tbuckley/cabot-search huggingface dataset:
Abstract 463: The role of cysteinyl leukotriene receptors and tumour associated macrophages in colon cancer progression
Authors: Yuan Zhang, Wondossen Sime, Anita Sjölander
Journal: Cancer Research (2011)

Abstract The pro-inflammatory cysteinyl leukotrienes (CysLT) have been implicated to play a role in colon cancer. The biological effects of CysLTs are mainly mediated through two different G-protein coupled receptors CysLT1 and CysLT2. We have shown that LTD4 signaling via CysLT1 receptors is linked to tumourigenic processes in cancer cells1. On the other hand, signaling via CysLT2 receptors is involved in cancer cell differentiation2. Colon cancer patients with high CysLT1R and low CysLT2R expression demonstrate poor prognosis3. Tumor-associated macrophages (TAMs, M2 phenotype, CD68+) are not only a source of CysLTs in tumor tissue, but also promote cancer cell invasion. High macrophage content is associated with poor patient prognosis in many tumors. In breast carcinoma, EGF is secreted by activated macrophages, but not by normal or malignant epithelial cells4. CD47, expressed on tumor cells, is capable of interacting with its receptor Signal-regulatory protein α (SIRPα) on macrophages to negatively regulate phagocytosis. Our aim is to investigate how TAMs affect tumor behavior, and to investigate the role of CysLT1 and CysLT2 receptor-switch, which might be caused by EGF, in cancer progression. Our preliminary data shows that TAMs are the source of EGF in cancer patient tissue. EGF up-regulates CysLT1R and downregulates CysLT2R expression. Migration of colon cancer cell is enhanced by M2 compared to M1 macrophages in wound healing-assay. Boyden Chamber-assay shows that conditioned medium from colon cancer cells cultured enhances migration of M2 (150%) but not M1 macrophages. We are now investigating the influence of the CysLT1R activity on phagocytosis and proliferation. These findings suggest TAMs secret various molecular factors, which potentially influence the overall process of tumor initiation. TAMs may also change the balance between CysLT1R and CysLT2R, and there by play an important role in colon cancer progression. References 1 Öhd JF, Nielsen CK, Campbell J, Landberg G, Löfberg H, Sjölander A. Gastroenterology. 2003 124:57-70. 2 Magnusson C, Ehrnstrom R, Olsen J, Sjölander A. Cancer Res 2007 67:9190-8. 3 Magnusson C, Mezhybovska M, Lörinc E, Fernebro E, Nilbert M, Sjölander A. Eur J Cancer. 2010 46:826-35. 4 O'Sullivan C, Lewis CE, Harris AL, McGee JO. Lancet. 1993 342:148-9. 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 463. doi:10.1158/1538-7445.AM2011-463
Abstract 2250: PKR signaling pathway plays an important role in prognosis for non-small cell lung cancer
Authors: Apar Pataer, Yong He, Arlene M. Correa, Bingliang Fang, Jack A. Roth, Ignacio I. Wistuba, Stephen G. Swisher
Journal: Cancer Research (2011)

