tbuckley/cabot-search huggingface dataset:
PTH-036 Human psychophysiological responses to visceral and somatic pain: towards an integrated reproducible pain endophenotype?
Authors: A D Farmer, S J Coen, M Kano, Q Aziz
Journal: Gut (2010)

<h3>Introduction</h3> Chronic pain is a characteristic feature of functional gastrointestinal disorders (FGID), which are more prevalent in neurotic individuals. A recent meta-analysis has demonstrated that abnormalities in the parasympathetic nervous system (PNS) and hypothalamic pituitary adrenal (HPA) axis may be implicated in the pathogenesis of FGID.1 Moreover, accumulating evidence suggests that the PNS plays an important role in anti-nociception. <h3>Methods</h3> 120 healthy subjects (68 males, median age 29.2 years, range 19–55 years) had personality and anxiety variables assessed using validated questionnaires. All subjects had validated autonomic nervous system (ANS) parameters measured at baseline and continuously thereafter. Seven painful visceral stimuli (mid-oesophageal balloon distension) followed by seven painful somatic stimuli (nail bed pressure) were administered to the subject9s pain tolerance, with an inter-stimulus interval of two minutes. Subjects were asked to rate stimuli for pain intensity and unpleasantness. Serum cortisol was measured at baseline, following visceral and somatic stimulation. A cohort of 30 subjects (18 males, median age 29 years, range 20–54 years) had the study repeated at 1 year to evaluate reproducibility of responses. <h3>Results</h3> Neuroticism correlated positively with trait anxiety (p&lt;0.0001, r=0.52). Neuroticism was negatively correlated with the mean intensity of visceral and somatic stimuli (p=0.001, r=−0.38 and p=0.003, r=−0.45, respectively) but positively correlated with baseline, post-somatic and post-visceral pain cortisol (p&lt;0.0001, r=0.42, p&lt;0.0001, r=0.48 and p&lt;0.0001, r=0.53, respectively). Hierarchical cluster analysis identified two psychophysiological clusters: Cluster 1 (n=59) were more neurotic (p&lt;0.0001), less extrovert (p&lt;0.0001), more anxious (p&lt;0.0001), had lower resting PNS tone (p=0.01), higher baseline cortisol (p=0.006), habituated less to visceral and somatic pain (p=0.005 and p=0.04, respectively) with an increase in PNS tone to visceral and somatic pain (p&lt;0.0001 and p&lt;0.0001, respectively). Cluster 2 (n=61) had the opposite profile. In a demographically representative reproducibility cohort, intra–subject personality traits, baseline cortisol and ANS parameters were not significantly different between studies. Bland-Altman plots showed no proportional, magnitude-related, or systematic error between the degree and direction of ANS responses to visceral or somatic pain between studies. <h3>Conclusion</h3> In health, two distinct and reproducible psychophysiological profiles exist in response to visceral and somatic pain. The clinical relevance and prevalence of these pain endophenotypes as vulnerability factors for FGID warrants further investigation.
GW26-e4499 Long-term Outcome and the Mechanisms of Pulmonary Antrum Radial-linear Ablation in Patients with Paroxysmal Atrial Fibrillation
Authors: Xue Zhao, Dening liao, Xingui Guo, Yawei Xu, Yanzhou Zhang, Hui Gong, Zhenguo Liu
Journal: Journal of the American College of Cardiology (2015)
GW26-e2399 The Use of Noninvasive Vagal Nerve Stimulation to Inhibit Sympathetically Induced Sinus Node Acceleration
Authors: Liping Zhou, Xiaoya Zhou, Lilei Yu, Zhuo Wang, Songyun Wang, Bing Huang, Mingxian Chen, Kai Liao, Gaowa Saren, Hong Jiang
Journal: Journal of the American College of Cardiology (2015)
A non-intensive gemcitabine-cisplatin regimen in pancreatic cancer significantly improves quality of life and pharmacoeconomics with high response rates
Authors: A. M. Waterston, A. Glasgow, A. Thiliginayam, R. Williamson, H. Wasan
Journal: Journal of Clinical Oncology (2004)

