tbuckley/cabot-search huggingface dataset:
Tumor drug distribution and target engagement of MLN9708, an investigational proteasome inhibitor, in patients with advanced solid tumors.
Authors: Alessandra Di Bacco, Allison Berger, Neeraj Gupta, Feng Gao, Stephen Blakemore, Mark Qian, Susan Chen, Bradley Stringer, Yu Yang, Ray Liu, Stephen Tirrell, Doug Bowman, David C. Smith, Daniel Sullivan, Jeffrey R. Infante, John S. Kauh, Lillian L. Siu, Gordana Vlahovic, John A. Thompson, Thea Kalebic
Journal: Journal of Clinical Oncology (2012)

3077 Background: MLN9708 is a potent investigational proteasome inhibitor, which upon intravenous (IV) administration immediately hydrolyzes to the active form MLN2238. MLN9708 is currently being evaluated in a phase 1 trial in solid tumors (NCT00830869). This trial has a dose-escalation arm and five expansion cohorts: non-small cell lung cancer (NSCLC), soft tissue sarcoma, head and neck cancer, prostate cancer, and a tumor biopsy cohort of mixed histology. The purpose of the tumor biopsy cohort was to obtain pre- and post-dose biopsies to determine drug distribution and target engagement in post-dose tumor samples. The latter was measured by the increase in levels of ATF-3, a marker of unfolded protein response/endoplasmic reticulum stress, which is upregulated in response to proteasome inhibition. Methods: The tumor biopsy cohort included 20 patients dosed at the maximum tolerated dose who consented to core needle biopsies during screening and after either the first or second dose of MLN9708 (IV 1.76 mg/m 2 ; 4–20 hours post-dose). Tumor biopsies were individually weighed, homogenized, and analyzed for the presence of MLN2238 using a quantified LC/MS/MS methodology. ATF-3 levels in tumors were determined by an immunohistochemical assay (IHC) on six sections for each tumor biopsy. Tumor area was identified using Aperio Genie, a machine learning program for pattern recognition, and the percentage of ATF-3 positive area in the tumor was measured. Results: Biopsies from 20 patients were collected for assessment of drug distribution and target engagement. Ten patients with paired pre- and post-dose biopsies of sufficient size were considered evaluable for PK analysis; MLN2238 was present in all 10 (100%) post-dose biopsies analyzed. Tumor pairs from 7 patients passed quality control by H&amp;E staining for tumor content and were evaluable for ATF-3 IHC. Six of 7 paired samples (86%) showed a statistically significant (p&lt;0.05) increase in post-dose ATF-3 levels. Conclusions: Overall, emerging data from MLN9708 phase 1 solid tumor analysis show that MLN2238 is present in tumors and demonstrates target engagement upon inhibition of the proteasome in tumor tissue biopsies.
Survival outcomes in marginal zone lymphomas in the rituximab era: Analysis of the Surveillance, Epidemiology, and End Results (SEER) database.
