bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2340: Evaluation of metabolic and hormonal disorders in Yemeni women with breast cancer attending national oncology center in Mukalla, Yemen
Authors: Dahman Lotfi Saeed Bin , Sanoon Zaki Farag , Kaleem Waleed Khalid , Humam Mariam Ahmed , Bamhraz Shaima Adeeb , Bamatraf Noor Adeeb , Humran Khadija Mohmmed , Albada Fatima Lutfi , Obad Yaser Saeed 
Published: June 2022

Abstract
Background: Metabolic syndrome has been linked to many adverse health consequences, including breast cancer. This study aimed to evaluate the metabolic and hormonal disorders and assess the effect on estrogens in Yemeni women with breast cancer.
Patients and Methods: A total of 69 Yemeni women with breast cancer were recruited into the cross-sectional study. This study was conducted at the National Oncology Center in Mukalla, Yemen, from15th March to 30th July 2021. Anthropometric data and blood pressure were taken from each participant. Fasting blood glucose FBG, HbA1c, lipid profile, C-reactive protein (CRP), were measured using the chemical autoanalyzer (Mindray Bs230 autoanalyzer, Mindray Diagnostics). Insulin, estradiol, and testosterone were measured using Mindray CL-960i, Mindray Diagnostics ). Data were analyzed by using SPSS.
Results: The mean age of the participants was 48.17±11.0 years. The majority were normal weight(40.6%), and some were obese (30.4%) and overweight (29.0%). The majority had breast cancer stage2 (53.6%), and some were stage 4 (24.6%) and stage 3 (21.7%). Obese breast cancer women had significantly higher weight (P&lt;0.001), BMI (P&lt;0.001), waist (P&lt;0.001), and hips (P&lt;0.001) than the normal weight group. Furthermore, obese breast cancer women had significantly higher HbA1c(P=0.016), TC (P&lt;0.001), and LDL-C (P=0.032) than the normal weight group. Insulin was positively associated with FBG (P=0.001) and HOMA-IR (P&lt;0.001). Estradiol was positively associated with total cholesterol (P=0.004), triglycerides (P=0.007), and CRP (P=0.026). testosterone was negatively associated with CRP (P=0.011) and estradiol (P=0.019) in the combined groups studied.
Conclusion: Metabolic syndrome is more prevalent in breast cancer patients and is more likely to develop breast cancer.
Citation Format: Lotfi Saeed Bin Dahman, Zaki Farag Sanoon, Waleed Khalid Kaleem, Mariam Ahmed Humam, Shaima Adeeb Bamhraz, Noor Adeeb Bamatraf, Khadija Mohmmed Humran, Fatima Lutfi Albada, Yaser Saeed Obad. Evaluation of metabolic and hormonal disorders in Yemeni women with breast cancer attending national oncology center in Mukalla, Yemen [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 2340.
Abstract 2349: SAP30, a novel drug response specific transcription factor in high-risk neuroblastoma
Authors: Prathipati Philip , Pathania Anup S. , Chaturvedi Nagendra K. , Gupta Subash C. , Byrareddy Siddappa N. , Coulter Don W. , Challagundla Kishore B. 
Published: June 2022

Abstract
Neuroblastoma is the most devastating extracranial solid malignancy in children. Despite an intense treatment regimen, the prognosis for high-risk neuroblastoma patients remains poor, with less than 40% survival. So far, MYCN status/amplification is considered the most prognostic factor but corresponds to only 25% of neuroblastoma patients. Therefore, it is essential to identify a better prognosis and prediction marker of therapy response in neuroblastoma patients. The identification of master regulators with good prognostic and drug response abilities are not successful due to the complexity and lack of data-driven bioinformatic workflows. We applied robust bioinformatic data mining tools such as Weighted Gene Co-expression Network Analysis, cisTarget, and Single-Cell rEgulatory Network Inference and Clustering on three neuroblastoma patient datasets (n=1252). We found Sin3A Associated Protein 30 (Sap30), a driver transcription factor positively associated with high-risk, progression, stage 4, and poor survival in high-risk neuroblastoma patient cohorts. Tumors of high-risk neuroblastoma patients and relapse-specific patient-derived xenografts showed higher Sap30 levels. The Genomics of Drug Sensitivity in Cancer, The Cancer Cell Line Encyclopedia, and CRISPR-Cas9 screens indicated that Sap30 essentiality is associated with Cisplatin resistance and further showed higher levels in Cisplatin resistant patient-derived xenograft tumor cell lines. The silencing of Sap30 in cells reduced cell growth, induced cell death, mitochondrial membrane potential loss in vitro, and reduced tumorigenicity in vivo. Altogether, these results indicate that Sap30 is a novel prognostic and Cisplatin resistant marker and thus a potential drug target in high-risk neuroblastoma patients.
Citation Format: Philip Prathipati, Anup S. Pathania, Nagendra K. Chaturvedi, Subash C. Gupta, Siddappa N. Byrareddy, Don W. Coulter, Kishore B. Challagundla. SAP30, a novel drug response specific transcription factor in high-risk neuroblastoma [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 2349.
Abstract 2405: Expression of the low affinity neurotrophin receptor (p75NTR) correlates with perineural invasion in adenoid cystic carcinoma of the lacrimal gland
Authors: Moeyersoms Acadia H. , Gallo Ryan A. , Weiss Madison , Maeng Michelle M. , Tse David T. , Pelaez Daniel 
Published: June 2022

