tbuckley/cabot-search huggingface dataset:
Anti-VEGF drugs, endothelial dysfunction, and hypertension: Is there a relationship?
Authors: S. Thanigaimani, A. Mangoni, C. S. Karapetis, G. Kichenadasse
Journal: Journal of Clinical Oncology (2010)

e13585 Background: Hypertension is one of the most frequently reported adverse event with the use of anti-vascular endothelial growth factor (VEGF) drugs during cancer treatment. The underlying mechanism(s) of this complication is still unclear. This study aims at determining possible mechanisms of anti-VEGF drug induced hypertension. Methods: The effect of anti-VEGF drugs on 1. various cardiovascular parameters using Task Force Monitor and PulseTrace PCA 2 equipments and 2. serum endogenous nitric oxide (NO) metabolites like asymmetric dimethyl arginine (ADMA), symmetric dimethyl arginine (SDMA) and L-Arginine levels using HPLC coupled with mass spectrometry at different time points including pre-treatment, 6 weeks and 12 weeks during treatment were studied in consenting patients. Results: Six participants with advanced cancers requiring anti-VEGF therapy were enrolled in this study. Five patients received bevacizumab at 5 mg/kg and the other patient received pazopanib 400 mg twice daily. Five patients were eligible for clinical evaluation. Cardiovascular parameters were compared and calculated between baseline and 6 weeks. At 6 weeks, all patients had an increase in sympathetic tone while parasympathetic tone and L-Arginine levels decreased compared to baseline. Two (2/5) subjects developed grade I hypertension during the study and they had an increase in sympathetic tone (20.25 % ± 4.87), decrease in vagal tone (−20.75 % ± 5.58) and decrease in L-Arginine levels (−28.5 μmol/ml ± 7.77) at 6 weeks whereas these parameters were unchanged in the other patients who did not develop hypertension. There was no significant change in baroreflex sensitivity, heart rate and ADMA/SDMA levels in both the groups. Conclusions: These results indicate that anti-VEGF drugs could cause endothelial dysfunction by decreasing L-Arginine bioavailability for NO synthesis and increasing sympathetic tone thereby resulting in hypertension. They do not alter the levels of endogenous NO inhibitors in short-term. These results require confirmation in the ongoing study with larger patient population. No significant financial relationships to disclose.
The prognostic role of tumor-infiltrating CD8+ T lymphocytes in breast cancer
Authors: A. Lacko, I. Gisterek, R. Matkowski, A. Halon, K. Szewczyk, U. Staszek, M. Pudelko, B. Szynglarewicz, A. Zolnierek, J. Kornafel
Journal: Journal of Clinical Oncology (2008)

11024 Background: There is no definitive conclusion regarding the importance of T cell- dependent immune mechanisms and the tumor progression in breast cancer. Anti-tumor effects are mediated through the induction of CD8+ T cell response against specific antigen. The aim of the study was to assess the prognostic role of CD8 expression in patients with breast cancer. Methods: Tissue samples were obtained from 88 breast cancer patients (median age 62 years; range: 29 to 79 years). All patients presented with operable disease (AJCC stage I: n=34; 38.64%; stage II: n=29; 32.95%, stage III: n=25; 28.41%) and had ductal histology. Forty three (48.86%) women had pathologically confirmed axillary lymph node involvement. Patients were treated with surgery followed by standard adjuvant chemotherapy (n=59, 67.04%), hormonal therapy (n=57; 64.77%) and radiotherapy (n=38; 43.18%). The expression of CD8 was evaluated in tumor samples using mouse monoclonal antibody. Overall, CD8 expression was found in 84 (95.46%) tumors: in 11 (12.50%) mild, in 34 (38.64%) moderate and in 39 (44.32%) strong expression was seen. Results: Statistical analysis showed correlation (Pearson’s correlation coefficient = 0.32, p<0.05) between expression of CD8 in tumor cells and involvement of axillary lymph nodes. During 48 months of follow-up 12 patients relapsed (11 with distant metastases, 1 local reccurence). Nine of 12 women with disease recurrence (81.8%) had strong expression of CD8 in primary tumor, which was statistically significant (Pearson’s correlation coefficient = 0.31, p<0.05). Conclusions: The presence of CD8+ cells correlates with lymph node involvement and unfavourable prognosis. These results suggest that immune response has an influence on behaviour of breast cancer tumors. The analysis of tumor-infiltrating immune cells may therefore be a valuable prognostic tool and a marker of lymph node involvement. No significant financial relationships to disclose.
Randomized phase III comparison of paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan, both followed by gefitinib, in patients (pts) with carcinoma of unknown primary site (CUP)
Authors: J. D. Hainsworth, C. Lane, D. R. Spigel, D. Shipley, D. Waterhouse, M. Bury, F. A. Greco
Journal: Journal of Clinical Oncology (2009)

