bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4279: Automated TRB locus haplotype analysis by long-amplicon TCRB chain sequencing for immune-related adverse events biomarker research
Authors: Burke Jennifer , Chan Frances , Huang Jiajie , Sedova Marina , Looney Timothy , Hyland Fiona 
Published: September 2020

Abstract
Introduction: Identifying predictive biomarkers for immune related adverse events (irAEs) following checkpoint blockade inhibition (CPI) remains an outstanding goal of immune-oncology translational research. Polymorphism within the T cell receptor variable gene (TRBV) has been proposed as a potential risk factor for irAEs owing to the potential link between TRBV polymorphism and chronic autoimmune disease. Efforts to interrogate the potential biomarker utility of TRBV polymorphism have been hampered by the repetitive nature of the TRB locus. We previously demonstrated a method for inferring TRB locus haplotypes from long amplicon TCRB chain sequencing data, which we used to identify major haplotype groups in a set of 81 Caucasians. Here we present an automated method for haplotype group assignment from TCRB chain sequencing data.
Methods: Rearranged TCRB chains from 10 blood samples were amplified and sequenced from 25ng peripheral blood total RNA via the Oncomine™ TCRB-LR assay using the Genexus™ Integrated Sequencer. 12 samples were run per chip with 4 samples run in each lane. TCRB clonotyping and repertoire feature analysis was performed using the Genexus™ software v5.107.14. Automated haplotype group assignment was performed by generation and comparison of TRBV allele profiles to those presented in DOI: 10.4103/JIPO.JIPO_16_19. For context, TCR evenness, convergence, and haplotype group assignment were compared to values obtained following analysis of the same samples via the GeneStudio™ S5 platform and Ion Reporter™ 5.12 software.
Results: TCR Evenness and convergence values were highly correlated across replicates run on the Genexus™ Integrated Sequencer (Spearman correlation &gt;0.95 and &gt;.70, respectively). Evenness at equivalent clone count and convergence at equivalent sequencing depth were not significantly different across platforms (Spearman correlation &gt;0.88). Haplotype group assignments demonstrated 100% agreement across replicates on both platforms.
Conclusions: We demonstrate an automated and reproducible research method for TRB haplotype group assignment via the Oncomine™ TCR-Beta LR Assay, GX run on the Genexus™ Integrated Sequencer. Future studies will evaluate the potential biomarker utility of TRB haplotyping for the prediction of irAEs.
Citation Format: Jennifer Burke, Frances Chan, Jiajie Huang, Marina Sedova, Timothy Looney, Fiona Hyland. Automated TRB locus haplotype analysis by long-amplicon TCRB chain sequencing for immune-related adverse events biomarker research [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4279.
Abstract 4298: The gut microbiome is associated with clinical responses to anti-PD-1 immunotherapy in gastrointestinal cancer patients in China
Authors: Peng Zhi , Cheng Siyuan , Zhang Quan , Kou Yan , Wang Ziqi , Jin Rong , Hu Han , Zhang Xiaotian , Gong Jifang , Li Jian , Lu Ming , Wang Xicheng , Zhou Jun , Lu Zhihao , Bi Dongtao , Tan Yan , Shen Lin 
Published: September 2020