Abstract The role of RNA-dependent protein kinase (PKR) in antiviral defence mechanisms and in cellular differentiation, growth, and apoptosis is well known, but the role of PKR in human lung cancer remains poorly understood. To explore the role of PKR in human lung cancer, we evaluated PKR's expression in tissue microarray specimens from both non-small cell lung cancer (NSCLC) and normal human bronchial epithelium tissue. The NSCLC cells showed lower levels of PKR expression than normal bronchial epithelium cells did. We also found a significant association between lower levels of PKR expression and lymph node metastasis. We found that loss of PKR expression is correlated with a more aggressive behavior, and that a high PKR expression predicts a subgroup of patients with a favorable outcome. Univariate and multivariate Cox proportional hazards regression models showed that a lower level of PKR expression was significantly associated with shorter survival in NSCLC patients. We further validated and confirmed that PKR to be a powerful prognostic factor in TMA-2 lung cancer (HR=0.22, P&amp;lt;0.0001). We also observed that the patients with high p-PKR or p-eIF2a expression had a significantly longer median survival than those with little or no p-PKR or p-eIF2a expression (P = 0.03 and P = 0.032, respectively). Combined expression of PKR and p-PKR or PKR and p-eIF2a increased patient survival (P = 0.001). Combined expression levels of PKR and p-PKR or p-eIF2a can be new markers for predicting the prognosis of patients with NSCLC. 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 2250. doi:10.1158/1538-7445.AM2011-2250
Negative immunomagnetic ex vivo purging combined with high-dose chemotherapy with peripheral blood progenitor cell autograft in follicular lymphoma patients: evidence for long-term clinical and molecular remissions
Authors: C Tarella, P Corradini, M Astolfi, P Bondesan, D Caracciolo, C Cherasco, M Ladetto, F Giaretta, I Ricca, U Vitolo, A Pileri, D Ferrero
Journal: Leukemia (1999)
Efficacy of protracted dose-dense temozolomide (TMZ) in patients with progressive high-grade glioma
Authors: M. U. Abacioglu, H. B. Caglar, P. F. Yumuk, Z. Akgun, B. M. Atasoy, M. Sengoz
Journal: Journal of Clinical Oncology (2009)

e13018 Background: The study was aimed to evaluate the efficacy of TMZ on a protracted dose-dense schedule after standard 5-day TMZ regimen in patients with progressive high-grade glioma. Methods: In this phase II prospective study, patients who had progression on standard 5-day TMZ for recurrence (group 1) or recurrence after concurrent radiotherapy+TMZ and ≥ 2 cycles of adjuvant TMZ (group 2) for high-grade glioma received TMZ 100 mg/m2× 21 q28 days until progression according to MacDonald's criteria. Patients were included in the study after ethical committee approval and written informed consent. The primary end-point was 6 months PFS. Secondary end-points were OS and toxicity. Results: Between October 2006 and October 2008, 25 patients were included in the study. Nine of the patients were group 1 and 16 of them were group 2. Male/female ratio was 18/7. The median age was 50 (range, 18–70) and median KPS score was 80 (range, 50–100). The histopathology was glioblastoma in 18 and grade 3 glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma) in 7. The median cycles of 5-day TMZ received before study entry was 6 (range, 2–18) in group 1 and 6 (2–7) in group 2. With a median follow up of 6 months (1–14 months) the median number of 21-day TMZ cycles received was 2 (range, 1–8). Radiological evaluation could not be performed in 5 patients because of early clinical progression. The best response during treatment was partial response in 2 (8%), stable disease in 9 (36%), and progression in 9 (36%) out of 20 patients assessed. The median time to progression was 2 months (1–8 months) and 6 months PFS rate was 11%. The median OS time was 8 months and 1 year OS rate was 38%. Out of 80 cycles received there was no anemia; 5 (6%) grade 1, 8 (10%) grade 2, 2 (3%) grade 3 leucopenia; 1 (1%) grade 1, 2 (3%) grade 2, 1 (1%) grade 3, 1 (1%) grade 4 thrombocytopenia; 9 (11%) grade 1, 7 (9%) grade 2, 32 (40%) grade 3, and 11 (14%) grade 4 lymphopenia. Study was terminated in 2 patients (one with grade 4 thrombocytopenia and the other with grade 4 hepatic toxicity). There was no dose reduction in the study drug due to toxicity. Conclusions: Protracted dose-dense TMZ after 5-day schedule for recurrent or progressive disease has modest efficacy with tolerable toxicity. No significant financial relationships to disclose.
PMO-160 Liver transplantation for chronic hepatitis C in Northern Ireland
Authors: J Addley, N McDougall, I Cadden, J Cash, J O'Grady
Journal: Gut (2012)

