but not with gender, primary site, and number of metastatic sites (p&gt;0.05). The status of PD-L1 expression was statistically associated with progression-free survival (PFS) for first-line systemic treatment (p = 0.047). Moreover, the status of PD-L1 expression could significantly predict overall survival (p = 0.037).
The expression of PD-L1 was associated with higher WHO tumor grade (grade 3) in metastatic GEP-NETs. PD-L1 expression had both predictive and prognostic value for survival of patients with metastatic GEP-NETs.
Citation Format: Seung T. Kim, Won Lee. The impact of PD-L1 expression in patients with metastatic GEP-NETs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3997.