tbuckley/cabot-search huggingface dataset:
Targeting of erbB3 receptor to overcome resistance in cancer treatment
Authors: Jian Ma, Hui Lyu, Jingcao Huang, Bolin Liu
Journal: Molecular Cancer (2014)

The erbB receptors, including the epidermal growth factor receptor (EGFR), erbB2 (also known as HER2/neu), erbB3 (or HER3), and erbB4 (or HER4), are often aberrantly activated in a wide variety of human cancers. They are excellent targets for selective anti-cancer therapies because of their transmembrane location and pro-oncogenic activity. While several therapeutic agents against erbB2 and/or EGFR have been used in the treatment of human cancers with efficacy, there has been relatively less emphasis on erbB3 as a molecular target. Elevated expression of erbB3 is frequently observed in various malignancies, where it promotes tumor progression via interactions with other receptor tyrosine kinases (RTKs) due to its lack of or weak intrinsic kinase activity. Studies on the underlying mechanisms implicate erbB3 as a major cause of treatment failure in cancer therapy, mainly through activation of the PI-3 K/Akt, MEK/MAPK, and Jak/Stat signaling pathways as well as Src kinase. It is believed that inhibition of erbB3 signaling may be required to overcome therapeutic resistance and effectively treat cancers. To date, no erbB3-targeted therapy has been approved for cancer treatment. Targeting of erbB3 receptor with a monoclonal antibody (Ab) is the only strategy currently under preclinical study and clinical evaluation. In this review, we focus on the role of erbB3-initiated signaling in the development of cancer drug resistance and discuss the latest advances in identifying therapeutic strategies inactivating erbB3 to overcome the resistance and enhance efficacy of cancer therapeutics.
Should we judge a mask by its cover?
Authors: A A Jeffrey, P M Warren
Journal: Thorax (1992)

