tbuckley/cabot-search huggingface dataset:
Associations between oncogenic risk markers and clinical outcomes among black and white colorectal cancer patients.
Authors: Victoria Starks, Edith P. Mitchell
Journal: Journal of Clinical Oncology (2020)

e16078 Background: Blacks have a 25% higher incidence of colorectal cancer compared to their white societal counterparts 1 . Additionally, the overall mortality rate among black colorectal cancer patients is 50% higher than that of whites 2 . However, little is known about the biomarkers prevalent among blacks and their possible correlation to treatment response and patient outcomes. Objective: The objective of this study is to explore disease trends that may unveil a correlation between molecular markers, pathologic stage at presentation and poor clinical outcomes among black colorectal cancer patients. Methods: De-identified patient data was obtained from The Oncology Data Services Department (Cancer Registry) of TJUH. The population cohort (n = 836) included newly diagnosed colorectal cancer patients treated at TJUH from 2000-2019, &amp; included information regarding patient race, sex, age at presentation, stage at presentation, histological code, tumor markers: KRAS, NRAS, BRAF, MS1, treatment received, surgical findings: tumor size, lymph node involvement, presence of distant metastases at first surgery, response to chemotherapy &amp; disease-free survival. Results: Findings reveal a higher prevalence of BRAF mutations among whites compared to blacks within this population, while black patients were diagnosed later according to AJCC pathological stage at presentation. Future analysis of this cohort will further divide the population by age ( &lt; 50, 50-65, &amp; &gt; 65). This facet of the study will explore relationships between age &amp; stage at presentation among patients of different races. Conclusions: Both oncogenic risk markers and AJCC stage at presentation differ between black and white colorectal cancer patients within this population. Additional analysis regarding age at presentation will further inform us as to how these findings may contribute to the comparatively higher incidence and mortality rates among black colorectal cancer patients. Researchers should continue to explore possible etiologies for the prevalent racial disparities seen among black colorectal cancer patients.
Abstract P2-15-15: Evaluation of the efficacy and safety of the combination of Gemcitabine and Nedaplatin for patients with metastatic breast cancer
Authors: Jian Yue, Peng Yuan, Nanlin Hu, Yiran Si, Xue Wang
Journal: Cancer Research (2020)

