tbuckley/cabot-search huggingface dataset:
Prevalence of BRCA1 and BRCA2 founder mutations in Brazilian hereditary breast and ovarian cancer families
Authors: I. P. Ewald, F. R. Vargas, M. A. Moreira, C. M. Filho, D. R. da Cunha, J. P. Ramos, P. L. Ribeiro, M. Caleffi, R. Giugliani, P. Ashton-Prolla
Journal: Journal of Clinical Oncology (2008)

22108 Background: Breast cancer (BC) is a significant health care problem in Brazil and only a few studies have been conducted to verify the contribution of founder mutations in BRCA genes to the occurrence of these tumors, especially in high risk families. Two recent studies in the State of Rio de Janeiro described a higher than expected prevalence of the BRCA founder mutations usually seen in individuals of Ashkenazi Jewish origin in non-Jewish breast cancer-affected women. The largest of these studies, conducted by Gomes et al., described a prevalence of 2.3% of the BRCA1 mutation 5382insC these patients were unselected for family history of the disease. Methods: Patients affected with breast cancer or other tumors of the HBOC spectrum, whose familiy histories fulfilled the ASCO criteria for HBOC and/or who had a prior probability of carryng a BRCA mutation ≥30% (using the Myriad prevalence tables and/or the Penn II model) were recruited from high risk genetics clinics in the cities of Rio de Janeiro and São Paulo. All patients denied Ashkenazi Jewish ancestry. Mutation detection was performed by PCR-amplification of the regions of interest in BRCA1 and BRCA2 followed by DNA sequencing. All mutations were confirmed in an independent sample. Results: A total of 145 unrelated patients were tested. None of them carried the 185delAG or 6174delT mutations in BRCA1 and BRCA2, respectively. Five (5) patients carried the BRCA1 mutation 5382insC in the germline, resulting in a prevalence of 3.44% for this mutation in the HBOC families studied. Conclusions: Testing for the three common BRCA founder mutations in non-Ashkenazi Brazilian women is probably not justified, especially not for the 185delAG and 6174delT mutations; the BRCA1 mutation 5382insC however, was relatively frequent. Additional haplotyping studies will be necessary to determine if these mutants share a common haplotype with those identified in individuals of Ashkenazi origin. No significant financial relationships to disclose.
IRF4 upregulates pro-inflammatory genes and downregulates anti-inflammatory genes in seasonal allergic rhinitis
Authors: R Mobini, B Andersson, Lars-Olaf Cardell, B Egan, M Hahn-Zoric, M Langston, I Oancea, A Perkins, J Soini, S Rak, M Benson
Journal: Allergy (2008)
ENaC-activating effect of AP301 in type II alveolar cells isolated from dog, pig and rat lungs
Authors: Susan Tzotzos, Bernhard Fischer, Hendrik Fischer, Helmut Pietschmann, Rudolf Lucas, Gilles Dupre, Waheed Shabbir, Rosa Lemmens-Gruber
Journal: European Respiratory Journal (2012)

The synthetic peptide, AP301, mimics the TIP, or lectin-like, domain of human TNF-α (Lucas, R. et al Science 1994; 263:814-817). TNF-α and AP301 activate sodium uptake through the amiloride-sensitive sodium channel (ENaC) in alveolar epithelial cells (AEC), their oedema-reducing capacity having been demonstrated in various studies in rodents. AP301 has also been shown to improve alveolar liquid clearance and lung function in a porcine model of ALI.  Ventilation strategies excepted, no specific therapy presently exists for treatment of pulmonary permeability oedema, ALI or ARDS. AP301, currently undergoing clinical trials, is being developed as a therapy for these conditions.  For pre-clinical regulatory assessment, dog, pig and rat are standard models; accordingly, pre-clinical toxicology studies have been conducted with AP301 in dogs and rats. Hitherto, no studies have assessed the effect of AP301 on primary canine or porcine type II AEC. This study describes the pharmacodynamic effect of AP301 on type II AEC isolated from dog, pig and rat lungs. In whole cell patch clamp experiments with dog type II AEC, AP301 increased the amiloride-sensitive Na current from a control value of 6.1 ± 2.4 pA to 51.8 ± 1.9 pA; in pig type II AEC, an increase from 23.63 ± 1.32 to 173.23 ± 7.44 pA was observed, and in rat AEC, from 10.7 ± 3.8 pA to 66.2 ± 5.3 pA.  These results show that AP301 activates ENaC in type II AEC from dog, pig and rat. To our knowledge, this is the first cell-based analysis of the oedema-clearing effect of AP301 observed in the porcine model of pulmonary oedema. Furthermore, the results validate the dog and pig models in pre-clinical assessment of AP301.
Clinical prognostic and predictive factors for primary chemotherapy in operable breast cancer.
Authors: P Ellis, I Smith, S Ashley, G Walsh, S Ebbs, M Baum, N Sacks, J McKinna
Journal: Journal of Clinical Oncology (1998)

