tbuckley/cabot-search huggingface dataset:
Bevacizumab in combination with TMZ in patients with recurrent GBM: Final OS and PFS analysis.
Authors: Juan Manuel Sepulveda, Cristobal Belda-Iniesta, Miquel Gil, Pedro Pérez Segura, Alfonso Berrocal, Gaspar Reynes, Oscar Gallego, Jose Manuel Ordonez, Beatriz La Orden, Carmen Balana
Journal: Journal of Clinical Oncology (2013)

2087 Background: BEV provides a consistent clinical benefit in the treatment of relapsing GBM in terms of a delayed progression and increased median overall survival compared to historical controls. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of BEV with dose dense TMZ, reporting the final results of PFS, OS and the toxicity experienced. Methods: A phase II multicenter, national, open-label study in pts diagnosed of recurrent GBM treated with BEV 10 mg/kg day q2w and TMZ 150 mg/m 2 days 1-7 and 15-21 q28d d until disease progression or unacceptable toxicity or medical decision, as first line of treatment all pts received radiotherapy and at least 3 cycles of adjuvant TMZ. This study evaluates efficacy by PFS as primary endpoint and as secondary endpoints: OS, RR based on the adapted MacDonald criteria and toxicity profile (NCI CTC v3.0). Results: From June 10 to July 11, 32 evaluable pts were recruited in 8 sites. The baseline characteristics were as follows: 17 males and 15 females, median age 57.5 y (29-74), ECOG PS 0: 25%, PS 1: 50% and PS 2: 25%, 44% patients had gross total resection, 50% had subtotal resection and 6% biopsy only, MGMT promotor was methylated in 12 pts, unmeth in 6 pts and missing in 14 pts. The median number of TMZ or BEV cycles administered across all patients was 4 (TMZ range 1-9 and BEV range 1-25) The median PFS was 4.4 m [IC 95% (3.7 – 5.6)]. The 6m-PFS probability was 29.25%. The median OS (75% events) was 7.5 m[IC 95% (5.98 – 9.11)]. No significant association with MGMT status was found in terms of OS or PFS. BEV related AEs have been reported in 56.2% of the population being most of them mild or moderate. Grade 3-4 most frequent toxicity: lymphopenia 31% and fatigue 12.5%. Six of 32 pts were long term survivors, in this population the median PFS was 9.8 m [IC 95% (8.2 – 24.4)] and median OS (50% events) was 15.9 m [IC 95 %( 9.2 – NA)], no differences in baseline characteristics were identified in comparison with total population. The median number of TMZ cycles administered was 4 and median BEV cycles were 9. Conclusions: Although the combination don’t met the previous reported activity of BEV, 19% of patients had longer survivals which suggest the need to identify patients that benefit for this treatment. Clinical trial information: NCT01115491.
A new parameter of bone scintigraphy: Relation between bone scan index and bone metabolic markers in prostate cancer patients with bone metastases.
Authors: Hiroshi Wakabayashi, Kenichi Nakajima, Atsushi Mizokami, Mikio Namiki, Anri Inaki, Junichi Taki, Seigo Kinuya
Journal: Journal of Clinical Oncology (2013)

