tbuckley/cabot-search huggingface dataset:
The role of KRAS, BRAF, NRAS, and PIK3CA mutations as markers of resistance to cetuximab in chemorefractory metastatic colorectal cancer
Authors: D. Lambrechts, W. De Roock, H. Prenen, J. De Schutter, B. Jacobs, B. Biesmans, B. Claes, G. De Hertogh, E. Van Cutsem, S. Tejpar
Journal: Journal of Clinical Oncology (2009)

4020 Background: KRAS mutations (MUT) negatively affect outcome after cetuximab (CTX) in metastatic colorectal cancer (mCRC). As only 40% of KRAS wild-type (WT) respond it is possible that other MUT, constitutively activating the Ras/Erk or PI3K/Akt pathways, are present in the non-responding KRAS WT. We analyzed the KRAS, BRAF, NRAS &amp; PIK3CA MUT status in 276 chemorefractory CRC treated with CTX +- irinotecan and correlated the MUT status with outcome. Methods: KRAS codon 12,13, 61&amp;146, BRAF V600E, NRAS codon 12&amp;13, PIK3CA E542K, E545K, A, G, V (exon 9), H1047Y, R, L (exon 20), N345K, R88Q and Q546K MUT were evaluated on FFPE primary CRC using the Sequenom MALDI TOF MassArray system. A two- sided Fisher's exact test was used to evaluate the association between PIK3CA, KRAS, BRAF &amp; NRAS MUT and objective response (OR). Progression-free (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: 116/276 (42%) CRC had a KRAS MUT, 96% of which occurred in codon 12 or 13. KRAS WT was associated with OR (p&lt;.0001), longer median PFS (p&lt;.0001) and OS (p&lt;.0001). 15/153 (9.8%) KRAS WT had a BRAF MUT. BRAF WT was associated with OR (p=.01), longer PFS (p&lt;.0001) and OS (p=.007). 5/98 (5%) KRAS WT had an NRAS MUT and none of these showed OR. KRAS, BRAF and NRAS MUT were mutually exclusive. The combined KRAS/BRAF/NRAS WT state was associated with OR (p&lt;.0001), longer PFS (p&lt;.0001) and OS (p&lt;.0001). 23/200 (12%) CRC carried a PIK3CA mutation: 5/39 (13%) of responders and 18/160 (11%) of non-responders (p=.781). Median PFS and OS were not associated with PIK3CA MUT state (p=.760 &amp; p=.698) overall, nor in the KRAS/BRAF/NRAS WT subgroup (p=.946 &amp; p=.509). 5/13 (38.5%) PIK3CA MUT KRAS/BRAF/NRAS WT CRC showed an OR. 13/107 (12%) of KRAS/BRAF/NRAS WT and 10/93 (11%) of KRAS/BRAF/NRAS MUT tumors harbored a PIK3CA MUT (p=.826). Conclusions: KRAS, BRAF &amp; NRAS MUT are mutually exclusive and occur in at least 47% of CRC. Like KRAS WT, BRAF WT state of the primary is significantly associated with outcome in mCRC treated with CTX. The combined KRAS/BRAF/NRAS WT state is significantly associated with outcome. PIK3CA MUT occur independently of the KRAS/BRAF/NRAS MUT status. We cannot provide any evidence for a strong role of PIK3CA MUT as a marker in determining outcome to CTX. [Table: see text]
Tc-99m DISIDA Hepatobiliary Scintigraphy Showing Bile Leakage into the Thoracic Cavity
Authors: JONG-KANG LEE
Journal: Clinical Nuclear Medicine (2001)

From the Nuclear Medicine Department, China Medical College Hospital, Taichung, Taiwan Received for publication July 31, 2000. Revision accepted January 22, 2001. Reprint requests: Jong-Kang Lee, Nuclear Medicine Department, China Medical College Hospital, 2 Yue-Der Road, Taichung, Taiwan.
S68 Evaluation of non-invasive ventilation in management of acute severe asthma
Authors: D. Chaudhry, M. Indora, V. Sangwan, I. P. S. Sehgal, A. Chaudhry
Journal: Thorax (2010)

