bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5920: Multi-cancer early detection with a spectroscopic liquid biopsy platform
Authors: Cameron James M. , Sala Alexandra , Antoniou Georgios , Brennan Paul M. , Conn Justin J. A. , Connal Siobhan , Palmer David S. , Smith Benjamin R. , Baker Matthew J. 
Published: June 2022

Abstract
The development of a robust multi-cancer early detection (MCED) test would be transformational within the cancer diagnostics field, as earlier detection is vital to inhibit disease progression, improve patient prognosis and reduce mortality rates. In this large-scale spectroscopic study, we present the Dxcover® Cancer Liquid Biopsy, the world’s first infrared spectroscopy-based blood test for the early detection of multiple cancers. The full cohort (n=2094) was comprised of patients with a confirmed cancer diagnosis (n=1543), symptomatic non-cancer patients (n=460) and healthy volunteers (n=91). For the cancer versus non-cancer classification, receiver operating characteristic analysis produced a mean curve with an area under the curve (AUC) value of 0.86. When adjusted for greater sensitivity, our model achieved 90% sensitivity with 61% specificity, and yielded a sensitivity of 56% with 91% specificity when tailored for higher specificity. We also tuned for maximized sensitivity or specificity, whilst the other parameter was fixed above a minimum value of 45% for the cross-validation result, based upon performance levels of currently available clinically benchmarked tests. This resulted in a 94% sensitivity where specificity was 47%, and a 94% specificity with 48% sensitivity. The overall detection rates were 93% for stage I, 84% for stage II, 92% for stage III and 95% for stage IV for the sensitivity-tuned model. The specificity-tuned model detected 90% of non-cancer patients accurately, resulting in few false negatives (54/551). For the binary classifiers of individual cancer types against symptomatic control patients, promising AUC values were reported for all cancers: brain (0.90), breast (0.74), colorectal (0.91), kidney (0.91), lung (0.90), ovarian (0.85), pancreatic (0.81) and prostate (0.85). Importantly, the detection rates did not vary significantly according to cancer stage, suggesting the technology is very effective at detecting early-stage tumors, which is a necessity for MCED tests.
Citation Format: James M. Cameron, Alexandra Sala, Georgios Antoniou, Paul M. Brennan, Justin J. A. Conn, Siobhan Connal, David S. Palmer, Benjamin R. Smith, Matthew J. Baker. Multi-cancer early detection with a spectroscopic liquid biopsy platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5920.
Abstract 5949: Aspirins metabolites inhibit human colon cancer cell growth: Potential role in colorectal cancer prevention
Authors: Tummala Poojitha , Sankaranarayanan Ranjini , Dachineni Rakesh , Bhat Jayarama Gunaje 
Published: June 2022

Abstract
Aspirin’s role in colorectal cancer (CRC) prevention is evidential from several epidemiological data. Numerous theories and targets have been proposed, a consensus has not been reached regarding its mechanism of action. One of the unexplored area in aspirin’s CRC prevention is the role of Dihydroxy benzoic acids (DHBAs), which are generated from aspirin’s metabolism by gut microflora and cytochrome P450 (CYP450). Out of the screened DHBAs, 2,3-DHBA and 2,5-DHBA showed concentration dependent inhibition of CDK1, CDK2, CDK4 and CDK6 enzyme activity in-vitro. We demonstrated that 2,3-DHBA and 2,5-DHBA inhibits CDK-1 enzyme activity beginning at 500 µM, while CDK2 and CDK4 activity was inhibited only at higher concentrations (&gt;750 µM). 2,3-DHBA inhibited CDK6 enzyme activity from 250 µM, while 2,5-DHBA inhibited its activity &gt;750 µM. Using colony formation assays, we further demonstrated the role of 2,3-DHBA and 2,5-DHBA in cancer cell cycle inhibition in 3 different cancer cell lines. Out of the 2 DHBAs, 2,5-DHBA was highly effective in inhibiting clonal formation in HCT-116 and HT-29 CRC cell lines (250-500 µM), and in the MDA-MB-231 breast cancer cell line (~100 µM); whereas both aspirin and salicylic acid failed to inhibit all four CDKs and colony formation. Based on the present results, it is suggested that 2,3-DHBA and 2,5-DHBA may contribute to the chemopreventive properties of aspirin, possibly through the inhibition of CDKs. The present data and the proposed mechanisms should open new areas for future investigations.
Citation Format: Poojitha Tummala, Ranjini Sankaranarayanan, Rakesh Dachineni, Jayarama Gunaje Bhat. Aspirins metabolites inhibit human colon cancer cell growth: Potential role in colorectal cancer prevention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5949.
Abstract 5975: Dual-channel near-infrared fluorescence imaging for simultaneous identification of lung cancer and intersegmental plane
Authors: Quan Yu Hua , Bao Kai , Kim Kyungsu , Wang Haoran , Yokomizo Shinya , Park G. Kate , Choi Byeong Hyeon , Rho Jiyun , Kim Chungyeul , Choi Hak Soo , Kim Hyun Koo 
Published: June 2022

