tbuckley/cabot-search huggingface dataset:
Risk of Cancer Among Children and Young Adults With Congenital Heart Disease Compared With Healthy Controls
Authors: Zacharias Mandalenakis, Christina Karazisi, Kristofer Skoglund, Annika Rosengren, Georgios Lappas, Peter Eriksson, Mikael Dellborg
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Adult patients with congenital heart disease (CHD) have an increased incidence of cancer, presumably owing to repeated radiation exposure, genetic predisposition, or repeated stress factors during heart interventions. However, there are limited data on the risk of cancer in children and young adults with CHD compared with the general population. <h3>Objective</h3> To determine the risk of developing cancer from birth to age 41 years among patients with CHD compared with healthy matched controls. <h3>Design, Setting, and Participants</h3> This registry-based, matched, prospective cohort study in Sweden used data from the Patient and Cause of Death Registers. Successive cohorts of patients with CHD born from 1970 to 1979, 1980 to 1989, and 1990 to 1993 were identified. Each patient (n = 21 982) was matched for birth year, sex, and county with 10 controls without CHD from the general population (n = 219 816). Follow-up and comorbidity data were collected from 1970 until 2011. Data analysis began in September 2018 and concluded in February 2019. <h3>Main Outcomes and Measures</h3> Risk of cancer among children and young adults with CHD and among healthy controls. <h3>Results</h3> Among 21 982 individuals with CHD and 219 816 healthy matched controls, 428 patients with CHD (2.0%) and 2072 controls (0.9%) developed cancer. Among patients with CHD, the mean (SD) age at follow-up was 26.6 (8.4) years, and 11 332 participants (51.6%) were men. Among healthy controls, the mean (SD) age at follow-up was 28.5 (9.1) years, and 113 319 participants (51.6%) were men. By the age of 41 years, 1 of 50 patients with CHD developed cancer. The overall hazard ratio (HR) for cancer was 2.24 (95% CI, 2.01-2.48) in children and young adults with CHD compared with controls. Risk increased by each successive birth cohort to an HR of 3.37 (95% CI, 2.60-4.35) among those born from 1990 to 1993. The risk of cancer was similar in men and women with CHD (men: HR, 2.41; 95% CI, 2.08-2.79; women: HR, 2.08; 95% CI, 1.80-2.41). The HR for cancer among patients with CHD who underwent surgery was 1.95 (95% CI, 1.58-2.33) compared with controls; for patients with CHD who had not undergone surgery, the HR was 2.43 (95% CI, 2.12-2.76). According to a hierarchical classification, a significantly increased risk of cancer was found among patients with complex heart lesions, such as conotruncal defects (HR, 2.29; 95% CI, 1.62-3.25), compared with healthy controls. <h3>Conclusions and Relevance</h3> Children and young adult patients with CHD had an increased risk of developing cancer compared with healthy matched controls, and the risk was significantly higher among patients with CHD from the most recent birth cohort. An increased risk of cancer in all CHD lesion groups was found, and a systematic screening for cancer could be considered for this at-risk group of patients.
Abstract 2054: A novel Bcl-2/Bcl-XL inhibitor APG-1252-12A as a potential therapeutic strategy for gastric carcinoma
Authors: Xianglei Yan, Hanjie Yi, Qiuyun Luo, Luping Yuan, Suna Zhou, Wentao Pan, Lin Zhang, Miaozhen Qiu, Dajun Yang
Journal: Cancer Research (2019)

