bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 7300: Synergistic inhibition of prostate cancer growth by the combination of xanthohumol and ursolic acid
Authors: Clark Rachel , Saha Achinto , Friedman Chelsea A. , Gorgoglione Ruggiero , Tiziani Stefano , DiGiovanni John 
Published: March 2024

Abstract
Within the United States, prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer, and approximately 1 in 8 men will receive a diagnosis in their lifetime. As the second leading cause of cancer deaths in American men, about 1 in 41 will die because of prostate cancer. The World Health Organization has suggested that approximately one-third of all cancer deaths are preventable, and one of the suggested means of prevention is through the increased consumption of fruits and vegetables. Fruits and vegetables contain natural compounds known as phytochemicals which possess biological activity including some anti-cancer effects. By adapting the ATP-bioluminescence assay for cell viability, our laboratory screened a natural compound library to find combinations of these compounds that may synergistically inhibit PCa cell viability. One of the combinations to emerge from this screening process was xanthohumol (XAN) and ursolic acid (UA). We examined the ability of the combination to inhibit tumor growth in a mouse HMVP2 PCa allograft tumor model. Mice were fed diets supplemented with either XAN (0.2%) or UA (0.2%) alone or the combination. Mice on the combination diet showed a significant inhibition of HMVP2 PCa tumor growth compared to mice on the single-agent diets. In addition, in vitro studies were performed to support the allograft tumor study and to further examine the mechanism of action of the combination. A cell survival assay utilizing six different PCa cell lines indicated that the combination of XAN and UA synergistically inhibited the survival of all cell lines as calculated by the Bliss index. Mechanistic studies performed in PCa cells indicate that the combination of XAN and UA inhibits oncogenic signaling better than either agent alone. Additionally, unbiased metabolomics revealed that the tumors from mice fed the combination diet had significantly less S-adenosyl-L-methionine compared to all other groups. Overall, 13 metabolic pathways were significantly different in the tumors from mice fed the combination diet compared to all other groups. The current data suggest that using a combination of XAN and UA may be a valuable chemopreventive strategy for PCa in humans. Funding: This work was supported by NIH Grant CA228404.
Citation Format: Rachel Clark, Achinto Saha, Chelsea A. Friedman, Ruggiero Gorgoglione, Stefano Tiziani, John DiGiovanni. Synergistic inhibition of prostate cancer growth by the combination of xanthohumol and ursolic acid [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 7300.
Abstract 7305: Chemoprevention of colorectal cancer: Role of trace minerals in conjunction with calcium
Authors: Harber Isabelle , McClintock Shannon , Varani James , Aslam Muhammad N. 
Published: March 2024

Abstract
Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. CRC usually develops from adenomas (CRC precursors) after a long latency period. Prevention is crucial in reducing CRC incidence and progression to cancer. Among several prevention options, calcium has been a widely considered chemo-preventative agent.
Aims: Calcium plays a vital role in the regulation of epithelial cell differentiation, which is essential for epithelial growth control. Epidemiological studies have demonstrated that adequate calcium intake is crucial for protection against colonic polyp formation and colorectal cancer. However, recent interventional trials with calcium have had only modest and mixed results, and the question is how to improve efficacy. One potential strategy is to use calcium in combination with additional minerals and trace elements.
Results: Our preclinical studies employing monolayer cultures with CRC cell lines and colon organoids cultures from colon polyps have shown that a calcium-rich mineral combination derived from fossilized red algae (Aquamin) is more effective than calcium alone in inducing differentiation, suppressing growth and upregulation of calcium-sensing receptor. When colonic adenomas in culture were subjected to differential proteomic analysis, Aquamin upregulated several proteins involved in proliferation suppression, DNA mismatch repair and inducing differentiation, and apoptosis. Two long-term mouse studies have demonstrated that Aquamin is more effective in suppressing polyp & CRC incidence compared to calcium alone. Based on these findings, we conducted a 90-day FDA-approved trial (a pilot study with ten subjects per arm) comparing the two interventions in human subjects at risk for CRC. Results showed that Aquamin treatment reduced proliferation and increased cell differentiation observed by immunohistochemistry. Proteomic analysis also revealed that the minerals upregulated several proteins related to growth suppression, inducing differentiation and those contributing to cell-cell and cell-matrix adhesion functions and downregulated proteins involved in proliferation and nucleic acid metabolism.
Conclusion: These results provide convincing evidence that a multi-mineral combination derived from red algae can provide benefits in preventing CRC that are not seen with calcium alone. Further studies, such as a polyp-prevention trial in human subjects, are warranted to advance these CRC prevention efforts.
Citation Format: Isabelle Harber, Shannon McClintock, James Varani, Muhammad N. Aslam. Chemoprevention of colorectal cancer: Role of trace minerals in conjunction with calcium [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 7305.
Abstract 7340: Investigating the function and impact of UBASH3B in head and neck squamous cell carcinoma and its implications for racial health disparities
Authors: Ndahayo Madeleine , Mukhina Vera , Gupta Ishita , Gaykalova Daria A. 
Published: March 2024

