Integrin expression in correlation to clinicopathological features and prognosis of prostate cancer: A systematic review and meta-analysis

Background: The prompt identification of patients with poor prognosis is essential in order to improve the treatment outcomes in prostate cancer (CaP); as a novel approach, several molecular markers, including integrins, have been discussed as prognostic biomarkers. Our aim was to comprehensively examine aberrant expression of integrins in correlation with clinicopathological features and prognosis in CaP by synthesizing all available evidence, in a systematic review and meta-analysis. Methods: A systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Scientific literature databases (Pubmed, Embase, and Scopus) were systematically searched until May 10, 2020. Random-effects (DerSimonian-Laird) models were used to estimate pooled odds ratios (ORs) for cross-sectional correlations with clinicopathological characteristics and relative risks for longitudinal associations with prognosis. Results: Fourteen studies were included with a total number of 3,194 CaP cases examined (13 cross-sectional and four longitudinal cohort study arms). Correlation of low expression of α₆ (pooled OR = 0.10, 95% confidence interval [CI]: 0.04–0.28, P < 0.001) and β₁ (pooled OR = 0.45; 95% CI: 0.21–1.00, P = 0.049) integrin with high Gleason score was noted. A borderline trend between reduced expression of α₆ integrin and an advanced clinical stage of CaP (pooled OR = 0.48; 95% CI: 0.22-1.03, P = 0.06) was observed. No associations with biochemical recurrence and survival were documented. Conclusions: Evidence on the association of low expression of integrins α₆ and β₁ and more advanced CaP exist, whereas significant results on survival were not documented; further studies are warranted.     

Obesity and risk of malignant melanoma: A meta-analysis of cohort and case–control studies

Although obesity is an established risk factor for several cancer types, its possible role in the aetiology of malignant melanoma remains unclear. This meta-analysis aims to examine the association between obesity and melanoma risk, exploring any tentative gender-specific associations. After the identification of eligible studies, we estimated pooled effect estimates (odds ratios and relative risks), undertook a meta-regression analysis and analysed separately risk of malignant melanoma among males and females in relation to body mass index (BMI) and body surface area (BSA). Out of the 21 eligible articles, 11 used a case–control design encompassing 4460 cases/6342 controls; 10 used a cohort design whose total size comprised 7895 incident cases/6,368,671 subjects. Among males, the pooled effect estimate was 1.31 (95% confidence interval (CI): 1.18–1.45) for overweight and 1.31 (95% CI: 1.19–1.44) for obese. Meta-regression revealed no significant slope, most probably due to the underlying plateau in effect estimates. Among females, no significant association was documented; the pooled effect estimate for overweight and obese subjects was 0.98 (95% CI: 0.92–1.05) and 0.99 (95% CI: 0.83–1.18), respectively. Noticeably, there was evidence for confounding between sunlight exposure and obesity in females. All results were reproducible upon analyses on BSA. In conclusion, overweight and obesity are associated with increased risk of malignant melanoma among males. Meticulous assessment of sunlight exposure is needed especially in women, since self limited public sun exposure may be prevalent among overweight or obese females. Higher-order associations between BMI and melanoma risk should be addressed and examined by the future studies.     

An internet survey on self‐reported food allergy in Greece: clinical aspects and lack of appropriate medical consultation

Background Food allergy (FA) represents a common and worldwide disorder but in publications referring to FA the reported diagnosis is rarely confirmed. Consequently, the subjectively assessed FA may negatively affect the quality of life of patients and their families. Objective We have conducted this internet survey in order to estimate the self‐reported perception of FA in Greece. Methods A standard anonymous questionnaire was posted for a 3‐month period on http://www.in.gr , a Greek popular Internet portal. Each individual could participate only once. Participants were screened for the presence or history of FA by a key question and were then asked to provide information on symptoms, course and management. Results A total of 3673 adult subjects (mean age 34.2 years, range 18–74, females 61.3%), reporting FA were included in analysis. Most reported reactions were related to fruits (14.9%), seafood (10.7%) and nuts (9.2%). The first episode occurred principally during the second (29.2%) and third (30.9%) decade within 3 h from consumption (82.2%). Predominant symptoms were urticaria and oral allergy syndrome (almost 25% each one). Nearly half of the participants sought no medical advice, while 31.4% asked for an allergist’s consultation. Almost 21% of reactors were hospitalized; nuts, severity of symptoms (lower respiratory and/or cardiovascular), onset in lower age, previous exercise and concomitant alcohol and/or aspirin intake were positively associated with hospitalization. Conclusion Although FA causes severe anaphylactic episodes, almost 50% of individuals who experience symptoms perceived as FA do not seek medical advice. Awareness programmes must be carried out in order to increase consciousness about this potentially fatal medical condition.     