Authors: Jorge J. Castillo, Adam J. Olszewski
Journal: Journal of Clinical Oncology (2012)

8045 Background: Despite prognostic models developed for marginal zone lymphoma (MZL), the impact of different characteristics and treatments on survival in the population is largely unknown. We studied survival of MZL patients included in the SEER database. Methods: Records of MZL adult cases diagnosed between 1989-2008 were studied using descriptive methods and analysis of overall (OS) and lymphoma-specific (LSS) survival based on Kaplan-Meier function, stratified log-rank tests and Cox proportional hazard models. Results: 13,957 patients with MZL were identified and classified as splenic (SMZL; n=1,111, 8%), nodal (NMZL; n=4,101, 29%) or extranodal MALT-type MZL (MALT; n=8,745, 63%). The median age was 68 years, 74% of patients were white and 55% were women. Median follow-up was 40 months. MALT was more common in non-Caucasians (p&lt;10 -27 ). B-symptoms were more common in SMZL (p&lt;10 -5 ). Both LSS and OS were significantly better for MALT (p&lt;10 -60 ) with no difference between SMZL and NZML (p=0.30). 10-year LSS estimates were 67% for SMZL, 67% for NMZL, 84% for MALT. There was evidence for improved LSS since 2000 in MALT (HR 0.69, 95% CI 0.59-0.82, p=0.0003) and NMZL (HR 0.64, 95% CI 0.54-0.77, p&lt;10 -5 ), but not for SMZL (HR 0.85, 95% CI 0.56-1.28, p=0.43). Similar results were found for OS. There were differences in survival in MALT subtypes depending on primary site (p&lt;10 -12 ; Table). Conclusions: In the rituximab era, survival has improved for MALT and NMZL, but not for SMZL, possibly due to disparate treatment paradigms. The prognosis of MALT is different depending on primary site of involvement. [Table: see text]
VARIABILITY IN CLINICAL DECISION-MAKING FOR VENTRICULAR ASSIST DEVICE IMPLANTATION IN PEDIATRICS: RESULTS FROM A MULTI-CENTER SURVEY OF PEDIATRIC HEART FAILURE CARDIOLOGISTS AND SURGEONS
Authors: Anna Joong, Jeffrey G. Gossett, Elizabeth Blume, Philip Thrush, Elfriede Pahl, Michael Monge, Carl L. Backer, Angira Patel
Journal: Journal of the American College of Cardiology (2020)
Sequential evaluation of reduced radiotherapy doses in a phase II trial of induction chemotherapy (IndCT) followed by concomitant chemoradiotherapy (CTX) for advanced head and neck cancer (HNC)
Authors: E. E. Vokes, K. M. Stenson, E. Kistner, B. Mittal, E. E. Cohen, M. A. List, B. E. Brockstein, F. R. Rosen, M. Witt, D. J. Haraf
Journal: Journal of Clinical Oncology (2006)

5528 Background: CTX constitutes a standard for locoregionally advanced HNC. IndCT may decrease distant failure rates (Brockstein Ann Oncol, 2003). The combination of these approaches has resulted in favorable early survival outcomes. CTX is limited by acute mucositis and long-term functional impairment. We examined the feasibility of lowering radiotherapy doses in sequential groups of patients (pts) to maintain high antitumor activity while decreasing toxicities. Methods: This was a 3-part, nonrandomized, phase II trial. Pts with stage IV (M0) HNC received 8 weeks of IndCT with carboplatin and paclitaxel (groups A &amp; B ); carboplatin, AUC 2, and paclitaxel 135 mg/m 2 weekly x 6; group C carboplatin AUC 6 day 1, and paclitaxel 100 mg/m 2 days 1, 8, and 15 with cycle 2 beginning day 28. All pts received alternating week CTX with paclitaxel, infusional fluorouracil, oral hydroxyurea, and twice daily radiotherapy (T-FHX) (Kies JCO 2001). Radiotherapy to gross disease, high risk, and low risk microscopic disease consisted of group A (n = 68): 75, 60, 45 Gy; group B (n = 64): 75, 54, 39 Gy; group C (n = 90): 72, 51, 36 Gy. We have previously reported outcome data on groups A &amp; B (Vokes JCO 2002 &amp; Haraf CCR 2003). Results: A total of 222 pts were treated between 11/1998 and 2/2001. 74% were male, median age was 57. Best overall response (groups A/B/C): CR: 83/93/68%. With median follow-up time of 64/53/39 months; 3-year overall survival is 72%/67%/67% (logrank p = 0.76), progression-free survival 72%/65%/59% (logrank p = 0.44), time to progression (TTP, in which deaths prior to progression are censored unless due to treatment-related toxicity) 82%/86%/67% (logrank p = 0.019), and local control92%/97%/86% (logrank p = 0.10). Acute toxicities during concurrent chemoradiotherapy included grade 3/4 mucositis 72/2%; 65/11%; 57/8%; and dermatitis 47/15%; 19/26%; 28/2%. Conclusions: This 3-stage study suggests that acute toxicity can be reduced and high overall survival rates maintained while reducing doses of radiotherapy. The lower 3 year TTP rate in cohort C suggests a dose-response curve in the CTX setting. Schedule B may represent the best therapeutic index. Functional outcomes data are presented separately. [Table: see text]
Abstract 15559: Contributions of Electronegative Low-Density Lipoprotein to Arterial Stiffness and Cognitive Decline in Patients With Alzheimer’s Disease
Authors: Mei-Chuan Chou, Shiou-Lan Chen, Liang-Yin Ke, Ming-Hsien Tasi, Sharon Chia-Ju Chen, Chih-Sheng Chu, Chiou-Lian Lai, Chu-Huang Chen, Ching-Kuan Liu
Journal: Circulation (2019)

Introduction: Cardiometabolic disorders are increasingly viewed as pathogenic contributors to neurodegenerative processes. L5, a highly electronegative low-density lipoprotein (LDL) subfraction wit...
