tbuckley/cabot-search huggingface dataset:
Correlation of molecular profiling and in vitro sensitivity in the TORC20 cell line panel
Authors: Ian Cree, Augusta Fernando, Louise Knight, Sharon Glaysher, Katherine Parker, Francis Gabriel
Journal: Clinical Cancer Research (2008)

A17    Background:  We have developed a panel of 20 cell lines which grow in serum-free media and show similar chemosensitivity to that obtained from tumour-derived cells. In this study, the expression of a profile of 92 genes involved in anticancer drug resistance and sensitivity has been compared with the  in vitro  chemosensitivity data.   Methods:  In vitro chemosensitivity was measured by ATP-based tumour chemosensitivity assay (ATP-TCA) and expressed as an index for each drug tested. Gene expression was measured by quantitative RT-PCR array using a (Applied Biosystems), standardised against HMBS/PBGD as the least variable housekeeping gene. Comparison of the ATP-TCA data with gene expression was performed by multiple linear regression (forward selection) for the 92 genes divided according to their role in apoptosis, DNA repair, drug metabolism, or proliferation by SPSS.   Results:  There was correlation between gene expression and in vitro sensitivity for the cell lines examined across a range of drugs and combinations as follows, given as adjusted R 2  values: cisplatin - 0.830, cyclophosphamide - 0.848, 5-fluorouracil - 0.590, vinorelbine - 0.372, paclitaxel - 0.590, epirubicin - 0.499, and topotecan - 0.637. A variety of genes entered the models, predominantly those involved in apoptosis and DNA repair.   Conclusion:  Similar results have been obtained from tumour-derived cells using the same gene sets, and previously presented at this meeting. The results suggest that it may be possible to use cell lines exposed to drugs in the ATP-TCA to develop companion diagnostics for new drugs in those tumours in which tissue is rarely available for sensitivity testing.
The correlation between urbanization and mortality of common respiratory diseases in China
Authors: Chun Wan, Fengfu Zhan, Liuqun Jia, Qianjing Hu, Fuqiang Wen
Journal: European Respiratory Journal (2013)

Background  Urbanization is associated with the mortality of respiratory diseases. This study aimed to analyze the relation between urbanization and the mortality of common respiratory diseases in China.  Methods  10 representative urbanization indicators (Total industrial output, Energy consumption, Civilian automobile, Length of Railways and Civil aviation routes, Paper, Cement, Plastic and Cigarette production, Selling area of commodity house) were retrieved from the State Statistical Database (2003-2009). Mortality of the common respiratory diseases were retrieved from the Health Statistics Yearbook of China. The correlation between the 10 indicators and mortality of common respiratory diseases was analyzed by Spearman rank correlation.  Results  Both levels of the 10 indicators and mortality of pneumonia, pneumoconiosis and lung cancer increased constantly, the mortality of chronic lower respiratory disease was downtrend from 2003 to 2009. The 10 indicators were positively correlated to mortality of pneumonia, pneumoconiosis and lung cancer (RS>0,P 0.05).  The 10 indicators significantly correlated with the mortality of pneumonia, pneumoconiosis and lung cancer in large city (RS>0,P 0.05). Conclusion  Urbanization may contribute to the increasing mortality of pneumonia, pneumoconiosis and lung cancer in China.
Decreased Wnt/β-catenin signaling in COPD: Possible involvement of Wnt antagonists
Authors: Ling-li Guo, Tao Wang, Lian Liu, Chun Wan, Fu-qiang Wen
Journal: European Respiratory Journal (2012)

