tbuckley/cabot-search huggingface dataset:
Neoadjuvant ipilimumab in patients with stage IIIB/C melanoma: Immunogenicity and biomarker analysis.
Authors: A. A. Tarhini, H. Edington, L. H. Butterfield, M. Sinha, S. J. Moschos, H. Tawbi, Y. Shuai, J. Shipe-Spotloe, M. Simonettta, C. Milburn, M. Horak, C. Sander, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2011)

8536 Background: Regional lymph node metastasis from melanoma has a high relapse and mortality risk. Neoadjuvant ipilimumab (ipi) may improve the clinical outcome and through access to tumor before and after ipi may allow new insight into the biologic and immunologic response. Methods: Pts (stage IIIB-C melanoma) were treated with ipi (10 mg/kg IV q3weeks x2doses) as preoperative induction followed by lymphadenectomy (at week ≥ 6) and 2 additional doses of maintenance ipi (3 weeks apart). Tissue samples were obtained at baseline and at definitive surgery and blood (serum/PBMC) collected at baseline, 6 weeks, 3, 6, 9, 12 months and/or progression for immunologic/mechanistic studies comparing pre- and post-treatment tumor and blood features. Results: Seventeen pts (14 M, 3 F), age 44-87 have been enrolled since Feb/2010 (14 cutaneous primary and 3 mucosal). Two had stage IIIB (1N2b, 1N2c) and 15 IIIC (N3) melanoma. Seven pts had recurred after receiving adjuvant IFN. Fifty three cycles have been delivered (median 4). Grade 3 (worst) toxicities include diarrhea/colitis (6 pts; 35%), hepatic enzyme elevations (1; 5%), rash (1; 5%), lipase (1; 5%), all manageable. Among 16 evaluable pts (surgery is pending for1), median follow-up is 7.9 months and 13 pts (81%) continue disease free. The probability of 6 and 12 months PFS is 84.4% (95% CI=0.50, 0.95) and 63.3% (95% CI=0.17, 0.88) respectively. There is significant increase in the frequency of circulating T-regulatory cells (CD4+CD25hi+ Foxp3+; p=0.009. CD4+CD25hi+CD39+; p=0.011) from baseline to 6 wks. In parallel there is significant decrease in circulating MDSCs: (1) monocytic: lin1neg/HLA-DRneg/ CD33+/CD11b+; p=0.038, (2) other monocytic: HLA-DR+/low/CD14+; p<0.0001 and less significant for (3) lymphoid: Lin1neg/HLA-DR-/CD33+/CD11b+; p=0.067. Immune monitoring comparing baseline and 6 wk tumor samples is ongoing. Conclusions: Our preliminary results show that neoadjuvant ipilimumab is clinically promising and immunologically appears to significantly modulate host immune responses. Ongoing functional and tissue biomarker studies will seek correlations between systemic findings and the tissue impact of ipilimumab that are uniquely assailable using the neoadjuvant model.
Abstract 17979: Prognostic Value of Aldosterone Breakthrough in Systolic Heart Failure Patients
Authors: Giuseppe Vergaro, Roberta Poletti, Alessandra Gabutti, Chiara Mammini, Annamaria Del Franco, Nicola Riccardo Pugliese, Alessandro Valleggi, Pastormerlo Luigi Emilio, Passino Claudio, Michele Emdin
Journal: Circulation (2013)

Purpose: Antagonism of the renin-angiotensin-aldosterone system (RAAS) represents a cornerstone of current therapy of heart failure (HF). Nonetheless, up to half of HF patients show elevated aldost...
Exploring and exploiting the systemic effects of deregulated replication licensing
Authors: Theodoros G. Petrakis, Eirini-Stavroula Komseli, Marilena Papaioannou, Kostas Vougas, Alexandros Polyzos, Vassilios Myrianthopoulos, Emmanuel Mikros, Ioannis P. Trougakos, Dimitris Thanos, Dana Branzei, Paul Townsend, Vassilis G. Gorgoulis
Journal: Seminars in Cancer Biology (2015)
Religious coping and depression among elderly, hospitalized medically ill men
Authors: H G Koenig, H J Cohen, D G Blazer, C Pieper, K G Meador, F Shelp, V Goli, B DiPasquale
Journal: American Journal of Psychiatry (1992)

