tbuckley/cabot-search huggingface dataset:
Improving care for patients with lung cancer in the UK
Authors: Tariq Sethi, Eric Lim, Mick Peake, John Field, John White, Marianne Nicolson, Corinne Faivre-Finn, Paul Cane, John Reynolds, Henrik Møller, Hilary Pinnock
Journal: Thorax (2013)

The care of patients with lung cancer in the UK today has improved over the last 10 years, primarily because we are now able to measure and quantify the differences in patient care pathways and outcomes. The National Lung Cancer Audit started in 2004 with 40% case ascertainment and today it is inconceivable that any NHS hospital that manages patients with lung cancer would not contribute. With 100% case ascertainment since 2010,1 active treatment rates increased from 45% in 2005 to 61% in 2012 and the overall surgical resection rates rose from 9% to 16% in the same period. Measurements of performance and outcome data can drive improved survival in patients with lung cancer, and the establishment of national data collection is an important step towards improving the quality of patient care.2

However, even with these improvements, survival from lung cancer in the UK lags behind that of comparable countries.3 ,4 The reasons for this in part are due to late diagnosis and huge variations in the delivery of care across the country. A round table meeting assembled experts with the remit to explore what changes were needed in the current management of patients with lung cancer in the UK to improve their survival.

To provide a snapshot of how respiratory physicians view the current state of lung cancer management in the UK, Thorax sent out an online survey in August 2013 to 6000 hospital physicians identified as having an interest in respiratory medicine. This group was chosen as respiratory physicians are the ‘gatekeepers’ who determine entry into lung cancer diagnostic and care pathways: their attitudes have great influence on lung cancer patients. Responses were received from 3–4% of the survey group, who are likely to represent a particularly motivated group of respiratory physicians with an interest …
Statins and Cancer Risk: A Literature-Based Meta-Analysis and Meta-Regression Analysis of 35 Randomized Controlled Trials
Authors: Stefanos Bonovas, Kalitsa Filioussi, Nikolaos Tsavaris, Nikolaos M. Sitaras
Journal: Journal of Clinical Oncology (2006)

A growing body of literature suggests that statins may have chemopreventive potential against cancer. Our aim was to examine the strength of this association through a detailed meta-analysis and meta-regression analysis of randomized controlled trials (RCTs).A comprehensive search for trials published up to 2005 was performed, reviews of each study were conducted, and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random- and fixed-effects models. Subgroup, sensitivity, and meta-regression analyses were also conducted.Thirty-five RCTs of statins for cardiovascular outcomes contributed to the analysis (n = 109,143). The degree of variability between trials was consistent with what would be expected to occur by chance alone. Statin use was not associated with a substantially increased or decreased overall risk of cancer (RR = 0.99; 95% CI, 0.94 to 1.04). Similarly, statin use did not significantly affect respiratory cancer risk (RR = 0.95; 95% CI, 0.83 to 1.09). However, the meta-regression analysis indicated that age of study participants modified the association between statin use and cancer risk (P = .003).Our findings do not support a protective effect of statins against cancer. However, this conclusion is limited by the relatively short follow-up periods (4.5 years on average) of the studies analyzed. Thus, it is important to continue monitoring the long-term safety profiles of statins. Until then, physicians need to be vigilant in ensuring that statin use remains restricted to the approved indications.
The prevalence of unplanned pregnancy and associated factors in Britain: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)
Authors: Kaye Wellings, Kyle G Jones, Catherine H Mercer, Clare Tanton, Soazig Clifton, Jessica Datta, Andrew J Copas, Bob Erens, Lorna J Gibson, Wendy Macdowall, Pam Sonnenberg, Andrew Phelps, Anne M Johnson
Journal: The Lancet (2013)