Background : COPD is a devastating disease characterized by chronic bronchitis and emphysema. The Wnt/β-catenin signaling has been implicated in emphysema, but its role in the pathogenesis of chronic bronchitis remains unknown.   Methods : Human lung tissues were obtained from 4 groups of patients: healthy nosmokers (n=7), healthy smokers (n=7), COPD nosmokers (n=10) and COPD smokers (n=18). Human airway epithelial cells ( 16HBE ) were treated with cigarette smoke extract (CSE; 0, 2%, 4% or 8%) for 24h. Mice were treated with cigarette smoke (CS) exposure (200mg TPM/m3, 4h/d, 5d/wk) and SB-216763 injection (a GSK3β inhibitor, 3mg/kg/d,  i.p. ) for 1 month. The activation of Wnt /β-catenin signaling was analyzed by RT-PCR and western blot.   Results : We observed a significant increase in mRNA levels of Wnt antagonist Wif-1 (10.5-fold) and a decrease in Wnt receptor Fzd4 expression in COPD smokers as compared to COPD nonsmokers. Expression of β-catenin/Tcf4 was also reduced in COPD smokers compared with healthy smokers, indicating impaired Wnt activity in smoking-related COPD. In 16HBE cells, CSE induced the expression of Wnt antagonists Wif-1 and Dkk1, while reduced β-catenin and Tcf4/Lef1 expression. In vivo, the mRNA levels of Wnt antagonists Wif-1 and Sfrp1 were elevated 2.5-fold and 1.6-fold respectively in CS-exposed mice. SB-216763 treatment attenuated CS–induced BALF total leukocyte and macrophage accumulation, airway inflammation and β-catenin downregulation.   Conclusion : Decreased Wnt/β-catenin signaling may be involved in airway inflammation and airway epithelium injury. Overexpression of Wnt antagonists may contribute to this process, implicating potential therapeutic targets for the treatment of COPD.
Neuromuscular Blockade and Skeletal Muscle Weakness in Critically Ill Patients
Authors: Zudin Puthucheary, Jaikirty Rawal, Gamunu Ratnayake, Stephen Harridge, Hugh Montgomery, Nicholas Hart
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Section:ChooseTop of pageAbstract <<NMBAs in Clinical Practic...Studies and Trials Evalua...Sedation as a Potential R...Application of Historic N...Translational Pitfalls Wi...Future Clinical and Resea...ReferencesCITING ARTICLES
Second Malignancies After Treatment of Early-Stage Breast Cancer: Lumpectomy and Radiation Therapy Versus Mastectomy
Authors: Edward Obedian, Diana B. Fischer, Bruce G. Haffty
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the risk of second malignancies after lumpectomy and radiation therapy (LRT), and to compare it with that in a similar cohort of early-stage breast cancer patients undergoing mastectomy without radiation (MAST). PATIENTS AND METHODS: Between January 1970 and December 1990, 1,029 breast cancer patients at our institution underwent LRT. A cohort of 1,387 breast cancer patients who underwent surgical treatment by mastectomy (MAST), and who did not receive postoperative radiation during the same time period, served as a comparison group. Second malignancies were categorized as contralateral breast versus nonbreast. In the cohort of patients undergoing LRT, a detailed analysis was carried out with respect to age, disease stage, smoking history, radiation therapy technique, dose, the use of chemotherapy or hormone therapy, and other clinical and/or pathologic characteristics. RESULTS: As of March 1999, the median follow-up was 14.6 years for the LRT group and 16 years for the MAST group. The 15-year risk of any second malignancy was nearly identical for both cohorts (17.5% v 19%, respectively). The second breast malignancy rate at 15 years was 10% for both the MAST and LRT groups. The 15-year risk of a second nonbreast malignancy was 11% for the LRT and 10% for the MAST group. In the subset of patients 45 years of age or younger at the time of treatment, the second breast and nonbreast malignancy rates at 15 years were 10% and 5% for patients undergoing LRT versus 7% and 4% for patients undergoing mastectomy (P, not statistically significant). In the detailed analysis of LRT patients, second lung malignancies were associated with a history of tobacco use. There were fewer contralateral breast tumors in patients undergoing adjuvant hormone therapy, although this did not reach statistical significance. The adjuvant use of chemotherapy did not significantly affect the risk of second malignancies. CONCLUSION: There seems to be no increased risk of second malignancies in patients undergoing LRT using modern techniques, compared with MAST. Continued monitoring of these patient cohorts will be required in order to document that these findings are maintained with even longer follow-up periods. With nearly 15 years median follow-up periods, however, these data should be reassuring to women who are considering LRT as a treatment option.
Evaluation of unilateral complete occlusion and bilateral partial occlusion endobronchial valve treatments using quantitative CT
Authors: Maren Schuhmann, Daniela Gompelmann, Youbing Yin, Melissa Jensen, Philippe Raffy, Derek Hornberg, Claus Peter Heussel, Susan Wood, Felix J.F. Herth, Ralf Eberhardt
Journal: European Respiratory Journal (2013)

