As compared with conventional anticoagulant therapy, combined antiplatelet therapy after the placement of coronary-artery stents reduces the incidence of both cardiac events and hemorrhagic and vascular complications.
This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.
Diagnostic and prognostic biomarkers are useful tools in defining cancer patients at risk, some are also useful in defining and following therapy (1). In view of the recent discovery in cancer biology that proteolytic factors of the plasminogen activation system not only are associated with the regulation and control of established cancer but also with poor prognosis, various investigations have been conducted to elucidate protease-mediated cellular mechanisms of tumor invasion and metastasis (2-6). Furthernore, rational anticancer drug development has identified substances able to block, bypass or re-regulate tumor-associated proteolysis and thereby diminish tumor spread (3). During tumor invasion and metastasis, tumor cells cross host cellular and extracellular matrix barriers by attachment to and interaction with components of the basement membrane and the extracellular matrix, and by local proteolysis (Figs. I and 2). Penetrating tumor cells focus proteolytic activity to the cell surface through receptors for the serine proteases plasmin and the plasminogen activator UPA (urokinase-type plasminogen activator). The tumor cell receptor for uPA, uPA-R (CD87), binds uPA released from surrounding tumor cells or stroma cells (7). Binding of the protease UPA to uPA-R focusses proteolytic action to the surface of tumor cells. uPA converts enzymatically inactive plasminogen into the serine protease plasmin (Fig. 3). Plasmin degrades proteins of the extracellular matrix thus facilitating extracellular matrix degradation, tumor cell proliferation, invasion, and metastasis. Proteolytic action of uPA is controlled by its inhibitors PAI-1 and PAI-Z which may bind to the cell surface associated uPA-R/uPA complex forming an en zymati call y inactive trimeric receptor-protease-inhibitor complex which is internalized by the tumor cell (8,9).
ObjectiveGastrointestinal microbiota may be involved in Helicobacter pylori-associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection.DesignDeep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment, relative to 49 H.pylori negative subjects.ResultsIn H. pylori positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in H. pylori positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between Helicobacter and Fusobacterium, Neisseria, Prevotella, Veillonella, Rothia were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased Bifidobacterium after successful H. pylori eradication and more upregulated drug-resistant functional orthologs after failed treatment.ConclusionH. pylori infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful H. pylori eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.
Background-Retrospective postinfarction studies revealed that decreased heart rate turbulence (HRT) indicates increased risk for subsequent death. This is the first prospective study to validate HRT in a large cohort of the reperfusion era. Methods and Results-One thousand four hundred fifty-five survivors of an acute myocardial infarction (age Ͻ76 years) in sinus rhythm were enrolled. HRT onset (TO) and slope (TS) were calculated from Holter records. Patients were classified into the following HRT categories: category 0 if both TO and TS were normal, category 1 if either TO or TS was abnormal, or category 2 if both TO and TS were abnormal. The primary end point was all-cause mortality. During a follow-up of 22 months, 70 patients died. Multivariately, HRT category 2 was the strongest predictor of death (hazard ratio, 5.9; 95% CI, 2.9 to 12.2), followed by left ventricular ejection fraction (LVEF) Յ30% (4.5; 2.6 to 7.8), diabetes mellitus (2.5; 1.6 to 4.1), age Ն65 years (2.4; 1.5 to 3.9), and HRT category 1 (2.4; 1.2 to 4.9). LVEF Յ30% had a sensitivity of 27% at a positive predictive accuracy level of 23%. The combined criteria of LVEF Յ30%, HRT category 2 or LVEF Ͼ30%, age Ն65 years, diabetes mellitus, and HRT category 2 had a sensitivity of 24% at a positive predictive accuracy level of 37%. The combined criteria of LVEF Յ30% or LVEF Ͼ30%, age Ն65 years, diabetes mellitus, and HRT category 1 or 2 had a sensitivity of 44% at a positive predictive accuracy level of 23%. Conclusions-HRT is a strong predictor of subsequent death in postinfarction patients of the reperfusion era. (Circulation.
In patients with diabetes mellitus and coronary artery disease, use of the sirolimus-eluting stent is associated with a decrease in the extent of late luminal loss, as compared with use of the paclitaxel-eluting stent, suggesting a reduced risk of restenosis.
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