tbuckley/cabot-search huggingface dataset:
Dominant Papillary Subtype Is a Significant Predictor of the Response to Gefitinib in Adenocarcinoma of the Lung
Authors: Young Hak Kim, Genichiro Ishii, Koichi Goto, Kanji Nagai, Koji Tsuta, Satoshi Shiono, Junichi Nitadori, Testuro Kodama, Yutaka Nishiwaki, Atsushi Ochiai
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Gefitinib (IRESSA; AstraZeneca, Osaka, Japan) shows excellent antitumor activity against advanced non–small-cell lung cancer, especially for the treatment of adenocarcinoma. However, the predictive factors for the response to gefitinib are still controversial. The aim of this study was to identify the clinicopathological and immunohistochemical features that are favorable to the use of gefitinib in adenocarcinoma patients. Experimental Design: Between June 2002 and October 2003, 36 adenocarcinoma patients who experienced a relapse after surgical resection were treated with gefitinib at our hospital. The histologic patterns of the tumors were divided into four distinctive subtypes according to the revised World Health Organization histologic classification, and the dominant histologic subtype for the maximum cut surface of each resected specimen was documented. Association between the response to gefitinib and the clinicopathological features or immunohistochemical expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, or c-erbB-2 were then investigated. Results: A significant association between the response to gefitinib and dominant papillary subtype findings was observed (P = 0.0021); the survival time of papillary subtype patients was also significantly prolonged compared with that of non-papillary subtype patients (P = 0.03). No other clinicopathological features or the expression of EGFR, phosphorylated EGFR, or c-erbB-2 were associated with the response to gefitinib. Conclusions: The results of the present study indicate that dominant papillary subtype findings of lung adenocarcinomas can be an important predictor of the response to gefitinib. Thus, this type of adenocarcinoma might be susceptible to postoperative adjuvant treatment with gefitinib.
Tirapazamine, Cisplatin, and Radiation Versus Fluorouracil, Cisplatin, and Radiation in Patients With Locally Advanced Head and Neck Cancer: A Randomized Phase II Trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02)
Authors: Danny Rischin, Lester Peters, Richard Fisher, Andrew Macann, Jim Denham, Michael Poulsen, Michael Jackson, Lizbeth Kenny, Michael Penniment, June Corry, David Lamb, Bev McClure
Journal: Journal of Clinical Oncology (2004)

To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial.One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost).Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms.Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.
Initial Evidence of Sustained Efficacy of House Dust Mite Synthetic Peptide Immuno Regulatory Epitopes 2 Years after a Short Course of Treatment in House Dust Mite (HDM) Allergic Subjects
Authors: Rod Hafner, AnneMarie Salapatek, Mark Larché, Brenda Ahenkorah, Piyush Patel, Stephen Pawsey
Journal: Journal of Allergy and Clinical Immunology (2015)
Defective repair of O6-methylguanine-DNA in primary Sjogren's syndrome patients predisposed to lymphoma.
Authors: K Guo, G Major, H Foster, M Bassendine, J Collier, D Ross, I Griffiths
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To investigate a role for mutation in the aetiogenesis of autoimmune disease by examining levels of repairing enzyme for the promutagenic DNA base lesion, O6-methylguanine, in lymphocyte extracts from patients with autoimmune diseases. We included primary Sjögrens syndrome (PSS) patients because of the additional relevance of their being at increased risk (&gt; 40-fold) of developing lymphoma. METHODS--Lymphocytes were prepared from patients with PSS (n = 22) (12 with parotid gland enlargement, an indicator of extensive lymphoproliferation), rheumatoid arthritis (n = 12), primary biliary cirrhosis (n = 11), osteoarthritis (n = 12), and healthy individuals (n = 11). MGMT amounts were determined in lymphocyte extracts by direct enzyme assay and expressed in relation to total extract DNA, protein, or cell number. RESULTS--We found no defect in the repairing methyltransferase enzyme between any of the groups, except in PSS patients at increased risk of developing lymphoma (those with enlarged parotid glands): p &lt; 0.0001 and p = 0.0056, compared with healthy controls and PSS patients without parotid gland swelling, respectively. CONCLUSIONS--Our findings implicate persistence of O6-methylguanine-DNA in the aetiology of lymphoma associated with PSS, and raise the possibility that an alternative repair process for O6-methylguanine-DNA, nucleotide excision repair, might be defective in autoimmune disease.
Adiponectin Concentrations in Sera From Patients With Type 2 Diabetes Are Negatively Associated With Sympathovagal Balance as Evaluated by Power Spectral Analysis of Heart Rate Variation
Authors: Sadao Wakabayashi, Yoshimasa Aso
Journal: Diabetes Care (2004)