4631 Background: Empiric chemotherapy for pts with CUP has resulted in modest survival improvements. Several regimens have been active in phase II trials, but no randomized comparison of newer regimens have been completed. In this multicenter randomized phase III trial, we compared the efficacy and toxicity of 2 active regimens. Methods: Previously untreated pts with CUP (adenocarcinoma, poorly differentiated adenocarcinoma, poorly differentiated carcinoma, poorly differentiated squamous carcinoma) were eligible. Pts with specific treatable syndromes were excluded. Additional eligibility: ECOG PS 0–2; controlled brain metastases; adequate organ function. Pts were randomized (1:1) to paclitaxel 200mg/m 2 day 1/carboplatin AUC 6.0 day 1/etoposide 50mg/100mg alternating po days 1–10 (PCE) or gemcitabine 1000mg IV days 1, 8/irinotecan 100mg/m 2 IV days 1, 8 (GI). Both regimens were repeated at 21-day intervals for 4–6 courses. Responding/stable pts then received gefitinib 250mg po qd until tumor progression. The primary endpoint was the 2-year survival rate. Initially, a total of 320 pts were planned, to allow detection of a 50% improvement in 2-year survival (from 20% to 30%). However, due to slow accrual, enrollment was stopped after 198 pts were randomized. Results: Between September 2003 and July 2008, 198 pts were randomized (PCE, 93 patients; GI 105 patients). Pt characteristics were similar in both groups. Median progression-free survival for PCE versus GI was 3.2 months versus 5.3 months, p=0.19. Median overall survivals were 7.4 months (PCE) versus 8.6 months (GI), p=0.34; 2-year survivals were 16% (PCE) and 19% (GI). Response rates were similar (PCE 19%, GI 20%). GI was less toxic, with lower rates of grade 3/4 neutropenia (11% vs. 35%; p&lt; 0.01), febrile neutropenia (0% vs. 9%; p&lt;0.01), thrombocytopenia (3% vs. 8%; p=.05), anemia (3% vs. 9%; p=0.05), and RBC transfusions (10% vs. 24%; p&lt;0.01). Conclusions: The PCE and GI regimens had comparable efficacy in the treatment of CUP, while the GI regimen was better tolerated. The 2-year survival was similar (16%, 19%). Better treatments are needed for pts with CUP. [Table: see text]
Significant efficacy of 2-CdA with or without rituximab in the treatment of splenic marginal zone lymphoma (SMZL).Ann Oncol. 2010 Apr;21(4):851-4. Epub 2009 Oct 13.
Authors: G Cervetti, Sara Galimberti, E Sordi, Gabriele Buda, E Orciuolo, N Cecconi, Mario Petrini
Journal: Annals of Oncology (2009)
Growth &lt;italic&gt;In Vitro&lt;/italic&gt; and Ultrastructure of Cells From a Medullary Carcinoma of the Human Thyroid Gland: Transformation by Simian Virus 40 and Evidence of Thyrocalcitonin and Prostaglandins
Authors: Philip M. Grimley, Leonard J. Deftos, James R. Weeks, Alan S. Rabson
Journal: JNCI Journal of the National Cancer Institute (1969)

Continuous single layer tissue cultures were established with explants from a metastatic nodule of medullary carcinoma primary in the thyroid gland. Some cultures were infected with simian virus 40 and the cells acquired morphologic and growth characteristics associated with viral transformation. Thyrocalcitonin activity was detected by radioimmunoassay of culture fluids as late as 7 months after initiation of the single layers. Substances with the chemical and biological properties of (PG) prostaglandins E2 and F2alpha were extracted from culture fluids after 4 months. The original carcinoma cells contained abundant cyctoplasmic secretory granules, which were demonstrated by electron microscopy. These granules disappeared during subculture of the monolayers, and electron-dense secretory substance accumulated within dilated cisternae of the ribosome-bound endoplasmic reticulum. Ultrastructural differences in surface organization of the virus transformed and uninfected culture cells were noted. Amyloid was present in the original tumor stroma and tissue culture explants, but could not be identified in those serial subcultures derived from the monolayer outgrowths.
“Exorbitant” regulator fee rises will damage patient care, warns BMA
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Doctors’ leaders have warned that “exorbitant” and “inexplicable” planned rises in the fees that GPs and hospitals have to pay to England’s healthcare regulator amount to a “raid” on overstretched NHS budgets. They say that the rises could undermine the care of patients and threaten the future of small general practices.

