tbuckley/cabot-search huggingface dataset:
Effects of nintedanib (BIBF 1120) on QTc interval in previously untreated patients with renal cell cancer (RCC): Results from an open-label, phase II study.
Authors: Tim Eisen, Yaroslav Shparyk, Nicholas James MacLeod, Gudrun Wallenstein, Graham Temple, Yasser Khder, Claudia Dallinger, Matus Studeny, Arsene Bienvenu Loembe, Igor N. Bondarenko
Journal: Journal of Clinical Oncology (2012)

e15037 Background: Nintedanib (BIBF 1120), an angiokinase inhibitor of VEGFR 1–3, PDGFR-α/-β, and FGFR 1–3, has shown clinical activity with a good safety profile in patients (pts) with solid tumors in previous Phase II clinical trials. Several classes of targeted agents are associated with QT prolongation, including the multi-targeted tyrosine kinase inhibitors. Here, we prospectively evaluated the cardiac safety of nintedanib, specifically assessing the QT liability in an open-label, randomized, phase II efficacy and safety study of nintedanib vs sunitinib in pts with previously untreated RCC. Methods: Eligible pts (advanced, measurable, unresectable, recurrent RCC, ECOG PS 0–1, chemo-naïve, life expectancy &gt;3 months) were randomized to receive either nintedanib 200 mg bid or sunitinib 50 mg od in a 2:1 ratio. Time-matched electrocardiograms of patients treated with nintedanib were collected over 12 hrs. Primary endpoint was the time-matched change from baseline (Day –1 prior nintedanib dosing) to Day 15 (steady-state) in the QTcF interval (QT interval corrected for heart rate dependency by the Fridericia formula) observed at each timepoint. PK parameters were determined and AEs were reported until Day 15. Results: 64 pts were treated with nintedanib. Estimated mean time-matched changes in the QTcF interval (ms) from baseline to Day 15 ranged from –1.7 (90% CI: –4.9, 1.6) at 2 hrs to 3.1 (90% CI: –0.2, 6.4) at 7 hrs. Upper CIs at all timepoints were &lt;10 ms, the ICH E14 guideline threshold level of regulatory concern. Changes from baseline to Day 1 and changes in QT interval were also within the threshold of 10 ms. No pts showed a QTcF or a QT value &gt;500 ms at baseline, Day 1 or Day 15, and no patient experienced an increase from baseline in QTcF &gt;60 ms on Days 1 and 15. PK/QTc analyses did not indicate any relationship between exposure to nintedanib and a change from baseline in QTcF or the QT interval. The most frequently reported drug-related AEs were nausea (14.1%), diarrhea (12.5%) and vomiting (6.3%). Conclusions: Single and multiple doses of 200 mg nintedanib administered until steady-state did not prolong the QTcF interval compared with baseline in pts with RCC.
Targeting AML-associated FLT3 mutations with a type I kinase inhibitor
Authors: LaQuita M. Jones, Katelyn Melgar, Lyndsey Bolanos, Kathleen Hueneman, Morgan M. Walker, Jian-Kang Jiang, Kelli M. Wilson, Xiaohu Zhang, Jian Shen, Fan Jiang, Patrick Sutter, Amy Wang, Xin Xu, Gregory J. Tawa, Scott B. Hoyt, Mark Wunderlich, Eric O’Brien, John P. Perentesis, Daniel T. Starczynowski, Craig J. Thomas
Journal: Journal of Clinical Investigation (2020)