<h3>Objectives</h3> To study the role of non-invasive positive pressure ventilation (NIPPV) in management of acute severe asthma. <h3>Study design</h3> Open randomised controlled trial. <h3>Methods</h3> 50 patients of acute severe asthma having asthma for at least 1 year duration with exacerbation of less than 7 days duration, FEV1 &lt;50% of predicted, respiratory rate of &gt;25 breaths/min and pulse rate &gt;110/min after half hour of 5 mg nebulised salbutamol were included in the study over 1 year. Patients with known COPD, history of smoking &gt;10 years, HR &gt;140/min, systolic BP &lt;90 mm Hg, facial deformity, pulmonary oedema, pneumonia and pregnancy were excluded. Patients were divided into two groups A and B. All patients received nebulisation with salbutamol 5 mg and ipratropium bromide 0.5 mg and hydrocortisone 100 mg IV at zero hour and later 5 mg salbutamol with small volume oxygen driven nebuliser @ 6 l/min at 1, 2, 3, 5 h of the study. Group B patients were given NIV support in addition to medical therapy for 6 h. All patients received O<sub>2</sub> at 6–8 l/min for 6 h. NIV and medical treatment were stopped after 6 h. Spirometry, ABG, respiratory rate (RR), accessory muscles of respiration (AMR) and Borg dyspnoea score were assessed at 0, 1, 3, 6 and 7th hour of study. <h3>Results</h3> Out of 308 patients 246 were excluded because of non-fulfilment of inclusion criteria. Eight patients refused consent, three had pneumonia and claustrophobia to mask respectively. One patient deteriorated in Group A and was withdrawn. The use of accessory muscles of respiration (AMR) reduced significantly in group B at 3, 6 and 7 h (p&lt;0.01), BORG dyspnoea score improved significantly (p&lt;0.01) in group B after 1 h. There was no difference between two groups in terms of improvement in RR, HR, FEV1 and ABG. In group B, the mean IPAP and EPAP used was 14.32±0.945 and 7.16±0.472 cm of water, respectively. <h3>Conclusion</h3> The use of NIPPV in patients with acute severe asthma though found to be useful in terms of faster resolution of dyspnoea and decrease in use of AMR but did not improve pulmonary functions significantly.
89Sr Imaging With Bremsstrahlung in Patients With Metastatic Breast Cancer
Authors: Mana Yoshimura, Norio Kohno, Kimito Yamada, Hiroshi Kaise, Junichi Okamoto, Kenji Uchida, Tsuyoshi Hashimoto, Kiyoshi Koizumi, Koichi Tokuuye
Journal: Clinical Nuclear Medicine (2012)

In this study, we investigated the clinical and laboratory factors that may enhance (89)Sr uptake to strengthen its tumoricidal effect.We enrolled 21 patients with multiple bone metastases (n = 23) from breast cancer and classified them into 2 groups according to their zoledronic acid (ZOL) treatment history. (89)Sr imaging with bremsstrahlung was performed 2 to 6 weeks after administration and (89)Sr index was measured using combined imaging with bone scintigraphy. We compared the Sr index with the levels of alkaline phosphatase, bone-specific alkaline phosphatase, serum cross-linked N-telopeptides, carboxy-terminal telopeptide of type 1 collagen, C-reactive protein, calcium, and hemoglobin on administration and evaluated the differences among the groups.The (89)Sr index ranged from 0.01 to 2.0 and was significantly correlated with C-reactive protein and alkaline phosphatase and moderately correlated with carboxy-terminal telopeptide of type 1 collagen, serum cross-linked N-telopeptides, and bone-specific alkaline phosphatase. The (89)Sr index was not significantly correlated with calcium or hemoglobin. The group with less than 1 year of ZOL treatment demonstrated a mean (SD) (89)Sr index of 1.11 (0.59), and the group with 1 or more years of ZOL treatment showed a mean (89)Sr index of 0.36 (0.26). The Wilcoxon signed-rank test demonstrated a significant difference between the 2 groups (P < 0.001).(89)Sr accumulation seemed to be associated with bone turnover, in particular bone resorption, and vascularization due to inflammation or tumor growth. Long-term ZOL treatment may reduce bone resorption and vascularization. To enhance the tumoricidal effect and palliation of bone pain by (89)Sr, combined therapy must be established.
P185 Public attitudes to smoking in cars
Authors: E. De Lacy, R. Morrison, M. Dockrell, T. Buchanan, K. E. Lewis
Journal: Thorax (2010)