The Care Quality Commission has been consulting on its fee rises since November, for implementation in April 2016.1

It has proposed that charges for a general practice operating at one location that …
A randomised prospective study of prolonged treatment with tocopherol and pentoxifylline, in addition to carbogen in the management of radiation late effects
Authors: S. M. Brennan, C. O Shea, O. Salib, M. Moriarty
Journal: Journal of Clinical Oncology (2007)

19682 Background: Pentoxifylline (PTX) and tocopherol (Vitamin E) are antioxidants previously shown to be useful in combination in the treatment of late radiation effects. To our knowledge, this is the first study to examine the clinical benefit of combination therapy with carbogen, tocopherol and pentoxifylline in the mitigation of late radiation effects. The optimal duration of PTX and tocopherol treatment has not been fully established. Therefore, we also studied short versus extended treatment duration. Methods: We conducted a phase II prospective randomised study of inhaled carbogen (95% oxygen + 5% carbon dioxide) over 90 minutes, 5 days per week for 3 weeks in addition to short versus prolonged treatment with pentoxifylline (800 mg) and tocopherol (1,000 IU) orally once daily. All 18 patients received carbogen therapy. Patients with grade 3 toxicity post radical radiotherapy for a variety of cancer primaries were eligible for the trial. The primary endpoint was improvement in maximum Lent-Soma toxicity scores. Ethical approval was obtained. Results: Maximum Lent-Soma scores improved with treatment in six of the eighteen patients giving a 33% response rate. The proportion of patients responding to treatment in the prolonged treatment arm B was more than double than in the shorter arm A (Fisher’s exact test: p = 0.321). Two patients in arm B had complete resolution of their symptoms, which was maintained at 2 and 3 years follow up. Conclusions: As late radiation effects are progressive by nature and have such a negative impact on quality of life in long-term cancer survivors, any treatment, which may ameliorate their symptoms, should be considered of benefit. This study confirms the benefit of prolonged treatment and we would recommend clinical use of these agents with treatment duration of at least 12 months, in the management of late radiation effects. No significant financial relationships to disclose.
Clonality of Epstein-Barr virus in lymphoproliferative disorders in patients treated with immunosuppressive therapy for rheumatoid arthritis.
Authors: M van de Rijn, O W Kamel
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.11.3050 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8918505 Clonality of Epstein-Barr virus in lymphoproliferative disorders in patients treated with immunosuppressive therapy for rheumatoid arthritis. M van de RijnxM van de RijnSearch for articles by this author , O W KamelxO W KamelSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.11.3050 PDF "Clonality of Epstein-Barr virus in lymphoproliferative disorders in patients treated with immunosuppressive therapy for rheumatoid arthritis.." Journal of Clinical Oncology, 14(11), pp. 3050–3051© 1996 by American Society of Clinical Oncology
Abstract 16180: Blockade of Norepinephrine Transporter Magnifies Tachycardia and Worsens Symptoms in Postural Tachycardia Syndrome
Authors: Satish R Raj, Italo Biaggioni, Bonnie K Black, Cyndya A Shibao, David Robertson, Sachin Y Paranjape
Journal: Circulation (2010)

Background: The role of pharmacological norepinephrine transporter (NET) antagonists in the management POTS (heart rate [HR] increase >30 bpm on standing) is unsettled. NET inhibitors can promote increased peripheral sympathetic tone via decreased NE clearance. However, supratherapeutic doses of NET inhibitors can cause orthostatic tachycardia in healthy volunteers. Many physicians prescribe NET inhibitors for POTS in an effort to increase vascular resistance & blood pressure and improve symptoms. We prospectively tested the acute effects of atomoxetine, a potent NET inhibitor, on tachycardia and symptoms in POTS. Methods: Patients with POTS (n=18;16 female,35±8 years) underwent a randomized single-blind crossover trial with oral atomoxetine 40 mg and placebo on separate mornings in a post-absorptive and drug-free state. Non-invasive HR and blood pressure (BP) were measured with the patient seated comfortably. At baseline, and hourly for 4h post-medication, the patients stood for up to 10 min, and their s...
Echocardiographic speckle tracking strain and right ventricular function assessment during non-invasive ventilation in acute respiratory failure patients
Authors: Bouchra Lamia, Stéphanie VanMossevelde, Luis-Carlos Molano, Antoine Cuvelier, Jean-François Muir
Journal: European Respiratory Journal (2012)