Abstract
We report the first and largest cohort, to the best of our knowledge, on the gut microbiome of 126 gastrointestinal (GI) cancer patients in China receiving the immune checkpoint inhibitors (ICI) targeting PD-1. The cohort included 31 patients with colon cancer, 23 with esophageal carcinoma, 47 with gastric cancer, and 25 with other cancer types. 43 of the patients had samples collected before treatment. 35 of patients were assessed as microsatellite-instability-High (MSI-High) and 71 as non-MSI-High. 408 fecal samples from the patients were collected. We performed 16s rRNA amplicon sequencing (V4 region) of the patients' samples to investigate the relationship between microbial profiles and patients' immunotherapy treatment response (RECIST 1.1). Principal coordinate analysis (PCoA) showed a subgroup of responders exhibiting a microbiome profile which was enriched in Prevotella. Hierarchical clustering of patients' microbiome profiles also suggested that for each gastric and colon cancer, patients with the same response tend to share similar microbiome profiles. By comparing the microbiome profiles between R and NR group using samples collected before treatment or within 3 weeks since the start of treatment, we identified 16s rRNA V4 sequences from Prevotella enriched in R group for each tumor type, which suggests positive association between Prevotella and tumor response. Our data also suggested that MSI as good marker for tumor response, although more data is required to achieve the significance level. Besides, no significant difference in alpha diversity was observed between R and NR group for each tumor type. In sum, we studied the microbiome profiles of 126 GI cancer patients and evaluated their association with anti-PD-1 immunotherapy. Patients with the same tumor type and response tend to share similar microbiome profiles, where Prevotella and a few other taxa contributed to the pattern.
Citation Format: Zhi Peng, Siyuan Cheng, Quan Zhang, Yan Kou, Ziqi Wang, Rong Jin, Han Hu, Xiaotian Zhang, Jifang Gong, Jian Li, Ming Lu, Xicheng Wang, Jun Zhou, Zhihao Lu, Dongtao Bi, Yan Tan, Lin Shen. The gut microbiome is associated with clinical responses to anti-PD-1 immunotherapy in gastrointestinal cancer patients in China [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4298.
Abstract 4302: Molecular profile of KRAS G12C-mutant non-small-cell lung cancer and colorectal cancer in Brazilian patients
Authors: Souza Bianca Mendes , Leite Laura Rabelo , Parma Sabrina A. , Lopes Natália P. , Malta Frederico S. , Araujo Luiz Henrique , Freire Maíra C. 
Published: September 2020

Abstract
Background: Cancer is one of the leading causes of death and one of the main barriers to increasing life expectancy worldwide. The development of therapeutic strategies directly targeting mutant oncogenes, such as EGFR and BRAF, has resulted in substantial benefits for patients with a variety of cancers. KRAS is one of the most frequently mutated oncogenes, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) from Brazilian patients tested in a clinically-certified laboratory.
Methodology: 4,842 NSCLC patients were tested for KRAS, NRAS, EGFR and BRAF mutations by next generation sequencing (NGS), while 4,815 CRC patients were tested for KRAS and NRAS mutations, by pyrosequencing, between 2017 and 2019
Results and Discussion: From the 4,842 NSCLC samples tested, KRAS G12 mutations were identified in 1013 cases (20.9%) and, 336 of these (6.9% of total) were KRAS G12C. Additionally, from 4,815 CRC samples tested, KRAS G12 mutations were identified in 1633 cases (33.9%), and 166 of these (3.4% of total) were KRAS G12C. In the literature, KRAS G12C has been reported in 14 to 16% of all lung adenocarcinomas, and 5% of colorectal adenocarcinomas. Our data illustrate a relevance of this mutation in a significant number of patients and highlight an opportunity for targeted therapy. Some studies characterizing lung cancers have indicated that KRAS mutations, including KRAS G12C, are mutually exclusive with other known oncogenic driver mutations in NSCLC. However, in the current analysis, we identified 30 cases of NSCLC harboring multiple mutations, such as KRAS G12C mutations co-existing with EGFR, BRAF or NRAS mutations. This finding is probably due to the multiclonal presentation in selected cases.
Conclusions: A relatively high number of patients may present with KRAS G12C-mutant cancers in Brazil, indicating the relevance of identifying such cases for targeted therapy. Further studies will deepen the analysis of clonality and heterogeneity in this cohort.
Citation Format: Bianca Mendes Souza, Laura Rabelo Leite, Sabrina A. Parma, Natália P. Lopes, Frederico S. Malta, Luiz Henrique Araujo, Maíra C. Freire. Molecular profile of KRAS G12C-mutant non-small-cell lung cancer and colorectal cancer in Brazilian patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4302.
Abstract 4309: A novel immune prognostic index for the stratification of high-risk patients with early breast cancer
Authors: Lee Hannah , Kwon Mi Jeong , Koo Beom-Mo , Han Jinil , Shin Young Kee 
Published: September 2020

