bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 780: Racial disparities in death from cardiovascular disease for patients with prostate cancer: A population-based study
Authors: Nikita Nikita , Banks Joshua , Keith Scott , Yamoah Kosj , Naik Ulhas P. , Kim Felix J. , Shipon David M. , Kelly Wm Kevin , Rebbeck Timothy R. , Yao Grace Lu 
Published: July 2021

Abstract
Introduction: Prostate cancer (PCa) is the most common cancer diagnosis among men in the United States. However, a vast majority of patients with PCa die of causes other than PCa, the most common being cardiovascular disease (CVD). We hypothesize that CVD-related mortality in PCa patients is disproportionately higher among Blacks as compared to Whites.
Methods: We identified patients with PCa from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked files between 1/1/2004 and 12/31/2015. The PCa risk groups were created based on the National Comprehensive Cancer Network criteria: low, intermediate, and high risk. The primary endpoint was CVD-related mortality. The following CVD conditions were included in the CVD-specific mortality: acute myocardial infarction, stroke, congestive heart failure, atrial fibrillation, and ischemic heart disease. A proportional hazards model that considered the competing risks was fitted to address the hypothesis. The model was adjusted for age, year of diagnosis, marital status, income level, SEER-region, state buy-in, radiation, surgery, and education level.
Results: We identified 394,323 patients with PCa. Among these 80% were Whites, 15% were Blacks, and 5% were other races. The median age at diagnosis for Whites, Blacks, and other races was 69, 66, and 70 years, respectively. The incidence of CVD-related mortality was 5.6%, 6.6%, and 5% among Whites, Blacks, and Other races, respectively. Compared to Whites, Blacks had a significantly higher risk of mortality due to CVD across all PCa risk groups (Table). Similar results were not seen when the Other races was compared to Whites.
Conclusion: Blacks with PCa have a significantly higher risk of mortality due to CVD as compared to Whites across all PCa risk groups. Our study highlights the importance of cardio-oncology in the setting of PCa. Further studies are warranted to confirm the findings.
Table: Risk of CVD-related mortality among PCa patients; stratified by PCa risk group.Low-Risk (N=84,367)Intermediate-Risk(N=146,411)High-Risk(N=96,502)HR (95%CI); p-valueHR (95%CI); p-valueHR (95%CI); p-valueWhites(N=316,803)RefRefRefBlacks(N=58,046)1.23 (1.09-1.39); p&lt;0.0011.24 (1.14-1.34); p&lt;0.0011.09 (1.01-1.20); p=0.029Other Races(N=19,474)0.79 (0.60-1.04); p=0.0890.87 (0.74-1.03); p=0.1120.79 (0.69-0.91); p&lt;0.001
Citation Format: Nikita Nikita, Joshua Banks, Scott Keith, Kosj Yamoah, Ulhas P. Naik, Felix J. Kim, David M. Shipon, Wm Kevin Kelly, Timothy R. Rebbeck, Grace Lu Yao. Racial disparities in death from cardiovascular disease for patients with prostate cancer: A population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 780.
Abstract 920: Harnessing multiple mechanisms of action to target Nectin-4 as anti-tumor therapeutics
Authors: Pei Yi , Pohl Thomas , Hassan Ahmed , Przybyla Anna , Yu Raymond , Lu Huarui , Tang Fangqiang , Chen Kevin , Jin Wei , Dominguez Krizia , Huang Haichun , Lei Ming , Liu Zhong , Li Han 
Published: July 2021

