tbuckley/cabot-search huggingface dataset:
Choriocarcinoma in males: A Surveillance, Epidemiology, and End Results (SEER) analysis.
Authors: Alexander Howard, Lane Drury, Yimei Han, Jennifer Lynne Ersek, James Thomas Symanowski, Stephen Boyd Riggs, Rebecca Feldman, Edward S. Kim
Journal: Journal of Clinical Oncology (2017)

e13079 Background: Choriocarcinoma (CCA) is a rare tumor. In men, the main site is testis. Pure CCA composes &lt; 0.3% of testicular germ cell tumors. Other sites may represent metastatic disease (dz) or a non-testicular primary CCA. Surgery (S) is the preferred treatment as diagnosis prior to resection is difficult. We analyzed SEER data to determine demographic/clinical characteristics of male CCA patients (pts) and assess survival outcomes. Methods: Male pts with a confirmed diagnosis of CCA as their only primary tumor were included. Pts were grouped into cohorts by dz site (testis, other primary sites, all). S was defined as any type of surgery or no surgery. Stage was defined as local/regional or distant. Dz type was defined as pure or mixed. Overall survival (OS) and disease-specific survival (DSS) were analyzed with Cox proportional hazards (PH) models and Kaplan-Meier methods (5-yr landmark rates reported). Results: 1221 men were identified from 1988-2013. Median age = 28 (range 0-84). Other characteristics included: White (86.9%), mixed CCA (64.9%), local/regional (45.4%), S (78.7%) and testis (83.0%). For other primary site pts (17.0%), lung/mediastinum was most common (36.7%). Stage and S significantly impacted OS and DSS, regardless of dz site. For testis pts, OS (95% vs 56%; p &lt; .001) and DSS (96% vs 61%; p &lt; .001) were significantly better for pts with local/regional dz, as were OS (68% vs 27%; p = 0.032) and DSS (68% vs 29%; p = 0.042) for other primary site pts. Testis pts with S had significantly improved OS (83% vs 34%; p &lt; .001) and DSS (85% vs 40%; p &lt; .001), as did other primary site pts with S (OS: 54% vs. 23%; p = 0.004 and DSS: 62% vs. 34%; p = 0.002). OS for all pts was analyzed with a multivariable Cox PH model, including age, marital status, dz site and type, stage, and S. Testis pts had a reduced risk of death compared to other primary site pts (HR 0.66; 95% CI 0.47-0.92). Pure CCA pts had a 61% increased risk of death compared to mixed CCA pts (HR 1.61; 95% CI 1.24-2.08). S pts had a 48% reduced risk of death compared to pts without S (HR 0.52; 95% CI 0.40-0.67). Conclusions: Pure CCA and non-testicular primary pts have poorer outcomes. S is an important component to survival in men with CCA. This is the first descriptive analysis of male CCA utilizing SEER.
CXCR4/SDF-1 expression in HER2/neu breast cancer biopsies and its relation to adjuvant treatment.
Authors: Natalia CAROLINA Ayala, Angel Alsina, Mariana MARIA Gomez Pescie, Guillermo Luis Lerzo, Jorge Zimerman, Maria Zimmermann
Journal: Journal of Clinical Oncology (2016)

e12090 Background: Chemokines have a fundamental role in inflammation and in cancer progression. Chemokine receptor 4 (CXCR4) is a transmembrane receptor that belongs to the CXC chemokine receptor family and is the only known receptor for the Stromal Cell derived Factor-1(SDF-1). Many retrospective studies have documented that the expression of various chemokine receptors, particularly CXCR4, was associated with a poor prognosis in patients with breast cancer. In the present study, we proposed an SDF-1/CXCR4 induced expression in HER2/neu positive breast cancer biopsies. We, additionally, study its relation to patient’s treatment, prior and post adjuvant therapy. Methods: Immunohistochemical staining of her2/neu and ki64 were analyzed in mammary tumor biopsies. Reduction mammoplasty of normal patients were also studied as normal controls. Stained hematoxilyn and eosin slides where previously revised to confirm histological diagnostic and tumoral classification based on established criteria. Additional information considering biological markers such as estrogen receptor (ER), progesterone receptor (PR) expression were also observed in histopathological reports. Quantitative PCR was performed by amplifying a conserved region of the CXCR-4 and SDF-1 genes, and their correlation to Her2/neu expression and adjuvant therapy were analyzed. Statistical analysis was assess using appropriate parametric and nonparametric tests. Results: Her2/neu breast tumor specimens expressed SDF-1 at varying levels and differed upon tumor classification. Expression of the receptor correlates mainly with the tumor type and degree. Quantitative PCR showed low constitutive CXCR4 expression in normal breast tissue that increased in breast tumor tissue, particularly in those expressing her2/neu. Variations upon treatment correspond to those of tumor progression to malignancies and recurrence. Conclusions: We established a correlation between the expression of SDF-1/CXCR4 and the tumoral characteristics prior and post adjuvant treatment. A more careful examination of experimental/clinical data may help to explain the mechanism(s) involving the SDF-1/CXCR4 signaling axis in the breast cancer pathophysiology.
Abstract 10581: Cardio Renal Arrhythmia Study in Hemodialysis Patients Using Implantable Loop Recorders (CRASH-ILR)
Authors: Paul R Roberts, Donah Zachariah, Natalie Borman, John M Morgan, Arthur M Yue, Elizabeth F Greenwood, Patrick C Phillips, Darren Green, Kalra A Philip, Robert J Lewis, Paul Kalra
Journal: Circulation (2013)