Abstract
The prognostic or predictive value of current commercial multigene assays for breast cancer are limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer. Despite the prognostic or predictive significance of immune response-related genes in breast cancer, immune gene signatures have not been incorporated into most current assays. Here, we developed a novel immune gene based-prognostic model to predict the risk of recurrence in high-risk women with early breast cancer. Using public gene expression microarray datasets for breast cancer, we classified breast cancer patients into three risk groups according to clinical risk and proliferation risk, and identified the most significant five immune response-related genes (TRAT1, IL2RB, CTLA4, IGHM and IL21R) associated with clinical outcome in the clinical and proliferation high-risk (CPH) subgroup. Immune prognostic index based on the combination of the expression of five immune response-related genes and lymph node status was developed to predict the risk of recurrence in high-risk breast cancer patients and its prognostic significance was validated in independent validation datasets. Disease-free survival (DFS) or distant metastasis-free survival (DMFS) of patients classified as high risk according to the immune prognostic index was significantly lower than those of patients classified as intermediate and low risk in the CPH group. Multivariate analysis demonstrated that the immune prognostic index is an independent prognostic factor for DFS or DMFS. Moreover, c-index showed that the immune prognostic index is superior to clinicopathological variables in predicting the prognosis. Our immune index was also prognostic in independent validation datasets. Our immune prognostic index identified low-risk patients among patients classified as CPH group in all molecular subtypes of breast cancer and may be used to overcome the limitations of the current multigene assay.
Citation Format: Hannah Lee, Mi Jeong Kwon, Beom-Mo Koo, Jinil Han, Young Kee Shin. A novel immune prognostic index for the stratification of high-risk patients with early breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4309.
Abstract 4342: Histological variants and sites of presentation of malignant melanoma in a resource poor setting: A histopathological review
Authors: Adoke Kasimu Umar , Faruk Mohammed , Iliyasu Yawale , Ahmed Saad Aliyu 
Published: September 2020

Abstract
Background: Melanoma is a malignant tumour that arises from melanocytic cells. The incidence is increasing worldwide in white population where fair skin people receive excessive sun exposure. Although relatively uncommon in Africa-Americans, recent trends shows increase incidence in Africa- Americans. Data on the incidence and biology of melanoma are few in Africa. This study review the variants and sites of melanoma in a resource poor setting in Nigeria with some immunohistochemical stains performed.
Method: All cases of melanoma diagnosed in the Department of Pathology in a tertiary hospital in Nigeria over a three year period (2016-2018) were retrieved. Patient's information including site and age were also retrieved from their case notes. Immunohistochemistry using two antibodies S-100, HMB-45 was done.
Results: A total 38 cases were seen during the study period with a male female ratio of 1:1.1. The age range was 5-80 years with a mean age of 48.8±18.1. The most common site for melanoma is the foot 19(50%), followed by the uvea 7(18.4%), skin and inguinal lymph node 4(10.5%), anorectal and conjunctiva had 2(5.3%). The commonest histological variant of melanoma was acral lentigenous melanoma 19(50%), Superficial spreading melanoma 4(10.5%), nodular melanoma 3(7.9%) and desmoplastic melanoma 1(2.6%). Immunohistochemistry was used on three cases to rule out differentials.
Conclusion: Malignant melanoma in our setting is in contrast with African-Americans and Caucasians population base on site and histological type, hence future studies on molecular pathways of melanoma in Africa needs to be explored to show similarity or difference and the possibility of targeted immunotherapy.
Citation Format: Kasimu Umar Adoke, Mohammed Faruk, Yawale Iliyasu, Saad Aliyu Ahmed. Histological variants and sites of presentation of malignant melanoma in a resource poor setting: A histopathological review [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4342.
Abstract 435: Mouse models of human cancer
Authors: Bult Carol J. , Krupke Debra M. , Neuhauser Steven B. , Richardson Joel E. , Sundberg John P. 
Published: September 2020