Abstract
Nectin-4 belongs to an immunoglobulin superfamily (IgSF) of cell adhesion molecules that mediate cell-cell adhesion through homophilic or heterophilic interactions. In addition to the role in cell-cell adhesion, the Nectin family plays important role in regulating a diverse range of physiologic cellular activities, in viral entry, and in immune modulation. Nectin-4 has been reported to be upregulated in various epithelial cell cancers, such as breast cancer, lung cancer, and bladder cancer. The therapeutic value of Nectin-4 as an anti-tumor target has been demonstrated by a recently approved antibody-drug conjugate (ADC), Enfortumab vedotin. To fully exploit the potential of Nectin-4 as an anti-tumor target, we discovered a panel of monoclonal antibodies. These antibodies not only bind specifically to human Nectin-4 with high affinity, but also show differentiating characteristics including cell internalization, blockage of interaction with Nectin-1, blockage of interaction with TIGIT, and ADC-independent cytotoxicity. Our results suggest that in addition to ADC, other mechanisms targeting Nectin-4 can be utilized for therapeutics, such as immunomodulation and antibody- or immune cell-mediated tumor cell killing.
Citation Format: Yi Pei, Thomas Pohl, Ahmed Hassan, Anna Przybyla, Raymond Yu, Huarui Lu, Fangqiang Tang, Kevin Chen, Wei Jin, Krizia Dominguez, Haichun Huang, Ming Lei, Zhong Liu, Han Li. Harnessing multiple mechanisms of action to target Nectin-4 as anti-tumor therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 920.
Abstract 972: Pharmacological targeting CDC7 sensitizes oxaliplatin treatment in colorectal cancer
Authors: Chen Yufeng , Yu Zhaoliang , Deng Peng , Wu Xiaojian 
Published: July 2021

Abstract
The cell division cycle 7 (CDC7) is a serine/threonine kinase that plays a critical role in the initiation of DNA replication by phosphorylating MCM 2-7 complex, which is frequently overexpressed in various human cancers. This study aimed to investigate the roles of CDC7 in colorectal cancer (CRC) and its potential pharmacological value. We found CDC7 expression was associated with tumor recurrence and poor outcome in CRC patients. We depleted CDC7 expression with siRNA and found CDC7 depletion dramatically inhibits colony formation in CRC cells treated with oxaliplatin. Importantly, pharmacological inhibition of CDC7 with inhibitor (XL413 or PHA767491) could overcome oxaliplatin resistance of CRC cells in cells proliferation, clone formation and tumorsphere formation. To further validated these findings in vivo, we examined the efficacy of CDC7 inhibitor and oxaliplatin in a DLD1-derived xenograft mouse model and two PDX models. The combination of oxaliplatin and XL413 significantly inhibit xenograft tumor growth, which showed remarkably decreased Ki-67 and increased cleaved-caspase 3 by IHC analysis. Collectively, our findings unveil the critical role of CDC7 in colon cancer cells and targeting CDC7 is a potential effective therapeutic for CRC patients.
Citation Format: Yufeng Chen, Zhaoliang Yu, Peng Deng, Xiaojian Wu. Pharmacological targeting CDC7 sensitizes oxaliplatin treatment in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 972.
Abstract 989: Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triple-negative breast cancer cells
Authors: An Haein , Heo Jin Sun , Ooshima Akira , Wu Zhaoyan , Kim Seong-Jin , BAE ILLJU , Yang Kyung-Min 
Published: July 2021

Abstract
Modified arsenic derivative compounds such as arsenic trioxide (As2O3), arsenic trisulfide (As2S3), and tetraarsenic hexoxide (As4O6) have been known to be one of the potent anti-cytotoxic effects in various cancer cells, including leukemia, glioma, colon, breast, and cervix cancer cells. Particularly, tetraarsenic hexoxide was developed as a chemotherapeutic agent for patients with advanced cancers. Although anti-cancer effect of tetraarsenic hexoxide has been extensively studied in various cancer cells, the molecular basis of its tumor inhibitory activity remains poorly understood. In this study, we suggest a mechanism of tetraarsenic hexoxide induces pyroptosis through the increase of mitochondrial ROS by targeting phosphorylation of mitochondrial STAT3, subsequently activating caspase-3/GSDME that eventually leads to suppression of cancer progression of TNBC cells. Interestingly, we first found that tetraarsenic hexoxide markedly induced pyroptotic cell death through caspase-3 in releading N-terminal fragments of GSDME in TNBC cells. Indeed, tetraarsenic hexoxide-treated TNBC cells exhibited pyroptotic cell death and the release of LDH. Supporting this observation, inhibition of active caspase-3 attenuated tetraarsenic hexoxide-induced pyroptotic features by blocking the cleavage of GSDME. In conclusion, our results suggest a mechanism of tetraarsenic hexoxide by inducing pyroptosis through the increase of mitochondrial ROS by targeting phosphorylation of mitochondrial STAT3, subsequently activating caspase-3/GSDME that eventually leads to suppression of cancer progression of TNBC cells. Also, given that traditional chemotherapeutic agents, tetraarsenic hexoxide may be useful for aggressive TNBC cells showing resistance to apoptosis as a new GSDME-targeted therapeutic strategy.
Citation Format: Haein An, Jin Sun Heo, Akira Ooshima, Zhaoyan Wu, Seong-Jin Kim, ILLJU BAE, Kyung-Min Yang. Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 989.
Abstract CT172: Phase 2 clinical trial of dianhydrogalactitol (VAL-083) in patients with newly diagnosed MGMT-unmethylated GBM
Authors: Chen Zhong-ping , Guo Cheng-cheng , Yang Qun-ying , Li Jia-wei , Wu Shao-xiong , Langlands John , Johnson Gregory , Kwan Claire , Kanekal Sarath , Schwartz Richard , Bacha Jeffrey , Steino Anne , Brown Dennis 
Published: July 2021