Abstract Background: Gastric cancer (GC) is the fourth most common type of malignant tumor and is the second leading cause of cancer-related mortality. Surgery and chemotherapy play important role in the treatment of GC, however the overall survival of gastric cancer patients is not promising. APG-1252-12A specifically binding to Bcl-2 and Bcl-xl has shown efficacy in some solid tumor. We intend to investigate the anticancer effect and combination enhancement of Fluorouracil (5-FU) in gastric cancer. Materials and methods: Human gastric cancer cell lines (AGS, NCI-N87, SGC7901, BGC823, MKN45 and NUGC3) were treated with different concentrations and time of APG-1252-12A. CCK-8, survival assays, flow cytometry and western blot were used to assess cell survival, cell cycle progression and apoptosis. In vivo, xenograft mouse models (NCI-N87) were established to analyze the anticancer effect and combination enhancement of 5-FU. Results: In vitro, APG-1252-12A inhibited proliferation of gastric cancer cell lines, without cell-cycle arrest. Meanwhile, APG-1252-12A increased protein expression of apoptosis signal pathway. The combination of APG-1252-12A and 5-FU resulted in the accumulation of apoptosis protein such as PARP and cleaved caspase3, which indicating an increasing of chemosensitivity. In xenograft mouse models, single therapy with APG-1252-12A obviously suppressed tumor growth, especially in 100mg/kg group. Combination group delayed tumor growth more significantly compared with APG-1252-12A and 5-FU single therapy. By analyzing proliferation marker Ki67 in xenograft tumor specimens, we found that the number of proliferating cells significantly decreased in tumors receiving combination treatment of APG-1252-12A and 5-FU compared with tumors receiving single treatment. The results strongly confirmed the antitumor capacity of APG-1252-12A combined with 5-FU. Conclusions: The results strongly suggest that Bcl-2 and Bcl-xl inhibitor APG-1252-12A may serve not only as a single therapy, but also as an effective adjunct to current chemotherapeutic regimens for treating gastric cancer through apoptosis signal pathway. Citation Format: Xianglei Yan, Hanjie Yi, Qiuyun Luo, Luping Yuan, Suna Zhou, Wentao Pan, Lin Zhang, Miaozhen Qiu, Dajun Yang. A novel Bcl-2/Bcl-XL inhibitor APG-1252-12A as a potential therapeutic strategy for gastric carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2054.
Carfilzomib-lenalidomide-dexamethasone in the management of lenalidomide-refractory multiple myeloma.
Authors: Claudio Cerchione, Giovanni Martinelli, Davide Nappi, Anna Emanuele Pareto, Maria Di Perna, Katia Ferrara, Fabrizio Pane, Lucio Catalano
Journal: Journal of Clinical Oncology (2019)

e19522 Background: Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, whose prognosis is particularly severe. Methods: 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43-82), median age at start of treatment 67 years (r. 48-84) previously treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2-18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. Results: According to IMWG criteria, after a median follow-up of 9 months (r. 2-18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1-4), median OS from diagnosis was 62 months (r. 9-170), median OS from start of Carfilzomib was 11 months (r. 2-18). Carfilzomib was well tolerated, with grade 2 anemia in 39% (16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion-dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2-3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Conclusions: Carfilzomib-Lenalidomide-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT.
Clinical validation of long-range PCR assay for MLL partial tandem duplications for acute myeloid leukemia.
Authors: Sun Hee Rosenthal, Hai-Rong Li, Kevin Qu, Yan Liu, Renius Owen, Frederick KARL Racke, Felicitas L. Lacbawan
Journal: Journal of Clinical Oncology (2019)