The investigators examined the frequency of religious coping among older medical inpatients, the characteristics of those who use it, and the relation between this behavior and depression.The subjects were 850 men aged 65 years and over, without psychiatric diagnoses, who were consecutively admitted to the medical or neurological services of a southern Veterans Administration medical center. Religious coping was assessed with a three-item index. Depressive symptoms were assessed by self-rating (the Geriatric Depression Scale) and observer rating (the Hamilton Rating Scale for Depression).One out of every five patients reported that religious thought and/or activity was the most important strategy used to cope with illness. Variables that were associated with religious coping included black race, older age, being retired, religious affiliation, high level of social support, infrequent alcohol use, a prior history of psychiatric problems, and higher cognitive functioning. Depressive symptoms were inversely related to religious coping, an association which persisted after other sociodemographic and health correlates were controlled. When 202 men were reevaluated during their subsequent hospital admissions an average of 6 months later, religious coping was the only baseline variable that predicted lower depression scores at follow-up.These findings suggest that religious coping is a common behavior that is inversely related to depression in hospitalized elderly men.
Acute non-invasive ventilation during pregnancy in a patient with amyotrophic lateral sclerosis
Authors: D.B.M. Kock-Cordeiro, A.J. Eggink, C.D. van der Marel, R.J.M. van den Biggelaar
Journal: European Respiratory Journal (2014)

One of the most common progressive neurodegenerative diseases is amyotrophic lateral sclerosis (ALS). It is diagnosed in the 5 th  to 7 th  decade and is common in males. ALS in women of childbearing age and coexisting pregnancy is uncommon. We would like to describe the first reported case in which non-invasive ventilation (NIV) was acutely initiated in a pregnant patient with ALS   Case report   A 25-year-old patient, G2P1, had complaints of speech, swallowing difficulty and tiredness that she credited to her pregnancy. She later developed weakness in her right arm and sought consultation. Physical exam revealed myopathic facies, dysarthria, tongue atrophy and fasciculation, weakness in neck flexor and right arm muscles. After two months ALS was diagnosed. Fetal development was uncomplicated. At her first visit to the respiratory department at 32 weeks of gestation, she had no pulmonary complaints. Examination revealed weak cough capacity, peripheral saturation 98% (room air) and decreased forced vital capacity (42% of predicted). Transcutaneous CO2 and O2 measurement was normal during sleep. Four days later she was admitted with progressive dyspnea, orthopnea and respiratory exhaustion. NIV with oronasal mask was acutely initiated and well tolerated despite poor bulbar function. Due to rapid deterioration a caesarian section was performed under NIV and spinal anesthesia. Intubation and total anesthesia with was averted. A healthy male baby was born. Postoperative NIV could be weaned slowly to only nighttime use and she was discharged with domiciliary NIV.   Conclusion   Acute NIV in pregnant ALS patient with respiratory distress could be safely initiated.
Development and validation of an HPLC–MS/MS method to determine clopidogrel in human plasma
Authors: Gangyi Liu, Chunxia Dong, Weiwei Shen, Xiaopei Lu, Mengqi Zhang, Yuzhou Gui, Qinyi Zhou, Chen Yu
Journal: Acta Pharmaceutica Sinica B (2015)

A quantitative method for clopidogrel using online-SPE tandem LC-MS/MS was developed and fully validated according to the well-established FDA guidelines. The method achieves adequate sensitivity for pharmacokinetic studies, with lower limit of quantifications (LLOQs) as low as 10 pg/mL. Chromatographic separations were performed on reversed phase columns Kromasil Eternity-2.5-C18-UHPLC for both methods. Positive electrospray ionization in multiple reaction monitoring (MRM) mode was employed for signal detection and a deuterated analogue (clopidogrel-d 4) was used as internal standard (IS). Adjustments in sample preparation, including introduction of an online-SPE system proved to be the most effective method to solve the analyte back-conversion in clinical samples. Pooled clinical samples (two levels) were prepared and successfully used as real-sample quality control (QC) in the validation of back-conversion testing under different conditions. The result showed that the real samples were stable in room temperature for 24 h. Linearity, precision, extraction recovery, matrix effect on spiked QC samples and stability tests on both spiked QCs and real sample QCs stored in different conditions met the acceptance criteria. This online-SPE method was successfully applied to a bioequivalence study of 75 mg single dose clopidogrel tablets in 48 healthy male subjects.
Postprogression Prolongation of Survival in<i>EGFR</i>-Mutated Lung Cancer
Authors: David R. Gandara, Mary Redman, Fred R. Hirsch
Journal: JAMA Oncology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Hypocholesterolemia in patients treated with recombinant interleukin-2: appearance of remnant-like lipoproteins.
Authors: D E Wilson, G R Birchfield, J S Hejazi, J H Ward, W E Samlowski
Journal: Journal of Clinical Oncology (1989)