Apolipoprotein E and Paraoxonase 1 polymorphisms are associated with lower serum thyroid hormones in postmenopausal women

Objective  Autoimmune thyroiditis and overt or subclinical hypothyroidism have been associated with increased prevalence of cardiovascular disease (CVD).
Design  Cross-sectional investigation of the association between gene polymorphisms related to CVD with thyroid function and autoimmunity.
Patients  In total 84 healthy postmenopausal women aged 49–69 years.
Measurements  FT3, FT4, anti-TPO and anti-TG were assessed in the sera of participants. The following polymorphisms were assessed from peripheral lymphocyte DNA: Apolipoprotein E E2/E3/E4, paraoxonase 1 A/B, Glycoprotein IIIa leu33pro, MTHFR ala222val, ApoBarg3500gln, plasminogen activator inhibitor 1 4G/5G, cholesterol 7-α hydroxylase A204C and cholesterol ester transfer protein B1/B2.
Results  A statistically significant correlation was found between Apolipoprotein E and paraoxonase1 polymorphisms and serum thyroid hormones: carriers of the E2 or E4 allele of the ApoE gene had lower levels of FT4 ( P  = 0·0005) than women with the E3/E3 genotype. Carriers of the B allele of paraoxonase 1 gene had lower levels of FT3 compared to women with the wild-type genotype ( P =  0·047). A statistically significant positive association ( P =  0·049) was also observed between anti-TG antibodies and the presence of the E2 allele of the Apolipoprotein E gene.
Conclusions  Polymorphisms of apolipoprotein E and paraoxonase 1 are associated with different levels of thyroid hormone and anti-Tg antibody levels in the study population in this pilot study. The mechanism underlying this association remains to be elucidated.     

LC-MS/MS测定人血浆中对乙酰氨基酚及其人体药动学和生物等效性研究

目的 建立一种快速、灵敏的高效液相色谱-串联质谱（HPLC-MS/MS）方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1～8.0 μg·mL-1范围内线性良好（r2 > 0.99）,最低检测限为 0.1 μg·mL-1,提取回收率为91.0%～98.7%,日内和日间准确度分别为98.8%～111.3% （精密度：CV ? 9.03%）和94.9%～102.6% （精密度：CV ? 10.68%）。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%～105.79%,94.25%～101.54%和93.24%～101.02%,均落在生物等效可接受标准80.00%～125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。     

Does Pregnancy-Associated Breast Cancer Imply a Worse Prognosis? A Matched Case-Case Study

Zusammenfassung

Hintergrund: Die Auswirkungen einer Schwangerschaft auf die Prognose des Mammakarzinoms werden in der Literatur kontrovers diskutiert. Wir haben eine gepaarte Fall-Fall-Studie konzipiert, in der schwangerschaftsasso-ziierte Mammakarzinom (SAM)-Fälle entsprechend ihres Stadiums, Alters und Jahr der Diagnosestellung mit Mammakarzinom-Patientinnen gepaart wurden. Patientinnen und Methoden: 39 aufeinanderfolgende SAM-Fälle wurden mit 39 prämenopausalen Fällen von Brust-krebs gepaart. Univariate und multivariate Überlebens-analysen mit Anpassung an Stadium, Grad, Östrogen-rezeptorstatus und Alter zum Zeitpunkt der Diagnose wurden durchgeführt. Ergebnisse: Hinsichtlich des Gesamtüberlebens deutete die univariate Analyse auf ein längeres Gesamtüberleben für nicht-SAM-Fälle vs. SAM-Fälle hin. Gleichzeitig war ein fortgeschritteneres Stadium ein Prädiktor für ein kürzeres Überleben. Die multivariate Analyse bestätigte die unabhängige ver-schlechternde Auswirkung einer Schwangerschaft. Inter-essanterweise ergab eine genestete Post-hoc-Analyse der SAM-Fälle Hinweise auf ein kürzeres Gesamtüberleben für das dritte Trimester. Die oben erwähnten Ergebnisse für das Gesamtüberleben konnten desweiteren bei der Untersuchung des rezidivfreien Überlebens reproduziert werden. Schlussfolgerung: Mit ihrem gepaarten Fall-Fall-Design deutet die vorliegende Studie darauf hin, dass Schwangerschaft ein schlechter Prognosefaktor beim Mammakarzinom ist.     