e16072 Background: A computer-aided diagnosis system for bone scan with semiquantitative index of Bone Scan Index (BSI) may be used to quantify the spread of bone metastases. This retrospective study aimed to examine associations between BSI, bone metabolic markers, and prostate specific antigen (PSA) in prostate cancer patients with bone metastases. Methods: A total of 158 scintigraphy of 52 patients (mean examinations/person 3, range 1-8; mean age 71 years, range 46 to 86) were studied. The intervals between bone scan and blood examinations were 0 to 16 days (median 0 day). Subjects were divided into 4 groups according to BSI; Group A: 0 - &lt;2, Group B: 2 - &lt;4, Group C: 4 - &lt;8, and Group D: 8&lt;. The markers of PSA, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1-CTP), bone alkaline phosphatase (BAP), and tartate resistant acid phosphatase-5b (TRAP-5b) were examined. As the values of PSA, BAP, and TRAP-5b covered a large range of scales, we also used the logarithms of the variables. BSI, which corresponded amount of metastatic lesions, was automatically calculated by BONENAVI software (FUJIFILM RIPharma, Co. Ltd., Tokyo, Japan; Exini Bone, Exini Diagnostics, Sweden). Results: All scans showed increased uptake at bone metastases. BSI correlated significantly with 1-CTP, BAP, logBAP, TRAP-5b, logTRAP-5b, and logPSA (r=0.39, 0.66, 0.71, 0.69, 0.61 and 0.41, respectively). Statistical F value was 11 in 1-CTP, 31 in BAP, 29 in logBAP, 19 in TRAP-5b, 14 in logTRAP-5b, 3 in PSA, and 9 in logPSA by ANOVA, respectively. Comparison by Dunnett’s test showed significantly higher values in Group D for all bone metabolic markers and logPSA, Group C for BAP, logBAP, TRAP-5b, and logTRAP-5b, and Group B for logTRAP-5b compared with Group A, respectively. However, PSA did not correlate significantly with extent of bone metastases as assessed by BSI. Conclusions: The changes in BSI showed close relationship with all bone metabolic markers but not with PSA. The BSI reflected the activity and extent of bone metastases, and might be used as an imaging biomarker.
Infusion-related reactions (IRR) during NGR-hTNF therapy as potential predictors of clinical outcome.
Authors: Gilda Rossoni, Vanesa Gregorc, Alessandra Bulotta, Maria Grazia Viganò, Gabriele Todisco, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2013)

e13593 Background: NGR-hTNF, a selective antivascular agent, transiently modulates the systemic release of cytokines/chemokines. Intravenous infusion of NGR-hTNF is distinguished by an early on-target effect, IRR, which mostly consists of short-lived grade 1/2 chills. Methods: Incidence, predictors of development and relationships of IRR with treatment outcome were assessed in a pooled analysis of individual patient data from 5 phase II trials with NGR-hTNF. Global data set comprised 205 previously treated patients (pts) who had received NGR-hTNF 0.8 µg/m 2 every 3 weeks (q3w) or weekly (q1w) alone in mesothelioma, colon and liver cancers or in combination with doxorubicin in small cell lung and ovarian cancers. In all trials, response to therapy (RECIST) was measured q6w until progression. Regression models estimated the effect size of IRR on response rate (RR; complete and partial response), disease control rate (DCR; RR plus stable disease) and progression free survival (PFS). Results: 137/205 pts (67%) experienced IRR on treatment, while 68 pts (33%) did not. In the IRR group, 63% of pts had grade 1 and 37% grade 2. By time to onset, 88% of pts developed IRR during first 6 weeks of therapy and 12% later. According to dosing schedule, IRR rates were higher with q1w than with q3w (85% vs 62%; p=.008). Baseline characteristics were (IRR vs non-IRR groups): median age: 66 vs 64; male: 50% vs 56%; PS ≥ 1: 34% vs 35%, range of prior lines: 1-4 vs 1-5. Among baseline characteristics, logistic regression analysis retained only a lower number of prior lines associated with higher IRR rates (OR=1.4; p=.02). Onset of IRR was related to better treatment outcome. RR was 12% in the IRR and 3% in the non-IRR group (OR=4.4; p=.05), while DCR was 50% in pts who had IRR and 34% in pts who did not (OR=2.0; p=.02). In pts with or without IRR, 6-month PFS was 21% vs 7% (HR=0.62; p=.001), respectively. Improvement in PFS time remained significant in a landmark analysis set at the 6-week time point (p=.004). On multivariate analyses adjusted for baseline variables, IRR independently predicted higher odds of tumor response (p=.05) and lower risk of progression or death (p=.009). Conclusions: Onset of IRR on NGR-hTNF treatment may predict subsequent clinical outcome. Clinical trial information: NCT00483080-NCT00483509-NCT00484211-NCT00484276-NCT00484432.
HYPERTRIGLYCERIDEMIA, INFLAMMATION, HYPERCHOLESTEROLEMIA, AND FUTURE CARDIOMETABOLIC DISEASE RISK: A DATA DRIVEN CLUSTER ANALYSIS IN THE WOMEN's HEALTH STUDY
Authors: Edward Duran, Nancy R. Cook, Aaron W. Aday, Julie E. Buring, Paul M. Ridker, Aruna Das Pradhan
Journal: Journal of the American College of Cardiology (2020)
5-YEAR HEALTH STATUS OUTCOMES AFTER SELF-EXPANDING TRANSCATHETER OR SURGICAL AORTIC VALVE REPLACEMENT IN HIGH-RISK PATIENTS WITH SEVERE AORTIC STENOSIS
Authors: Suzanne Arnold, Khaja Chinnakondepalli, Elizabeth Magnuson, Michael Reardon, Jeffrey J. Popma, G. Michael Deeb, Thomas G. Gleason, Steven J. Yakubov, David J. Cohen
Journal: Journal of the American College of Cardiology (2020)
Prevalence of gene amplifications of SOX-2, c-MET, and FGFR1 in Asian patients with esophageal squamous cell carcinoma.
Authors: Ta-Chen Huang, Wei-Wu Chen, Ta-Wen Hsu, Chia-Chi J. Lin, Kun-Huei Yeh, Ann-Lii Cheng, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2013)

