tbuckley/cabot-search huggingface dataset:
Abstract 2264: K-ras mutations in colorectal cancer may predict a pattern of organ-specific metastasis
Authors: Ignacio Garrido-Laguna, Filip Janku, Gerald S. Falchook, Siqing Fu, Aung Naing, Jennifer Wheler, Apostolia Tsimberidou, David S. Hong, Razelle Kurzrock
Journal: Cancer Research (2011)

Abstract Background: Activating mutations of the K-ras oncogene in colorectal cancer (CRC) are associated with resistance to EGFR antibodies and poor prognosis. We systematically analyzed clinical and pathological characteristics associated with K-ras mutations. Methods: Patients with CRC referred to the phase I program for targeted therapy were analyzed for K-ras mutations using PCR-based DNA sequencing. Patients with mutant K-ras were matched with wild-type (wt) K-ras controls. Multiple clinical and pathological characteristics were analyzed to determine, whether there is a phenotype associated with K-ras mutations. Results: A total of 151 patients with CRC were identified; 61 with K-ras mutations; 80 with wt K-ras and 10 with unknown K-ras status. Patients with K-ras mutations compared with wt K-ras had more frequently lung metastases (80% vs. 63%, p = 0.03). Patients whose tumors had K-ras mutations had higher number of metastatic sites of disease (3.18 vs. 2.65; p = 0.013). There were no associations between K-ras mutations and gender, age at diagnosis, liver metastases, peritoneal metastases, lymphatic involvement or Duke stage at diagnose. Patients with K-ras wt had a trend for longer median survival (283 vs. 222 weeks, p=0.09). There was no difference in the median survival from diagnosis in patients with different types of K-ras mutations (codon 12, codon 13, and codon 61). Dukes staging was the only statistically significant prognostic factor on multivariate analysis (p &amp;lt; 0.05). Conclusions: K-ras mutations in CRC in comparison with wt K-ras were associated with more frequent lung metastases and shorter survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2264. doi:10.1158/1538-7445.AM2011-2264
Unification of European Trials Is Ahead of Maastricht
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Unification of European Trials Is Ahead of Maastricht Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 16, August 1993, Pages 1274–1276, https://doi.org/10.1093/jnci/85.16.1274 Published: 01 August 1993
The Clinical Significance of Serum Transaminase in Infectious Mononucleosis Complicated by Hepatitis
Authors: Laurie E. Rennie, Felix Wroblewski
Journal: New England Journal of Medicine (1957)

INFECTIOUS mononucleosis is complicated by nonicteric hepatitis in most patients.1 , 2 Confirmation of this generalization is found in a study of patients with infectious mononucleosis during which serial liver biopsies were obtained.3 Although during infectious mononucleosis liver involvement is suggested by liver-function tests, these tests do not actually appear dynamically to reflect the clinical course of the hepatitis.Studies of serum glutamic pyruvic transaminase (SGP-T) and serum glutamic oxaloacetic transaminase (SGO-T) in patients with icteric as well as nonicteric hepatitis indicate that these serum enzymatic parameters are more sensitive reflections of liver injury than the conventionally employed tests of liver function. . . .
Abstract P3-10-38: Histopathological Subclassification of Triple Negative Breast Carcinoma Using Prognostic Scoring System
Authors: M Miyashita, T Ishida, K Tamaki, M Amari, N Ohuchi, H. Sasano
Journal: Cancer Research (2010)