Abstract Background: Owing to the need for the effective and tolerable new regimens for the treatment of patients with metastatic breast cancer (MBC) previously treated with anthracyclines and/or taxanes, we aimed to assess the activity and safety of the gemcitabine plus nedaplatin combination chemotherapy. Methods: Forty-five patients were enrolled. All the patients received gemcitabine and nedaplatin from November 2014 to February 2019.Gemcitabine 1000mg/m2 was administered on days 1 and 8. nedaplatin 60mg/m2 was given over 60mins on day 2 and 3. The primary end point was the overall response rate (ORR). Secondary objectives included overall survival (OS), progression-free survival (PFS), toxicity, and predictive factors. Results: Patients received treatment for a median of four Cycles. One of the 45 patients achieved a complete response, but 21 achieved a partial response, for an overall response rate of 48.9(95% confidence interval,33.7-64.1%). The median overall survival time was 17 months and the median progression-free survival was 5.0 months. Grades 3-4 hematological toxicities include leukopenia in 22.2% of patients, neutropenia in 28.9%, thrombocytopenia in 17.6%. Grade 3-4 nonhematological toxicities included nausea and vomiting in 31.1% of patients. There were no treatment-related deaths. Conclusion: The combination of gemcitabine and nedaplatin is an effective and tolerable treatment for MBC previously treated with anthracyclines and/or taxanes. Table 1 Patient characteristicPatient characteristicNumber of patients45Age53(29-72)Molecular subtypeLuminal A9Luminal B14HER2 positive1Triple negative21 Table 2: Response rateNumber of patients(n=45)%Complete response12.2Partial response2146.7Stable disease1635.6Progressive disease715.6 Table 3 Non-hematological toxicityToxicityGrade≥3(%)1234Nausea/vomiting1512204.4Elevation of transaminase173000Alopecia63000 Table 4 Hematological toxicityToxicityGrade≥3(%)1234Leukopenia14159122.2Neutropenia13129428.9Thrombocytopenia124417.8Anemia224000 Figure 1 progression-free survival time Figure 2 Overall survival time from the start of treatment with gemcitabine and nedaplatin. Citation Format: Jian Yue, Peng Yuan, Nanlin Hu, Yiran Si, Xue Wang. Evaluation of the efficacy and safety of the combination of Gemcitabine and Nedaplatin for patients with metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-15.
Identification and validation of dichotomous immune subtypes based on intratumoral immune cells infiltration in clear cell renal cell carcinoma patients
Authors: Ying Xiong, Zewei Wang, Quan Zhou, Han Zeng, Hongyu Zhang, Zhaopei Liu, Qiuren Huang, Jiajun Wang, Yuan Chang, Yu Xia, Yiwei Wang, Li Liu, Yu Zhu, Le Xu, Bo Dai, Qi Bai, Jianming Guo, Jiejie Xu
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Increasing evidence has elucidated the clinical significance of tumor infiltrating immune cells in predicting outcomes and therapeutic efficacy. In this study, we comprehensively analyze the tumor microenvironment (TME) immune cell infiltrations in clear cell renal cell carcinoma (ccRCC) and correlated the infiltration patterns with anti-tumor immunity and clinical outcomes. Methods We analyzed immune cell infiltrations in four independent cohorts, including the KIRC cohort of 533 patients, the Zhongshan ccRCC cohorts of 259 patients, the Zhongshan fresh tumor sample cohorts of 20 patients and the Zhongshan metastatic ccRCC cohorts of 87 patients. Intrinsic patterns of immune cell infiltrations were evaluated for associations with clinicopathological characteristics, underlying biological pathways, genetic changes, oncological outcomes and treatment responses. Results Unsupervised clustering of tumor infiltrating immune cells identified two microenvironment subtypes, TMEcluster-A and TMEcluster-B. Gene markers and biological pathways referring to immune evasion were upregulated in TMEcluster-B. TMEcluster-B associated with poor overall survival (p&lt;0.001; HR 2.629) and recurrence free survival (p=0.012; HR 1.870) in ccRCC validation cohort. TMEcluster-B cases had worse treatment response (p=0.009), overall survival (p&lt;0.001; HR 2.223) and progression free survival (p=0.015; HR 2.7762) in metastatic ccRCC cohort. The predictive accuracy of International Metastatic Database Consortium risk score was improved after incorporation of TME clusters. Conclusions TMEcluster-A featured increased mast cells infiltration, prolonged survival and better treatment response. TMEcluster-B was a heavily infiltrated but immunosuppressed phenotype enriched for macrophages, CD4 + T cells, Tregs, CD8 + T cells and B cells. TMEcluster-B predicted dismal survival and worse treatment response in clear cell renal cell carcinoma patients.
Abstract P3-12-02: Anlotinib in pre-treated metastatic HER2-negative breast cancer: A phase II, single-arm clinical study
Authors: Nanlin Hu, Yang Luo, Jiayu Wang, Qing Li, Pin Zhang, Fei Ma, Binghe Xu, Peng yuan
Journal: Cancer Research (2020)