Treating non-responders: pitfalls and implications for cancer immunotherapy trial design
Authors: Zhenzhen Xu, Yongsoek Park, Ke Liu, Bin Zhu
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Conventional trial design and analysis strategies fail to address the typical challenge of immune-oncology (IO) studies: only a limited percentage of treated patients respond to the experimental treatment. Treating non-responders, we hypothesize, would in part drive non-proportional hazards (NPH) patterns in Kaplan-Meier curves that violates the proportional hazards (PH) assumption required by conventional strategies. Ignoring such violation incurred from treating non-responders in the design and analysis strategy may result in underpowered or even falsely negative studies. Hence, designing innovative IO trials to address such pitfall becomes essential. Methods We empirically tested the hypothesis that treating non-responders in studies of inadequate size is sufficient to cause NPH patterns and thereby proposed a novel strategy, p-embedded , to incorporate the dichotomized response incurred from treating non-responders, as measured by the baseline proportion of responders among treated patients p %, into the design and analysis procedures, aiming to ensure an adequate study power when the PH assumption is violated. Results Empirical studies confirmed the hypothetical cause contributes to the manifestation of NPH patterns. Further evaluations revealed a significant quantitative impact of p % on study efficiency. The p-embedded strategy incorporating the properly pre-specified p % ensures an adequate study power whereas the conventional design ignoring it leads to a severe power loss. Conclusion The p-embedded strategy allows us to quantify the impact of treating non-responders on study efficiency. Implicit in such strategy is the solution to mitigate the occurrence of NPH patterns and enhance the study efficiency for IO trials via enrolling more prospective responders.
A RARE CASE OF PULMONARY ATRESIA WITH INTACT VENTRICULAR SEPTUM, CONGENITALLY UNGUARDED TRICUSPID VALVE ORIFICE AND MASSIVE RIGHT-SIDED DILATION
Authors: Laura Wilson, Kavisha Shah, Diane Spicer, Himesh Vyas, Jennifer Co-Vu
Journal: Journal of the American College of Cardiology (2020)
Hormone replacement therapy (HRT) prescribing patterns among gynecologic oncologists.