Abstract Purpose: Triple negative breast carcinoma (TNBC) is currently being required to be classified pluralistically in order to provide the most appropriate therapy to the patients. We attempted to subclassify TNBC cases into subgroups based on clinical outcome or prognosis of the patients with TNBC using archival specimens. Materials and Methods: We analyzed 102 Japanese cases of invasive TNBC who underwent surgery between January 1998 and December 2007. The clinicopathological factors and clinical information of these patients were retrospectively retrieved from charts of the patients. Immunohistochemical staining was performed for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor 1 (EGFR1), CK5/6, Ki-67 and CD31 for microvessel density (MVD). Results: Median follow-up time of the patients was 68.5 months. Multivariable analysis demonstrated that the pathologic node status was the most significantly associated with relapse-free survival (RFS) and breast cancer-specific survival (BCSS) of the patients. Pathological tumor size, basal-like type, Ki-67 labeling index (LI) and MVD were also independently associated with RFS and BCSS. Based on these results, we devised the Risk Score system reflecting Hazard ratios (HRs) of these prognostic factors above. Multivariate analysis and the Risk Score for TNBC patients. With this system, TNBC patients in this study were classified into three subgroups; patients with score 0-3 are in low risk group, score 4-7 in intermediate risk group and score 8- in high risk group. These three groups had statistically significant differences for risk of relapse and breast cancer-specific death, respectively. Conclusions: We propose the Risk Score system, which incorporated pathologic nodal status, size of the primary tumor, the presence or absence of basal-like features, Ki67 LI and MVD of the patients in order to predict postoperative clinical course of the Japanese patients with TNBC. Such a classification which can be performed in diagnostic pathology laboratory can be useful as a decision-making tool for triple negative patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-38.
Endoscopic trimming of a migrated gastroduodenal stent using a loop cutter and a two-channel endoscope
Authors: Takashi Sasaki, Hiroyuki Isayama, Shuntaro Yoshida, Yousuke Nakai, Hiroharu Yamashita, Yasuyuki Seto, Kazuhiko Koike
Journal: Endoscopy (2014)

A 69-year-old man with gastric cancer was admitted to our hospital because of vomiting. Two gastroduodenal stents (Niti-S D pyloric/duodenal stent; TaeWoong Medical Inc., Seoul, South Korea) had previously been inserted from the first portion of the duodenum to the body of the stomach because of antral obstruction. Esophagogastroduodenoscopy revealed migration of the proximal stent ([Fig. 1]). The stent required trimming to resolve the symptoms.
Effects of time-variant exposure on toxic substance response.
Authors: P F Morrison
Journal: Environmental Health Perspectives (1987)

Sources of time-variant exposure to toxic substances are identified and examined for their effects on the estimation of response. It is shown that only time-averaged target tissue concentrations are required to obtain rigorous risk estimates from the one-hit and multihit models. In contrast, detailed concentration histories need to be retained throughout analyses involving two-event models with intermediate-stage clonal growth advantage (clonal two-stage) and multistage models. Cumulative incidence ratios, based on the exact to time-averaged treatment of concentration time dependencies, are evaluated for substances whose toxic responses exhibit moderate (arsenic) and strong (ethylene dibromide) dependence on time of actual exposure. These ratios reveal that time-averaged dose approximations may lead to several orders of magnitude error in both the multistage and clonal two-stage models if exposure periods are short, and that 3.4-fold (arsenic) and 8-fold (ethylene dibromide) errors still exist even when an actual two-thirds lifetime exposure is averaged over a full lifetime. Finally, the effects of time-variant exposure on risk estimation due to migration and birth-death in an epidemiological setting are examined. A residence time distribution calculation shows that, if these effects are ignored for a population orally exposed to arsenic and characterized by an out-migration rate in excess of 5%/yr, response errors will exceed an order of magnitude.
Abstract A32: Pretargeted immunoPET of CEA-expressing in intraperitoneal human colonic tumor xenografts in nude mice
Authors: Rafke Schoffelen, Robert M. Sharkey, Gerben M. Franssen, David M. Goldenberg, William J. McBride, Edmund A. Rossi, Chien-Hsing Chang, Peter Laverman, Winette T.A. Graaf, Wim J.G. Oyen, Otto C. Boerman
Journal: Clinical Cancer Research (2010)

