bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3557: Genetic algorithms to identify homologous recombination deficiency (HRD) in pancreas adenocarcinoma
Authors: Park Wungki , Chen Jiapeng , Chou Joanne F. , Iacobuzio-Donague Christine , Riaz Nadeem , O'Reilly Eileen M. 
Published: September 2020

Abstract
Introduction: Homologous recombination deficiency (HRD) is an emerging biomarker for DNA-damage-response (DDR)-targeted therapies in pancreatic cancer (PDAC). There are different methods available to identify HRD in other cancers, however these have not been evaluated comprehensively in PDAC for their response prediction to first-line platinum-based therapies (1L-platinum).
Methods: Patients with advanced (stage 3-4) PDAC who had germline and somatic MSK-IMPACT were included. We evaluated genetic methods for HRD and their association with clinical outcomes on 1L-platinum or 1L-non-platinum therapies. Homologous recombination (HR)-genes included: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1. We evaluated the status of pathogenic HR-gene mutations (HRm): (1) germline vs. somatic HRm; (2) core HRm (cHRm) (BRCA1, BRCA2, PALB2) vs. non-core (ncHRm); (3) zygosity (monoallelic vs. biallelic HRm). Additionally, HRD genetic signatures using large-scale state transition (LST) and signature 3 (Sig3) were evaluated.
Results: Two-hundred and sixty-two patients with advanced PDAC who received care at Memorial Sloan Kettering were included. There was no difference in overall survival (OS) for patients with either germline or somatic HRm, hence they were analyzed together as HRD. Median [95% CI] follow-up among surviving patients (n=75) was 21.9 [1.4-57.0] months, median OS was 15.5 [14.6-19] months, and median progression-free survival (PFS) was 7 [6.1-8.1] months. The effect of HRD on PFS was dependent on whether the patient received 1L-platinum or not. After controlling for stage at diagnosis, patients with HRD had a reduced risk of progression or death compared to patients without HRD when treated with 1L-platnium (HR: 0.44 [95%CI: 0.29-0.67], p&lt;0.01). Biallelic HRm and cHRm were associated with higher LST and tumor mutation burden. Sig3-positive patients were also associated with improved PFS compared to Sig3-negative patients when treated with 1L-platinum.
Conclusion: Patients who have PDAC with HRD defined by HRm had better OS irrespective of 1L-platinum, although they had better PFS when treated with 1L-platinum compared to 1L-non-platinum. Among methods to identify HRD, pathogenic HR-gene mutations remain the standard when using a targeted-sequencing approach. Further investigation is warranted.
Citation Format: Wungki Park, Jiapeng Chen, Joanne F. Chou, Christine Iacobuzio-Donague, Nadeem Riaz, Eileen M. O'Reilly. Genetic algorithms to identify homologous recombination deficiency (HRD) in pancreas adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3557.
Abstract 3571: Oxidative stress and the ovarian surface epithelium: TGF-β1 stimulation of IOSE cell lines reveals novel upregulation of NADPH oxidase 4, a membrane bound hydrogen peroxide producing enzyme
Authors: Meitzler Jennifer L. , Diebold Becky A. , Antony Smitha , Wu Yongzhong , Juhasz Agnes , Dahan Iris , Jiang Guojian , Lu Jiamo , Wang Stephen , Konaté Mariam M. , Roy Krishnendu , Doroshow James H. 
Published: September 2020

