tbuckley/cabot-search huggingface dataset:
Prospective randomized trial of high-dose cisplatin and fluorouracil infusion with or without sodium diethyldithiocarbamate in recurrent and/or metastatic squamous cell carcinoma of the head and neck.
Authors: J Paredes, W K Hong, T B Felder, I W Dimery, A J Choksi, R A Newman, A M Castellanos, K T Robbins, K McCarthy, N Atkinson
Journal: Journal of Clinical Oncology (1988)

Previous studies have indicated that sodium diethyldithiocarbamate (DDTC) can reduce cisplatin's (CP) toxic effects without altering the antitumor activity. DDTC has also been shown to have immunostimulative properties. Sixty patients with objectively measurable recurrent and/or metastatic squamous cell carcinoma (SCC) of the head and neck were randomized to receive either (A) CP at 120 mg/m2 over one hour on day 1, plus fluorouracil (5-FU) at 1,000 mg/m2 over 24 hours as a continuous infusion on days 1 through 5, or (B) CP/5-FU as in A, plus DDTC at 600 mg/m2 over 30 minutes administered intravenously (IV) exactly 30 minutes after CP infusion. Group B also received DDTC at 200 mg/m2 administered IV over 30 minutes on days 8 and 15. Each cycle was repeated at 3-week intervals. Objective responses were achieved in 41% of the CP/5-FU group and in 29% of the CP/5-FU with DDTC group (P = .26). Median survival was 9 months in group A and 10 months in group B. CP-related toxicity between the groups was equivalent with respect to nausea and vomiting, renal impairment, neurotoxicity, ototoxicity, and hematologic toxicity. The pharmacokinetics of reactive platinum species in plasma ultrafiltrate and urine samples obtained from both groups were comparable. The immune status of 48 patients was evaluated before and after completion of therapy. There were no significant differences in mean pretreatment and posttreatment values within or between groups A or B, except for absolute pretreatment OKT4 values (P = .02). We conclude that (1) the present dose and infusion schedule of DDTC did not significantly reduce CP-mediated toxic effects, (2) DDTC did not alter the disposition of ultrafilterable platinum species, (3) DDTC did not affect immune responses, and (4) the addition of DDTC improved neither the clinical response nor the survival of patients with recurrent SCC of the head and neck.
Government made concessions on weekend working for junior doctors, leaked letter shows
Authors: Abi Rimmer
Journal: BMJ (2016)

The UK government has offered concessions on weekend pay for junior doctors, as part of negotiations on proposed changes to the contract for doctors in training, HSJ ( Health Service Journal ) has reported.

The concessions were outlined in a leaked letter sent by the government’s lead negotiator, David Dalton, to Johann Malawana, chair of the BMA’s Junior Doctors Committee, HSJ reports.1

Negotiations between the government and the …
Abstract 13516: Impact of Carotid Artery Pulsatility on Left Ventricular Diastolic Function in Patients With Subclinical Coronary Risk Factors
Authors: Ki-Hyun Kim, Jung Jun Cha, Hyemoon Chung, Jong-Youn Kim, Young Won Yoon, Byoung Kwon Lee, Bum-Kee Hong, Se-Joong Rim, Hyuck Moon Kwon, Eui-Young Choi
Journal: Circulation (2014)

