tbuckley/cabot-search huggingface dataset:
Abstract 1749: The downregulated expression of adiponectin receptors (AdipoR1, R2) in human colorectal cancer
Authors: Masaya Hiyoshi, Joji Kitayama, Nelson H. Tsuno, Eiji Sunami, Kazusige Kawai, Kensuke Otani, Takeshi Nishikawa, Yasutaka Shuno, Koji Yasuda, Kumiko Hongo, Yoshiko Kikkawa, Kazuhito Sasaki, Manabu Kaneko, Koki Takahashi, Hirokazu Nagawa
Journal: Cancer Research (2010)

Abstract [Background] Adiponectin is 30 kDa adipocytokine hormone secreted by the adipose tissues, which mediates antineoplastic as well as anti-angiogenic effects after binding to its receptors, Adipo-R1 and Adipo-R2, which has been reported to be expressed in colorectal cancer tissue and cell lines. Recent studies have shown decreased levels of adiponectin in sera of patients with various types of cancer, including colorectal. And a recent study demonstrated that adiponectin expression is significantly associated with high histological grade tumors and low microvessel density count in colorectal cancer, suggestive of an anti-angiogenic role for adiponectin in colorectal cancer. However, presently, the expression and function of adiponectin receptors in tumor tissue have not been well characterized. Thus, in the present study, we aimed to study the expression of adiponectin receptors in colorectal cancer tissues, and investigate on their clinicopathological implications. [Methods] Surgically resected specimens from 48 patients with colorectal cancer, receiving surgical operation in our surgical department in the period between November 2008 and July 2009, were analyzed. The study was approved by the Human Ethics Committee of the University of Tokyo. The messages and protein expressions of AdipoR1 and AdipoR2 were evaluated by real-time RT-PCR and immunohistochemistry, respectively, in cancer tissues and the matched normal counterparts. [Results] The mean age of the patients was 66.79±11.85 years. The levels of expression of both AdipoR1/AdipoR2, normalized with the internal control (beta-actin), were significantly lower in cancer specimens compared with normal mucosa (0.966±0.392, vs1.366±0.408, p&amp;lt;0.001 and 0.918±0.309, vs1.596±0.459, p&amp;lt;0.001, respectively for AdipoR1 and Adipo R2). The mRNA levels of AdipoR1 and AdipoR2 showed a tendency of decrease in tumors with nodal metastases and the difference was significant with AdipoR2 (p&amp;lt;0.05). Immunohistochemistry with polyclonal Abs showed a consistent reduction in protein expression of both receptors in cancer tissues in comparison with the normal counterparts. [Conclusion] Both receptors were downregulated in colorectal cancer, as confirmed by the mRNA and the protein expressions, and AdipoR2 seemed to be associated with nodal metastases. This downregulation seems to be associated with poorer prognosis of colorectal cancer, and may be an escape mechanism of cancer cells from the suppressive effects of adiponectin. 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 1749.
P389Role of truncated plakophilin-2 in arrhythmogenic right ventricular cardiomyopathy
Authors: M Alcalde, O Campuzano, P Beltran-Alvarez, S Pagans, M Verges, R Brugada
Journal: Cardiovascular Research (2014)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare cardiac disease characterized by fibrofatty replacement of the right ventricular myocardium, which may cause ventricular arrhythmias and sudden cardiac death (SCD). Mutations in genes encoding desmosome proteins have been associated with ARVC: plakophilin-2 (PKP2), desmoplakin (DSP), desmocolin-2 (DSC2), desmoglein-2 (DSG2) and plakoglobin (PG). Plakophilin-2 (PKP2) is the most prevalent gene associated with ARVC, especially stop-gained mutations, which lead to truncated PKP2 (PKP2TR). Our recent genetic studies have shown that PKP2TR is associated to a later age of ARVC onset (37 years old) compared to missense carriers (27 years old). This raised an alternative hypothesis as to the pathogenicity of missense and truncated proteins, and their role in phenotype. We hypothesize that PKP2TR is associated with trafficking to the plasma membrane, which can be compensated by the normal allele; while missense variations may act through a dominant negative effect, disrupting the function of the wild type protein since they are mostly incorporated to desmosome. To explore this hypothesis, we performed an in vitro study with the three following aims: (1) to examine the subcellular location of PKP2TR forms in the in HL-1 cardiac-like cells, (2) how PKP2TR length affect to their proper traffic to plasma membrane and (3) PKP2TR effect on desmosome assembly. Based on mutations associated to ARVC in our genetic study, we selected four PKP2TR versions (at amino acids 91, 412, 637 and 734), which were transiently co-transfected in HL-1 cells with major desmosome proteins (DSP,DSC2, DSG2 and PG). We observed that these PKP2TR forms are not localized efficiently to the plasma membrane; PKP2TR-91 remained diffuse in the cytoplasm; PKP2TR-412 was retained in the endoplasmic reticulum displaying a dotted pattern. In contrast PKP2TR-637 and PKP2TR-734 were only partially located to the plasma membrane with a major fraction still cytosolic. We also observed that all PKP2TR caused deficient localization of other desmosome proteins, especially DSP, which requires PKP2 for its proper trafficking to the plasma membrane. Thus, these data suggest that the degree of the truncation in PKP2 does not correlate with a clear effect in desmosome assembly. Results clearly show that PKP2TR forms are not efficiently incorporated to the plasma membrane, and they affect desmosome assembly. These data favour the idea that PKP2TR may be associated to trafficking defect, while missense mutations may act in a dominant negative way disrupting function of the wild-type protein.
