213 research outputs found

    Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease

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    Copyright @ 2010 Cancer Research UK. This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.Background: α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients. Methods: We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-γ. Results: Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P=0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child–Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child–Pugh A score and in 46% with a B or C score. Conclusion: These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more likely to be present in patients with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC.Association for International Cancer Research and Polkemmet Fund, London Clinic

    Label-free multiplex immunoassay of AFP, CEA and CA19-9 by integrated microfluidic biosensor based on imaging ellipsometry

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    This study describes the development of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate 19-9(CA19-9) multiplex immunoassay by integrated microfluidic device based on imaging ellipsometry (IMBIE). Different strategies for AFP, CEA and CA 19-9 simultaneous immunoassay on the same aldehyde-substrate were developed. Unifying the reaction steps of CA19-9 for antigen direct detection, CEA for secondary antibody (rabbit-antiCEA) addition, AFP for secondary (rabbit antiAFP) and an enhancer (goat IgG) application, and comprehensively considering the dynamic ranges and detection sensitivities, we combined these three markers into multiplex analysis in serial format.The sensitivities and dynamic ranges for CA19-9, CEA and AFP were 10.0U/mL, 1.0 ng/mL, 1.0 ng/mL and 2.0-100.0 U/mL, 0.1-64.0 ng/mL, 1.0-128.0 ng/mL, respectively. The intra-assay and inter-assay (coefficient variations) CVs of CA19-9, CEA and AFP were between 1.6-8.9% and 2.1-7.8%. The specificities tested for both cross-reaction and heterogeneous proteins of CA19-9, CEA and AFP were not more than 6.7%. Quantitative detection of 49 sera from gastric patients demonstrated that the accuracy for gastric cancer diagnosis was 83.4%. The total detection time is only 60min for an automated process. The proposed assay has the potential for practical application

    French News Agency AFP-an Agency with a Special Status

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    The thesis titled "French News Agency AFP - the Agency with Special Statutes" deals with the world agency AFP and its public statutes. The news agency is defined on the most general base and there is described the history of the first news agency Havas which is followed by AFP. The author is also interested in foundation of AFP and its transformation into the public institution. The thesis deals with reporting tasks, financial sources, composition and competence of the inspecting authority and statutory authority of Agence France-Presse and Czech News Agency. The content of the work is comparison of agencies above. In the final chapter the author reminds the attempt to change the special statutes of AFP

    Pension reform in Latin America : quick fixes or sustainable reform?

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    Because of better health and higher standards of living, people are living longer. By 2030, more than 16 percent of the world's population will be older than 60, compared with 9 percent today. As a result, pension systems will need reform. Most current systems have substantial unfunded liabilities that will impose significant financial burdens onfuture generations without providing adequate protection for older individuals and lower-income workers. Pension reform is inevitable because of demographic imperatives and because many pension systems are financially unsustainable. Unfunded public pension systems pose political risk if promises to future retirees cannot be met. Pension reform is both technically and politically complex but more and more countries are beginning to address the problem. The question is whether to adopt quick fixes or sustainable changes that will benefit the macroeconomy and protect elderly and lower-income citizens. Quick fixes--typical in many economies--generally involve changes in eligibility (such as retirement age), changes in the rate of contribution or the population of workers on which contributions are calculated, or changes in the structure of benefits. Countries in Latin America have been ahead of other regions in undertaking major reform from pay-as-you-go defined-benefit pension plans to fully funded, defined-contribution pension plans. Because of the successful Chilean pension model, a notable number of Latin American countries have undertaken deep pension reform. The author highlights reform efforts in a sample of countries: Argentina, Brazil, Chile, Mexico, and Peru. Vigilance is still needed, says the author. Effective oversight is essential, and so is complementary reform in the banking, insurance, and securities markets. In capital markets, for example, regulation must be strengthened and the requirement that pension fund investments be made only in government-related securities must be eliminated. New types of insurance must be made available and there must be increased competition among insurance providers. More work must be done but the region's pension systems have started on the right course.Banks&Banking Reform,Payment Systems&Infrastructure,Public Health Promotion,Pensions&Retirement Systems,Environmental Economics&Policies,Pensions&Retirement Systems,Economic Stabilization,Banks&Banking Reform,Environmental Economics&Policies,Economic Theory&Research