Abstract
Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The majority of glioblastoma multiforme (GBM) patients have an unmethylated MGMT promoter status, leading to limited response to TMZ and decreased survival. Current standard-of-care includes surgery followed by chemoradiation and TMZ. An unmethylated promoter for O6-methylguanine DNA methyltransferase (MGMT) is a validated biomarker for TMZ-resistance and is strongly correlated with poor outcomes. VAL-083 is a novel bi-functional DNA targeting agent that induces inter-strand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated drug-resistance and has demonstrated cytotoxicity in MGMT-unmethylated GBM cell lines, cancer stem cells (CSCs) and in vivo models. Furthermore, VAL-083 acts as a radiosensitizer in GBM CSCs and non-CSCs. A Phase 2, open-label, biomarker-driven, study is being conducted to evaluate the tolerability and efficacy of VAL-083 in combination with radiation therapy (RT) in newly diagnosed MGMT-unmethylated GBM patients. A treatment regimen, consisting of a 6-week induction period of VAL-083 given IV at 20, 30, or 40 mg/m2/day x 3 days every 21 days and concurrent radiation (2 Gy daily, 5 days/week) followed by up to 24 weeks of maintenance therapy with single-agent VAL-083, is being evaluated. The study has 2 stages: Stage 1, dose-escalation, has identified a recommended dose of 30 mg/m2/day of VAL-083 in combination with RT as generally safe and well-tolerated. Stage 2, an expansion stage, has enrolled 20 additional patients at 30 mg/m2/day IV infusion on days 1, 2, and 3 of 21-day cycles. As of January 11, 2021, all 29 subjects in the study have been enrolled and completed the treatment stage of the study. Tumor response are assessed by MRI, according to RANO criteria. Efficacy endpoints include progression-free survival (PFS) and overall survival (OS). Additional endpoints include safety evaluations and pharmacokinetic assessments of plasma and CSF samples. The trial is continuing as planned and an update on primary results on safety and efficacy, and pharmacokinetics will be provided at the meeting. Clinicaltrials.gov identifier: NCT03050736.
Citation Format: Zhong-ping Chen, Cheng-cheng Guo, Qun-ying Yang, Jia-wei Li, Shao-xiong Wu, John Langlands, Gregory Johnson, Claire Kwan, Sarath Kanekal, Richard Schwartz, Jeffrey Bacha, Anne Steino, Dennis Brown. Phase 2 clinical trial of dianhydrogalactitol (VAL-083) in patients with newly diagnosed MGMT-unmethylated GBM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT172.
Abstract CT239: ENVASARC: A Pivotal Trial of Envafolimab, and Envafolimab in Combination with Ipilimumab, in Patients with Advanced or Metastatic Undifferentiated Pleomorphic Sarcoma or Myxofibrosarcoma who have Progressed on Prior Chemotherapy
Authors: D'Angelo Sandra , Robinson Steven , Lam Joelle , Adams Bonne , Freddo James , Theuer Charles P. , Maki Robert 
Published: July 2021