To investigate whether cardiac autonomic activity, particularly sympathovagal balance as estimated by power spectral analysis (PSA) of heart rate variation (HRV), is associated with serum adiponectin concentrations in patients with type 2 diabetes.We studied 105 patients with type 2 diabetes (51 women and 54 men). Serum adiponectin concentrations were measured by sandwich enzyme-linked immunosorbent assay. HRV was determined automatically every 5 min over 24 h using Holter electrocardiographic recording. PSA of R-R intervals was performed using fast Fourier transformation. Low-frequency (both sympathetic and parasympathetic activities), high- frequency (pure parasympathetic activity), and the ratio of low-frequency-to-high-frequency power (LF-to-HF ratio), an index of sympathovagal balance, were used as indexes of cardiac autonomic activity.We found no significant correlation between serum adiponectin and low-frequency or high-frequency power in patients with diabetes. Serum adiponectin concentration correlated negatively with the 24-h LF-to-HF ratio (r = -0.343, P = 0.0009) and creatinine clearance (r = -0.411, P < 0.0001). Serum adiponectin concentrations were significantly higher in patients with overt albuminuria than in those with normoalbuminuria or microalbuminuria. In multivariate analysis controlling for sex, BMI, glycemic control, lipid profile, and renal function, serum adiponectin concentration showed an independent negative association with 24-h LF-to-HF ratio (beta = -0.332, P = 0.020). Furthermore, sex, HDL cholesterol, and renal function retained significant influence on the serum adiponectin concentration in patients with diabetes.Sympathovagal balance favoring relative sympathetic activation was associated with low serum concentrations of adiponectin in patients with type 2 diabetes.
Prepregnancy Diabetes and Risk of Placental Vascular Disease
Authors: Taryn Becker, Marian J. Vermeulen, Philip R. Wyatt, Chris Meier, Joel G. Ray
Journal: Diabetes Care (2007)

Maternal diabetes before pregnancy is associated with adverse maternal and perinatal outcomes, including acquired hypertension during pregnancy (1,2,3). The maternal placental syndromes preeclampsia and abruption or infarction of the placenta (4) are also more prevalent in women with insulin resistance, diabetes, and the metabolic syndrome (3,5–8). We evaluated the risk of placental vascular disease in association with prepregnancy diabetes.

We completed a retrospective population-based study of all women who underwent antenatal maternal serum screening (MSS) in Ontario, Canada, between 1993 and 2000, as described elsewhere (9). Those with a multiple gestation pregnancy at the time of MSS were excluded.

Maternal characteristics (Table 1) were recorded on a standardized form and completed by the patients’ caregivers at the time of MSS. Data on obstetrical outcomes and the health status of each newborn were also linked to the Discharge Abstract Database of the Canadian Institute for Health Information, providing up to eight ICD-9 diagnostic codes for each woman and each newborn (see the online appendix [available at http://dx.doi.org/10.2337/dc07-0364]).

The primary study outcome was a diagnosis of either preeclampsia and abruption or infarction, according to the relevant ICD-9 codes recorded at the delivery hospital (online appendix). Secondary study outcomes included an individual diagnosis of preeclampsia and abruption or infarction, maternal preeclampsia/eclampsia, and poor fetal growth or fetal growth restriction.