Abstract
Lacrimal gland adenoid cystic carcinoma (LGACC) is a rare but highly lethal indolent cancer originating in the cells of secretory glands, primarily of the head and neck. With the 10-year survival rate of 20%, the only life extending technique is to remove the eye and surrounding socket contents followed by extensive chemoradiation. Despite radical treatment, LGACC has a poorer prognosis than head and neck adenoid cystic carcinoma in part due to its propensity for perineural invasion (PNI) and intracranial spread. Analysis of LGACC tumors has revealed signatures enriched for pathways known to be involved in normal LG development, suggesting LGACC tumor cells re-engage or hijack developmental programs during its progression. This project sought to evaluate if developmental pathways involved in embryologic LG innervation were similarly recapitulated by LGACC tumors, and whether any of those markers could be correlated to perineural invasion phenotypes. We performed microarray analysis of embryonic and adult murine lacrimal glands and generated a differential expression signature associated with normal LG developmental pathways. Among other pathways, Notch and FGF signaling are significantly upregulated during LG organogenesis and our group and others have shown that activating mutations in these pathways are correlated with poor prognosis in LGACC. Interestingly, among the highest differentially expressed genes in the embryonic LG was the low-affinity nerve growth factor receptor (p75NTR). We thus subsequently evaluated the expression of p75NTR in LGACC tumors and its correlation to PNI. Our immunofluorescent imaging of histologically confirmed tumors with PNI demonstrated that p75NTR is highly correlated to cancer cells that have invaded the nerve. This correlation of p75NTR expression in nerve infiltrating LGACC cells can inform our investigation into the mechanisms for LGACC PNI and elucidate possible therapeutic targets to limit this aggressive manifestation in LGACC.
Citation Format: Acadia H. Moeyersoms, Ryan A. Gallo, Madison Weiss, Michelle M. Maeng, David T. Tse, Daniel Pelaez. Expression of the low affinity neurotrophin receptor (p75NTR) correlates with perineural invasion in adenoid cystic carcinoma of the lacrimal gland [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 2405.
Abstract 2415: Loss of Krüppel-like factor 4 facilitates disruption of epithelial barrier function in gastric cancer and promotes metastasis
Authors: Goswami Sandeep , Sarkar Chandrani , Frankel Wendy L. , Basu Sujit , Chakroborty Debanjan 
Published: June 2022