Unplanned pregnancy is a key public health indicator. We describe the prevalence of unplanned pregnancy, and associated factors, in a general population sample in Britain (England, Scotland, and Wales).We did a probability sample survey, the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), of 15,162 men and women aged 16-74 years in Britain, including 5686 women of child-bearing age (16-44 years) who were included in the pregnancy analysis, between Sept 6, 2010, and Aug 31, 2012. We describe the planning status of pregnancies with known outcomes in the past year, and report the annual population prevalence of unplanned pregnancy, using a validated, multicriteria, multi-outcome measure (the London Measure of Unplanned Pregnancy). We set the findings in the context of secular trends in reproductive health-related events, and patterns across the life course.9·7% of women aged 16-44 years had pregnancies with known outcome in the year before interview, of which 16·2% (95% CI 13·1-19·9) scored as unplanned, 29·0% (25·2-33·2) as ambivalent, and 54·8% (50·3-59·2) as planned, giving an annual prevalence estimate for unplanned pregnancy of 1·5% (1·2-1·9). Pregnancies in women aged 16-19 years were most commonly unplanned (45·2% [30·8-60·5]). However, most unplanned pregnancies were in women aged 20-34 years (62·4% [50·2-73·2]). Factors strongly associated with unplanned pregnancy were first sexual intercourse before 16 years of age (age-adjusted odds ratio 2·85 [95% CI 1·77-4·57], current smoking (2·47 [1·46-4·18]), recent use of drugs other than cannabis (3·41 [1·64-7·11]), and lower educational attainment. Unplanned pregnancy was also associated with lack of sexual competence at first sexual intercourse (1·90 [1·14-3·08]), reporting higher frequency of sex (2·11 [1·25-3·57] for five or more times in the past 4 weeks), receiving sex education mainly from a non-school-based source (1·84 [1·12-3·00]), and current depression (1·96 [1·10-3·47]).The increasing intervals between first sexual intercourse, cohabitation, and childbearing means that, on average, women in Britain spend about 30 years of their life needing to avert an unplanned pregnancy. Our data offer scope for primary prevention aimed at reducing the rate of unplanned conceptions, and secondary prevention aimed at modification of health behaviours and health disorders in unplanned pregnancy that might be harmful for mother and child.Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.
Differential Effects of Delivery of Omega-3 Fatty Acids to Human Cancer Cells by Low-Density Lipoproteins <b> <i>versus</i> </b> Albumin
Authors: Iris J. Edwards, Isabelle M. Berquin, Haiguo Sun, Joseph T. O’Flaherty, Larry W. Daniel, Michael J. Thomas, Lawrence L. Rudel, Robert L. Wykle, Yong Q. Chen
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Omega-3 (n-3) fatty acids (FA) have been proposed to confer tumor-inhibitory properties. In vivo, dietary FA are delivered to tumor cells by two main routes: low-density lipoproteins (LDL) and albumin complexes. High FA concentration in LDL and up-regulation of LDL receptors in tumor cells suggest that the LDL receptor pathway may be the major route for FA delivery. We compared effects of n-3FA delivered to human cancer cells by LDL and albumin. Experimental Design: LDL was isolated from plasma of African Green monkeys fed diets enriched in fish oil (n-3 FA) or linoleic acid (n-6FA) and used to deliver FA to MCF-7 and PC3 cancer cells. Cell proliferation, apoptosis, and changes in global gene expression were monitored. Results: Both LDL and albumin were effective in delivering FA to tumor cells and modifying the composition of cell phospholipids. The molar ratio of 20:4 (n-6) to 20:5 (n-3) in phosphatidylcholine and phosphatidylethanolamine was profoundly decreased. Although cell phospholipids were similarly modified by LDL and albumin-delivered FA, effects on cell proliferation and on transcription were markedly different. LDL-delivered n-3 FA were more effective at inhibiting cell proliferation and inducing apoptosis. Expression microarray profiling showed that a significantly higher number of genes were regulated by LDL-delivered than albumin-delivered n-3 FA with little overlap between the two sets of genes. Conclusions: These results show the importance of the LDL receptor pathway in activating molecular mechanisms responsible for the tumor inhibitory properties of n-3FA.
Endothelin-Dependent Actions in Cultured AT-1 Cardiac Myocytes
Authors: Tianrong Jiang, Elena Pak, HongLu Zhang, Richard P. Kline, Susan F. Steinberg
Journal: Circulation Research (1996)