Very Early and Standard Tc-99m Ethyl Cysteinate Dimer SPECT Imaging in a Patient with Reperfusion Hyperemia After Acute Cerebral Embolism
Authors: KUNIAKI OGASAWARA, HIROMU KONNO, SHIGERU YASUDA, HIROTSUGU YUKAWA, AKIRA OGAWA
Journal: Clinical Nuclear Medicine (2002)

It has been reported that Tc-99m ethyl cysteinate dimer (ECD) SPECT imaging may not show reperfusion hyperemia in patients with subacute stroke. The authors describe a patient with embolic middle cerebral artery occlusion who was examined using xenon-133 and dynamic and standard Tc-99m ECD SPECT immediately after early recanalization. Standard Tc-99m ECD SPECT images revealed hypoactivity in the ipsilateral middle cerebral artery territory. In contrast, the dynamic Tc-99m ECD SPECT images from the first scan (very early images acquired 36 seconds after injection) showed hyperactivity in the same region and provided imaging contrast comparable to what would be obtained with xenon-133 tomography. Hemorrhagic transformation later developed in this region. These results indicate that images from very early dynamic Tc-99m ECD SPECT of areas with irreversible changes produced by acute stroke can reveal reflow hyperemia that standard Tc-99m ECD SPECT images fail to show.
COMPLEMENTARY PROGNOSTIC VALUE OF RENAL FUNCTION AND CORONARY ARTERY CALCIUM SCORE IN PATIENTS WITHOUT KNOWN CORONARY ARTERY DISEASE: UP TO 5-YEAR FOLLOW-UP
Authors: Kongkiat Chaikriangkrai, Alejandro Trevino, Naveed Anwar, Farshad Forouzandeh, Faisal Nabi, John Mahmarian, Su Min Chang
Journal: Journal of the American College of Cardiology (2015)
Bargaining power and the evolution of un-fair, non-mutualistic moral norms
Authors: Francesco Guala
Journal: Behavioral and Brain Sciences (2013)

Abstract Mutualistic theory explains convincingly the prevalence of fairness norms in small societies of foragers and in large contemporary democratic societies. However, it cannot explain the U-shaped curve of egalitarianism in human history. A theory based on bargaining power is able to provide a more general account and to explain mutualism as a special case. According to this approach, social norms may be more variable and malleable than Baumard et al. suggest.