Abstract
Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the top cancers with significant cancer health disparities among racial and ethnic groups. African Americans (AAs) with HNSCC demonstrate worse overall survival compared to European Americans (EAs). While the reasons behind this disparity are multifaceted, recent findings suggest that biological features in HNSCC may contribute to differences in disease progression. However, race-related biological factors in HNSCC have been relatively little explored. We have identified the gene UBASH3B, a protein tyrosine phosphatase that plays a role in the stabilization of the Epidermal Growth Factor Receptor (EGFR). High expression of UBASH3B in AAs is associated with significantly worse overall survival compared to high expression in EAs and low expression in AAs. This study seeks to examine the role of UBASH3B in HNSCC and determine its impact on tumorigenesis. We hypothesize that the upregulation of UBASH3B in AAs contributes to the survival disparity by promoting tumor progression through EGFR signaling. Preliminary data using The Cancer Genome Atlas (TCGA) shows overexpression of UBASH3B in tumor samples of both AAs and EAs HNSCC samples. Plus, the overexpression of UBASH3B is associated with perineural invasion. Additionally, among AA-HNSCC patients, advanced T-stage is associated with increased UBASH3B expression. Elucidating the role UBASH3B plays in tumorigenesis will give us a further understanding of HNSCC in African Americans and can serve as a potential therapeutic target for new treatment options, as well as the biomarkers for the detection of the high-risk group.
Citation Format: Madeleine Ndahayo, Vera Mukhina, Ishita Gupta, Daria A. Gaykalova. Investigating the function and impact of UBASH3B in head and neck squamous cell carcinoma and its implications for racial health disparities [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 7340.
Abstract 7344: Role of ubiquitin receptor ADRM1 (Rpn13) in prostate cancer
Authors: Chowdhury Shahjalal , Wang Honghe , Nayak Chitra , Karanam Balasubramanyam 
Published: March 2024

Abstract
Adhesion-regulating molecule 1 (ADRM1)/Rpn13 is a component of the 19S regulatory subunit of the 26S proteasome [1]. ADRM1 plays a crucial role in the recognition of polyubiquitinated substrates of the proteasome and their subsequent deubiquitination and degradation [2]. ADRM1 transcript levels are commonly upregulated in diverse tumor types [3]. The androgen receptor (AR) plays a predominant role in prostate cancer (PCa) pathology. In this study, we investigated the expression of ADRM1/Rpn13 in different stages of prostate cancer and its association with AR expression. TCGA data from UALCAN was used for understanding ADRM1 expression on different stages of diseases and single-cell RNA-sequencing data of prostate cancer cell line was obtained from Prostate Cancer Atlas. TCGA (cell, 2015) data set was used for investigating the correlation between ADRM1 and AR by using R programming. Our study from the TCGA dataset reveals that ADRM1 expression increased significantly with the aggressiveness of prostate cancer (increase consistently with the Gleason score) from the TCGA dataset. We analyzed ADRM1 and AR expression in different prostate cancer cell lines and obtained that ADRM1 expressed significantly higher in prostate cancer cell lines which had lower AR expression. TCGA (cell, 2015) dataset indicated a negative correlation between ADRM1 and AR expression in prostate cancer. Our preliminary analysis indicated that ADRM1 inhibitor might be a potential therapeutic option for AR-independent prostate cancer.
Citation Format: Shahjalal Chowdhury, Honghe Wang, Chitra Nayak, Balasubramanyam Karanam. Role of ubiquitin receptor ADRM1 (Rpn13) in prostate cancer [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 7344.
Abstract 7361: The prognostic value of TP53 and tumor suppressor gene mutations in temozolomide-treated IDH1 mutant low-grade glioma
Authors: Salem Yahia E. , Alragheb Bayan O. Abu 
Published: March 2024