Abstract The consequences of endothelin receptor activation were examined in atrial tumor myocytes derived from transgenic mice (AT-1 cells). Endothelin-1 (endothelin) stimulates phosphoinositide hydrolysis in a dose-dependent manner. Endothelin also induces the rapid and transient translocation of protein kinase C (PKC)-ε immunoreactivity from the soluble to the particulate cell fraction. The subcellular distributions of PKCα and PKCζ (also expressed by AT-1 cells) are not influenced by endothelin. Using quantitative fluorescence microscopy with fura 2, we examined the effects of endothelin on intracellular calcium. In electrically driven myocytes, endothelin induces a rapid and transient increase in the amplitude of the calcium transient. This is blocked by both phorbol 12-myristate 13-acetate (PMA) pretreatment to downregulate PKC and the PKC inhibitor chelerythrine, arguing that PKCε plays a critical role in endothelin receptor–dependent increases in intracellular calcium. Endothelin also stimulates mitogen-activated protein kinase (MAPK). MAPK activation is markedly attenuated by pretreatment with PMA or pertussis toxin (PTX, to inactivate susceptible G protein α subunits); it is completely prevented by combined pretreatment with PMA and PTX. In contrast, it is not attenuated by chelation of intracellular calcium with BAPTA. These findings indicate that the pathway for endothelin receptor stimulation of MAPK involves PKCε and PTX-sensitive G protein(s). Thus, these studies identify a functional role for PKCε as a mediator of endothelin receptor–dependent increases in cytosolic calcium and MAPK activity in AT-1 cells. Accordingly, the AT-1 cell system should provide a uniquely useful model to identify the intracellular targets for PKCε and investigate their function in the regulation of intracellular calcium homeostasis and the induction of the growth response in cardiac myocytes.
FDA chief wants other rich countries to share drug development costs
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

Trying to make new drugs “affordable, safe, and innovative” is a “global crisis,” said Mark McClellan, commissioner of the US Food and Drug Administration, in a speech to the first international colloquium on generic medicine in Cancun, Mexico. He said the United States was paying too high a price for developing new drugs and called for other rich countries to share development costs, perhaps in proportion to their national income.

Developing a new drug costs more than $800m (£480m; €690m), Dr McClellan said. As countries tighten their price regulations, drug companies …
Treatment of Anaplastic Histology Wilms' Tumor: Results From the Fifth National Wilms' Tumor Study
Authors: Jeffrey S. Dome, Cecilia A. Cotton, Elizabeth J. Perlman, Norman E. Breslow, John A. Kalapurakal, Michael L. Ritchey, Paul E. Grundy, Marcio Malogolowkin, J. Bruce Beckwith, Robert C. Shamberger, Gerald M. Haase, Max J. Coppes, Peter Coccia, Morris Kletzel, Robert M. Weetman, Milton Donaldson, Roger M. Macklis, Daniel M. Green
Journal: Journal of Clinical Oncology (2006)

An objective of the fifth National Wilms' Tumor Study (NWTS-5) was to evaluate the efficacy of treatment regimens for anaplastic histology Wilms' tumor (AH).Prospective single-arm studies were conducted. Patients with stage I AH were treated with vincristine and dactinomycin for 18 weeks. Patients with stages II to IV diffuse AH were treated with vincristine, doxorubicin, cyclophosphamide, and etoposide for 24 weeks plus flank/abdominal radiation.A total of 2,596 patients with Wilms' tumor were enrolled onto NWTS-5, of whom 281 (10.8%) had AH. Four-year event-free survival (EFS) and overall survival (OS) estimates for assessable patients with stage I AH (n = 29) were 69.5% (95% CI, 46.9 to 84.0) and 82.6% (95% CI, 63.1 to 92.4). In comparison, 4-year EFS and OS estimates for patients with stage I favorable histology (FH; n = 473) were 92.4% (95% CI, 89.5 to 94.5) and 98.3% (95% CI, 96.4 to 99.2). Four-year EFS estimates for patients who underwent immediate nephrectomy with stages II (n = 23), III (n = 43), and IV (n = 15) diffuse AH were 82.6% (95% CI, 60.1 to 93.1), 64.7% (95% CI, 48.3 to 77.7), and 33.3% (95% CI, 12.2 to 56.4), respectively. OS was similar to EFS for these groups. There were no local recurrences among patients with stage II AH. Four-year EFS and OS estimates for patients with bilateral AH (n = 29) were 43.8% (95% CI, 24.2 to 61.8) and 55.2% (95% CI, 34.8 to 71.7), respectively.The prognosis for patients with stage I AH is worse than that for patients with stage I FH. Novel treatment strategies are needed to improve outcomes for patients with AH, especially those with stage III to V disease.
Evolution of the Inflated Calyx Syndrome in Solanaceae
Authors: Jin-Yong Hu, Heinz Saedler
Journal: Molecular Biology and Evolution (2007)