Abstract
Background: Metastatic undifferentiated pleomorphic sarcoma (UPS) and the genetically related myxofibrosarcoma (MFS) are soft tissue sarcoma (STS) subtypes with poor prognoses. While responses to front line chemotherapy can approach 20%, in the 2nd line setting and beyond, efficacy remains limited. Pazopanib, the only approved treatment in the refractory setting has demonstrated an objective response rate (ORR) of 4%. Envafolimab is a single domain PD-L1 antibody administered rapidly by subcutaneous (SQ) injection that is being studied in two additional pivotal trials: MSI-H cancer and biliary tract cancer. The activity of envafolimab is similar to other PD-1 antibodies administered intra-venously. Envafolimab demonstrated a 32% ORR in MSI-H colorectal cancer that failed three approved chemotherapeutics, similar to the ORR of 28% and 33%, with nivolumab and pembrolizumab, respectively. The rationale for the ENVASARC trial is based on the previously reported efficacy of checkpoint inhibition in UPS/MFS. Single agent pembrolizumab demonstrated a 23% ORR, while the combination of nivolumab and ipilimumab demonstrated a 29% ORR in refractory UPS/MFS. Methods: ENVASARC (NCT 04480502) is a pivotal multicenter (at ~25 U.S. centers) open-label, randomized, non-comparative, parallel cohort study of treatment with envafolimab 300 mg every 3 weeks by SQ injection (cohort A; n=80) or envafolimab 300 mg every 3 weeks by SQ injection combined with ipilimumab 1 mg/kg every 3 weeks intra-venously for four doses (cohort B; n=80) in patients with locally advanced, unresectable or metastatic UPS/MFS who have progressed on one or two lines of prior therapy. The primary objective of each of parallel cohort is to demonstrate an ORR with a lower limit of the 95% confidence interval that excludes 5.0% in each cohort. If ≥ 9 responders are observed of the 80 patients enrolled in each cohort, then the lower bound of the 95% confidence interval will exclude 5.0%. Secondary endpoints include duration of response (DOR), PFS and OS. Key inclusion criteria: ≤ 2 prior lines of therapy (neoadjuvant and adjuvant therapy excluded), ECOG ≤ 1.
Citation Format: Sandra D'Angelo, Steven Robinson, Joelle Lam, Bonne Adams, James Freddo, Charles P. Theuer, Robert Maki. ENVASARC: A Pivotal Trial of Envafolimab, and Envafolimab in Combination with Ipilimumab, in Patients with Advanced or Metastatic Undifferentiated Pleomorphic Sarcoma or Myxofibrosarcoma who have Progressed on Prior Chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT239.
Abstract LB045: Identification of plasma-derived, EV-based biomarkers for glioblastoma
Authors: Khodor Yevgenia L. , Chakrabortty Sudipto K. , Fischer Christian , Rauscher Martina , Balaj Leonora , Carter Bob S. , Yu Seth , Skog Johan 
Published: July 2021

Abstract
Background: Glioblastoma (GBM) is the most malignant and aggressive primary brain cancer in adults, with an incidence of 3.2 per 100,000 people. Currently, diagnosis is only performed via histopathological investigation of a tissue sample from a GBM lesion, complemented with molecular diagnostics for identification of select biomarkers. MRI is the standard of care for follow-up and monitoring of treatment response. Therefore, development of a “liquid biopsy” to obtain disease-relevant information from body fluids is highly desirable.Methods: We present the results from a clinical study in which extracellular vesicle (EV)-derived mRNAs were profiled from the plasma of GBM patients and control individuals for a total of 32 individual RNAseq libraries. Initial biomarker discovery was performed on plasma from 16 patients (8 GBM patients at the time of initial diagnosis and 8 age and sex matched controls). Hybrid capture and RNA-seq were performed via our proprietary pipeline on EV-associated mRNA isolated from 1-2mL plasma. Sequencing data was analyzed for differential gene expression. Validation was done with plasma samples from a new cohort of 8 patients and 8 control individuals.Results: We observed 98 mRNAs as differentially detected between GBM and control samples, with 83 mRNAs enriched in GBM samples and 15 mRNAs decreased (p &lt; 0.05). Correlation based on differentially detected mRNAs separated GBM and control samples into two unique populations. We were able to use the differentially expressed gene signature from the first cohort to separate GBM patients and control individuals in the second cohort. We are currently following up these results with a larger patient population. These data, while preliminary, provide a potential basis for the further development of a GBM gene panel test.Conclusions: We have identified a novel gene signature for GBM in plasma-derived EVs, which differs from previously identified biomarkers isolated from tissue. Further work will refine this signature to enable detection, characterization, and patient monitoring for GBM with less invasive and intensive methods.
Citation Format: Yevgenia L. Khodor, Sudipto K. Chakrabortty, Christian Fischer, Martina Rauscher, Leonora Balaj, Bob S. Carter, Seth Yu, Johan Skog. Identification of plasma-derived, EV-based biomarkers for glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB045.
Abstract LB064: Long-term application of TTFields in anaplastic astrocytoma - a case study
Authors: Markovic Darko 
Published: July 2021

