bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 771: A TGF-β superfamily member, myostatin contributes to MASH and HCC via muscle atrophy by disrupting TGF-β signaling, and is a potential marker with PKM2 for human HCC
Authors: Ohshiro Kazufumi , Bhowmick Krishanu , Xiang Xiyan , Kapoor Shivani , Amdur Richard , Dasarathy Srinivasan , Krainer Adrian R. , Mishra Lopa 
Published: March 2024

Abstract
Background: In patients with cirrhosis and hepatocellular carcinoma (HCC), sarcopenia or skeletal muscle loss, as well as metabolic alterations are frequent and progressive comorbidities. Myostatin, a TGF-β superfamily member is expressed primarily in skeletal muscle, inhibits muscle growth, and causes sarcopenia in cirrhosis. Previously, we had observed liver-specific knockout of the SMAD3 adaptor, βII-spectrin -Sptbn1 (βS-LSKO) or siRNA targeting βII-spectrin blocks sarcopenia, fatty liver disease-MASH and HCC (Sci TM 2021), suggesting that βII-spectrin may be a viable strategy to identify mechanisms, as well as new biomarkers of MASH and HCC.
Methods: 1. SPTBN1Flox (control) and liver-specific βII-spectrin knockout (SPTBN1LSKO) mice were fed Western diet (WD) and treated with Diethylnitrosamine (DEN) for obesity-associated HCC. Muscle mass, body weight and multiple enzymes involved in glycolysis as well as sarcopenia were measured in mutant mice. 2. In tumors, a rate-limiting enzyme in glycolysis, pyruvate kinase isozyme M2 (PKM2) that mediates inflammation and aerobic glycolysis in Warburg effect. Therefore, we further examined TGF-β pathway-enriched biomarkers such as Myostatin and PKM2 for markers of HCC and whether these could stratify risk in patients with cirrhosis for HCC, in a four-institution cohort, (n=157) compared to cirrhosis patients (n=380).
Results: 1. Like human fatty liver disease, obese mutant mice show marked sarcopenia with increased PKM2 and Myostatin levels with decreased p-RPS6/total-RPS6 ratio (indicating mTOR signaling inhibition) in striated muscle tissue. In contrast, levels are restored to normal in the liver specific knockout of SPTBN1. 2. Using the 108 markers as well as PKM2 and myostatin (MSTN), we found 31 markers with false discovery rate (FDR) p values &lt; 0.10 from univariable Kruskal-Wallis tests for the associations of markers with HCC vs. cirrhosis.
Conclusions: Our results reveal that SMAD3 adaptor, βII-spectrin liver-specific knockout decreases Myostatin and PKM2 expression, providing new insight into molecular mechanisms in MASH and HCC. These studies reflect that these are biologically functional circuits that could provide new serum markers, such as Myostatin and PKM2 for risk stratification of HCC.
Citation Format: Kazufumi Ohshiro, Krishanu Bhowmick, Xiyan Xiang, Shivani Kapoor, Richard Amdur, Srinivasan Dasarathy, Adrian R. Krainer, Lopa Mishra. A TGF-β superfamily member, myostatin contributes to MASH and HCC via muscle atrophy by disrupting TGF-β signaling, and is a potential marker with PKM2 for human HCC [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 771.