Species that express the inflated calyx syndrome (ICS) are found in several genera of the Solanaceae. The MADS-box protein MPF2, together with the plant hormones cytokinin and gibberellin, has been shown to be responsible for this trait in Physalis floridana. We have used sequence data from 114 species belonging to 35 genera to construct a molecular phylogeny of Solanaceae. Apart from the 2 Witheringia species analyzed, species within a given genus cluster together on the resulting cladogram. Witheringia solanacea is embedded within the Physalinae, but Witheringia coccoloboides is placed basal to the Iochrominae. The ICS trait seems to be of multiple origins both within the Solanaceae and the Physaleae. Surprisingly, expression of MPF2-like genes in floral organs appears to be plesiomorphic in both the Physaleae and the Capsiceae. Some species in these tribes that show neither ICS nor calyx accrescence fail to express the MPF2-like gene in floral organs. Among those that do express this gene in the calyx are the species Capsicum baccatum, Lycianthes biflora, Tubocapsicum anomalum, W. solanacea, and Vassobia breviflora, all of which form small calyces that do not respond to externally applied hormones. The plesiomorphic nature of MPF2-like gene expression in the calyx of the Physaleae and Capsiceae raises the possibility that originally ICS also was actually a plesiomorphic character in these 2 groups. However, this trait might have undergone changes in a number of species due to secondary loss of components in ICS formation, like hormone response of calyx development. These findings are discussed in an evolutionary context of a molecular pathway leading to ICS.
Pulmonary Manifestations in the Diffuse Collagen Diseases
Authors: P. Ellman, L. Cudkowicz
Journal: Thorax (1954)

<h3>SUMMARY</h3> Understanding how invading pathogens are sensed within the brain is necessary to uncover how effective immune response are mounted in immunoprivileged sites. The eukaryotic parasite <i>Toxoplasma gondii</i> colonizes the brain of its hosts and initiates robust immune cell recruitment, but little is known about innate recognition of <i>T. gondii</i> within brain tissue. The host damage signal IL-33 is one protein that has been implicated in control of chronic <i>T. gondii</i> infection, but the specific impact of IL-33 signaling within the brain is unclear. Here, we show that IL-33 is expressed by oligodendrocytes and astrocytes during <i>T. gondii</i> infection, is released into the cerebrospinal fluid of <i>T. gondii</i>-infected animals, and is required for control of infection. IL-33 signaling promotes chemokine expression within brain tissue and is required for the recruitment of peripheral anti-parasitic immune cells, including IFN-γ-expressing T cells and iNOS-expressing monocytes. Importantly, we find that the beneficial effects of IL-33 during chronic infection are not a result of signaling on infiltrating immune cells, but rather on radio-resistant responders, and specifically, astrocytes. Mice with IL-33R-deficient astrocytes fail to promote an adaptive immune response in the CNS and control parasite burden, demonstrating that astrocytes can directly respond to IL-33 <i>in vivo</i>. Together, these results indicate a brain-specific mechanism by which IL-33 is released and sensed locally, to engage the peripheral immune system in controlling a neurotropic pathogen.
Cancer Mortality After Nasopharyngeal Radium Irradiation in The Netherlands: a Cohort Study
Authors: C M Ronckers, C E Land, P G Verduijn, R B Hayes, M Stovall, F E van Leeuwen
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Nasopharyngeal radium irradiation (NRI) was used widely from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for cancer-related deaths than were nonexposed individuals. Methods: We conducted a retrospective cohort study of all-cause and cancer-related mortality in 5358 NRI-exposed subjects and in 5265 frequency-matched nonexposed subjects, who as children were treated at nine ear, nose, and throat clinics in The Netherlands from 1945 through 1981. We recorded personal and medical data from original patient medical records and assessed vital status through follow-up at municipal population registries. Risk of mortality was evaluated by standardized mortality ratios (SMRs). All statistical tests were two-sided. Results: The average radiation doses were 275, 10.9, 1.8, and 1.5 cGy for the nasopharynx, pituitary, brain, and thyroid, respectively. The median follow-up was 31.6 years. Three hundred two NRI-exposed subjects had died, with 269.2 deaths expected (SMR = 1.1; 95% confidence interval [CI] = 1.0 to 1.3); among nonexposed subjects, 315 died, with 283.5 deaths expected (SMR = 1.1; 95% CI = 0.99 to 1.2). Cancer-related deaths of 96 exposed subjects (SMR = 1.2; 95% CI = 0.95 to 1.4) and 87 nonexposed subjects (SMR = 1.0; 95% CI = 0.8 to 1.3) were documented. There were no excess deaths from cancers of the head and neck area among exposed subjects. However, there were excess deaths from cancers of lymphoproliferative and hematopoietic origin (SMR = 1.9; 95% CI = 1.1 to 3.0), mainly from non-Hodgkin's lymphoma (SMR = 2.6; 95% CI = 1.0 to 5.3). We found no evidence that breast cancer deaths were less than expected (SMR = 1.7; 95% CI = 0.9 to 2.8) in contrast to an earlier study. Conclusions: Our findings do not indicate an increased cancer mortality risk in a population exposed to NRI in childhood. More prolonged follow-up of this and other NRI cohorts is recommended.
Mindfulness-Based Stress Reduction Compared With Cognitive Behavioral Therapy for the Treatment of Insomnia Comorbid With Cancer: A Randomized, Partially Blinded, Noninferiority Trial
Authors: Sheila N. Garland, Linda E. Carlson, Alisa J. Stephens, Michael C. Antle, Charles Samuels, Tavis S. Campbell
Journal: Journal of Clinical Oncology (2014)