Abstract
Normal ovarian surface epithelium (OSE) has been widely studied as the origin of ovarian cancer. Repetitive ovulation has been implicated in cancer initiation based on damage and inflammation incurred to the OSE upon continuous cycles of tear and repair. Transforming growth factor-beta (TGF-β) plays a role in this normal ovulatory cycle, having been shown to inhibit human OSE proliferation and induce apoptosis, which may prevent the over-proliferation of cells. NADPH oxidase 4 (NOX4), a membrane-associated hydrogen peroxide-producing enzyme, has previously been shown to be sensitive to TGF-β1, with increased expression stimulated in smooth muscle cells and fibroblasts. Here we describe for the first time TGF-β1 induced upregulation of NOX4 in immortalized OSE (IOSE) cells (IOSE121, IOSE144, IOSE364, IOSE386 and IOSE397). This time-dependent increased expression (&gt;5 fold at 2 ng/ml TGF-β1, 24 h) was simulated by direct overexpression of NOX4 in IOSE397 cells and has demonstrated that increased NOX4, in the absence of further growth factor related effects, affords induction of p18 and p21. In addition, using immunohistochemical evaluation of human ovarian cancers in tissue microarrays (n=17 patients), we observed significantly increased expression of NOX4, suggesting that NOX4 upregulation may contribute to the malignant transformation of ovarian cells.
Citation Format: Jennifer L. Meitzler, Becky A. Diebold, Smitha Antony, Yongzhong Wu, Agnes Juhasz, Iris Dahan, Guojian Jiang, Jiamo Lu, Stephen Wang, Mariam M. Konaté, Krishnendu Roy, James H. Doroshow. Oxidative stress and the ovarian surface epithelium: TGF-β1 stimulation of IOSE cell lines reveals novel upregulation of NADPH oxidase 4, a membrane bound hydrogen peroxide producing enzyme [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3571.
Abstract 3627: Comparison of genetic profiles of small and large duct type intrahepatic cholangiocarcinoma with distal extrahepatic cholangiocarcinoma
Authors: Kim Hayeon , Lee Soo Yeon , Kim Aeree , Kim Baek-hui , Kim Chung-yeul 
Published: September 2020

Abstract
Cholangiocarcinoma comprises epithelial malignancy that occurs in various sites in the biliary tree. Cholangiocarcinoma is categorized into intrahepatic, perihilar, and distal bile duct carcinomas according to its anatomical position. According to the fifth edition of World Health Organization Classification of Tumors, intrahepatic cholangiocarcinoma (ICC) is further classified into small- and large duct types on histopathological basis. We analyzed molecular profiles of different types of cholangiocarcinoma by next-generation sequencing (NGS). We utilized the Oncomine Comprehensive Assay (OCA) panel v2 on the IonTorrent™ NGS platform to explore genetic differences among the two histologic types of ICC and distal extrahepatic cholangiocarcinoma (DEC). Formalin-fixed paraffin-embedded tumor tissues were obtained from 25 patients who underwent surgical resection of cholangiocarcinoma in Korea University Guro Hospital between 2010 and 2018. We analyzed 7 and 8 small- and large duct type ICCs and 10 DECs. NGS assay of the included cases showed distinct genetic alterations between ICC and DEC, which were enriched in different biological pathways. Unsupervised hierarchical clustering analysis showed two distinct groups. The first group consisted of 12 cases (9 DECs and 3 large duct type ICCs). The second group included 13 cases (7 large duct type and 6 small duct type ICCs). Molecular alteration patterns of a subset of large duct type ICCs were more closely related to DECs than small duct type ICCs. All included small duct type ICCs were considered genetically distinct from DECs. Our study suggested an association between anatomical and histopathological classifications of intra- and extrahepatic cholangiocarcinomas.
Citation Format: Hayeon Kim, Soo Yeon Lee, Aeree Kim, Baek-hui Kim, Chung-yeul Kim. Comparison of genetic profiles of small and large duct type intrahepatic cholangiocarcinoma with distal extrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3627.
Abstract 3789: Therapeutic targeting of the YAP/TAZ pathway in glioblastoma with verteporfin
Authors: Boyd Nathaniel H. , Vigneswaran Krish , Lallani Shoeb , Oh Se-Yeong , Boucher Andrew , Olson Jeffrey , Read Renee 
Published: September 2020