7033 Background: Partial tandem duplication of the mixed lineage leukemia gene ( MLL-PTD) occurs in about 3% to 5% of adult acute myeloid leukemia (AML), mostly in patients with normal karyotypes, and is associated with poor prognosis. Real-time PCR on cDNA or RT-PCR followed by gel electrophoresis are the most commonly used methods for the detection of the mutation. However, those methods require RNA extraction, which is not often performed for molecular cytogenetic testing or next generation sequencing (NGS) for AML. In this study, we developed an MLL-PTD detection assay that uses long-range PCR on extracted DNA, a commonly processed sample type for AML molecular testing, to reduce sample processing requirements. Methods: DNA was extracted from de-identified 72 whole blood and 30 bone marrow aspirate specimens. Two PCR reactions were performed for each DNA sample: one to detect MLL-PTD and another to detect CHEK2 to monitor DNA integrity. The 3 most frequent forms of MLL-PTD (exons 2~8, 2~9, and 2~10) were detected using a forward DNA primer on exon 8 and a reverse primer on exon 2. MLL-PTD positivity was determined by the intensity of amplified DNA fragment at or above the lower detection limit control of this assay. Intra-assay precision, inter-assay precision, and limit of detection (LOD) were performed according to standard laboratory protocols. Results of this method were compared to those of NGS. Results: Intra-assay precision studies on 5 specimens yielded 100% genotype concordance. Inter-assay precision studies on 20 specimens yielded 100% concordance between replicates. LOD studies using a human eosinophilic leukemia cell line (EoL-1) with 12.5-kb PTD in size showed assay sensitivity of 5%; for smaller MLL-PTD positives (PTD ~3 kb and ~5 kb), LOD was 1%. For method comparison studies, 71 specimens (52 whole blood and 19 bone marrow) were also analyzed by NGS; concordance between the methods was 97.2% (69/71). Conclusions: We developed and validated long-range MLL-PTD detection assay for AML. The developed method uses DNA, which is commonly used for molecular testing for AML, and thus may reduce sample processing time by consolidating sample type across tests.
Bayesian machine learning on CALGB/SWOG 80405 (Alliance) and PEAK data identify a heterogeneous landscape of clinical predictors of overall survival (OS) in different populations of metastatic colorectal cancer (mCRC)
Authors: R. Das, F. Ou, C. Washburn, F. Innocenti, A. Nixon, H. Lenz, C. Blanke, D. Niedzwiecki, I. Khalil, B. Harms, A. Venook
Journal: Annals of Oncology (2019)
Abstract 5124: A machine learning based approach to identify biomarkers of environmental toxicant exposures relevant to liver cancer disparities in rural Illinois
Authors: Brandi Smith, Zeynep Madak-Erdogan
Journal: Cancer Research (2019)

Abstract Although there have been nationwide reductions in recent cancer death, liver cancer mortality remains to be a problem in rural Illinois. Researchers anticipate that exposure to environmental toxicants in rural Illinois, may be possible causes of increased liver cancer mortality in females. The purpose of our study is to identify potential biomarkers, which are related to early liver toxicity through machine learning. We accessed gene expression data from the open source Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (TG-GATES) database from rats that had been exposed to over 170 toxicants relevant to liver cancer. We performed a differential gene expression analysis to identify significant features or genes, which are related to hepatotoxicity endpoints, specifically necrosis. Then we built our predictive model using supervised machine learning (ML) through feature selection and classification models. We performed differential gene expression analysis and feature selection to decrease the dimensionality of the gene set. We then used classification modeling to classify genes related to necrosis. Lastly, we tested our predictive model, on an independent data set. Our model predicted specific genes that were highly related to liver toxicant exposure. Note: This abstract was not presented at the meeting. Citation Format: Brandi Smith, Zeynep Madak-Erdogan. A machine learning based approach to identify biomarkers of environmental toxicant exposures relevant to liver cancer disparities in rural Illinois [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5124.
Abstract 19571: Atrial Septal Interventions After Ductal Stenting and Bilateral Pulmonary Artery Banding
Authors: Andrea Wan, Kyong-Jin Lee, Lee Benson, Christopher Caldarone, Rajiv R Chaturvedi
Journal: Circulation (2012)

