tbuckley/cabot-search huggingface dataset:
Augmentation of Specific Cell-Mediated Immune Responses to Responses to in Tumor-Bearing Rats Pretreated With the Antileukemia Drug Busulfan&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Mizushima, Yutaka, Sendo, Fujiro, Miyake, Takayoshi, Kobayashi, Hiroshi
Journal: JNCI Journal of the National Cancer Institute (1981)

Lethal growth of a syngeneic transplanted tumor (KMT-17) was inhibited in inbred WKA rats pretreated with the antileukemia drug busulfan (BU). However, the lethal growth of KMT-17 was not inhibited by pretreatment with cyclophosphamide, adriamycin, or ftorafur. With the Winn assay, spleen cells from BU-pretreated KMT-17-bearing rats (TBR) inhibited the growth of admixed KMT-17 cells more strongly than did spleen cells from BU-untreated TBR. The augmented tumor inhibitory activity of spleen cells was KMT-17-specific, and this activity was abrogated by in vitro treatment of spleen cells with anti-T serum and guinea pig complement. Augmentation of the immune response to KMT-17-associated antigen(s) in BU-pretreated TBR was also demonstrated in lymphocyte-mediated cytotoxicity, as detected by a 51Cr release assay and by a delayed-type hypersensitivity with a radioisotope footpad assay. Tumor regression in BU-pretreated rats was demonstrated to be mediated by the augmentation of T-cell-mediated immune responses to tumor-associated antigens. The tumor inhibitory effect of BU was abrogated by adoptive transfer with thymus cells from normal rats but not with those from BU-pretreated rats 1 day before tumor inoculation. The augmentation oif the antitumor immune responses by pretreatment with BU was suggested to be due to the fact that BU selectively inhibited the suppressor cells of their precursors.
Sixty seconds on . . . greening the NHS
Authors: Nigel Hawkes
Journal: BMJ (2016)

Yes, it has more than met its commitment to reduce greenhouse gas emissions by 10% between 2007 and 2015. Emissions have fallen from 25.7 to 22.8 million tonnes of carbon dioxide equivalent a year—a reduction of 11.3%.

Yes, given that world emissions amount to nearly 36 000 million tonnes a year. But it’s not when you put the figure in …
Abstract 14888: State-Trait Anger is Significantly Associated With Mental Stress Induced Myocardial Ischemia
Authors: Pratik M Pimple, Amit J Shah, Cherie Rooks, J. Douglas Bremner, Jonathon A Nye, Ijeoma Ibeanu, Nancy Murrah, Xinwei Hua, Paolo Raggi, Viola Vaccarino
Journal: Circulation (2013)

Objective: Mental stress-induced myocardial ischemia (MSMI) is associated with worse prognosis in CAD patients and is a marker of the effects of psychological stress on cardiac function. Acute ange...
Gastrointestinal stromal tumors (GISTs): Our experience in the management of 26 patients
Authors: E. Maiello, L. Tozzi, T. P. Latiano, A. De Bonis, M. Bisceglia, C. D’Addetta, P. Di Sebastiano, L. Nanni, V. M. Valori, A. Piano
Journal: Journal of Clinical Oncology (2006)