Abstract
Intraoperative delineation of the tumor with minimal negative margins is the holy grail of lung cancer surgery. Segmentectomy is a minimal resection surgery required for elderly patients or small sized early-stage lung cancer patients, in which accurate detection of tumor margins with simultaneous identification of the lung intersegment plane is the key to success. However, non-small cell lung cancer is difficult to detect intraoperatively, and the identification of intersegmental plane is challenging during minimal resection surgery. Here, we report dual-channel image-guided lung cancer surgery using renal clearable and physiochemically stable targeted fluorophores to visualize the tumor margins and intersegmental plane separately with different colors but simultaneously: cRGD-ZW800-PEG (800 nm channel) allows for tumor-specific targeting and ZW700-1C (700 nm channel) for discrimination of segmental planes. Armed with the dual-channel imaging, image-guided surgery enables complete tumor resection with minimal negative margins that can reduce the recurrence rate and increase the survival rate of lung cancer patients.
Citation Format: Yu Hua Quan, Kai Bao, Kyungsu Kim, Haoran Wang, Shinya Yokomizo, G. Kate Park, Byeong Hyeon Choi, Jiyun Rho, Chungyeul Kim, Hak Soo Choi, Hyun Koo Kim. Dual-channel near-infrared fluorescence imaging for simultaneous identification of lung cancer and intersegmental plane [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5975.
Abstract 6009: Developing drug-induced resistant tumor models for efficacy evaluation of next-generation anticancer therapies
Authors: Ni Ting , Liu Gaoxiang , Huo Tongxin , Shi Wenting , Gu Qingyang , Ji Qunsheng 
Published: June 2022

Abstract
The therapeutic landscape of cancer has been transformed over the last few decades. Our understanding of cancer and its therapeutic approach has improved greatly due to advanced cancer biology, functional imaging and next-generation sequencing. One of the key challenges in cancer therapy is how to effectively kill cancer cells while leaving normal cells intact. As specific oncogenic drivers have been successfully identified, targeted treatments have achieved great success in clinical practice. However, acquired drug resistance remains the major barrier to sustained success of targeted cancer therapy. Those patients who initially respond well to targeted therapies eventually become resistant to the treatments. Uncovering the underlying mechanism would help develop novel therapies that overcome the drug resistance.To mimic the clinical resistance after long-term drug treatment, we established a panel of drug-induced resistant tumor models by continuous dosing of targeted drugs to tumor-bearing mice or cancer cell lines, covering a series of first-line targeted drugs including Sotorasib, Palbociclib, Ibrutinib, Capmatinib, Fulvestrant, Tamoxifen and TDM-1. Resistant models were derived from sensitive ones harboring specific oncogenic drivers. After treated with targeted drugs and passaged several times, resistant models exhibited stable resistance phenotype. Given that target gene mutation, alternative pathway activation or tumor microenvironment evolution could promote therapy resistance and cancer progression, we performed transcript and protein analysis to explore the molecular mechanism, and evaluated the potential therapeutic strategies overcoming drug resistance in the established models. Taken together, drug-induced resistant tumor models provide a promising opportunity to the better understanding of drug resistance mechanisms and to the accelerated development of next-generation anticancer agents.
Citation Format: Ting Ni, Gaoxiang Liu, Tongxin Huo, Wenting Shi, Qingyang Gu, Qunsheng Ji. Developing drug-induced resistant tumor models for efficacy evaluation of next-generation anticancer therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6009.
Abstract 6018: Expansion of mouse mammary epithelial stem cells in serum-free organoid growth medium
Authors: Rowbotham David , Rothwell Samantha , Eaves Allen C. , Louis Sharon A. , Stingl John 
Published: June 2022