Tyrosine kinase domain (TKD) mutations contribute to acquired resistance to FMS-like tyrosine kinase 3 (FLT3) inhibitors used to treat FLT3-mutant acute myeloid leukemia (AML). We report a cocrystal structure of FLT3 with a type I inhibitor, NCGC1481, that retained potent binding and activity against FLT3 TKD and gatekeeper mutations. Relative to the current generation of advanced FLT3 inhibitors, NCGC1481 exhibited superior antileukemic activity against the common, clinically relevant FLT3-mutant AML cells in vitro and in vivo.
QUANTITATIVE PREDICTION OF MYOCARDIAL RELAXATION FROM SURFACE ELECTROCARDIOGRAM FOR DIAGNOSIS OF LEFT VENTRICULAR DIASTOLIC DYSFUNCTION
Authors: Nobuyuki Kagiyama, Marco Piccirilli, Sirish Shrestha, Peter Farjo, Marton Tokodi, Grace Casaclang-Verzosa, Wadea Tarhuni, Negin Nezarat, Matthew J. Budoff, Jagat Narula, Partho Sengupta
Journal: Journal of the American College of Cardiology (2020)
Measuring quality of care in the treatment of colorectal cancer: The Moffitt Network Initiative on Practice Quality (MNIPQ)
Authors: P. B. Jacobsen, D. Shibata, E. Siegel, J. Lee, M. Druta, J. Marshburn, R. Levine, A. Gondi, J. Defelice, M. Malafa
Journal: Journal of Clinical Oncology (2006)

6001 Background: As the first step in a larger effort to improve quality of care among its member institutions, the MNIPQ sought to develop and implement methods to assess quality of care in the treatment of colorectal cancer. The current report focuses on our initial experience conducting quality assessments at 4 of 20 member institutions. Methods: Medical chart reviews were conducted of all patients diagnosed with colon or rectal cancer in 2004 and seen by a medical oncologist at the Moffitt Cancer Center or at any of three affiliate institutions. Abstractors, who were trained and periodically monitored, conducted the reviews using a web-based abstraction tool. Abstraction focused on assessing adherence to quality indicators consistent with evidence-, consensus-, and regulatory-based guidelines. Variability in adherence across sites was evaluated by conducting Fisher’s exact tests. The 186 patients whose charts were reviewed were predominantly female (57%) and diagnosed with colon cancer (74%). Results: Adherence was consistently (p values&gt;.05) high across all four study sites for: presence of a pathology report confirming malignancy (91–100%); evidence of staging based on established criteria (88–94%); documentation of discussion or referral for chemotherapy in cases of lymph node (colon and rectal cancer) or rectal wall (rectal cancer) involvement (89–100%); and presence of chemotherapy flow sheets (92–100%). Adherence was consistently (p values&gt;.05) lower across sites for: performance of complete colon evaluation within 12 months of surgery (24–47%) and performance of CEA test before (48–74%) or in the 6 months after (56–82%) surgery or chemotherapy. Adherence varied significantly (p &lt; .001) across sites only for documentation of consent for patients treated with chemotherapy (41–100%). Discussion: Findings identified several areas where efforts should be made to improve the quality of colorectal cancer care at one or more member institutions. In addition, the methods developed have laid the groundwork for future efforts to measure and improve quality of care for other cancers and among a larger number of member institutions. No significant financial relationships to disclose.
Phase Ib study of AMG 386 in combination with paclitaxel (P) and carboplatin (C) in high-risk stage I and stages II-IV epithelial ovarian, primary peritoneal, or fallopian tube cancers.
Authors: Antonio Casado, Ana Oaknin, Jean-Francois Baurain, Shirley S. Wong, Xinqun Yang, Benjamin Wu, Zhandong Don Zhong, Markus Puhlmann, Ignace B. Vergote
Journal: Journal of Clinical Oncology (2012)