<h3>Background</h3> Passive smoking is increasingly associated with adverse health effects. The new UK Government is considering its tobacco control policy. <h3>Aim</h3> To record public attitudes on potential legislation regarding smoking in cars. <h3>Methods</h3> We commissioned a survey of the YouGov<sup>®</sup> Plc British panel of 185 000+ people (aged 18+). An email was sent to panellists, selected at random using a sophisticated sampling matrix, to be representative of each country. Three surveys were conducted between 25 and 30 March 2009. We obtained answers from n=10 895 adults in England, n=1023 adults in Wales, and n=1157 adults in Scotland. The results for all three countries were merged at analysis stage and re-weighted to be representative of the overall GB population. We had data from 13 075 adults, 52% female, mean age 45.5 (range 18–88 years), 22% of whom reported continued smoking at least occasionally. <h3>Results</h3> Overall, 76% of adults support a ban on smoking in cars carrying children, 55% support a ban on smoking in cars carrying any passenger. Regarding a total ban on smoking in cars, 44% support a complete ban, with 37% opposing a complete ban and 19% were undecided. The Abstract P185 Table 1 shows responses by smoking status for support for a ban in cars. <h3>Conclusions</h3> There remain differences in opinion between smokers and non-smokers but there appears widespread public support among both groups for a ban on smoking in cars, especially any carrying children.
Inhaled Endotoxin and Decreased Spirometric Values
Authors: Robert M. Castellan, Stephen A. Olenchock, Kathleen B. Kinsley, John L. Hankinson
Journal: New England Journal of Medicine (1987)

The early stages of byssinosis, the chronic lung disorder caused by the inhalation of cotton dust, are characterized by repeated episodes of mild and reversible obstruction of airways on exposure to cotton dust. To define the relation between exposure to endotoxin and the airway response to inhaled cotton dust, we pooled and analyzed data from several previous studies of experimental exposure. The pooled data set involved a total of 108 separate sessions of exposure to dust and 32 different cottons. Each dust-exposure session had involved exposing a group of 24 to 35 prescreened healthy subjects to dust from one of the cottons for six hours. The following data were obtained for each session: average concentrations of airborne dust (range, 0.12 to 0.55 mg per cubic meter) and endotoxin (range, 6 to 779 ng per cubic meter) as determined in air samples collected by vertical elutriators, and group mean percentage change in forced expiratory volume in one second (range, +0.5 to -9.1 percent), as determined by preexposure and postexposure spirometry. When data from the 108 exposure sessions were pooled, the dust concentration was not correlated with the group mean percentage change in forced expiratory volume in one second (r = -0.08; P = 0.43). In contrast, a clear exposure-response relation was observed between endotoxin concentration and group mean percentage change in forced expiratory volume in one second (r = -0.74; P less than 0.0001). Logarithmic transformation of endotoxin values clarified this relation at low-exposure concentrations and improved the correlation (r = -0.85; P less than 0.0001). Our observations strongly support the hypothesis that endotoxin has a causative role in the acute pulmonary response to inhaled cotton dust.
Detection of Barrett’s Esophagus Superimposed by Esophageal Cancer by FDG Positron Emission Tomography
Authors: Carlos A. C. Pereira Neto, Hongming Zhuang, Nasrin Ghesani, Abass Alavi
Journal: Clinical Nuclear Medicine (2001)

Neto, Carlos A. C. Pereira M.D.; Zhuang, Hongming M.D., Ph.D.; Ghesani, Nasrin M.D.; Alavi, Abass M.D. Author Information
Aerosolized Ribavirin Treatment of Infants with Respiratory Syncytial Viral Infection
Authors: Caroline Breese Hall, John T. McBride, Edward E. Walsh, David M. Bell, Christine L. Gala, Stephen Hildreth, Lawrence G. Ten Eyck, William J. Hall
Journal: New England Journal of Medicine (1983)

We evaluated a new antiviral agent, ribavirin, in the treatment of infants hospitalized with lower-respiratory-tract disease from respiratory syncytial virus. Ribavirin or placebo was administered to 33 infants in a double-blind manner by continuous aerosol for three to six days. Seventeen infants were treated with placebo, and 16 with ribavirin. By the end of treatment, infants receiving ribavirin had significantly greater improvement in their overall score for severity of illness, in lower-respiratory-tract signs, and in arterial oxygen saturation. Viral shedding was also diminished in the treated groups as compared with the placebo group. No side effects or toxicity were associated with the aerosol therapy. Isolates of respiratory syncytial virus obtained from the infants over the course of therapy showed no change in sensitivity to ribavirin. (N Engl J Med 1983; 308:1443–7.)
Safety and efficacy of R-THP-COP for over 80 years elderly patients with diffuse large B-cell lymphoma
Authors: Fusako Waki, Uchida Shumpei, Fukumoto Tetsuya, Ide Makoto, Izumi Yoichiro, Kawachi Yasunori, Ohnishi Hiroaki
Journal: Annals of Oncology (2015)
Abstract 36: The Importance of sticking together; Cdh1 loss in the gastric zymogenic lineage
Authors: Jessica Harrison Geahlen, Filip A. Swat, Jason C. Mills
Journal: Cancer Research (2012)