BACKGROUND: A table of the approximate ranges of inspired oxygen delivered at given oxygen flow rates is often given on the packaging of oxygen masks. A study was carried out to check the inspired oxygen concentration given by one of the new masks, which has been designed to be used with or without the Venturi attachment as a result of the proposal to use it without the Venturi attachment as a general purpose mask for emergency use. METHODS: Measurements were made at resting respiratory rate and 26 breaths/min in 12 normal subjects. Continuous oxygen and carbon dioxide concentrations were recorded at the lips with a mass spectrometer, and inspired oxygen concentrations were calculated from end tidal values by means of the alveolar gas equation. Measurements were made at oxygen flow rates of 2, 4, and 6 l/min for the mask alone and at 2 and 4 l/min with both the 24% and the 28% Venturi attachments. RESULTS: Without the Venturi attachment the mask gave average inspired oxygen concentrations 8-10% greater than are stated on the packaging at oxygen flow rates of 2, 4, and 6 l/min at resting respiratory rates of 8-20 breaths/min, some individuals receiving 30% more than expected. Addition of the interchangeable Venturi attachments designed to give 24% and 28% inspired oxygen delivered average concentrations within 2% of the expected concentrations, no individual receiving more than 5% above the expected concentrations. CONCLUSIONS: The labelling on the packaging of oxygen masks may lead to inappropriate use by those not expert in prescribing oxygen therapy. Caution is still needed when a single multipurpose mask is being selected for emergency use, where accurate delivery of low concentrations of oxygen is vital for some patients.
Recommendations for the content and conduct of European League Against Rheumatism (EULAR) musculoskeletal ultrasound courses
Authors: E Naredo, J W J Bijlsma, P G Conaghan, C Acebes, P Balint, H Berner-Hammer, G A W Bruyn, P Collado, M A D'Agostino, J J de Agustin, E de Miguel, E Filippucci, W Grassi, A Iagnocco, D Kane, J M Koski, B Manger, L Mayordomo, I Moller, C Moragues, E Rejon, M Szkudlarek, L Terslev, J Uson, R J Wakefield, W A Schmidt
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To develop education guidelines for the conduct of future European League Against Rheumatism (EULAR) musculoskeletal ultrasound (MSUS) courses. <h3>Methods:</h3> We undertook a consensus-based, iterative process using two consecutive questionnaires sent to 29 senior ultrasonographer rheumatologists who comprised the faculty of the 14th EULAR ultrasound course (June 2007). The first questionnaire encompassed the following issues: type of MSUS educational model; course timing; course curriculum; course duration; number of participants per teacher in practical sessions; time spent on hands-on sessions; and the requirements and/or restrictions for attendance at the courses. The second questionnaire consisted of questions related to areas where consensus had not been achieved in the first questionnaire, and to the topics and pathologies to be assigned to different educational levels. <h3>Results:</h3> The response rate was 82.7% from the first questionnaire and 87.5% from the second questionnaire. The respondents were from 11 European countries. The group consensus on guidelines and curriculum was for a three-level education model (basic, intermediate and advanced) with timing and location related to the annual EULAR Congresses. The topics and pathologies to be included in each course were agreed. The course duration will be 20 h. There will be a maximum of six participants per teacher and 50–60% of total time will be spent on practical sessions. There was also agreement on prerequisite experience before attending the intermediate and advanced courses. <h3>Conclusion:</h3> We have developed European agreed guidelines for the content and conduct of EULAR ultrasound courses, which may also be recommended to national and local MSUS training programmes.
<i>ERCC1</i> and Thymidylate Synthase mRNA Levels Predict Survival for Colorectal Cancer Patients Receiving Combination Oxaliplatin and Fluorouracil Chemotherapy
Authors: Yoshinori Shirota, Jan Stoehlmacher, Jan Brabender, Yi-Ping Xiong, Hiroyuki Uetake, Kathleen D. Danenberg, Susan Groshen, Denise D. Tsao-Wei, Peter V. Danenberg, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To test the hypotheses of whether the relative mRNA expression of the thymidylate synthase (TS) gene and the excision cross-complementing (ERCC1) gene are associated with response to and survival of fluorouracil (5-FU)/oxaliplatin chemotherapy in metastatic colorectal cancer. PATIENTS AND METHODS: Patients had progressive stage IV disease after unsuccessful 5-FU and irinotecan chemotherapy. All patients were evaluated for eligibility for a compassionate 5-FU/oxaliplatin protocol. cDNA was derived from paraffin-embedded tumor specimens to determine TS and ERCC1 mRNA expression relative to the internal reference gene beta-actin using fluorescence-based, real-time reverse transcriptase polymerase chain reaction. RESULTS: The median TS gene expression level from 50 metastasized tumors was 3.4 × 10 −3 (minimum expression, 0.18 × 10 −3 ;maximum expression, 11.5 × 10 −3 ), and the median ERCC1 gene expression level was 2.53 × 10 −3 (minimum, 0.0; maximum, 14.61 × 10 −3 ). The gene expression cutoff values for chemotherapy nonresponse were 7.5 × 10 −3 for TS and 4.9 × 10 −3 for ERCC1. The median survival time for patients with TS ≤ 7.5 × 10 −3 (43 of 50 patients) was 10.2 months, compared with 1.5 months for patients with TS greater than 7.5 × 10 −3 (P &lt; .001). Patients with ERCC1 expression ≤ 4.9 × 10 −3 (40 of 50 patients) had a median survival time of 10.2 months, compared with 1.9 months for patients with ERCC1 expression greater than 4.9 × 10 −3 (P &lt; .001). A TS of 7.5 × 10 −3 segregated significantly into response, stable disease, and progression (P = .02), whereas the association between ERCC1 and response did not reach statistical significance (P = .29). CONCLUSION: These data suggest that intratumoral ERCC1 mRNA and TS mRNA expression levels are independent predictive markers of survival for 5-FU and oxaliplatin combination chemotherapy in 5-FU–resistant metastatic colorectal cancer. Precise definition of the best TS cut point will require further analysis in a large, prospective study.
The effect of an 8-week outpatient rehabilitation programme on chest expansion and ventilatory parameters in patients with COPD
Authors: Katerina Neumannova, Jakub Zatloukal, Vitezslav Kolek
Journal: European Respiratory Journal (2011)

Background:  Dysfunction of the breathing mechanisms could lead to an increased inspiratory effort and to a higher prevalence of breathing disorders during activities of daily living in patients with COPD.   Aim:  To assess whether patients with COPD have different chest expansion (CE) in comparison with healthy controls and whether the rehabilitation programme (RP) can influence CE and ventilatory parameters in COPD patients.   Methods:  The examined group consisted of 36 medically stable adults with COPD (aged 62.9±6.7 years, stage II) who have undergone an 8-week outpatient RP (breathing and postural control exercises, airway clearance techniques and soft tissue techniques) and 30 healthy controls (aged 63.5±3.0 years). Lung function test and CE were measured at baseline and after 8 weeks.   Results:  COPD patients had significantly reduced CE in comparison with control group at baseline. CE was significantly higher after RP in patients with COPD and there was no significant difference among control group and COPD patients after RP.  There was an improvement of ventilatory parameters in COPD patients after RP, although the severity of the peripheral airway obstruction remained at the same level.   Conclusion:  Our results show that physiotherapy treatment approaches can influence chest mobility and improve breathing mechanisms in COPD patients.
α-Glucosidase Inhibitors for Patients With Type 2 Diabetes
Authors: Floris A. van de Laar, Peter L. Lucassen, Reinier P. Akkermans, Eloy H. van de Lisdonk, Guy E. Rutten, Chris van Weel
Journal: Diabetes Care (2005)