Abstract Objective: Radiolabeled antibodies were being developed commercially for the detection of several cancer types. However, imaging with radiolabeled antibodies require a relatively long interval between injection and imaging acquisition for adequate contrast to develop. The pretargeting method is a 2-step method: a unlabeled bsMAb with affinity for the tumor and a small radiolabeled molecule is injected, followed by the a radiolabeled compound. This aims to optimize the imaging system by specific tumor accumulation and fast blood clearance of the radiopharmacon, which allows imaging within one hour. Short-lived positron emitting radionuclides, e.g. 68Ga (half life: 68 min) match the pharmacokinetics of the small molecule. In this study, pretargeted immunoPET with a bispecific monoclonal anti-carcinoembryonic antigen (CEA) x anti-histamine-succinyl-glycine (HSG) antibody, TF2, and a radiolabeled peptide, IMP288, was compared to 18F-FDG in detecting CEA-expressing tumors in nude mice. Methods: Groups of five BALB/c nude mice were inoculated with CEA-expressing human colonic tumor cells intraperitoneally. One group received 5 MBq 18F-FDG intravenously (i.v.). Another group received TF2 and 5 MBq 68Ga-IMP288 i.v. 16 h later. After one hour PET/CT images were acquired. One day later this was repeated vice versa. Uptake of 68Ga-IMP288 or 18F-FDG in the tumors and other dissected tissues was determined. Results: High, specific tumor uptake of 68Ga-IMP288 (23.4 ± 7.2% ID/g) was observed, with very low accretion in the normal tissues (intestines: 0.50 ± 0.19 % ID/g; liver: 1.83 ± 0.45 % ID/g). This resulted in high tumor-to-background ratios (e.g. tumor-to-intestines 57.5 ± 22.4) and in the clear visualization of the small intra-abdominal tumor lesions (1.5–5 mm), as soon as one hour after the injection of 68Ga-IMP288. 18F-FDG localized efficiently in the tumors (8.7 ± 3.1 % ID/g), but with physiological uptake in various normal tissues (intestines: 2.15 ± 0.61 % ID/g; liver: 2.78 ± 0.52 % ID/g). The low tumor-to-background ratio (e.g. tumor-to-intestines 4.0 ± 0.9) complicated the detection of the tumors. Conclusions: This study indicated that pretargeted immunoPET with TF2 and 68Ga-IMP288 is a specific and sensitive method for detecting colon cancer. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A32
The lung microbiome: the perfect culprit for COPD exacerbations?
Authors: Carine Gomez, Pascal Chanez
Journal: European Respiratory Journal (2016)

Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of diseases which affects more and more patients in Europe and represents an important challenge for the respiratory community. These airway diseases present different faces from a clinical, functional and pathophysiological point. So, we should better understand the underlying mechanisms contributing to the various phenotypes, which are probably the consequences of interactions between genes and environmental factors. Our current treatments are mainly symptom-driven and do not interfere with the natural history of the disease. The accelerated decline in lung function and the recurrence of severe exacerbations are important features representing most of the patient burden. Exacerbations are clearly defined at least from a clinical perspective, now, but still represent a challenging goal to be fully deciphered. A better understanding of the pathophysiological mechanisms of these acute events is required to optimise their management and their prevention. Interaction between lung microbiota and inflammation is closely related to the pathogenesis of COPD exacerbation <http://ow.ly/Z1B7o>
AB0792 Regenerative Power of Autologous Peripheral Blood Stem Cell Injection in Knee Osteoarthritis by A NON Invasive Approach - MRI Study-
Authors: N. Abdelmoaty, E. Alattar, K. Ahmed, Y. Ibrahim, B. Darwish
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteoarthritis (OA) describes age-related, heterogeneous group of disorders characterized pathologically by focal areas of loss of articular cartilage in synovial joints, associated with varying degrees of osteophyte formation, subchondral bone change, and synovitis. Currently, cartilage repair remains a major challenge for physicians, being avascular with limited regenerative capacity. Stem cell therapy opened new horizons for hyaline cartilage repair. Peripheral blood stem cells (PBSC) due to their multi-lineage potential, immunosuppressive activities, limited immunogenicity, were tried as intra articular injection <h3>Objectives</h3> To find out the regenerative effect of repeated intra articular injection of autologous PBSC in knee joints of OA patients by a non invasive technique <h3>Methods</h3> The research carried out here with human subjects was in compliance with the Helsinki Declaration. 10 Egyptian patients (3 males and 7 females) diagnosed with bilateral knee joints OA were included in this study, they underwent full history taking, clinical examination, WOMAC index, 6 minutes walking distance test 6, and MRI cartilage imaging by using the semi-quantitative whole joint assessment score of knee for OA (MOAKS). Three intra articular injections of 8 ml of autologous PBSC in each knee after enhancement in quartz tube in a custom made machine. <i>Patent application number: 2011101817.</i> Clinical and radiological assessments were repeated after 1 year. <h3>Results</h3> Post injection WOMAC index sections revealed a significant reduction in all parameters. 6 MWD was increase by more than 54 meters. Improvement was expressed as percentage of change of the maximum scores. MR images analysis showed that the mean % of change of the maximum score of full thickness cartilage loss was 44 + 27. Total WOMAC index was significantly inversely correlated with % of change of maximum score of full thickness cartilage loss; denoting cartilage repair (r= -0.073, P≤0.05). <h3>Conclusions</h3> Limited good level of evidence showed that repeated intra-articular injection of autologous PBSC resulted in improvement of the quality of articular cartilage repair and physical function as observed from the MRI and clinical assessment. Keywords: cartilage repair, intra-articular injection autologous PBSC,WOMAC index, MRI cartilage imaging <h3>Acknowledgements</h3> We are appreciating dr. Sayed ElOkda for his effort in doing the statistics needed for addressing these results <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1323
P5-01-02: Wnt5a Is a Prognostic Biomarker in Estrogen Receptor-Positive Premenopausal Breast Cancer.
Authors: JT Sand-Dejmek, R Ehrnstrom, T Andersson, L Ryden
Journal: Cancer Research (2011)