Abstract Background: There is no standard treatment strategy for patients with locally advanced or metastatic breast cancer suffering progression after one prior chemotherapy with metastasis setting. Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. This study is performed to assessed the efficacy and safety of anlotinib in patients with HER2 negative locally advanced or metastatic breast cancer for whom at least one lines of prior chemotherapy had failed. Method: This open-label, single arm study enrolled patients with HER2-negative breast cancer, pretreated with anthracycline, taxanes, and who failed in the metastatic setting at least 1 prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients. Anlotinib was administered 12mg d1-d14 for a 21-day cycle. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. The treatment duration is until disease progression or intolerability of anlotinib. Results: From July 12th in 2018 to July 1st in 2019, 18 eligible patients were enrolled in this, open-label, single arm study and received anlotinib with a median age of 56 years old(range 32 to 74 years). Median follow-up time was 2.8 months(range 1.0 to 9.9 months). Median 18 patients were eligible for efficacy analysis. Median PFS was 4.43 months (95% confidence interval (CI), 3.15m - 5.71 m). ORR was 22.2% (4/18). DCR was 55.6% (10/18). Only 2/18(11.1%) patients was reported dead, so median OS was not reached for now. The most common grade 3/4 treatment-related AEs were hypertension (3/18,16.7%), and the blood pressure got back to grade 1/2 as soon as the antihypertensive drugs were offerd. No other grade 3/4 adverse events were observed. No patients had dose reduction because of adverse events. Conclusion: Anlotinib exhibited objective efficacy in heavily pretreated, metastatic HER2-negative breast cancer with mild toxicity. Multi-center prospective studies enrolling more patients are needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04002284 Citation Format: Nanlin Hu, Yang Luo, Jiayu Wang, Qing Li, Pin Zhang, Fei Ma, Binghe Xu, Peng yuan. Anlotinib in pre-treated metastatic HER2-negative breast cancer: A phase II, single-arm clinical study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-12-02.
Abstract BS1-2: Genome regulation by long noncoding RNA genes
Authors: HY Chang
Journal: Cancer Research (2020)

Abstract The discovery of extensive transcription of long noncoding RNAs (lncRNAs) provide an important new perspective on the centrality of RNA in gene regulation. I will discuss genome-scale strategies to discover and characterize lncRNAs, including RNA chemical modifications and RNA structures. LncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators, and target these enzymatic activities to appropriate locations in the genome. Long noncoding RNAs can function as modular scaffolds to specify higher order organization in RNP complexes and in chromatin states. A new emerging theme is that DNA elements that mediate lncRNA expression can also have powerful effects in controlling chromatin neighborhoods, which alter oncogene expression and activity. The importance of these modes of regulation is underscored by the newly recognized roles of long RNAs in human diseases. Citation Format: HY Chang. Genome regulation by long noncoding RNA genes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr BS1-2.
miR-128-3p Is a Novel Regulator of Vascular Smooth Muscle Cell Phenotypic Switch and Vascular Diseases
Authors: Floriana Maria Farina, Ignacio Fernando Hall, Simone Serio, Stefania Zani, Montserrat Climent, Nicolò Salvarani, Pierluigi Carullo, Efrem Civilini, Gianluigi Condorelli, Leonardo Elia, Manuela Quintavalle
Journal: Circulation Research (2020)

MicroRNAs (miRNAs, miRs) are small noncoding RNAs that modulate gene expression by negatively regulating translation of target genes. Although the role of several miRNAs in vascular smooth muscle cells (VSMCs) has been extensively characterized, the function of miRNA-128-3p (miR-128) is still unknown.To determine if miR-128 modulates VSMC phenotype and to define the underlying mechanisms.We screened for miRNAs whose expression is modulated by an altered DNA methylation status in VSMCs, and among the hits, we selected miR-128. We found that miR-128 was expressed in various tissues, primary murine cells, and pathological murine and human vascular specimens. Through gain- and loss-of-function approaches, we determined that miR-128 affects VSMC proliferation, migration, differentiation, and contractility. The alterations of those properties were dependent upon epigenetic regulation of key VSMC differentiation genes; notably, Kruppel-like factor 4 was found to be a direct target of miR-128 and able to modulate the methylation status of the pivotal VSMC gene myosin heavy chain 11 (Myh11). Finally, in vivo lentiviral delivery of miR-128 prevented intimal hyperplasia in a mouse model of carotid restenosis without modifying vital cardiovascular parameters.miR-128 is a critical modulator of VSMCs and is regulated by epigenetic modifications upon stress. Its modulation in the context of disease could be exploited for therapeutic purposes.
Abstract ES12-3: Clinically relevant biomarkers of PARP1 inhibitor resistance and indicators of targeted combinatorial treatments
Authors: V Serra
Journal: Cancer Research (2020)