Abstract
Growing mammary epithelial cells as organoids in a three-dimensional (3D) cell culture environment represents a more physiological model system than conventional 2D adherent cell culture systems for studying many different aspects of mammary epithelial cell biology. We have developed MammoCult™ Organoid Growth Medium (Mouse), a serum- and phenol red-free medium for the long-term propagation of organoids from mouse mammary tissue. To initiate the cultures, mouse mammary glands are resected and enzymatically dissociated sequentially in Gentle Collagenase/Hyaluronidase, trypsin, and dispase/DNase I to generate a single-cell suspension, and 4.5 x 103 of the liberated cells are then embedded in Corning® Matrigel® and maintained in MammoCult™ Organoid Growth Medium (Mouse). Alternatively, freshly dissociated mammary cells can be expanded in adherent culture in EpiCult™ Plus Medium prior to seeding into Matrigel®. Approximately 8.4 ± 0.6% (mean ± SEM; n=10) of the freshly dissociated cells seeded in the Corning® Matrigel® will proliferate and generate organoids that are typically &gt; 200 µm in diameter and have a highly branched morphology, although organoids with a cystic morphology are also observed. Immunostaining of these branched organoids reveals that they are composed of a polarized epithelium made up of keratin (K) 8-expressing luminal cells and K5/14-expressing basal cells (n=7). Organoids upregulate transcripts for caseins (Csn1s1, Csn2), whey acidic protein (Wap), and lactoferrin (Ltf) upon stimulation with prolactin, hydrocortisone, and insulin (n=4). These multilineage organoids can be established from multiple inbred mouse strains, including C57Bl6/J, FVB, BALB/c, and CD-1. Organoids can be passaged every 10 - 14 days as small fragments at a 1:3 to 1:4 split ratio, and can be maintained for a minimum of 10 passages while still maintaining multilineage potential and a normal karyotype. These results demonstrate that MammoCult™ Organoid Growth Medium (Mouse) efficiently generates and expands mammary epithelial cell-derived organoids and offers researchers a novel tool for in vitro mammary studies.
Citation Format: David Rowbotham, Samantha Rothwell, Allen C. Eaves, Sharon A. Louis, John Stingl. Expansion of mouse mammary epithelial stem cells in serum-free organoid growth medium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6018.
Abstract 6027: Layered 3D co-cultured tumor model including vascularized stromal tissue may reflect drug sensitivities in vivo tumor
Authors: Takahashi Yuki , Kitano Shiro , Shinozaki Eiji , Nagayama Satoshi , Katayama Ryohei , Fujita Naoya 
Published: June 2022

Abstract
Background: Multiple 3D culture models have been reported as a superior tumor model than 2D culture. The importance of interaction between cancer and stromal cells has been widely recognized in tumor progression and resistance to treatment. Therefore, ex vivo model recapturing the tumor microenvironment is needed to evaluate the drug efficacy under the condition imitating the patient tumor tissue. Purpose: We developed a unique 3D co-cultured tumor model with stromal tissues containing a microvascular network. Here, we investigated drug sensitivity in conventional 2D culture, our 3D co-cultured model and in vivo tumor.
Methods: Drug sensitivity and gene expression on our model were evaluated using patient-derived cancer cells (PDC) established from colorectal cancer (CRC) patients in JFCR. The characteristics were compared with those of conventional 2D cultured cells or patient-derived xenograft (PDX).
Results: In our 3D model, the drug sensitivities tended to be decreased in comparison with those of 2D. However, some drugs presented potent efficacy in our 3D model rather than 2D, and such drugs showed significant tumor growth suppression or tumor regression in vivo. Transcriptome profiles of our 3D model showed relatively higher similarity to those of in vivo tumors than those of 2D.
Conclusion: Our study proposed the unique 3D co-cultured tumor model which may enable more accurate evaluation of drug sensitivities reflecting the in vivo circumstances.
Citation Format: Yuki Takahashi, Shiro Kitano, Eiji Shinozaki, Satoshi Nagayama, Ryohei Katayama, Naoya Fujita. Layered 3D co-cultured tumor model including vascularized stromal tissue may reflect drug sensitivities in vivo tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6027.
Abstract 603: Discovery of CD200R1 as a novel immuno-oncology target using pleiotropic signals from 23andMe’s genetic and health survey database
Authors: Fang Xin , Chung Wei-Jen , Fenaux Jill , Chen Alice , Batada Nizar , Schmidt Maike , Majeed Sophia R. , Kumar Sushil , Pitts Steven 
Published: June 2022