Abstract
Stomach or gastric cancer (GC) is one of the most common malignancies observed in men and women worldwide. It is also a leading cause of cancer-related deaths. The disease is potentially curable when diagnosed early with survival records of more than 90%. This number, however, sharply declines to less than 20% when diagnosed at advanced stages. Therefore identification of functional molecular markers that can predict the progression of the disease is of utmost importance as early diagnosis enhances the chances of successful therapeutic intervention. Krüppel-like Factors (KLFs) are a family of evolutionarily conserved transcriptional regulators with zinc finger DNA binding domains. KLFs have been shown to play important roles both in normal development as well as in disease progression. In cancers, KLFs have been reported to regulate diverse cellular processes like cell growth, proliferation and differentiation. Of the 17 KLFs identified to date, KLF4 and KLF 5 show significantly altered expression in GC tissues compared to normal gastric tissues (TCGA sample analysis of gene expression pattern for KLFs). WhileKLF5 typically pro-proliferative and acts as a tumor promoter, KLF4 has been both oncogenic and tumor-suppressive. KLF4 downregulation is associated with a poor prognosis in GC. However, the specific role of KLF4 in GC progression has not been fully elucidated. Using human GC tissues, orthotropic gastric tumors developed in athymic nude mice, and in vitro functional assays, we hereby report that loss of KLF4 in GC disrupts tight junction stability of epithelial cells. Loss of KLF4 expression correlates with altered expression of tight junction proteins such as claudins and ZO1 in GC. Altered expression of these proteins results in disruption of epithelial barrier integrity leading to cell detachment and metastasis. Therefore, our work indicates that loss of KLF4 observed in GC may promote cell metastasis and can serve as a prognostic marker for GC metastasis. The knowledge generated from this study not only imparts insight into the pathogenesis of GC metastasis but also will be helpful in the development of newer treatment strategies in the future.
Citation Format: Sandeep Goswami, Chandrani Sarkar, Wendy L. Frankel, Sujit Basu, Debanjan Chakroborty. Loss of Krüppel-like factor 4 facilitates disruption of epithelial barrier function in gastric cancer and promotes metastasis [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 2415.
Abstract 2438: Determining the role of non-mutated C-Raf kinase in metastatic disease
Authors: Ta Lisa H. , Carr-Ascher Janai R. , Deng Weixian , Tsai Brandon L. , Tran Wendy , Gun Donny , Cheng Donghui , Sha Jihui , Hwang Yeonjoo , Phillips John W. , Obusan Matthew B. , Bangayan Nathanael J. , Noguchi Miyako , Mao Zhiyuan , Chen Chia-Chun , Wang Liang , Varuzhanyan Grigor , Gordon John D. , Wohlschlegel James W. , Witte Owen N. 
Published: June 2022

Abstract
Many aggressive epithelial cancers do not carry targetable driver mutations (Mendiratta et al. 2021, NCI-MATCH Clinical trial NCT02465060). Commonly altered signaling pathways highlight the propensity for tumors to depend on such pathways for growth and survival where genomic alterations may not be required for pathway activation. The Raf family kinases are crucial mediators of the Ras/Raf/MEK/ERK (MAPK) cascade, which has been shown to be upregulated in a subset of metastatic cancers and are mutated in many epithelial cancers. A recent study suggests non-mutated C-Raf can drive metastasis to the lungs, bone, and various other tissues (Faltermeir et al. 2016). Though the mechanism of C-Raf driven metastasis is likely through MAPK activation, C-Raf has been demonstrated to possess MAPK independent roles that may also contribute to this phenotype. In this study, we explored various C-Raf functions as drivers of metastasis in an intracardiac mouse model system. Using a series of Raf knock-out cell lines and mutants targeting functional residues in C-Raf, we demonstrated that C-Raf dimerization is necessary to drive metastasis. We further showed that the metastasis-promoting activity of C-Raf is dependent on co-expression of its family member, B-Raf, for an accelerated metastatic phenotype. However, overexpression of a kinase-dead C-Raf mutant was still able to produce metastases albeit with lower efficiency, suggesting C-Raf possesses non-kinase dependent functions that also contributed to metastasis. Together, these results point to the importance of Raf non-canonical roles in oncogenic processes that may be unappreciated in metastatic disease.
Citation Format: Lisa H. Ta, Janai R. Carr-Ascher, Weixian Deng, Brandon L. Tsai, Wendy Tran, Donny Gun, Donghui Cheng, Jihui Sha, Yeonjoo Hwang, John W. Phillips, Matthew B. Obusan, Nathanael J. Bangayan, Miyako Noguchi, Zhiyuan Mao, Chia-Chun Chen, Liang Wang, Grigor Varuzhanyan, John D. Gordon, James W. Wohlschlegel, Owen N. Witte. Determining the role of non-mutated C-Raf kinase in metastatic disease [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 2438.
Abstract 2440: Investigating the role of Eya3 in the regulation of NF-kB signaling and tumor progression in TNBC
Authors: Hughes Connor J. , Mallo Rebecca , Fields Kaiah , Zhou Hengbo , Gustafson Annika , Kong Deguang , Slansky Jill , Zhao Rui , Ford Heide L. 
Published: June 2022

