bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO-038: DCE-MRI of tumor hypoxia in cervical carcinoma and pancreatic ductal adenocarcinoma xenografts
Authors: Gaustad Jon-Vidar , Hauge Anette , Wegner Catherine S. , Hansem Lise Mari K. , Rofstad Einar K. 
Published: December 2020

Abstract
Tumor hypoxia is associated with resistance to treatment, aggressive growth, and poor clinical outcome in many cancer types, and is a result of an imbalance between oxygen supply and oxygen consumption. We have previously shown that Ktrans and ve images derived by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) reflect blood perfusion and cell density which are important determinants of oxygen supply and oxygen consumption respectively. The purpose of the current study was to investigate whether Ktrans and/or ve images can be used to produce images of tumor hypoxia. Cervical carcinoma and pancreatic ductal adenocarcinoma xenografts were used as models of human cancer, and xenografted tumors were subjected to antiangiogenic treatment or left untreated. Ktrans and ve images were derived from DCE-MRI data by using Tofts standard pharmacokinetic model, and images of tumor hypoxia were produced by applying threshold values to Ktrans and/or ve. Tumor hypoxia was also assessed by immunohistochemistry by using pimonidazole as a hypoxia marker. Ktrans and ve images were highly heterogeneous. Strong correlations were found between hypoxic fractions determined by immunohistochemistry and hypoxic fractions calculated by using Ktrans but not ve images. Importantly, hypoxia images produced by using Ktrans images reflected both naturally occurring and treatment-induced hypoxia. Moreover, hypoxia images produced by combining Ktrans and ve images were not superior to the hypoxia images produced by using only Ktrans images. These observations imply that Ktrans images reflected blood perfusion and oxygen supply, and that the heterogeneity in hypoxia was caused by heterogeneity in oxygen supply rather than heterogeneity in cell density and oxygen consumption in these tumor models.
Citation Format: Jon-Vidar Gaustad, Anette Hauge, Catherine S. Wegner, Lise Mari K. Hansem, Einar K. Rofstad. DCE-MRI of tumor hypoxia in cervical carcinoma and pancreatic ductal adenocarcinoma xenografts [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-038.
Abstract PO-068: Intratumoral heterogeneity of prognostic multigene signatures for breast cancer
Authors: Hurson Amber N. , Hamilton Alina , Olsson Linnea T. , Kirk Erin L. , Calhoun Benjamin C. , Geradts Joseph , Sherman Mark E. , Troester Melissa A. 
Published: December 2020

Abstract
Background Multigene assays for breast cancer are becoming more commonly used for research, diagnostic, and treatment-selection purposes. These assays are commonly based on a single tumor sample, so this study assesses whether clinically-relevant multigene scores are subject to misclassification due to technical variation or intratumoral heterogeneity. Methods Using FFPE blocks, tumors from 37 patients were sampled at different pathologist-selected spatial locations, targeting regions with distinct histological appearance. A second pathologist assessed mitotic activity and presence of immune infiltration for each specimen. Gene expression was quantified using the PAM50 assay. Samples were classified with respect to intrinsic subtype (Luminal A, Luminal B, HER2-enriched, or Basal-like) and risk of recurrence with proliferation score (ROR-P, high vs. med/low). Euclidean distances between samples were calculated across the 50 genes, and the distribution of Euclidean distances were compared for samples that were concordant vs. discordant for each multigene classifier for PAM50 or ROR-P. Results Of the 37 tumors, 11 had samples with discordant PAM50 subtype and 7 had samples with discordant ROR-P group (75% and 83% agreement, respectively). The Euclidean distance between paired samples with discordant PAM50 intrinsic subtype or ROR-P score was significantly greater than that among concordant tumors. Samples discordant for ROR-P had more heterogeneity in histological characteristics, while discordance of PAM50 subtype call was generally not predicted by heterogeneity of these histological characteristics. Conclusion The concordance of PAM50 subtype calls and ROR-P, despite oversampling of heterogenous-appearing tumor regions, demonstrates reproducibility of the PAM50 classifier for breast cancer tumor intrinsic subtyping. However, assay sampling strategies for histologically heterogeneous tumors merit further consideration.
Citation Format: Amber N. Hurson, Alina Hamilton, Linnea T. Olsson, Erin L. Kirk, Benjamin C. Calhoun, Joseph Geradts, Mark E. Sherman, Melissa A. Troester. Intratumoral heterogeneity of prognostic multigene signatures for breast cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-068.
Abstract PO-105: The fibrinolytic factor tPA drives LRP1-mediated melanoma growth and metastasis
Authors: Heissig Beate , Salama Yousef , Osada Taro , Tsuda Yuko , Takahashi Satoshi , Hattori Koichi 
Published: December 2020

