bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5021: Circulating mutated and methylated tumor DNA detection for colorectal cancer diagnosis
Authors: Bains Pushpinder Kaur , Kulak Mikhail , Cui Zhen , Babu Alisha , Tran Stella , Zhang Aiguo , Sha Michael 
Published: March 2024

Abstract
Introduction: Detection of mutation and methylation patterns in liquid biopsies has emerged as a promising approach for screening early-stage cancers. We have developed a targeted next-generation sequencing (NGS)-based assay “OptiSeqTM Colorectal Cancer Detection Panel”, a combined platform for assessing mutation and methylation in both low-quantity (plasma cfDNA) and low-quality formalin-fixed paraffin-embedded (FFPE) tissue for colorectal cancer (CRC) detection.
Methods: The OptiSeqTM Colorectal Cancer Detection Panel targets 442 SNVs and 434 CpG sites to detect circulating tumor DNA (ctDNA) in early-stage patients. With this panel, we profiled 6 early-stage and 6 metastatic CRC samples (matching cfDNA and FFPE) along with 2 primary colon specimens with adjacent normal tissue DNA. We also profiled 2 matching cfDNA and FFPE samples from precancerous adenomas (advanced adenomas (AA)) and 6 AA FFPE tissue DNA. In addition, we characterized the mutation and methylation pattern in 10 CRC fresh-frozen tissue DNA samples. For healthy individuals, we profiled 12 normal colon FFPE samples and 10 plasma cfDNA. The clinical performance for the CRC detection panel was calculated using AA, CRC, and cancer-free individuals.
Results: For CRC early and metastatic matching cfDNA and FFPE samples, clinical samples testing showed that the CRC detection panel had a sensitivity of 100% (95% CI: 69.8-100.0) and specificity of 100% (95% CI: 81.5-100). For precancerous AA FFPE tissues, combined DNA mutation and methylation increased the CRC detection sensitivity to 100% (95% CI: 51.6-100.0) and specificity to 100% (95% CI: 61.8-100). More clinical samples testing is underway.
Conclusion: We have developed the targeted NGS-based panel to detect clinically relevant mutation and methylation patterns and demonstrate its potential using the combined genetic and epigenetic markers making it a highly sensitive assay for early CRC diagnosis.
Citation Format: Pushpinder Kaur Bains, Mikhail Kulak, Zhen Cui, Alisha Babu, Stella Tran, Aiguo Zhang, Michael Sha. Circulating mutated and methylated tumor DNA detection for colorectal cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5021.
Abstract 5026: Microfluidic capillary electrophoresis optimization of high-throughput cfDNA and pDNA measurements for enabling cancer diagnostics and gene therapy development
Authors: Mehta Dipti , Gautam Gayatri , de Pena Adriana Coll , Frej Menel Ben , Tripathi Anubhav , White James 
Published: March 2024

Abstract
Rapid and accurate electrophoresis characterization can be an important tool for cancer researchers and therapy manufacturers. Advances in NGS of low molecular weight cfDNA for diagnostics may benefit from high-throughput checks of cfDNA sample quality with ultra-low quantities of sample. On the other hand, high molecular weight pDNA characterization and separation of supercoiled, linear and open-linear conformations aids in quality control of these payloads for personalized medicine and in particular cancer vaccines and gene therapies. This work shows optimization of established microfluidic capillary electrophoresis to enable the measurement of cfDNA and pDNA. cfDNA study was completed on plasma reformatted from whole blood tubes using Janus G3 Blood iQ workstation. The cfDNA samples were extracted using commercial cfDNA extraction kits. Using a LabChip GX Touch Biologics Characterization system: gel optimization, marker solution dilution, and inclusion of a low molecular weight DNA standard improved the sensitivity of cfDNA detection. This afforded a new electrophoresis assay with linear dynamic range of 50-1000 pg/uL and sensitivity of &lt;25 ng/uL. pDNA, supercoiled DNA and linear DNA standards were prepared according to published procedures and measured on the LabChip GX Touch Biologics Characterization system. A new ladder system was developed along with gel optimization to develop a new High Sensitivity Assay platform capable of baseline resolving each conformation and providing fragment DNA sizing and purity information. Taken together, this work provides researchers new tools to leverage automated microfluidic capillary electrophoresis for DNA analysis in both upstream and manufacturing processes.