Abstract
Mouse models play a crucial role in understanding the genetic and genomic basis of cancer and for the development of novel cancer therapies. Because data and information about these models are distributed and heterogeneous, gaining an appreciation for which models have been developed and what their characteristics are presents a major challenge for cancer researchers. The Mouse Models of Human Cancer Database (MMHCdb; http://tumor.informatics.jax.org) solves this challenge by providing a comprehensive, expertly curated on-line information resource about genetically engineered (GEMMs) and inbred mouse models of human cancer. In partnership with the European Bioinformatics Institute (EMBL/EBI), MMHCdb has also developed and implemented PDX Finder, a global catalog of Patient Derived Xenograft models (https://www.pdxfinder.org). Both MMHCdb and PDX Finder employ metadata standards to simplify the process of searching for relevant mouse models by diverse criteria including cancer type, type of strain, and genetic alteration. MMHCdb contains more than100,000 records on tumor frequency data for over 7,600 different mouse strains. These data are linked to over 4,700 references, 2,900 pathology reports, and 6,900 images. PDX Finder provides researchers with one stop access to information about more than 2,800 PDX models in repositories from around the world. MMHCdb and PDX Finder are supported, in part, by NIH/NCI CA089713. MMHCdb was formerly called the Mouse Tumor Biology database (MTB).
Citation Format: Carol J. Bult, Debra M. Krupke, Steven B. Neuhauser, Joel E. Richardson, John P. Sundberg. Mouse models of human cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 435.
Abstract 4363: A-FABP and estrogens are independently involved in the development of breast cancer
Authors: Li Bing , Hao Jiaqing , Yan Xiaofang , Kong Maiying , Sauter Edward 
Published: September 2020

Abstract
Background: We previously reported that postmenopausal obese women exhibit increased levels of circulating adipocyte fatty acid binding protein (A-FABP), which is associated with breast cancer (BC) development. In postmenopause, increased estrogen levels are associated with increased BC risk.
Hypothesis: Estrogens (estrone: E1, estradiol: E2 and estriol: E3) are associated with A-FABP in the setting of obesity and obesity-related BC development.
Methods: Immunoassays for E1, E2, E3, and A-FABP were performed using serum samples from women with and without BC.
Results: Statistical analysis was conducted using the Mann-Whitney test and multiple linear regression models. Considering all subjects, E1 and E2 but not E3 levels were significantly higher in pre- than in postmenopause among both non-obese and obese individuals (p&lt;0001). E3 (p&lt;0.01) and E1 (p&lt;0.05) levels were higher in non-obese than in obese women. A-FABP levels were significantly higher in obese postmenopausal women with and without BC, but not in premenopausal women, regardless of BC status. When stratified by BC status, E2 levels were significantly higher, while E1 and E3 levels were significantly lower in postmenopausal healthy obese than non-obese women. These body mass index (BMI) based differences were not observed among women with BC. E3 levels were higher in obese pre (p=0.003) and postmenopausal (p=0.001) women with BC than those without. A-FABP levels were significantly higher in postmenopausal obese healthy women and women with BC. A-FABP was not highly associated with E1, E2 or E3.
Impact: 1) A-FABP expression is increased in postmenopausal obese women with and without BC; 2) E1 and E2 expression is higher in pre- than postmenopausal women, regardless of BMI; 3) E1 and E3 levels are higher in lean than obese individuals, regardless of menopausal status; 4) the influence of obesity on E1, E2 and E3 expression in postmenopause is lost in women with BC, 5) E3 is increased in obese vs. non-obese women with BC, and 6) A-FABP and estrogens are independently involved in the development of BC.
Citation Format: Bing Li, Jiaqing Hao, Xiaofang Yan, Maiying Kong, Edward Sauter. A-FABP and estrogens are independently involved in the development of breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4363.
Abstract 4370: Lasofoxifene alone or in combination with palbociclib as an effective treatment for therapy-resistant ER-positive metastatic breast cancer
Authors: Laine Muriel , Kurleto Justyna D. , Greene Marianne E. , Phung Linda , Komm Barry S. , Greene Geoffrey L. 
Published: September 2020