This study aimed to identify clinical factors that are of prognostic significance or that predict for subsequent treatment outcome in patients with large operable breast cancer treated with primary chemotherapy (PCT) at our institution.One hundred eighty-five patients received the following regimens: CMF or MMM (76 patients), ECF (75 patients), AC or FEC (34 patients), followed by surgery, with radiotherapy (RT) given to those with breast conservation. A number of common clinical variables were assessed in relation to local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS).Clinical responders had improved DFS (P = .009) and OS (P = .08) compared with nonresponders. There was no association between clinical or pathologic complete remission (CR) and survival. Pretreatment clinical axillary node positivity was a significant predictor of worsened DFS (P = .0001), OS (P = .0001), and LRFS (P = .03). Patients remaining clinically node-positive postchemotherapy had an inferior outcome compared with those becoming node-negative (DFS, P = .03; OS, P = .03) but pathologic axillary node status was not shown to predict for survival. Twenty-nine patients in clinical CR following PCT who electively did not have surgery and were treated with RT alone had significantly increased local recurrence rate compared with partial responders having surgery and RT (P = .02). There were no differences in DFS or OS between these groups. On multivariate analysis, clinical axillary node status was the only independent predictor of OS and DFS, and LRFS.Pretreatment and posttreatment clinical axillary node status is a major predictor of outcome following PCT. Complete clinical response does not define a more favorable subgroup compared with those not obtaining CR.
WPA and disaster response: new policies and actions.
Authors: Juan E Mezzich
Journal: World Psychiatry (2006)

As we have come to know, massive natural disasters are becoming increasingly frequent, affecting directly many areas of the world and indirectly humanity as a whole. The WPA, embodying 130 national psychiatric societies, over 180,000 psychiatrists, and 64 scientific sections, feels concerned to respond solidariously in each case to the suffering of the directly involved psychiatric societies, individual colleagues and the population they serve.

Our response, based on our constitution and particular expertise and resources, must focus on assisting our member societies and related health professional groups to fulfill their responsibilities in helping local populations and organizations to deal with the psychosocial consequences of disasters. This would often involve educational efforts based on adequate situational assessments and carefully prepared and culturally informed health actions. These activities would be promoted by engaging and assisting competent and committed local member societies and groups organizationally and financially to carry out assessments and action programs in coordination with national and international efforts, including those of the World Health Organization (WHO).
Abstract 4456: Aurora-A is a downstream target of RAS and forms a positive feedback regulation loop with NF-κB in non-small cell lung cancer
Authors: Donghwa Kim, Masayuki Kanai, Xiangqian Zheng, Dali Zheng, Domenico Coppola, Jin Q. Cheng
Journal: Cancer Research (2014)

Abstract Previous studies have shown that inhibition of Aurora-A reduces mutant RAS oncogenic activity and that both Aurora-A and RAS activate NF-κB pathway through phosphorylation of IkBa and upregulation of GSKa, respectively. Here we show that Aurora-A expression and kinase activity are regulated by activating mutation of KRAS. Blockage of NF-κB by IκB-S32/36A abrogated KRAS-induced Aurora-A expression and kinase activity. Furthermore, we demonstrated that NF-κB directly bound to Aurora-A promoter and induces Aurora-A transcription. In addition, depletion of Aurora-A by siRNA and pharmacological inhibitor MLN8237 suppresses RAS-induced NF-κB activity and selectively induces cell death in KRAS mutant NSCLC cells. We also show that Aurora-A is induced by nicotine and is frequently overexpressed in NSCLCs. Overexpression of Aurora-A is associated with tobacco smoke and poor prognosis in lung adenocarcinoma but not squamous lung cancer. These data suggest that Aurora-A is regulated by RAS through NF-κB and that the feedback regulation loop between Aurora-A and NF-κB could play a pivotal role in NSCLC. Citation Format: Donghwa Kim, Masayuki Kanai, Xiangqian Zheng, Dali Zheng, Domenico Coppola, Jin Q. Cheng. Aurora-A is a downstream target of RAS and forms a positive feedback regulation loop with NF-κB in non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4456. doi:10.1158/1538-7445.AM2014-4456
Cryobiopsy shows better safety profile and diagnostic yield as compared to conventional forceps for interstitial lung disease
Authors: Hamidreza Jabbardarjani, Arda Kiani, Mahdi Karimi, Mohammad Fakhri
Journal: European Respiratory Journal (2013)

