tbuckley/cabot-search huggingface dataset:
Clinical features of bronchioloalveolar carcinoma with new histologic and staging definitions.
Authors: P. Yang, J. Ebbert, L. Chhatwani, J. A. Wampfler, S. Stoddard, F. Zhang, M. de Andrade, M. Aubry
Journal: Journal of Clinical Oncology (2010)

7097 Background: The description of disease consistent with bronchioloalveolar carcinoma (BAC) dates back to the 1800's. Lack of precision in prevalence and survival estimates of BAC relates to wide variations in criteria distinguishing BAC from adenocarcinoma. Our goal was to assess clinical features of BAC based on the 1999 WHO Classification (“pure BAC”), compare pure BAC patients with patients previously diagnosed as BAC not meeting the 1999 definition, and compare survival changes of pure BAC based on the old and new (2009) staging systems. Methods: A pulmonary pathologist reviewed each BAC tumor diagnosed from 1997 to 2007 identifying cases meeting the new criteria. Cases were restaged according to the 7th edition of the TNM classification. Pure BAC patients were analyzed under both staging systems for changes in overall survival. Results: Of 338 total patients who were diagnosed with BAC, 117 were classified as pure and 221 were non pure BAC. Of the 117 and 221, 78 and 178, respectively had no other primary lung cancer. One- and five-year survival for the 78 pure BAC patients were 94.8% and 83.5%, and for the 178 patients were 92.6% and 46.4%, respectively. Restaging for pure BAC cases resulted in a change in 9 of the 78 cases (12%). Compared to the old staging, patients with advanced stage under the new stage had a worse 5-year survival (53% vs. 45%); whereas, no change was observed for stage IA. Conclusions: For patients with pure BAC, the new pathologic system favorably affects survival and the new staging system may more accurately reflect prognosis in advanced stage cancer. Our results have important implications for researchers, clinicians, and patients. No significant financial relationships to disclose.
Allogeneic NK Cell Therapy After Autologous Stem Cell Transplant: Results of a Phase I Study
Authors: Hans-Georg Klingemann, Carrie Grodman, Andreas K. Klein, Kellie Sprague, Kenneth B. Miller, Tarun Kewalramani, Raymond L. Comenzo, Neng Yu, Marvin Duque, Richard A. Van Etten, David McKenna
Journal: Blood (2010)
Prognostic Value of Metabolic Tumor Volume and Total Lesion Glycolysis on Preoperative 18F-FDG PET/CT in Patients With Very Early and Early Hepatocellular Carcinoma
Authors: Sang Hyun Hwang, Jeong Won Lee, Ho Jin Cho, Kyung Sik Kim, Gi Hong Choi, Mijin Yun
Journal: Clinical Nuclear Medicine (2016)

The aim of this article was to evaluate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on preoperative F-FDG PET/CT for predicting intrahepatic recurrence-free survival (IHRFS), extrahepatic metastasis-free survival (EHMFS), and overall survival (OS) in patients with very early/early hepatocellular carcinoma (HCC).We retrospectively enrolled 132 patients with very early/early HCC who underwent F-FDG PET/CT followed by surgery. The maximum tumor SUV-to-mean normal liver SUV ratio, MTV, and TLG were measured for each patient. Prognostic significances of PET/CT parameters and clinicopathologic factors for IHRFS, EHMFS, and OS were evaluated. Cumulative IHRFS, EHMFS, and OS were calculated using the Kaplan-Meier method.Thirty-three (25%) and 21 (15.9%) of 132 patients experienced intrahepatic and extrahepatic recurrence, respectively, during a median follow-up period of 38.1 months. In multivariate analysis, none of the factors were significant for IHRFS. Metabolic tumor volume and TLG were only significant factors for EHMFS and OS (P < 0.05). The 5-year EHMFS rates were 94.8% in patients with low MTV and TLG, and 62.1% and 63.2% in patients with high MTV and TLG, respectively (P < 0.001). The 5-year OS rates were 92.6% and 92.4% in patients with low MTV and TLG, and 63.3% and 64.3% in patients with high MTV and TLG, respectively (P < 0.001).Metabolic tumor volume and TLG on preoperative PET/CT were independent prognostic factors for EHMFS and OS but not IHRFS in patients with very early/early HCC. Therefore, patients with high MTV or TLG should be closely observed for extrahepatic metastasis using systemic evaluations.