Cardiac mortality in hemodialysis (HD) patients accounts for 43% of deaths, 58% of these are attributed to arrhythmias. Explanations for an arrhythmic cause in this population include left ventricular hypertrophy, coronary artery disease, electrolyte imbalance, volume changes, myocardial fibrosis/hypertrophy. Palpitations/syncope are frequently reported by this population. The true incidence of arrhythmic burden in the HD population has never been comprehensively studied. We report the interim analysis of the prospective use of an ILR in this population.   Methods:  18 pts (15 male, EF 55±8%) aged 68±8 yrs consented to implantation of an ILR (Reveal XT, Medtronic, USA). Pts had been on HD for 33±22 months prior to recruitment with a variety of aetiologies of CKD including diabetes, hypertension, amyloid, glomerulonephritis. Device programming was standardized to include automatic detection of brady/tachy arrhythmias and patient activated recordings (PAR). After ILR implantation pts were encouraged to remotely transmit at each dialysis session. All transmissions were reviewed and events analysed by an events committee.   Results:  To date there have been 124,512 hours continuous monitoring (6917±4281). 1059 transmissions (62±48) have been made and 11 PARs. There have been significant clinical events in 4 pts: ILR demonstrated >3 sec pauses requiring pacemaker implantation, one died from SCD and ILR interrogation identified ventricular fibrillation, one required ILR explantation due to infection and died from unrelated SCD several weeks later, one had sudden onset of atrial tachycardia requiring anti arrhythmic drugs. All PARs corresponded to sinus rhythm. Automatic detection identified 756 bradycardic events (99.6% due to device undersensing) and 5520 tachycardic events (99.9% due to oversensing).   Conclusions:  Clinical research involving multiple specialities is challenging but this study has successfully bridged the cardiorenal interface. In >5000 days of continuous ECG recording in pts on HD >22% had significant events. PARs were not associated with arrhythmias. This study aims to document >30,000 days of monitoring and so will offer a significant insight into the event rate and true nature of the arrhythmic burden of HD.
Fibroblast‐derived exosomes promote epithelial cell proliferation through <scp>TGF</scp>‐β2 signalling pathway in severe asthma
Authors: I. Haj‐Salem, S. Plante, A. S. Gounni, M. Rouabhia, J. Chakir
Journal: Allergy (2017)

Bronchial fibroblasts play a key role in airway remodelling in asthma. They regulate epithelial cell functions such as proliferation through growth factors, cytokines, chemokines and exosomes. The role of exosomes in the communication between epithelial cells and fibroblasts by vehiculing these mediators in asthma remains to be determined.To evaluate the role of exosomes released by bronchial fibroblasts on epithelial cell proliferation in severe asthma.Exosomes were obtained from culture media of primary bronchial fibroblasts and characterized using Western blot, electron microscopy and flow cytometry. Uptake profile of fluorescent-labelled exosomes in epithelial cells was assessed by flow cytometry. Exosome cytokine content was analysed by Cytokine Arrays. Bronchial epithelial cell proliferation was evaluated by BrdU incorporation test. Exosome biogenesis/release was blocked using sphingomyelinase inhibitor. Plasmid transfection was used to modulate transforming growth factor beta 2 (TGF-β2) gene expression.We showed that bronchial fibroblasts secreted exosomes, which were internalized by bronchial epithelial cells. Exosomes of severe asthmatic subjects' fibroblasts showed a lower level of TGF-β2 and significantly increased the epithelial cell proliferation of both healthy and severe asthmatic subjects compared to healthy controls' exosomes. Overexpression of TGF-β2 in severe asthmatics' fibroblasts induced enhanced TGF-β2 in exosomes leading to a reduced proliferation of epithelial cells, whereas knockdown of TGF-β2 enhanced epithelial cell proliferation.Our study shows that exosomes are involved in fine-tuning intercellular communication in asthma. Exosomes of severe eosinophilic asthmatics' fibroblasts can contribute to airway remodelling, at least in part, by modulating epithelial cell proliferation observed in severe asthma.
Contribution of the <i>TP53</i> R337H mutation to the cancer burden in families with a proband with adrenocortical tumor.
Authors: Maria Jose Mastellaro, Guolian Kang, Ana Luiza Seidinger, Eliana C. M. Miranda, Renata AbrahÃ, Bonald Cavalcante de Figueiredo, Carlos Rodriguez-Galindo, Jose A Yunes, Antonio A Barros, Raul Correa Ribeiro
Journal: Journal of Clinical Oncology (2016)