Abstract
Glioblastoma (GBM) is a particularly lethal brain neoplasm accounting for half of malignant primary brain tumors diagnosed in adults and maintains a devastating diagnosis, with a median survival of 14 months despite standard clinical interventions of surgical, chemotherapeutic, and radiation treatments. GBM tumorigenicity is often driven by aberrations in receptor tyrosine kinases (RTKs) such as EGFR, and the Pi-3 kinase (PI3K) signaling pathway. Using a Drosophila glioma model and human patient-derived glioma cells, we identified YAP/TAZ, effectors of the Hippo pathway that promote expression of stemness factors and oncogenes via activation of the TEAD transcription factors, as drivers of glioma tumorigenicity. This led to the discovery that YAP/TAZ are highly expressed in human patient-derived glioma stem cells and that knockdown of these inhibits cell growth. We hypothesized that Verteporfin, a benzoporphyrin derivative approved by the FDA for the treatment of macular degeneration, may have therapeutic benefit for glioblastoma due to its published ability to inhibit interaction between YAP and TEAD transcription factors. Using in vitro culture-based assays and in vivo in GBM xenograft models, we observed Verteporfin specifically induces apoptosis in GBM cells, slows tumor growth, and durably suppressesexpression of known and novel TEAD transcriptional targets in tumor tissue. We validated several direct targets using chromatin immunoprecipitation, and are seeking to further identify the full transcriptional program controlled by YAP/TAZ-TEAD in GBM. Our efforts have led to a phase 0 clinical trial where we were able to observe Verteporfin uptake in GBM tumors in human patients. These data indicate that Verteporfin is a promising therapeutic target for GBM.
Citation Format: Nathaniel H. Boyd, Krish Vigneswaran, Shoeb Lallani, Se-Yeong Oh, Andrew Boucher, Jeffrey Olson, Renee Read. Therapeutic targeting of the YAP/TAZ pathway in glioblastoma with verteporfin [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3789.
Abstract 3958: Establishment of an in vitro model to study cancer associated fibroblasts and their direct effect on desmoplasia
Authors: Nissen Neel Ingemann , Karsdal Morten , Willumsen Nicholas 
Published: September 2020

Abstract
Background: The extracellular matrix (ECM) and desmoplasia is emerging as key components in defining prognosis and response to treatment. Cancer associated fibroblasts (CAFs) are vital contributors to the desmoplastic reaction and novel ambitious therapies targeting tumor specific ECM and CAFs are being developed. However, it is still debated whether in fact desmoplasia acts as a barrier to- or promoter of - tumor growth. Therefore, there is a need to establish novel models of desmoplasia to improve the understanding of CAFs and associated cancer specific ECM alterations in order to be successful in drug development and prediction of treatment success. By applying the “Scar-in-a-jar” (SiaJ) model, we established an in vitro model including healthy fibroblasts and CAFs derived from the pancreas to study ECM changes and desmoplasia.
Methods: Primary healthy fibroblasts and CAFs were cultured for up to 12 days in the presence or absence of TGF-β. Type I (PRO-C1), type III (PRO-C3) and type VI (PRO-C6) collagen formation were quantified in cell supernatant using enzyme-linked immunosorbent assays. Metabolic activity was evaluated by AlamarBlue.
Results: In healthy fibroblasts no collagen formation could be detected without TGF-β. However, the presence of TGF-β induced PRO-C1, PRO-C3 and PRO-C6 formation with levels increasing up to 20-fold (p&lt;0.0001). Furthermore, PRO-C1, PRO-C3 and PRO-C6 levels where significantly increased in CAFs compared to healthy fibroblasts independent of TGF-β stimulation. There was no difference in metabolic activity across cell line.
Conclusions: TGF-β stimulation led to increased ECM protein expression in healthy fibroblasts but not in CAFs. However, CAFs expressed higher levels of collagens than healthy fibroblasts independent of TGF-β. These results suggest a distinct role of CAFs in their contribution to desmoplasia compared to healthy fibroblasts. The “Scar-in-a-Jar” model can provide a novel in vitro tool to study CAF activity and their direct effect on desmoplasia.
Citation Format: Neel Ingemann Nissen, Morten Karsdal, Nicholas Willumsen. Establishment of an in vitro model to study cancer associated fibroblasts and their direct effect on desmoplasia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3958.
Abstract 4: Choking cancer: Developing a pathway of Withaferin A for the prevention of angiogenesis
Authors: Samant Rishab Rajeev , Samant Rajeev S. 
Published: September 2020