SP0136 Extremely early inflammatory arthritis: How can the GP diagnose
Authors: K. Raza
Journal: Annals of the Rheumatic Diseases (2013)

New onsets of inflammatory sounding joint symptoms and of overt inflammatory arthritis are common occurrences. In many individuals the episodes are of short duration, resolving spontaneously. A key clinical challenge is to be able to identify which patients will not get better spontaneously, and in particular which patients will develop rheumatoid arthritis, thus allowing early targeted interventions. Within this session: –Barriers to early assessment and diagnosis in primary care, and approaches to overcoming these barriers, will be discussed. –Currently available strategies to predict outcomes in patients with early arthritis will be reviewed. –Novel approaches to the early identification of inflammatory arthritis and the prediction of outcome, including the use of imaging, will be reviewed. –Finally, important aims for future research in this area will be highlighted. <h3>Disclosure of Interest</h3> None Declared
Multi-drug chemotherapy for pancreatic cancer
Authors: H. W. Bruckner, M. Myo, K. Zaw, O. Filipova, S. Heidarian, N. Rafiq, K. Julliard
Journal: Journal of Clinical Oncology (2005)

4267 Background: G-FLIP, a low dose, multi-drug regimen, produced an objective response and stable disease rate of (7+6/34) 38% and overall median survival (MST) of 10.3 additional mos on adding 80 mg/M2 of Irinotecan to a ‘failed’ q2 wk Gemzar-Fluorouracil-Cisplatin regimen (The Oncologist 6:488 2001). Methods: Subsequently, G-FLIP was used for all non-adjuvant applications. Interim analysis found overall MST of 15–18 mos (Bruckner et al, ICACT 2001; 2003). In part, treatment after G-FLIP ‘failure’ substituted Taxotere (Xeloda) or Methotrexate for Irinotecan in multi-drug regimens with a 20% rate of objective response (Bruckner et al, ASCO, San Francisco, 2004.) Currently, all new patients (pts) were updated. Results: Overall MST for 102 intent-to-treat pts from diagnosis is 15.5 mos, and 28% at 2 yrs. Survival of these new pre-registered pts matches MST of ideally resected pts in the pre-G-FLIP period (Snady et al, Cancer, 2001), in spite of currently excluding the successfully resected and including therapy-resistant pts. The role of pt characteristics in this poor-risk group is now under study: 70 received G-FLIP as primary therapy, 23 had stage III cancer, 57 had CA 19–9 of greater than 1000, 16 required substantial narcotics, and 23 had failed resection of the tumor. Overall analysis included pts normally too sick to be eligible for registration or protocol trials. 37 of 57 (65%) pts with data had at least a 50% reduction in 19–9 levels, and only 3 (5%) increased 25% or more over 3 mos. Recently Avastin partnered with failed drugs has also produced major RECIST responses, mixed responses, and even clearing of intra-hepatic jaundice. Avastin experience is too early to contribute to overall survival. Conclusions: Findings support testing of broad applications for drug additions to failed drugs. Experience demonstrates heterogeneity of drug response, and crossover response with clinical benefit. Pancreatic cancer is a promising subject for testing laboratory-directed development efforts. No significant financial relationships to disclose.
A Phase II Trial of Capecitabine and Docetaxel Followed by 5-FU/Epirubicin/Cyclophosphamide (FEC) as Preoperative Treatment in Women with Stage II/III Breast Cancer.
Authors: H. Jinno, M. Takahashi, T. Hayashida, M. Sakata, M. Mukai, Y. Kitagawa
Journal: Cancer Research (2009)

Abstract Backgound: capecitabine (X) and docetaxel (T) have demonstrated synergistic effect in preclinical models and survival benefit in metastatic breast cancer. The sequential combination of anthracycline and taxane is a standard of care as preoperative setting, as well as adjuvant setting. This study's purpose was to determine the efficacy of X and T followed by 5-FU/epirubicin/cyclophosphamide (FEC) in the preoperative setting.Patients and Methods: Patients with stage II/III breast cancer received 4 cycles of XT (capecitabine 1650 mg/m2 on days 1-14 and docetaxel 60 mg/m2 on day 8 every 3 weeks), followed by 4 cycles of FEC (fluorouracil 500 mg/m2, epirubicin 90 mg/m2, cyclophosphamide 500 mg/m2 on day 1 every 3 weeks). Primary endpoints were the pathological complete response (pCR) rate and adverse drug reactions. pCR was defined as no microscopic evidence of residual viable tumor cells, invasive or noninvasive, in all resected specimens of the breast. Secondary endpoints were the clinical response rate, the breast conservation rate, and predictors for pCR.Results: From February 2005 to October 2008, 72 patients were enrolled and 71 patients were assessable for clinical and pathologic responses. The median age was 51 years (range, 27-69 years). The median tumor size was 3.5 cm (range, 2-8.3 cm). Forty-six (64.8%) patients were clinically node-positive. Overall, 50 (50.1%) patients had hormonal receptor (HR)-positive tumors, and 21 (29.6%) had HR-negative tumors. The overall response rate was 91.5%, including a complete response in 29 patients and a partial response in 36 patients. No patients showed clinical progression of disease. The pCR rate was 14.1% (10/71). Fifty-six patients (78.9%) underwent breast-conserving surgery. The breast-conserving rate in patients whose tumor size was 3 cm or smaller was 92.6%, and 69.0% of patients whose tumor size was larger than 3 cm underwent breast-conserving surgery. Grade 3/4 neutropenia was observed in 32.4% of patients, and febrile neutropenia was observed in 5.6% of patients. The most common grade 3/4 non-hematologic adverse event was hand-foot syndrome, observed in 11.3% of patients. The median relative dose intensities of FEC, T, and X were 0.982, 0.968, and 0.933, respectively. HR status and Ki67 expression were significantly correlated with pCR.Conclusions: These data indicate that the sequential combination of XT followed by FEC is a well-tolerated, effective preoperative treatment for stage II/III breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1101.