Abstract
Using large genetic and phenotypic datasets, 23andMe has developed a novel immuno-oncology target-identification platform. 23andMe has assembled a genetic database of nearly 12 million individuals, with 80 percent consented to research, coupled with health survey data comprising billions of responses. We identified hundreds of shared GWAS signals across phenotypes that appear to be driven by pleiotropic causal variants whose direction of effect (risk versus protection) systematically differs across cancer and autoimmune diseases including a signal linked to a clinically validated immune checkpoint receptor. This observation suggests that genes linked to such signals may be utilized by tumor cells to evade the immune system. We hypothesize that such signals indicate nodes of critical importance for anti-tumor immune response. By utilizing expression quantitative trait loci (eQTLs) and coding single nucleotide polymorphisms (SNPs) to link these signals to causal effects on genes, we identified CD200R1, an inhibitory receptor expressed on T cells and myeloid cells, as an immune checkpoint target. Immune-oncology associations were observed in multiple components of the CD200R1 pathway, including the receptor, its cognate ligand, CD200, and its downstream adaptor protein, DOK2. Expression of CD200R1 was validated in tumor-infiltrating lymphocytes using bulk and single-cell RNA-seq from various tumor types. This genetics-driven target discovery platform facilitated the development of a fully humanized monoclonal antibody that binds CD200R1 on immune cells with high affinity and enhances killing of tumor cells expressing CD200.
[X. F. and W-J. C. contributed equally to this work.]
Citation Format: Xin Fang, Wei-Jen Chung, Jill Fenaux, Alice Chen, Nizar Batada, Maike Schmidt, Sophia R. Majeed, Sushil Kumar, Steven Pitts. Discovery of CD200R1 as a novel immuno-oncology target using pleiotropic signals from 23andMe’s genetic and health survey database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 603.
Abstract 6117: Clinical and molecular correlates of immune marker profiling and PD-L1 expression in non-small cell lung cancer
Authors: Shi Yunfei , Lei Youming , Liu Yinqiang , Duan Jin , Zhao Wei , Zhang Fujun , Lv Guoli , Wu Qian , Wu Mengmeng , Yin Jiani C. , Shao Yang 
Published: June 2022

