scholarly journals Assessing the impact of organ-specific lesion dynamics on survival in patients with recurrent urothelial carcinoma treated with atezolizumab or chemotherapy

ESMO Open ◽  
2022 ◽  
Vol 7 (1) ◽  
pp. 100346
Author(s):  
M. Kerioui ◽  
S. Desmée ◽  
F. Mercier ◽  
A. Lin ◽  
B. Wu ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Organ Specific ◽  
The Impact

scholarly journals Tumor Necrosis with Adjunction of Preoperative Monocyte-to-Lymphocyte Ratio as a New Risk Stratification Marker Can Independently Predict Poor Outcomes in Upper Tract Urothelial Carcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2983
Author(s):  
Kun-Che Lin ◽  
Hau-Chern Jan ◽  
Che-Yuan Hu ◽  
Yin-Chien Ou ◽  
Yao-Lin Kao ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Necrosis ◽  
Roc Analysis ◽  
Upper Tract Urothelial Carcinoma ◽  
Postoperative Treatment ◽  
Rank Test ◽  
Prognostic Impact ◽  
Lymphocyte Ratio ◽  
Upper Tract ◽  
The Impact

Objectives: This study aimed at investigating the prognostic impact of tumor necrosis and preoperative monocyte-to-lymphocyte ratio (MLR) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods: A total of 521 patients with UTUC treated with RNU from January 2008 to June 2019 at our institution were enrolled. Histological tumor necrosis was defined as the presence of microscopic coagulative necrosis. The optimal value of MLR was determined as 0.4 by receiver operating characteristic (ROC) analysis based on cancer-specific mortality. The Kaplan–Meier method with log-rank test and Cox proportional hazards regression models were performed to evaluate the impact of tumor necrosis and MLR on overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Furthermore, ROC analysis was used to estimate the predictive ability of potential prognostic factors for oncological outcomes. Results: Tumor necrosis was present in 106 patients (20%), which was significantly associated with tumor location, high pathological tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, tumor size, and increased monocyte counts. On multivariate analysis, the combination of tumor necrosis and preoperative MLR was an independent prognosticator of OS, CSS, and RFS (all p < 0.05). Moreover, ROC analyses revealed the predictive accuracy of a combination of tumor necrosis and preoperative MLR for OS, CSS, and RFS with the area under the ROC curve of 0.745, 0.810, and 0.782, respectively (all p < 0.001). Conclusions: The combination of tumor necrosis and preoperative MLR can be used as an independent prognosticator in patients with UTUC after RNU. The identification of this combination could help physicians to recognize high-risk patients with unfavorable outcomes and devise more appropriate postoperative treatment plans.

scholarly journals Thioredoxin-dependent control balances the metabolic activities of tetrapyrrole biosynthesis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Daniel Wittmann ◽  
Neha Sinha ◽  
Bernhard Grimm
Keyword(s):  
Environmental Changes ◽  
Nuclear Gene ◽  
Tetrapyrrole Biosynthesis ◽  
Nuclear Gene Expression ◽  
Light Levels ◽  
Organ Specific ◽  
Intracellular Compartments ◽  
The Face ◽  
Metabolic Activities ◽  
The Impact

AbstractPlastids are specialized organelles found in plants, which are endowed with their own genomes, and differ in many respects from the intracellular compartments of organisms belonging to other kingdoms of life. They differentiate into diverse, plant organ-specific variants, and are perhaps the most versatile organelles known. Chloroplasts are the green plastids in the leaves and stems of plants, whose primary function is photosynthesis. In response to environmental changes, chloroplasts use several mechanisms to coordinate their photosynthetic activities with nuclear gene expression and other metabolic pathways. Here, we focus on a redox-based regulatory network composed of thioredoxins (TRX) and TRX-like proteins. Among multiple redox-controlled metabolic activities in chloroplasts, tetrapyrrole biosynthesis is particularly rich in TRX-dependent enzymes. This review summarizes the effects of plastid-localized reductants on several enzymes of this pathway, which have been shown to undergo dithiol-disulfide transitions. We describe the impact of TRX-dependent control on the activity, stability and interactions of these enzymes, and assess its contribution to the provision of adequate supplies of metabolic intermediates in the face of diurnal and more rapid and transient changes in light levels and other environmental factors.