Reversible acute hypocholesterolemia was observed during treatment of metastatic cancer with high-dose intravenous recombinant interleukin-2 (IL-2). Further analysis revealed virtual disappearance of high-density lipoproteins (HDLs) and marked reduction in the concentration of low-density lipoproteins (LDL); the remaining LDL and intermediate-density lipoproteins (IDL) were enriched in triglyceride relative to cholesterol and had broad-beta electrophoretic mobility, properties reminiscent of remnant lipoproteins. These changes differ qualitatively and quantitatively from those previously reported for other cytokines such as tumor necrosis factor (TNF) or the interferons (IFNs).
Prognostic and biologic significance of high LCK expression in ovarian cancer
Authors: Amir Jazaeri, Cherie Paquette, Sarah M Kelting, Mark H Stoler, Qian Zhang, Melinda Yates, Caitlin Creasy, Chantale Bernatchez, Patrick Hwu
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Epithelial ovarian cancer is the most lethal and second most common gynecologic cancer in the United States. Previous studies have demonstrated the favorable prognostic value of tumor infiltrating lymphocytes in this disease. The objective of this study was to evaluate the
A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H–Related 3 Gene in Atypical Hemolytic Uremic Syndrome
Authors: Rachel C. Challis, Geisilaine S.R. Araujo, Edwin K.S. Wong, Holly E. Anderson, Atif Awan, Anthony M. Dorman, Mary Waldron, Valerie Wilson, Vicky Brocklebank, Lisa Strain, B. Paul Morgan, Claire L. Harris, Kevin J. Marchbank, Timothy H.J. Goodship, David Kavanagh
Journal: Journal of the American Society of Nephrology (2015)

The regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H-related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination. We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3-kb deletion that arose through microhomology-mediated end joining rather than nonallelic homologous recombination. We confirmed a transcript from this hybrid gene and showed a secreted protein product that lacks the recognition domain of factor H and exhibits impaired cell surface complement regulation. The fact that the formation of this hybrid gene arose as a de novo event suggests that this cluster is a dynamic area of the genome in which additional genomic disorders may arise.
Phase I–II study of vinorelbine in combination with 5-fluorouracil and folinic acid as first-line chemotherapy in metastatic breast cancer: A regimen with a low subjective toxic burden
Authors: F. Nolè, F. de Braud, M. Aapro, I. Minchella, M. De Pas, M.G. Zampino, S. Monti, G. Andreoni, A. Goldhirsch
Journal: Annals of Oncology (1997)
Abstract MP95: Association between Artificially Sweetened Beverages and the Incidence of Type 2 Diabetes in Postmenopausal Women
Authors: Lynda J Stinson, Asha Bansari, Abdullah Quddus, Randa M Kutob, James M Shikany, Barbara V Howard, JoAnn E Manson, Bing Lu, Charles B Eaton
Journal: Circulation (2013)

Background. Evidence demonstrating a relationship between artificially sweetened beverages (ASB) and the incidence of type 2 diabetes (T2D) is limited with mixed results. Among postmenopausal women...
Comparative Genomics of Early-Diverging Mushroom-Forming Fungi Provides Insights into the Origins of Lignocellulose Decay Capabilities
Authors: László G. Nagy, Robert Riley, Andrew Tritt, Catherine Adam, Chris Daum, Dimitrios Floudas, Hui Sun, Jagjit S. Yadav, Jasmyn Pangilinan, Karl-Henrik Larsson, Kenji Matsuura, Kerrie Barry, Kurt Labutti, Rita Kuo, Robin A. Ohm, Sukanta S. Bhattacharya, Takashi Shirouzu, Yuko Yoshinaga, Francis M. Martin, Igor V. Grigoriev, David S. Hibbett
Journal: Molecular Biology and Evolution (2015)