Abstract Tumors with defective DNA repair by the homologous recombination repair (HRR) pathway are exquisitely sensitive to DNA damaging agents and to novel agents that block parallel pathways, including PARP inhibitors (PARPi). PARPi have been approved for the treatment of metastatic ovarian cancer (OvC) or breast cancer (BC). Currently used selection biomarkers to enrich the population of patients (pt) most likely to respond, namely the platinum-sensitive or BRCA1/2-mutated patients (pts), have limited predictive capacity. There is a need for more specific biomarkers to guide personalized treatment. Genomic scars/signatures have been proposed as putative biomarkers associated with DNA repair deficiency. A major limitation of these assays is the lack of specificity in HRR-altered tumors once they have restored the HRR function as mechanism of drug resistance. Functional assays are therefore needed to assess the actual status of tumor HRR, both in BRCA1/2-mutated pts and in BRCA1/2-wt, to identify tumors with germline/somatic HRR deficiency that could benefit of PARPi treatment. In this sense, the RAD51 foci assay is a functional and dynamic biomarker of HRR that correlates with PARPi response. In this educational talk, we will review the current knowledge on PARPi sensitivity and resistance in breast cancer, response biomarkers and the potential of targeting the replication stress response to revert PARPi resistance, namely using WEE1 or ATR inhibitors (WEE1i, ATRi). Our preclinical work using patient-derived tumor xenoimplant models (PDX) from triple negative breast cancer (TNBC) identified selection biomarkers for WEE1i or ATRi as single agents or in combination with PARP1/2 inhibitors, and highlights the potential of DNA damage repair inhibitors for the treatment of TNBC, an approach currently being tested in the clinic. Citation Format: V Serra. Clinically relevant biomarkers of PARP1 inhibitor resistance and indicators of targeted combinatorial treatments [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES12-3.
Abstract P6-10-30: Developing 3D subtyping model for breast cancer patients based on absolute quantitation or ER, PR and Her2 at protein level
Authors: Jiandi Zhang
Journal: Cancer Research (2020)

Abstract The concept of intrinsic subtypes of breast cancer have been well accepted with several predictor applications based on this concept achieved success in clinical practice. However, all these predictor applications are based on gene expression profiling, and the surrogate assay at protein level is based on immunohistochemistry (IHC), which is known to be associated with inherent problems of subjectivity and inconsistency. Consequently, subtyping of breast cancer patients in clinical practice is limited either by the cost or the inaccuracy (surrogate assay). In this study, we proposed the first predictor model at protein level based on the three-dimensional (3D) distribution of samples using ER, PR and Her2 protein levels as coordinates. Method: Quantitative dot blot (QDB) method was used as a universal platform to achieve absolute quantitative of ER, PR, Her2 and Ki67 protein levels using total tissue lysates prepared from 2 × 15 um Formalin Fixed Paraffin Embedded (FFPE) slices. Total of 1248 FFPE slices were provided from local hospitals sequentially and non-selectively. The measured tissue biomarker levels were plotted in 3D scatterplot for analysis, in combination with provided clinicopathological parameters and overall survival data. Results: We observed natural segregation of these samples into three distinct groups to mimic “balls falling from ceiling corner” distribution pattern. This distribution pattern disappeared when the scatterplot was narrowed in a small box of ER&amp;lt;0.2 nmole/g, PR &amp;lt;0.8 nmole/g and Her2&amp;lt;0.3 nmole/g. When the observed Her2 level at 0.3 nmole/g was used as cutoff to convert samples dichotomously, we achieved overall concordance with IHC at 94.8%. In addition, 260 out 271 Her2 positive samples were either with ER&amp;lt;0.2 nmole/g or PR&amp;lt;0.8 nmole/g or both, with 8 more samples at the vicinity of corner group. The model was further evaluated with both the overall recurrence and survival of the patients. Conclusion: We developed the first 3D predictor model for subtyping of breast cancer patients based on the absolute and quantitative levels of ER, PR and Her2 at protein level. We propose this model the projection of intrinsic types at protein level. The adoption of this predictor model in clinical practice should significantly lower the barrier to allow practicing subtyping of breast cancer patients in daily clinical practice worldwide. Citation Format: Jiandi Zhang. Developing 3D subtyping model for breast cancer patients based on absolute quantitation or ER, PR and Her2 at protein level [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-30.
Echocardiographic Pulmonary Hypertension and Right Heart Function—The Big Picture—Reply
Authors: Jessica H. Huston, Evan L. Brittain
Journal: JAMA Cardiology (2020)