Abstract
Background: Temozolomide has been extensively utilized in the treatment of gliomas across various grades, offering significant therapeutic benefits. However, the impact of concurrent mutations in TP53 and other tumor suppressor genes (TSG) on treatment outcomes in patients with IDH1 mutant low-grade glioma (LGG) treated with temozolomide remains to be fully understood. This study aims to explore the influence of these genetic factors on the response to temozolomide therapy, focusing on identifying potential genetic markers that can predict therapeutic outcomes.
Methods: Our study exclusively analyzed The Cancer Genome Atlas (TCGA) LGG PanCancer dataset from cBioPortal, focusing on IDH1 mutant cases treated with temozolomide. Data analysis was carried out using Python 3.11. The cohort was categorized based on genetic alterations: TP53 mutation with additional TSGs (ATRX, CIC, FUBP1, NOTCH1) mutations (TP53mut/TSGmut), TP53 mutation without additional TSG mutations (TP53mut/TSGwt), and no TP53 mutations (TP53wt).
Results: In our study, 178 LGG samples with IDH-1 mutation treated with temozolomide were selected. Of these, 113 samples had a mutation in TP53, and 88 had an additional mutation in a TSG. For TP53mut/TSGmut compared to TP53wt, the analysis revealed significant differences in clinical outcomes (PFS: HR 1.95, CI: 1.17-3.26, p=0.011; OS: HR 1.6, CI: 1.13-2.26, p=0.008). When comparing TP53mut/TSGwt with TP53mut/TSGmut, the findings were (PFS: HR 1.36, CI: 0.63-2.92, p=0.432; OS: HR 0.93, CI: 0.31-2.79, p=0.896). Finally, the comparison between TP53wt and TP53mut/TSGwt showed (PFS: HR 1.45, CI: 0.62-3.39, p=0.397; OS: HR 2.31, CI: 0.64-8.3, p=0.200).
Conclusion: The presence of concurrent mutations in TP53 and other TSGs in IDH1 mutant LGG patients (TP53mut/TSGmut) is indicative of a more aggressive disease course and reduced response to temozolomide treatment, as evidenced by significantly worse clinical outcomes. In contrast, the TP53mut/TSGwt group did not exhibit significant differences in treatment outcomes. These findings underscore the importance of detailed genetic profiling in developing personalized treatment strategies for this patient population.
Citation Format: Yahia E. Salem, Bayan O. Abu Alragheb. The prognostic value of TP53 and tumor suppressor gene mutations in temozolomide-treated IDH1 mutant low-grade glioma [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 7361.
Abstract 7387: Fully automated segmentation and volumetric measurement of intracranial meningioma using deep learning
Authors: Kang Ho , Witanto Joseph N. , Pratama Kevin , Lee Doohee , Choi Kyu Sung , Choi Seung Hong , Kim Min-Sung , Kim Jin Wook , Kim Yong Hwy , Park Sang Joon , Park Chul-Kee 
Published: March 2024