<h3>Introduction</h3> Chronic hepatitis C (CHC) is a leading cause of chronic liver disease in the UK. Orthotopic liver transplantation (OLT) is commonly used for end stage cirrhosis or hepatocellular cancer secondary to CHC. Unfortunately recurrence of CHC in the graft of transplant recipients is almost universal, often leading to accelerated liver damage. Our aim was to assess the outcome of patients attending a Regional Liver Unit in Northern Ireland who underwent OLT for liver disease due to CHC. <h3>Methods</h3> A retrospective study was carried out of patients from Northern Ireland who had OLT between 1998 and 2010 for CHC associated chronic liver disease. Cases were identified by review of the regional OLT database and cross-referenced with the centre where OLT was carried out (KCH, London). <h3>Results</h3> Sixteen patients (11 male) underwent 20 OLTs for CHC between April 1998 and December 2010 (&lt;10% of all OLTs). Mean age was 54 years. 13 patients had single OLT and 3 required multiple transplants. The HCV genotypes were 1 (7), 3 (5) and 2 (4). Prior to OLT, 10 patients received antiviral therapy—all failed (five non-responders, two relapsed following treatment and three failed to tolerate treatment). Data were only available on 19 OLT episodes. Immunosuppressant maintenance therapy was as follows: tacrolimus (9), tacrolimus + mycophenolate (4), cyclosporine (1) and mycophenolate + prednisolone (1). Short-term complications included acute cellular rejection in 5 (26.3%) requiring pulsed methylprednisolone (4) or IL2 blockade (1). Two patients developed renal failure requiring short-term dialysis post transplantation. Long-term complications included biliary anastomotic stricture in 6 (31%) patients and vascular complications in 3 (2 hepatic artery thrombus, 1 hepatic vein stenting). One patient acquired hepatitis B from the transplanted liver. Reasons for re-transplantation were hepatic artery thrombosis (2), recurrent cirrhosis with portal hypertension (1) and primary non-function of the graft (1). Seven (35%) transplants had cirrhosis confirmed on biopsy (5) or clinically (ascites (1) or oesophageal varices (1)) at a mean time of 25.6 months post transplant (range 12–48 months). Five-year mortality in the cohort was 25%. <h3>Conclusion</h3> Hepatitis C accounted for &lt;10% of OLT episodes in Northern Ireland during the study period. This demand may increase in the future as the chronic complications of previously undiagnosed hepatitis C are seen. One third of this small cohort developed cirrhosis within a few years of OLT. <h3>Competing interests</h3> None declared.
The Continuous Bacteremia of Lepromatous Leprosy
Authors: David J. Drutz, Thomas S. N. Chen, Wen-Hsiang Lu
Journal: New England Journal of Medicine (1972)

Abstract Twenty-five of 32 patients with leprosy and high concentrations of acid-fast bacilli (AFB) in the skin had bacteremia of a magnitude that permitted identification of Mycobacterium leprae in smears of peripheral blood. In patients with untreated lepromatous leprosy, AFB are continuously present approximately at a concentration of 105 per milliliter of blood and are unassociated with signs or symptoms of septicemia. AFB are found extracellularly as well as in polymorphonuclear leukocytes, monocytes and large circulating histiocytes. Bacilli appear to enter the bloodstream through invasion of skin arterioles, capillaries and venules. The presence of bacteremia can be predicted from the appearance of skin and liver biopsies. Bacteremia gradually subsides within four months after therapy with diaminodiphenylsulfone is begun, and the disappearance of bacilli from the blood provides an indicator of early response to chemotherapy.
P780 TRENDS IN THE SEROPREVALENCE OF HBV, HCV AND HIV INFECTION AT A REFERENCE MEDICAL AREA IN SPAIN OVER THE LAST FIVE YEARS
Authors: Á. Mena De Cea, L. Moldes Suarez, M. Pérez-Abeledo, I. Torres Beceiro, H. Meijide, A. Cañizares Catellanos, A. Castro-Iglesias, J.D. Pedreira Andrade, G. Bou Aréivalo, E. Poveda Lóipez
Journal: Journal of Hepatology (2014)
Adjuvant Immunotherapy with BCG in Treatment of Regional-Lymph-Node Metastases from Malignant Melanoma
Authors: Frederick R. Eilber, Donald L. Morton, E. Carmack Holmes, Frank C. Sparks, Kenneth P. Ramming
Journal: New England Journal of Medicine (1976)