8155 AIM: This Prospective Phase II study was undertaken to determine whether a dose-modified gemcitabine-cisplatin regimen improved QOL, reduced toxicity, increased compliance and improved delivered dose-intensity, with lowered costs, while preserving response rates. METHODS: 34 Chemotherapy naive patients with inoperable, locally advanced or metastatic pancreatic cancer were enrolled. Quality of life, clinical benefit response, albumin and CA19.9 were assessed cyclically: Patients received gemcitabine 1000mg/m2 day 1 and 8 and Cisplatin 60mg/m2 day 1 only (Q=21 days), all on an out-patient basis, with an intended minimum of 6 cycles. Objective response and toxicity were evaluated with WHO & CTC criteria. RESULTS: A total of 28 patients (19 male 9 female) are assessable currently. 89% (25 patients) had no increase in their analgesia. 77% (21 patients) had at least a 10% increase in dry weight or stabilization. Of the 13 patients with low serum albumin, 8 patients (29% of the total) had an increase or stabilization. This improvement in quality of life was mirrored in the tumor markers and objective disease response.12 patients (43%) had a decrease in their CA19.9 of >50%, and 9 patients had a partial or complete response with a further12 patients having stable disease. Critically, we were able to downstage 3/28 patients to successful pancreatectomies. This regimen caused little clinical toxicity ( 3 patients grade 3 nausea/lethargy). There was mild hematological toxicity with mainly anemia (26 patients (93%) grade 1+2, 2 patients (7%) grade 3+4) and neutropenia (13 patients (46%) grade 1+2, 5 patient (17%) grade 3+4). This regime produced cost savings of up to 1/3 when compared to other standard published regimens of either gemcitabine alone (+/− cisplatin), and more convenient with significantly fewer visits to hospital. CONCLUSION: By adding cisplatin to gemcitabine, at a reduced dose and frequency, we have been able to significantly improve patients quality of life, maintain responses and save on health costs. Currently the projected median survival for patients in this cohort is greater than 11 months. No significant financial relationships to disclose.
Concomitant chemoradiotherapy in adjuvant treatment of breast cancer: A retrospective study of 296 cases
Authors: H. Errihani
Journal: Journal of Clinical Oncology (2007)

11099 Background: Concomitant chemo-radio-therapy in adjuvant treatment of breast cancer is an attractive method which is under ongoing research program. We are trying by this retrospective study to document and support the feasibility of concomitant methods at the Oncology Institute in Rabat. Methods: Two hundred ninety six patients having breast cancer were investigated in a retrospective study. All patients were either treated by radical chirurgy (86.5%) or conservative treatment (13.5%). The study compares two adjuvant treatments associating concomitant chemotherapy and radiotherapy. In the first treatment (first brace) the patients were treated by chemotherapy and radiotherapy in concomitant way using anthracycline [(doxorubicine 60mg and cyclophosphamide 600mg/m 2 (AC60), 5-fluorouracile 500mg/m 2 , doxorubicine 50mg/m 2 , and cyclophosphamide 500mg/m 2 (FAC50), 5- fluorouracile 500mg/m 2 , epirubicine 75mg/m 2 , and cyclophosphamide 500mg/m 2 FEC75)] (N=123). In the second treatment (second brace) the chemotherapy was CMF type (cyclophosphamide 500mg/m 2 , methotrexate 60mg/m 2 and 5-fluorouracil 500mg/m 2 ) (N=173). Chemotherapy was administered in six cycles, one each 3 weeks. Radiotherapy delivered a radiation dose of 50 Gy on the breast (or on the external layer) Results: With an average time of 37 months after the end of the treatment, only one patient was recidivist of the breast cancer disease as a loco regional breast cancer when the treatment was based on anthracycline. So in 3 years the rate of recidivism of the disease was 0.6%. All the other recidivists were metastasic. The survival rate without disease, after 3 years, in the anthracycline brace was 87% compared to 86.5% in the CMF brace (p&gt; 0,5). The global survival probability after 3 years was 93% in the anthracycline brace and was 90.84% in the CMF treatment. Conclusions: From the three year retrospective investigation we showed a similarity of the two cancer treatment results with higher haematological toxicity in the concomitant treatment based on anthracycline. Waiting for the results of ongoing research we recommend the use of adjuvant treatments in sequential mode by using the chemotherapy prior to radiotherapy. No significant financial relationships to disclose.
