tbuckley/cabot-search huggingface dataset:
G34, Another Connection between MYCN and a Pediatric Tumor
Authors: Miller Huang, William A. Weiss
Journal: Cancer Discovery (2013)

Abstract Summary: Recurrent mutations in H3F3A at K27 and G34 are frequent in pediatric glioblastoma, but it is unclear how these mutations promote tumorigenesis. In this issue of Cancer Discovery, Bjerke and colleagues identify mutations at G34 in H3F3A that result in elevated expression of MYCN as a potential mechanism in gliomagenesis. Cancer Discov; 3(5); 484–6. ©2013 AACR. See related article by Bjerke et al., p. 512
Let-7 Expression Is a Significant Determinant of Response to Chemotherapy through the Regulation of IL-6/STAT3 Pathway in Esophageal Squamous Cell Carcinoma
Authors: Keijiro Sugimura, Hiroshi Miyata, Koji Tanaka, Rie Hamano, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichiro Doki
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Cisplatin-based chemotherapy is widely used for esophageal cancer, sometimes in combination with surgery/radiotherapy, but poor response to chemotherapy is not uncommon. The aim of this study was to examine whether miRNA expression is useful to predict the response to chemotherapy in patients with esophageal cancer. Experimental Design: Using pretreatment biopsy samples from 98 patients with esophageal cancer who received preoperative chemotherapy, we measured the expression level of several miRNAs whose expression was altered in cisplatin-resistant esophageal cancer cell lines compared with those parent cell lines and examined the relationship between the miRNA expression and response to chemotherapy. In vitro assays were conducted to clarify the mechanism of miRNA-induced changes in chemosensitivity. Results: The expression levels of 15 miRNAs were altered in cisplatin-resistant cells. Of these, low expression of let-7b and let-7c in before-treatment biopsies from 74 patients of the training set correlated significantly with poor response to chemotherapy, both clinically and histopathologically. Low expression of let-7c also correlated with poor prognosis (P = 0.032). The relationship between let-7b and let-7c expression and response to chemotherapy was confirmed in the other 24 patients of the validation set. In in vitro assay, transfection of let-7c restored sensitivity to cisplatin and increased rate of apoptosis after exposure to cisplatin. Let-7c directly repressed cisplatin-activated interleukin (IL)-6/STAT3 prosurvival pathway. Conclusions: Let-7 expression in esophageal cancer can be potentially used to predict the response to cisplatin-based chemotherapy. Let-7 modulates the chemosensitivity to cisplatin through the regulation of IL-6/STAT3 pathway in esophageal cancer. Clin Cancer Res; 18(18); 5144–53. ©2012 AACR.
Depressive and Anxiety Disorders in Women With HIV Infection
Authors: Mary F. Morrison, John M. Petitto, Thomas Ten Have, David R. Gettes, Margaret S. Chiappini, Anita L. Weber, Priscilla Brinker-Spence, Russell M. Bauer, Steven D. Douglas, Dwight L. Evans
Journal: American Journal of Psychiatry (2002)

This study examined whether there were differences in the rate of depressive and anxiety disorders between HIV-infected women (N=93) and a comparison group of uninfected women (N=62). Secondary objectives were to examine correlates of depression in HIV-infected women-including HIV disease stage and protease inhibitor use-and the associations between symptoms of depression or anxiety and other potential predictor variables.Subjects underwent extensive semiannual clinical, psychiatric, neuropsychological, and immunological evaluations. Depressive and anxiety disorder diagnoses were assessed by using the Structured Clinical Interview for DSM-IV. Symptoms of depression and anxiety were evaluated with the Hamilton Depression Rating Scale (the 17-item version and a modified 11-item version) and the Hamilton Anxiety Rating Scale, respectively.The rate of current major depressive disorder was four times higher in HIV-seropositive women (19.4%) than in HIV-seronegative women (4.8%). Mean depressive symptom scores on the 17-item Hamilton depression scale also were significantly higher, overall, in the HIV-infected women (mean=8.7, SD=8.0) relative to comparison subjects (mean=3.3, SD=5.8). There was no significant between-group difference in the rate of anxiety disorders. However, HIV-seropositive women had significantly higher anxiety symptom scores (mean=8.8, SD=8.9) than did HIV-seronegative women (mean=3.6, SD=5.5). Both groups had similar substance abuse/dependence histories, but adjusting for this factor had little impact on the relationship of HIV status to current major depressive disorder.HIV-seropositive women without current substance abuse exhibited a significantly higher rate of major depressive disorder and more symptoms of depression and anxiety than did a group of HIV-seronegative women with similar demographic characteristics. These controlled, clinical findings extend recent epidemiologic findings and underscore the importance of adequate assessment and treatment of depression and anxiety in HIV-infected women.
Distearoyl phosphatidylglycerol liposomes improve surface and transport properties of CF mucus
Authors: S Girod de Bentzmann, D Pierrot, C Fuchey, JM Zahm, JL Morancais, E Puchelle
Journal: European Respiratory Journal (1993)