Abstract
Background: Understanding the genomic landscape and tumor immune microenvironment of non-small cell lung cancer (NSCLC) may provide critical insight into the biology of tumor immune response and novel strategies for overcoming immunotherapy resistance. The association of clinical and genomic features with tumor immune microenvironment in NSCLC patients remains unclear.
Methods: In this retrospective cohort study, we profiled PD-L1 and immune cell marker expressions and performed targeted next-generation sequencing (Geneseeq Technology Inc., Nanjing) of baseline tissue samples from 100 NSCLC patients. The levels of CD8+, CD68+ and HLA-DR+ immune cells were assessed by multiplexed immunohistochemistry (mIHC) assay. Immune microenvironment markers and PD-L1 expression was analyzed for associations with clinical features and mutations at both the single gene and pathway levels.
Results: Mutations in TP53, SETD2, RET and the p53 signaling pathway were significantly associated with high PD-L1 high expression (P&lt;0.001; P=0.002; P=0.04; P=0.001, respectively). Patients with high PD-L1 expression showed a trend towards higher stromal CD8+ lymphocytes (P=0.1), Alterations in T cell and B cell pathways were also associated with increased stromal CD8+ T cells (P=0.03 and P=0.08, respectively). The infiltration of intratumoral CD68(+)HLA-DR(+) M1-like macrophages positively correlated with high PD-L1 high expression (P=0.07), Hippo pathway alterations (P=0.06). By contrast, the levels of intratumoral M1-like macrophages negatively correlated with alterations in the NRF2/KEAP1 pathway (P=0.005), which might account for the poor immunotherapy outcome in this subset of patients.
Conclusions: Our study demonstrates the complex relationship between gene mutations and aberrations in signaling pathways with the immune microenvironment in NSCLC. Specific molecular features are associated with unique immune profiles and may impact the response to immune checkpoint inhibitors.
Citation Format: Yunfei Shi, Youming Lei, Yinqiang Liu, Jin Duan, Wei Zhao, Fujun Zhang, Guoli Lv, Qian Wu, Mengmeng Wu, Jiani C. Yin, Yang Shao. Clinical and molecular correlates of immune marker profiling and PD-L1 expression in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6117.
Abstract 6118: Tumor-derived GDF-15 promotes immune escape of tumors by functional alteration of the myeloid compartment
Authors: Haake Markus , Haack Beatrice , Genßler Sabrina , Weigandt Julia , Auer Marlene , Thiemann Vincent , Haq Wahid M. , Haag Melanie , Wedekink Florian , Fischer Birgitt , Klar Kathrin , Wölfl Matthias , Schuberth-Wagner Christine , Wischhusen Jorg 
Published: June 2022

Abstract
Background: Growth and differentiation factor 15 (GDF-15), a divergent member of the TGF-β protein superfamily, shows low physiological baseline expression. GDF-15 is, however, strongly upregulated during pregnancy. It is further induced in stressed and damaged tissues, where it limits immune infiltration and inflammation. In solid tumors, GDF-15 was shown to be a key inhibitor of T-cell infiltration. While this might already explain the strong correlation between GDF-15 overexpression and poor survival with or without checkpoint-based immunotherapy, effects of GDF-15 on dendritic cells and monocytes may further shape the tumor microenvironment.
Methods: To analyze the impact of GDF-15 in murine tumor models, GDF-15 was either deleted by CRISPR/CAS9 gene editing or neutralized by administration of a blocking antibody. Effects on tumor growth were recorded and the composition of the tumor microenvironment was characterized by flow cytometry. More detailed insight into tumor-immune interactions was obtained via the CrownBio Mouse I/O RNA-Seq Panel. Specific effects on polarization of innate and on antigen-specific priming of adaptive immune cells were confirmed in cellular assays in vitro.
Results: Tumor-derived GDF-15 modulates the tumor microenvironment by inhibiting infiltration and activation of myeloid cells. GDF-15 thereby impairs the induction of antitumoral immune responses. Deletion of GDF-15 enhances infiltration of innate cells into immune-excluded tumors, supports the priming of naïve T cells by dendritic cells and generates a pro-inflammatory tumor microenvironment. In vitro, GDF-15 inhibits DC maturation and synapse formation, thus preventing successful T-cell activation. Moreover, GDF-15 interferes with M1 polarization of macrophages.
Conclusion: GDF-15 secretion helps tumors to generate a microenvironment that is poorly infiltrated by immune cells. GDF-15 further polarizes myeloid cells towards a tumor-promoting, anti-inflammatory phenotype. By inducing a more pro-inflammatory tumor phenotype, anti-GDF-15 antibodies may synergize with other immunotherapeutic agents. A clinical trial combining anti-GDF-15 (CTL002) with anti-PD-1 (NCT04725474) is ongoing.
Citation Format: Markus Haake, Beatrice Haack, Sabrina Genßler, Julia Weigandt, Marlene Auer, Vincent Thiemann, Wahid M. Haq, Melanie Haag, Florian Wedekink, Birgitt Fischer, Kathrin Klar, Matthias Wölfl, Christine Schuberth-Wagner, Jorg Wischhusen. Tumor-derived GDF-15 promotes immune escape of tumors by functional alteration of the myeloid compartment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6118.