GW26-e1435 Tanshinone IIA Reduces Atrial Fibrillation by Inhibiting Left Atrial Fibrosis Via MMP-9 / TIMP-1 Pathway in Isoproterenol-Induced Myocardial Infarction Rats
Authors: Jin Ma, Shiyu Ma, Huiliang Qiu, Chunhua Ding
Journal: Journal of the American College of Cardiology (2015)
Expression of scavenger receptor‐AI promotes alternative activation of murine macrophages to limit hepatic inflammation and fibrosis
Authors: Adam C. Labonte, Sun‐Sang J. Sung, Lucas T. Jennelle, Aditya P. Dandekar, Young S. Hahn
Journal: Hepatology (2016)

The liver maintains an immunologically tolerant environment as a result of continuous exposure to food and bacterial constituents from the digestive tract. Hepatotropic pathogens can take advantage of this niche and establish lifelong chronic infections causing hepatic fibrosis and hepatocellular carcinoma. Macrophages (Mϕ) play a critical role in regulation of immune responses to hepatic infection and regeneration of tissue. However, the factors crucial for Mϕ in limiting hepatic inflammation or resolving liver damage have not been fully understood. In this report, we demonstrate that expression of C-type lectin receptor scavenger receptor-AI (SR-AI) is crucial for promoting M2-like Mϕ activation and polarization during hepatic inflammation. Liver Mϕ uniquely up-regulated SR-AI during hepatotropic viral infection and displayed increased expression of alternative Mϕ activation markers, such as YM-1, arginase-1, and interleukin-10 by activation of mer receptor tyrosine kinase associated with inhibition of mammalian target of rapamycin. Expression of these molecules was reduced on Mϕ obtained from livers of infected mice deficient for the gene encoding SR-AI (msr1). Furthermore, in vitro studies using an SR-AI-deficient Mϕ cell line revealed impeded M2 polarization and decreased phagocytic capacity. Direct stimulation with virus was sufficient to activate M2 gene expression in the wild-type (WT) cell line, but not in the knockdown cell line. Importantly, tissue damage and fibrosis were exacerbated in SR-AI–/– mice following hepatic infection and adoptive transfer of WT bone-marrow–derived Mϕ conferred protection against fibrosis in these mice. Conclusion: SR-AI expression on liver Mϕ promotes recovery from infection-induced tissue damage by mediating a switch to a proresolving Mϕ polarization state. (Hepatology 2017;65:32-43).
Implications of the Patient Protection and Affordable Care Act on Insurance Coverage and Rehabilitation Use Among Young Adult Trauma Patients
Authors: Cheryl K. Zogg, Fernando Payró Chew, John W. Scott, Lindsey L. Wolf, Thomas C. Tsai, Peter Najjar, Olubode A. Olufajo, Eric B. Schneider, Elliott R. Haut, Adil H. Haider, Joseph K. Canner
Journal: JAMA Surgery (2016)

Trauma is the leading cause of death and disability among young adults, who are also among the most likely to be uninsured. Efforts to increase insurance coverage, including passage of the Patient Protection and Affordable Care Act (ACA), were intended to improve access to care and promote improvements in outcomes. However, despite reported gains in coverage, the ACA's success in promoting use of high-quality care and enacting changes in clinical end points remains unclear.To assess for observed changes in insurance coverage and rehabilitation use among young adult trauma patients associated with the ACA, including the Dependent Coverage Provision (DCP) and Medicaid expansion/open enrollment, and to consider possible insurance and rehabilitation differences between DCP-eligible vs -ineligible patients and among stratified demographic and community subgroups.A longitudinal assessment of DCP implementation and Medicaid expansion/open enrollment using risk-adjusted before-and-after, difference-in-difference, and interrupted time-series analyses was conducted. Eleven years (January 1, 2005, to September 31, 2015) of Maryland Health Services Cost Review Commission data, representing complete patient records from all payers within the state, were used to identify all hospitalized young adult (aged 18-34 years) trauma patients in Maryland during the study period.Of the 69 507 hospitalized patients included, 50 548 (72.7%) were male, and the mean (SD) age was 25 (5) years. Before implementation of the DCP, 1 of 4 patients was uninsured. After ACA implementation, the number fell to less than 1 of 10, with similar patterns emerging in emergency department and outpatient settings. The change was primarily driven by Medicaid expansion/open enrollment, which corresponded to a 20.1 percentage-point increase in Medicaid (95% CI, 18.9-21.3) and an 18.2 percentage-point decrease in uninsured (95% CI, -19.3 to -17.2). No changes were detected among privately insured patients. Rehabilitation use increased by 5.4 percentage points (95% CI, 4.5-6.2)-a 60% relative increase from a baseline of 9%. Mortality (-0.5; 95% CI, -0.9 to -0.1) and failure-to-rescue rates (-4.5; 95% CI, -7.4 to -1.6) also significantly declined. Stratified changes point to significant differences in the percentage of uninsured patients and rehabilitation access across the board, mitigating or even eradicating disparities in certain cases.For patients who are injured, young, and uninsured, Medicaid expansion/open enrollment in Maryland changed insurance coverage and altered patient outcomes in ways that the DCP alone was never intended to do. Implementation of Medicaid expansion/open enrollment transformed the landscape of trauma coverage, directly affecting the health of one of the country's most vulnerable at-risk groups.