1538 Background: The TP53R337H mutation, a loss-of-function founder mutation in the Southern Brazilian population, predisposes children to adrenocortical tumor (ACT), choroid plexus carcinoma, and, rarely, other tumors, but its impact on adult-onset cancer remains to be determined. We describe the history of cancer in R337H carrier lineages and compare the frequency and types of cancer in carrier and noncarrier parental lineages and in selected families reported to the IARC database. Methods: The history of cancer in 55 families with a proband with ACT carrying the R337H mutation was updated yearly. Quasi-likelihood score, generalized disequilibrium, chi-square, and Fisher’s exact tests were used to analyze cancer frequency and spectrum. Results: The R337H status was determined for 175 of 179 first-degree relatives of the probands. At a median follow-up time of 9.7 years (3–32 years), new-onset cancer had been diagnosed in 12 (15%) of 81 first-degree relatives of probands in the R337H carrier lineages but in only 1 (1.1%) of 94 first-degree relatives in the noncarrier lineages (P = 0.0022). At 45 years of age, the cumulative incidence of cancer was 17% (95%CI, 5%–29%) in carriers compared to 2% (95%CI, 0%–4%) in noncarrier lineages (p < 0.001). The frequency of cancer in 1410 individuals in the R337H carrier lineages was significantly higher than that in 984 individuals in the noncarrier lineages (249 vs. 66; P < 0.0001). The odds ratio of developing cancer was 54% higher for R337H carrier individuals (OR = 1.54; 95%CI, 1.50–1.58). In these carriers, 93 of 135 cancers (68.9%) occurred in individuals older than 45 years. Compared with 37 families with probands with ACT carrying TP53 mutations other than R337H (from the IARC database), adults in R337H carrier lineages were significantly older at diagnosis of cancer (median age, 45 vs. 35 years; P < 0.0001) and had a higher incidence of GI tract cancer (31.5% vs. 8.33%; P < 0.0001). Conclusions: TP53 R337H carriers have an increased lifetime cancer risk with a bimodal age distribution: one peak (ACT) occurs in the first decade and the other in the fifth decade (diverse cancer types). Our findings have implications for genetic counseling and surveillance of R337H carriers.
L'utilisation des critères d'EPAGE (European Panel on Appropriateness of Gastrointestinal Endoscopy) pour déterminer le caractère approprié ou non d'une coloscopie permet-elle de mieux sélectionner les malades susceptibles de bénéficier de l'examen?
Authors: B Kaliszan, T Vallot, N Mathieu, N Bouarioua, T Aparicio, A Ramdani, N Bonin, JC Soulé
Journal: Endoscopy (2006)

En 1999 un panel d'Experts Européens l'EPAGE a élaboré un programme interactif, accessible par internet: www.epage.ch, permettant d'évaluer la pertinence des indications des coloscopies. But: évaluer l'applicabilité des critères de l'EPAGE en pratique clinique et a confronter la classification de l'indication selon EPAGE avec le résultat de l'endoscopie et le jugement de l'opérateur après la coloscopie sur l'utilité clinique de l'examen.
Манометрія в дослідженні рухової функції верхніх відділів травної системи
Authors: Yu.M. Stepanov, V.M. Ratchik, N.V. Prolom, A.A. Galinskyi, S.A. Tarabarov
Journal: GASTROENTEROLOGY (2017)