### Statistical analysis

The association between prepregnancy diabetes …
P0647 : Proactive dose adjustments are necessary in many ADV-experienced patients treated with TDF monotherapy for 5 years: A prospective cohort study in 320 patients
Authors: P. Lampertico, R. Soffredini, M. Borghi, M. Viganò, F. Facchetti, E. Galmozzi, F. Invernizzi, M. Colombo
Journal: Journal of Hepatology (2015)
Letter concerning: 'Enhanced expression of DYRK1A in cardiomyocytes inhibits acute NFAT activation but does not prevent hypertrophy in vivo': reply
Authors: C. Grebe, T.-M. Klingebiel, S. P. Grau, K. Toischer, M. Didie, C. Jacobshagen, C. Dullin, G. Hasenfuss, T. Seidler
Journal: Cardiovascular Research (2011)

We would like to thank da Costa Martins and De Windt for giving us the opportunity to discuss our recent paper in more detail.1 They state that ‘… a quantitative analysis of endogenous or transgenic Dyrk1a expression was not provided …’ and ‘… it remains unclear what level of overexpression over endogenous myocardial Dyrk1a was actually achieved by the transgenic system …’. The authors may have overlooked that we provide exactly this information in detail in our article: see Fig. 2A displaying the protein overexpression time course, see page 523 line 101 where we state that the level of overexpression was 5.1-fold, and see the quantitative real-time RT–PCR data on the level of Dyrk1a mRNA expression (see Supplementary material online, Figure S2B ). Furthermore, da Costa Martins and De Windt state that ‘… endogenous Rcan1 protein expression was not measured in the study by Grebe et al. ’ However, endogenous Rcan1–4 mRNA expression was indeed quantified in both the TAC and calcineurin transgenic disease models and is displayed in Fig. 4B . da Costa Martins and De Windt ask whether we observed alterations in endogenous DYRK1A expression following aortic banding or calcineurin co-expression. Although the data were not fully included in the paper (but see Supplementary material online, Figure S2C …
The Ontario oncology electronic medical record (EMR): The integration of end user and provincial needs.
Authors: Vishal Kukreti, Sara Lankshear, Arthur G. Manzon, Nancy Wolf, Shafiq Habib, Sherrie Hertz, Saul Melamed, Tim Yardley, Lisa Sarsfield
Journal: Journal of Clinical Oncology (2013)

248 Background: The use of ambulatory electronic medical record (EMR) systems within oncology provides an opportunity for aligning provincial, local and end-user patient-centred quality indicators in the design, delivery and evaluation of clinical care and resource utilization. The aim of this provincial initiative is to define the “meaningful use” for the Oncology EMR by identifying the essential data elements and functional requirements required to facilitate integrated care, information standards (both local and provincial), and system integration needs. This paper presents the results of a provincial field study designed to determine end-user needs for information and quality metrics. Methods: Data collection included two separate onsite focus groups at each of the 13 regional cancer programs, with a focus on Clinical and Operational requirements. A total of 141 participants, representing physicians, interprofessional clinical team members, administrators and health information specialists were involved. An additional online survey was used for optimal engagement, with a total of 194 respondents, primarily nurses and physicians. Inclusion and exclusion criteria were developed to assist in coding and distillation of concepts generated. Results: A total of 1,598 ideas were generated (Clinical = 997, Operational = 601). Multiple rounds of content analysis were used to eliminate duplicates, identify common themes and distill the wealth of information down to the “vital few” discrete information requirements that should be included in the oncology EMR. At this time, 63 clinical and 55 operational concepts have been identified to support clinical care as well as operational planning and system evaluation. The online survey has helped define the data required for a Provincial Oncology Patient Profile within the EMR. Conclusions: The study employed significant consultation to merge end user and existing provincial quality measurement needs in order to define the Ontario Oncology EMR. A full spectrum of quality indicators identified through these processes will inform the future provincial priorities for information standards and quality monitoring that will be facilitated by a standardized EMR.
A crucial role for thiol antioxidants in estrogen-deficiency bone loss
Authors: Jenny M. Lean, Julie T. Davies, Karen Fuller, Christopher J. Jagger, Barrie Kirstein, Geoffrey A. Partington, Zoë L. Urry, Timothy J. Chambers
Journal: Journal of Clinical Investigation (2003)