Longitudinal Trends in Peripheral Blood Parameters Predict Development of Therapy-Related Myelodysplasia/Acute Myeloid Leukemia (t-MDS/ AML) after Autologous Transplantation for Lymphoma.
Authors: Liton Francisco, Can-Lan Sun, Lester Laddaran, Melanie Sabado, Alysia Bosworth, Karen L. Chang, Leslie Popplewell, Auayporn P. Nademanee, Marilyn L. Slovak, Stephen J. Forman, Ravi Bhatia, Smita Bhatia
Journal: Blood (2008)
Inhibition of <i>STAT3</i> with the Generation 2.5 Antisense Oligonucleotide, AZD9150, Decreases Neuroblastoma Tumorigenicity and Increases Chemosensitivity
Authors: Seiichi Odate, Veronica Veschi, Shuang Yan, Norris Lam, Richard Woessner, Carol J. Thiele
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Neuroblastoma is a pediatric tumor of peripheral sympathoadrenal neuroblasts. The long-term event-free survival of children with high-risk neuroblastoma is still poor despite the improvements with current multimodality treatment protocols. Activated JAK/STAT3 pathway plays an important role in many human cancers, suggesting that targeting STAT3 is a promising strategy for treating high-risk neuroblastoma. Experimental Design: To evaluate the biologic consequences of specific targeting of STAT3 in neuroblastoma, we assessed the effect of tetracycline (Tet)-inducible STAT3 shRNA and the generation 2.5 antisense oligonucleotide AZD9150 which targets STAT3 in three representative neuroblastoma cell line models (AS, NGP, and IMR32). Results: Our data indicated that Tet-inducible STAT3 shRNA and AZD9150 inhibited endogenous STAT3 and STAT3 target genes. Tet-inducible STAT3 shRNA and AZD9150 decreased cell growth and tumorigenicity. In vivo, STAT3 inhibition by Tet-inducible STAT3 shRNA or AZD9150 alone had little effect on growth of established tumors. However, when treated xenograft tumor cells were reimplanted into mice, there was a significant decrease in secondary tumors in the mice receiving AZD9150-treated tumor cells compared with the mice receiving ntASO-treated tumor cells. This indicates that inhibition of STAT3 decreases the tumor-initiating potential of neuroblastoma cells. Furthermore, inhibition of STAT3 significantly increased neuroblastoma cell sensitivity to cisplatin and decreased tumor growth and increased the survival of tumor-bearing mice in vivo. Conclusions: Our study supports the development of strategies targeting STAT3 inhibition in combination with conventional chemotherapy for patients with high-risk neuroblastoma. Clin Cancer Res; 23(7); 1771–84. ©2016 AACR.
GW26-e2449 The Role of Calpain in Myocardial Apoptosis Induced by Oxidative Stress in Mouse cardiomyocytes Hypoxia/Reoxygenation
Authors: Shuang Zhang, Houxiang Hu, Lei Xu, Rongchuan Yue, Chunyan Tan, Haiyan Chen, Rongyi Zhang
Journal: Journal of the American College of Cardiology (2015)
Use of serum autoantibodies to identify early-stage lung cancer.