Abstract Background Wnt proteins belong to a family of secreted growth factors, which are involved in a wide range of cellular processes. Wnt signaling can be broadly divided into two categories; the canonical, β-catenin-dependent pathway and the non-canonical β-catenin-independent pathway. Wnt5a is a non-canonical signaling member of the Wnt family. Studies in two smaller cohorts of breast cancer revealed that loss of Wnt5a was associated with early relapse, metastatic disease and poor survival. Moreover, reconstitution of Wnt5a signalling decreased the migratory capacity and invasiveness of cultured breast cancer cells and administration of a Wnt5a-mimicking peptide was proven to inhibit metastases in a mouse model. Material and methods: Premenopausal women (n=564) were included in a controlled randomised trial and allocated to tamoxifen for two years versus no adjuvant treatment. A tumour tissue microarrays was constructed and 390/500 samples were evaluable for Wnt5a protein expression by immunohistochemistry. Only cases with at least 2 evaluable cores were included. Wnt5a levels were determined semiquantitatively (scores 0–3). Clinical and pathological data such as patient age, histological subtype, pT stage, tumor size, pN stage, ER, PR, Ki67 and HER2 status were available. The end-point was 10 year recurrence-free survival. Results: Wnt5a protein expression was lost in 158/390 of the analyzed tumors and more common in younger (&amp;lt;45 yrs) women (p=0.032). Furthermore, loss of Wnt5a was significantly associated with ER and PR negativity (p=0.019 and p= 0.033, respectively). Loss of Wnt5a was significantly correlated to poor survival in the whole cohort, p=0.02. When analyzing the data according to breast cancer subtype, we found that Wnt5a was a strong independent prognostic factor in ER+ breast cancer p=0.009, but not in ER- breast cancer p=0.8. This was true both in the adjuvantely treated and untreated cohorts, verifying that Wnt5a indeed is a true prognostic factor and not a predictor of response to therapy. Discussion: While associated with a better short-time prognosis than ER negative tumors, a subset of ER positive breast cancer patients are known to experience tumor recurrencies &amp;gt;5 years after primary treatment and hence have a dismal prognosis. Those patients need to be identified and their tumors targeted with more aggressive treatment regimens. We have identified and validated Wnt5a as a prognostic biomarker in ER positive breast cancer in premenopausal women. Wnt5a signalling could potentially be reconstituted by administration of a Wnt5a-mimicking peptide, shown to inhibit metastases in mice, thereby offering ER positive premenopausal patients a targeted adjuvant therapy that potentially could lower their risk of metastatic disease. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-02.
The Diagnosis of Cystic Fibrosis
Authors: R C Stern
Journal: New England Journal of Medicine (1997)

Cystic fibrosis is an autosomal recessive disease caused by mutations of a gene located on the long arm of chromosome 7.1 The gene product is the 1480-amino-acid cystic fibrosis transmembrane conductance regulator (CFTR), a protein that normally regulates and participates in the transport of electrolytes across epithelial-cell membranes and probably across intracellular membranes as well.2 Recent advances in genetics and molecular biology have led to the introduction of new tests for cystic fibrosis and to a reconsideration of the spectrum of the disease.Although the primary manifestations are presumably related, at least in part, to abnormal transport of electrolytes, the . . .
Consensus on Early Melanoma: Less Surgery, Fewer Tests
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Consensus on Early Melanoma: Less Surgery, Fewer Tests Get access Jim Mathews Jim Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 4, 19 February 1992, Pages 222–223, https://doi.org/10.1093/jnci/84.4.222 Published: 19 February 1992
A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier
Authors: Do-Geun Kim, Margaret S. Bynoe
Journal: Journal of Clinical Investigation (2016)