Abstract Stomach Cancer is the second leading cause of cancer related death worldwide. The adult stomach is a renewing system with cells simultaneously differentiating and migrating along invaginations termed gastric units. One such lineage is the zymogenic lineage in which neck cells differentiate to form mature zymogenic cells at the base of the gastric units. The transcription factor Mist1 plays a key role in this differentiation and is lost in the formation of precancerous metaplasia. Another important protein in proper zymogenic cell formation is the cellular adhesion protein Cdh1. Cdh1 has been characterized as a tumor suppressor protein and is often lost in cancer cells allowing for metastasis. In some forms of Hereditary Diffuse Gastric Cancer, loss of Cdh1 is thought to be an initiating event in tumor formation. I have genetically engineered mice in which I can temporally knock out Cdh1 within zymogenic cells both in the presence and absence of Mist1. It is my hypothesis that cells lacking both of these tumor suppressors will be more likely to develop gastric tumors. Preliminary immune-fluorescence analysis of these stomachs indicates that in absence of both MIST1 and CDH1, fully differentiated and normally post mitotic zymogenic cells show greatly reduced size and increased re-entry into the cell cycle. This data suggests that deletion of both MIST1 and CDH1 disrupts the terminal differentiation program of zymogenic cells and promotes metaplastic growth in a manner that could resemble the origins of gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 36. doi:1538-7445.AM2012-36
Une nouvelle prothèse métallique couverte pour traiter les fistules et déhiscences anastomotiques œsogastriques en diminuant le risque de migration?
Authors: R Garces Duran, G Vanbiervliet, JM Gonzalez, JC Grimaud, M Barthet
Journal: Endoscopy (2014)

La déhiscence anastomotique et la fistule œsogastrique post opératoire sont toujours difficiles à gérer. Les prothèses complètement couvertes ont un risque élevé de migration. Le but de notre étude est d'évaluer l'efficacité d'une nouvelle type de prothèse dite double type en cas de déhiscence anastomotique ou de fistule post opératoire œsogastrique.
FRI0133 Does rheumatoid arthritis predispose to abnormal left ventricular geometry?
Authors: H. B. Midtbø, E. Gerdts, I. C. Olsen, T. K. Kvien, E. S. Davidsen, A. G. Semb
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Left ventricular (LV) geometry is a strong predictor of cardiovascular death. Less is known about the relation between LV geometry and RA. <h3>Objectives</h3> Our objective was to study if RA or RA disease activity was associated with abnormal LV geometry measured as increased LV relative wall thickness (RWT) or mass (LVM). <h3>Methods</h3> Echocardiography, clinical and laboratory assessment was performed in 137 RA patients without prior myocardial infarction or valvular disease and 50 healthy controls. Age-adjusted RWT and LVM were calculated by validated equations. <h3>Results</h3> The RA group was older, had higher blood pressure (BP) and included more women compared to controls (all p&lt;0.01). Among RA patients, higher RWT correlated with higher systolic BP, wall stress, and RA disease activity measured by modified health assessment questionnaire (MHAQ), Clinical Disease Activity Index (CDAI), simple DAI (SDAI) and Disease Activity Score in 28 joints (DAS-28) in univariate analyses (all p&lt;0.05). Wall stress and systolic BP were the main covariates of higher RWT in multivariate analyses both among RA patients and controls (all p&lt;0.01). However, the analyses showed that among RA patients, RWT was associated with 4 different disease activity measures independently of gender, systolic BP and wall stress (Table). Higher LVM was independently associated with higher systolic BP, age and body weight, male gender and lower LV ejection fraction (all p&lt;0.05), but was not associated with markers of RA disease activity. <h3>Image/graph</h3> <h3>Conclusions</h3> Abnormal LV geometry is associated with markers of increased disease activity in RA, independent of systolic BP and wall stress, pointing to the importance of disease activity control in RA patients. <h3>Disclosure of Interest</h3> None Declared
THU0036 Discriminating Central Nervous System Infection and Neuropsychiatric Involvement in Patients with Systemic Lupus Erythematosus: A Single-Center Experience
Authors: J. Chen, X. Feng, H. Wang, B. Hua, L. Sun
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Despite the improvement of survival rates in SLE patients over the past decades, patients still have higher mortalities compared with the general population that can be largely attributed to uncontrolled disease activities and, most importantly, various kinds of severe infections. <h3>Objectives</h3> The aim of this study is to identify the clinical differences between central nervous system (CNS) infection and neuropsychiatric lupus (NPSLE) in patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> Clinical manifestations, laboratory test results and prognoses of 14 SLE patients complicated with various CNS infections, hospitalized in the Drum Tower Hospital in the past seven years, were reviewed and compared with those of 34 concomitantly treated NPSLE patients. The sensitivity and specificity for each variable to identify CNS infection was assessed by receiver operating characteristic (ROC) curves. <h3>Results</h3> Our study shows that mortality rate was much higher in SLE patients with CNS infection than in NPSLE patients. Compared to NPSLE, those with CNS infection had lower lupus disease activity (SLEDAI), but took higher doses of corticosteroids one month before the occurrence of CNS symptoms. Headache, high fever and vomiting were more common in patients with CNS infections, accompanied with the elevation of C-reactive protein level. Cerebrospinal fluid examination (CSF) examination showed increased leukocytes and protein level but decreased glucose level in patients with CNS infections. Of all the variables, the combination of abnormal CSF test, low SLEDAI score, high fever and high intake of prednisone could best discriminate CNS infection from NPSLE in SLE patients (AUC=0.999, p=4.48x10<sup>–19</sup>). <h3>Conclusions</h3> We conclude that for SLE patients who have CNS symptoms, low SLE disease activity but high intake of corticosteroids, together with abnormal CSF and high fever, may suggest the existence of CNS infection. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2205
ORAL ANTICOAGULANTS WITH DUAL VERSUS SINGLE ANTIPLATELET THERAPY IN PATIENTS AFTER PERCUTANEOUS CORONARY INTERVENTION: AN UPDATED META-ANALYSIS
Authors: Alexandros Briasoulis, Emmanuel Androulakis, Nikolaos Papageorgiou, Effimia Zacharia, Mohan Palla, Marietta Charakida, Sagar Mallikethi-Reddy, Gerasimos Siasos, Konstantinos Toutouzas, Luis Afonso, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2016)
Abstract 1460: Piceatannol suppresses the migration and invasion of DU145 human prostate cancer cells
Authors: Gyoo Taik Kwon, Jin-Kyung Kim, Jung Han Yoon Park
Journal: Cancer Research (2010)

