64 research outputs found

    Cardiovascular disease related circulating biomarkers and cancer incidence and mortality:is there an association?

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    Aims Recent studies suggest an association between cardiovascular disease (CVD) and cancer incidence/mortality, but the pathophysiological mechanisms underlying these associations are unclear. We aimed to examine biomarkers previously associated with CVD and study their association with incident cancer and cancer-related death in a prospective cohort study. Methods and results We used a proteomic platform to measure 71 cardiovascular biomarkers among 5032 participants in the Framingham Heart Study who were free of cancer at baseline. We used multivariable-adjusted Cox models to examine the association of circulating protein biomarkers with risk of cancer incidence and mortality. To account for multiple testing, we set a 2-sided false discovery rat

    Rapid single-cell identification of Epstein-Barr virus-specific T-cell receptors for cellular therapy

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    BACKGROUND AND AIMS: Epstein-Barr virus (EBV) is associated with solid and hematopoietic malignancies. After allogeneic stem cell transplantation, EBV infection or reactivation represents a potentially life-threatening condition with no specific treatment available in clinical routine. In vitro expansion of naturally occurring EBV-specific T cells for adoptive transfer is time-consuming and influenced by the donor's T-cell receptor (TCR) repertoire and requires a specific memory compartment that is non-existent in seronegative individuals. The authors present highly efficient identification of EBV-specific TCRs that can be expressed on human T cells and recognize EBV-infected cells. METHODS AND RESULTS: Mononuclear cells from six stem cell grafts were expanded in vitro with three HLA-B*35:01- or four HLA-A*02:01-presented peptides derived from six EBV proteins expressed during latent and lytic infection. Epitope-specific T cells expanded on average 42-fold and were single-cell-sorted and TCRαβ-sequenced. To confirm specificity, 11 HLA-B*35:01- and six HLA-A*02:01-restricted dominant TCRs were expressed on reporter cell lines, and 16 of 17 TCRs recognized their presumed target peptides. To confirm recognition of virus-infected cells and assess their value for adoptive therapy, three selected HLA-B*35:01- and four HLA-A*02:01-restricted TCRs were expressed on human peripheral blood lymphocytes. All TCR-transduced cells recognized EBV-infected lymphoblastoid cell lines. CONCLUSIONS: The authors' approach provides sets of EBV epitope-specific TCRs in two different HLA contexts. Resulting cellular products do not require EBV-seropositive donors, can be adjusted to cell subsets of choice with exactly defined proportions of target-specific T cells, can be tracked in vivo and will help to overcome unmet clinical needs in the treatment and prophylaxis of EBV reactivation and associated malignancies

    Association of Cardiometabolic Disease With Cancer in the Community

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    BACKGROUND: Obesity and cardiometabolic dysfunction have been associated with cancer risk and severity. Underlying mechanisms remain unclear. OBJECTIVES: The aim of this study was to examine associations of obesity and related cardiometabolic traits with incident cancer. METHODS: FHS (Framingham Heart Study) and PREVEND (Prevention of Renal and Vascular End-Stage Disease) study participants without prevalent cancer were studied, examining associations of obesity, body mass index (BMI), waist circumference, visceral adipose tissue (VAT) and subcutaneous adipose tissue depots, and C-reactive protein (CRP) with future cancer in Cox models. RESULTS: Among 20,667 participants (mean age 50 years, 53% women), 2,619 cancer events were observed over a median follow-up duration of 15 years. Obesity was associated with increased risk for future gastrointestinal (HR: 1.30; 95% CI: 1.05-1.60), gynecologic (HR: 1.62; 95% CI: 1.08-2.45), and breast (HR: 1.32; 95% CI: 1.05-1.66) cancer and lower risk for lung cancer (HR: 0.62; 95% CI: 0.44-0.87). Similarly, waist circumference was associated with increased risk for overall, gastrointestinal, and gynecologic but not lung cancer. VAT but not subcutaneous adipose tissue was associated with risk for overall cancer (HR: 1.22; 95% CI: 1.05-1.43), lung cancer (HR: 1.92; 95% CI: 1.01-3.66), and melanoma (HR: 1.56; 95% CI: 1.02-2.38) independent of BMI. Last, higher CRP levels were associated with higher risk for overall, colorectal, and lung cancer (P < 0.05 for all). CONCLUSIONS: Obesity and abdominal adiposity are associated with future risk for specific cancers (eg, gastrointestinal, gynecologic). Although obesity was associated with lower risk for lung cancer, greater VAT and CRP were associated with higher lung cancer risk after adjusting for BMI

    Treatment principles for osteochondral lesions in foot and ankle

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    Osteochondral lesion of the talus (OLT) is a broad term used to describe an injury or abnormality of the talar articular cartilage and adjacent bone. A variety of terms have been used to refer to this clinical entity, including osteochondritis dissecans (OCD), osteochondral fracture and osteochondral defect. Whether OLT is a precursor to more generalised arthrosis of the ankle remains unclear, but the condition is often symptomatic enough to warrant treatment. In more than one third of cases, conservative treatment is unsuccessful, and surgery is indicated. There is a wide variety of treatment strategies for osteochondral defects of the ankle, with new techniques that have substantially increased over the last decade. The common treatment strategies of symptomatic osteochondral lesions include nonsurgical treatment, with rest, cast immobilisation and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Surgical options are lesion excision, excision and curettage, excision combined with curettage and microfracturing, filling the defect with autogenous cancellous bone graft, antegrade (transmalleolar) drilling, retrograde drilling, fixation and techniques such as osteochondral transplantation [osteochondral autograft transfer system (OATS)] and autologous chondrocyte implantation (ACI). Furthermore, smaller lesions are symptomatic and when left untreated, OCDs can progress; current treatment strategies have not solved this problem. The target of these treatment strategies is to relieve symptoms and improve function. Publications on the efficacy of these treatment strategies vary. In most cases, several treatment options are viable, and the choice of treatment is based on defect type and size and preferences of the treating clinician. © 2013 Springer-Verlag Berlin Heidelberg

    From all to (nearly) none

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    Pyoderma gangrenosum.

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    Autologous bone-marrow transplantation: host effects of high-dose BCNU.

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    Correction to: Genome size and chromosome number of ten plant species from Kerguelen Islands (Polar Biology, (2020), 43, 12, (1985-1999), 10.1007/s00300-020-02755-7)

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    International audienceThe original article was published with missing information in Table 1. The complete Table 1 is now provided: this correction stands to correct the original article
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