We have previously shown that a decreased level of phosphatidylglycerol in cystic fibrosis (CF) respiratory mucus is partly responsible for its marked adhesiveness and stickiness, which impair mucus transport, and that distearoyl phosphatidylglycerol (DSPG) was the most efficient form of phosphatidylglycerol in the enhancement of respiratory mucus clearance. The aim of our study was to analyse the effect of distearoyl phosphatidylglycerol liposomes on the transport by cough and cilia of cystic fibrosis respiratory mucus. The surface and transport properties of mucus were measured: 1) on native cystic fibrosis mucus; 2) on cystic fibrosis mucus complemented with DSPG liposomes at a non-cytotoxic concentration; and 3) on cystic fibrosis mucus complemented with water. The work of adhesion of cystic fibrosis mucus was significantly decreased by DSPG liposomes, but not by water. For mucociliary transport, the cystic fibrosis mucus was transported at a higher rate with DSPG liposomes and water compared to native cystic fibrosis mucus. The cough clearance of cystic fibrosis respiratory mucus was significantly improved in the presence of DSPG and water, but the effect was more pronounced with DSPG liposomes than with water. We conclude that the use of DSPG liposomes as a lubricating agent proves to be an interesting therapeutic approach for improving the cough and mucociliary transport in cystic fibrosis patients.
Silica Dust and Lung Cancer: Results From the Nordic Occupational Mortality and Cancer Incidence Registers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E Lynge, K Kurppa, L Kristofersen, H Malker, H Sauli
Journal: JNCI Journal of the National Cancer Institute (1986)

Autopsy studies of the relationship between silicosis and lung cancer have been mainly negative; but recent epidemiologic studies have indicated a positive association, and an excess lung cancer risk has been observed in some occupational groups with exposure to silica dust. For the further shedding of light on the possible association between silica dust and lung cancer, analysis was made on mortality and cancer incidence data available in census-based record linkage studies from the Nordic countries for males in occupational groups with potential exposure to silica dust. The study showed an excess lung cancer risk for foundry workers in all the Nordic countries and for miners in Sweden. These results were consistent with findings from previous in-depth epidemiologic studies. The lung cancer risk did not differ significantly from that of the respective national populations for males working in excavation; stone quarries; sand and gravel pits; and glass, porcelain, ceramic, and tile manufacture. Stonecutters, who are probably not exposed to known lung carcinogens at the workplace but in some places to high concentrations of silica dust, showed a significant excess lung cancer risk in both Finland and Denmark. Excess lung cancer risks furthermore were seen for Finnish miners, for Finnish males in excavation work, and for Danish glassworkers.
Life Expectancy Gains From Cancer Prevention Strategies for Women With Breast Cancer and &lt;EMPH TYPE="ITAL"&gt;BRCA1&lt;/EMPH&gt; or &lt;EMPH TYPE="ITAL"&gt;BRCA2&lt;/EMPH&gt; Mutations
Authors: Deborah Schrag, Karen M. Kuntz, Judy E. Garber, Jane C. Weeks
Journal: JAMA (2000)