Authors: Marilyn Huang, Charlotte C. Sun, Shannon Neville Westin, Diane C. Bodurka
Journal: Journal of Clinical Oncology (2013)

e20637 Background: Gynecologic cancer survivors have indicated inadequate treatment of their menopausal symptoms; and while HRT can significantly improve quality of life (QOL) its safety is still debated. Our objective was to evaluate HRT practice patterns and identify potential barriers to prescribing HRT among gynecologic oncologists (GO). Methods: SGO members with active electronic mail (n=823) were queried with single answer and Likert-style questions using an internet-based program. Email reminders were sent at 3, 6, and 9 weeks. Results: Of 207 respondents (25%), 123 (59%) were male and 84 (41%) female. Providers identified personal history of blood clot (81.5%) or breast cancer (75.6%) as contraindications to prescribing HRT. More women than men cited breast cancer and personal history of a blood clot (p=0.038, p=0.08) as contraindications. HRT candidates were women with vasomotor symptoms (sx)(96.1%), those at risk for osteoporosis (55.1%), and postmenopausal women (47.8%). Sx considered amenable to HRT were hot flashes (98.5%), vaginal atrophy (89.3%) and osteoporosis (60%). Fewer women than men (p=0.02) thought HRT was acceptable treatment for vaginal atrophy. Most practitioners would recommend HRT for sexual dysfunction (61.5%). Physicians indicated that they would prescribe HRT for ovarian (55.1%) and endometrial (58.7%) cancer survivors in surveillance. Compared to females, males were more likely to prescribe HRT to ovarian cancer patients who were newly diagnosed (p=0.005), disease-free after adjuvant chemotherapy (p=0.004), on surveillance (p&lt;0.001), or with recurrent disease (p=0.008). Similar trends occurred with endometrial cancer patients. 75% of physicians would prescribe HRT for women with cervical, vaginal, or vulvar cancer following definitive treatment. There was no consensus regarding the duration of HRT once initiated for any cancer. Interestingly, 56-71% of respondents cited evidence- based medicine as the basis for their recommendations. Conclusions: Our survey demonstrated a wide spectrum in HRT prescribing patterns of GO. As more emphasis is placed on QOL and survivorship, rigorous study of the outcomes of HRT use in our patients is of paramount importance.
A 31 YEAR OLD MAN WITH ANGINA DUE TO AORTIC VASCULITIS EXTERNALLY COMPRESSING BOTH CORONARY OSTIA
Authors: Giselle M. Statz, Noah N. Williford, Vivian R. Sardone, James Rossen, Ballas K. Zuhair, Svjetlana Dolovcak, Milena A. Gebska
Journal: Journal of the American College of Cardiology (2020)
APPLICATION OF AN ARTIFICIAL INTELLIGENCE-ENABLED ECG ALGORITHM TO IDENTIFY PATIENTS WITH LEFT VENTRICULAR SYSTOLIC DYSFUNCTION PRESENTING TO THE EMERGENCY ROOM WITH DYSPNEA
Authors: Demilade Adedinsewo, Rickey Carter, Zachi Itzhak Attia, Patrick W. Johnson, Anthony Kashou, Jennifer L. Dugan, Sheele Jonathan, Albus Michael, Paul Friedman, Francisco Lopez-Jimenez, Peter Noseworthy
Journal: Journal of the American College of Cardiology (2020)
ELIGIBILITY FOR AND USE OF SODIUM GLUCOSE COTRANSPORTER-2 INHIBITORS AND GLUCAGON-LIKE PEPTIDE-1 AGONISTS IN VETERANS WITH TYPE 2 DIABETES AND CORONARY ARTERY DISEASE: PROSPECTIVE ANALYSIS FROM THE CARDIAC CATHETERIZATION LAB CLINICAL ASSESSMENT, REPORTING, AND TRACKING (CART) PROGRAM
Authors: Demetria McNeal, Taufiq Salahuddin, Javier Valle, Kamal Henderson, Vanessa Richardson, Sridharan Raghavan, David Saxon, Paul Hess, Michael Ho, Gregory G. Schwartz
Journal: Journal of the American College of Cardiology (2020)
TAMPONADE, HEMOPERICARDIUM AND HEMOTHORAX FROM IVC STRUT FRACTURE, MIGRATION: RARE BUT DEADLY COMPLICATION!