Authors: L. Peek, S. Lam, G. Healey, H. A. Fritsche, C. Chapman, A. Murray, P. Maddison, J. F. Robertson, W. Wood
Journal: Journal of Clinical Oncology (2010)

7032 Background: EarlyCDT-Lung measures autoantibodies to a panel of six cancer-associated antigens (p53, NY-ESO1, CAGE, GBU4-5, Annexin1, and SOX2) with a specificity of 90% and a sensitivity of 45% for small cell lung cancer (SCLC) and 34% for non-small cell lung cancer (NSCLC). We report confirmatory data for clinical sensitivity and specificity determined in an independent, prospective, post-validation dataset. Methods: Four hundred and fifty three (453) patients with newly diagnosed, untreated lung cancer were matched for age, sex, and smoking history to high-risk individuals. Patient and control samples were collected from multiple locations in the USA, Canada, and Europe and measured on EarlyCDT-Lung. 258/359 (72%) of NSCLC were known early-stage disease (ie stage 1 or 2), 10/28 (36%) of SCLC were limited disease, and 66 were unknown stage. A larger series of 211 SCLC patients with matched high-risk controls obtained from a single European center was measured for autoantibodies to the same six cancer-associated antigens (Oncimmune Ltd, Nottingham, UK). Results: In the multicentre group (n=453), for early-stage disease the positivity rate was 35% (89/258) for NSCLC and 40% (4/10) for SCLC. In the single center SCLC dataset (n=211) the positivity rate for limited disease was 47% (41/87). Combining both groups (n=664 lung cancers) gave an overall positivity of 40% of lung cancers. For early-stage disease, the positivity rate was 35% (89/258) of NSCLC and 46% (45/97) for SCLC. Overall specificity for all high-risk individuals (n=1,029) was 88%. Conclusions: This large dataset further confirms that up to 40% of lung cancer, including early-stage disease, can be identified through a blood test. EarlyCDT-Lung and CT scanning have the potential for early detection of a large subset of lung-cancers. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncimmune Oncimmune Oncimmune Oncimmune
A Longitudinal Study of Adjustment Disorder After Trauma Exposure
Authors: Meaghan L. O’Donnell, Nathan Alkemade, Mark Creamer, Alexander C. McFarlane, Derrick Silove, Richard A. Bryant, Kim Felmingham, Zachery Steel, David Forbes
Journal: American Journal of Psychiatry (2016)

Objective: Adjustment disorder has been recategorized as a trauma- and stressor-related disorder in DSM-5. The aim of this study was to determine the prevalence of adjustment disorder in the first 12 months after severe injury; to determine whether adjustment disorder was a less severe disorder compared with other disorders in terms of disability and quality of life; to investigate the trajectory of adjustment disorder; and to examine whether the subtypes described in DSM-5 are distinguishable. Method: In a multisite, cohort study, injury patients were assessed during hospitalization and at 3 and 12 months postinjury (N=826). Structured clinical interviews were used to assess affective, anxiety, and substance use disorders, and self-report measures of disability, anxiety, depression, and quality of life were administered. Results: The prevalence of adjustment disorder was 19% at 3 months and 16% at 12 months. Participants with adjustment disorder reported worse outcomes relative to those with no psychiatric diagnosis but better outcomes compared with those diagnosed with other psychiatric disorders. Participants with adjustment disorder at 3 months postinjury were significantly more likely to meet criteria for a psychiatric disorder at 12 months (odds ratio=2.67, 95% CI=1.59−4.49). Latent-profile analysis identified a three-class model that was based on symptom severity, not the subtypes identified by DSM-5. Conclusions: Recategorization of adjustment disorder into the trauma- and stressor-related disorders is supported by this study. However, further description of the phenomenology of the disorder is required.
Inhibition Of Autophagy By ACY-1215, a Selective HDAC6 Inhibitor Accelerates Carfilzomib-Induced Cell Death In Multiple Myeloma
Authors: Yuko Mishima, Loredana Santo, Diana D. Cirstea, Homare Eda, Neeharika Nemani, Shirin Arastu-Kapur, Christopher J. Kirk, Simon S Jones, Raje Noopur
Journal: Blood (2013)
WT1 snp rs16754 Genotype Predicts Treatment Related Mortality (TRM) in African-American and Asian Pediatric AML Patients: A Report From the Children's Oncology Group
Authors: Phoenix A. Ho, Todd A. Alonzo, Robert B. Gerbing, Lillian Sung, Richard Aplenc, Jessica A. Pollard, Julia Kuhn, Nyla A. Heerema, Beverly J. Lange, Alan S. Gamis, Soheil Meshinchi
Journal: Blood (2012)
Utility of the vulnerable elders survey for predicting sixth-month functional decline among older patients with newly diagnosed breast cancer.