Citation Format: Dipti Mehta, Gayatri Gautam, Adriana Coll de Pena, Menel Ben Frej, Anubhav Tripathi, James White. Microfluidic capillary electrophoresis optimization of high-throughput cfDNA and pDNA measurements for enabling cancer diagnostics and gene therapy development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5026.
Abstract 5054: Optimization and evaluation of an FFPE dual extraction protocol for next-generation sequencing applications
Authors: Hong Rebecca , Chu Jieying , Hsiao Steven , Whang Daniel , Rivera Steven P. , Xie Heng , Guo Jiannan 
Published: March 2024

Abstract
Formalin-fixed paraffin-embedded (FFPE) biopsies are highly valuable and widely used tissue specimens for clinical diagnostics. However, obtaining sufficient and high-quality nucleic acid material from limited FFPE samples presents a challenge for downstream molecular analysis, such as next-generation sequencing (NGS). We present an optimized sequential extraction method that generates high-quality DNA and RNA from a single set of input tissues that is automatable and operation-friendly. This workflow performs well with reduced FFPE tissue input and efficiently supports various high-throughput clinical NGS applications. The DNA/RNA yield, quality, purity, and impacts on NGS assay performances were on par or better than an existing validated comparator extraction method. With comparable FFPE input, the new method demonstrated a superior extraction performance with significantly higher yield, quality, and purity. For DNA, NGS libraries were made with two different library preparation methods: a TA-ligation-based method and a single-strand-based method, followed by hybrid capturing and sequencing. The DNA from the new extraction method demonstrated a superior library conversion rate and improved target enrichment uniformity with both chemistries. This provides the potential of reduced input requirements, allowing very limited tissue, such as fine needle aspirate or core needle biopsy, for clinical NGS testing. The sequencing results were highly concordant between the existing and new extraction methods when the extracted DNA was subjected to a validated comprehensive genomic profiling (CGP) clinical test, demonstrating the quality and robustness of the extraction. For RNA, NGS libraries were made following the validated CGP clinical test with hybrid capturing, and the results were comparable between the two extraction methods. In conclusion, an FFPE extraction method was optimized to allow more clinical biopsy samples to be tested with different NGS workflows, providing a better diagnostic value for patient care.
Citation Format: Rebecca Hong, Jieying Chu, Steven Hsiao, Daniel Whang, Steven P. Rivera, Heng Xie, Jiannan Guo. Optimization and evaluation of an FFPE dual extraction protocol for next-generation sequencing applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5054.