Despite current surgical therapy, about 80 per cent of patients with malignant melanoma metastatic to lymph nodes succumb to systemic metastatic disease. To determine if postoperative adjuvant immunization with BCG was an effective systemic treatment in these patients with microscopic subclinical metastatic disease, the clinical course of 42 patients treated by operation alone was compared with that of 84 treated by operation and BCG. At two years, the incidence of metastasis in BCG-treated patients was half that of the control group. BCG was more effective in patients with a smaller tumor burden at the time of initial surgical treatment. In patients receiving BCG adjuvant therapy, 90 per cent with microscopic disease in one lymph node appeared free of disease as compared to 40 per cent with macroscopic disease in multiple nodes. In patients with recurrences, an immunotherapeutic effect was demonstrated by a delay of six months in the time to recurrence. Thus, BCG immunotherapy appears to have an inhibiting effect on the "micrometastases" of malignant melanoma. (N Engl J Med 294:237–240, 1976)
S35 Bmp9 And Bmp10 Mediate Connexin Expression In Endothelial Cells: Implications For Pah And Hht
Authors: P. Upton, J. Wilkinson, K. Wiggins, N. Morrell
Journal: Thorax (2014)

<h3>Background</h3> Germ-line mutations in the bone morphogenetic protein type-II receptor, BMPR-II, underlie 80% of heritable pulmonary arterial hypertension (PAH) cases and approximately 25% of idiopathic PAH cases. PAH may arise due to endothelial dysfunction as mice with BMPR-II deficiency exhibit increased pulmonary vascular permeability. BMP9 is an endothelial quiescence factor and is thought to maintain the integrity of the endothelium. We previously reported that BMPR-II and ALK1 are the key receptors through which BMP9 inhibits the proliferation of human pulmonary artery endothelial cells (hPAECs). We hypothesised that BMPR-II deficiency impacts on endothelial cell connectivity and may contribute to endothelial dysfunction in PAH. <h3>Methods</h3> Human pulmonary artery endothelial cells were obtained from Lonza and blood outgrowth endothelial cells (BOECs) were isolated from peripheral blood of unaffected controls or PAH patients with identified BMPR-II mutations. Cells were transfected with siRNAs targeting BMPR-II followed by stimulation with BMP9. RNA was extracted and the expression of candidate genes determined by quantitative PCR. Further siRNA studies were performed for ALK1 and endoglin siRNAs. The promotion of gap junction assembly by BMP9 and BMP10 were assessed by immunofluorescence, Western blotting and functionally using parachute assays. <h3>Results</h3> Screening of candidate BMP9-induced junctional and structural proteins highlighted a subset of endothelial connexins that are BMP9 and BMP10-responsive and dependent on BMPR-II and ALK1. BMP9 and BMP10 increased the expression of the connexins, assessed by Western blotting and immunostaining. In addition, BMP9 and BMP10 significantly increased the transfer of calcein from labelled donor cells to unlabelled acceptor cells, indicating a promotion of endothelial cell connectivity. <h3>Conclusion</h3> In addition to their roles promoting endothelial quiescence, BMP9 and BMP10 directly promote endothelial cell connectivity by increasing connexin expression and assembly. The central contributions of BMPR-II and ALK1 to this process may implicate impaired endothelial connectivity as a pathological component of PAH and HHT.
SAT0119 The relationship between inflammation and joint damage in rheumatoid arthritis is dependent on anti-CCP status
Authors: Y. De Punder, J. Hendrikx, E. Valls Pascual, P. van Riel, J. Fransen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Joint inflammation in Rheumatoid Arthritis is strongly associated with the development of joint damage. However, this association is highly different between patients, which may be explained by the presence of anti-CCP. Therefore it can be hypothesized that anti-CCP modifies the effect of joint inflammation on progression of joint damage. <h3>Objectives</h3> To analyze whether the association between joint damage progression and Swollen Joint Count (SJC44), Erythrocyte Sedimentation Rate (ESR) or Disease Activity Score (DAS) is different for anti-CCP positive versus negative RA patients in the first three years of the disease. <h3>Methods</h3> Follow-up data were used of the first three years from a subset of patients from the Nijmegen Inception Cohort with rated X-rays. Joint damage progression was assessed 1) as the absolute difference in Ratingen score and 2) dichotomized as erosive progression in at least one previously unaffected joint. Time averaged SJC44, ESR and DAS over three years were calculated. Anti-CCP titer ≥25 u/l was regarded as positive. Linear and logistic regression were used for analyses. <h3>Results</h3> Data of 264 RA-patients were used, 180 (68%) were anti-CCP positive. In linear regression, anti-CCP was an effect modifier for the relationship between SJC44 and absolute joint damage progression (p=0.031). Stratification by anti-CCP resulted in beta's of 0.46 and 1.12 for respectively anti-CCP negative and anti-CCP positive patients (see figure left). With up to five swollen joints, the probability of erosive progression in a previously unaffected joint was &lt;20% in anti-CCP negative patients and &gt;70% in anti-CCP positive patients (see figure right). The relationship between DAS and joint damage progression was modified by anti-CCP concerning the chance on progression in at least one new joint. The relationship between ESR and joint damage was not influenced by anti-CCP. <h3>Conclusions</h3> The relationship between SJC44 and joint damage progression is different for anti-CCP positive and anti-CCP negative RA-patients (effect modification). For clinical practice, this means that the treatment target regarding swollen joint count should be lower for anti-CCP positive patients than for anti-CCP negative patients to prevent joint damage progression. <h3>Disclosure of Interest</h3> None Declared
Integrating holism and reductionism in the science of art perception
Authors: Daniel J. Graham
Journal: Behavioral and Brain Sciences (2013)