5038 Background: AMG 386 is a first-in-class investigational peptibody that inhibits angiopoietin-1/-2 binding to Tie2. We report on an ongoing, 2-part, open-label phase 1b study of AMG 386 + PC as first-line treatment of high-risk ovarian cancer. Methods: Part 1 enrolled women, GOG performance status 0/1, with newly diagnosed, FIGO high-risk stage I or stages II, IIIA-B (primary debulking surgery; PDS) or IIIC &amp; IV (PDS or interval debulking surgery; IDS) ovarian cancer. Patients (pts) received AMG 386 at 15 mg/kg QW IV + P at 175 mg/m 2 Q3W + C at AUC 6 Q3W for 6 cycles (or until disease progression or unacceptable toxicity); AMG 386 was withheld 4 weeks pre-/post-debulking. Pts completing 6 cycles continued AMG 386 QW as maintenance for up to 18 months. Part 1: incidence of dose-limiting toxicities (DLTs) dictated expansion to 25 pts (part 2). Primary endpoint: DLT incidence; secondary: adverse events (AEs), PK and efficacy measures. Results: At the time of analysis, 16 pts had received ≥1 dose of AMG 386 + PC and completed ≥2 cycles of therapy (PDS, n=8; IDS, n=8). No DLTs occurred in part 1. 15 pts continue on-study; 6 pts have received a median of 6 doses of maintenance AMG 386. One pt discontinued due to progression. AEs are tabulated below. One serious AE (decreased appetite; maintenance phase) required hospitalization. AE incidence and type were similar for PDS or IDS. Combination therapy did not affect the PK of AMG 386 or PC. Non-neutralizing antibodies against AMG 386 were detected in 2 pts. Conclusions: AMG 386 at 15 mg/kg QW + PC is tolerable in pts with high-risk ovarian cancer. AMG 386 maintenance was tolerated and associated with few AEs. Updated toxicity and efficacy data will be presented. [Table: see text]
Increasing overall survival with neoadjuvant and concomitant hormonal therapy plus conformal radiotherapy for high risk prostate cancer patients
Authors: M. R. Cruz, R. A. Nakamura, C. R. Monti, J. C. Prestes, F. A. Trevisan, R. Ferrigno
Journal: Journal of Clinical Oncology (2006)

14641 Objective: To evaluate the value of neoadjuvant (NHT) and concomitant hormonal therapy (CHT) for high risk prostate cancer patients treated with conformal radiotherapy (3DCRT). Methods: From October 1997 to January 2002, 116 patients with high risk prostate cancer were submitted to 3DCRT and were analyzed retrospectively. High risk patients were defined as patients with PSA &gt;20 ng/ml, and/or T3 clinical stage and/or Gleason score &gt;7, or two factors of intermediate risk (PSA ≥10 and &lt;20 ng/ml, T2b-T2c and Gleason score &gt;7). The NHT and CHT were performed on 69 (59.5%) and 79 (68.1%) patients, respectively. The prostate and seminal vesicles median doses were 81 Gy (72–82.8) and 61.2 Gy (45–77.4) respectively. The median time from diagnosis to 3DCRT was 2,9 months (0.9–134.9). Results: On median follow-up of 54.5 months (13.5–93.9), the 5-year actuarial overall (OS) and 5-year biochemical progression-free survival (BPFS) were 84.3% and 64.7% respectively. The OS for patients submitted to NHT was 89.8% versus 76.4% for patients that were not submitted to (p = 0.0139). Patients that received CHT had an OS of 89.6% versus 73.4% for patients that did not receive CHT (p = 0.0201). Gleason score, clinical stage and seminal vesicles irradiation were significant to BPFS (p = 0.0372, p = 0.0412 and p = 0.0321 respectively). Conclusions: NHT and CHT increased OS of high risk prostate cancer of patients. Gleason score and clinical stage were important prognostic factors to BPFS. Seminal vesicles irradiation is recommended for high risk patients. No significant financial relationships to disclose.
Abstract #3243: Dacetuzumab (SGN-40), a humanized anti-CD40 monoclonal antibody, has chemosensitization activity and improves gemcitabine efficacy in NHL xenograft models
Authors: Timothy Lewis, Renee McCormick, Ivan Stone, Hans-Peter Gerber, Brianna Mbow, Nancy Whiting, Jonathan Drachman, Iqbal Grewal, Che-Leung Law
Journal: Cancer Research (2009)