Abstract 773: Overexpression of phosphoserine phosphatase (PSPH) in prostate cancer and in tumor microenvironment promotes tumor cell proliferation
Authors: Song Liankun , Yokoyama Noriko , Xie Jun , Hu Yunjie , Jia Zhenyu (Arthur) , Wang Beverly , Mercola Dan , Uchio Edward , Ahlering Thomas , Lilly Michael , Zi Xiaolin 
Published: March 2024

Abstract
Reprogrammed cellular metabolism is one of the key features of cancer and tumor microenvironment. L-3-phosphoserine phosphatase (PSPH) is one of the five rate-limiting enzymes in the biosynthesis of serine from glucose that supports cell proliferation. Here, we aim to study the role of PSPH in prostate cancer (PCa) and its tumor microenvironment. We find that PSPH not only is overexpressed in prostate cancer cell lines compared to normal prostate epithelial cells (PrEC) and benign prostate epithelial cells (BPH-1), but also exhibits a higher level in patient-derived carcinoma-associated fibroblasts (CAFs) compared to the matched benign associated fibroblasts (BAFs), which are derived from fresh radical prostatectomy specimens of African American (AA) and European American (EA) men. Notably, MDAPCa2b cells derived from an AA prostate cancer patient and AA CAFs have even higher expression of PSPH protein. The mRNA levels of PSPH are also significantly elevated in prostate cancer tissues in AA men compared to EA men and predict poor survival in PCa patients. Knock-down of PSPH expression significantly inhibits the proliferation and colony formation of prostate cancer cells. Growth of xenograft tumors derived from PSPH knockdown MDAPCa2b cells has also been suppressed markedly. Gene expression profiling revealed that suppression of PSPH expression by shRNAs in LNCaP and MDAPCa2b cells is associated with the regulation of gene expression related to metabolism, immunity, extracellular matrix remodeling, and Ion channels. Similarly, analysis of publicly available PCa RNA seq databases also demonstrates that PSPH amplification or over-expression is associated with alterations of gene expression related to metabolism and immunity. Our results suggest that PSPH is upregulated in prostate cancer cells and their surrounding fibroblasts to support tumor growth via reprogramming metabolic pathways and transcriptomes.
Citation Format: Liankun Song, Noriko Yokoyama, Jun Xie, Yunjie Hu, Zhenyu (Arthur) Jia, Beverly Wang, Dan Mercola, Edward Uchio, Thomas Ahlering, Michael Lilly, Xiaolin Zi. Overexpression of phosphoserine phosphatase (PSPH) in prostate cancer and in tumor microenvironment promotes tumor cell proliferation [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 773.
Abstract 780: Normal breast tissues harbor rare populations of aneuploid epithelial cells
Authors: Lin Yiyun , Wang Junke , Wang Kaile , Bai Shanshan , Thennavan Aatish , Wei Runmin , Yan Yun , Li Jianzhuo , Elgamal Heba , Sei Emi , Casasent Anna , Rao Mitchell , Tang Chenling , Montalvan Jessica , Nagi Chandandeep , Winocour Sebastrian , Lim Bora , Thompson Alastair , Navin Nicholas 
Published: March 2024

Abstract
Although aneuploidy is a hallmark of invasive breast cancers, the presence of aneuploid cells in breast tissues of disease-free women is poorly understood. Furthermore, the expansion of aneuploid cells and the specific copy number events that they harbor, as well as their relationship to invasive breast cancers has not been characterized in large cohorts of women. In this study, we obtained viable cell suspensions from 31 disease-free women that underwent reduction mammoplasty surgeries and fresh tissue collection in the HBCA project along with the collection of clinical metadata. The viable cell suspensions from 31 women were enriched for epithelial cells and used to perform high-thoughput nanowell scDNA-seq. In total, 55,321 cells were analyzed. The normal breast tissue samples were also embedded into OCT and frozen to perform Spatial Transcriptomics (Visium 10X Genomics) profiling and embedded into FFPE to perform histopathological analysis. Our data shows that all women harbored rare populations of aneuploid epithelial cells (mean 4.3%) that increased in frequency and their number of copy number aberrations with age. Many aneuploid epithelial cells (mean 79%) in normal breast tissues underwent clonal expansions of their genomes and harbored chromosomal aberrations detected in invasive breast cancers (gain of 1q and loss of 7q, 10q, 16q). Spatial mapping showed that aneuploid cells are localized in focal regions of ductal and lobular epithelial structures with normal histopathological features. Collectively, these data show that aneuploid epithelial cells exist in the normal breast tissues of disease-free women and increase with age. In many women, the aneuploid cells expand and harbor CNA events associated with invasive breast cancer.