19506 Background: GISTs represents 0.1–3% of gastrointestinal neoplasms; most cases occur in people 40 to 80 years old, and are more common in men than in women. More than half of all GISTs patients present with locally advanced, recurrent, or metastatic disease (mainly to liver or peritoneum). Methods: From January 2001 to December 2005 we observed in our Institution 26 pts with GISTs; all were CD117+.The main characteristics of these pts were as follows: median age: 61 yr; sex (F/M): 14/12; primary tumor site: stomach 13 (50 %), small intestine 7 (27 %), rectum 1 (4 %), retroperitoneum 4 (15 %), liver 1 (4 %); first symptoms: epigastric pain 10 (38 %); abdominal pain 4 (15 %); hematemesis 1 (3 %); anemia 5 (18,5 %), palpable abdominal mass 1 (3 %), defecation disorders 2 (7 %); melena 3 (11 %); rectal bleeding 1 (3 %); ascites 1 (3 %). Results: Radical surgical resection was performed in 21 patients (81 %), 2 patients received a debulking surgery, and no postoperative mortality or major complications were observed; 3 pts showed an advanced disease. Seven pts (33%) developed recurrence, local or at distance, and the median time to relapse was 7,5 months (range 2–11). One pt with advanced disease dead before any treatment and 11 pts received Imatinib (I), at the standard dose (400 mg/d), starting from the date of diagnosis of advanced disease or metastatic relapse and given until development of intolerance or progressive disease. Main toxicities of I included: neutropenia G3 (4%), skin rash (4%), periorbital oedema (4%). We achieved 3 PR (lasting 12+, 21+ and 40 mos), 6 SD and 2 PD. With a median follow-up of 30 months, all but three pts (dead for progressive diseases) are alive. The overall survival rate was 88.5 % and the median overall survival was 16 mos (range 1–49). Conclusions: Surgical resection remains the only effective treatment for GISTs. However, in pts with advanced or relapsed disease treatment with I is effective with an high disease control rate. No significant financial relationships to disclose.
Abstract P335: Building Assessment Tools for Unrecognized Myocardial Infarction: The REasons for Geographic and Racial Differences in Stroke Study
Authors: Emily B Levitan, Monika M Safford, Meredith L Kilgore, Elsayed Z Soliman, Stephen P Glasser, Suzanne E Judd, Paul Muntner
Journal: Circulation (2012)

Introduction: People with unrecognized myocardial infarction (UMI) have elevated risk for cardiovascular events and death. Population-wide electrocardiogram screening for detection of UMI would be resource intensive. We therefore sought to develop assessment tools for targeted UMI screening. Methods: Using logistic regression and a backward selection procedure, we developed two models among 16,653 participants without coronary revascularization or known myocardial infarction in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. UMI was defined as electrocardiogram evidence (using the Minnesota Code system) of myocardial infarction without a self-reported history (n = 740). The basic model used demographics, self-reported medical history, blood pressure, and body mass index; the expanded model used information on 51 potential variables including health behaviors, clinical measurements, and participant-reported health scales and symptoms. Results: The basic model had a c-statistic of 0.638 (95% CI 0.617 − 0.659) and included age, race, smoking status, body mass index, systolic blood pressure, transient ischemic attack, deep vein thrombosis, falls, diabetes, and hypertension. The expanded model had a c-statistic of 0.654 (95% CI 0.634−0.674) and included age, race, income, smoking status, self-reported hypertension, unrecognized dyslipidemia, perceived stress score, waking at night due to breathlessness, body mass index and body mass index squared, HDL cholesterol squared, systolic blood pressure, albumin:creatinine ratio, heart rate, and heart rate squared. The Framingham coronary heart disease risk score had a c-statistic of 0.587 (95% CI 0.566−0.609). Conclusions : Even with a large number of potential risk factors, the models did not provide sufficient discrimination to warrant use as an assessment tool. Identifying individuals at high risk of UMI for further screening using an assessment tool may be challenging.
A set of nomograms predicting acute gastrointestinal syndrome after prostate cancer conformal radiation
Authors: R. Valdagni, T. Rancati, C. Fiorino, G. Fellin, L. Vera Righi, A. Magli, L. Mariani, A. Monti, C. Bianchi, V. Vavassori
Journal: Journal of Clinical Oncology (2007)