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Annals Graphic Medicine - True Tales From the Outbreak: Life in the Hot Zone
Authors: Alex Thomas
Journal: Annals of Internal Medicine (2020)

Web Exclusives5 May 2020Annals Graphic Medicine - True Tales From the Outbreak: Life in the Hot ZoneFREEAlex Thomas, MDAlex Thomas, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0022 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G20-0022.Author/Illustrator Information: Alex Thomas, MD (e-mail, [email protected]com), is a pediatric allergist/immunologist and a cartoonist and illustrator. He is a cofounder of Booster Shots Comics and Booster Shot Media (Twitter: @BoosterShotCmx; Facebook: https://www.facebook.com/BoosterShotComics/).This article was published at Annals.org on 31 March 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 May 2020Volume 172, Issue 9Page: W119-W120KeywordsConflicts of interestDisclosureHealth care ePublished: 31 March 2020 Issue Published: 5 May 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract P3-07-11: BRCA mutations and association with discordance in a large oncotype database
Authors: Julia Blanter, Brittney Zimmerman, Serena Tharakan, Krystal Cascetta, Meng Ru, Amy Tiersten
Journal: Cancer Research (2020)

Abstract BACKGROUND: BRCA mutated tumors have been shown to be associated with higher recurrence scores as compared to BRCA negative breast cancer patients. Prior studies have demonstrated 7-19% discordance between oncotype RS and tumor grade (TG) in breast cancer patients. We developed a large oncotype database to determine if BRCA mutation status is associated with discordance. METHODS: We identified 723 patients (32 (4%) BRCA positive patients and 691 (96%) BRCA negative patients) with early-stage, hormone positive BC treated between 2006-2018, with tumor characteristics available for analysis. Discordance was defined as one or two-step difference between RS (low, intermediate, high risk) and TG (well (WD), moderately (MD) and poorly (PD) differentiated). BRCA status was defined as BRCA 1 deleterious mutation, BRCA 2 deleterious mutation, BRCA mutation of unknown type, BRCA variant of undetermined significance (VUS) or other mutation. N(%) or median were used to describe patients’ characteristics between groups and compared by Mann-Whitney U test at the confidence level of 5%. RESULTS: Among these patients, there were 32 patients (4% of total) who had any documented mutation or VUS. 16% had documented deleterious mutation in BRCA 1, 22% BRCA 2, 6% BRCA unknown type, 25% BRCA VUS, and 31% other VUS (most commonly CHEK2 and ATM). Median RS was 23.5 in patients with deleterious BRCA mutations (1, 2 or unknown) vs. 16 in patients in the BRCA negative database which was statistically significant (p&amp;lt;0.01). One step and two-step discordance was present in 46% and 8% respectively of patients with deleterious BRCA mutations vs. 53% and 11% respectively in the BRCA negative database. CONCLUSIONS: Patients with deleterious BRCA mutations demonstrated no difference in rates of discordance as compared to BRCA negative patients. We further demonstrated that patients with BRCA positive tumors display higher recurrence scores than patients with BRCA negative tumors. Citation Format: Julia Blanter, Brittney Zimmerman, Serena Tharakan, Krystal Cascetta, Meng Ru, Amy Tiersten. BRCA mutations and association with discordance in a large oncotype database [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-07-11.