Abstract
The multifunctional endocytic receptor low-density lipoprotein receptor-related protein (LRP)1 has recently been identified as a hub within a biomarker network for multicancer clinical outcome prediction. The mechanismhowLRP1 modulates cancer progression is poorly understood. In this studywe found that LRP1 and one of its ligands, tissue plasminogen activator (tPA), are expressed inmelanoma cells and control melanoma growth and lung metastasis in vivo. Mechanistic studies were performed on 2 melanoma cancer cell lines, B16F10 and the B16F1 cells, both of which formprimary melanoma tumors, but only B16F10 cells metastasize to the lungs. Tumor-, but not niche cell–derived tPA, enhanced melanoma cell proliferation in tPA2/2 mice. Gain-of-function experiments revealed that melanoma LRP1 is critical for tumor growth, recruitment of mesenchymal stem cells into the tumor bed, and metastasis. Melanoma LRP1 was found to enhance ERK activation, resulting in increased matrix metal-loproteinase (MMP)-9 RNA, protein, and secreted activity, a well-known modulator of melanoma metastasis. Restoration of LRP1 and tPA in the less aggressive, poorly metastatic B16F1 tumor cells enhanced tumor cell proliferation and led to massive lung metastasis in murine tumor models. Antimelanoma drug treatment induced tPA and LRP1 expression. tPA or LRP1 knockdown enhanced chemosensitivity in melanoma cells. Our results identify the tPA-LRP1 pathway as a key switch that drives melanoma progression, in part by modulating the cellular composition and proteolytic makeup of the tumor niche. Targeting this pathway may be a novel treatment strategy in combination treatments for melanoma.
Citation Format: Beate Heissig, Yousef Salama, Taro Osada, Yuko Tsuda, Satoshi Takahashi, Koichi Hattori. The fibrinolytic factor tPA drives LRP1-mediated melanoma growth and metastasis [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-105.
Abstract PO-123: Distinct subpopulations of osteosarcoma cells cooperate to establish lung metastases
Authors: Reinecke James B. , Hinckley John M. , Gross Amy C. , Cam Maren , Rajan Sanjana , Roberts Ryan D. 
Published: December 2020

Abstract
Four decades of intense multinational efforts to improve outcomes for children and teenagers with osteosarcoma have failed. Today, we still treat patients with a regimen first developed in 1982. The same 35-40% of young people diagnosed with osteosarcoma die from their disease, almost always from complications related to lung metastasis. Believing that therapies targeting lung metastasis could dramatically improve outcomes, we have sought to understand the mechanisms that drive lung colonization in this disease. We previously found that interactions with lung epithelium cause osteosarcoma cells to produce IL6 and CXCL8 and that this activity is necessary for metastasis. Inhibiting IL6 and CXCL8 signaling prevents metastasis entirely in 85% of mice with osteosarcoma. While conducting these studies, we learned that individual tumor cells react differently to signals from lung epithelium. Nearly all the IL6 and CXCL8 produced by osteosarcoma cells come from a small subset of cells. Interactions with pulmonary epithelium cause this discrete subset of tumor cells to produce large quantities of inflammatory cytokines, become strongly p21+, and stop proliferating. Early metastatic lesions consist almost entirely of cells with this phenotype, positioning them to orchestrate the development of the metastatic niche. Thus, we call these hypo-proliferative, cytokine-producing cells that survive early attrition "anchor cells." In the initial stages of metastasis, anchor cells alter the surrounding lung tissue in ways that facilitate subsequent colonization by tumor cells with proliferating phenotypes ("growth cells"). Growth cells then divide to create expanding, clinically-relevant metastasis. Importantly, one can leverage the biology of these anchor cells to develop rational targeting strategies. Anchor cells exhibit profound sensitivity to known senolytic agents. Combining these with conventional therapies (which effectively target growth cells) can eradicate established metastatic lesions and prevent new metastases from forming. These novel findings fundamentally alter our understanding of osteosarcoma and metastasis biology and have direct implications for approaches to treatment.
Citation Format: James B. Reinecke, John M. Hinckley, Amy C. Gross, Maren Cam, Sanjana Rajan, Ryan D. Roberts. Distinct subpopulations of osteosarcoma cells cooperate to establish lung metastases [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-123.
Abstract PO-132: CaTCH - A barcode-guided CRISPRa-inducible reporter to isolate clones from heterogeneous populations
Authors: Umkehrer Christian , Holstein Felix , Formenti Laura , Jude Julian , Froussios Kimon , Neumann Tobias , Cronin Shona M. , Haas Lisa , Lipp Jesse , Burkard Thomas R. , Fellner Michaela , Wiesner Thomas , Zuber Johannes , Obenauf Anna C. 
Published: December 2020