Introduction  During acute respiratory failure (ARF), right ventricular (RV) function can be abnormal due to increased afterload and/or decreased contractility or preload. Speckle tracking strain analysis can diagnose RV dyssynchrony. We aimed to test whether RV dyssynchrony exists during ARF and can be reversed during non-invasive ventilation (NIV).  Methods  Prospective study including 13 patients admitted for ARF. Trans thoracic echocardiography (TTE) was performed during spontaneous breathing (SB) activity and during NIV. Usual echo parameters and speckle tracking strain were measured. The software generated 6 segmental RV strain curves. Time to peak strain from each of 6 time-strain curves was determined with dyssynchrony defined as the difference between earliest and latest segments.  Results  13 patients aged 69(11) y were included. 11 had chronic respiratory failure. Compared to SB, left ventricular ejection fraction and stroke volume increased during NIV: 59 (6) vs 66 (6) %, 61 (9) vs 65 (11) mL, p   Conclusion  RV dyssynchrony measured using speckle tracking strain is observed in our ARF patients. NIV can improve LVEF, RV afterload and RV dyssynchrony.
Comparison of Site of Death, Health Care Utilization, and Hospital Expenditures for Patients Dying With Cancer in 7 Developed Countries
Authors: Justin E. Bekelman, Scott D. Halpern, Carl Rudolf Blankart, Julie P. Bynum, Joachim Cohen, Robert Fowler, Stein Kaasa, Lukas Kwietniewski, Hans Olav Melberg, Bregje Onwuteaka-Philipsen, Mariska Oosterveld-Vlug, Andrew Pring, Jonas Schreyögg, Connie M. Ulrich, Julia Verne, Hannah Wunsch, Ezekiel J. Emanuel
Journal: JAMA (2016)

<h3>Importance</h3> Differences in utilization and costs of end-of-life care among developed countries are of considerable policy interest. <h3>Objective</h3> To compare site of death, health care utilization, and hospital expenditures in 7 countries: Belgium, Canada, England, Germany, the Netherlands, Norway, and the United States. <h3>Design, Setting, and Participants</h3> Retrospective cohort study using administrative and registry data from 2010. Participants were decedents older than 65 years who died with cancer. Secondary analyses included decedents of any age, decedents older than 65 years with lung cancer, and decedents older than 65 years in the United States and Germany from 2012. <h3>Main Outcomes and Measures</h3> Deaths in acute care hospitals, 3 inpatient measures (hospitalizations in acute care hospitals, admissions to intensive care units, and emergency department visits), 1 outpatient measure (chemotherapy episodes), and hospital expenditures paid by insurers (commercial or governmental) during the 180-day and 30-day periods before death. Expenditures were derived from country-specific methods for costing inpatient services. <h3>Results</h3> The United States (cohort of decedents aged &gt;65 years, N = 211 816) and the Netherlands (N = 7216) had the lowest proportion of decedents die in acute care hospitals (22.2.% and 29.4%, respectively). A higher proportion of decedents died in acute care hospitals in Belgium (N = 21 054; 51.2%), Canada (N = 20 818; 52.1%), England (N = 97 099; 41.7%), Germany (N = 24 434; 38.3%), and Norway (N = 6636; 44.7%). In the last 180 days of life, 40.3% of US decedents had an intensive care unit admission compared with less than 18% in other reporting nations. In the last 180 days of life, mean per capita hospital expenditures were higher in Canada (US $21 840), Norway (US $19 783), and the United States (US $18 500), intermediate in Germany (US $16 221) and Belgium (US $15 699), and lower in the Netherlands (US $10 936) and England (US $9342). Secondary analyses showed similar results. <h3>Conclusions and Relevance</h3> Among patients older than 65 years who died with cancer in 7 developed countries in 2010, end-of-life care was more hospital-centric in Belgium, Canada, England, Germany, and Norway than in the Netherlands or the United States. Hospital expenditures near the end of life were higher in the United States, Norway, and Canada, intermediate in Germany and Belgium, and lower in the Netherlands and England. However, intensive care unit admissions were more than twice as common in the United States as in other countries.
SWOG S0342 and S0536: Expression of EGFR protein and markers of epithelial-mesenchymal transformation (EMT) in cetuximab/chemotherapy-treated non-small cell lung cancer (NSCLC)
Authors: W. A. Franklin, D. R. Gandara, E. S. Kim, R. S. Herbst, J. Moon, M. W. Redman, C. Olsen, F. R. Hirsch, P. Mack, K. Kelly
Journal: Journal of Clinical Oncology (2009)