scholarly journals Ureteral Involvement and Diabetes Increase the Risk of Subsequent Bladder Recurrence after Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Che-Yuan Hu ◽  
Yu-Chieh Tsai ◽  
Shuo-Meng Wang ◽  
Chao-Yuan Huang ◽  
Huai-Ching Tai ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Urinary Tract ◽  
Urothelial Carcinoma ◽  
Cox Model ◽  
Medical Center ◽  
Upper Urinary Tract ◽  
Increased Risk ◽  
The Impact ◽  
Bladder Recurrence ◽  
Urinary Tract Urothelial Carcinoma

Objectives.To investigate the prognostic factors for bladder recurrence after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UUT-UC).Methods.From 1994 to 2012, 695 patients with UUT-UC treated with RNU were enrolled in National Taiwan University Medical Center. Among them, 532 patients with no prior bladder UC history were recruited for analysis. We assessed the impact of potentially prognostic factors on bladder recurrence after RNU.Results.The median follow-up period was 47.8 months. In the Cox model, ureteral involvement and diabetes mellitus (DM) were significantly associated with a higher bladder recurrence rate in the multivariate analysis (hazard ratio [HR]: 1.838;P=0.003and HR: 1.821;P=0.010, resp.). In the Kaplan-Meier analysis, DM patients with concomitant ureteral UC experienced about a threefold increased risk of bladder recurrence as compared to those without both factors (HR: 3.222;P<0.001). Patients with either of the two risk factors experienced about a twofold increased risk as compared to those without both factors (with DM, HR: 2.184,P=0.024; with ureteral involvement, HR: 2.006,P=0.003).Conclusions.Ureteral involvement and DM are significantly related to bladder recurrence after RNU in patients with UUT-UC.

scholarly journals The impact of genetic background and sex on the phenotype of IL-23 induced murine arthritis

2021 ◽  
Author(s):  
Emma Haley ◽  
Mederbek Matmusaev ◽  
Imtiyaz N. Hossain ◽  
Sean Davin ◽  
Tammy M. Martin ◽  
...  
Keyword(s):  
Weight Loss ◽  
Genetic Background ◽  
Skin Inflammation ◽  
Control Mechanisms ◽  
Adult Mice ◽  
Severe Arthritis ◽  
Cytokine Levels ◽  
Clinical Arthritis ◽  
Organ Specific ◽  
The Impact

AbstractBackgroundOverexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles has been reported to result in spondyloarthritis-like disease. The impact of genetic background and sex on the disease phenotype in this model has not been investigated.MethodsWe compared male B10.RIII mice with male C57BL/6 mice, and male with female B10.RIII mice after hydrodynamic injection of IL-23 enhanced episomal vector (EEV) at 8-12 weeks of age. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks and tissues were harvested for histology, flow cytometry and gene expression analysis. Serum cytokine levels were determined by ELISA.FindingsMale B10.RIII mice developed arthritis in the forepaws and feet within 6 days after IL-23 EEV injection; they also exhibited psoriasis-like skin disease, colitis, weight loss, and osteopenia. In contrast to previous reports, we did not observe spondylitis or uveitis. Male C57BL/6 mice injected with IL-23 EEV had serum IL-23 levels comparable with B10.RIII mice and developed skin inflammation, colitis, weight loss, and osteopenia but failed to develop arthritis. Female B10.RIII mice had more severe arthritis than male B10.RIII mice but did not lose weight.ConclusionsSystemic IL-23 overexpression results in spondyloarthritis-like disease in B10.RIII mice. The development of extra-articular manifestations but absence of arthritis in C57BL/6 mice suggests organ-specific genetic control mechanisms of IL-23 driven inflammation. Discrepancies regarding the phenotype of IL-23 induced disease in different labs and the sexual dimorphism observed in this study warrant further exploration.

scholarly journals Transcriptional Changes in Regulatory T Cells From Patients With Autoimmune Polyendocrine Syndrome Type 1 Suggest Functional Impairment of Lipid Metabolism and Gut Homing