Abstract
Most intracranial meningiomas are small, asymptomatic, and incidentally found tumors. Since the growth of meningioma is the principal indication of treatment, accurate and rapid measurement of the volume of intracranial meningiomas is essential in clinical practice to determine the growth rate of the tumor. It could be useful for the management of meningiomas given their increasing incidence and the wait-and-see policy currently in use for asymptomatic meningiomas. The aim of this study was to develop and validate a computational model for fully automated meningioma segmentation and volume measurement on contrast-enhanced MR scans using deep learning.
The retrospectively collected axial contrast-enhanced T1-weighted section images from patients diagnosed with meningioma were manually segmented and used to construct automatic segmentation models with six U-Net- and nnU-Net-based architectures. The performance of each model was evaluated with the Sørensen-Dice similarity coefficient (DSC) with internal (IVS) and external validation sets (EVS), each consisting of 100 independent MRI examinations.
A total of 12,909 section images from 459 patients were applied for the training (median age 58 [52-66] [IQR]; 385 women [83.9%]). The median tumor volume of the training set was 2.36 cm3. A 2D nnU-Net showed the highest median DSCs of 0.922 and 0.893 for the IVS and EVS, respectively. The nnU-Nets achieved superior performance in meningioma segmentation than the U-Nets. The DSCs of the 2D nnU-Net for small meningiomas less than 1 cm3 were 0.769 and 0.780 with the IVS and EVS, respectively.
We successfully developed a fully automated and accurate volumetric measurement tool for meningioma using nnU-Net. The volumetry performance for small meningioma was significantly better than that achieved in previous studies. The results of this study are clinically applicable and are expected to be of great use in the management of monitored meningioma patients.
Citation Format: Ho Kang, Joseph N. Witanto, Kevin Pratama, Doohee Lee, Kyu Sung Choi, Seung Hong Choi, Min-Sung Kim, Jin Wook Kim, Yong Hwy Kim, Sang Joon Park, Chul-Kee Park. Fully automated segmentation and volumetric measurement of intracranial meningioma using deep learning [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 7387.
Abstract 7415: Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment
Authors: Vangara Raviteja , Diaz-Gay Marcos , Barnes Mark D. , Wang Xi , Islam S M Ashiqul , Vermes Ian , Duke Stephen , Narasimman Nithish Bharadhwaj , Yang Ting , Jiang Zichen , Moody Sarah , Senkin Sergey , Brennan Paul , Stratton Michael R. , Alexandrov Ludmil B. 
Published: March 2024

Abstract
Analysis of mutational signatures is a powerful approach for understanding the mutagenic processes that have shaped the evolution of a cancer genome. To evaluate the mutational signatures operative in a cancer genome, one first needs to quantify their activities by estimating the number of mutations imprinted by each signature, a process known as refitting of mutational signatures. Although multiple tools for refitting known signatures were developed in the past decade, most provide support almost exclusively for single base substitution signatures and lack an online interface. Further, these tools have never been compared, and no existing tool supports probabilistically assigning signatures to a single somatic mutation. Here, we present SigProfilerAssignment, a desktop and online computational framework for assigning all types of mutational signatures to individual samples. SigProfilerAssignment is the first tool that allows both analysis of copy-number signatures and probabilistic assignment of signatures to individual somatic mutations. As its computational engine, the tool uses a custom implementation of the forward stagewise algorithm for sparse regression and nonnegative least squares for numerical optimization. The analysis of 2,700 synthetic cancer genomes with and without noise demonstrates that SigProfilerAssignment outperforms four commonly used approaches for assigning mutational signatures, with consistent top performance across cancer types and most signatures. SigProfilerAssignment stands out as the most precise and sensitive tool while maintaining high computational performance and bringing novel capabilities. SigProfilerAssignment is distributed as an open-source Python/R package available at https://github.com/AlexandrovLab/SigProfilerAssignment, with an online interface available as part of the COSMIC Mutational Signatures website at https://cancer.sanger.ac.uk/signatures/assignment/.
Citation Format: Raviteja Vangara, Marcos Diaz-Gay, Mark D. Barnes, Xi Wang, S M Ashiqul Islam, Ian Vermes, Stephen Duke, Nithish Bharadhwaj Narasimman, Ting Yang, Zichen Jiang, Sarah Moody, Sergey Senkin, Paul Brennan, Michael R. Stratton, Ludmil B. Alexandrov. Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment [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 7415.
Abstract 7418: LongFuse: Detecting gene fusion transcripts from high throughput long-read single cell RNA sequencing data
Authors: Shiau Cheng-Kai , He Yueying , Lin Hsiao-Yun , Lu Lina , Lu Xiao-Dong , Yu Jindan , Gao Ruli 
Published: March 2024