Background: Unilateral complete occlusion (UCO) and bilateral partial occlusion (BPO) methods have been used in bronchoscopy-guided device therapies for severe emphysema patients.  Purpose: To evaluate UCO and BPO treatments using quantitative CT.  Methods: Lobe volumes of baseline and 3-month follow-up CT scans were analyzed for each patient in the two groups (UCO: 9; BPO: 10). Fissure integrity (FI), emphysema score (ES), and heterogeneity score (HS) were calculated from baseline scans and valves were reviewed in follow-up scans.  Results: The targeted lobe volume reduction (TLVR) in the UCO group (-769.4±652.8cc) was significantly larger than in the BPO group (-67.0±125cc, p=0.01). FI, EP and HS did not show significant differences between the two groups. In the UCO group, TLVR≥350cc was observed in 6 cases, of which 4 had fully collapsed lobes. By contrast, only 1patient in the BPO group had TLVR≥350cc. There were incomplete lobar occlusions in all BPO cases as defined by treatment protocol. 3 non-responding UCO cases showed evidence of incomplete occlusion (e.g. incomplete fissures, inadvertent open airways).  Conclusions: Complete occlusion of the target lobe seems essential for responsive therapy. Quantitative CT has promise to effectively plan lobar reduction therapies and monitor treatment response to increase the yield of these promising therapies.
Low-Dose 5-Aza-2′-Deoxycytidine, a DNA Hypomethylating Agent, for the Treatment of High-Risk Myelodysplastic Syndrome: A Multicenter Phase II Study in Elderly Patients
Authors: P. Wijermans, M. Lübbert, G. Verhoef, A. Bosly, C. Ravoet, M. Andre, A. Ferrant
Journal: Journal of Clinical Oncology (2000)

PURPOSE: 5-Aza-2′-deoxycytidine (decitabine; DAC) is a DNA hypomethylating agent that has shown a 50% response rate in a small phase II study in elderly patients with high-risk myelodysplastic syndrome. We performed a second, multicenter phase II study in a larger group of patients to confirm our findings and to study the toxicity of DAC. PATIENTS AND METHODS: Between June 1996 and September 1997, 66 patients (median age, 68 years) from seven centers received DAC 45 mg/m 2 /d for 3 days every 6 weeks. For patients in whom a complete response (CR) was reached after two courses, two further cycles were administered as consolidation therapy. In case of a stable disease situation, improvement, or a partial response (PR), a maximum of six cycles was administered. The primary end points were response rate and toxicity. The secondary end points were response duration, survival from the start of therapy, and overall survival. RESULTS: The observed overall response rate was 49%, with a 64% response rate in the patients with an International Prognostic Scoring System (IPSS) high-risk score. The actuarial median response duration was 31 weeks, with a response duration of 39 weeks and 36 weeks for patients who reached a PR or CR, respectively. The actuarial median survival time from the time of diagnosis was 22 months and from the start of therapy was 15 months. For the IPSS high-risk group, the median survival time was 14 months. The median progression-free survival time was 25 weeks. Myelosuppression was rather common, and the treatment-related mortality rate was 7% and was primarily associated with pancytopenia and infection. Significant responses were observed with regard to megakaryopoiesis, with increases in platelet counts having already occurred after one cycle of DAC therapy in the majority of the responding patients. CONCLUSION: We were able to confirm our previous observation that DAC therapy was effective in half of the studied patients with high-risk myelodysplastic syndrome and is especially active in the patients with the worst prognoses. Myelosuppression was the only major adverse effect observed.
Assessment of the time course of chronic inflammation in the murine house dust mite model
Authors: Stephen Jordan, Robert Carrington, David Lanham, James Cartwright, Rachel Armstrong, Kenneth Meecham
Journal: European Respiratory Journal (2012)