15555 Background: To predict acute toxicities (tox) of the gastrointestinal syndrome (SOMA LENT) in prostate cancer (PCa) patients (pts) undergoing 3D-CRT using a tool (nomogram) with clinical as well as dosimetric variables which has proved to be significant in the AIROPROS 01–02 trial. Methods: Acute rectal tox was scored in 1,132 pts using a 10 item self assessed questionnaire (QST) describing radio-induced GI symptoms profiles for bowel frequency, tenesmus, fecal continence, rectal pain and bleeding. The correlation between hormonal therapy (HT), drug prescription, diabetes or hypertension, pelvic node or seminal vesicles irradiation, mean rectal dose, DVH constraints and rectal tox was investigated by uni- and multivariate (MVA) logistic analyses. MVA results were used the R-project software to create nomograms predicting the symptoms of the acute GI syndrome. Results: 4/10 items of the QST are reported: moderate/severe bleeding, increased bowel frequency, moderate/severe bowel urgency and severe fecal incontinence. Bleeding is related to haemorrhoids (OR=1.9), HT (protective factor, OR=0.78) and mean rectal dose (continuous variable (cv), OR=1.024). Bowel frequency is related to seminal vesicles irradiation (OR=2.8) and V60 (cv, OR=1.024), while bowel urgency is correlated to seminal vesicles irradiation (OR=3.3) and mean rectal dose (cv, OR=1.027). Fecal incontinence depends on seminal vesicles irradiation (OR=4.6) and V70 (cv, OR=1.029). MVA results were used to create a set of nomograms. Conclusions: The combined effect of several independent, prognostically valuable variables for a specific disease can be expressed using nomograms. They can evaluate clinical and technical parameters of the single pt and offer clinicians a tailored probability of a specific outcome. To our best knowledge, this work presents the first set of nomograms available in the literature specific symptoms of the GI syndrome. The prediction capability of these tools will be validated on a independent set of patients. This work was partly supported by Fondazione I. Monzino, Milan No significant financial relationships to disclose.
DNA repair, multidrug resistance and metabolic enzyme genes polymorphisms as predictors of clinical outcome in resected non-small cell lung cancer (NSCLC)
Authors: N. Viñolas, S. Jansa, E. Carcereny, E. Gallardo, T. Diaz, F. Casas, R. Artells, J. Ramirez, J. Gimferrer, M. Monzo
Journal: Journal of Clinical Oncology (2008)

22121 Background: Early stage NSCLC is considered a potentially curable disease following complete resection. Gene expression profiles can identify patients (pts) with a higher risk of recurrence. We hypothesized those differents polymorphisms profiles could help to predict disease outcome. Methods: NSCLC paraffin-embebed samples were obtained from 58 pts who underwent curative pulmonary resection. We analyze 17 polymorphisms: 8 DNA repair polymorphisms: XRCC5(T/C), XRCC5(A/G), XPA(T/C), XPC(Gln939Lys), ERCC1(Lys259Thr), ERCC2(Lys751Gln), ERCC5(Asp1104His) and ERCC5(His49His); 7 metabolic enzyme polymorphisms: EPOXH1(His139Arg), EPOXH1(Tyr113His), CYP2C8(Arg139Lys), CYP2C8(Lys399Arg), GSTP1(G/A), GSTT1(C/T), NAT2–1(Arg197Gln); and 2 multidrug resistance polymorphisms: MDR1(Ile1145Met), MDR1(G412G). The analysis were performed using real-time polymerase chain reaction allelic discrimination TaqMan assay. Results: 58 primary lung cancer cases were included between January 1997 to December 2001. 56 males, 2 females. Median age was 65. Histology: 44.8% adenocarcinoma and 50% squamous cell carcinoma. Stage: I 36.9%, II 25.9% and III 15.5%. 56% relapsed. The presence of ERCC1 (34.5 vs 71 m wild type (WT); p=0.022), XPC (39.6 vs 73.9 m WT; p=0.035), XRCC5(A/G)(12.5 vs 66.9 m WT; p=0.006) or CYP2C8 (Arg139Lys) (26.8 vs 70.8 WT m; p=0.009) polymorphism were associated with worse time to progression (TTP). A metabolic enzyme polymorphisms (NAT 2–1) better outcome (87.6 vs 43 m WT, p=0.008). For survival (OS) pts with XRCC5(A/G) (31.5 vs 65.9 m WT, p=0.054), ERCC1 (38.5 vs 71.5 m WT; p=0.017) and MDR-1(Ile1145Met) (34.7 vs 69.7 m WT; p=0.021) showed worse results. In multivariate analysis stage (p=0.001), sex (p=0.003), XRCC5 (A/G) (p=0.006), ERCC1 (p=0.004), NAT 2–1 (p=0.006) for TTP and stage (p=0.008) and sex (p=0.054) for survival were identified as an independent prognostic factors. Conclusions: we report associations between some DNA repair, metabolic enzyme and multidrug resistance polymorphisms and clinical outcome in resected NSCLC pts. No significant financial relationships to disclose.
Costs of initial, continuing and terminal care in US patients with recurrence following early breast cancer
Authors: L. Lamerato, S. Havstad, S. Gandhi, D. Jones
Journal: Journal of Clinical Oncology (2005)