Background:  Ventricular-arterial interaction is an important pathophysiology of heart failure with preserved ejection fraction. Carotid artery (CA) intima-media thickness (IMT) and pulsatility can be used as an index of pan-arterial stiffening. In this study we sought to evaluate relationship between CA characteristics and left ventricular (LV) diastolic function in patients with subclinical coronary risk factors.   Methods:  We retrospectively analyzed consecutive images of 3,511 primary patients who underwent both carotid ultrasound and echocardiography within a month. After exclusion of overt coronary artery disease, valvular heart diseases, cardiomyopathies, congenital heart diseases and LV ejection fraction less than 50%, we analyzed their relationship in 946 patients. Carotid plaque characterization, IMT, peak systolic velocity (PSV) and end-diastolic velocity (EDV) and resistive index (RI) were measured in common, external and internal carotid arteries. As an index of LV diastolic function, E/e’ was used.   Results:  Their mean age was 60.2±12.3 years and 404 (43%) were women. Five hundred fifty-three (59%) had hypertension and 209 (22%) had diabetes. E/e’ was correlated with age, sex, LV mass index, carotid IMT, presence of plaque, common CA-EDV, -RI and internal CA-RI. In multivariable analysis, common-EDV and RI were independently correlated with E/e’ after controlling for significant parameters in univariate analysis but not with IMT and presence of plaque.   Conclusion:  Carotid EDV and RI rather than IMT were independently related to diastolic function in patients with preserved ejection fraction and subclinical risk factors. Therefore carotid-EDV and RI can be used as an index of atherosclerosis and LV diastolic function.
Proposal of new CT response criteria in non-small cell lung cancer patients treated with EGFR tyrosine kinase inhibitor.
Authors: H. Lee, K. Lee, M. Ahn, H. Hwang, J. Lee, K. Park, T. Kim, C. Yi, M. Chung
Journal: Journal of Clinical Oncology (2010)

7035 Background: Given the cytostatic nature of molecular targeted agents, the response to targeted agents might be inadequately assessed by traditional size-based radiologic criteria. We devised novel CT response criteria in consideration of tumor constituents (solid and ground-glass opacity [GGO] components), the presence of cavitation, and attenuation changes within target lesions during treatment, and evaluated the efficacy of the criteria for stratifying patient response and for predicting patient prognosis as compared with that of the RECIST 1.1 in patients treated with EGFR TKIs. Methods: Eighty NSCLC patients who were enrolled prospective clinical trial and treated with EGFR TKIs were analyzed. Tumor response was assessed by using both RECIST 1.1 and new criteria and compared between two criteria. To evaluate the ability of RECIST 1.1 and new criteria in predicting patients' prognosis, overall survival (OS) were compared between responders by using a log-rank test. The interobserver agreement between two radiologists was also assessed by calculating the k value for response according to each response criterion. Results: On CT scans, 27 patients had GGO component and five patients had cavitation within target lesions. A decrease in tumor attenuation of ≥ 15% on follow-up CT scans was found in 28 patients. According to RECIST 1.1 and new criteria, the response rate (CR or PR) were 45% and 60%, respectively, while the disease control rates (CR, PR or SD) were 76% and 89%, respectively. New criteria showed a significant difference in prediction of OS among three (PR, SD and PD) response groups to EGFR-TKI therapy, with the median OS of three groups at 14 months, 7.6 months, and 2.2 months, respectively (p = 0.003). In contrast, RECIST 1.1 method failed to show the distinctive prediction of OS among three response groups. The interobserver agreements for RECIST 1.1 and new criteria were quite consistent (k = 1.00, 0.98, respectively). Conclusions: These results suggest that the novel CT criteria reflecting additional morphologic characteristics of target lesions are reproducible and might provide complementary information to traditional RECIST method for prognosis prediction. No significant financial relationships to disclose.
HE2100 and HE3204 protect Rhesus Macaques from chemotherapy or radiation induced myelosuppression
Authors: D. R. Stickney, C. Dowding, C. Reading, J. Frincke
Journal: Journal of Clinical Oncology (2004)