Dacetuzumab (SGN-40) is a humanized monoclonal antibody that targets CD40, an antigen expressed on a variety of malignancies including non-Hodgkin lymphoma (NHL). Previous studies have shown that dacetuzumab mediates antitumor activity through multiple mechanisms of action, including effector functions (ADCC/ADCP) and direct proapoptotic signal transduction. Here we report the combined activity of dacetuzumab (D) with rituximab-gemcitabine (R-Gem) in mouse xenograft models of NHL, and explore the mechanism behind its chemosensitization activity. Two diffuse large B cell lymphoma (DLBCL) subcutaneous xenograft models, WSU-DLCL2 and SU-DHL-8, were developed and treated with combinations of dacetuzumab, rituximab, and/or gemcitabine. In the WSU-DLCL2 model both dacetuzumab and rituximab significantly improved the activity of gemcitabine, and both R-Gem and D-R-Gem produced durable complete remissions. However, in the more aggressive and chemoresistant SU-DHL-8 xenograft model dacetuzumab enhanced the antitumor effect of gemcitabine, and also significantly (P   Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3243.
DESCRIPTION OF POST-HIP FRACTURE ANTICOAGULATION MANAGEMENT FOR ATRIAL FIBRILLATION PATIENTS AND ASSOCIATED OUTCOMES
Authors: Terence J. McLaughlin, Nicole T. Gordon, Aditya Bhonsale, Krishna Kancharla, Andrew Voigt, Norman Wang, N.A. Mark Estes, Samir F. Saba, Suresh Mulukutla, Sandeep Jain
Journal: Journal of the American College of Cardiology (2020)
Detection of epidermal growth factor receptor mutation in transbronchial aspiration cytology of non-small cell lung cancer
Authors: A. Horiike, H. Kimura, M. Nishio, F. Ohyanagi, Y. Satoh, S. Okumura, K. Nishio, Y. Ishikawa, K. Nakagawa, T. Horai
Journal: Journal of Clinical Oncology (2006)

7175 Background: Somatic mutations of epidermal growth factor receptor (EGFR) strongly associate with objective response to EGFR tyrosine kinase inhibitors. There are some problems to practically use it as prognostic markers. Since it is difficult to obtain sufficient tumor samples from non-small cell lung cancer (NSCLC) patients, they are often diagnosed by cytological procedure alone. Therefore, it is very useful if EGFR mutations are able to be detected in cytological samples. The aims of this study are to detect EGFR mutations in the samples of transbronchial aspiration cytology (TBAC) by using direct sequencing and Scorpion ARMS method, and to compare the sensitivities of these methods. Patients and Methods: 94 patients diagnosed as NSCLC in our institute were enrolled in this study, consisting of 63 males and 31 females with a median age of 66. In cytologic diagnosis, they were adenocarcinoma in 58, squamous carcinoma in 24, and the others in 12. DNA was extracted from the TBAC samples, and EGFR mutations were analyzed using direct sequencing (exon 19 and exon 21) and Scorpion ARMS method (E746-A750del and L858R). Results: The mutations were detected in 31patients (33%). 13 mutations (14%) (E746-A750del; 6 patients, L858R; 7 patients) were detected by direct sequencing. 27 mutations (29%) (E746-A750del; 16 patients, L858R; 11 patients) were detected by Scorpion ARMS method. Conclusion: EGFR mutations were able to be detected in TBAC samples by both methods. Scorpion ARMS method is more sensitive for the detection of EGFR mutations than direct sequencing. No significant financial relationships to disclose.
18F-FDG PET/CT Findings in a Patient With Neutrophilic Leukemoid Reaction Associated With Multiple Myeloma
Authors: Caixia An, Luoping Zhai, Huixia Geng, Pingzhi Wang, Wanchun Zhang
Journal: Clinical Nuclear Medicine (2020)

