Author
Francisca C. Gushiken
Bio: Francisca C. Gushiken is an academic researcher from University of Texas Health Science Center at Houston. The author has contributed to research in topics: Binding site & Vesicle. The author has an hindex of 5, co-authored 6 publications receiving 624 citations.
Papers
More filters
TL;DR: Findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplasticThrombocytosis, which fuels tumor growth.
Abstract: From the Departments of Gynecologic Oncology and Reproductive Medicine (R.L.S., A.M.N., H.D.H., J.B.-M., W.H., H.G., K.M., M.M.K.S., E.R.K., A.K.S.), Cancer Biology (R.R., G.L.-B., A.K.S.), Experimental Therapeutics (G.N.A.-P., I.T., B.O., G.L.-B.), Hematology and Oncology (C.V.P.), Pathology (M.T.D.), Benign Hematology (H.G.V., V.A.-K.), Biostatistics (D.U.), and Leukemia (F.G.), and the Center for RNA Interference and Non-Coding RNA (H.D.H., G.L.-B.,
643 citations
TL;DR: The prevalence of mutations in the fifth domain of β2GPI in patients with SLE and/or APS were similar to those previously reported for the general population, and Heterozygosity for either mutation does not influence the incidence of aPL, but in patientsWith SLE, the mutation at exon 8 may predispose to thrombosis as an independent factor.
Abstract: Objective
To determine the frequency of mutations in the phospholipid binding domain of β2-glycoprotein I (β2GPI) in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS), and to analyze the clinical correlations of such mutations with thromboembolic complications.
Methods
Exons 7 and 8 of β2GPI, which encode for its fifth domain, were amplified by polymerase chain reaction, and the presence of mutations was determined by restriction digestion and single-strand conformation polymorphism analysis. A clinical correlation with these mutations and the presence of antiphospholipid antibodies (aPL), lupus anticoagulant (LAC), anti-β2GPI antibody, and the development of thromboembolic complications was performed using chi-square and Fisher's exact tests.
Results
From a total of 143 patients studied, we found that 5.6% were heterozygous for the mutation at exon 7 (codon 306), and 7.7% were heterozygous for the mutation at exon 8 (codon 316). No homozygous subjects were found for either mutation. No significant correlation between these mutations and the presence of aPL, LAC, or anti-β2GPI antibodies was found. In patients with SLE (n = 95), 4 of 6 patients with exon 8 mutation had thrombosis, compared with 22 of 82 patients without the mutation (P = 0.043).
Conclusion
The prevalence of mutations in the fifth domain of β2GPI in these patients with SLE and/or APS were similar to those previously reported for the general population. Heterozygosity for either mutation does not influence the incidence of aPL, but in patients with SLE, the mutation at exon 8 may predispose to thrombosis as an independent factor.
36 citations
TL;DR: Insight is offered into the mechanism of formation of antiphospholipid antibodies and the possible role of the deficiency of β2‐glycoprotein I in the pathogenesis of thrombosis is suggested.
Abstract: β2-Glycoprotein I, an anionic phospholipid-binding 50-kDa plasma protein, circulates in the plasma at a concentration of 30–200 μg/ml. Its physiological role remains uncertain, but an important clue to this role is suggested by the finding that antibodies to this protein are frequently found in patients with antiphospholipid antibodies and thrombosis. β2-Glycoprotein I belongs to the complement control protein (CCP) superfamily with five CCP domains. The fifth CCP domain of β2-glycoprotein I has a unique structure and contains a stretch of positively charged amino acids that mediates the binding to phospholipids. This interaction may mediate the clearance of anionic phospholipid-containing surfaces from the circulation. Mutations in this domain affect its binding to phospholipids. We have identified a patient with primary antiphospholipid syndrome who is a compound heterozygous for two mutations in the fifth CCP. One mutation is located in exon 7 (codon 306), and the second mutation is in exon 8 (codon 316). The mutant β2-glycoprotein I was present in normal quantities in his plasma but did not bind to cardiolipin. He had recurrent deep vein thrombosis and pulmonary embolism at age 28 and a thrombotic stroke at age 35, with no other identifiable risk factor for a hypercoagulable state. This report offers some insight into the mechanism of formation of antiphospholipid antibodies and suggests the possible role of the deficiency of β2-glycoprotein I in the pathogenesis of thrombosis. Am. J. Hematol. 65:160–165, 2000. © 2000 Wiley-Liss, Inc.
26 citations
Journal Article•
TL;DR: This is the first report of peliosis hepatis associated with administration of 2-chloro-3'-deoxyadenosine and the literature is reviewed.
Abstract: Peliosis hepatis is an unusual disorder associated with a variety of diseases and treatments. This is the first report of peliosis hepatis associated with administration of 2-chloro-3'-deoxyadenosine. The literature is reviewed.