Abstract
Triple Negative Breast Cancer (TNBC), characterized by low/absent expression of the estrogen receptor and the HER2 growth factor receptor, has high rates of metastasis and an overall poor prognosis largely due to a lack of targeted therapeutic options. The Eyes absent (Eya) family of proteins are transcriptional cofactors with both intrinsic tyrosine phosphatase and associated serine/threonine phosphatase activities. In addition to developmental functions, Eyas have been shown to play a role in promoting many hallmarks of cancer. Published work from our laboratory demonstrated that Eya3 is capable of upregulating expression of PD-L1 in TNBC tumors thereby suppressing anti-tumor CD8+ T-cell responses, and preliminary data suggests that Eya3 may also regulate the expression of various cytokines in this context. In tumor cells, innate immune signaling pathways, such as NF-kB, have been shown to promote tumor progression, immune evasion, and metastasis in many distinct tumor types. We hypothesize that, in addition to regulating CD8+ T-cell responses, Eya3 regulates innate immune signaling in TNBC cells to facilitate enhanced primary tumor growth and metastasis. Preliminary findings suggest that Eya3 is a key mediator of tumor progression and metastasis in TNBC and a strong regulator of NF-kB signaling in this context. Further exploration is warranted to determine the mechanism through which Eya3 regulates these phenotypes, whether Eya3-mediated NF-kB activation is a major contributor to the pro-metastatic phenotype of Eya3, and whether Eya3 could serve as a therapeutic target for preventing or treating disseminated TNBC.
Citation Format: Connor J. Hughes, Rebecca Mallo, Kaiah Fields, Hengbo Zhou, Annika Gustafson, Deguang Kong, Jill Slansky, Rui Zhao, Heide L. Ford. Investigating the role of Eya3 in the regulation of NF-kB signaling and tumor progression in TNBC [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 2440.
Abstract 2456: Mass spectrometry imaging reveals distinct differences in glycogen accumulation in lung tumors from Appalachian patients
Authors: Buoncristiani Michael D. , Conroy Lindsey R. , Clarke Harrison , Young Lyndsay E. , Sun Ramon C. 
Published: June 2022

Abstract
Lung cancer is the leading cause of cancer related death in the United States, with patients from rural Appalachia having drastically higher incidence and mortality rates, driven by largely unknown mechanisms. Identifying molecular features that contribute to this health disparity is a critical step in lung cancer research that could lead to predictive biomarkers and personalized therapy for the Appalachia population. Recently, aberrant glycogen accumulation in lung tumors has been reported to promote lung cancer progression. However, the full clinical implications of dysregulated glycogen metabolism and its role in lung cancer health disparities has yet to be explored. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is a new and innovative technique that combines mass spectrometry with high resolution imaging, enabling the detection of hundreds of analytes with spatial distribution. We recently developed an advanced method to analyze glycogen content in formalin-fixed paraffin-embedded tissues using MALDI-MSI. With this technique, we analyzed glycogen chain length and glycogen phosphate content from tissue microarrays containing over 100 lung cancer patient samples banked at the University of Kentucky. Our patient cohort included adenocarcinoma and squamous cell carcinoma patients from Appalachian and non-Appalachian counties, with diverse cytopathological features. We found significant glycogen accumulation and higher glycogen phosphate content in lung tumor tissue compared to match normal lung across all patients. Further, we found glycogen accumulation is markedly high in adenocarcinoma patients compared to other lung cancer subtypes. Interestingly, Appalachian adenocarcinoma patients exhibit increased glycogen accumulation and higher glycogen phosphate content than patients from non-Appalachian counties. These data suggest differential glycogen accumulation is a unique feature of lung tumors from Appalachian adenocarcinoma patients. Our study highlights the potential clinical applications of MALDI-MSI for digital pathology, biomarker applications, and reveals molecular features that contribute to the health disparity in Appalachian lung cancer patients that warrant further molecular analysis.
Citation Format: Michael D. Buoncristiani, Lindsey R. Conroy, Harrison Clarke, Lyndsay E. Young, Ramon C. Sun. Mass spectrometry imaging reveals distinct differences in glycogen accumulation in lung tumors from Appalachian patients [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 2456.
Abstract 247: Targeting Notch4 with a novel neutralizing antibody inhibits tumor growth and alters immune cell populations within the tumor microenvironment
Authors: Eng Jason , Naiche L.A. , Swaminathan Bhairavi , Kato Yu , Thakkar Krishna , Vadakath Rahul , Herts James , Emmadi Rajyasree , Matsui Junji , Kitajewski Jan 
Published: June 2022