634 Background: Little is known regarding the economic impact of breast cancer (BC) recurrence on different phases of patient care (i.e. initial, continuing, and terminal). The objective of this study was to evaluate the economic impact of recurrence on different phases of care for such patients. Methods: A retrospective cohort study of 1616 patients (mean age 60 yrs) with early BC (stage I and II) was conducted using data from a large integrated health care system. Information on demographics, disease characteristics/treatment, charges for care, evidence/type of recurrence, and death was obtained. Phases of care were defined as initial care (6 months following diagnosis or recurrence), terminal care (6 months prior to death), and continuing care (period between initial and terminal phases of care). Tests were used for comparisons of charges between initial care after BC diagnosis and recurrence, continuing care (in quarterly estimates) pre- and post-recurrence, and terminal care between recurred and non-recurred patients. Charges were log-transformed and adjusted to 2003 US dollars. Results: During a median follow-up of 44.5 (range 6.1–98.3) months, there were 192 (11.9%) recurrence events (26.1% loco-regional, 15.6% contralateral, 58.3% distant) and 188 (11.6%) deaths due to any cause, of which 85 (5.3% of study population) were BC-related. For women experiencing recurrence of BC (n=74), the mean charges for care provided during the 6-month post-recurrence period were significantly higher compared with the initial 6-month period after BC diagnosis ($50,355 vs $38,254, p<.01). Quarterly charges for continuing care during the post-recurrence period were significantly higher than the pre-recurrence period ($4,934 vs $1,825, p<.001). Mean charges for terminal care were significantly higher (p<.01) for women experiencing a recurrence (n=27, $63,434) compared with non-recurred patients (n=65, $53,872). Conclusion: The study shows that BC recurrence among patients with early BC poses a significant economic burden during the entire continuum of care. Therapies shown to reduce the risk of BC recurrence may significantly reduce the costs of care of patients with early BC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Phase I clinical trials of ticilimumab: Tumor responses are sufficient but not necessary for prolonged survival
Authors: C. A. Bulanhagui, A. Ribas, D. Pavlov, V. Bozon, A. Sharma, J. Gomez-Navarro, L. Camacho
Journal: Journal of Clinical Oncology (2006)