19 citations
TL;DR: The normal cardiolipin binding in heterozygous state for mutations at phospholipid-binding domain may be due to the multimeric structure of beta2-glycoprotein I, which is found in plasma at a concentration of approximately 200 microg/ml.
16 citations
Cited by
More filters
TL;DR: It is asserted that inflammation and innate immunity are important targets in patients with cancer on the basis of extensive preclinical and epidemiological data and potential for novel cancer prevention and treatment strategies.
Abstract: Tumour-promoting inflammation is considered one of the enabling characteristics of cancer development. Chronic inflammatory disease increases the risk of some cancers, and strong epidemiological evidence exists that NSAIDs, particularly aspirin, are powerful chemopreventive agents. Tumour microenvironments contain many different inflammatory cells and mediators; targeting these factors in genetic, transplantable and inducible murine models of cancer substantially reduces the development, growth and spread of disease. Thus, this complex network of inflammation offers targets for prevention and treatment of malignant disease. Much potential exists in this area for novel cancer prevention and treatment strategies, although clinical research to support targeting of cancer-related inflammation and innate immunity in patients with advanced-stage cancer remains in its infancy. Following the initial successes of immunotherapies that modulate the adaptive immune system, we assert that inflammation and innate immunity are important targets in patients with cancer on the basis of extensive preclinical and epidemiological data. The adaptive immune response is heavily dependent on innate immunity, therefore, inhibiting some of the tumour-promoting immunosuppressive actions of the innate immune system might enhance the potential of immunotherapies that activate a nascent antitumour response.
836 citations
TL;DR: How a clearer understanding of systemic regulation of cancer progression could guide development of new therapeutic modalities and efforts to prevent disease relapse following initial diagnosis and treatment is discussed.
Abstract: Recent pre-clinical and clinical research has provided evidence that cancer progression is driven not only by a tumour's underlying genetic alterations and paracrine interactions within the tumour microenvironment, but also by complex systemic processes. We review these emerging paradigms of cancer pathophysiology and discuss how a clearer understanding of systemic regulation of cancer progression could guide development of new therapeutic modalities and efforts to prevent disease relapse following initial diagnosis and treatment.
713 citations
TL;DR: Elevated pre-treatment NLR and PLR are associated with shorter OS and PFS and with lower response rates in patients with metastatic NSCLC treated with nivolumab independently of other prognostic factors.
563 citations
TL;DR: A high PLR is associated with worse OS in various solid tumors and is a readily available and inexpensive biomarker with independent prognostic value in solid tumors.
Abstract: Background: Inflammation influences cancer development and progression. An elevated platelet to lymphocyte ratio (PLR), a marker of inflammation, has been linked to poor prognosis in several malignancies. Here, we quantify the prognostic impact of this biomarker.
Methods: A systematic review of databases was conducted to identify publications exploring the association of blood PLR and overall survival (OS) in solid tumors. Data were pooled in a meta-analysis. Pooled HRs for OS by disease group and by PLR cutoff groups were computed and weighted using generic inverse-variance and random-effect modeling.
Results: Twenty studies comprising 12,754 patients were assessed. Cutoffs for PLR defining risk groups ranged from 150 to 300 and were dichotomous (12 studies; group 1) or split into three groups ( 300, 8 studies; group 2). Higher PLR was associated with significantly worse OS in group 1 [HR = 1.87; 95% confidence interval (CI, 1.49–2.34); P < 0.001] and with a nonsignificant association in group 2 (HR per higher category = 1.21; 95%CI, 0.97–1.50; P = 0.10). The size of effect of PLR on OS was greater for metastatic disease (HR[group 1] = 2.0; 95% CI, 1.6–2.7; HR[group 2] = 1.6; 95% CI, 1.1–2.4) than for early-stage disease (HR[group 1] = 1.5; 95% CI, 1.0–2.2; HR[group 2] = 1.0; 95% CI, 0.8–1.3). A significant association was observed for colorectal, hepatocellular, gastroesophageal, ovarian, and pancreatic carcinoma in group 1 and for colorectal cancers in group 2.
Conclusion: A high PLR is associated with worse OS in various solid tumors. Further research of its regulation and relevance in daily practice is warranted.
Impact: PLR is a readily available and inexpensive biomarker with independent prognostic value in solid tumors. Cancer Epidemiol Biomarkers Prev; 23(7); 1204–12. ©2014 AACR .
This article is featured in Highlights of This Issue, [p. 1137][1]
[1]: /lookup/volpage/23/1137?iss=7
501 citations
TL;DR: The basic scientist studying platelet function can think beyond the traditional hemostasis and thrombosis paradigms, while the practicing hematologist must appreciate platelet relevance in a wide range of disease processes.
450 citations