Abstract 508: Determining the nuclear and cytoplasmic function of BMI-1 in diffuse intrinsic pontine glioma during M phase
Authors: Pang Hao-Han , Umaru Banlanjo , Kumar Shiva Senthil , Drissi Rachid 
Published: March 2024

Abstract
Diffuse Intrinsic Pontine Glioma (DIPG) represents one of the most aggressive malignancies of the central nervous system, predominantly affecting children. DIPG is a particularly poor prognosis brain tumor with a median overall survival of less than 1 year. Hence, there is an urgent need to develop novel therapies that not only improve outcome but mitigate long-term complications in children with DIPG. The protein BMI-1, a critical component of the Polycomb Repressive Complex 1 (PRC1), is a proto-oncogene implicated in development, stemness of normal and malignant cells, and self-renewal. BMI-1 has emerged as a potential therapeutic target in DIPG; however, its role in DIPG tumorigenesis and progression remains elusive. We have previously shown that PTC596, a potent BMI-1 modulator, induces chromosome scattering, M phase cell-cycle arrest, BMI-1 phosphorylation and translocation to the cytoplasm leading to the inhibition of its PRC1 canonical function and cell death. These findings imply the induction of the spindle assembly checkpoint (SAC), thereby preventing mitotic exit followed by BMI-1 phosphorylation, probably at multiple sites, suggesting a survival role of BMI-1 in M phase in DIPG. The objective of the present study is to delineate the molecular pathways governing BMI-1 function during M phase and to establish the temporal sequence of these biochemical events related to BMI-1. Our data demonstrated that following PTC596 treatment, BMI-1 is actively transported from the nucleus to the cytoplasm. Furthermore, we observed colocalization of BMI-1 with COX4 in the mitochondria during M phase. Moreover, using Alphafold prediction model, BMI-1 could interact with CRM1 transporter. These findings suggest a potential PRC1-independent role of BMI-1 during early M phase required for DIPG proliferation. We are currently investigating potential pathways involved in BMI-1 nuclear-cytosol translocation through bioinformatic analyses, protein-protein interaction simulations, and pharmacological inhibitor assays. Collectively, these studies aim to elucidate the molecular mechanisms underlying BMI-1 functions in DIPG, thereby potentially paving the way for the development of targeted therapeutic strategies related to M phase progression.
Citation Format: Hao-Han Pang, Banlanjo Umaru, Shiva Senthil Kumar, Rachid Drissi. Determining the nuclear and cytoplasmic function of BMI-1 in diffuse intrinsic pontine glioma during M phase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 508.
Abstract 5087: ILB-3101, a novel B7H3-targeting ADC with Eribulin as payload, demonstrates strong tumor killing activities and favorable PK/TOX profile in preclinical evaluation
Authors: Shang Yushuan , Qiu Junzhuan , Xin Yanfei , Zhao Min , Liu Qiang , Wang Zhengsheng , Gong Xiaojing , Xu Yan , Li Yan , Xia Mingde , Chen Rulei 
Published: March 2024

Abstract
B7H3, a B7 family member of immune checkpoint proteins, is overexpressed in a broad spectrum of malignant tumors. It has become an attractive target for cancer therapies in recent years. ILB-3101, a potential best-in-class ADC, was constructed by conjugating a potent mitotic inhibitor Eribulin to a proprietary anti-B7H3 mAb through a proprietary linker. This ADC molecule has been developed and preclinically evaluated as both the 1st line ADC treatment with B7H3 expressed patients in Eribulin sensitive cancer types and the later line treatment for patients whose cancer are B7H3 positive but TopoI inhibitor resistant.
The humanized antibody of ILB-3101 is IgG1 type and shows high affinity to both human and monkey B7H3 proteins. It also shows better internalization than benchmark antibodies such as that of DS-7300 analog. The DAR value of ILB-3101 is 3.5. ILB-3101 has potent and dose-dependent cytotoxicity to B7H3-positive tumor cells and shows better activities than DS-7300 analog as positive control. In vivo studies based on xenograft tumor models reveal that ILB-3101 has potent anti-tumor activities in various tumor types including TNBC, sarcoma, ovarian cancer and AML etc., which are superior or comparable to DS-7300 analog. Furthermore, ILB-3101 shows strong anti-tumor activity on Dxd based ADC resistant tumors in xenograft tumor models. The PK study of ILB-3101 in cynomolgus monkeys shows dose-dependent exposure and desirable PK profile. ILB-3101 was well tolerated in cynomolgus monkeys with HNSTD at 6 mg/kg. No serious adverse events were observed, and the main safety findings were limited and reversible hematological and immunological effects, which are consistent with the safety profile of Eribulin as an approved chemotherapy.
The in vitro and in vivo preclinical results above demonstrate that ILB-3101 has good efficacy and safety profile and it is a promising and potentially best-in-class B7H3 targeting ADC drug candidate. ILB-3101 is worthy of further translational research and clinical trials. Its IND application has been submitted in China, followed by US FDA filing soon.