    Lessons for Asian Countries from Pension Reforms in Chile

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    Chile's 1981 reform revolutionized pension design and created a system that was lauded and emulated widely. The main feature of the system was the creation of state-mandated, privately managed individual pension capitalization accounts based on contributions of employees. After nearly three decades of experience, there is a reassessment of the extent to which the pension system has achieved its objectives, particularly with respect to coverage and adequacy. In March 2006, the newly elected President Bachelet set up a Presidential Advisory Council on Pension Reform under the chairmanship of Mario Marcel to evaluate the existing pension system. This paper examines the rationale and the nature of the recommendations made by the Council. The analysis focuses on the structure of the proposed new pension system and risk-sharing implications of different pillars of the system, the accessibility of the existing pension system in terms of coverage, particularly for women and self-employed persons, the impact of reform on transaction costs; investment policies and management and their implications for rates of return and financial market development. The implications of the new system on pension design and policy debate in Asian countries are addressed. The paper suggests that must imbibe lessons from countries such as Chile and urgently undertake the task of constructing sustainable, robust and adequate pension systems and social safety nets.Chile, Asia, Pension Reform

    Sensitivity of Ultrasounds and AFP for Detection of Hepatocellular Carcinoma in Patients with Cirrhosis

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    The 55th Annual Medical Student Research Forum at UT Southwestern Medical Center (Monday, January 17, 2017, 2-5 p.m., D1.600)Each year the Medical Student Research Program awards students for the best oral presentation and the best poster presentation as judged by faculty across campus. This author received an award as one of the best poster presentations at this forum.BACKGROUND: Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer related mortality in the United States. Prognosis is strongly tied to early detection, which facilitates curative treatment and long-term survival. Therefore, HCC screening is recommended in at risk patients, i.e. those with cirrhosis. Although ultrasonography is routinely used to screen at-risk patients for HCC, it is operator dependent and its sensitivity outside of prospective cohort studies is poorly described. Further, the benefit of adding serum biomarkers, such as alpha fetoprotein, has also been poorly studied. The aim of our study was to quantify the effectiveness of ultrasound and AFP for HCC detection in patients with cirrhosis. METHODS: We performed a retrospective chart review of patients newly diagnosed with HCC at UT Southwestern and Parkland Health and Hospital System between January 2009 and December 2015. We excluded patients who did not have at least one ultrasound within 12 months prior to HCC diagnosis. Ultrasounds were categorized as positive if there was a suspicious mass > 1 cm and AFP as positive if ≥20 ng/mL, the most common cut-off in clinical practice. Sensitivity was compared between ultrasound alone and combination of ultrasound + AFP using the chi-square test, with statistical significance defined as p<0.05. RESULTS: Of the 925 patients diagnosed with HCC between January 2009 and December 2015, 521 patients had an ultrasound within 12 months prior to HCC diagnosis. The overall sensitivity of ultrasound for HCC detection was 77.5% n=404/521). Of the 521 included patients, 400 had at least one AFP within 12 months of HCC diagnosis. There were 154 patients who had both positive ultrasound and AFP, 143 with positive ultrasound alone, 59 with positive AFP alone, and 44 with negative ultrasound and AFP. The sensitivity of ultrasound alone was 74.3% compared to 89.0% with ultrasound and AFP p<0.001). CONCLUSION: Ultrasound alone has suboptimal sensitivity for HCC detection in clinical practice, highlighting the need for better screening tools. Adding serum biomarkers, such as AFP, can significantly improve HCC detection in clinical practice.Southwestern Medical Foundatio

    Annuity markets in Chile : competition, regulation - and myopia ?