House dust mite (HDM) allergens are associated with allergic disorders and the use of this clinically relevant allergen is increasing in animal models. We assessed the chronic inflammatory time course and the anti-inflammatory efficacy of a phosphodiesterase 4 inhibitor and a corticosteroid. BALB/c mice were challenged intranasally with HDM for 5 days/week for 5 weeks. Animals were sacrificed weekly 24 hours after final challenge and recruitment of inflammatory cells assessed in bronchoalveolar lavage fluid (BALF). Lung tissue was stained for the evaluation of a histopathological response. Roflumilast (10 mg/kg) and prednisolone (10 mg/kg) were administered orally twice daily from week 3. Chronic HDM extract exposure resulted in significant recruitment of eosinophils, neutrophils, lymphocytes and macrophages as early as week 1, peaking (1.13±0.32, 0.31±0.05, 0.66±0.10 and 0.33±0.04 x106cells/animal respectively) between Weeks 3 and 5. Within the lymphocyte population the proportion of B cells increased from 4 to 46% over the 5 week exposure period. Mice developed perivascular, peribronchiolar and alveolar inflammation which increased in severity during the five week exposure period. The inflammation was accompanied by epithelial and mucus cell hypertrophy/hyperplasia in the bronchi and bronchioles which reached maximum severity during weeks 3 to 5. Perivascular/peribronchiolar fibrosis peaked in week 5. Therapeutic treatment with prednisolone and roflumilast significantly (P<0.001) inhibited BALF cell recruitment and reduced the severity of the airway remodelling suggesting this model, in our laboratory, has the potential to test novel compounds for the treatment of allergic disorders.
Corneel Heymans and his work on respiratory reflexes
Authors: AF De Schaepdryver
Journal: European Respiratory Journal (1988)

For many years is was universally believed that the effects of hypoxia and/or hypercapnia were exerted directly on the ponto-medullary respiratory centres.This belief persisted until 1926, when Jan-Frans and Corneel Heymans published their discovery of peripheral chemoreceptor reflexogenic zones (1].Jan-Frans Heymans (1859-1932) was the founder of the Department of Experimental Pharmacology at the University of Ghent, the first of its kind in Belgium.Heymans's early interest was in tuberculosis.He was the first to use on a large scale, in 1905, in laboratory animals and cattle, a vaccine prepared from attenuated tubercle bacilli.Famous son following famous father, Corneel Heymans (1892-1968), his medical studies interrupted by voluntary military service in the trench artillery during World War I, completed his medical training at his home town University in 1921.
Lack of Prognostic Significance of p53 and <i>K-ras</i> Mutations in Primary Resected Non–Small-Cell Lung Cancer on E4592: A Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy
Authors: Joan H. Schiller, Sudeshna Adak, Richard H. Feins, Steven M. Keller, Willard A. Fry, Robert B. Livingston, M. Elizabeth M. Hammond, Barbara Wolf, Linda Sabatini, James Jett, Leslie Kohman, David H. Johnson
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. RESULTS: Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. CONCLUSION: p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.
Heart rate recovery after pulmonary rehabilitation is associated with improvement of autonomic nervous system, quality of life and daily physical activity
Authors: Mathieu Berger, Pierre Labeix, Jean Claude Barthelemy, Frederic Roche, Frederic Costes
Journal: European Respiratory Journal (2014)

Autonomic nervous system (ANS) is severely altered in COPD patients and is improved after pulmonary rehabilitation. It was also shown that heart rate recovery (HRR)≥12 beats one minute after exercise was a good index of parasympathetic tone.  We studied 33 COPD patients before and after a 2-month pulmonary rehabilitation (PR) and recorded HRR at the first minute following a symptom limited cycling exercise and ANS measured from a night ECG recording. Quality of life was assessed by the CAT questionnaire. Daily physical activity was evaluated using an actimeter.  At baseline, the group with a HRR≥12 (10 patients, 30%), did not differ from HRRl12 group for global ANS activity (SDNN) and parasympathetic index (PNN50 and rMSSD). After PR, HRR tends to increase from 8.3±9.0 to 11.2±9.5 (P=0.06). In the HRR≥12 group only, SDNN, PNN50 and rMSSD improved significantly (all p=0.01). CAT score was also significantly better and steps count increased in this group. In the whole population, we found weak but significant correlations between HRR after PR and night parasympathetic tone (PNN50, r=0.39, p=0.03; rMSSD, r=0.41, p=0.03). CAT score was inversely related to HRR (r=0.45, p=0.01) and steps count increased with HRR (r=0.55, p=0.008).  We conclude that HRR≥ 12 is not a reliable index of parasympathetic tone in COPD patients before PR but reflects the improvements of ANS index, quality of life and daily physical activity induced by PR.
Growth Factors in Leukemia
Authors: Olga Frankfurt, Martin S. Tallman
Journal: Journal of the National Comprehensive Cancer Network (2007)