Citation Format: Yushuan Shang, Junzhuan Qiu, Yanfei Xin, Min Zhao, Qiang Liu, Zhengsheng Wang, Xiaojing Gong, Yan Xu, Yan Li, Mingde Xia, Rulei Chen. ILB-3101, a novel B7H3-targeting ADC with Eribulin as payload, demonstrates strong tumor killing activities and favorable PK/TOX profile in preclinical evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5087.
Abstract 5091: Response to neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective observational study
Authors: Li Jinsong , Li Bowen , Xie Shule , Cao Haotian , Lin Zhaoyu , Li Qunxing , Fan Song 
Published: March 2024

Abstract
Background: This study aims to investigate the effectiveness of neoadjuvant chemoimmunotherapy (NACI) regimens in treating advanced oral squamous cell carcinoma (OSCC).
Methods: We analyzed clinicopathologic features of advanced OSCC patients who received PD-1 inhibitors in combination with carboplatin and paclitaxel before surgical tumor resection between 2020 and 2022. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and pathologic response were used to evaluate the efficacy of the NACI treatment. Adverse events apparently related to NACI treatment were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier survival curves and compared using the log rank test. Additionally, we calculated the area under curve (AUC) to compare the predictive value of PD-L1 expression with baseline serum lipid biomarkers for patient response.
Results: Our analysis involved 104 advanced OSCC patients who received NACI. Notably, the top three grade 1-2 treatment-related adverse events (TRAEs) were Alopecia (104; 100%), Anemia (81; 77.9%) and Pruritus (62; 59.6%). Only one patient developed grade 3-4 TRAEs due to increased aminotransferases. The pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. Importantly, patients achieving MPR exhibited higher CPS. The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol (TC) level. Our findings from DFS and OS suggested that patients who underwent NACI before surgery experienced improved survival compared to those who accepted the surgery alone.
Conclusions: The data from this study proved evidence that NACI treatment is safe and encouragingly efficacious in treating advanced OSCC patients.
Citation Format: Jinsong Li, Bowen Li, Shule Xie, Haotian Cao, Zhaoyu Lin, Qunxing Li, Song Fan. Response to neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective observational study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5091.
Abstract 5097: Effectiveness and safety of atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: A multicenter, retrospective real-world study in China
Authors: Zhang Hui , Shao Minghua , Tan Binbin , Fu Yin , Yuan  , Chen Hailei 
Published: March 2024

Abstract
Background: Atezolizumab plus bevacizumab (Atezo+Bev) has shown better benefits than sorafenib as the first-line treatment for unresectable hepatocellular carcinoma (uHCC) in IMbrave 150. However, the real-world evidence of Atezo+Bev in uHCC is limited, especially in China. We aimed to investigate the real-world effectiveness and safety of Atezo+Bev in Chinese patients with uHCC.
Methods: Patients with uHCC treated with Atezo+Bev were included at 5 centers in China from Jan. 2021 to Jan. 2023. Overall response (ORR), organ-specific response rate (OSRR), disease control rates (DCR), time to disease progression (TPP), progression-free survival (PFS), metastasis-specific PFS and overall survival (OS) were calculated.
Results: Among 48 patients, the median age was 58.4 years with 85.4% being male. A total of 35 and 13 patients received Atezo+Bev as 1st and 2nd line treatment, respectively. The median number of treatment cycles were 8, and 27 (56.3%) patients received locoregional therapies. Detailed treatment response is in the Table. The overall ORR and DCR assessed by mRECIST were 60.4% and 75.0%, while the intra- and extrahepatic OSRR were 59.4% and 62.5%, respectively. With a median follow-up of 14.5 months, the median PFS was 8.5 months (95%CI: 4.4, 11.2) in 1st line setting and 5.1 months (95%CI: 2.1, 7.9) in 2nd line setting. Median intra- and extrahepatic metastasis-specific PFS were 7.9 and 7.6 months, respectively. Median overall TTP was 7.6 months. The median OS was not reached. A total of 36 patients (75%) experienced any grade adverse events, most commonly being thrombocytopenia (27.1%, n=13), lymphopenia (25%, n=12) and abnormal liver function (14.6%, n=7).