Eradication of Axillary Lymph Node Metastases Occurs in 74% of Patients Receiving Neoadjuvant Chemotherapy with Concurrent Trastuzumab for HER2 Positive Breast Cancer.
Authors: L. Dominici, V. Negron Gonzalez, A. Buzdar, A. Lucci, E. Mittendorf, L. Pusztai, S. Krishnamurthy, H. Le-Petross, G. Babiera, I. Bedrosian, F. Meric-Bernstam, K. Hunt, V. Valero, H. Kuerer
Journal: Cancer Research (2009)

Abstract Background:Administration of neoadjuvant chemotherapy (NCT) can result in a pathologic complete response (pCR) in the breast and axilla which correlates with improved disease-free and overall survival. This study examines the incidence of axillary pCR and the effect of axillary pCR on disease-free survival (DFS) in patients (pts) with HER2 positive disease and biopsy-proven axillary metastases that received trastuzumab-based NCT.Material and Methods:The records of 109 consecutive pts with HER2 positive breast cancer and ultrasound-guided fine needle aspiration (FNA) biopsy-confirmed axillary metastases were analyzed. All pts received trastuzumab-based NCT prior to undergoing breast surgery with complete axillary lymph node (ALN) dissections. After surgery, patients were subdivided into those with and without residual ALN disease. Survival was evaluated by the Kaplan-Meier method.Results:Of patients with documented positive ALNs before chemotherapy, 81 (74%) had an ALN pCR. ALN pCR was not associated with estrogen receptor status, grade, tumor size or age (p=NS). The median number of nodes removed was 19 in the ALN pCR group and 18.5 in the group with residual axillary disease (p=NS). The only significant difference between the groups was that more patients in the ALN pCR group achieved complete pathologic response of disease within the breast (p&amp;lt;0.001) (78% with and 25% without ALN pCR, respectively). At a median follow-up of 29.1 months, DFS in the ALN pCR group (95%) was significantly greater than in the group with residual axillary disease (81%) on Kaplan-Meier analysis (p=0.02).Discussion:Trastuzumab-based NCT results in axillary pCR in 74% of patients with HER2 positive disease. These pts have improved DFS compared with patients with residual disease. The majority of patients with proven axillary metastases will have eradication of disease after treatment with trastuzumab-based NCT, and this has implications for the surgical management of the axilla in these types of pts. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1086.
AB1020 Ultrasonographic Evaluation of Articular Manifestations in Systemic Lupus Erythmatosus
Authors: T. Ogura, A. Hirata, N. Hayashi, R. Kujime, M. Imamura, S. Takenaka, K. Mizushina, N. Yamashita, H. Ito, Y. Fujisawa, H. Kameda
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ultrasonography is widely used in the evaluation of joint lesions in rheumatoid arthritis (RA). While arthritis in systemic lupus erythematosus (SLE), unlike that in RA, is usually non-erosive and often accompanied by Jaccoud9s deformity, ultrasonic characteristics of arthritis in SLE have scarcely been elucidated. <h3>Objectives</h3> Therefore, we examined characteristics of joint and tendon lesions in SLE using ultrasonography. <h3>Methods</h3> Fifty patients with SLE (45 female, the mean age of 47.5 years) treated in Toho University Ohashi Medical Center were subjected to ultrasonography on their wrists, metacarpophalangeal joints, (proximal) interphalangeal joints, and extensor/flexor tendons bilaterally. Their joints and tendons including tendon sheaths were evaluated using a gray-scale (GS) for synovial thickening and synovial fluid retention, and power Doppler (PD) for blood flow according to a semiquantitative method based on a scale of Grades 0 to 3, and patients graded with GS ≥2 or PD ≥1 were judged as having joint synovitis or tendinitis/tenosynovitis. <h3>Results</h3> Thirty-two of the 50 patients (64%) were found to have relevant lesions, and joint synovitis was detected in 27 patients (54%). Tendinitis/tenosynovitis were detected in 24 patients, of whom 5 patients (21%) were found to suffer tendinitis/tenosynovitis without any synovitis. In addition, 14 of 24 patients (58%) had tendon lesions in a site free of joint synovitis. There was no significant relationship between other clinical or immunological features and US-detected articular findings. <h3>Conclusions</h3> Our study using ultrasonography revealed that tendon lesions represent an important articular involvement in patients with SLE to the extent comparable to joint synovial lesions. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4979
S84 Can clinicians accurately predict non-adherence to medication in patients with difficult asthma? A comparison between clinical judgement and prescription issue data
Authors: A. C. Murphy, S. Belingheri, C. E. Brightling, A. J. Wardlaw, I. D. Pavord, P. Bradding, R. H. Green