Women with BRCA1- or BRCA2-associated breast cancer are at increased risk for contralateral breast cancer and ovarian cancer and therefore may consider secondary cancer prevention strategies, such as prophylactic surgery and tamoxifen therapy. It is not proven to what extent these strategies reduce risk of second cancers in such patients.To examine the effect of tamoxifen therapy, bilateral prophylactic oophorectomy (PO), prophylactic contralateral mastectomy (PCM), and combinations of these strategies on life expectancy for women with unilateral breast cancer and a BRCA1 or BRCA2 gene mutation.Decision analysis using a Markov model. Probabilities for developing contralateral breast cancer and ovarian cancer, dying from these cancers, dying from primary breast cancer, and the reduction in cancer incidence and mortality due to prophylactic surgeries and/or tamoxifen were estimated from published studies.Hypothetical breast cancer patients with BRCA1 or BRCA2 mutations facing decisions about secondary cancer prevention strategies.Seven strategies, including 5 years of tamoxifen use, PO, PCM, and combinations of these strategies, compared with careful surveillance.Total and incremental life expectancy (LE) with each intervention strategy.Depending on the assumed penetrance of the BRCA mutation, compared with surveillance alone, 30-year-old early-stage breast cancer patients with BRCA mutations gain in LE 0.4 to 1.3 years from tamoxifen therapy, 0.2 to 1.8 years from PO, and 0.6 to 2.1 years from PCM. The magnitude of these gains is least for women with low-penetrance mutations (assumed contralateral breast cancer risk of 24% and ovarian cancer risk of 6%) and greatest for those with high-penetrance mutations (assumed contralateral breast cancer risk of 65% and ovarian cancer risk of 40%.) Older age and poorer prognosis from primary breast cancer further attenuate these gains.Interventions to prevent second cancers, particularly PCM, may offer substantial LE gain for young women with BRCA-associated early-stage breast cancer. Estimates of LE gain may help women and their physicians consider the uncertainties, risks, and advantages of these interventions and lead to more informed choices about cancer prevention strategies.
Urbanisation, asthma and allergies
Authors: M. I. Asher
Journal: Thorax (2011)

Differences in asthma in urban and rural environments were first reported from Germany in 1965,1 followed by many reports of higher rates of asthma symptoms in urban than rural environments around the world including Africa,2 Asia3–5 and Papua New Guinea.6 Authors have suggested that wealth, lifestyle, housing and urban environmental exposures may contribute to increasing asthma prevalence. In relation to possible protective factors in the rural environment, studies have emerged on farming lifestyles in Westernised high-income countries, showing an inverse relationship between farm exposures early in life and asthma and rhinitis, but not eczema symptoms.7 8 The potential protective effect of microbial exposures from animals or unpasteurised milk on these diseases was highlighted. A recent review of these and other potential factors suggested a ‘package’ of factors may influence the lower prevalence in rural areas.9

In Thorax , two articles10 11 present new findings related to urbanisation in Latin America. Most of the readers of Thorax will not have visited the locations studied in these papers, as they are not on popular travel routes. However, they may represent the living circumstances of many of the world's children in low- and middle-income countries where the prevalence of asthma, rhinitis and eczema is mainly increasing.12

Rodriguez et al 11 undertook an ecological study in 59 communities in Esmeraldas Province, a humid, tropical, coastal region in Ecuador. This is one of the poorest and remotest areas of the country undergoing changes related to urbanisation over the last 20 years. From 2005 to 2008 all the 7–15-year-olds were studied within the communities using parent completed questionnaires and reported community infrastructure. This study is robust with a high number of participants (n=4183) and a 95% response rate. Asthma was defined as a positive response to the question ‘Has …
Effects of Vandetanib on Lung Adenocarcinoma Cells Harboring Epidermal Growth Factor Receptor T790M Mutation <i>In vivo</i>
Authors: Eiki Ichihara, Kadoaki Ohashi, Nagio Takigawa, Masahiro Osawa, Atsuko Ogino, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Cancer Research (2009)

Vandetanib is a novel multitarget tyrosine kinase inhibitor (TKI) that inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), with additional inhibition of epidermal growth factor receptor (EGFR) and rearranged during transfection receptor signaling, which has shown promising results in clinical trials for advanced non-small cell lung cancer. However, the mechanisms of acquired resistance to vandetanib remain unclear. Therefore, we established in vitro vandetanib-resistant PC-9/VanR cells from PC-9, a vandetanib-sensitive lung adenocarcinoma cell line, by chronic exposure to this agent. PC-9/VanR cells were 50-fold more resistant to vandetanib than PC-9 cells in vitro. Compared with PC-9 cells, PC-9/VanR cells showed emergence of an EGFR T790M mutation, moderately elevated MET amplification, and similar VEGFR-2 inhibition by vandetanib. Note that phospho-MET in PC-9/VanR was suppressed following EGFR inhibition by an irreversible EGFR-TKI, indicating that MET signaling of PC-9/VanR was dependent on EGFR signaling and that MET amplification was not the primary mechanism of resistance to vandetanib. In contrast to the in vitro experiment, vandetanib effectively inhibited the growth of PC-9/VanR tumors in an in vivo xenograft model through the antiangiogenesis effects of VEGFR-2 inhibition. In conclusion, the multitarget TKI vandetanib induced or selected for the EGFR T790M mutation as observed previously with highly selective EGFR-TKIs. However, vandetanib retained significant efficacy in vivo against xenografts harboring the T790M mutation, providing a strong scientific rationale for investigating vandetanib in clinical settings where acquired resistance through emergence of EGFR T790M mutations limits the effectiveness of highly selective EGFR-TKIs.
Number, size, and distribution of Peyer's patches in the human small intestine: Part I The development of Peyer's patches
Authors: J. S. Cornes
Journal: Gut (1965)