Conclusion: This study confirmed effectiveness and safety of Atezo+Bev in the 1st line treatment of uHCC, and observed its potential in 2nd line in a real-world setting. Further studies are warranted to confirm these observations and refine treatment strategies.
Table. Treatment response N (%) Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(N=48) Modified RECIST(N=48) Complete response (CR) 7 (14.6) 9 (18.8) Partial response (PR) 12 (25.0) 20 (41.7) Stable disease (SD) 15 (31.2) 7 (14.6) Progressive disease 11 (22.9) 12 (25.0) Not evaluated 3 (6.2) 0 ORR (CR+PR) 19 (39.6) 29 (60.4) DCR (CR+PR+SD) 34 (70.8) 36 (75.0)
Citation Format: Hui Zhang, Minghua Shao, Binbin Tan, Yin Fu, Yuan, Hailei Chen. Effectiveness and safety of atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: A multicenter, retrospective real-world study in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5097.
Abstract 5111: Rational synergistic radiosensitization strategies for group 3 medulloblastoma
Authors: Povilaikaite Julija , Stitz Kaitlin , Austin Nikhita , Ramaswamy Vijay 
Published: March 2024

Abstract
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. MB is comprised of 4 groups, termed Wnt, Shh, Group 3 and Group 4, each characterized by distinct molecular and clinical profiles. MYC-amplified Group 3 MB is associated imminent fatal metastatic relapse following standard treatment approaches, which currently include surgery, craniospinal irradiation and chemotherapy, highlighting an urgent need for identification of therapeutic vulnerabilities for these tumours. As such, using 4 novel patient-derived models of Group 3 MB that faithfully recapitulate the molecular and histological tumor characteristics, we characterised response to radiation of Group 3 MB in vitro to show that these tumors do not possess intrinsic radiation resistance. Furthermore, cumulative radiation experiments do not increase bulk radiation resistance in MB cells, highlighting the contribution of dynamic cell states to radiation response. In contrast, exposure to radiation leads to changes in cell clonogenic capacity as measured by limited dilution assays. Furthermore, RNA-seq data uncovered altered transcriptomic programs in response to cumulative radiation treatment. In particular, we observe differential regulation of genes encoding potassium ion channels and their regulators as well as genes encoding ECM and cell adhesion proteins. As part of our goal to evaluate the current multimodal treatment strategy of MB, we also show that a set of standard chemotherapeutic agents (etoposide, thiotepa and lomustine) currently used in the clinic do not produce a potent response at optimal doses in vitro, potentially accounting for abysmal survival outcomes seen in chemotherapy treated MB patients. As such, we conducted a screen of 144 FDA approved cancer drugs and identified therapeutics that selectively target Group 3 MB cells in contrast to normal tissue controls (foetal neural stem cells) in the low nanomolar dose range. In particular, topoisomerase inhibitor topotecan produces a potent response specific to MYC-amplified Group 3 MB, and sensitizes 2 patient-derived MB models to gamma irradiation. Altogether, our data characterizes Group 3 MB molecular and cellular responses to current treatment modalities and provides rationale for new clinical strategies to sensitize patients to radiation that will potentially allow to reduce the required radiation doses to treat these aggressive tumors, reduce the incidence of radiation treatment-related morbidity as well as improve cure rates.
Citation Format: Julija Povilaikaite, Kaitlin Stitz, Nikhita Austin, Vijay Ramaswamy. Rational synergistic radiosensitization strategies for group 3 medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5111.