e15127 Background: Amplifications of SOX-2, c-MET, and FGFR1 have recently been recognized as important molecular derangements with therapeutic implication in squamous cell carcinoma of lung. We investigated the significance of these molecular derangements in esophageal squamous cell carcinoma (ESCC). Methods: Locally advanced ESCC patients who had received curative- intent loco-regional therapy and had available pre-treatment endoscopic biopsy tissues at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. DNA was extracted from formalin-fixed paraffin-embedded tissues. Amplifications of SOX-2, c-MET, and FGFR1 were evaluated by quantitative PCR (TaqMan Copy Number Assay, Applied Biosystems, CA, USA), using TERT as a reference gene. Amplification of specific gene was defined as a copy number more than 4. Results: Forty locally advanced ESCC patients, M: F= 39: 1 with a median age of 56 years (range: 37 to 80), were included. The primary tumors located at cervical, upper thoracic, middle thoracic, and lower thoracic esophagus in 2, 9, 23, and 6 patients, respectively; the tumor staging according to AJCC 2002 version was T3N0, AnyTN1, and M1a in 1, 37, and 2 patients, respectively. Amplifications of SOX-2 and c-MET were identified in 14 (35%) and 7 (17.5%) patients, respectively. No FGFR1 amplification was detected. The amplifications of SOX-2 and c-MET were not associated with any known clinical features of the patients, including gender, age (&lt;60 vs ≧60), primary tumor location, clinical stage, and performance status (ECOG 0, 1). Conclusions: Amplifications of SOX-2 and c-MET, existing in significant portions of Asian patients with ESCC, are worthy of exploration as therapeutic targets of ESCC.
THE ASSOCIATION BETWEEN TYPE 2 MYOCARDIAL INFARCTION AND INCREASED IN HOSPITAL MORTALITY IN PATIENTS AGED GREATER THAN 85 YEARS PRESENTING WITH NON-ST ELEVATION MYOCARDIAL INFARCTION
Authors: Alexandra Murphy, Anoop Koshy, Phelia Kunniardy, Georgie Meehand, Jay Ramchand, H.M. Omar Farouque, David Clark, Matias Yudi
Journal: Journal of the American College of Cardiology (2020)
ACUTE AORTIC DISSECTION IN PATIENTS WITH MITRAL VALVE DISEASE
Authors: Joseph Kim, Christina Fanola, Maral Ouzounian, G. Chad Hughes, Reed E. Pyeritz, Thomas G. Gleason, Arturo Evangelista-Masip, Alan C. Braverman, Daniel G. Montgomery, Marek Ehrlich, Marc Schermerhorn, Guillaume Geuzebroek, Kevin Harris, Anil Bhan, Lori Conklin, Eric M. Isselbacher, Kim Eagle
Journal: Journal of the American College of Cardiology (2020)
Mammalian Target of Rapamycin Inhibition Synergistically Increases Cytotoxicity of Vinorelbine in Breast Cancer Cells.
Authors: Robert M. Audet, Nezha Alami, Kris Banerjee, Brian Leyland-Jones
Journal: Cancer Research (2006)