6668 Background: HE2100, androst-5-ene-3β,17β-diol, and HE3204 are naturally occurring and synthetic adrenal steroid hormones, respectively. Prophylactic and therapeutic HE2100 studies of lethally irradiated rodents demonstrated a significant survival advantage for treated groups (Whitnall et. al., Int. J. Immunopharm.2000). Rodent studies with either HE2100 or HE3204 demonstrated protection against chemotherapy-induced myelosuppression. Methods: The current study investigated the effects of these compounds in (1) a non-human primate model with induced myelosuppression from chemotherapy or ionizing radiation and (2) on primitive (Long-Term Culture-Initiating Cells-LTC-IC), lineage committed (Granulocyte-Macrophage Colony-Forming Cells-GM-CFC) and bone marrow mesenchymal progenitor cells. Non-human primates were given carboplatin, 35 mg/kg, 36 hrs. prior to 5 daily sc injections of HE2100 or HE3204 or 2–4 hours after sublethal total body irradiation. Blood counts were measured daily during severely neutropenic days. Results: HE2100 showed a decrease in the number of days of severe neutropenia (<500cells/uL) in the sub-lethally irradiated macaques from 7 days (vehicle) to 2 days at the highest dose (p=0.019) and reduced the days of severe neutropenia induced by carboplatin from 5.3 (vehicle) to 0.7. HE2100 increased: (1) GM-CFC-derived colony numbers by 36% using standard in vitro assays (p= <0.001); (2) at wk 4 of LTBMC the GM-CFC number by 280% (p=0.035): and (3) bone marrow mesenchymal progenitor cells in vitro. HE3204 completely eliminated severe neutropenia from chemotherapy, 5.3 days for vehicle control to 0 (p=0.03). Conclusions: This class of compounds expands committed and primitive bone marrow progenitor cells and affords significant protection from chemo or radiation induced myelosuppression in non-human primates. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hollis Eden Pharmaceuticals, Inc. Hollis Eden Pharmaceuticals, Inc. Hollis Eden Pharmaceuticals, Inc.
Commonly prescribed salt intake in continuous ambulatory peritoneal dialysis patients is too restrictive
Authors: A Fine, B Fontaine, M Ma
Journal: Journal of the American Society of Nephrology (1997)

Salt restriction in continuous ambulatory peritoneal dialysis (CAPD) patients is widely prescribed and thereby may reduce quality of life. It is presumed that this has a beneficial effect on BP and reduces the need for hypertonic dialysate. However, this has never been formally evaluated. A double-blind crossover study of placebo versus sodium chloride pills (60 mEq of sodium per day) is presented in 20 stable CAPD patients, 10 of whom were hypertensive. Dietary sodium was quantified throughout the study by 3-d dietary histories and remained unaltered throughout. There was a clinically unimportant but statistically significant rise in BP with added salt: 135/77 to 144/82 (P < 0.05). No rise in BP occurred in the hypertensive patients. Weights, use of hypertonic dialysate, and BP medications remained unaltered throughout the study. In conclusion, 200 mEq of sodium per day, i.e., a normal sodium intake, is easily tolerated in stable CAPD patients, and the recommended sodium intake commonly prescribed is too restrictive.
Abstract 13657: GLP-1[28-36] Exerts Direct Cardioprotective Effects, Activating Pro-Survival Kinases and Soluble Adenylyl Cyclase
Authors: Dhanwantee Mundil, Sanja Beca, Alison Cameron-Vendrig, Omar El-Mounayri, Abdul Momen, Peter H Backx, Mansoor Husain
Journal: Circulation (2012)

Background: GLP-1[7-36] (GLP-1), an incretin hormone that regulates glucose homeostasis, is rapidly degraded to GLP-1[9-36]. Both GLP-1 and [9-36] are cardioprotective against ischemia-reperfusion ...
Swine Monoclonal Antibodies of High Affinity and Specificity to Carcinoembryonic Antigen
Authors: F Buchegger, K Fournier, M Schreyer, S Carrel, J P Mach
Journal: JNCI Journal of the National Cancer Institute (1987)