Abstract
Cancer is arguably the most perplexing medical issue of today and manifests in many forms. Most cancers grow as solid tumors, and if they receive enough nutrients, they can metastasize. These tumors receive their nutrients from new blood vessels that grow in the direction of the tumor when the tumor sends bio-chemical signals such as VEGF (vascular endothelial growth factor). Stopping angiogenesis – new blood vessel formation – can cause the tumors to choke and die, which prevents metastasis. One-way of stopping angiogenesis is by using nutraceuticals: foods with a medical benefit. One well-recognized nutraceutical that stops angiogenesis is turmeric. However, not all nutraceuticals possess this property. This project determines if there exist any other easily accessible nutraceuticals possessing effective antiangiogenic properties. I used three different nutraceuticals: basil, ashwagandha, and valerian. Basil was my positive control because there are several published accounts of basil possessing antiangiogenic qualities. My negative control was saline. My hypothesis is that ashwagandha would have a strong antiangiogenic property. Although no study showed that ashwagandha possesses this property, several review articles stated that ashwagandha stopped cancer growth. I used CAMs (chick chorioallantoic membrane) as a to model study angiogenesis. I kept the CAMs, ex-ovo, in individual ceramic bowls lined with plastic wrap and incubated them for a certain number of days. I then took photos of my results and used Powerpoint to analyze them. My conclusion supported my hypothesis because ashwagandha blocked angiogenesis by 67%. This was almost identical to holy basil's rate of stopping angiogenesis.
To obtain clues as to how ashwagandha stopped angiogenesis, I used a previously published study by Szarc et.al. (PLoS One. 2014;9(2):e87850) and analyzed the results using Gene Expression Omnibus (Geo Database: GEO2R-GSE53O49) to obtain the top 250 changes in gene expression upon treatment of breast cancer cells (MCF7 and MDA-MB-231) with ashwaghanda. Examination of the list for angiogenesis related gene expression changes, revealed 19 significantly changing genes following ashwagandha treatment. I used the Search Tool for the Retrieval of Interacting Genes/Proteins: STRING- analysis, to reveal the interaction network between these 19 genes. I found that these genes were influencing DNA replication and cell cycle machinery. Thus, my findings suggest that ashwaghanda can inhibit the cell cycle of cancer cells to stop tumor growth. It possibly affects proliferation of endothelial cells to block angiogenesis.
Citation Format: Rishab Rajeev Samant, Rajeev S. Samant. Choking cancer: Developing a pathway of Withaferin A for the prevention of angiogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4.
Abstract 4617: Association between DNA oxidative damage and radiotherapy-induced skin toxicities in breast cancer patients
Authors: Mihyu Moody M. , Reis Isildinha M. , Takita Cristiane , Wright Jean L. , Lee Eunkyung , Nelson Omar L. , Yang George R. , Bakalar Johnna L. , Hu Jennifer J. 
Published: September 2020

Abstract
Background: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related death in the female population in the United States. Although radiotherapy (RT) has been shown to improve prognosis in breast cancer patients, RT may also lead to side effects that impact overall quality of life in some patients. The objective of this study was to investigate whether an oxidative damage biomarker, 8-hydroxy-2-deoxyguanosine (8-OHdG), is associated with RT-induced early adverse skin reactions (EASRs) in breast cancer patients.
Methods: 8-OHdG data before (pre-RT) and after RT (post-RT) were obtained from 475 breast cancer patients. RT-induced EASRs were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (v3.0) scale. Univariate logistic regression analyses were conducted to evaluate associations between above-median 8-OHdG (&gt; 85 ng/ml) and RT-induced grade 2+ EASRs. A propensity score (PS) was derived from a logistic regression model for predicting RT-induced EASRs on the basis of patient, tumor, and treatment characteristics. Then, the association between 8-OHdG and RT-induced EASRs was assessed in four risk groups defined by quartiles of PS.
Results: Overall, 59% of patients developed RT-induced grade 2+ EASRs and 28% developed moist desquamation. There were no significant associations between RT-induced EASRs and high 8-OHdG levels at both pre-RT and post-RT. However, there was a significant association between patients in the 2nd quartile PS that had high post-RT 8-OHdG levels and grade 2+ EASRs (OR=2.51, 95%CI=1.17, 5.40, p=0.0183).
Conclusions: The results from this study suggest that 8-OHdG is a potential biomarker for RT-induced EASRs in a breast cancer population with low to medium (2nd quartile) propensity for RT-induced EASRs.
Citation Format: Moody M. Mihyu, Isildinha M. Reis, Cristiane Takita, Jean L. Wright, Eunkyung Lee, Omar L. Nelson, George R. Yang, Johnna L. Bakalar, Jennifer J. Hu. Association between DNA oxidative damage and radiotherapy-induced skin toxicities in breast cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4617.
Abstract 4651: Interaction between outdoor ultraviolet radiation and indoor tanning bed use on skin cancer risk
Authors: Rhee Jongeun , Li Tricia , Li Wen-Qing , Qureshi Abrar A. , Cho Eunyoung 
Published: September 2020