Abstract
Background: Anaplastic astrocytomas WHO III° (AA) represent diffusely infiltrating, high grade gliomas (HGG). Despite advancements in the molecular characterization of HGG treatment options are limited and are often in analogy to grade IV glioblastoma treatment. Tumor Treating Fields therapy (TTF) is an established modality for newly diagnosed and recurrent glioblastoma (GBM) shown to significantly improve progression-free and overall survival. While TTF is under investigation in grade III gliomas in several clinical trials, we present an exemplary case of an AA undergoing mid-term TTF therapy and adjuvant chemotherapy to explore treatment adherence, feasibility and safety. Methods: We present case details of a patient from our specialized neurosurgical oncology center, with an anaplastic astrocytoma (WHO grade III) who began TTF treatment at first diagnosis while being in the adjuvant chemotherapy phase at the time of TTF commencement. We describe treatment details and the course of disease under continuous and ongoing TTF therapy. Results: In December 2016 a 43year-old male patient was diagnosed with an anaplastic astrocytomaIDH 1/2 mutant, MGMT promoter-hypermethylation without 1p/19q codeletion. After biopsy and consequent partial tumor resection, he received concomitant radiochemotherapy and adjuvant chemotherapy with temozolomide. TTF was started six months after initial diagnosis. He has now completed 1328 days of treatment with an average daily usage of 90% and has survived 48 months from first diagnosis (cutoff January, 8th, 2021). Since beginning TTF, he has undergone temozolomide treatment for 6 cycles. He continues TTF without further adjuvant therapy. The patient is symptomatically stable and his quality of life is maintained. Significant adverse events or longer treatment interruptions have not occurred. Conclusion: The treatment with TTFields was well tolerated and seems to be feasible in this patient with an anaplastic astrocytoma. Considering the long treatment duration and favorable average daily usage, this treatment might be suitable for a long-term treatment in high grade gliomas. Ongoing clinical trials will provide more information on safety and efficacy for the use of TTFields in patients with grade III gliomas.
Citation Format: Darko Markovic. Long-term application of TTFields in anaplastic astrocytoma - a case study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB064.
Abstract LB182: Vaccination by liposomes and synthetic short peptide eradicated HPV-associated tumor
Authors: He Xuedan , Zhou Shiqi , Quinn Breandan , Jahagirdar Dushyant , Ortega Joaquin , Abrams Scott I. , Lovell Jonathan F. 
Published: July 2021

Abstract
Human papilloma virus (HPV)-16 is associated with cervical cancers and induces expression of the E6 and E7 oncogenes. 6 major histocompatibility complex (MHC) class I (MHC-I) epitopes were predicted to be immunogenic by sequencing a murine cell line that expresses E6/E7. A liposomal vaccine made of cobalt-porphyrin-phospholipid (CoPoP) and synthetic 9-mer epitopes appended with 3 histidine residues, resulting in rapid formation of stable peptide-liposome particles. Immunization with these predicted 6 peptides led to protection from tumor challenge on mice. Of the 6 peptides screened, only the previously identified E749-57 epitope has anti-tumor efficacy. The peptide-liposome particles that formed upon mixing E7HHH49-57 with CoPoP liposomes were stable in serum and avidly taken up by immune cells in vitro and rapidly released in lysosome. As a prophylactic vaccine, liposomal E7HHH49-57 vaccine protected mice from tumor challenge and re-challenge. As a therapeutic vaccine, immunization with the synthetic short peptide at a dose of 100 ng protected mice when admixed with CoPoP liposomes, whereas 200-fold higher peptide doses were ineffective with the Poly(I:C) adjuvant. CoPoP induced strong infiltrating CD8+ T response within the tumor microenvironment with improved functional profile. Vaccine monotherapy using nanogram dosing of the E7HHH49-57 peptide admixed with CoPoP reversed the growth of large established tumors, permanently eradicating subcutaneous tumors upwards of 100 mm3, and also completely eradicated lung tumors in a metastasis model.
Citation Format: Xuedan He, Shiqi Zhou, Breandan Quinn, Dushyant Jahagirdar, Joaquin Ortega, Scott I. Abrams, Jonathan F. Lovell. Vaccination by liposomes and synthetic short peptide eradicated HPV-associated tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB182.