Abstract
The emergence of resistant cell clones to targeted therapies poses a significant issue in the treatment of metastatic melanoma. While these founding clones are often extremely rare in a starting population, their isolation and characterization holds unique potential for understanding disease processes, uncovering novel biomarkers and developing therapeutic concepts. The functional characterization of such founder clones and comprehensive comparisons to their post-selection counterparts requires live cells. To achieve this, we developed a novel lineage tracing tool termed CaTCH (CRISPRa tracing of clones in heterogeneous cell populations). CaTCH combines precise mapping of the lineage history of millions of cells with the ability to isolate any given clone alive from a complex population based on genetic barcodes. CaTCH thereby enables the retrospective isolation and analysis of founding clones from heterogeneous cell populations prior to evolutionary selection. In first applications, we use CaTCH to provide insights into the development of resistance to targeted cancer therapies. We demonstrate that CaTCH can be used to trace and isolate a single pre-existing therapy-resistant clone from a complex cancer cell population in vitro. Furthermore, we validate the utility of CaTCH for applications in vivo by investigating the origins of resistance to clinically relevant RAF/MEK inhibition in an immunocompetent melanoma mouse model. Here we find that most clones have the capacity to acquire resistance to combined RAF/MEK inhibitor therapy, indicating that resistance to this clinically relevant regimen is a universally achievable state in this model. We envision that CaTCH will address fundamental questions in basic and translational research (e.g., how cell identity states and trajectories are determined in therapy resistance, metastasis formation, tissue development and somatic cell re-programming), potentially revealing new vulnerabilities that can serve as targets for therapies.
Citation Format: Christian Umkehrer, Felix Holstein, Laura Formenti, Julian Jude, Kimon Froussios, Tobias Neumann, Shona M. Cronin, Lisa Haas, Jesse Lipp, Thomas R. Burkard, Michaela Fellner, Thomas Wiesner, Johannes Zuber, Anna C. Obenauf. CaTCH - A barcode-guided CRISPRa-inducible reporter to isolate clones from heterogeneous populations [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-132.
Abstract PR07: A systems biology approach to reprogramming drug-resistant breast cancer stem-like cells
Authors: Worley Jeremy , Ding Hongxu , Noh Heeju , Paull Evan , Bush Erin , Dalerba Piero , Sims Peter , Dela Cruz Fil , Kung Andrew , Califano Andrea 
Published: December 2020

Abstract
Breast cancer stem-like cells (CSCs) are hypothesized to be a cause of poor outcome in patients, and are drug-resistant in vitro and in PDX mice. We performed plate-based single-cell RNA sequencing (scRNA-seq) on flow sorted fresh tumor samples. These data were analyzed using our metaVIPER algorithm, which infers protein activity in a manner that is robust to the effects of noise and gene dropout. metaVIPER identified known breast CSC regulators, and analysis with our OncoTreat algorithm predicted several FDA approved drugs that could reprogram the breast CSCs into a state resembling that of differentiated tumor cells. We tested two of these predictions, ivermectin and albendazole, in TNBC PDX mice, and performed scRNA-seq on fresh tumor samples after 14 days of treatment. The results were exciting, as measured by single-cell entropy or lineage marker analysis. Breast CSCs were reprogrammed as predicted, while a tumor treated with a traditional chemotherapeutic (paclitaxel) had a dramatically higher proportion of CSCs. These results suggested a therapy in which cells are cyclically reprogrammed and treated with a conventional cytotoxic drug. This reprogram-kill-repeat therapy is being tested in TNBC PDX mice. We believe that the strategy developed here will prove to be a powerful tool for understanding and manipulating cell-state in heterogeneous populations.
Citation Format: Jeremy Worley, Hongxu Ding, Heeju Noh, Evan Paull, Erin Bush, Piero Dalerba, Peter Sims, Fil Dela Cruz, Andrew Kung, Andrea Califano. A systems biology approach to reprogramming drug-resistant breast cancer stem-like cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PR07.
Abstract IA04: Using white privilege to help end disparities
Authors: Maues Julia 
Published: December 2020