Authors: Karan Gupta, Som Aftabizadeh, Kimberly Wilson, Anand Subramanian, Aman Patel, Ahsan Khan, Daniel Jipescu, Sanjeev Nair, Senthil Thambidorai
Journal: Journal of the American College of Cardiology (2020)
MYOCARDIAL FLOW RESERVE FROM POSITRON EMISSION TOMOGRAPHY PREDICTS TREATMENT RESPONSE IN PATIENT WITH ISCHEMIC HEART FAILURE
Authors: Dominik Benz, Philippe A. Kaufmann, Elia von Felten, Georgios Benetos, Georgios Rampidis, Michael Messerli, Andreas A. Giannopoulos, Tobias Andreas Fuchs, Christoph Gräni, Catherine Gebhard, Aju Pazhenkottil, Andreas Flammer, Philipp A. Kaufmann, Ronny R. Buechel
Journal: Journal of the American College of Cardiology (2020)
Opportunities for emotion and mental health research in the resource-rationality framework
Authors: Evan M. Russek, Rani Moran, Daniel McNamee, Andrea Reiter, Yunzhe Liu, Raymond J. Dolan, Quentin J.M. Huys
Journal: Behavioral and Brain Sciences (2020)

Abstract We discuss opportunities in applying the resource-rationality framework toward answering questions in emotion and mental health research. These opportunities rely on characterization of individual differences in cognitive strategies; an endeavor that may be at odds with the normative approach outlined in the target article. We consider ways individual differences might enter the framework and the translational opportunities offered by each.
Crimean-Congo haemorrhagic fever (CCHF) virus-specific antibody detection in blood donors, Castile-León, Spain, summer 2017 and 2018
Authors: Lía Monsalve Arteaga, Juan Luis Muñoz Bellido, María Carmen Vieira Lista, María Belén Vicente Santiago, Pedro Fernández Soto, Isabel Bas, Nuria Leralta, Fernando de Ory Manchón, Ana Isabel Negredo, María Paz Sánchez Seco, Montserrat Alonso Sardón, Sonia Pérez González, Ana Jiménez del Bianco, Lydia Blanco Peris, Rufino Alamo-Sanz, Roger Hewson, Moncef Belhassen-García, Antonio Muro
Journal: Eurosurveillance (2020)

Background Crimean-Congo haemorrhagic fever virus (CCHFV) is considered an emerging or even a probable re-emerging pathogen in southern Europe. Presence of this virus had been reported previously in Spain in 2010. Aim We aimed to evaluate the potential circulation of CCHFV in western Spain with a serosurvey in asymptomatic adults (blood donors). Methods During 2017 and 2018, we conducted a CCHFV serosurvey in randomly selected asymptomatic blood donors from western Spain. Three assays using specific IgG antibodies against CCHFV were performed: the VectoCrimea ELISA test, an in-house ELISA and indirect immunofluorescence (EuroImmun) test with glycoprotein and nucleoprotein. Results A total of 516 blood donors participated in this cross-sectional study. The majority of the study participants were male (68.4%), and the mean age was 46.3 years. Most of the participants came from rural areas (86.8%) and 68.6% had contact with animals and 20.9% had animal husbandry practices. One in five participants (109/516, 21.1%) were engaged in at-risk professional activities such as agriculture and shepherding, slaughtering, hunting, veterinary and healthcare work (mainly nursing staff and laboratory technicians). A total of 15.3% of the participants were bitten by ticks in the days or months before the date of sampling. We detected anti-CCHFV IgG antibodies with two diagnostic assays in three of the 516 individuals and with one diagnostic assay in six of the 516 individuals. Conclusion Seroprevalence of CCHFV was between 0.58% and 1.16% in Castile-León, Spain. This is the first study in western Spain that showed circulation of CCHFV in healthy people.