Our study examined whether mindfulness-based stress reduction (MBSR) is noninferior to cognitive behavioral therapy for insomnia (CBT-I) for the treatment of insomnia in patients with cancer.This was a randomized, partially blinded, noninferiority trial involving patients with cancer with insomnia recruited from a tertiary cancer center in Calgary, Alberta, Canada, from September 2008 to March 2011. Assessments were conducted at baseline, after the program, and after 3 months of follow-up. The noninferiority margin was 4 points measured by the Insomnia Severity Index. Sleep diaries and actigraphy measured sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency. Secondary outcomes included sleep quality, sleep beliefs, mood, and stress.Of 327 patients screened, 111 were randomly assigned (CBT-I, n = 47; MBSR, n = 64). MBSR was inferior to CBT-I for improving insomnia severity immediately after the program (P = .35), but MBSR demonstrated noninferiority at follow-up (P = .02). Sleep diary-measured SOL was reduced by 22 minutes in the CBT-I group and by 14 minutes in the MBSR group at follow-up. Similar reductions in WASO were observed for both groups. TST increased by 0.60 hours for CBT-I and 0.75 hours for MBSR. CBT-I improved sleep quality (P < .001) and dysfunctional sleep beliefs (P < .001), whereas both groups experienced reduced stress (P < .001) and mood disturbance (P < .001).Although MBSR produced a clinically significant change in sleep and psychological outcomes, CBT-I was associated with rapid and durable improvement and remains the best choice for the nonpharmacologic treatment of insomnia.
In vivo microscopy of hepatic metastases: Dynamic observation of tumor cell invasion and interaction with Kupffer cells
Authors: Zuxing Kan, Krassnodar Ivancev, Anders Lunderquist, Patricia A. McCuskey, Robert S. McCuskey, Sidney Wallace
Journal: Hepatology (1995)

In vivo microscopy was used in the study of the biological behavior of tumor cells and of the activity of Kupffer cells in hepatic tumors in situ. Three tumor models, Friend erythroleukemia inoculated into Dilute Brown Aguti (DBA)/2 mice, murine colon adenocarcinoma (CT)-26 in Bagg Albino inbred albino (BALB)/c mice, and mammary cancer 13762 NF in Fischer rats, were investigated. Tumor cells showed a strong tendency to adhere to the sinusoidal endothelium, most frequently in the sinusoids near the tumors. Mechanical trapping of tumor cells in the narrow portion of hepatic sinusoids, a phenomenon suggested by previous investigators as a predominant pattern for tumor cells to arrest in the liver, was not confirmed. Our study documented that in tumor-bearing livers, as compared with normal control livers, the population size and the phagocytic capacity of Kupffer cells are increased in nontumorous areas but are significantly decreased inside the tumors. In vivo microscopic images showed that Kupffer cells are not only attracted to tumor cells in the hepatic circulation but also have the ability to phagocytose those tumor cells. In vivo microscopy has been shown to be a useful tool for dynamic studies in tumor biology, pathology, and pharmacology.