5080  Inhibition of the serine-threonine kinase mammalian target of rapamycin (mTOR) has been reported to enhance the efficacy of several cytotoxic agents. Recent findings suggest that mTOR may be involved in a signaling pathway activated by microtubule-damaging drugs. The PI3K and AKT kinase pathway is a direct upstream regulator of mTOR. Using cells containing constitutively active myristoylated AKT it has been shown that AKT markedly increases resistance to microtubule-directed agents and a significant component of this AKT-mediated protection is mTOR-dependent. Other downstream targets of mTOR include the insulin receptor substrate-1 (IRS-1), a key adapter transmitting signals from activated insulin/insulin-like growth factor-1 receptors (IGF-1R). When IRS-1 is phosphorylated on a serine by mTOR, it dissociates from IGF-1R resulting in its proteasomal degradation. Also, recent data has shown that a recombinant humanized anti-IGF-1R antibody enhances the antitumor activity of vinorelbine in a non small cell lung cancer cell line. The aim of this study was to determine the nature of the interactions between mTOR inhibitors and microtubule-directed agents. Experimental Design: MCF-7 breast cancer cells were exposed for 72 hours either to the mTOR inhibitor rapamycin, at concentrations ranging from 0.1 to 100 (nM), the microtubule-directed agent Vinorelbine, at concentrations ranging from 0.01 to 10 (μg/ml) or simultaneous combination of both agents at a fixed ratio . Growth inhibition was measured using the MTT assay and synergistic interactions between the drugs were measured using the median-effect plot analysis and calculations of the combination index (CI) by the method of Chou and Talalay. Expression of AKT, PTEN and IGF-1R was assessed using western blot analysis. Results: Treatment with rapamycin or vinorelbine, as single agents, induced dose dependent growth inhibition. Synergistic interaction was obtained with the combination of rapamycin and vinorelbine, as evaluated by median-effect plot analysis and a combination index isobologram method (CI
Cardio-Oncology in China
Authors: Yuhui Zhang, Zhiren Zhang, Ying Liu, Jian Zhang
Journal: JACC CardioOncology (2020)

As the most populous country in the world, in the year 2020, there will be approximately 4.5 million new cases of cancer in China ([1][1]). Cancer and cardiovascular disease are the 2 most common causes of mortality in China. However, because of the development of newer therapies, cancer patients
Baseline and dynamic plasma chromogranin A (CgA) level to predict clinical outcome and tumor response in Asian patients with gastroenteropancreatic neuroendocrine tumor (GEP-NET).
Authors: Wen-Chi Chou
Journal: Journal of Clinical Oncology (2013)