Authors: C. Owusu, M. D. Schluchter, S. M. Koroukian, P. Bakaki, N. A. Berger
Journal: Journal of Clinical Oncology (2010)

598 Background: Instruments specifically validated for predicting functional decline in geriatric-oncology are nonexistent. The Vulnerable Elders Survey (VES), an instrument predicting functional decline among community dwelling older adults, has never been validated in oncology patients. We sought to examine the ability of the VES to predict functional decline at 6 months among older women with newly diagnosed breast cancer undergoing treatment. Methods: Between April 2008 and September 2009 women ≥ 65 years with incident stage I-IV breast cancer, were enrolled into a prospective cohort study at an academic center. The primary end-point was functional decline at 6 months, (yes/no), defined as ≥ 1-point decrement in Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) scores or admission to a nursing home during the follow-up period. Multiple logistic regression and Receiver Operator Curve (ROC) analyses were used to examine the relation between VES scores at baseline and functional decline at 6 months. Results: Sixty-five women were enrolled within 3 months of diagnosis and completed baseline assessment. The median age was 74 years, 86% had stage I-II disease, 92% completed primary surgery and 21% received adjuvant chemotherapy. The mean baseline VES score was 2.8. As of 12/31/2009, 55 women had completed sixth-month assessment for functional decline, 5 women had pending assessments and 5 women had withdrawn or been lost to follow-up. The median duration of follow-up was 5.8 months. Twenty-four percent developed functional decline. The mean change in ADL/IADL score from baseline to 6 months was -0.42, 95% CI (-0.80, -0.03), p = 0.03. For each additional VES point, the odds ratio (OR) of functional decline was 1.42 (1.09-1.86), and the area under the ROC was 0.70, 95% Confidence Interval (CI: 0.54, 0.87). The VES score, but not cancer stage or comorbidity, remained the only significant predictor of functional decline. Conclusions: The VES is a useful tool for predicting risk of functional decline among older women with incident breast cancer who may then be targeted for early intervention to improve treatment tolerance and cancer outcomes. No significant financial relationships to disclose.
A phase II randomized, double-blind, placebo-controlled trial of clinical activity and safety of Å6 in patients with asymptomatic CA 125 progression of epithelial ovarian, fallopian tube, or primary peritoneal cancer
Authors: S. Ghamande, M. Silverman, M. Gold, W. Huh, K. Behbakht, G. Ball, L. Cuasay, N. Brunner
Journal: Journal of Clinical Oncology (2007)

16014 Background: Patients (pts) with epithelial ovarian cancer (EOC) often relapse and rising CA 125 levels predate clinical or radiological appearance of tumor. High tumor and serum levels of urokinase plasminogen activator (uPA) in EOC correlate to adverse outcomes. Å6 is a novel peptide derived from human uPA that down-regulates the uPA system and has anti-angiogenic and anti-metastatic activity in animals. Methods: Pts with EOC, fallopian tube, or primary peritoneal cancer in clinical remission after first line chemotherapy had to have 2 consecutive rises of CA 125 levels above normal with no disease on physical examination or imaging studies. Pts were randomized to receive daily subcutaneous injections of placebo, 150 mg Å6, or 300 mg Å6 until disease progression. The primary objectives were to assess safety and clinical activity of Å6 by the effect on the onset of disease progression. Results: 48 pts were planned for the study. The trial ended early with 24 patients {12 pts (50%) placebo, 8 pts (33%) low dose Å6, 4 pts (17%) high dose Å6} randomized, treated and followed for up to 9 months. Despite early study termination and small sample size, A6 therapy was associated with a statistically significant progression free survival (PFS) (log rank p value=0.01) with a median PFS of 100 days (95% CI 64,168) compared to 49 days (95% CI 29,67) in pts who received the placebo. The treatments were well tolerated with one serious adverse event (transient nausea and dyspnea ) possibly related to study drug. Treatment was not associated with CA 125 response (Fisher exact test p value= 0.44). Conclusions: Å6 therapy increases PFS of patients with EOC and asymptomatic progression of CA 125. This therapy is novel, safe, feasible and deserves further investigation [Table: see text]