The role of myeloid growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, in the management of acute myeloid and acute lymphoblastic leukemias has been evaluated extensively in multiple clinical trials. Growth factors have been given before, concurrently, or sequentially with chemotherapy with the goal of reducing the duration of neutropenia and consequently the incidence and severity of infections, and improving the rate of remissions and overall survival. They also have been studied as chemotherapy-sensitizing agents in an effort to recruit dormant myeloid stem cells into the sensitive phase of the cycle. Additionally, growth factors, shown to stimulate proliferation and differentiation of leukemia cells in vitro, were evaluated as monotherapy in patients with acute leukemia. Most studies show modest improvement in the duration of the neutropenia, which does not consistently correlate with the severity of infection, rate or duration of remissions, or disease-free and overall survival. Attempts to enhance the chemosensitivity of the leukemic cells and decrease drug resistance failed to improve the rate of remission and survival in several large series. However, more recent reports suggested an improved outcome in younger patients with acute myeloid leukemia with normal karyotype. Several anecdotal case reports have shown that growth factor monotherapy can induce a complete remission in patients with acute leukemia. Data from the published clinical trials do not seem to support emergence of drug-resistant leukemia, worsening toxicity, and bone marrow failure with growth factor administration.
Development of a viable bronchotracheal stent *th in vivo spray application of respiratory epithelial cells
Authors: Anja Lena Thiebes, Stefanie Albers, Stefan Jockenhoevel, Christian G. Cornelissen
Journal: European Respiratory Journal (2014)

A novel concept for a viable airway stent - the PulmoStent - was developed to overcome current limitations of airway stenting for bronchotracheal cancer. A custom-made nitinol stent is combined with a separating layer from polyurethane to inhibit restenosis. The distinguishing feature of this concept is a tissue-engineered respiratory epithelial layer on the luminal side which guarantees mucociliary clearance.  To avoid complications with crimping and implantation of a cell seeded stent, we have analyzed the possibility of  in vivo  seeding of respiratory cells with a spraying device. For better adherence to the polyurethane layer, cells will be embedded in a thin layer of fibrin gel, as fibrin gel was proven to be a suitable scaffold for respiratory epithelial cells (Cornelissen, C.G. et al. Ann Biomed Eng. 2012; 40(3): 679-687). In an  in vitro  study, survival of respiratory epithelial cells when spray processed with a nozzle and a catheter system for bronchoscopy was compared to non-sprayed controls and showed acceptable results of survival rates up to 88.5 % of the control. Furthermore, we have confirmed respiratory cell differentiation when embedded in a thin layer of fibrin gel  in vitro . As a next step, we will prove the PulmoStent-concept  in vivo  in a large animal model. Here, respiratory epithelial cells will be removed from ovine tracheal or nasal mucosa via brush biopsy, cultured and autologously transplanted.  Hence, the novel concept of the PulmoStent might improve palliative treatment of bronchotracheal stenoses by combination of stent-technology with tissue-engineered epithelial cells.
Brief Communication: Intracisternal A and C Particles in Mouse Neurons: A Thin-Section Study of Normal Trigeminal Ganglion and C1300 Neuroblastoma2
Authors: H. Herrlinger, A. P. Anzil, D. Stavrou, R. Heumann, B. Hamprecht, K. Blinzinger
Journal: JNCI Journal of the National Cancer Institute (1975)

Trigerminal ganglia of 4 adult albino mice of the NMRI outbred stock were examined by electron microscopy. In all animals, about 10% of the neurons contained intracisternal A particles. Isolated structures resembling intracisternal A particles could be detected in atleast 50% of the nerve cells and in a few Schwann cells. Budding at the cell surface and/or extracellular type-C particles were not observed. An intracerebrally transplanted mouse C1300 neuroblastoma was likewise studied. Most tumor cells exhibited large numbers of intracisternal A particles having the same ultrastructure as the particles in trigeminal neurons. In addition, budding and extracellular type-C particles were occasionally observed.