e15151 Background: The plasma CgA level is a reliable biomarker in diagnosing neuroendocrine tumors.The objective of this study is to correlate both the baseline value and the dynamic changes of plasma CgA level with disease status in Asian patients with advanced GEP-NET. Methods: Fifty-four patients with advanced GEP-NET were retrospectively evaluated between April 2010 and December 2012 in a single institution. Plasma CgA level and abdominal CT scan were obtained at diagnosis as a baseline and subsequently every 3 to 6 months after starting antitumor therapy.Statistical analysis of plasma CgA level was performed to predict the hazard ratio of clinical outcomes and also to correlate antitumor therapy responses with Response Evaluation Criteria in Solid Tumors Criteria 1.1. Results: Forty-six patients (85%) had elevated baseline CgA level. Twenty-one patients (39%) died at the end of the study with the medial follow-up duration of 292 days (range 12-992 days). Patients with baseline CgA level less than 2-fold of upper normal limit (UNL) had longer overall survival time than those with more than 2-fold of UNL (not reach vs. 272 days, hazard ratio = 0.39, 95% CI 0.15-0.99). Baseline CgA level less than 2-fold of UNL was still a favorable prognostic factor after adjusted for other variables (hazard ratio = 0.30, 95% CI 0.10-0.89). Twenty-eight patients with a total of 81 measurements of serial plasma CgA were available. An increase of plasma CgA level less than 15% predicted favorable antitumor response with a sensitivity of 86% and specificity of 91% (area under curve of receiving operating characteristics curves was 0.94). Conclusions: Baseline plasma CgA level and its dynamic change are useful values to predict clinical outcomes and antitumor responses in patients with GEP-NET.Baseline CgA level and serial measurements during antitumor therapy in patients with GEP-NET should be taken to assess their clinical outcomes.
Dupilumab as a novel therapy for bullous pemphigoid: A multicenter case series
Authors: Rana Abdat, Reid A. Waldman, Valeria de Bedout, Annette Czernik, Michael Mcleod, Brett King, Samantha Gordon, Razzaque Ahmed, Anna Nichols, Marti Rothe, David Rosmarin
Journal: Journal of the American Academy of Dermatology (2020)
Alzheimer’s Risk Factors Age, APOE Genotype, and Sex Drive Distinct Molecular Pathways
Authors: Na Zhao, Yingxue Ren, Yu Yamazaki, Wenhui Qiao, Fuyao Li, Lindsey M. Felton, Siamak Mahmoudiandehkordi, Alexandra Kueider-Paisley, Berkiye Sonoustoun, Matthias Arnold, Francis Shue, Jiaying Zheng, Olivia N. Attrebi, Yuka A. Martens, Zonghua Li, Ligia Bastea, Axel D. Meneses, Kai Chen, J. Will Thompson, Lisa St John-Williams, Masaya Tachibana, Tomonori Aikawa, Hiroshi Oue, Lucy Job, Akari Yamazaki, Chia-Chen Liu, Peter Storz, Yan W. Asmann, Nilüfer Ertekin-Taner, Takahisa Kanekiyo, Rima Kaddurah-Daouk, Guojun Bu
Journal: Neuron (2020)
Prophylaxis Against Invasive Fungal Disease for Neutropenic Children and Young Adults
Authors: Dylan W. de Lange, Roger J. M. Brüggemann
Journal: JAMA (2020)

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PRETREATMENT WITH SGLT2 INHIBITORS AMELIORATES CONTRAST-INDUCED NEPHROPATHY
Authors: Carlos G. Santos-Gallego, Gloria Palamara, Juan Antonio Requena-Ibanez, Ariana Patricia Vargas, Reza Mohebi, Vivian Abascal, Pedro Moreno, Juan J. Badimon
Journal: Journal of the American College of Cardiology (2020)
Identification and validation of plasma protein biomarker panels for breast cancer diagnosis by using multiple reaction monitoring-based mass spectrometry.
Authors: Hyeong-Gon Moon, Un-Beom Kang, Wonshik Han, Seock-Ah Im, Dong-Young Noh
Journal: Journal of Clinical Oncology (2012)