F-FDG PET/CT was performed on a 48-year-old woman with leukocytosis (white blood cell count 57.10 × 10/L, 84.0% neutrophils) and monoclonal gammopathy to investigate the possibility of reactive neutrophilia secondary to plasmacytoma. On the background of skeletal "superscan," the maximum intensity projection image of PET demonstrated the highest metabolic region in the left sacrum, which was confirmed as an osteolytic lesion by CT. Biopsy of the sacral lesion revealed a plasma cell myeloma, indicating the diagnosis of neutrophilic leukemoid reaction associated with multiple myeloma. The white blood cell counts dramatically dropped to the normal level after 1 cycle of chemotherapy for multiple myeloma.
Application of Managing Cancer and Living Meaningfully (CALM) in Advanced Cancer Patients: An Italian Pilot Study
Authors: Rosangela Caruso, Silvana Sabato, Maria Giulia Nanni, Sara Hales, Gary Rodin, Carmine Malfitano, Elisa Tiberto, Silvia De Padova, Tatiana Bertelli, Martino Belvederi Murri, Luigi Zerbinati, Luigi Grassi
Journal: Psychotherapy and Psychosomatics (2020)
OXIDIZED PHOSPHOLIPID, LIPOPROTEIN(A), AND AORTIC VALVE CALCIFICATION: A POOLED ANALYSIS OF THE FRAMINGHAM HEART STUDY AND THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Mehdi Afshar, Shayan Yazdan-Ashoori, Mary Hoekstra, Line Dufresne, Jian Rong, Wendy S. Post, Mary Cushman, Martin Larson, Matthew J. Budoff, Michael Tsai, Vasan S. Ramachandran, Sotirios Tsimikas, George Thanassoulis
Journal: Journal of the American College of Cardiology (2020)
The genome evolution and domestication of tropical fruit mango
Authors: Peng Wang, Yingfeng Luo, Jianfeng Huang, Shenghan Gao, Guopeng Zhu, Zhiguo Dang, Jiangtao Gai, Meng Yang, Min Zhu, Huangkai Zhang, Xiuxu Ye, Aiping Gao, Xinyu Tan, Sen Wang, Shuangyang Wu, Edgar B. Cahoon, Beibei Bai, Zhichang Zhao, Qian Li, Junya Wei, Huarui Chen, Ruixiong Luo, Deyong Gong, Kexuan Tang, Bing Zhang, Zhangguang Ni, Guodi Huang, Songnian Hu, Yeyuan Chen
Journal: Genome biology (2020)

Abstract Background Mango is one of the world’s most important tropical fruits. It belongs to the family Anacardiaceae, which includes several other economically important species, notably cashew, sumac and pistachio from other genera. Many species in this family produce family-specific urushiols and related phenols, which can induce contact dermatitis. Results We generate a chromosome-scale genome assembly of mango, providing a reference genome for the Anacardiaceae family. Our results indicate the occurrence of a recent whole-genome duplication (WGD) event in mango. Duplicated genes preferentially retained include photosynthetic, photorespiration, and lipid metabolic genes that may have provided adaptive advantages to sharp historical decreases in atmospheric carbon dioxide and global temperatures. A notable example of an extended gene family is the chalcone synthase (CHS) family of genes, and particular genes in this family show universally higher expression in peels than in flesh, likely for the biosynthesis of urushiols and related phenols. Genome resequencing reveals two distinct groups of mango varieties, with commercial varieties clustered with India germplasms and demonstrating allelic admixture, and indigenous varieties from Southeast Asia in the second group. Landraces indigenous in China formed distinct clades, and some showed admixture in genomes. Conclusions Analysis of chromosome-scale mango genome sequences reveals photosynthesis and lipid metabolism are preferentially retained after a recent WGD event, and expansion of CHS genes is likely associated with urushiol biosynthesis in mango. Genome resequencing clarifies two groups of mango varieties, discovers allelic admixture in commercial varieties, and shows distinct genetic background of landraces.
Dysregulation of smoldering multiple myeloma (SMM) progression to multiple myeloma (MM) via modulation of AKT kinase, proinflammatory cytokines, and insulin-like growth factor-1 (IGF-1) in human immunodeficiency virus-1 SMM ( HIVSMM ) patients treated with adjuvant selenomethionine (Se-Met) ritonavir-based HAART.
Authors: Eugene McPherson, Ervido Mejia, Philippe Tassy
Journal: Journal of Clinical Oncology (2013)