The presence of Peyer's patches is commonly taken for granted but this is the first serious study of the incidence and development of Peyer's patches before and after birth.found to be remarkably preserved in the majority of sections examined they were later used to study the 225 on August 14,
Reply to M.L. Lanthier et al
Authors: Charles L. Bennett, Jonathan R. Nebeker
Journal: Journal of Clinical Oncology (2010)

We appreciate comments by Lanthier et al 1 of the US Food and Drug Administration regarding whether accelerated approval (AA) has expedited approval of new molecular oncology entities. Based on nonpublicly available data, they report median development times of 6.3 years for AA versus 7.2 years for regular approval (RA). However, the US Food and Drug Administration reported to the General Accounting Office 2 that AA resulted in early approval for some cancer drugs “years before the drug would have been available under regular approval procedures” suggesting that the success metric should be years—not months. Ourcontentionisthatdrugsforrarecancershavedifferentchallenges than drugs approved for common cancers. The goals and mechanisms for marketing approval should reflect the particular circumstances. For drugs for common cancers, development times are similar for RA versus AA. The longer biologic licensing agreement development time for AA versus RA (median, 9.2 v 6.7 years) is explainedbyLanthieretalasbeingduetosmallnumbers.However,it is novel biologic agents for rare cancers that are the expected primary beneficiaries of AA. Lanthier et al 1 suggest that sponsors prefer RA versus AA. The reality is that over time, AA appears to be an increasingly difficult hurdle. Before 2003, AA supported 78% of new molecular oncology entities versus 33% since then. Another concern is lack of data transparency at US Food and Drug Administration. Despite extensive searching of public sources, we identified development times for only 75% of new molecular oncology entities. There have been several calls for improved data transparency and completeness including the General Accounting Office’s review of AA and of the US Food and Drug Administration’s nonpublicly available documents, Congressman Ed Markey’s review of the AA program, and a recent policy piece. 2-4 Some of these documents also point out that the US Food and Drug Administration has
Prevalence and Severity of Coronary Artery Disease and Adverse Events Among Symptomatic Patients With Coronary Artery Calcification Scores of Zero Undergoing Coronary Computed Tomography Angiography
Authors: Todd C. Villines, Edward A. Hulten, Leslee J. Shaw, Manju Goyal, Allison Dunning, Stephan Achenbach, Mouaz Al-Mallah, Daniel S. Berman, Matthew J. Budoff, Filippo Cademartiri, Tracy Q. Callister, Hyuk-Jae Chang, Victor Y. Cheng, Kavitha Chinnaiyan, Benjamin J.W. Chow, Augustin Delago, Martin Hadamitzky, Jörg Hausleiter, Philipp Kaufmann, Fay Y. Lin, Erica Maffei, Gilbert L. Raff, James K. Min
Journal: Journal of the American College of Cardiology (2011)
Effects of hypoxia-induced intrauterine growth restriction on cardiopulmonary structure and function during adulthood
Authors: Christian F. Rueda-Clausen, Jude S. Morton, Sandra T. Davidge
Journal: Cardiovascular Research (2008)