Abstract B25: Characterization, targeting, and modulation of carbonic anhydrase IX activity for the development of small-molecule inhibitors to treat triple-negative breast cancer
Authors: Mam Y. Mboge, Zhijuan Chen, Brian P. Mahon, Nicole Lamas, Shingkuang Tu, Fabrizio Carta, Claudiu T. Superan, Robert McKenna, Susan C. Frost
Journal: Cancer Research (2016)

Abstract The microenvironment within a solid tumor is usually heterogeneous with certain regions being acidic and hypoxic. These acidic and hypoxic regions arise from rapidly proliferating cells combined with poor tumor perfusion. Cancer cells cope with these hostile changes in their microenvironment by expressing genes that are essential for survival. One of the coping mechanisms is an upregulation of pH regulatory factors, including carbonic anhydrase IX (CAIX). The action of CAIX helps to maintain physiological pH inside the cell (pHi) while regulating extracellular acidification (pHe). Extracellular acidification of the tumor microenvironment promotes local invasion, metastasis and decreases the effectiveness of adjuvant therapies, thus contributing to poor clinical outcome. Our goal was to compare the structure of a CAIX-mimic bound to ureidosulfonamide inhibitors with the biological activity of these inhibitors in a triple negative breast cancer cell line. CAIX is a reversible enzyme and at low pH (high proton concentration), the enzyme will consume protons, raising pH. Our hypothesis is that CAIX inhibition, in the context of an acidic microenvironment, will dysregulate its ability to maintain the acidic pH preferred by cancer cells which favors their growth and migration. In this study, we have shown the interaction of sulfonamide-based inhibitors using X-ray crystallography methods. These structures show the inhibitors make multiple contacts within the active site cavity. This is consistent with the inhibitor-induced decrease in CAIX activity measured as 18O exchange between H2O16 and H13C18O3 . We have also investigated the effect CAIX inhibition on cancer cell metabolism and extracellular acidification using Seahorse technology. This reveals that CAIX may contribute to the “non-glycolytic” acidification process. In total, these observations indicate that CAIX is a viable small molecular drug target and contribute to our understanding of the function of CAIX in modulating pH in cancer cells. Citation Format: Mam Y. Mboge, Zhijuan Chen, Brian P. Mahon, Nicole Lamas, Shingkuang Tu, Fabrizio Carta, Claudiu T. Superan, Robert McKenna, Susan C. Frost. Characterization, targeting, and modulation of carbonic anhydrase IX activity for the development of small-molecule inhibitors to treat triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B25.
GW26-e5420 Strategies for Patients with Acute Myocardial Infarction Presenting as Out-of Hospital Cardiac Arrest
Authors: S. Mehra, J Efird, M Printz, Hau Van Tran, Hoang Quoc Bao, Ramesh Dagubati, Thach Nguyen, Gianluca Rigatelli
Journal: Journal of the American College of Cardiology (2015)
Abstract 3621: Deubiquitination of AXIN1 by USP9X promotes apoptosis in melanoma in response to BRAF or MEK inhibition
Authors: Harish Potu, Luke F. Peterson, Malathi Kandarpa, Eric Fearon, Moshe Talpaz, Nicholas J. Donato
Journal: Cancer Research (2015)

Abstract The Wnt/β-catenin pathway is important in development, transformation and self-renewal of various tissues and tumors. In contrast, Wnt/β-catenin signaling appears to play a paradoxical role in melanoma where its activation is anti-oncogenic and a marker of good prognosis. Previous studies have shown that activation of the NRAS/BRAF/MEK pathway suppresses Wnt/β-catenin signaling and reduces apoptotic sensitivity to BRAF or MEK inhibitors in melanoma. MEK pathway activation stabilized AXIN1, a Wnt/β-catenin inhibitor, in some melanoma cell lines through a proteasome-dependent process and co-treatment with Wnt3A and BRAF/MEK kinase inhibitors resulted in a reduction of AXIN1 and full activation of apoptosis. Further, AXIN1 knockdown sensitized BRAF/MEK inhibitor insensitive cells to kinase inhibition, providing a prominent role for AXIN1 in determining melanoma cell apoptotic responsiveness and exposing a potential mechanism for improving kinase inhibitor clinical activity. While AXIN1 protein levels appear to be regulated by ubiquitination, the enzymes involved in control of its