Adhesion of platelets to surface-bound fibrinogen under flow

After platelet activation, fibrinogen mediates platelet-platelet interactions leading to platelet aggregation. In addition, fibrinogen can also function as a cell adhesion molecule, providing a substratum for adhesion of platelets and endothelial cells. In this report, we studied the adhesion of platelets to surface-immobilized fibrinogen under flow in different shear rates. Heparinized whole blood containing mepacrine-labeled platelets was perfused for two minutes at various wall shear rates from 250 to 2,000 s-1 in a parallel plate flow chamber. The number of adherent fluorescent platelets was quantitated every 15 seconds with an epifluorescent videomicroscope and digital image processing system. When compared with platelet adhesion and aggregation seen on glass surfaces coated with type I bovine collagen, a significant increase in platelet adhesion was observed on immobilized fibrinogen up to wall shear rates of 800 s-1. The adherent platelets formed a single layer on fibrinogen-coated surfaces. Under identical conditions, no significant adhesion was observed on fibronectin- or vitronectin-coated surfaces. Although platelet adhesion to collagen was substantially inhibited by the platelet inhibitors prostaglandin E1 and theophylline, these inhibitors had no effect on platelet adhesion to fibrinogen. Platelets adhered to recombinant homodimeric wild-type (gamma 400-411) fibrinogen, but not to the recombinant homodimeric gamma' variant of fibrinogen. Platelet adhesion to recombinant fibrinogen with RGD to RGE mutations at positions alpha 95-97 and alpha 572-574 was similar to that with plasma-derived fibrinogen. These results show that platelets adhere to fibrinogen-coated surfaces under moderate wall shear rates, that the interaction is mediated by the fibrinogen 400-411 sequence at the carboxy-terminus of the gamma chain, and that the interaction is independent of platelet activation and the RGD sequences in the alpha chain.     

The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation

Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a potentially lethal complication during the first 6 months after allogeneic bone marrow transplantation (BMT). To determine whether deficiencies of EBV-specific cellular immunity contribute to EBV-LPD susceptibility and distinguish patients at risk, we performed limiting dilution analysis to quantify anti-EBV cytotoxic T-lymphocyte precursor (CTLp) frequencies in 26 recipients of unmodified or T-cell-depleted (TCD) grafts from EBV-seropositive donors. At 3 months post-BMT (n = 26), only five patients had EBV CTLp frequencies in the range of seropositive normal controls, irrespective of the type of transplant administered. By 6 months post-BMT, 9 of 13 patients tested had EBV CTLp frequencies within the normal range. The time period in which these patients had deficient cellular immunity to EBV corresponds to the period in which we have observed EBV-LPD in most prior patients. One patient with a low EBV CTLp frequency at 4 months post-BMT developed an EBV-LPD. Within 2 weeks of receiving an infusion of donor peripheral blood mononuclear cells (PBMC) providing less than 1,200 EBV- specific cytotoxic T-cell precursors, populations of EBV-specific CTL in the circulation were restored to levels detected in normal seropositive adults. Concurrently, the patient achieved a regression of the EBV-LPD, which has been sustained without further therapy. These studies indicate that recipients of both unmodified and TCD marrow grafts have profound deficiencies of EBV-specific T cell-mediated immunity early posttransplant, and that the period of risk for EBV-LPD closely corresponds to this interval of severe deficiency. Treatment of one patient with EBV-LPD with marrow donor-derived PBMC induced a rapid expansion of EBV-specific cytotoxic T-cell populations that occurred contemporaneously with the clinical regression of disease.