Evolution of lignocellulose decomposition was one of the most ecologically important innovations in fungi. White-rot fungi in the Agaricomycetes (mushrooms and relatives) are the most effective microorganisms in degrading both cellulose and lignin components of woody plant cell walls (PCW). However, the precise evolutionary origins of lignocellulose decomposition are poorly understood, largely because certain early-diverging clades of Agaricomycetes and its sister group, the Dacrymycetes, have yet to be sampled, or have been undersampled, in comparative genomic studies. Here, we present new genome sequences of ten saprotrophic fungi, including members of the Dacrymycetes and early-diverging clades of Agaricomycetes (Cantharellales, Sebacinales, Auriculariales, and Trechisporales), which we use to refine the origins and evolutionary history of the enzymatic toolkit of lignocellulose decomposition. We reconstructed the origin of ligninolytic enzymes, focusing on class II peroxidases (AA2), as well as enzymes that attack crystalline cellulose. Despite previous reports of white rot appearing as early as the Dacrymycetes, our results suggest that white-rot fungi evolved later in the Agaricomycetes, with the first class II peroxidases reconstructed in the ancestor of the Auriculariales and residual Agaricomycetes. The exemplars of the most ancient clades of Agaricomycetes that we sampled all lack class II peroxidases, and are thus concluded to use a combination of plesiomorphic and derived PCW degrading enzymes that predate the evolution of white rot.
Alveolar mechanics studied by closed-chest in-vivo microscopy
Authors: Enrico Mazzuca, Caterina Salito, Ilaria Rivolta, Andrea Aliverti, Giuseppe Miserocchi
Journal: European Respiratory Journal (2013)

In vivo microscopy is a useful tool to study lung alveolar mechanics (Schiller et al. Crit Care Med 2001; 29: 1049–1055). A new surgical approach is here proposed to image changes in alveolar morphology through the intact pleura in order to partition between elastic and surface tension (γ) forces involved in lung volume change.

In 6 male anesthetized, tracheotomized and mechanically ventilated rabbits, a “pleural window” was opened by stripping the endothoracic fascia (Fig. 1a). Subpleural alveoli were observed under microscopic view (60x) during stepwise inflation/deflation maneuvers, starting from FRC. Alveolar areas were measured through a custom software and median values from all rabbits were used to produce an overall local distending pressure Pld-alveolar radius curve (Fig. 1b). A mathematical model, based on an asymptotic increase of γ with increasing radius from a minimal value γ to a maximum γmax, allowed to derive surfactant (Pγ) and elastic (Pel) contributions to Pld.

Alveolar radius increased up to a maximum at a local distending pressure of 10 cmH2O with negligible hysteresis. Experimental data are well fitted by computed curves for Pγ, with (γ; γmax) values ranging from (3; 15) up to (3; 21) dynes/cm.

Our results suggest that Pγ is only responsible for alveolar distension within a lung volume change from FRC up to ∼80% of inspiratory capacity. An increase in Pel only allows a further minor increase in alveolar volume.

![Figure][1]  [1]: pending:yes
Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM
Authors: A. B. Heimberger, G. E. Archer, D. A. Mitchell, D. D. Bigner, R. J. Schmittling, J. E. Herndon, T. Davis, H. S. Friedman, T. Keler, D. A. Reardon, J. H. Sampson
Journal: Journal of Clinical Oncology (2009)

2021 Background: Unlike conventional therapies for GBM, immunologic targeting of tumor-specific gene mutations allows precise eradication of neoplastic cells with reduced toxicity. EGFRvIII is a constitutively activated and immunogenic mutation not expressed in normal tissues, but widely expressed in GBM and other neoplasms. The cancer vaccine CDX-110 is comprised of an EGFRvIII-specific peptide sequence linked to keyhole limpet hemocyanin (KLH). Methods: A phase II multi-center trial assessed the immunogenicity and efficacy of CDX-110 in patients with newly-diagnosed, EGFRvIII+ GBM. After resection and radiation / TMZ, patients received CDX-110 vaccinations biweekly x 3, then monthly until tumor progression. Sequential cohorts received CDX-110 alone [ACTIVATE (n = 18)] or in combination with TMZ (200 mg/m 2 x 5/28 days [ACT II A (n = 13)]) or (100 mg/m 2 x 21/28 days [ACT II B (n=10)]). Results: Reversible systemic drug hypersensitivity reactions were seen in 1 ACTIVATE and 4 ACT II patients. Two patients had non-specific changes on MRI which were possibly due to the vaccine but which resolved. Despite grade 2 or 3 lymphopenia in all ACT II patients, EGFRvIII-specific immune responses were generated in all patients, and all immune responses were sustained or enhanced during subsequent TMZ cycles. Although ACT II B patients had more severe TMZ-induced lymphopenia, they developed greater EGFRvIII-specific immune responses (p = 0.028) when compared to ACT II A. EGFRvIII-specific IgG1 also increased in avidity with vaccination (K a &gt;&gt;2x10 9 M -1 ) in a randomly selected subset of 4 patients (p = 0.000068). Of the 23 recurrent tumors studied, 18 lost EGFRvIII expression (p = 0.001). There are no significant differences between ACT II A and B in estimated median TTP (18.5 vs. 14.9 months, p = 0.31) and OS (23.6 vs. 19.9 months, p = 0.75). ACTIVATE TTP (14.2 months) and OS (26.0 months) and ACT II TTP (15.2 months) and OS (23.6 months) compare favorably to a TMZ-treated, matched historical control group (TTP: 6.3 months; OS: 15.0 months). Conclusions: CDX-110 vaccination in patients with GBM appears very promising. TMZ enhances immune responses despite lymphodepletion. CDX-110 with simultaneous TMZ is under further investigation in a larger phase II trial. [Table: see text]
Immunoprofiling of T cell responses in melanoma patients undergoing CPI therapy
Authors: Lee Ann Talarico, Daniel Grubaugh, Zheng Yan, Aula Alami, Jean-Luc Bodmer, Darren E Higgins, F Stephen Hodi, Jessica Flechtner
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Successful treatment of melanoma patients with checkpoint inhibitors (CPI) has reinforced the importance of T cells in anti-tumor efficacy. Despite significant progress, CPI therapy is effective in only 40-50% of treated subjects, with substantial toxicity. As a result, it is
The harmful haste of modern healthcare
Authors: Kamran Abbasi
Journal: BMJ (2015)