Abstract
Endothelial Notch signaling is critical for tumor angiogenesis and growth. Inhibition of Notch1 or its ligand, Dll4, can induce tumor vessel hypersprouting, which interferes with perfusion and reduces tumor development. Unfortunately, blocking Notch1 in endothelial cells of normal tissue can lead to tissue hypoxia and vascular neoplasms. Notch4, another member of the Notch family, is upregulated and increased in the endothelium of certain tumor types compared to normal vasculature. Reducing Notch4, unlike Notch1, causes reduction in developmental and tumor angiogenesis. Using a newly developed anti-Notch4 antibody, E7011, we assessed the effects on Notch4 inhibition on developmental retinal angiogenesis. E7011 treatment did not alter capillary density within the vascular plexus or endothelial tip cell number, but did decrease radial outgrowth and vein diameter, supporting the hypothesis that Notch4 functions as a pro-angiogenic signal. These findings suggest that the targeting of Notch4 could interfere with tumor angiogenesis and offer a novel therapeutic avenue. To establish the role of Notch4 within the tumor microenvironment, we analyzed its expression in both human and murine tumor samples. Immunofluorescent staining revealed a range of Notch4 expression in both tumor cells and endothelium in human triple negative breast cancers. Several murine syngeneic tumors examined expressed Notch4 primarily in the endothelium with only rare tumor expression. We treated orthotopically implanted Py8119 murine breast carcinomas and B16F10 melanomas with E7011, which significantly reduced tumor size compared to IgG treated controls, indicating that suppression of Notch4 is anti-tumorigenic. To determine mechanistically how E7011 delays tumor growth, we performed single cell RNA sequencing on E7011 and control treated Py8119 tumors. Surprisingly, we found that while Notch4 transcripts were present only in endothelial cells, E7011 administration dramatically altered macrophage and monocyte populations within the tumor. Taken together, these findings indicate that inhibition of tumor endothelial Notch4 by E7011 can regulate the presence of immune cells within the tumor microenvironment and improve tumor control.
Citation Format: Jason Eng, L.A. Naiche, Bhairavi Swaminathan, Yu Kato, Krishna Thakkar, Rahul Vadakath, James Herts, Rajyasree Emmadi, Junji Matsui, Jan Kitajewski. Targeting Notch4 with a novel neutralizing antibody inhibits tumor growth and alters immune cell populations within the tumor microenvironment [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 247.
Abstract 2487: Distinct venous brain vessels provide structures for T lymphocyte recruitment to brain tumors in mouse models of intracranial melanoma
Authors: Messmer Julia M. , Piechutta Manuel , Venkataramani Varun , Mayer Chanté , Berghoff Anna S. , Hinze Daniel , Hölzel Michael , Helfrich Iris , Schadendorf Dirk , Wick Wolfgang , Karreman Matthia A. , Winkler Frank 
Published: June 2022

Abstract
Immune checkpoint therapy has demonstrated potential for the treatment of brain metastases, but the mechanisms of lymphocyte recruitment to brain tumors are poorly understood. To monitor T cell infiltration and brain tumor growth in vivo in real time, we performed intravital microscopy of adoptively transferred and endogenous T cells in mouse models of intracranial melanoma. By spatio-temporal analysis of T cell infiltration dynamics in brain tumors we could identify a distinct type of venous blood vessels in the tumor vicinity, “peritumoral venous vessels” (PVVs). Intraluminal T cell attachment and T cell extravasation was increased at PVVs compared to intratumoral vessels. Moreover, PVVs were characterized by high perivascular T cell density, high T cell motility parameters and high expression of ICAM-1. PVVs were specifically exploited for the recruitment of T cells to melanoma brain tumors, whereas alternative T cell routes via brain structures such as brain capillaries, intratumoral blood vessels and parasagittal regions were not observed. Immune checkpoint inhibition increased T cell motility in the brain, facilitating the advance from PVV to tumor, which resulted in intracranial tumor growth inhibition. Our findings describe a distinct mechanism by which the immune system targets melanoma brain tumors, and, potentially, other intracranial pathologies.
Citation Format: Julia M. Messmer, Manuel Piechutta, Varun Venkataramani, Chanté Mayer, Anna S. Berghoff, Daniel Hinze, Michael Hölzel, Iris Helfrich, Dirk Schadendorf, Wolfgang Wick, Matthia A. Karreman, Frank Winkler. Distinct venous brain vessels provide structures for T lymphocyte recruitment to brain tumors in mouse models of intracranial melanoma [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 2487.