Citation Format: Yiyun Lin, Junke Wang, Kaile Wang, Shanshan Bai, Aatish Thennavan, Runmin Wei, Yun Yan, Jianzhuo Li, Heba Elgamal, Emi Sei, Anna Casasent, Mitchell Rao, Chenling Tang, Jessica Montalvan, Chandandeep Nagi, Sebastrian Winocour, Bora Lim, Alastair Thompson, Nicholas Navin. Normal breast tissues harbor rare populations of aneuploid epithelial cells [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 780.
Abstract 817: Establishing a niche to improve Africa’s contribution to cancer research
Authors: Malami Usman A. , Malami Sani A. , Nwokwu Uchechukwu E. , Mohammed Usman W. , Mohammed Faruk 
Published: March 2024

Abstract
Africa has been a key source of scientific discoveries to the global community, especially in areas of scientific experiments and implementation. However, Africans are underrepresented in their contribution to global science and within the African countries, access to adequate funding and infrastructure to do high quality science is limited. These inequities contribute to the 10/90 gap in which only an estimated 10% of global health research funding is used to address health problems in Africa. Thus, it is not surprising that today, Africa contributes just about 2 percent of world research output, 1.3 percent of research spending, and 0.1 percent of all patents. To bridge the aforementioned gaps, mitigate the effect of brain drain and structural constraints and improve support for the next generation scientists, the Nigerian Government recently established the National Institute for Cancer Research and Treatment (NICRAT). It is worthy to note that cancer incidence and mortality rates in Africa are increasing 1.1 million new cases, with 711,000 deaths reported in 2020. This indicate a mortality-to-incidence ratio (MIR) of 0.64. These cancer challenges in Africa necessitates a concerted approach towards effective cancer control and management. Here, we show in detail how the NICRAT support improving science while integrating with Nigerian national development plans and strategies. We also show how the NICRAT is establishing a mechanism for domestic funding, while fostering national and international collaborations for African scientists and encouraging women into careers in cancer research. Currently, the NICRAT’s key task also includes centralizing cancer control efforts, mobilizing funding from different sources for cancer research, and coordinating cancer treatment activities across Nigeria. In addition, the institute facilitates collaboration between researchers, healthcare providers, and patients, and provides guidance for cancer policy formulation and implementation. The establishment of NICRAT by Nigeria’s government as well as similar centers elsewhere in Africa may improve active participation of African scientists in scientific practice, discourse, and decision making and spotlight their intellectual contributions towards solving science-associated global problems.
Citation Format: Usman A. Malami, Sani A. Malami, Uchechukwu E. Nwokwu, Usman W. Mohammed, Faruk Mohammed. Establishing a niche to improve Africa’s contribution to cancer research [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 817.
Abstract 831: Occupational-related exposure to benzene and risk of breast cancer: Systematic review and meta-analysis
Authors: DeStefano Vincent , Shah Darshi , Shah Veer , Seyyedsalehi Monireh Sadat , Bonetti Mattia , Boffetta Paolo 
Published: March 2024

Abstract
Purpose: Benzene is a recognized carcinogen as evidenced by its association with leukemia; however, its association with breast cancer is not well established. Hence, a meta-analysis of cohort and case-control studies was performed to determine the association between benzene exposure and the risk of breast cancer.
Methods: A systematic literature review was conducted and 7221 publications were identified, from which 21 cohort and case-control studies were retained, and evaluated using meta-analyses (fixed effects model). PECOS criteria and STROBE guidelines were followed, and the study protocol was registered in the PROSPERO database (Registration No. 379720). Study quality was assessed using a modified Newcastle-Ottawa scale (NOS).