Abstract
Gene fusion resulted from genomic translocation plays important oncogenic roles including but not limited to gene activation and changing protein coding sequences. Historically, fusion gene analysis has been limited to bulk levels resulting in mixed oncogene activation models. Single cell Nanopore RNA sequencing (scNanoRNAseq) has the unique strength in detecting full-length chimeric transcripts in thousands of single cells in parallel. However, robust computational tools for detecting fusion genes in single cells from scNanoRNAseq data are missing. Here, we developed LongFuse, a fast and accurate tool, to detect fusion genes and their splicing isoforms in single cells from scNanoRNAseq data. LongFuse implements an XOR logic gate algorithm to speed up fusion candidate searching and stringent criteria to eliminate false discoveries due to trans-splicing events and randomly ligated chimeras. We applied LongFUSE onto scNanoRNAseq data of both human prostate cancer cell line, VCaP, and tumor tissues with known TMPRSS2-ERG fusion. Our results showed that both cancer cell line and prostate tumors harbored a mixture of fusion positive and fusion negative tumor cells. Gene expression analysis revealed transcriptional differences between fusion positive and negative cells including genes involved in cancer cell proliferation and invasion programs such as ELL2, ZBTB16, IGF1R, ANK3, MYPOP and PLPP1 genes. LongFUSE also calculates the splicing isoforms of fusion gene transcripts, allowing prediction of protein sequences of fusion gene transcripts. Taken together, our data demonstrated that LongFUSE is a robust computational tool for detecting gene fusions and their splicing isoforms at single cell level from scNanoRNAseq data.
Citation Format: Cheng-Kai Shiau, Yueying He, Hsiao-Yun Lin, Lina Lu, Xiao-Dong Lu, Jindan Yu, Ruli Gao. LongFuse: Detecting gene fusion transcripts from high throughput long-read single cell RNA sequencing data [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 7418.
Abstract 7451: Translational models of ovarian cancer-associated cognitive impairment and chemotherapy-induced peripheral neuropathy
Authors: Lomeli Naomi , Argueta Donovan , Pearre Diana C. , Lepe Javier , Gupta Kalpna , Bota Daniela A. 
Published: March 2024

Abstract
Cisplatin is widely used to treat ovarian malignancies, and over 70% of ovarian cancer patients report experiencing cancer-related cognitive impairment (CRCI) and chemotherapy-induced peripheral neuropathy (CIPN) during and after chemotherapy treatment. Most pre-clinical CRCI/CIPN studies have been conducted on non-tumor bearing rodents. We developed two novel clinically relevant models of CRCI/CIPN: (1) the ID8 syngeneic mouse model in B6(Cg)-Tyrc-2J/J female mice, and (2) the SKOV3.ip1 ovarian cancer xenograft model in female Cr:NIH-RNU rats. We examined cognitive function and serum cytokine levels with respect to cancer progression and/or in response to cisplatin. B6 female mice were injected with 107 ID8 cells or 0.9% saline, i.p. Mice received cisplatin (2.3 mg/kg/day, i.p.) or 0.9% saline (OvT+CIS, OvT+VEH, respectively) for 5d, followed by 5d of rest for two cycles. RNU rats were injected with 107 SKOV3.ip1 cells or 0.9% saline, i.p. Rats received cisplatin (5 mg/kg, i.p) or 0.9% saline (OvT+CIS, OvT+VEH, respectively) every other week for four cycles. OvT+CIS and OvT+VEH mice and rats showed impairments in novel object recognition (NOR), with discrimination ratios ≤0.5. Cisplatin transiently increased hyperalgesia in OvT+CIS mice, which persisted longitudinally in OvT+VEH mice. Serum cytokine levels were elevated in OvT+VEH mice (IL-2, IL-10, INFγ) and OvT+VEH rats (IL-4, IL-10) compared to OvT+CIS (P&lt;0.05). Ovarian cancer may evoke progressive sensory and neurocognitive deficits and increase systemic pro-inflammatory cytokine levels in the absence of chemotherapy. Future studies will address hyperalgesia and cognitive differences between healthy control and ovarian cancer models +/- cisplatin, and biological mechanisms underlying CRCI and CIPN.
Citation Format: Naomi Lomeli, Donovan Argueta, Diana C. Pearre, Javier Lepe, Kalpna Gupta, Daniela A. Bota. Translational models of ovarian cancer-associated cognitive impairment and chemotherapy-induced peripheral neuropathy [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 7451.