The mechanisms through which estrogen prevents bone loss are uncertain. Elsewhere, estrogen exerts beneficial actions by suppression of reactive oxygen species (ROS). ROS stimulate osteoclasts, the cells that resorb bone. Thus, estrogen might prevent bone loss by enhancing oxidant defenses in bone. We found that glutathione and thioredoxin, the major thiol antioxidants, and glutathione and thioredoxin reductases, the enzymes responsible for maintaining them in a reduced state, fell substantially in rodent bone marrow after ovariectomy and were rapidly normalized by exogenous 17-beta estradiol. Moreover, administration of N-acetyl cysteine (NAC) or ascorbate, antioxidants that increase tissue glutathione levels, abolished ovariectomy-induced bone loss, while l-buthionine-(S,R)-sulphoximine (BSO), a specific inhibitor of glutathione synthesis, caused substantial bone loss. The 17-beta estradiol increased glutathione and glutathione and thioredoxin reductases in osteoclast-like cells in vitro. Furthermore, in vitro NAC prevented osteoclast formation and NF-kappaB activation. BSO and hydrogen peroxide did the opposite. Expression of TNF-alpha, a target for NF-kappaB and a cytokine strongly implicated in estrogen-deficiency bone loss, was suppressed in osteoclasts by 17-beta estradiol and NAC. These observations strongly suggest that estrogen deficiency causes bone loss by lowering thiol antioxidants in osteoclasts. This directly sensitizes osteoclasts to osteoclastogenic signals and entrains ROS-enhanced expression of cytokines that promote osteoclastic bone resorption.
Elevated Evolutionary Rate in Genes with Homopolymeric Amino Acid Repeats Constituting Nondisordered Structure
Authors: J. Gojobori, S. Ueda
Journal: Molecular Biology and Evolution (2010)

Homopolymeric amino acid repeats are tandem repeats of single amino acids. About 650 genes are known to have repeats of this kind comprising seven residues or more in the human genome. According to the evolutionary conservativeness, we classified the repeats into three categories: those whose length is conserved among mammals (CM), those whose length differs among nonprimate mammals but is conserved among primates (CP), and those whose length differs among primates (VP). The frequency of each repeat, especially Ala, Leu, Pro, and Glu repeats, varies greatly in each category. The 3D structure of homopolymeric amino acid repeats is considered to be intrinsically disordered. As expected, a large proportion of the repeats had a disordered structure, and nearly half of the repeats were predicted as completely disordered. However, a number of the repeats predicted to have nondisordered structure: 13% and 25% of the repeats for categories CM and VP, respectively. Comparison of the substitution rates showed a higher Ka/Ks ratio for the genes with not disordered repeats than the genes with disordered repeats. These results indicate that amino acid substitution rates have been elevated in the genes with nondisordered repeats.
miR-125b Is Methylated and Functions as a Tumor Suppressor by Regulating the ETS1 Proto-oncogene in Human Invasive Breast Cancer
Authors: Yan Zhang, Li-Xu Yan, Qi-Nian Wu, Zi-Ming Du, Jing Chen, Ding-Zhun Liao, Ma-Yan Huang, Jing-Hui Hou, Qiu-Liang Wu, Mu-Sheng Zeng, Wen-Lin Huang, Yi-Xin Zeng, Jian-Yong Shao
Journal: Cancer Research (2011)

Abstract The microRNA miR-125b is dysregulated in various human cancers but its underlying mechanisms of action are poorly understood. Here, we report that miR-125b is downregulated in invasive breast cancers where it predicts poor patient survival. Hypermethylation of the miR-125b promoter partially accounted for reduction of miR-125b expression in human breast cancer. Ectopic restoration of miR-125b expression in breast cancer cells suppressed proliferation, induced G1 cell-cycle arrest in vitro, and inhibited tumorigenesis in vivo. We identified the ETS1 gene as a novel direct target of miR-125b. siRNA-mediated ETS1 knockdown phenocopied the effect of miR-125b in breast cell lines and ETS1 overexpression in invasive breast cancer tissues also correlated with poor patient prognosis. Taken together, our findings point to an important role for miR-125b in the molecular etiology of invasive breast cancer, and they suggest miR-125b as a potential theranostic tool in this disease. Cancer Res; 71(10); 3552–62. ©2011 AACR.
Compositional Biases among Synonymous Substitutions Cause Conflict between Gene and Protein Trees for Plastid Origins
Authors: Blaise Li, João S. Lopes, Peter G. Foster, T. Martin Embley, Cymon J. Cox
Journal: Molecular Biology and Evolution (2014)