Objectives: Transbronchial lung biopsy (TBLB) is an invasive procedure and is used for the diagnosis of interstitial lung diseases. TBLB by a flexible cryoprobe is a new method that is believed to be as efficacious as the conventional technique. This study wants to compare diagnostic yield and safety profile of the two techniques.

Methods: This study included 40 patients with exophitic and interstitial lung lesions who underwent transbronchial lung biopsy under guidance of C-arm fluoroscopy. All procedures were done by skilled pulmonologist after deep sedation. Definite diagnosis of patients was based on pathologic findings, patient’s history and radiologic reports. Wilcoxon signed-rank test was used to compare the diagnostic yield and complications between the two methods.

Results: The incidence of bleeding in the cryobiopsy technique was significantly lower when compared to the conventional forceps method (p<0.001). The mean ranges of alveolar spaces in cryobiopsy and forceps biopsy were 195.78 and 80.62, respectively and was statistically different (p<0.001). Preservation of the alveolar structure was significantly higher for the cryo technique (p < 0.001) while parenchymal artifacts were encountered in lower proportion of samples for this method (p<0.001). Twenty-two samples (55%) obtained from cryobiopsy resulted in definite diagnosis while this ratio for the conventional technique was significantly lower (32%, p<0.001).

Conclusions: Cryobiopsy shows superiority to the conventional forceps technique for evaluation of endobronchial tumors. This advantage was noted in both the diagnostic abilities and its safety profile.
Abstract 118: EGFL6, a potential novel ligand of EGFR, play roles in Nasopharyngeal cacinoma metastasis through establishing invasive and long-distant metastatic niche by paracrine and autocrine
Authors: Jinna Chen, Chen Jiang, Jing Yang, Ya-hui Yu, Lei Li, Yang-qun Xiang, Xinyuan Guan
Journal: Cancer Research (2015)

Abstract Distant metastasis is the leading cause of treatment failure in Nasopharyngeal carcinoma (NPC). Our study focused on the searching of potential targets for NPC metastasis treatment. cDNA microarray was applied in this screening. We compared gene expression level in metastatic NPC, non-metastatic NPC and inflammatory cases with different bioinformatic methods. EGFL6 was chosen for further study. The over-expression of EGFL6 was confirmed in NPC cell lines and 63% of the metastatic cases(n = 7/11, 3 years follow-up) by Q-PCR. EGFL6 was identified as an independent prognostic index for NPC distant metastasis survival prognostic, P = 0.023 (n = 96, QPCR). As a follicle stem cell specifically expressed secretion protein, EGFL6 showed its powerful strength in promoting cell migration and especially the formation of aggressive morphology in the matrix-gel based three-dimensional culture. With the overexpression of secreting EGFL6, CNE2 cells formed the follicle-like structure but with more aggressive leading edge, which invaded deep into the matrix-gel instead of forming single layer epithelial structure. EGFL6 overexpressed SUNE1 cells breakthrough the restriction of its regular sphere structure, and migrated for more spaces. In vivo study also showed that EGFL6 dramatically increased the tumorigenisis in subcutaneous injection assay and the growth of metastatic tumor in the mice tail vein injection experiment. Mechanism study showed that EGFL6 was a potential novel ligand of EGFR. Our resulted demonstrated that EGFL6 could bind to EGFR and caused its phosphorylation, which activated EGFR and leaded to its internalization. c-Src was subsequently phosphorylated, and the MAPK/ERK signalling cascade was activated. The EGFL6 bound cells down-regulated their expression of E-cadherin and loosed the connection with the adjacent cells, strength their F-actin and vimentin towards the direction they migrated, which indicated a transition from epithelial to mesenchymal characteristic. Further study is on going to investigate the potential of EGFL6 as a therapeutic target for NPC metastatic treatment. In conclusion, we found that EGFL6 was a potential novel ligand of EGFR, which played roles in NPC metastasis through establishing invasive and long-distant metastatic cancer niche by paracrine and autocrine. Citation Format: Jinna Chen, Chen Jiang, Jing Yang, Ya-hui Yu, Lei Li, Yang-qun Xiang, Xinyuan Guan. EGFL6, a potential novel ligand of EGFR, play roles in Nasopharyngeal cacinoma metastasis through establishing invasive and long-distant metastatic niche by paracrine and autocrine. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 118. doi:10.1158/1538-7445.AM2015-118
Frequency of the <i>Bcl-2/IgH</i> Rearrangement in Normal Individuals: Implications for the Monitoring of Disease in Patients With Follicular Lymphoma
Authors: Karin E. Summers, Lindsey K. Goff, A. Gerry Wilson, Rajnish K. Gupta, T. Andrew Lister, Jude Fitzgibbon
Journal: Journal of Clinical Oncology (2001)