Abstract Piceatannol (trans-3,4,3′,5′-tetrahydroxystilbene) is a polyphenol found in grapes, red wine, Rheum undulatum and seeds of Euphorbia lagascae. The purpose of the present study was to investigate the effects of piceatannol on the migration and invasion characteristics of DU145 prostate cancer cells. DU145 cells were cultured in the presence of 0 − 10 μmol/L piceatannol with or without 10 μg/L epidermal growth factor (EGF). Piceatannol inhibited the basal and EGF-induced cell migration and invasion of DU145 cells. Gelatin zymography and Western blot analysis, Fibrin zymography and real time RT-PCR analysis were conducted using conditioned media and cell extracts. Piceatannol reduced the secretion and mRNA levels of matrix metalloproteinase (MMP)-9, urokinase-type plasminogen activator (uPA), and vascular endothelial growth factor (VEGF). Piceatannol decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels in a concentration-dependent manner. Additionally, piceatannol inhibited the phosphorylation of signal transducer and activator of transcription (STAT)3. Furthermore, piceatannol decreased both basal and EGF-induced secretion of IL-6. IL-6 treatment increased the secretion of uPA and VEGF, the phosphorylation of STAT3, and migration of DU145 cells and these increase were suppressed by piceatannol. An IL-6 nutralizing antibody inhibited the EGF-induced phosphorylation of STAT3 and increase in cell migration and invasion of DU145 cells, which may be mediated via the inhibition of MMP-9 and uPA activities and secretion of VEGF. The inhibition of IL-6/STAT3 activation may be one of the mechanisms by which piceatannol regulates the expression of proteins involved in the rehulation of DU145 cell migration and invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1460.
Case 30-2014
Authors: Daniel P. Hunt, Dushyant V. Sahani, Kathleen E. Corey, Ricard Masia
Journal: New England Journal of Medicine (2014)

A 29-year-old man was seen in the walk-in clinic because of diarrhea of 1 year's duration and weight loss. Initial laboratory values included elevated hepatic aminotransferase levels and a ferritin level of 1716 ng per milliliter. A diagnostic procedure was performed.
Xeliri Regimen with Continuous Treatment of Bevacizumab is Well-Tolerated and Effective as Second-Line Chemotherapy in Patients with MCRC
Authors: Koichi Suzuki, Takaharu Kato, Yuta Muto, Shingo Tsujinaka, Junichi Sasaki, Yutaka Kawamura, Fumio Konishi, Toshiki Rikiyama
Journal: Annals of Oncology (2013)