Introduction Bilateral pulmonary artery banding with arterial duct stenting (H1) leaves the state of the atrial septum unresolved. Atrial communications can become restrictive and their management is an important problem. We reviewed our experience of atrial septal interventions (ASI) in H1 patients until their second stage procedure (H2). Methods and Results A retrospective analysis of the first 66 H1 patients between 2004 and 2011. Thirty-nine (59%) of these patients had hypoplastic left heart syndrome. 34/66 (52%) patients required 42 ASI. These were performed before (n=4), during (n=5) or after H1 (n=25). An ASI was frequently required for neonates on a path to a Fontan (29/48, 60%) or being bridged to transplantation (4/10, 40%), but was rare for borderline LV (1/8, 13%). An ASI was required if there was a small ASD on the initial echocardiogram (p&lt;0.01). A variety of percutaneous techniques were used: balloon septostomy/septoplasty (including cutting balloons), stenting and radio-frequency perforation of the atrial septum. Directly measured trans-septal mean gradient decreased from 12mmHg (range 2-25 mmHg) to 1mmHg (range 0-10mmHg). There were three ASI related deaths and 6 major complications. Three patients with LV sinusoids/fistulae experienced acute myocardial ischaemia following ASI. ASI was associated with an increased risk of death prior to H2. Conclusion Catheter techniques can produce minimally restrictive atrial communications, but can be associated with post-procedural instability. In patients with coronary sinusoids, myocardial ischaemia may occur if there is a large increase in pulmonary blood flow.
Abstract 15849: 15-year Prognostic Value of Coronary Artery Calcium Scoring for Predicting All-cause Mortality Beyond Traditional Risk Scoring Algorithms in Patients Without Conventional Cardiac Risk Factors
Authors: Donghee Han, Bríain Ó Hartaigh, Ji Hyun Lee, Asim Rizvi, Lohendran Baskaran, Joshua Schulman-Marcus, Fay Y Lin, Tracy Callister, James K Min, Hyuk-Jae Chang
Journal: Circulation (2016)

Introduction: Current guidelines for cardiovascular disease (CVD) risk assessment underline that coronary artery calcium (CAC) scoring should only be considered among patients at intermediate risk....
Systemic Mastocytosis: Management and Outcome. Data Analysis from the Greek Registry
Authors: Ioannis Tsonis, Nikolaos Kanellias, Vasileios Lazaris, Panayiotis Panayiotidis, Damianos Sotiropoulos, Theodoros Vassilakopoulos, Zoi Arapidou, Evangelos Eleutherakis-Papaiakovou, Dimitrios Boutsis, Athanasios Galanopoulos, Ioannis Kotsianidis, Marie-Christine Kyrtsonis, Theoni Leonidopoulou, Gerasimos Pangalis, Maria Papaioannou, Sophia Polychronopoulou, Charalampos Pontikoglou, Elias Poulakidas, Christos Poziopoulos, Panagiotis Repousis, Maria Topalidou, Kalliopi Vallianatou, Elina Vervessou, Nora-Athina Viniou, Maria Angelopoulou, Ioannis Baltadakis, Maria Dimou, Eleni Gavriilaki, Theodoros Iliakis, Argiris Symeonidis, Sossana Delibasi, Maria Papathanassiou, Theodoros Marinakis, Panagiotis Tsirigotis, Nikolaos Charchalakis, Evangelos Terpos, Maria Pagoni
Journal: Blood (2018)
Abstract 78: Potassium Chloride Improves the Outcome of Cardiopulmonary Resuscitation and Reduces the Cerebral Injury in a Rat Cardiac Arrest Model
Authors: Meng-Hua Chen, Xiao-Fen Tian, Dong-Ming Fang, Lu Xie, Qiao-Juan Huang, Feng-Qing Song
Journal: Circulation (2010)

Introduction: It is well known that potassium chloride (KCL) has protective effects on the myocardial ischemia reperfusion injury (IRI) in an isolated cardiac model. However, it is unclear whether ...
Abstract 2350: Type I interferon suppresses tumor growth through activating the STAT3-granzyme B pathway in tumor-infiltrating cytotoxic T lymphocytes
Authors: Chunwan Lu, John D. Klement, Mohammed L. Ibrahim, Priscilla S. Redd, Gang Zhou, Kebin Liu
Journal: Cancer Research (2019)