e19540 Background: Multiple myeloma is a B-cell malignancy involving germinal center B cells characterized by urinary monoclonal proteins, osteolytic bone lesions and infiltration of bone marrow with plasma cells and pathology involving aberrant chromosomal translocation with increased glucose uptake as glucose transporter (GLUT-4), AKT kinase activation, overexpressed proinflammatory cytokines produced by bone marrow stromal cells (BMSC) in smoldering multiple myeloma and multiple myeloma, These biomarkers are antiapoptotic and control growth, prognosis and survival. Interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) are major growth factors in MM. IGF-1 binds to IGF-1 receptor (IGF-1R) as a strong prognostic indicator. Dysregulation and modulation of IGF-1, proinflammatory cytokines, AKT kinase and IL-6 in HIVSMM patients with RTV-based HAART and selenomethionine (Se-Met) adjuvant therapy may suppress NF-kb and abrogate GLUT-4 HIVSMM progression. Methods: We evaluated several HIVSMM patient's biomarkers over four years: CD4, HIVRNA, beta-2-microglobulin, LDH, soluble interleukin -2 receptor (sIL-2R), CRP, SFLC ratio, selenium, bone survey, and bone marrow aspiration/biopsy. Results: CD4 increased to 456/cumm from &lt; 80/cumm, HIVRNA was undetectable from &gt; 1 million copies/ml, beta-2-microglobulin 2.24 mg/L from 14.40 mg/L, LDH 155 IU/L from 432IU/L, sIL-2R 75 pg/ml from 45,752 pg/ml, CRP 1.49 mg/L from 87.4 mg/L, SFLC ratio 0.93 from &gt;2.08, selenium kept &gt;140 mcg/L (high normal level), bone survey negative X 2, and bone marrow aspiration/biopsy plasmacytosis with plasma cells &lt; 5% from &gt; 10% and CD 138 positivity. Conclusions: Dysregulation and modulation of HIVSMM biomarkers with adjuvant Se-Met and RTV-based HAART may suppress AKT kinase and NF-kb activation preventing HIVSMM progression to HIVMM via IGF-1 recruitment of GLUT-4. Overall improved prognosis and survival may be extrapolated to non-HIVSMM patients with concommitant immunomodulary therapy.
PERFORMANCE OF THE ACADEMIC RESEARCH CONSORTIUM FOR HIGH BLEEDING RISK CRITERIA ACCORDING TO SEX
Authors: Davide Cao, Roxana Mehran, Rishi Chandiramani, Samantha Sartori, George D. Dangas, Johny Nicolas, Ridhima Goel, Anastasios Roumeliotis, Usman Baber, Giulio G. Stefanini, Jason Kovacic, Joseph Sweeny, Prakash Krishnan, Nitin Barman, Samin K. Sharma, Annapoorna Subhash Kini
Journal: Journal of the American College of Cardiology (2020)
Changes in Length and Complexity of Clinical Practice Guidelines in Oncology, 1996-2019
Authors: Benjamin H. Kann, Skyler B. Johnson, Hugo J. W. L. Aerts, Raymond H. Mak, Paul L. Nguyen
Journal: JAMA Network Open (2020)

practitioners. 4,5Strategies to organize oncologic knowledge, such as the creation of Drugs and Biologics and Imaging Compendia, 6 have been implemented.Further approaches, including guideline stratification by evidence level and the use of artificial intelligence for decision support, should be investigated as ways to synthesize data and improve cancer decision-making.
PROGNOSTIC VALUE OF THE RELATIVE PULMONARY PRESSURE RATIO AND ITS TRAJECTORY IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION
Authors: Shadi P Bagherzadeh, Myriam Amsallem, Andre Denault, Andrew John Sweatt, Kristina Kudelko, Yon Kyung Sung, Francois Haddad, Roham Zamanian
Journal: Journal of the American College of Cardiology (2020)