Results: The summary relative risk (RR) for ever-benzene exposure was 1.08 (95% CI=1.02-1.14, I2=43.6%, n=21); corresponding RR for cancer incidence and mortality were 1.08 (95% CI=1.02-1.14, I2=58.6%, n=15) and 1.09 (95% CI=0.87-1.38, I2&lt;0.001%, n=9), respectively. These main results were confirmed in sub-analyses by geographical region, industry type, publication year, and levels of exposure. No heterogeneity was detected amongst geographical regions (p-het=0.19), industry of employment (p-het=0.05) or and duration of the dose (low, high; p-het=0.64). Studies published before 2003 reported a summary RR of 1.24 (95% CI=1.13-1.37), compared to a summary RR of 1.02 (95% CI=0.95-1.08) for studies published later (p-het=0.001). Heterogeneity was observed when evaluating studies at and above, or below the NOS mean (p-het=0.00), with a summary RR of 1.25 (95% CI=1.13-1.28, I2&lt;0.001%, n=9) for studies below the median NOS score. Sub-group analysis of study design demonstrated heterogeneous results (p-het=0.001) with a summary RR of 1.19 (95% CI=1.10-1.29, I2&lt;0.001%, n=16) for cohort studies while compared to the findings of case-control studies. Publication bias was detected (p=0.04).
Conclusions: Our meta-analysis identified an association between occupational benzene exposure and risk of breast cancer. The association was restricted to studies published before 2003, below the median NOS score, and cohort studies. Residual confounding variables cannot be excluded, which, together with potential bias, prevents conclusions of causality.
Citation Format: Vincent DeStefano, Darshi Shah, Veer Shah, Monireh Sadat Seyyedsalehi, Mattia Bonetti, Paolo Boffetta. Occupational-related exposure to benzene and risk of breast cancer: Systematic review and meta-analysis [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 831.
Abstract 850: Androgenic alopecia and risks of overall and aggressive prostate cancer: An updated meta-analysis
Authors: Amar Sapir , Hanelin David , Agalliu Ilir 
Published: March 2024

Abstract
Background: Androgenic alopecia, known as male pattern baldness (MPB), is a common hair loss disorder among men. MPB has similar risk factors with prostate cancer (PrCa) including advancing age, family history, and sex hormones. Several studies have examined the associations between MPB and PrCa but the evidence remains unclear. We carried out a meta-analysis of epidemiological studies that examined the relationship between patterns of baldness: frontal, vertex, or both and PrCa risk.
Methods: A literature search was performed in October 2022 using PubMed and Web of Science databases for epidemiological studies published between 1/1/2000 and 10/31/2022, which examined the above hypothesis. From each eligible study, relevant data were extracted on study design, population, sample size, prevalence of MPB at various ages, and corresponding associations with risks of total and aggressive PrCa. Pooled relative risks (RR) and corresponding 95% confidence intervals (CI) were calculated using the DerSimonian and Laird random-effects models. Heterogeneity across studies was assessed by I2 statistic.
Results: A total of 14 studies: 14,573 cases and 132,434 controls/non-cases were included. The prevalence of MPB increased from 5% to 70% with aging and varied across studies. Vertex MPB at ages 40 years or older was associated with a pooled RR of 1.08 (95%CI 1.00-1.17) of total PrCa, but there was no association with frontal MPB. The onset of MBP at younger ages was also associated with RR=1.10 (95% CI 0.93 - 1.29) of PrCa, although results were not statistically significant. Results were similar when data were stratified by clinical features of PrCa, although there was large heterogeneity in the definition of aggressive PrCa across studies.
Conclusions: Men with vertex MPB may have modest increased risk of PrCa. However, the majority of studies were conducted in Caucasian men and they did not evaluate effect modifications by genetic variations in androgen metabolism pathway genes or changes in serum levels of androgens. Further, large well-designed prospective cohort studies are needed to better understand the complex relationship between genetic susceptibility, endogenous hormones, MBP and risk of PrCa.
Citation Format: Sapir Amar, David Hanelin, Ilir Agalliu. Androgenic alopecia and risks of overall and aggressive prostate cancer: An updated meta-analysis [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 850.