OBJECTIVE—To review the effects of monotherapy with α-glucosidase inhibitors (AGIs) for patients with type 2 diabetes, with respect to mortality, morbidity, glycemic control, insulin levels, plasma lipids, body weight, and side effects. RESEARCH DESIGN AND METHODS—We systematically searched the Cochrane Central register of Controlled Trials, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, and reference lists, and we contacted experts and manufacturers. Inclusion criteria were randomized controlled trials of at least 12 weeks’ duration, AGI monotherapy compared with any intervention, and one of the following outcome measures: mortality, morbidity, GHb, blood glucose, lipids, insulin levels, body weight, or side effects. Two independent reviewers assessed all abstracts, extracted all data, and assessed quality. We contacted all authors for data clarification. Continuous data were expressed as weighted mean differences and analyzed with a random-effects model. Possible influences of study characteristics and quality were assessed in sensitivity and meta-regression analyses. RESULTS—Forty-one studies were included in the review (30 acarbose, 7 miglitol, 1 voglibose, and 3 combined), and heterogeneity was limited. We found no evidence for an effect on mortality or morbidity. Compared with placebo, AGIs had a beneficial effect on GHb (acarbose −0.77%; miglitol −0.68%), fasting and postload blood glucose and postload insulin. With acarbose dosages higher than 50 mg t.i.d., the effect on GHb was the same, but the occurrence of side effects increased. Acarbose decreased the BMI by 0.17 kg/m2 (95% CI 0.08–0.26). None of the AGIs had an effect on plasma lipids. Compared with sulfonylurea, AGIs seemed inferior with respect to glycemic control, but they reduced fasting and postload insulin levels. For comparisons with other agents, little data were available. CONCLUSIONS—We found no evidence for an effect on mortality or morbidity. AGIs have clear beneficial effects on glycemic control and postload insulin levels but not on plasma lipids. There is no need for dosages higher than 50 mg acarbose t.i.d.
Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene
Authors: Y Berkun
Journal: Annals of the Rheumatic Diseases (2004)

There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity.To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis.A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group.The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed.1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.
A randomised trial of primary tamoxifen versus mastectomy plus adjuvant tamoxifen in fit elderly women with invasive breast carcinoma of high oestrogen receptor content: long-term results at 20 years of follow-up
Authors: S.J. Johnston, F.S. Kenny, B.M. Syed, J.F.R. Robertson, S.E. Pinder, L. Winterbottom, I.O. Ellis, R.W. Blamey, K.L. Cheung
Journal: Annals of Oncology (2012)
Intrinsic Renal Cells Are the Major Source of Tumor Necrosis Factor Contributing to Renal Injury in Murine Crescentic Glomerulonephritis
Authors: Jennifer R Timoshanko, Jonathon D Sedgwick, Stephen R Holdsworth, Peter G Tipping
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Macrophages are prominent participants in crescentic glomerulonephritis (GN) and have been suggested to be the major source of TNF in this cell-mediated form of glomerular inflammation. Intrinsic renal cells also have the capacity to produce TNF. For dissecting the contribution of local <i>versus</i> bone marrow (BM)-derived TNF in inflammatory renal injury, TNF chimeric mice were created by transplanting normal wild-type (WT) BM into irradiated TNF-deficient recipients (WT→TNF<sup>−</sup><sup>/</sup><sup>−</sup> chimeras) and <i>vice versa</i> (TNF<sup>−</sup><sup>/</sup><sup>−</sup>→WT chimeras). A model of crescentic GN induced by an intravenous injection of sheep anti-murine glomerular basement membrane antibody was studied in WT mice, mice with complete TNF deficiency (TNF−/−), and chimeric mice. Crescentic GN was attenuated in TNF−/− mice with fewer crescents (crescents, 13.7 ± 1.7% of glomeruli) and reduced functional indices of renal injury (serum creatinine, 15.2 ± 0.8 μmol/L). Similar protection (crescents, 14.3 ± 1.9% of glomeruli; serum creatinine, 18.9 ± 1.1 μmol/L) was observed in chimeric mice with intact BM but absent renal-derived TNF (WT→TNF<sup>−</sup><sup>/</sup><sup>−</sup> chimeras), suggesting a minor contribution of infiltrating leukocytes to TNF-mediated renal injury. Chimeric mice with TNF-deficient leukocytes but intact intrinsic renal cell-derived TNF (crescents, 20.5 ± 2.0% of glomeruli; serum creatinine, 21.6 ± 1.4 μmol/L) developed similar crescentic GN to WT mice (crescents, 22.3 ± 1.4% of glomeruli; serum creatinine, 24.8 ± 1.9 μmol/L). Cutaneous delayed-type hypersensitivity after subdermal challenge with the nephritogenic antigen was attenuated in the absence of BM cell-derived TNF but unaffected in WT→TNF<sup>−</sup><sup>/</sup><sup>−</sup> chimeric mice. These studies suggest that intrinsic renal cells are the major cellular source of TNF contributing to inflammatory injury in crescentic GN. E-mail: peter.tipping@med.monash.edu.au
Survival for colorectal cancer
Authors: S S CROSS
Journal: Gut (2001)