Abstract The contextualist claim that universalism is irrelevant to the proper study of art can be evaluated by examining an analogous question in neuroscience. Taking the reductionist-holist debate in visual neuroscience as a model, we see that the analog of orthodox contextualism is untenable, whereas integrated approaches have proven highly effective. Given the connection between art and vision, unified approaches are likewise more germane to the scientific study of art.
Abstract P4-03-05: The Clinical Trial of New Optical Mammography
Authors: H Ogura, K Yoshimoto, H Nasu, Y Hosokawa, R Matsunuma, Y Ide, E Yamaki, D Yamashita, T Suzuki, M Oda, Y Ueda, Y Yamashita, H Sakahara
Journal: Cancer Research (2012)

Abstract Objectives: Optical mammography (O-MMG), which utilizes near-infrared light for the detection of abnormal breast tissue, can be a potentially useful and non-invasive tool for the screening of breast cancer patients. Here we report on the preliminary results of our clinical trial using a time-resolved O-MMG system developed by Hamamatsu Photonics (Hamamatsu, Japan). In our past examination, negative results included cases with mismatch for breast cup because of small breast, lesion outside of cup because of big breast, and bad positioning. So, size and shape of a gantry was improved (3 cup sizes; S, M and L cup). We reported the initial experience of the improved O-MMG systems. Materials and Methods: In principle, the technique involves sequential irradiation of the breast tissue with a pulsed laser with a wavelength of 760, 800 and, 830nm, which is then detected by the variable capacity gantry at multiple sites after passing through the breast tissue. Measurement time has improved to about 7 minutes (a third of the conventional measurement time). The data are analyzed and tomographic images of the absorption coefficient of the breast are then reconstructed based on our tomographic reconstruction algorithm. Between October 2011 and May 2012, fifteen patients with breast cancer and one patient with fibroadenoma participated in the trial. Results: In patients with breast cancer, S cup was used for one patient, M cup for 12 patients and L cup for two patients. Five patients after neo-adjuvant chemotherapy were excluded from the analysis. The lesions were depicted as an area of high hemoglobin concentration in 7 of 10 patients with cancer. One lesion of fibroadenoma was also identified as an area of high hemoglobin concentration. Conclusion: Further examination with our new O-MMG systems will be of interest. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-05.
Neither moralists, nor scientists: We are counterfactually reasoning animals
Authors: Bence Nanay
Journal: Behavioral and Brain Sciences (2010)

Abstract We are neither scientists nor moralists. Our mental capacities (such as attributing intentionality) are neither akin to the scientist's exact reasoning, nor are they “suffused through and through with moral considerations” (Knobe's target article, sect. 2.2, last para.). They are more similar to all those simple capacities that humans and animals are equally capable of, but with enhanced sensitivity to counterfactual situations: of what could have been .