Archaeplastida (=Kingdom Plantae) are primary plastid-bearing organisms that evolved via the endosymbiotic association of a heterotrophic eukaryote host cell and a cyanobacterial endosymbiont approximately 1,400 Ma. Here, we present analyses of cyanobacterial and plastid genomes that show strongly conflicting phylogenies based on 75 plastid (or nuclear plastid-targeted) protein-coding genes and their direct translations to proteins. The conflict between genes and proteins is largely robust to the use of sophisticated data- and tree-heterogeneous composition models. However, by using nucleotide ambiguity codes to eliminate synonymous substitutions due to codon-degeneracy, we identify a composition bias, and dependent codon-usage bias, resulting from synonymous substitutions at all third codon positions and first codon positions of leucine and arginine, as the main cause for the conflicting phylogenetic signals. We argue that the protein-coding gene data analyses are likely misleading due to artifacts induced by convergent composition biases at first codon positions of leucine and arginine and at all third codon positions. Our analyses corroborate previous studies based on gene sequence analysis that suggest Cyanobacteria evolved by the early paraphyletic splitting of Gloeobacter and a specific Synechococcus strain (JA33Ab), with all other remaining cyanobacterial groups, including both unicellular and filamentous species, forming the sister-group to the Archaeplastida lineage. In addition, our analyses using better-fitting models suggest (but without statistically strong support) an early divergence of Glaucophyta within Archaeplastida, with the Rhodophyta (red algae), and Viridiplantae (green algae and land plants) forming a separate lineage.
Nursing home residents and pneumonia hospitalisation
Authors: S Surindran
Journal: Thorax (2006)

▴ Loeb M, Carusone SC, Goeree R, et al. Effect of a clinical pathway to reduce hospitalizations in nursing home residents with pneumonia. JAMA2006;295:2503–10 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This study compared outcomes in 680 nursing home residents aged ⩾65 years with pneumonia or lower respiratory tract infection treated in the community with a clinical pathway versus those treated in a standard manner. The primary outcome measure was hospital admissions. The … [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DLoeb%26rft.auinit1%253DM.%26rft.volume%253D295%26rft.issue%253D21%26rft.spage%253D2503%26rft.epage%253D2510%26rft.atitle%253DEffect%2Bof%2Ba%2Bclinical%2Bpathway%2Bto%2Breduce%2Bhospitalizations%2Bin%2Bnursing%2Bhome%2Bresidents%2Bwith%2Bpneumonia%253A%2Ba%2Brandomized%2Bcontrolled%2Btrial.%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.295.21.2503%26rft_id%253Dinfo%253Apmid%252F16757722%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=10.1001/jama.295.21.2503&link_type=DOI [3]: /lookup/external-ref?access_num=16757722&link_type=MED&atom=%2Fthoraxjnl%2F61%2F9%2F755.atom [4]: /lookup/external-ref?access_num=000238057300025&link_type=ISI
Overview of randomized perioperative polychemotherapy trials in women with early-stage breast cancer.
Authors: P C Clahsen, C J van de Velde, A Goldhirsch, J Rossbach, M R Sertoli, L Bijnens, R J Sylvester
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine whether perioperative polychemotherapy (PeCT) can significantly prolong the overall survival of women with early-stage breast cancer. METHODS A meta-analysis that used updated individual patient data from all available randomized trials of PeCT, both published and unpublished, was conducted. Data on 6,093 patients (1,124 deaths and 1,912 recurrences) from five clinical trials were available (median follow-up duration, 5.3 years; maximum, 11.3 years). RESULTS No significant effect of PeCT on overall survival was observed. However, patients who received PeCT had a significantly longer disease-free survival (hazards ratio [HR], 0.89; 95% confidence interval [CI], 0.82 to 0.98; P = .02). Time to local recurrence was significantly prolonged in the PeCT arm (HR, 0.68; 95% CI, 0.58 to 0.80; P &lt; .0001). Likewise, there was a borderline significant difference in favor of PeCT in terms of time to distant metastases (HR, 0.90; 95% CI, 0.81 to 1.00; P = .05). Subgroup analyses suggest that node-negative women benefited the most from treatment. CONCLUSION At present, there is no evidence that PeCT is able to prolong overall survival in patients with early-stage breast cancer; however, further follow-up evaluation is required. PeCT significantly prolongs disease-free survival, especially in node-negative women, which emphasizes once more the need for clinical trials in this subgroup.