Порушення моторики стравоходу, шлунка, дванадцятипалої кишки (ДПК) може виступати провідним патогенетичним чинником, що сприяє розвитку багатьох поширених захворювань травного тракту. Дослідження моторної функції має важливе значення для оцінки функціонального стану різних відділів шлунково-кишкового тракту (ШКТ). Клінічне значення дослідження рухової функції травної системи постійно зростає, діагностування порушення перистальтичної активності за клінічними симптомами доповнюється сучасними методами реєстрації рухової активності стравоходу, шлунка і кишечника. Манометр верхніх відділів травного тракту дає можливість оцінити показники внутрішньопорожнинного тиску стравоходу, шлунка і ДПК, а також сфінктерного апарату і є золотим стандартом у діагностиці порушень рухової активності верхніх відділів ШКТ, сфінктерного апарату.
Ips Technology Revealed the Genetic and Functional Diversity Present in a Secondary AML Patient
Authors: Kazuhisa Chonabayashi, Masahiro Kawahara, Akira Watanabe, Masahiro Nakamura, Masatoshi Nishizawa, Akifumi Takaori-Kondo, Shinya Yamanaka, Yoshinori Yoshida
Journal: Blood (2016)
Arterial Remodeling After Bioresorbable Scaffolds and Metallic Stents
Authors: Patrick W. Serruys, Yuki Katagiri, Yohei Sotomi, Yaping Zeng, Bernard Chevalier, René J. van der Schaaf, Andreas Baumbach, Pieter Smits, Nicolas M. van Mieghem, Antonio Bartorelli, Paul Barragan, Anthony Gershlick, Ran Kornowski, Carlos Macaya, John Ormiston, Jonathan Hill, Irene M. Lang, Mohaned Egred, Jean Fajadet, Maciej Lesiak, Stephan Windecker, Robert A. Byrne, Lorenz Räber, Robert-Jan van Geuns, Gary S. Mintz, Yoshinobu Onuma
Journal: Journal of the American College of Cardiology (2017)
A call for global harmonization of phase I oncology trials: Results from two parallel, first-in-human phase I studies of DS-7423, an oral PI3K/mTOR dual inhibitor in advanced solid tumors conducted in the United States and Japan.
Authors: Tomoya Yokota, Johanna C. Bendell, Patricia LoRusso, Takahiro Tsushima, Ved Desai, Hirotsugu Kenmotsu, Junichiro Watanabe, Akira Ono, Bhavani G. Murugesan, Joseph Silva, Tateaki Naito, Jonathan Greenberg, Prasanna Kumar, Yibin Wang, Takahiro Jikoh, Ryota Shiga, Alan Loh Ho, Mrinal M. Gounder
Journal: Journal of Clinical Oncology (2017)

2536 Background: The aim of this study was to determine the safety, maximum-tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of DS-7423, a novel inhibitor of PI3K/mTOR, in US and Japanese population. We further compared toxicities and recommended phase 2 dose (RP2D) of DS-7423 and approved oncology drugs in the two populations. Methods: We conductedparallel, first-in-human studies in US and Japan in patients with advanced solid tumors. We conducted a Pubmed search of pivotal and corresponding phase I studies to compare the RP2D and final approval doses of molecularly targeted agents (MTA) between US and Japan. Results: 69 patients were enrolled (n = 42 from US and n = 27 from Japan). Between populations, the only difference at baseline was body weight (BW) and body mass index (BMI). Dose-limiting toxicities included grade 3 rash (48 mg), grade 3 stomatitis (240 mg), grade 3 lung infection (240 mg), grade 4 hyperglycemia (240mg), grade 3 fatigue (320 mg), and grade 3 dehydration (320mg). The MTD and RP2D was 240 mg/d in both populations. Frequent treatment-related adverse events included diarrhea, fatigue, decreased appetite, rash, and stomatitis. No remarkable difference in AUC and Cmax were observed between populations. Prolonged stable disease was seen in cholangiocarcinoma, thymic cancer, non-small cell lung cancer, squamous cell carcinomas, carcinoid, and sarcoma. DS-7423 demonstrated PD effects on serum glucose, C-peptide and Akt phosphorylation and 18F-FDG uptake in tumors. The final RP2D of 17 MTA approved in US and Japan from 2001 to 2015 was near identical. The approved doses in both regions were identical. Conclusions: Despite differences in BW, BMI, and ethnicity, DS-7423 showed no difference in PK, PD, toxicity or efficacy between populations. We found near identical RP2D in phase I oncology studies and approved doses in pivotal studies. This supports increased international collaboration in the conduct of phase I oncology trials. Clinical trial information: NCT01364844, Japic CTI, 12766.
Evaluating genetic and genomic sequencing knowledge from parents and young adult cancer survivors.
Authors: Trisha Ali-Shaw, Jennifer Levine, Jenny Ruiz, Andrew L. Kung, Julia Lynne Glade Bender, Jennifer Oberg
Journal: Journal of Clinical Oncology (2016)