Abstract Type I interferons (IFN-I) have recently emerged as key regulators of tumor response to chemotherapy and immunotherapy. However, IFN-I function in immune cells in the tumor microenvironment is largely unknown. We determined that IFNα13 and IFNβ are selectively expressed in colon carcinoma tissues in vivo. Although IFNAR1 KO mice exhibited increased susceptibility to carcinogen and inflammation-induced sarcoma and colon tumorigenesis, IFNAR1-sufficient tumors grow significantly faster in IFNAR1 KO mice and in mice with IFNAR1 deficiency only in T cells, suggesting that IFN-I functions in T cells to enhance host cancer immunosurveillance. Surprisingly, unlike in an anti-viral immune response where IFN-I regulates T cell activation and clonal expansion, IFNAR1-deficient T cells exhibit no deficiency in generation of antigen-specific CTLs and IFNAR1-deficient CTLs infiltration level is similar as compared to that of WT CTLs in colon tumor-bearing mice. Gene expression profiling identified Gzmb as an IFN-I target gene in tumor-infiltrating CTLs and in antigen-specific CTLs in vivo. Mechanistically, we determined that IFN-I activates STAT3 that directly binds to the Gzmb promoter to activate Gzmb transcription in CTLs. IFN-I also regulates GZMB expression in human T cells, but IFNAR1 is not only significantly down-regulated in human colon carcinomas but also down-regulated in CTLs of human colon cancer patients as compared to normal colon and CTLs from healthy donors. Our data determined that IFN-I plays a more dominant role in CTLs than in tumor cells to execute its anti-tumor function, and doing so through activating the STAT3-granzyme B pathway in tumor-infiltrating CTLs. Citation Format: Chunwan Lu, John D. Klement, Mohammed L. Ibrahim, Priscilla S. Redd, Gang Zhou, Kebin Liu. Type I interferon suppresses tumor growth through activating the STAT3-granzyme B pathway in tumor-infiltrating cytotoxic T lymphocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2350.
Longitudinal quality of life (QOL) and sexual functioning in women undergoing pelvic exenteration for gynecologic malignancies.
Authors: Pamela T. Soliman, Charlotte C. Sun, Shannon Neville Westin, Lois M. Ramondetta, Diane C. Bodurka, Andrea Bradford
Journal: Journal of Clinical Oncology (2013)

5608 Background: Pelvic exenteration (PE) is en bloc resection of the pelvic organs including bladder, vagina, and rectum to treat central recurrence of a gynecologic malignancy. While this procedure has high morbidity, it is the only option for cure in some patients. The goal of this study was to assess QOL and sexual functioning in women who underwent PE with vaginal and/or bladder reconstruction. Methods: All patients were enrolled prior to PE. Surveys included the SF-12 (functional status), BIS (body image), SAQ (sexual functioning), SWD (satisfaction with decision), CES-D (depression), Stoma QOL, and DUFSS completed preoperatively (preop) and post-operatively at 4-6 wks, 6 mo, 1 yr, and 2 yrs. Descriptive statistics, chi-square, Mann-Whitney, and Kruskal Wallis tests were used to evaluate the data. Results: Between 2008 and 2012, 39 women participated. Median age was 56.7 yrs. Mean physical functional status scores (SF-12) declined through 6 mo postop, with improvements at 1 and 2 yrs (p=.002) but did not reach preop levels. SF-12 mental functioning scores declined immediately postop but returned to baseline by 6 mo. BIS was significantly worse at 1ys (p=0.02) and 2 yrs (p=0.025). Mean depression (CES-D) scores decrease but remained above the clinical cutoff of 17 at 6 mo. Poor sexual function was noted preop and did not improve. High scores for social support (DUFSS) remained constant. Stoma QOL improved in the first 2 yrs but not significantly. Pts reported high satisfaction with the decision to undergo PE, which did not change over time. Conclusions: While a majority of women remained satisfied with their decision to undergo PE, the procedure was associated with depression, worsening physical functioning and poor body image despite stable social support. Interventions are currently under development to improve QOL in this patient population. [Table: see text]