Abstract
Living with metastatic breast cancer since 2013, I have become engaged in cancer advocacy and connected with other advocates all over the country and the world. This work brought me close to a number of Black women with cancer, and I saw the realities they face with the double whammy of cancer and racism. I have always considered myself an ally to people of color and am passionate about social justice causes but am not free of racial prejudice being born and raised in a systematically racist society. It wasn’t until I experienced discrimination myself as a young woman with late-stage cancer that I realized how much unlearning and learning I have ahead of me about White privilege and racism against Black people. When a Black advocate called me and others out for not including the perspective of a person of color on a panel on researcher-advocate collaborations, I (after first making the mistake of feeling attacked and defensive) realized that White advocates have an important role in addressing disparities. While racism affects Black people, it isn’t a problem created by and kept alive by Black people. It is my responsibility as a White person who aspires for an equitable society to take a stand for representation of Black and LatinX people in the space that I have an influence in. In my case that space is cancer advocacy and unfortunately there are too many Black people living with cancer. My power is my voice in cancer advocacy, so I have pledged to not participate in any advocacy initiative that doesn’t include the experience of a person of color. I encourage every White person to evaluate their privilege and take a stand in the appropriate space using the pledge at https://www.change.org/p/diversity-and-inclusion-pledge-for-women-of-color.
Citation Format: Julia Maues. Using white privilege to help end disparities [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA04.
Abstract IA12: Cancer in LGBT populations: Differences, disparities, and strategies for change
Authors: Baker Kellen 
Published: December 2020

Abstract
In discussions of cancer research, prevention, and treatment, the needs and experiences of lesbian, gay, bisexual, and transgender (LGBT) people are routinely overlooked. The American Cancer Society estimates, however, that there are more than 130,000 newly diagnosed cases of cancer and more than 45,000 cancer deaths among LGBT people in the U.S. every year. Evidence indicates that LGBT populations are disproportionately affected by specific cancers, such as anal cancer in gay and bisexual men, breast cancer in lesbian women, and viral infection–induced cancers in LGB and transgender people. The drivers of these cancer disparities include risk factors that are often more common among LGBT people, such as tobacco use, nulliparity, and HIV. These risk factors are also compounded for LGBT populations by exposure to social determinants of health that include discrimination and other minority stressors—especially for Black, Indigenous, and other LGBT people of color, who experience discrimination that targets their race or ethnicity as well as their sexual orientation and/or gender identity—lower rates of insurance and other barriers to health care services, and inaccurate assumptions among providers about cancer risk and appropriate screenings, particularly for lesbian and bisexual women and transgender people. For LGBT people who have been diagnosed with cancer, a lack of cultural responsiveness in clinical settings and social and economic challenges outside the doctor’s office can exacerbate the difficulty of navigating cancer treatment.
Because data on sexual orientation and gender identity are not routinely collected in cancer registries, clinical records, and other sources of cancer data, the full spectrum of cancer risks, prevention, treatment, outcomes, and survivorship in LGBT communities remains unexplored. LGBT people are also often rendered invisible in cancer research by data collection that does not include sexual orientation or gender identity, by study protocols that make the tacit or overt assumption that all participants are cisgender and heterosexual, and by barriers to participation such as being overlooked in recruitment or even outright excluded from consideration.
This presentation provides an overview of cancer disparities in LGBT populations; describes patient-, provider-, and structural-level barriers to effective cancer prevention and treatment; and identifies promising opportunities to expand the evidence base and address LGBT cancer disparities.
Citation Format: Kellen Baker. Cancer in LGBT populations: Differences, disparities, and strategies for change [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA12.
Abstract IA31: Structural Inequities, Social Determinants, and Survivorship: Opportunities and Strategies to Advance Health Equity
Authors: Alcaraz Kassandra I. 
Published: December 2020

Abstract
Despite considerable progress against cancer in recent decades, disparities in cancer survivorship persist. Increasingly, upstream influences are recognized as key determinants of cancer-related disparities. However, predominant strategies often neglect to consider and/or address these influences, slowing progress toward achieving cancer health equity. This presentation will discuss an integrated framework that can be used to understand and address structural and social influences on disparities in cancer survivorship. Additionally, data from diverse sources will be used to illustrate the influence of social and structural factors on cancer-related outcomes. The presentation will underscore the importance of addressing structural inequities and social determinants to help cultivate equitable outcomes among cancer survivors.
Citation Format: Kassandra I. Alcaraz. Structural Inequities, Social Determinants, and Survivorship: Opportunities and Strategies to Advance Health Equity [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA31.