1579 Background: Increasing utilization of clinical comprehensive sequencing (CS) in pediatric oncology suggests that patients and/or their caregivers will need to understand the value and limitations of CS before undergoing testing. The Precision in Pediatric Sequencing Knowledge Questionnaire (PIPseqKQ) was developed to assess CS and genetic knowledge in pediatric oncology. Methods: The PIPseqKQ assesses 3 knowledge domains: general genetic concepts (GC, 7 items), genetic concepts related to health and cancer (HC, 12 items), and whole genome/exome sequencing concepts (SC, 16 items). The paper and pencil questionnaire was administered to parents or young adult cancer survivors > 1 year off-therapy. Health literacy was assessed using The Newest Vital Sign. Results: 91 participants completed the PIPseqKQ: 71% (n = 65) parents, 29% (n = 26) young adults, 73% of respondents were female (n = 66), white (56%, n = 50) and non-Hispanic (64%, n = 58). The most common diagnosis was leukemia/lymphoma (62%, n = 56). Results are presented for the group since no difference in PIPseqKQ total scores was found between parents and cancer survivors (p= 0.45). Participants answered correctly 71% and 68% of the time on GC and HC items, respectively. In the SC domain: 41%/ 46% of respondents were incorrect/ unsure about the likeliness of sequencing to guide initial treatment, 53% were unsure if CS could find changes related to non-cancerous diseases, 47% were unsure if secondary findings might be inherited and could be present in other family members, and 43%/ 44% were incorrect/ unsure about CS having no impact on care for most children with cancer. 78% of participants demonstrated adequate literacy. However, those with limited literacy (M= 22.5, SD = 4.0) had significantly lower PIPseqKQ total scores than those with adequate literacy (M= 25.4, SD = 3.1), p= .03. Conclusions: Participants had some knowledge of genetics and limited knowledge of CS. Lower overall knowledge scores were demonstrated in those with limited literacy. Next steps include validation of the PIPseqKQ in a larger number of participants. Further research is needed to optimize patient education to improve the informed consent process for CS in pediatric oncology.
Anterior continence enema for faecal incontinence
Authors: S Brophy, J Deasy, DA McNamara
Journal: Endoscopy (2006)

Aims: The anterior continence enema (ACE) is a novel method of treating faecal incontinence secondary to neuropathic bowel and involves formation of a continent catheterisable stoma connected to the caecum, through which enemas are flushed to aid evacuation. We present the first report of this procedure in an Irish setting.
Artery tertiary lymphoid organs in giant cell arteritis are not exclusively located in the media of temporal arteries
Authors: Jacoba Carolien Graver, Maria Sandovici, Arjan Diepstra, Annemieke M H Boots, Elisabeth Brouwer
Journal: Annals of the Rheumatic Diseases (2017)

With great interest, we read the article by Ciccia et al, about artery tertiary lymphoid organs (ATLOs) in giant cell arteritis (GCA) and the association with ectopic expression of constitutive lymphoid tissue-homing chemokines.1 In 50 patients with biopsy-proven GCA that fulfilled the 1990 ACR classification criteria2 and had temporal transmural inflammation, Ciccia et al  documented the presence of ATLOs in 60% of the patients. In their study, ATLOs were defined as inflammatory aggregates that displayed a well-defined compartmentalisation of T and B cells. The authors state that ATLOs were exclusively located in the media of the temporal artery. In addition, the authors mention that the location of ATLOs in the media of the inflamed temporal artery is peculiar and deviating from the ‘classic’ adventitial location of ATLOs, as, for instance, seen in atherosclerosis.3 4 However, the figures included in the article do not convincingly provide evidence that the ATLO location is in the media.

Until recently, B cells have received little attention as putative players in the immunopathology of GCA. B cells and germinal centre formation were reported to be absent from vascular infiltrates, and in spite of several attempts, no disease-specific autoantibody production has been identified. …
Effect of hypoxia on cadherin expression in colorectal cancer
Authors: S Brophy, DA McNamara, E Kaye, D Bouchier-Hayes
Journal: Endoscopy (2006)

Aims: Cadherins mediate cell-cell adhesion in epithelial tissues, and in epithelial tumours loss of E-cadherin expression is associated with reduced survival and increased metastases while neo-expression of N-cadherin increases tumour invasiveness. We investigated the effect of hypoxia on cadherin expression in colorectal cancer cell lines.