To avoid the exclusive use of rodent monoclonal antibodies (MAbs) in patients for the detection of tumors by immunoscintigraphy and for radioimmunotherapy, swine MAbs were produced that are directed against carcinoembryonic antigen (CEA). Spleen cells from 2 pigs immunized with purified colon carcinoma CEA were fused with a nonsecreting mouse myeloma cell line by conventional methods, except that a particularly long immunization protocol and large amounts of spleen and myeloma cells were used. Of 1,200 growing hybrids tested, 20 were found initially to produce antibodies binding to radiolabeled CEA. Seven stable clones producing anti-CEA MAbs for more than 6 months were derived from these hybrids by repeated subcloning. The pig origin of the seven MAbs was demonstrated in a solid-phase CEA enzyme immunoassay where anti-pig immunoglobin (Ig) antibodies coupled to peroxidase gave a positive reaction while anti-mouse Ig antibodies were entirely negative. All swine MAbs were of the IgG isotype. Three anti-CEA MAbs showed no cross-reactivity with granulocytes, while four others gave various degrees of reactivity with different granulocyte glycoproteins. Competitive binding to CEA performed for two purified swine MAbs showed that they recognized two different epitopes. The affinity constants measured for these two MAbs by Scatchard plot on purified CEA were high (1.2×109 and 1.2×1010 liter/mol). One of the MAbs was tested in vivo for tumor localization by injection, after radiolabeling, in nude mice bearing human colon carcinoma xenograft. High ratios of tumor to normal tissue were obtained with mean values of 10.5 for intact MAbs and of 26.8 for F(ab′)2 fragments of the porcine MAb. The results showed that heterofusion with this particular protocol can be used to produce swine MAbs of high affinity and specificity for a well-defined tumor marker. These reagents may have an important clinical utility, particularly in patients who became sensitized to mouse immunoglobulins.
Tropisetron does not induce arrhythmia in chemo-naive otherwise healthy cancer patients
Authors: H. Abali, G. Abalı, B. Öksüzoglu, M. Bakar, B. Budakoglu, B. Oyan, K. Aytemur, N. Zengin
Journal: Journal of Clinical Oncology (2005)

8259 Background: Chemotherapy induced emesis is one of the most distressing side effects of chemotherapy. Serotonin antagonists revolutionized its management. Although they are considered as relatively safe agents, they have significant cardiovascular side effects: Ondansetron and dolasetron are known to prolong corrected QT interval (QTc), which is a good predictor of arrhythmia. Package insert of tropisetron carries a warning against cardiovascular events and data on its cardiovascular effects are sparse. Our aim was to investigate the effects of tropisetron alone before combination chemotherapy on electrocardiographic parameters of patients with cancer. Methods: All the patients were monitorized with high resolution holter monitor (Ela Medical Inc.). Approximately 10 minutes after holter monitoring onset, 5 mg tropisetron was given intravenously, then 1 hour was allowed to elapse until chemotherapy administration to compare baseline values of QTc and QT dispersion with those during injection and the following 1 hour period in chemo-naive otherwise healthy cancer patients. Eleven patients, median age 45 years, without prior cardiovascular co-morbidities were enrolled. Ten (91%) patients were females with breast cancer and 1 (9%) was male with lymphoma. Results: In pre-tropisetron period, 3 patients (27.3%) had non-significant arrhythmias (2 supravetricular extrasystole [SVES] and 1 ventricular extrasystole [VES]). In during- and after-tropisetron period, 2 additional patients developed SVES and 3 developed bradycardia below 50 beats/minute (collectively 72.7%). Patients were asymptomatic and there was no statistical significance (Mc Nemar, p=0.063) in frequencies. QTc before (375msecs) and after (370 msecs) tropisetron injection were not different (Wilcoxon Signed Ranks Test, p=0.098), as was QT dispersion (30 vs. 40msecs, Wilcoxon Signed Ranks Test, p=0.180). There were no life threatening arrhythmias observed. Conclusions: Tropisetron did not seem to induce significant or non-significant arrhythmias. Predictors of arrhythmias were not affected, either. However, the number of patients is few and we continue to enroll patients. No significant financial relationships to disclose.
Attempting tissue diagnosis in performance status 3 and 4 lung cancer patients may not influence treatment or survival
Authors: John Farley, John Maclay, Conor Tweed, Paul Carroll, Robert Milroy
Journal: European Respiratory Journal (2013)