To determine the incidence and frequency of the Bcl-2/IgH rearrangement in the peripheral blood of normal individuals to define the potential complication this may pose for the molecular monitoring of disease in patients with follicular lymphoma (FL).The incidence and frequency of the major breakpoint cluster region rearrangement in DNA extracted from peripheral blood or lymphoblastoid cell lines from 481 normal individuals was determined using a TaqMan real-time polymerase chain reaction assay (PE Applied Biosystems, Foster City, CA).Twenty three percent of samples were positive for the Bcl-2/IgH rearrangement, with approximately 3% of these at levels of more than 1 in 10(4) cells.The presence of circulating Bcl-2/IgH+ cells, other than those derived from the malignant clone, could confound the detection and quantitation of minimal residual disease in patients with FL, particularly at low levels of tumor burden.
Don't blame the Junior Doctors Committee
Authors: A S. Carney
Journal: BMJ (1996)

Junior doctors' hoursShift work is poisoning juniors EDrrOR,-Christopher Wong is right when he says that the current trend towards a reduction in junior doctors' working hours has gone too far.'Doctors have always worked long hours and were paid nothing for being on call until the 1970s, when they began to be paid some 30% of their standard pay for night duty, weekends, etc.All that was needed to improve the system was to pay more than 100% for on call duties and perhaps double on bank holidays and for uncivilised hours.I can guarantee that no doctor would complain of overwork under this system.After all, what happens now is that they do locums and so earn a similar amount in a roundabout way.Keith Reid's reply to Wong's letter is woolly.2Absence of evidence is not evidence of absence, and therefore I cannot accept his point that British specialists may be no better than European specialists.If training has indeed been so bad in Britain should we let doctors who were ill trained decide what is good for junior doctors' training?To quote accident and emergency departments as
Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy.
Authors: W S Dalton, T M Grogan, P S Meltzer, R J Scheper, B G Durie, C W Taylor, T P Miller, S E Salmon
Journal: Journal of Clinical Oncology (1989)

The B-cell neoplasms, multiple myeloma and non-Hodgkin's lymphoma, frequently become drug resistant, despite initial responses to chemotherapeutic drugs. Tumor cells from eight patients with clinically drug-refractory disease were evaluated by immuno-histochemical staining for monoclonal immunoglobulin (Ig) expression, nuclear proliferation antigen, P-glycoprotein (P-gly) expression, and other cellular antigens. P-gly was detected on tumor cells from six of eight patients with drug-resistant disease. Of the six patients with P-gly-positive tumors, five patients had advanced multiple myeloma and one had a drug-refractory non-Hodgkin's lymphoma. Cellular RNA analysis confirmed the over-expression of P-gly. In an effort to overcome drug resistance, a pilot study evaluated possible verapamil enhancement of chemotherapy in these eight patients. All patients had developed progressive disease while receiving a regimen containing vincristine and doxorubicin, and seven of eight patients had previously received continuous infusion vincristine and doxorubicin plus oral dexamethasone (VAD). At the time of progressive disease, continuous infusion verapamil was added to the VAD regimen. Three of the eight patients who were refractory to vincristine and doxorubicin alone responded when verapamil was added to VAD. The three patients who responded had P-gly-positive tumors. Verapamil increased the intracellular accumulation of doxorubicin and vincristine in vitro for both a P-gly-positive myeloma cell line and tumor cells from two patients with end-stage myeloma which over-expressed P-gly. The dose-limiting side effect associated with the addition of verapamil to chemotherapy was temporary impairment of cardiac function, manifest as hypotension and cardiac arrhythmia. We conclude that P-gly expression occurs in drug-refractory B-cell neoplasms and may contribute to the development of clinical drug resistance. However, other factors, such as the proliferative activity of the tumor, may also play a role in determining response to chemotherapy. The administration of verapamil along with VAD chemotherapy may partially circumvent drug resistance in patients whose tumors over-express P-gly.
Association of inflammation and bronchial hyperresponsiveness
Authors: Irina Trofimenko, Boris Chernyak
Journal: European Respiratory Journal (2011)