ubiquitination or deubiquitination are not fully defined. Here we show that ubiquitin-specific peptidase 9, X-linked (USP9X), a deubiquitinating enzyme whose expression is elevated in melanoma, binds and deubiquitinates AXIN1. USP9X knockdown resulted in increased ubiquitination and proteasome-mediated depletion of AXIN1 (but not AXIN2), resulting in a reduction in AXIN1 cellular half-life. USP9X knockdown elevated β-catenin response genes (&amp;gt;2-fold) in melanoma cells treated with Wnt3A. USP9X depletion also increased apoptotic responsiveness to Wnt3A or BRAF/MEK inhibitor and overcame BRAF inhibitor resistance in A375R cells. In contrast, USP34 which was previously shown to regulate AXIN1 (and AXIN2) deubiquitination, did not alter AXIN1 levels or apoptotic responsiveness in melanoma. A previously identified small molecule USP9X inhibitor (EOAI3402143 or G9) replicated the effects of USP9X knockdown on AXIN1 depletion in vitro and in vivo, suppressed melanoma tumor growth in animals and fully blocked in vivo tumor growth when combined with BRAF kinase inhibitor. Thus, we identify USP9X as a potential therapeutic target in melanoma and established G9 as a lead compound for the development of AXIN1 depleting agents that may add to the targeted therapies already used in the treatment of melanoma. Note: This abstract was not presented at the meeting. Citation Format: Harish Potu, Luke F. Peterson, Malathi Kandarpa, Eric Fearon, Moshe Talpaz, Nicholas J. Donato. Deubiquitination of AXIN1 by USP9X promotes apoptosis in melanoma in response to BRAF or MEK inhibition. [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 3621. doi:10.1158/1538-7445.AM2015-3621
A phase II study of irinotecan, oxaliplatin, 5-fluorouracil, leucovorin (FOLFOXIRI) as a first-line chemotherapy in metastatic gastric cancer
Authors: J. Lee, W. Kang, S. Lee, J. Kwon, H. Kim, H. Lee, H. Lim, J. Park, Y. Park, K. Park
Journal: Journal of Clinical Oncology (2006)

4076 Background: Previous phase II study showed a high efficacy and safety of FOLFOXIRI (irinotecan, oxaliplatin, 5-fluorouracil, leucovorin) combination chemotherapy in metastatic colorectal cancer. This non-randomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients. Methods: Patients with: histologically proven, bidimensionally measurable, metastatic gastric adenocarcinoma, age 18 - 70 years, with a performance status 0 - 2, no prior chemotherapy or at least 12 months after adjuvant therapy, life expectancy &gt; 3 months, signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m 2 day 1, oxaliplatin 85 mg/m 2 day 1, leucovorin 100 mg/m 2 day and 5-fluorouracil 2000 mg/m 2 as a 48-h continuous infusion starting on day 1, repeated every 2 weeks until unacceptable toxicity, patients’ refusal, or up to 12 cycles. The planned sample size was 48 and the primary endpoint was response rate. Results: From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24 - 69) and male:female ratio was 1.3:1. In total, 379 cycles were administered with a median of 9 cycles per patient (range, 1–12) and 45/48 patients were evaluable for treatment response. Three patients were not assessable for response due patients’ refusal for further chemotherapy following the first cycle. By per-protocol analysis, the objective response rate was 73.3 % (95% CI, 60.8–85.8) with 2 CRs and 31 PRs. Four patients (9%) had stable disease and 8 patients (18%) had progressive disease. The estimated median survival of all patients was 14.0 months (95% CI, 11.8 - 16.2 ) and the estimated median time-to-progression was 8.9 months (95% CI, 6.7–11.0). In total of 379 cycles administered, most common grade 3/4 toxicities were neutropenia (11% of all cycles) and emesis (12%). Grade 2 peripheral neuropathy occurred in 5 patients. One (2%) patient had severe tumor bleeding and 5 (10%) patients experienced grade 3 diarrhea. Conclusions: FOLFOXIRI combination chemotherapy showed a very promising preliminary anti-tumor activity and was generally well tolerated as a first-line treatment for patients with metastatic gastric cancer. No significant financial relationships to disclose.
Phase IB Study of PKC412, an Oral FLT3 Kinase Inhibitor, in Sequential and Simultaneous Combinations with Daunorubicin and Cytarabine (DA) Induction and High-Dose Cytarabine Consolidation in Newly Diagnosed Adult Patients (pts) with Acute Myeloid Leukemia (AML) under Age 61.