8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with ticilimumab, a fully human anti-CTLA4 mAb, have been reported previously. In both studies, objective responses (OR) were seen in some patients (pts) with melanoma. In addition, we observed highly favorable outcomes among several pts who did not experience objective responses. This may indicate a positive impact of ticilimumab on melanoma in these pts, not well reflected by traditional response criteria. Long-term follow-up data on survival for pts enrolled in these Phase 1 studies is now reported. Methods: We studied the safety, pharmacokinetics, immunostimulatory activity, and clinical activity of ticilimumab in 53 pts with solid malignancies. Ticilimumab was administered, as a single agent, at single dose levels ranging from 0.01 to 15 mg/kg and at multiple dose levels ranging from 3 to 15 mg/kg. The dosing regimens included either a single dose, multiple doses given q3 months, or multiple doses given q1 month. Results: The two studies included 43 pts with measurable melanoma. Ticilimumab proved safe and overall was well tolerated (Ribas et al. ProcASCO 2005, and JCO Dec2005). Of the 43 pts with measurable melanoma, 18 were alive at &gt;12 months (range: 13 - 42+) after initial treatment with ticilimumab. This includes 5 pts with an OR who continue on ticilimumab, either on-study or as part of a single IND, and 13 pts without an objective response. Among the pts who did not experience an OR, 5 had surgical resection of metastatic lesions and remain relapse free, and 8 are alive with disease. Conclusions: In pts with melanoma treated with ticilimumab, long-term survival has been achieved by all 5 pts who experienced an OR and in 13 pts who did not experience an OR. These findings suggest that lack of objective response is a poor predictor of long-term survival following ticilimumab therapy. [Table: see text]
Trust pays cardiologist £1.22m for unfair dismissal
Authors: Clare Dyer
Journal: BMJ (2016)

A whistleblowing consultant cardiologist who fought a 14 year battle against the NHS trust that employed him has won £1.22m for unfair dismissal.

Raj Mattu was suspended by the University Hospitals Coventry and Warwickshire NHS Trust in February 2002, five months after he spoke to the BBC about the death of a 35 year old patient in an overcrowded bay at Walsgrave Hospital, Coventry. The trust accused him of bullying two junior doctors in an attempt to persuade them to join him in his dispute with management.

After …
BCR/ABL mRNA and the P210BCR/ABL Protein Are Downmodulated by Interferon- in Chronic Myeloid Leukemia Patients
Authors: Fabrizio Pane, Ilaria Mostarda, Carmine Selleri, Rossella Salzano, Anna Maria Raiola, Luigia Luciano, Giuseppe Saglio, Bruno Rotoli, Francesco Salvatore
Journal: Blood (1999)
Preglomerular and Postglomerular Resistance Responses to Different Levels of Sympathetic Activation by Hypoxia
Authors: Kate M. Denton, Amany Shweta, Warwick P. Anderson
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. This study investigated the effects of graded reflex increases in renal sympathetic nerve activity (RSNA) on renal preglomerular and postglomerular vascular resistances. With the use of hypoxia to reflexly elicit increases in RSNA without affecting mean arterial pressure, renal function and stop-flow pressures were measured in three groups of rabbits before and after exposure to room air and moderate (14% O2) or severe (10% O2) hypoxia. Moderate and severe hypoxia increased RSNA, primarily by increasing the amplitude of the sympathetic bursts rather than their frequency. RSNA amplitude increased by 20 ± 6% (P < 0.05) and 60 ± 16% (P < 0.05), respectively. Moderate hypoxia decreased estimated renal blood flow (ERBF; 26 ± 7%; P = 0.07), whereas estimated glomerular capillary pressure (32 ± 1 versus 34 ± 1 mmHg; P < 0.05) and filtration fraction (FF; P < 0.01) increased. In response to moderate hypoxia, calculated preglomerular (≈20%) and postglomerular (≈70%) resistance both increased, but only the increase in postglomerular resistance was significant (P < 0.05). In contrast, severe hypoxia decreased ERBF (56 ± 8%; P < 0.01), GFR (55 ± 9%; P < 0.001), and glomerular capillary pressure (32 ± 1 versus 29 ± 1 mmHg; P < 0.001), with no change in FF, reflecting similar preglomerular (≈240%; P < 0.05) and postglomerular (≈250%; P < 0.05) contributions to the vasoconstriction and a decrease in calculated Kf (P < 0.05). These results provide evidence that reflexly induced increases in RSNA amplitude may differentially control preglomerular and postglomerular vascular resistances.
Randomized phase III study of paclitaxel plus carboplatin with or without sorafenib as second-line treatment in patients with advanced melanoma
Authors: S. S. Agarwala, U. Keilholz, D. Hogg, C. Robert, P. Hersey, A. Eggermont, S. Grabbe, R. Gonzalez, K. Patel, A. Hauschild
Journal: Journal of Clinical Oncology (2007)