Editor,—The EUROCARE study of Gatta et al ((2000) Gut 47:533–8; [OpenUrl][1][PubMed][2][Web of Science][3]) provides important information on survival for colorectal cancer in different parts of Europe. In particular, it relates survival to stage, a feature which was absent from earlier studies.1-3 The study also looks at procedures used in determining stage which may be important factors in accurate staging—for example, higher numbers of lymph nodes sampled will be more likely to detect lymph node metastases and consequent upstaging of tumours.4 However, the usefulness of this study is reduced by inaccuracies in the descriptions of staging and choice of staging system. The authors have chosen to use Dukes' staging system which has been in use for at least 50 years and has been well characterised by many studies with long term follow up.5-9 Unfortunately, they have given incorrect labels to some of the stages in this system. In tables 2 and 3, Dukes' stages A and B are described as being “confined to the bowel wall” which is incorrect. Dukes' stage A is invasion into, but not through, the bowel wall whereas Dukes' stage B is invasion through the bowel wall but without lymph node metastases.7 Dukes' stages A and B combined could have been correctly labelled as no lymph node metastases. In the methods section … [1]: {openurl}?query=rft.jtitle%253DInternational%2Bjournal%2Bof%2Bcancer.%2B%2BJournal%2Binternational%2Bdu%2Bcancer%26rft.stitle%253DInt%2BJ%2BCancer%26rft.aulast%253DSant%26rft.auinit1%253DM.%26rft.volume%253D63%26rft.issue%253D1%26rft.spage%253D43%26rft.epage%253D48%26rft.atitle%253DComparisons%2Bof%2Bcolon-cancer%2Bsurvival%2Bamong%2BEuropean%2Bcountries%253A%2BThe%2BEurocare%2BStudy.%26rft_id%253Dinfo%253Apmid%252F7558450%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=7558450&link_type=MED&atom=%2Fgutjnl%2F48%2F6%2F868.atom [3]: /lookup/external-ref?access_num=A1995RX63400008&link_type=ISI
Longitudinal study of lung function in a cohort of primary ciliary dyskinesia
Authors: A Ellerman, H Bisgaard
Journal: European Respiratory Journal (1997)

Patients with primary ciliary dyskinesia (PCD) have pronounced stasis of their respiratory secretions and therefore recurrent lower airway infections, which raises concerns for the development of lung function. Twenty four patients with PCD have been studied prospectively with a standardized regime in our clinic for 2-16 yrs with clinic visits, including spirometry 2-4 times per year, daily physiotherapy and monthly sputum cultures with subsequent specific antibiotic treatment. Lung function was significantly lower in the 12 PCD patients entering the cohort as adults when compared to the PCD patients entering as children (forced vital capacity (FVC) 70 versus 85% predicted; forced expiratory volume in one second (FEV1) 59 versus 72% pred). The lung damage did not relate to the type of ciliary dyskinesia. During the subsequent surveillance of the groups for a median of 14 and 7 yrs, respectively, the lung function remained stable in most patients. It is concluded that primary ciliary dyskinesia is accompanied by a progressive deterioration in lung function if undertreated, but lung function can be maintained with appropriate antibiotic treatment and regular physiotherapy. This emphasizes the need for early diagnosis of primary ciliary dyskinesia.
Depression and Cognitive Complaints Following Mild Traumatic Brain Injury
Authors: Jonathan M Silver, Thomas W McAllister, David B Arciniegas
Journal: American Journal of Psychiatry (2009)

Traumatic brain injury (TBI) is a common occurrence with multiple possible neuropsychiatric sequelae, including problems with cognition, emotion, and behavior. While many individuals experience significant improvement over the first months following mild TBI, a nontrivial minority will develop persistent, functionally impairing post-TBI symptoms. Depression and cognitive impairment are among the most common such symptoms, and they may respond to a combination of rehabilitative and pharmacologic treatments. This article discusses the clinical approach to treating an individual with depression and cognitive complaints following mild TBI. Recommendations regarding the diagnosis, evaluation, and treatment of these problems are offered.