Journal: Thorax (2011)

<h3>Background</h3> It is increasingly recognised that sub-optimal adherence to prescribed medication regimes is common in patients with difficult asthma and may be associated with adverse clinical outcomes. Simple reliable methods of measuring non-adherence have not been developed and clinicians9 judgement is often relied upon as the only assessment of adherence. We have previously shown that checking prescription data are a useful method of investigating non-adherence in this patient population. We aimed to determine how well a clinician9s judgement of adherence correlated to adherence as measured by prescription issue data. <h3>Methods</h3> Adult asthma patients attending a difficult asthma clinic during July/August 2010 were included. GP retrospective prescription issue data and hospital dispensing data for asthma medications, patient demographics and clinical outcome data were collated. The medication adherence score was calculated as the number of doses issued/number of doses prescribed × 100 for a mean duration of 12 months. Clinicians with an expertise in the management of difficult asthma were asked to stratify each patient according to their perceived adherence, classified as adherent (=80% adherence score; partially adherent 50%–79%; non-adherent &lt;50%). Agreement between clinician judgement and adherence score was analysed using a weighted κ coefficient. Logistic regression was performed to determine whether any clinical features could predict better agreement. <h3>Results</h3> Data from 63 consecutive patients was included in the analysis (41 female, median (range) age 51.2(61.3)). Clinicians suspected non-adherence in 11/63 (17.4%) of patients, partial non-adherence in 23/63 (36.5 %) and good adherence in 29/63 (46%). Agreement between clinician assessment and prescription issue data were seen in only 23/63 (36.5%) of cases and overall agreement using a weighted κ coefficient was poor (weighted agreement 63.5%, expected agreement 58.8%, κ 0.11, SE 0.1, z=1.16, p=0.12). There was no relationship between patients9 age, gender, Juniper asthma control score, prescribed inhaled corticosteroid dose or FEV<sub>1</sub> percent predicted and the chances of agreement or disagreement between the two methods. <h3>Conclusions</h3> Clinical judgement alone appears to be a poor predictor of adherence to medication in patients with difficult asthma. The assessment of non-adherence requires objective measurements. Prescription issue data are one such measurement; but further work is required.
CB-18 * INTERROGATION OF SUB-CLONAL GENETIC DIVERSITY OF HUMAN GBM REVEALS GENETIC HETEROGENEITY IN TUMOUR-PROPAGATING CELLS, WHICH DISPLAY VARIABLE COMPETITIVE CAPACITY FOR TUMOUR PROPAGATION IN VIVO
Authors: C. Watts, S. Piccirillo, L. Kearney, N. Potter, F. van Delft, S. Coleman, S. Lillis, M.-J. Carnicer, M. Greaves
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma (GB) is a lethal malignancy whose clinical intransigence has been linked to extensive intra-clonal genetic and phenotypic diversity and the common emergence of therapeutic resistance. This interpretation embodies an implicit assumption that cancer stem cells or tumour propagating cells are themselves genetically and functionally diverse. Sub-clonal evolution and cancer stem cells (CSCs) have been considered as alternative mechanisms for disease progression but it can also be argued that they are part of the same process because clonal diversity is likely to be generated and sustained by genetically distinct CSCs, which provide the units for evolutionary selection. However, this has yet to be demonstrated in GB. METHODS: We screened primary GB tumours by SNP array to identify copy number alterations (minimum of three) that could be visualised in single cells by multi-colour FISH. Interrogation of neurosphere-derived cells (from four patients) and cells derived from secondary transplants of these same cells in NOD-SCID mice allowed us to infer the clonal and phylogenetic architectures. RESULTS: In all four cases studied by multicolour FISH there was genetic heterogeneity in the neurosphere cells, with each case showing a unique, branched phylogenetic architecture. In each case, more than one sub-clone was capable of propagating tumours in secondary transplanted mice. CONCLUSIONS: Our interrogation of sub-clonal genetic diversity of human GB has revealed for the first time that tumour-propagating cells in GB are genetically heterogeneous, with variable competitive capacity for tumour propagation in vivo. The link forged between genetic diversity, clonal architecture and propagating activity in vivo may facilitate the characterisation of mutational variants responsible for disease recurrence and therapeutic resistance in patients.