BackgroundInflammation is a critical component of tumorigenesis, and many cancers arise from sites of infection, chronic irritation, and inflammation. Inflammatory cytokines triggered by tumors alter hematologic components, including neutrophil, lymphocyte, and monocyte counts. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios have been shown to be valuable prognostic markers in various types of cancers, including bladder cancer. Risk stratification based on clinicopathologic data is insufficient to support treatment-related choices in patients with bladder cancer. Novel prognostic markers are therefore needed. An elevated pretreatment lymphocyte-to-monocyte ratio (LMR) is reportedly associated with improved overall survival (OS) and a longer time to treatment recurrence (TTR) in some types of cancers. However, these data are lacking in patients with bladder cancer. The aim of the present study was to investigate the effect of the preoperative LMR on OS and TTR in a cohort of patients with bladder cancer.MethodsSixty-eight patients with transitional cell carcinoma of the bladder were included in this retrospective analysis. The associations between a high and low LMR with OS and TTR were analyzed using Kaplan–Meier curves and compared by the log-rank test.ResultsIn our study cohort, an elevated preoperative LMR was significantly associated with an increased TTR (P = 0.001) and OS (P = 0.020). Patients with an LMR of ≤2.87 showed a median TTR of 2.0 years (95% CI, 0.27–3.73), whereas patients with an LMR of >2.87 had a median TTR of 11.1 years (95% CI, 2.31–19.88) (P = 0.001). Patients with an LMR of ≤2.81 showed a median OS of 2.7 years (95% CI, 0.63–4.70), whereas patients with an LMR of >2.81 had a median OS of 6.0 years (95% CI, 3.60–8.40) (P = 0.020). The clinical stage at diagnosis was the only clinicopathologic feature associated with the LMR, while tumor invasion depth showed borderline significance.ConclusionsThe LMR is an easily measured and inexpensive prognostic marker that was significantly correlated with OS and TTR in the present retrospective analysis. However, because of the small sample size in this study, larger multicenter, prospective studies are needed.
Background and Aims: Hypertension and obesity are important risk factors of cardiovascular disease. They are both associated with high leptin levels and have been shown to promote vascular hypertrophy, through the RhoA/ROCK and ERK1/2 phosphorylation. Calcineurin/NFAT activation also induces vascular hypertrophy by upregulating various genes. This study aimed to decipher whether a crosstalk exists between the RhoA/ROCK pathway, Ca2+/calcineurin/NFAT pathway, and ERK1/2 phosphorylation in the process of mechanical stretch-induced vascular smooth muscle cell (VSMC) hypertrophy and leptin synthesis.Methods and Results: Rat portal vein (RPV) organ culture was used to investigate the effect of mechanical stretch and exogenous leptin (3.1 nM) on VSMC hypertrophy and leptin synthesis. Results showed that stretching the RPV significantly upregulated leptin secretion, mRNA, and protein expression, which were inhibited by the calcium channel blocker nifedipine (10 μM), the selective calcineurin inhibitor FK506 (1 nM), and the ERK1/2 inhibitor PD98059 (1 μM). The transcription inhibitor actinomycin D (0.1 μM) and the translation inhibitor cycloheximide (1 mM) significantly decreased stretch-induced leptin protein expression. Mechanical stretch or leptin caused an increase in wet weight changes and protein synthesis, considered as hypertrophic markers, while they were inhibited by FK506 (0.1 nM; 1 nM). In addition, stretch or exogenous leptin significantly increased calcineurin activity and MCIP1 expression whereas leptin induced NFAT nuclear translocation in VSMCs. Moreover, in response to stretch or exogenous leptin, the Rho inhibitor C3 exoenzyme (30 ng/mL), the ROCK inhibitor Y-27632 (10 μM), and the actin depolymerization agents Latrunculin B (50 nM) and cytochalasin D (1 μM) reduced calcineurin activation and NFAT nuclear translocation. ERK1/2 phosphorylation was inhibited by FK506 and C3.Conclusions: Mechanical stretch-induced VSMC hypertrophy and leptin synthesis and secretion are mediated by Ca2+/calcineurin/NFAT activation. RhoA/ROCK and ERK1/2 activation are critical for mechanical stretch-induced calcineurin activation.
Severe hypertension is associated with multiple symptoms that reflect the end-organ damage effect of rapidly increasing blood pressure. Encephalopathy is a manifestation of the clinical spectrum of hypertensive emergencies. Hypertensive encephalopathy was initially described as part of the posterior reversible encephalopathy syndrome, which mostly involved the parieto-occipital white matter of the brain. A more detailed review of this syndrome reveals many cases where the brain abnormalities are distributed in a more random pattern. We describe a case of diffuse leukoencephalopthy in a young male who presented with altered mental status, ataxia, and blurred vision. This is the most diffuse brain involvement ever described in hypertensive statuses.
Hypertension is considered one of the major risk factors in developing cardiovascular diseases. Hemodynamic abnormality in hypertension is associated with structural and functional alterations which are mainly mediated via leptin. Molecular mechanisms associated with leptin‐mediated blood vessels remodeling both in vivo and in vitro have not been fully elucidated. In this study, we investigated the effect of partial portal vein ligation (PPVL) on leptin expression in vascular smooth muscle (VSMC) and secretion. We used blood vessels organ culture under mechanical stretch in order to investigate molecular mechanisms of leptin‐induced VSMC remodeling. Data showed that leptin expression and ROS production significantly increased in VSMC after 7 and 14 days post PPVL. A significant increase in serum leptin levels was observed in PPVL. Exposing the blood vessels to mechanical stretch (mimicking hypertension) significantly increased nuclear translocation of GATA‐4 and NFAT which were attenuated by the co‐administration of an anti‐leptin receptor antibody and the RhoA inhibitor C3. In addition, vascular‐proteomics platform was performed assessing differential proteome/systems biology profile between stretched and unstretched blood vessels to investigate the underlying mechanisms involved in vascular hypertrophy. A differential display of proteins were identified (7 proteins were upregulated vs. 12 downregulated) using PANTHER (Protein Analysis Through Evolutionary Relationships) system and Pathway Studio 8. Our results indicate that the activation of GATA‐4 & ROS production plays a pivotal role in hypertension signaling, leading to leptin synthesis and VSMC hypertrophy. Grant Funding Source: Supported by CNRS and MPP at AUB
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