11076 Background: High EGFR gene copy number is associated with efficacy in NSCLC patients (pts) receiving combined chemotherapy and cetuximab (S0342). EGFR protein is typically overexpressed in tumors with high copy number but no consistent association has yet been demonstrated between EGFR protein expression and outcome in pts treated with chemotherapy plus cetuximab. EMT is associated with aggressive biological behavior and resistance to anti-EGFR TKI therapy in NSCLC. Our objective was to identify any association between EGFR protein and EMT and to correlate findings with pt outcomes from cetuximab/chemotherapy in SWOG trials S0342 (paclitaxel [P]-carboplatin [CB] plus sequential or concurrent cetuximab [CX]) and S0536 (P-CB-CX + bevacizumab). Methods: Paraffin sections were stained by immunoperoxidase methods using monoclonal antibodies against EGFR and the EMT markers vimentin, E-cadherin and Zeb1. Sections were scored on continuous scale ranging from 0–300 based on the H score (sum of % positive at each intensity from 0–3). Results were compared to outcome by Kaplan-Meier plot. Results: 79 samples from S0342 were evaluated for EGFR and EMT markers. 67 samples from S0536 were assessed for EGFR only. Mean EGFR H score was 153 and 137 for S0342 and S0536 respectively. At all cut points tested (scores 0, &lt;100, &lt;300) no association between EGFR H score and response or progression-free survival (PFS) was detected in either trial. There was a trend for overall survival and EGFR level at each cutpoint in S0536 but the results did not achieve statistical significance (15 vs 11 mos, p=0.14; 15 vs 11 mos, p=0.20 and 14 mos vs not reached, p=0.10, respectively). Vimentin (6 positive pts) was associated with a shorter PFS, HR=2.60 (1.10–6.14), p=0.03. ECAD and Vimentin were significantly inversely correlated with one another (Spearman p-value&lt;0.01) Conclusions: EGFR protein level by IHC does not significantly correlate with efficacy parameters in chemotherapy/cetuximab-treated NSCLC pts. Patients with vimentin producing tumors (and possible other EMT markers) had shorter PFS, suggesting possible relative resistance to EGFR blockade from cetuximab. [Table: see text]
Histopathologic and immunohistochemical findings in triple-negative breast cancers showing clinical progressive disease during neoadjuvant chemotherapy.
Authors: Yuko Tanabe, Hitoshi Tsuda, Masayuki Yoshida, Takayuki Kinoshita, Makoto Kodaira, Mayu Yunokawa, Kan Yonemori, Harukaze Yamamoto, Chikako Shimizu, Yasuhiro Fujiwara, Kenji Tamura
Journal: Journal of Clinical Oncology (2014)

1109 Background: Clinical progressive disease (cPD) occurs during neoadjuvant therapy (NAC)in 3–5% of triple negative breast cancer (TNBC) patients. Predictive biomarkers are required for subtype specific characterization given the heterogeneous response to NAC in TNBC. This case-control study retrospectively analyzed histopathological and immunohistochemical data with the aim of detecting potential predictors of cPD. Methods: Using a pathology database of patients who had undergone surgical resection, 102 patients with TNBC were identified: 22 with cPD during NAC (PD group) and 80 controls (C group). Formalin-fixed paraffin-embedded tumor tissue sections were immunohistochemically examined for expression of 14 molecules, including ABCB1, which is a member of the ABC transporter family, and the following epithelial-to-mesenchymal transition (EMT) markers: vimentin, Twist NB, E-cadherin, ZEB1, and Snail2. Chi-square tests were conducted to compare differences between the groups. Results: Histologically, the PD group included 14 (64%) invasive ductal carcinomas (IDCs) and 8 (36%) metaplastic carcinomas (MPCs). In the C group, 59 (74%) were IDCs, 20 (25%) were types other than IDC or MPC, and only 1 was an MPC (1%) (p<0.001). The positive expressions of cytoplasmic vimentin (77%), nuclear Twist NB (27%), nuclear ZEB1 (36%), and nuclear Snail2 (59%) in the PD group were higher than those in the C group (54%, p=0.049; 3%, p=0.0011; 13%, p=0.0093; 48%, p=0.049, respectively). Nuclear ABCB1 expression was higher in the PD group (64%) than in the C group (6%) (p<0.001); conversely, cytoplasmic ABCB1 was present more frequently in the C group (96%) than in the PD group (77%) (p=0.011). The positive expression of nuclear ABCB1, nuclear ZEB1, or cytoplasmic vimentin occurred in 95% of the PD group compared to 61% in the C group (p= 0.002). Conclusions: A metaplastic phenotype, cytoplasmic vimentin or nuclear ZEB1 expression, and increased nuclear localization of ABCB1 could be predictors for cPD during NAC in TNBC patients.