Introduction  After a radiological diagnosis of lung cancer, further investigation and treatment is influenced by the fitness of a patient, taking into account the risks and potential benefits. Tissue diagnosis is usually deemed essential prior to administration of radical radiotherapy and chemotherapy, but less so for palliative radiotherapy.  Aims and objectives  To determine if obtaining a tissue diagnosis altered management in patients with performance status (PS) 3 and 4.  Methods  Details of all patients with lung cancer diagnosed in North Glasgow between 2009-2011 were prospectively recorded at a multidisciplinary meeting. We subsequently investigated the relationships between PS and tissue diagnosis, treatment and survival.  Results   1842 patients were diagnosed with lung cancer. PS was recorded in 92%. Overall, tissue diagnosis was achieved in 81% of patients. Tissue diagnosis was attempted in 97% of patients with PS 0. Treatment was influenced in 85% of these patients in that they underwent chemotherapy, surgery or radical radiotherapy. Tissue diagnosis was attempted in 62% and 33% of PS 3 and 4 respectively, with tissue diagnosis influencing treatment in 7% and 0%. There was no difference in survival in patients with PS of 3 or 4 that had tissue diagnosis attempted (median days (95%CI): tissue 42 (31-53) vs no tissue 37 (25-49)).  Conclusions  Diagnostic tests were performed in a significant proportion of patients with PS 3 and 4 to establish a tissue diagnosis, but treatment was only influenced by this in a small minority. Attempting tissue diagnosis in these patients did not give any survival benefit.
Nodal Upstaging Is More Common with Thoracotomy than with VATS During Lobectomy for Early-Stage Lung Cancer: An Analysis from the National Cancer Data Base
Authors: Rachel L. Medbery, Theresa W. Gillespie, Yuan Liu, Dana C. Nickleach, Joseph Lipscomb, Manu S. Sancheti, Allan Pickens, Seth D. Force, Felix G. Fernandez
Journal: Journal of Thoracic Oncology (2016)
In vitro synergistic cellular proliferation inhibition in pancreatic cancer cells Su86 and Mia-PaCa-2 with fluvastatin and nab-paclitaxel.
Authors: Doron Feinsilber, Cliff Whatcott, Marc Ryan Matrana, John T. Cole, Ruben Munoz, Qingyang Luo, Jyotsna Fuloria, Suma Satti
Journal: Journal of Clinical Oncology (2015)

331 Background: Statins have been shown to possess antiproliferative activity in-vitro. Synergism with multiple drug combinations has been of great interest in pancreatic cancer. We examined 2 in-vitro cell models for synergism using a combination of fluvastatin and nab-paclitaxel. Methods: Pancreatic cancer cell lines Mia-Paca-2 (MP2) and Su86 were cultivated and seeded to 25,000 cells/mL and subsequently grown in 96 well plates for 24 hours. The cells were then treated with a fixed concentration of fluvastatin in 9 rows, 8 receiving serial 1:2 dilutions 16 times in triplicate of nab-paclitaxel, 1 fluvastatin only row, and 1 untreated. Upon dosing cells were incubated for 72 hrs. Cellular proliferation was determined by sulforhodamine B proliferation assays and read at 570 nm. A nab-paclitaxel only assay was done as well for comparison. Results: The lowest inhibitory concentration of fluvastatin in combination with nab-paclitaxel was between 500-600 micro mole (mm). Fluvastatin alone at these concentrations attenuated cellular proliferation. Synergism was seen on IC50 curves that are available. Anti-proliferative effects were reduced by 1:256 dilution. Conclusions: Preliminary studies show fluvastatin has an in-vitro anti proliferative effect on Su86 and MP2 cells and synergism in combination with nab-paclitaxel. Fluvastatin is more cytotoxic in Su86 than MP2. Future experimental design will focus on in-vivo models.
Potential economic impact of the 21-gene expression panel according to tumor (T) size in lymph-node-negative (LNN), estrogen-receptor (ER)-positive early breast cancer (BC)
Authors: F. E. Prisco, E. D. Saad, F. M. Carvalho, E. B. Ojopi, C. E. Bacchi
Journal: Journal of Clinical Oncology (2009)