Patient characteristics influencing quality of life in gynecologic cancer
Authors: K. Gil, H. Frasure, E. Jenison, M. Hopkins, V. Von Gruenigen
Journal: Journal of Clinical Oncology (2006)

6132 Background: The Functional Assessment of Cancer Therapy general (FACT) questionnaire was developed to assess disease and treatment specific issues affecting patients’ quality of life (QoL). Factors other than cancer and its treatment, such as age, general physical and emotional health, and socio-economic status, may have significant effects on QoL and patients’ response to treatments. This study examined the effect of these variables on the domains of the FACT in gynecologic oncology patients undergoing surgery for pelvic mass suspected to be malignant or endometrial cancer. Methods: Demographic information and patient characteristics were obtained pre-operatively. Patients also completed the FACT and the SF-36, a general health questionnaire that measures physical and mental well-being but is not designed to be sensitive to the detection of small treatment effects. Correlation and multiple regression analysis were used to assess the effect of diagnosis, age, body mass index (BMI), educational level, marital status, smoking status, physical (PCS) and mental (MCS) summary scores of the SF-36 on FACT domain scores. Results: Data were collected on 157 women at their pre-operative visit (endometrial cancer, n=45; benign masses, n=79; ovarian cancer, n=33). PCS, MCS and age were positively correlated with scores on the FACT, while BMI and smoking were negatively correlated ( Table ). Educational level was negatively correlated with scores on the social domain but positively correlated with physical scores on the FACT. PCS and MCS accounted for a significant amount of the variance (R 2 ) in regression models for each of the FACT domains ( Table ). Conclusion: Patients’ QoL, as measured by a questionnaire that is sensitive to their disease and treatment, is affected by their baseline characteristics. As treatment options become more complex, these variables are likely to be of increasing importance in evaluating QoL. [Table: see text] No significant financial relationships to disclose.
IMPACT OF MITRAL CALCIUM VOLUME ON MITRAL VALVE FUNCTION AND CLINICAL OUTCOMES IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Taishi Okuno, Nicolas Brugger, Masahiko Asami, Dik Heg, Stefan Stortecky, Thomas Pilgrim, Stephan Windecker, Omar Khalique, Fabien Praz
Journal: Journal of the American College of Cardiology (2020)
Use of an optimized primary ovarian cancer xenograft model to mimic patient tumor biology and heterogeneity.
Authors: Zachary C. Dobbin, Ashwini A. Katre, Angela Ziebarth, Monjri Shah, Adam D. Steg, Ronald David Alvarez, Michael G. Conner, Charles N. Landen
Journal: Journal of Clinical Oncology (2012)

5036 Background: Current xenograft and transgenic models of ovarian cancer are mainly homogeneous and poorly predict response to therapy. Use of patient tumors may represent a better model for tumor biology and offer potential to test personalized medicine approaches, but poor take rates and questions of recapitulation of patient tumors have limited this approach. We have developed a protocol for improved feasibility of such a model and examined its similarity to the patient tumor. Methods: Under IRB and IACUC approval, 23 metastatic ovarian cancer samples were collected at the time of tumor reductive surgery. Samples were implanted either subcutaneously (SQ), intraperitoneally (IP), in the mammary fat pad (MFP), or in the subrenal capsule (SRC) and monitored for tumor growth. Cohorts from 8 xenolines were treated with combined carboplatin and paclitaxel or vehicle, and response to therapy compared between xenografts and patients. Expression of tumor-initiating cell (TIC) markers ALDH1, CD133, and CD44 was assessed by immunohistochemistry in tumors from patients and treated and untreated xenografts. Results: At least one SQ implanted tumor developed in 91.3% of xenografts, significantly higher than in the MFP (63.6%), IP (23.5%), or SRC (8%). Xenografts were similar in expression of putative TIC’s compared to patient tumors. The patients and the xenografts also have similar responses to chemotherapy in that xenografts from patients with a partial response responded more slowly than those from patients achieving a complete response (45 vs 21 days, p=.004). Treated xenografts were more densely composed of TICs. ALDH1 increased to 36.1% from 16.2% (p=0.002) and CD133 increased to 33.8% from 16.2% (p=0.026). Conclusions: Xenoline development can be achieved at a high rate when tumors collected from metastatic sites are implanted SQ. These xenografts are similar to patient tumors with regard to chemotherapy response and TIC expression.. This model may be a more accurate model for in vivo pre-clinical studies as compared to current models. Also, as treated xenografts become chemoresistant, this model is well positioned to evaluate targeted therapies aimed at the most aggressive populations in a heterogeneous tumor.