Intrauterine growth restriction (IUGR), a condition affecting 7-15% of all pregnancies, is associated with an increased mortality rate during adulthood. Several animal models have been developed to study the effects of IUGR during adulthood. However, the in vivo characteristics of these models are still unknown. The main aim of this work was to evaluate, in vivo, the effects of IUGR on cardiopulmonary structure and function during adulthood.Pregnant Sprague Dawley rats were exposed to hypoxic (12% O2) or normoxic (21% O2) environments between day 15 and 21 of pregnancy. Offspring were raised to 4 or 12 months old when a complete in vivo echocardiographic study was performed. In addition, ex vivo morphometry and isolated working heart experiments were performed. At birth, pups exposed to hypoxia had a smaller body weight and larger heart/body weight than controls. At 4 months of age, there were no significant differences between the groups. At 12 months of age, male but not female offspring exposed to prenatal hypoxia had smaller body weights and signs of left ventricular hypertrophy. In addition, both male and females animals exposed to prenatal hypoxia showed in vivo and ex vivo signs of left ventricular diastolic dysfunction and pulmonary hypertension by 12 months of age.Our study demonstrated that hypoxia-induced IUGR is associated with the development of chronic cardiopulmonary dysfunction during ageing. The implication of these findings is the potential usefulness of neonatal diagnosis as a predictor of cardiopulmonary outcomes during adulthood.
Pneumococcal serotypes in adult non-invasive and invasive pneumonia in relation to child contact and child vaccination status
Authors: Chamira Rodrigo, Thomas Bewick, Carmen Sheppard, Sonia Greenwood, Vanessa MacGregor, Caroline Trotter, Mary Slack, Robert George, Wei Shen Lim
Journal: Thorax (2013)

<h3>Background</h3> On a population level, pneumococcal conjugate vaccination in children has reduced the incidence of vaccine-type disease in all age groups, including older adults. Few individual level studies have been performed describing the pneumococcal serotypes associated with adult community acquired pneumonia (CAP) and quantifying associations with child contact and child vaccination status. <h3>Methods</h3> Pneumococcal serotypes were determined using a validated multiplex immunoassay (Bio-Plex) in a large prospective cohort of adults hospitalised with CAP. Child (&lt;16 years old) contact history and child pneumococcal vaccination status were obtained from patients and public health records, respectively. <h3>Results</h3> Of 1130 participants, 329 (29.1%) reported child contact, and pneumococcal infection was identified in 410 (36.3%). Pneumococcal CAP was commoner in adults with child contact (148/329 (45.0%) vs 262/801 (32.7%); adjusted OR 1.63, CI 1.25 to 2.14; p&lt;0.001). A serotype was determined in 263 of 410 (64.1%) adults with pneumococcal CAP; 112 (42.6%) reported child contact, 38 (33.9%) with a vaccinated child. Adults in contact with a vaccinated child were significantly less likely to have vaccine-type CAP compared with adults in contact with an unvaccinated child (6 of 38 (15.8%) vs 25 of 74 (33.8%), respectively; OR 0.37, 95% CI 0.14 to 0.99; p=0.044). <h3>Conclusions</h3> Pneumococcal aetiology in adult CAP is independently associated with child contact and implicated serotypes are influenced by child vaccination status. This is the first study to demonstrate these associations at an individual rather than population level; it affirms that ‘herd protection’ from childhood vaccination extends beyond adult invasive disease to pneumococcal CAP.
Development of a Smooth Muscle–Targeted Cre Recombinase Mouse Reveals Novel Insights Regarding Smooth Muscle Myosin Heavy Chain Promoter Regulation
Authors: Christopher P. Regan, Ichiro Manabe, Gary K. Owens
Journal: Circulation Research (2000)

Abstract —The use of genetically modified mice has been an important model system to study gene function in cardiovascular development and under pathophysiological conditions. Although conventional gene knockout studies have provided important insights into gene function in the cardiovascular system, they may be limited by upregulation of compensatory pathways and the inability to differentiate direct versus indirect functions in vivo. As a first step in developing systems that can target gene activation or inactivation specifically to smooth muscle cells (SMCs), we coupled the smooth muscle myosin heavy chain (SMMHC) promoter to the cre recombinase gene and generated transgenic mice that express cre in SMCs. In addition, we used these mice to address whether the heterogeneous staining observed in SMMHC-LacZ mice was due to subsets of SMCs that required different regulatory cassettes of the promoter or if it reflected episodic expression of the transgene. To address both the feasibility of SMC targeting and the apparent heterogeneous expression, we bred SMMHC-cre mice to indicator mice containing a cre-activated LacZ gene. Results showed high-level expression in SMCs at various embryonic time points and in adult tissues. Because breeding of SMMHC-cre mice to an indicator line provided an integration of cre activity over time, results of this study revealed that expression of the SMMHC promoter fragment more closely resembled the expression of the endogenous gene, both with respect to the onset of activation during development and uniformity of staining among individual cells within tissues. Overall, these mice will provide a powerful tool to researchers to study gene function in vascular development/disease by using cre/lox technology to direct smooth muscle–specific gene activation or inactivation in vivo.