Nature does not hurry," said the Chinese philosopher Lao Tzu, "yet everything is accomplished."In our rush to achieve targets, profits, success, and even happiness, it seems we have pitted ourselves against nature.We allow no time for reflection.Everything needs to be done now, sooner, faster-each journey completed, each meal consumed, each promotion obtained, each status updated.When we rush we surely accomplish less.Modern medicine and healthcare are in the business of haste, to provide rapid diagnoses and innovative treatments, to deliver immediate care at every second of every day.Therein lie problems, especially when an urgent political or commercial agenda is superimposed.
Patient-centered validation of 11 symptom indices to evaluate response to chemotherapy for advanced cancer
Authors: S. K. Rosenbloom, J. Beaumont, P. Diaz, S. E. Yount, A. P. Abernethy, P. B. Jacobsen, D. Paul, K. Syrjala, J. H. Von Roenn, D. Cella
Journal: Journal of Clinical Oncology (2007)

6524 Background: Symptom burden in advanced disease has relevance both for clinical practice and in evaluating the efficacy of new chemotherapeutic agents. This study aimed to identify patients’ highest priority symptoms for 11 advanced cancers, compare priority ratings with those obtained from clinicians, and construct brief symptom indices based on their combined input. Methods: 534 patients with advanced bladder, brain, breast, colorectal, head/neck, hepatobiliary/pancreatic, kidney, lung, lymphoma, ovarian or prostate cancer from a subset of National Comprehensive Cancer Network (NCCN) member institutions and 4 Cancer Health Alliance of Metropolitan Chicago organizations completed a survey of priority symptoms and concerns and a disease-specific FACT QOL measure. 112 physicians at NCCN institutions completed a rating of whether symptoms and concerns were considered disease- or treatment-related. Symptoms endorsed more often than chance probability were retained. Expert clinician and patient ratings were equally weighted in item selection. Responses to symptom index items drawn from the QOL questionnaires allowed for validation analyses. Results: Items comprising 2 to 3 subscales (up to 20 items in length) were retained for each of the 11 disease-specific symptom indices. Content-determined subscales consisted of symptoms and concerns that were 1) exclusively or predominantly disease-related symptoms (DRS); 2) exclusively or predominantly treatment side effects (TSE); and 3) descriptive of general function or well-being (F/WB). For example, the NCCN/FACT Breast Cancer Symptom Index (FBSI) contains 17 items: 8 DRS, 4 TSE and 5 F/WB. Data on 14 of 17 FBSI items showed good internal consistency (a=.89). Correlations between FBSI and FACT-B scores were high for physical well-being, functional well-being and breast cancer subscales (r = 0.83, 0.77, and 0.61 respectively). Correlation with emotional well-being subscale was 0.55. FBSI scores differed across PSR groups in the appropriate direction (p&lt;0.0001). Conclusions: NCCN/FACT disease-specific questionnaires have been transformed into brief, patient-centered symptom indices that can be used as stand-alone measures in oncology research and practice. No significant financial relationships to disclose.