e11518 Background: Use of the 21-gene panel may save costs in patients with LNN, ER-positive BC. Our previous analysis suggests that such would be the case in Brazil (SABCS 2008). However, the impact of the test may vary according to T size. Methods: Using a web-based survey with 30 (of a total of nearly 700) medical oncologists and literature data, we developed a model of direct medical expenses in two hypothetic cohorts (one without and one with access to the 21-gene panel) of Brazilian women with LNN, ER-positive BC, from the perspective of third-party payers. The questionnaire assessed patterns of care relating to chemotherapy (CT) regimens in each T size, type of premedication, use of G-CSF, and use of intravenous antibiotics for febrile neutropenia. Medication and 21-gene panel costs were the manufacturers’ recommended prices at the time of the survey. T size and recurrence score distributions followed those reported by Paik et al (NEJM 2004). CT use in the cohort with no access to the 21-gene panel was modeled according to the survey. In the cohort with access to the test, we assumed that patients with intermediate or high scores would receive CT, whereas patients with low score would not. Results: The table displays the number of patients receiving CT and the costs (CT, premedication, G-CSF, antibiotics, and the 21-gene panel) for two hypothetic cohorts of 100 patients. Conclusions: Our economic analysis suggests that the 21-gene panel overall would be cost-saving in Brazil, from the perspective of third-party payers. However, testing could actually increase direct medical costs in LNN, ER-positive T1 tumors, and decrease costs in T &gt;2 cm. [Table: see text] [Table: see text]
Adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 in patients with metastatic malignant melanoma and renal cell carcinoma: a pilot study.
Authors: P S Goedegebuure, L M Douville, H Li, G C Richmond, D D Schoof, M Scavone, T J Eberlein
Journal: Journal of Clinical Oncology (1995)

PURPOSE The objective of this study was to determine the tolerance and effect of moderate-dose recombinant human interleukin-2 (rHu IL-2) and tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) refractory to standard therapy. PATIENTS AND METHODS Twenty-six patients (18 MM and eight RCC) were entered onto this pilot study. TIL were isolated from fresh biopsy material and activated with anti-CD3 antibody, OKT3, for 48 hours and expanded in 100 IU/mL r-methionyl Hu IL-2 alanine 125 (r-met Hu IL-2 [ala-125]). At least 10(10) TIL were reinfused intravenously in three divided injections on days 2, 4, and 6 of the protocol. A maximum dose of 30,000 U/kg of IL-2 per injection was administered every 8 hours from day 2 through day 11 for a total of 28 doses. RESULTS Sixteen melanoma patients completed the study. Of these, three (19%) showed a durable complete response (CR), nine (56%) had no response (NR), and four (25%) had progressive disease (PD). One nonresponder demonstrated complete tumor regression within 1 year of treatment. Of four assessable RCC patients, two experienced a minor response (MR) and two showed NR. All TIL cultures showed comparably high cytotoxic activity as determined by antibody-redirected lysis (ARL). More importantly, melanoma TIL from responders possessed significantly higher cytotoxicity against autologous tumor cells than TIL from nonresponders (P &lt; .05). Production of granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-4 was similar for TIL from melanoma responders and nonresponders, or TIL from RCC patients. CONCLUSIONS Immunotherapy with polyclonally activated TIL and moderate-dose IL-2 could be successfully used for the treatment of immunogenic tumors with less toxicity and lower costs as compared with high-dose IL-2 protocols.