Abstract
Patients with Estrogen Receptor positive (ER+) metastatic breast cancer (MBC) are currently treated with fulvestrant, a selective estrogen receptor degrader (SERD), or a combination of fulvestrant and palbociclib, a CDK4/6 inhibitor. Approximately 25-40% of patients with MBC have activating mutations in the ERα ligand-binding domain. The two most common mutations are Y537S and D538G, which confer constitutive activity to ERα, resulting in AI/tamoxifen/fulvestrant resistance. Lasofoxifene, a selective estrogen receptor modulator (SERM), was developed for the treatment of vaginal atrophy and osteoporosis. Previous studies from this lab, performed in a mutant ERα MCF-7 xenograph MBC mouse model, showed that lasofoxifene was significantly more effective than fulvestrant at inhibiting tumor growth, as well as metastasis to the lung and liver. In the current dose/response study, we compared the efficacy of lasofoxifene + palbociclib combinations to fulvestrant + palbociclib combinations. Engineered and luciferase-GFP tagged MCF-7 Y537S cells were injected into the mammary ducts of NSG mice (MIND model) and tumor progression was monitored by live luminescence imaging of primary tumors as well as ex vivo imaging of metastatic sites at study endpoint. Our results showed that all dose combinations of lasofoxifene + palbociclib were more effective than fulvestrant + palbociclib at inhibiting primary tumor growth as well as bone, lung, liver and brain metastasis. These data strongly suggest that patients with ERα+ MBC would benefit from orally delivered lasofoxifene + palbociclib therapy and that this combination could be superior to fulvestrant + palbociclib.
Citation Format: Muriel Laine, Justyna D. Kurleto, Marianne E. Greene, Linda Phung, Barry S. Komm, Geoffrey L. Greene. Lasofoxifene alone or in combination with palbociclib as an effective treatment for therapy-resistant ER-positive metastatic breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4370.
Abstract 4374: CE+BZA combination therapy decreases breast cancer outgrowth in part through activation of the AHR pathway
Authors: Dembo Anna G. , Aledort Emily S. , Greene Geoffrey L. 
Published: September 2020

Abstract
Menopause occurs in all women, usually between the ages of 45 and 55. As a result of menopause, women often experience undesirable vasomotor symptoms, which can be alleviated by hormone replacement therapy (HRT). The Women's Health Initiative (WHI) trial concluded that PremPro, a HRT formulation that combines conjugated equine estrogens (CE) with medroxyprogesterone acetate, increases the risk of breast cancer. Over the years, the number of women taking HRT has dramatically decreased due to the perceived risk based largely on the results of the WHI trial. Follow-up studies suggest that breast cancer cases from PremPro treatment were primarily due to the outgrowth of occult tumors, not the formation of new disease. Duavee, a more recent form of HRT that combines CE and bazedoxifene (BZA), a selective estrogen receptor modulator (SERM) and degrader (SERD), has been approved by the FDA for treatment of moderate to severe hot flashes and to reduce the risk of osteoporosis. More importantly, this CE+BZA mixture not only relieves symptoms associated with menopause, but it also does not stimulate the breast or uterus. Several preclinical studies suggest that CE+BZA might be protective in the breast, however the mechanism of action of this new combination therapy is not known. Our goal, therefore, was to elucidate the underlying molecular mechanisms by which CE+BZA differentially affects estrogen receptor alpha (ERα) action in the mammary gland. Pathway analysis from RNA-sequencing revealed Aryl Hydrocarbon Receptor (AHR) signaling as the top canonical pathway affected by treatment with CE+BZA. Previous studies reported that 4-hydroxytamoxifen, a metabolite of the SERM tamoxifen, was able to activate the AHR pathway. In our study we determined that BZA treatment activated the AHR pathway in both ERα-positive and ERα-negative cell lines. BZA increased expression of aryl hydrocarbon receptor repressor (AHRR) in cell lines and increased expression of two AHR pathway members, CYP1A1 and CYP1B1, in tumors of estrogen-sensitive polyoma middle T antigen (PyMT) mice. AHRR has been reported to act as a tumor suppressor in breast cancer; therefore activation of AHR by BZA in women taking CE+BZA combination therapy might be one mechanism by which outgrowth of occult tumors is decreased. Further evaluation of the role of AHR in breast cancer is necessary to improve our understanding of CE+BZA action.
Citation Format: Anna G. Dembo, Emily S. Aledort, Geoffrey L. Greene. CE+BZA combination therapy decreases breast cancer outgrowth in part through activation of the AHR pathway [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4374.