2021 ◽  
Vol 12 ◽  
Author(s):  
Amund Holte Berger ◽  
Eirik Bratland ◽  
Thea Sjøgren ◽  
Marte Heimli ◽  
Torgeir Tyssedal ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Type I ◽  
Syndrome Type ◽  
Functional Studies ◽  
Autoimmune Polyendocrine Syndrome ◽  
Organ Specific ◽  
Hla Dqa1 ◽  
And Function ◽  
The Impact

Autoimmune polyendocrine syndrome type I (APS-1) is a monogenic model disorder of organ-specific autoimmunity caused by mutations in the Autoimmune regulator (AIRE) gene. AIRE facilitates the expression of organ-specific transcripts in the thymus, which is essential for efficient removal of dangerous self-reacting T cells and for inducing regulatory T cells (Tregs). Although reduced numbers and function of Tregs have been reported in APS-I patients, the impact of AIRE deficiency on gene expression in these cells is unknown. Here, we report for the first time on global transcriptional patterns of isolated Tregs from APS-1 patients compared to healthy subjects. Overall, we found few differences between the groups, although deviant expression was observed for the genes TMEM39B, SKIDA1, TLN2, GPR15, FASN, BCAR1, HLA-DQA1, HLA-DQB1, HLA-DRA, GPSM3 and AKR1C3. Of significant interest, the consistent downregulation of GPR15 may indicate failure of Treg gut homing which could be of relevance for the gastrointestinal manifestations commonly seen in APS-1. Upregulated FASN expression in APS-1 Tregs points to increased metabolic activity suggesting a putative link to faulty Treg function. Functional studies are needed to determine the significance of these findings for the immunopathogenesis of APS-1 and for Treg immunobiology in general.

Impact of clinicopathological features on survival in patients treated with immune-based combinations for metastatic urothelial carcinoma: A meta-analysis of randomized clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16534-e16534
Author(s):  
Veronica Mollica ◽  
Alessandro Rizzo ◽  
Matteo Santoni ◽  
Andrea Marchetti ◽  
Matteo Rosellini ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Liver Metastases ◽  
Urothelial Carcinoma ◽  
Meta Analysis ◽  
Clinicopathological Features ◽  
Cochrane Library ◽  
Risk Of Death ◽  
Metastatic Urothelial Carcinoma ◽  
Ecog Ps ◽  
The Impact

e16534 Background: Immune checkpoint inhibitors (ICIs) have recently revolutionized the treatment landscape of metastatic urothelial carcinoma (mUC). Nonetheless, little is known regarding the impact of clinicopathological features in this setting. We performed a meta-analysis aiming to evaluate the predictive value of ECOG-PS, age, gender, liver metastases, and histology in randomized controlled trials (RCTs) comparing ICI-based combinations versus chemotherapy in mUC patients. Methods: We retrieved all the relevant RCTs through PubMed/Med, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible studies included RCTs comparing ICI-based combinations versus chemotherapy alone in mUC patients. The primary endpoint was overall survival (OS), measured as hazard ratio (HR) with corresponding 95% confidence interval (CI). All statistical analyses were performed using R studio software. Results: Overall, 1032 mUC patients were included in the analysis. Compared with chemotherapy, ICI-based combinations significantly decreased the risk of death in several clinicopathological subgroups, including no liver metastases (HR, 0.84; 95% CI, 0.74-0.95) and ECOG-PS 0 patients (HR, 0.84; 95% CI, 0.72-0.97). Similarly, ICI-based combinations were associated with prolonged OS in mUC patients who were < 65 years old (HR, 0.82; 95% CI, 0.72-0.95), as well as in male (HR, 0.90; 95% CI, 0.82-0.99) and female patients (HR, 0.81; 95% CI, 0.68-0.97). Conversely, a non-statistically significant benefit was observed for chemotherapy alone in mUC patients with liver metastases (HR, 1.06; 95% CI, 0.86-1.31). Conclusions: According to our results, the magnitude of benefit of ICI-based combinations over chemotherapy in mUC was consistent across a number of clinicopathological subgroups, while a proportion of patients could respond to chemotherapy alone.Despite several limitations affect our analysis, we believe these results could guide in everyday treatment decision-making, also assisting in the design and interpretation of future clinical trials on ICIs in mUC.

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