Abstract 88: Novel cell-based bioassays enable preclinical animal studies during immuno-oncology drug development
Authors: Wang Jun , Garvin Denise , Paguio Aileen , Perrin Elizabeth , Hartnett Jim , Cong Mei , Grailer Jamison 
Published: March 2024

Abstract
Translation of immuno-oncology research into novel therapies relies on animal models to advise target selection and portray mechanism of action (MoA) and pharmacokinetics of lead candidates. Mouse, monkey, and more recently, canine models of human cancers are being utilized to this end. However, one major challenge in developing and utilizing these models is the lack of technology to characterize non-human analogs of therapeutic antibodies. Herein, we report the development of novel cell-based bioassays for mouse, monkey, and canine targets to enable immuno-oncology preclinical studies. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important MoAs for antibody-based cancer immunotherapies. We have developed a suite of cell-based bioassays, each expressing a corresponding animal Fcγ receptor (FcγR) and a luciferase reporter that responds to FcγR activation. These assays exhibit sensitive and quantitative luciferase readouts of FcγR activation. Animal models are further used to provide insight into the potential efficacy of immune checkpoint (IC) inhibitors. Programmed cell death protein 1 (PD-1) is an IC receptor that negatively regulates T cell function. Blockade of PD-1 has demonstrated clinical efficacy, but there remains a significant fraction of patients unresponsive to this therapy. Combination of PD-1 inhibitors with other interventions has been a significant focus for many programs. However, tools for functional validation of non-human PD-1 inhibitors are lacking. We report here the development of two new bioassays for functional characterization of PD-1/PD-L1 inhibitors for mouse and canine targets. Each of these assays consists of two engineered cell lines: a T effector cell line that express a luciferase reporter driven by specific promoter/response elements responding to the intracellular signals mediated by the T cell receptor (TCR), with modulation from PD-1, and an artificial antigen presenting cell line (aAPC). The bioassays are sensitive, quantitative, and have demonstrated characteristics required for potency assays for validation of antibodies in preclinical combination studies.
Citation Format: Jun Wang, Denise Garvin, Aileen Paguio, Elizabeth Perrin, Jim Hartnett, Mei Cong, Jamison Grailer. Novel cell-based bioassays enable preclinical animal studies during immuno-oncology drug 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 88.
Abstract 889: Machine learning-enhanced targeted versus whole-exome sequencing as a guide to cancer care
Authors: Woo Hyung Jun , Chavan Shweta S. , Hanrahan Aphrothiti J. , Richards Allison L. , Noronha Anne Marie , Zehir Ahmet , Drilon Alexander , Berger Michael F. , Solit David B. , Donoghue Mark T. 
Published: March 2024

Abstract
Targeted DNA sequencing of cancer-associated genes has been widely adopted clinically. In addition, the increasing availability of targeted and whole-exome/genome sequencing (WES/WGS)-derived big data suggests avenues of computationally enhancing power of targeted assays via machine learning. We directly compared targeted (MSK-IMPACT) and WES in a cohort of 1,483 cancer patients using the same DNA libraries. We found high sensitivity and specificity of mutation detection by WES for overlapping genes. Comparatively higher estimates of tumor mutation burden by MSK-IMPACT arose from enrichment of oncogenic mutations in the targeted gene set. WES had minimal value in identifying actionable alterations beyond those from MSK-IMPACT, whereas RNA-sequencing identified additional targetable fusions that led to durable responses. We developed a deep learning-based algorithm (DeepSig) that enhances power of mutational signature detection, enabling detection of a select group of signatures with mutation counts of ~5 or less. Hypermutation-associated signatures, including POLE, temozolomide, and mismatch repair deficiency could be detected robustly using targeted sequencing data. In summary, WES had limited clinical value over targeted sequencing panels and future clinical diagnostic development should focus on transcriptome and WGS that can detect additional signatures and gene fusions.
Citation Format: Hyung Jun Woo, Shweta S. Chavan, Aphrothiti J. Hanrahan, Allison L. Richards, Anne Marie Noronha, Ahmet Zehir, Alexander Drilon, Michael F. Berger, David B. Solit, Mark T. Donoghue. Machine learning-enhanced targeted versus whole-exome sequencing as a guide to cancer care [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 889.