Bronchial hyperresponsiveness (BHR) is known to be linked to decline in lung function, only limited data are available as to whether BHR is associated with systemic inflammation in COPD.   Aim:  To compare serum biomarkers of patients with COPD and chronic bronchitis (CB) and to assess local and systemic inflammation in COPD depending on BHR.   Methods:  At 59 outpatients (50-COPD II st and 9-CB) with smoking more 10 pack/years serum concentrations IL-6, IL-8, TNF-a, CRP were analyzed. BHR was assessed in metacholine challenge. Induced sputum samples were obtained from 42 COPD patients.   Results:  Serum IL-6 and IL-8 in COPD patients were higher in comparison to CB patients: the medians difference was 1,44 pg/ml and 2,10 pg/ml, respectively (p  Serum IL-6 and IL-8 in COPD patients with BHR were higher in comparison to COPD patients without BHR: the means difference was 2,80 and 2,67 pg/ml, respectively (p  COPD patients with BHR had significantly higher numbers of total cell counts and macrophages in induced sputum than COPD patients without BHR: 3,63 vs 2,30×10 6  cells mL -1  and 1,31 vs 0,37×10 6  cells mL -1  (p 1  and pack/years in COPD patients.   Conclusion:  Serum biomarkers at COPD patients with BHR were considerably higher in comparison to CB and COPD patients without BHR. BHR in COPD is associated with more intensive local airway and systemic inflammation.
Abstract 3480: Neopterin Levels Improve Risk Prediction for Heart Failure Hospitalization Over and Above C-reactive Protein and B-type Natriuretic Peptide in the PROVE IT-TIMI 22 Study
Authors: Babak Nazer, Kausik K Ray, Sarah Sloan, Benjamin M Scirica, David A Morrow, Christopher P Cannon, Eugene Braunwald
Journal: Circulation (2009)

Background There is increasing evidence that immune mechanisms are involved in the pathogenesis of CHF. We assessed the relationship between neopterin, a marker of monocyte activation, and the risk of CHF hospitalization. Methods Among subjects in the PROVE IT-TIMI 22 trial, 3,946 had neopterin levels measured at study entry. The relationship between neopterin and risk of CHF was assessed in multivariable Cox regression models, which included demographics, type of index event, treatment allocation, as well as BNP and CRP. The incremental predictive value of neopterin over and above any given model was assessed using the likelihood ratio test (LRT). Results Unadjusted hospitalization rates for CHF increased across quartiles of neopterin (Figure 1). Per 1SD increment in log (neopterin), the risk of CHF increased by 47% (HR 1.47, 95% CI 1.24 to 1.72) after multivariable adjustment. Even after excluding individuals with a prior history of CHF or recurrent ischemic events, the relationship between neopterin an...
Human papillomavirus type 56-associated Bowen disease
Authors: A. Shimizu, A. Tamura, M. Abe, H. Amano, S. Motegi, Y. Nakatani, H Hoshino, O. Ishikawa
Journal: British Journal of Dermatology (2012)

Some cases of human papillomavirus (HPV) type 56 infection in Bowen disease have been reported. However, the incidence and clinical characteristics are still unclear.To clarify the prevalence of HPV type 56-positive Bowen disease in our department and to characterize the clinical manifestations.Sixty-eight specimens of Bowen disease were examined by polymerase chain reaction using HPV consensus primers, and the amplified products were subjected to DNA sequence analyses. Moreover, positive samples were investigated by in situ hybridization. These findings were used to clarify the clinical characteristics of HPV-positive Bowen disease.Eight out of 68 specimens (12%) of Bowen disease were HPV-positive, of which six specimens were HPV type 56-positive. The HPV type 56-positive lesions were characterized by a longitudinal melanonychia or a deeply pigmented keratotic lesion. The remaining two specimens were genital Bowen disease in which HPV type 16 was detected. In situ hybridization demonstrated the positive cells in the upper layer of epidermis. The HPV type 56 detected in the samples of longitudinal melanonychia can be divided into at least into two types.This study determined the prevalence of HPV type 56-positive Bowen disease. Longitudinal melanonychia is the most characteristic manifestation of HPV type 56-associated Bowen disease.