The blood-brain barrier (BBB) protects the brain from toxic substances within the peripheral circulation. It maintains brain homeostasis and is a hurdle for drug delivery to the CNS to treat neurodegenerative diseases, including Alzheimer's disease and brain tumors. The drug efflux transporter P-glycoprotein (P-gp) is highly expressed on brain endothelial cells and blocks the entry of most drugs delivered to the brain. Here, we show that activation of the A2A adenosine receptor (AR) with an FDA-approved A2A AR agonist (Lexiscan) rapidly and potently decreased P-gp expression and function in a time-dependent and reversible manner. We demonstrate that downmodulation of P-gp expression and function coincided with chemotherapeutic drug accumulation in brains of WT mice and in primary mouse and human brain endothelial cells, which serve as in vitro BBB models. Lexiscan also potently downregulated the expression of BCRP1, an efflux transporter that is highly expressed in the CNS vasculature and other tissues. Finally, we determined that multiple pathways, including MMP9 cleavage and ubiquitinylation, mediated P-gp downmodulation. Based on these data, we propose that A2A AR activation on BBB endothelial cells offers a therapeutic window that can be fine-tuned for drug delivery to the brain and has potential as a CNS drug-delivery technology.
FEASIBILITY AND REPRODUCIBILITY OF COMPUTED TOMOGRAPHY: ECHOCARDIOGRAPHY FUSION IMAGING IN STABLE CORONARY ARTERY DISEASE
Authors: Piotr Lipiec, Paulina Wejner-Mik, Katarzyna Wdowiak-Okrojek, Ewa Szymczyk, Adam Skurski, Andrzej Napieralski, Konrad Szymczyk, Jaroslaw D. Kasprzak
Journal: Journal of the American College of Cardiology (2015)
FRI0596-HPR The efficacy of aerobic high-intensity interval training on disease activity in patients with ankylosing spondylitis: a proof of concept randomized controlled trail
Authors: S. Halvorsen, K. B. Hagen, C. Fongen, I. J. Berg, S. A. Provan, T. Ueland, P. Aukrust, N. Vøllestad, H. Dagfinrud
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Exercise is recommended for patients with ankylosing spondyltis (AS). Yet, the efficacy and safety of aerobic high-intensive training has not been investigated in this patient group. <h3>Objectives</h3> To assess the safety (disease control) and efficacy of aerobic high-intensive training on disease activity in patients with AS. <h3>Methods</h3> In a randomized controlled trial, 28 subjects were allocated to either an exercise group (EG) or a control group (CG). The exercise program consisted of aerobic high intensity training 40 minutes three days a week and muscular strength training 20 minutes two days a week for 3 months. Primary outcome was disease activity measured with the AS Disease Activity Scale (ASDAS). Secondary outcome measures were the disease specific Bath AS (BAS) measures (DAI, FI, MI) and several biomarkers of inflammation: interleukin (IL)-6, IL-17A, IL-18, IL-23 assessed by enzyme immunoassays. The training was supervised twice a week to observe any possible adverse effects in disease symptoms. <h3>Results</h3> <h3>Conclusions</h3> This proof of concept study showed that aerobic high-intensity training was well tolerated by patients with AS and resulted in improvements in disease activity and physical function accompanied by a decrease in IL-23. <h3>Disclosure of Interest</h3> None Declared
Characterising the taxonomic composition of children and livestock gut microbiomes and of environmental samples and the potential role for household-level microbiome sharing in western Kenya
Authors: Emily Mosites, Thumbi Mwangi, Elkanah Otiang, Gemina Garland-Lewis, Matt Sammons, Clayton Onyango, Alexander Eng, Cecilia Noecker, Ohad Manor, Sarah Hilton, Doug Call, Njenga Kariuki, Jennifer Zambriski, Judith Wasserheit, Judd Walson, Guy Palmer, Joel Montgomery, Elhanan Borenstein, Richard Omore, Peter Rabinowitz
Journal: The Lancet Global Health (2016)

Background Humans and animals living in close proximity may share microbiome constituents at the household level because of daily domestic contact. Such sharing could affect enteric and metabolic functions of the gut microbiome of humans and livestock living in such households. We sought to characterise the microbiome of children, cattle, chickens, and environmental surfaces within households in western Kenya to determine the degree of microbiome sharing.