10621 Background: Multiple reaction monitoring-based mass spectrometry (MRM-MS) has the ability to perform a wide range of proteome analysis in a single experiment using a small volume of specimen. We aimed to develop a plasma protein signature for breast cancer diagnosis using the MRM-MS technology. Methods: Previously, we have identified lists of breast cancer-related proteins from various models of proteomic discovery including cancer plasma vs healthy plasma, cancer cell line secretome vs non-tumorigenic cell line secretome, cancer tissue vs normal tissue, and literature search. Based on these protein panels, total of 29 proteins were selected for further experiments. We verified and validated the protein signature in two independent cohorts of breast cancer patients and healthy women. Results: In the verification cohort of 80 breast cancer patients and 80 healthy women, MRM-MS showed significant differences in plasma concentration for 11 proteins. Among them, the difference was not significant for 4 proteins when the cases were limited to stage I and II patients. Based on p values and consistent expression level along the AJCC stages, we have created a plasma protein signature comprised of 3 plasma proteins. The 3 plasma protein signature effectively discriminated cancer and healthy cases with the AUC of 0.831 (sensitivity 78.7%, specificity 78.7%). The performance of the 3 plasma protein signature was validated in the cohort of 100 cancer patients and 100 healthy women. The accuracy of the 3 protein signature was still meaningful with the AUC of 0.746 and 0.797 for all stages and stage I or II patients, respectively. Conclusions: The 3 plasma protein signature for breast cancer diagnosis, developed by the MRM-MS technology, showed promising results in the present study.
THE VALUE OF HEART-FATTY ACID BINDING PROTEIN (H-FABP) IN THE EARLY DIAGNOSTIC OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Thach N. Nguyen, Phuc Xuan Minh Le, Truong Xuan Le, Khoa D.A. Nguyen, Tram Thanh Nguyen, Thanh Minh Nguyen, Vinh Thanh Tran
Journal: Journal of the American College of Cardiology (2020)
Diagnosis of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism
Authors: Fredrikus A. Klok, Francis Couturaud, Marion Delcroix, Marc Humbert
Journal: European Respiratory Journal (2020)

Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). Untreated CTEPH is fatal, but, if diagnosed in time, successful surgical (pulmonary endarterectomy), medical (pulmonary hypertension drugs) and/or interventional (balloon pulmonary angioplasty) therapies have been shown to improve clinical outcomes, especially in case of successful pulmonary endarterectomy. Early diagnosis has however been demonstrated to be challenging. Poor awareness of the disease by patients and physicians, high prevalence of the post-PE syndrome (i.e. persistent dyspnoea, functional limitations and/or decreased quality of life following an acute PE diagnosis), lack of clear guideline recommendations as well as inefficient application of diagnostic tests in clinical practice lead to a reported staggering diagnostic delay >1 year. Hence, there is a great need to improve current clinical practice and diagnose CTEPH earlier. In this review, we will focus on the clinical presentation of and risk factors for CTEPH, and provide best practices for PE follow-up programmes from expert centres, based on a clinical case.
THE IMPACT OF PULMONARY EMBOLISM RESPONSE TEAMS ON THE UTILIZATION OF ADVANCED THERAPIES IN INTERMEDIATE AND HIGH RISK PULMONARY EMBOLISM PATIENTS
Authors: Alexander Murphy, Robert Zilinyi, Danial Saleem, Mahesh Madhavan, Shayan Nabavi Nouri, Andrew Jeffrey Einstein, Sowmya Sreekanth, Hui Qing Su, John Capua, Daniel Brodie, Jay Leb, Erika Berman Rosenzweig, Nadira Hamid, Koji Takeda, Ajay Kirtane, Sahil Parikh, Sanjum S. Sethi, Philip Green
Journal: Journal of the American College of Cardiology (2020)
Prognostic Value of Myocardial Extracellular Volume Fraction and T2-mapping in Heart Transplant Patients
Authors: Kongkiat Chaikriangkrai, Muhannad Aboud Abbasi, Roberto Sarnari, Ryan Dolan, Daniel Lee, Allen S Anderson, Kambiz Ghafourian, Sadiya S Khan, Esther E Vorovich, Jonathan D Rich, Jane E Wilcox, Julie A Blaisdell, Clyde W Yancy, James Carr, Michael Markl
Journal: JACC. Cardiovascular imaging (2020)
QIM20-132: A Tool Preparing Patients with Stage III Non-Small Cell Lung Cancer for Shared Decision-Making: Validating Acceptability and Usability
Authors: Courtney Ramus, Candice Yong, Domitilla Masi, Camille Boler, Rina Bardin, Joshua Seidman, Alecia Clary, Bjorn Bolinder
Journal: Journal of the National Comprehensive Cancer Network (2020)

"QIM20-132: A Tool Preparing Patients with Stage III Non-Small Cell Lung Cancer for Shared Decision-Making: Validating Acceptability and Usability" published on 20 Mar 2020 by National Comprehensive Cancer Network.