Authors: Richard M. Stone, Thomas Fischer, Ronald Paquette, Gary Schiller, Charles A. Schiffer, Gerhard Ehninger, Jorge Cortes, Hagop Kantarjian, Daniel A. DeAngelo, Georgio Massimini, Xiaoming Li, Penny Phillips, Francis Giles
Journal: Blood (2006)
Myocardial Extracellular Volume Estimation by CMR Predicts Functional Recovery Following Acute MI
Authors: Ananth Kidambi, Manish Motwani, Akhlaque Uddin, David P. Ripley, Adam K. McDiarmid, Peter P. Swoboda, David A. Broadbent, Tarique Al Musa, Bara Erhayiem, Joshua Leader, Pierre Croisille, Patrick Clarysse, John P. Greenwood, Sven Plein
Journal: JACC. Cardiovascular imaging (2016)

In the setting of reperfused acute myocardial infarction (AMI), the authors sought to compare prediction of contractile recovery by infarct extracellular volume (ECV), as measured by T1-mapping cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) transmural extent. The transmural extent of myocardial infarction as assessed by LGE CMR is a strong predictor of functional recovery, but accuracy of the technique may be reduced in AMI. ECV mapping by CMR can provide a continuous measure associated with the severity of tissue damage within infarcted myocardium. Thirty-nine patients underwent acute (day 2) and convalescent (3 months) CMR scans following AMI. Cine imaging, tissue tagging, T2-weighted imaging, modified Look-Locker inversion T1 mapping natively and 15 min post–gadolinium-contrast administration, and LGE imaging were performed. The ability of acute infarct ECV and acute transmural extent of LGE to predict convalescent wall motion, ejection fraction (EF), and strain were compared per-segment and per-patient. Per-segment, acute ECV and LGE transmural extent were associated with convalescent wall motion score (p < 0.01; p < 0.01, respectively). ECV had higher accuracy than LGE extent to predict improved wall motion (area under receiver-operating characteristics curve 0.77 vs. 0.66; p = 0.02). Infarct ECV ≤0.5 had sensitivity 81% and specificity 65% for prediction of improvement in segmental function; LGE transmural extent ≤0.5 had sensitivity 61% and specificity 71%. Per-patient, ECV and LGE correlated with convalescent wall motion score (r = 0.45; p < 0.01; r = 0.41; p = 0.02, respectively) and convalescent EF (p < 0.01; p = 0.04). ECV and LGE extent were not significantly correlated (r = 0.34; p = 0.07). In multivariable linear regression analysis, acute infarct ECV was independently associated with convalescent infarct strain and EF (p = 0.03; p = 0.04), whereas LGE was not (p = 0.29; p = 0.24). Acute infarct ECV in reperfused AMI can complement LGE assessment as an additional predictor of regional and global LV functional recovery that is independent of transmural extent of infarction.
Development of a Splenic Marginal Zone Lymphoma Associated with Active Chronic Visceral Leishmaniasis
Authors: Maja Ølholm Vase, Ylva Kristina Hellberg, Carsten Schade Larsen, Jørgen Eskild Petersen, Henrik Schaumburg, Knud Bendix, Christophe Ravel, Patrick Bastien, Mariann Christensen, Charlotte Guldborg Nyvold, Francesco d'Amore
Journal: Blood (2011)
Chlamydia related bacteria (Chlamydiales) in early pregnancy: community-based cohort study
Authors: F. Reid, P. Oakeshott, S.R. Kerry, P.E. Hay, J.S. Jensen
Journal: Clinical Microbiology and Infection (2016)

ObjectivesSerological case–control studies suggest that certain chlamydia-related bacteria (Chlamydiales) which cause cows to abort may do the same in humans. Chlamydiales include Waddlia chondrophila, Chlamydia abortus and Chlamydia trachomatis. Data on prevalence of Chlamydiales in pregnancy are sparse. Using stored urine samples from a carefully characterised cohort of 847 newly pregnant women recruited from 37 general practices in London, UK, we aimed to investigate the prevalence and types of Chlamydiales infections. We also explored possible associations with miscarriage or spontaneous preterm birth.MethodsSamples were tested using W. chondrophila and pan-Chlamydiales specific real-time PCRs targeting the 16S rRNA gene. Samples positive on either PCR were subjected to DNA sequencing and C. trachomatis PCR.ResultsThe overall prevalence of Chlamydiales was 4.3% (36/847, 95% CI 3.0% to 5.8%). The prevalence of W. chondrophila was 0.6% (n = 5), C. trachomatis 1.7% (n = 14), and other Chlamydiales species 2.0% (n = 17). Infection with C. trachomatis was more common in women aged <25, of black ethnicity or with bacterial vaginosis, but this did not apply to W. chondrophila or other Chlamydiales.Follow up was 99.9% at 16 weeks gestation and 90% at term. No infection was significantly associated with miscarriage at ≤12 weeks (prevalence 10%, 81/827) or preterm birth <37 weeks (prevalence 4%, 23/628). Of 25 samples sequenced, seven (28%) were positive for Chlamydiales bacterium sequences associated with respiratory tract infections in children.ConclusionIn the first study to use the pan-Chlamydiales assay on female urine samples, 4% of pregnant women tested positive for Chlamydiales, including species known to be pathogenic in mothers and neonates.