Abstract
Background: Solar ultraviolet (UV) radiation and the use of UV-emitting tanning devices are risk factors for melanoma and non-melanoma skin cancer (NMSC). Despite abundant evidence, frequent outdoor sunbathers are more likely to use indoor tanning beds. In our study, we aim to investigate the interaction between indoor tanning bed use and exposure to solar UV radiation associated with the risk of skin cancer.
Methods: The study population was participants of the Nurses' Health Study II, which started in 1989 including 116,430 registered female nurses aged 25-42. Participants biennially self-reported diagnosis of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Cases for melanoma and SCC were confirmed by medical records. Information on indoor tanning bed use during high school/college or age 25-35 was collected. Cumulative average UV exposure at residence during follow-up was calculated for each participant. We built Cox proportional hazards models adjusting for potential confounders. Interactions between cumulative UV exposure and indoor tanning use were tested in multivariable-adjusted models for three types of skin cancer.
Results: We found significant interactions between cumulative average UV during follow-up and indoor tanning bed use during high school/college years (P for interaction=0.01) on the risk of BCC, but not during the age 25-35 (P for interaction=0.15). Subjects who were exposed to high UV and used tanning bed during high school/college (RR: 1.54, 95% CI 1.38, 1.72) or during age 25-35 (RR: 1.56, 95% CI: 1.43, 1.69) had nearly 50% increased risk of BCC compared to subjects who were exposed to low UV and did not use tanning bed. Increased risk but non-significant interactions were found for SCC (indoor tanning during high school/college years: P for interaction=0.29, during age 25-35: P for interaction=0.09). Subjects who were exposed to high UV and used tanning bed during age 25-35 had approximately double the risk of SCC (RR:
2.04, 95% CI: 1.51, 2.76), compared to the reference group. No significant interactions were found for the risk of melanoma.
Conclusions: We found significant interaction between outdoor UV and indoor tanning bed use during high school/college years on the risk of BCC but not SCC or melanoma.
Citation Format: Jongeun Rhee, Tricia Li, Wen-Qing Li, Abrar A. Qureshi, Eunyoung Cho. Interaction between outdoor ultraviolet radiation and indoor tanning bed use on skin cancer risk [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4651.
Abstract 4654: Supplemental one-carbon metabolism related B vitamins and lung cancer risk in the Women's Health Initiative
Authors: Brasky Theodore M. , Ray Roberta M. , Navarro Sandi L. , Schenk Jeannette M. , Newton Alison M. , Neuhouser Marian L. 
Published: September 2020

Abstract
We and others have reported associations between B vitamins principally involved in one-carbon metabolism and increased lung cancer risk; however results for women have been inconsistent. Here we report on the association of supplemental vitamins B6, folic acid, and B12 intake and lung cancer risk using data from the Women's Health Initiative (WHI) study of postmenopausal women. Between 1993 and 1998, 161,808 women were recruited to participate in the WHI at 40 US clinical centers. After exclusions, 159,232 women were available for analysis and followed prospectively for 18.3 years. Among them, 3,836 incident lung cancer cases were diagnosed. At baseline, supplemental B vitamins from multivitamins, vitamin mixtures, and individual supplements were assessed. Adjusted Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between supplemental B vitamin intake and lung cancer risk. Relative to non-users, women who took ≥50 mg/d of vitamin B6 had 18% (HR 0.82, 95% CI: 0.70-0.97) reduced lung cancer risk. Associations did not differ significantly by smoking status or lung cancer histology. Intakes of folic acid and vitamin B12 were not associated with risk. There is a need for replication of our findings from large, prospective studies with high-quality measurement of supplement intakes. As such, no recommendation can be made at present on the use of B6 supplements for lung cancer prevention in women.
Citation Format: Theodore M. Brasky, Roberta M. Ray, Sandi L. Navarro, Jeannette M. Schenk, Alison M. Newton, Marian L. Neuhouser. Supplemental one-carbon metabolism related B vitamins and lung cancer risk in the Women's Health Initiative [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4654.