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    The author studies annuity rates in Chile and relates them with industry competition. He finds (1) that annuity insurance companies paying higher broker commissions paid lower annuity rates; and (2) a structural break of the long-run elasticity of annuity rates to the risk-free rate in 2001. Moreover, this structural break coincided with the submission of a new draft pension law proposing greater transparency in annuity markets and a generalized drop in broker commissions. The high commissions charged in the 1990s were partly returned to annuitants as informal (and illegal) cash rebates. Myopic pensioners preferred cash rebates over present values. Thus, the legal threat caused the drop in broker commissions, reduced the illegal practice of cash rebates, increased competition by way of annuity rates, and raised the long-run elasticity to one.Insurance&Risk Mitigation,Economic Theory&Research,Pensions&Retirement Systems,Investment and Investment Climate,Non Bank Financial Institutions

    Simultaneous Measurements of Serum AFP; GPC-3 and HCCR for Diagnosing Hepatocellular Carcinoma

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    Background/Aims: Hepatocellular carcinoma (HCC) is a prevalent malignant tumor. Tumor markers are very useful in early diagnosis; however a single marker is rather limited. We launched a test to increase the diagnostic sensitivity through the combined detection. Methodology: Serum concentration of three tumor-markers, Glypican-3 (GPC-3), Human-Cervical-Cancer-Oncogene (HCCR) and alpha-fetoprotein (AFP), were determined in 189 samples: 101 cases of HCC, 40 cases of cirrhosis, 18 cases of hepatitis and 30 cases of control healthy donors. Every marker was evaluated for its diagnostic value by one-way-analysis-of-variance and receiver-operating-characteristics analysis. Results: GPC-3 was the best marker with an area under the curve (AUC) of 0.892; using 26.8ng/mL as the cut-off for HCC diagnosis, GPC-3 has a sensitivity of 51.5% and maintains a specificity of 92.8%. HCCR, with an AUC of 0.831, can reach a sensitivity of 22.8% and maintain a specificity of 90.9% if the cut-off is set as 58.8mAU/mL With an AUC of 0.827, the efficacy and sensitivity of AFP were 36.6% and 98.5% when using 199.3ng/mL as the cut-off. No significant correlation was found between these three markers. Simultaneously detecting three markers can significantly increases the sensitivity to 80.2%, much higher than AFP alone. Conclusions: GPC-3 and HCCR are useful tumor markers complementary to AFP for clinical diagnosis of HCC.Gastroenterology &amp; HepatologySurgerySCI(E)PubMed11ARTICLE1101718-17245

    Combined analysis of AFP and HCCR-1 as an useful serological marker for small hepatocellular carcinoma: A prospective cohort study

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    Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world. The only serological marker widely used for the diagnosis of HCC is alpha-fetoprotein (AFP). Despite that AFP is widely used for the diagnosis of HCC, it has a limit as a serological marker due to its low sensitivity and specificity. The human cervical cancer proto-oncogene 1 (HCCR-1) was previously reported as a new biomarker for HCC. To further evaluate the HCCR-1 as a biomarker for HCC, we conducted the prospective cohort study. We evaluated the significance of simultaneous measurement of 2 tumor markers in the diagnosis of HCC in China, Japan and Korea. Two markers for HCC, AFP and HCCR-1, were measured in the sera obtained from 1,338 patients at the time of initial diagnosis of HCC. Of the 1338 HCC patients, 616 (46%) and 686 (51.3%) were sero-positive for AFP and HCCR-1, respectively. The positive rate for HCC was increased up to 74.1% in combined use of AFP and HCCR-1. Many cases (54%) for AFP-negative HCC were positive for HCCR-1 and vice versa. More importantly, the diagnostic rate for small HCC (&lt; 2 cm) was significantly improved in the combined analysis of AFP and HCCR-1 to 56.9% although it was only 40.1% and 23.4% in the single analysis of HCCR-1 and AFP, respectively. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000301947100007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biotechnology &amp; Applied MicrobiologyGenetics &amp; HeredityMedicine, Research &amp; ExperimentalPathologySCI(E)9ARTICLE4265-2713
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