8510 Background: Sorafenib (SOR), a potent and selective multi-kinase inhibitor, exerts its anti-tumor and anti-angiogenic effects via inhibition of VEGFR-1, -2, -3, PDGFR-a, -β, and Raf. Promising results from a single-arm study of paclitaxel and carboplatin plus sorafenib (PC+SOR) in advanced melanoma warranted further investigation in a randomized phase III trial. Methods: Eligibility criteria: measurable disease by RECIST, progressive disease (PD) on dacarbazine or temozolomide-containing regimen. Prior adjuvant immunotherapy was allowed; pts with active brain metastases were excluded. Pts stratified by stage (unresectable III vs IV, M1a/M1b vs M1c) and ECOG PS (0 vs 1) were randomized to receive P 225 mg/m 2 and C AUC=6 on day 1 every 3 wks + oral placebo (PL) or oral SOR 400 mg bid on Days 2–19 every 3 wks until the occurrence of PD or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Using a two-sided test with a = 0.01, 173 PFS events were needed to detect a hazard ratio (HR) of 0.56 (SOR/PL) with 90% power. The secondary endpoints were overall survival, objective response rate (ORR) and time to progression. Results: 270 pts randomized over 12 mos in equally balanced groups had: median age 57 yrs, male 63%, ECOG PS 1 46%, Stage IV M1c 69% and elevated LDH 46%. At the time of analysis by independent assessment, the median PFS of PC+PL vs PC+SOR was 17.9 wks (99% CI: 11.3, 22.9) vs 17.4 wks (99% CI: 11.9, 23.1), HR 0.906 [p=0.492]; PFS rate at Day 180 was 29% vs 32%, ORR was 11% vs 12%. Both regimens were well-tolerated with the following selected = Grade 3 toxicities in PC+PL vs PC+SOR: neutropenia (46% vs 49%), febrile neutropenia (7% vs 9%), thrombocytopenia (12% vs 28%), sensory neuropathy (13% vs. 20%), thrombosis/embolism (6% vs 4%), rash/desquamation (0 vs 7%), hand-foot skin reaction (0 vs 7%), fatigue (10% vs 16%), diarrhea (3% vs 8%) and hemorrhage (3% vs 2%). There were 2 deaths, possibly related to treatment with PC+SOR. Conclusions: The addition of SOR to PC did not improve PFS or ORR in this second-line patient population. Toxicity of PC+SOR is tolerable. The utility of PC+SOR in chemotherapy-naïve advanced melanoma pts remains an important question and a phase III trial is currently in progress (E2603). [Table: see text]
Effects of Riboflavin on the Dimethylnitrosamine Demethylase System in the Rat Liver
Authors: M Ruchirawat, S Saengchan
Journal: JNCI Journal of the National Cancer Institute (1984)

The effects of riboflavin on the dimethylnitrosamine [(DMN) CAS: 62-75-9; N-nitrosodimethylamine] demethylase system in inbred F344 rat liver were investigated. Dietary riboflavin deficiency markedly stimulated the activity of DMN demethylase I operating at a low substrate concentration (4 mM), but it caused no change in the activity of DMN demethylase II operating at a high substrate concentration (200 mM). This effect could be reversed by short-term supplementation of the vitamin by a series of three ip injections (0.5 mg/dose/day) to the deficient animals. This dosage regimen of riboflavin did not change the activity of DMN demethylase I in the normal animals. The study in vitro demonstrated that flavins were inhibitory to DMN demethylase I. The enzyme activity in the microsomes of both control and deficient animals was inhibited by preincubation with flavins, suggesting that the interaction between flavins and the enzyme rendered the enzyme inactive. Flavin adenine dinucleotide(FAD) appeared to have a more pronounced effect than riboflavin. In agreement with the earlier observation, DMN demethylase II was unaffected by FAD or riboflavin.