Plasmacytoid urothelial carcinoma (UC) are luminal tumors with similar immune microenvironment as compared to conventional UC.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 477-477
Author(s):  
Myriam Kossai ◽  
Camélia Radulescu ◽  
Julien Adam ◽  
Anaïs Dziegielewski ◽  
Nicolas Signolle ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Checkpoint Inhibitors ◽  
Clinicopathological Characteristics ◽  
Control Group ◽  
Histopathological Analysis ◽  
Her2 Overexpression ◽  
Cd8 Cells ◽  
Chemotherapeutic Sensitivity ◽  
Pathological Variant ◽  
Lower Expression

477 Background:Plasmacytoid urothelial carcinoma (UC) is a rare pathological variant of UC with low chemotherapeutic sensitivity and dismal outcomes. The molecular and immune profiles of such tumors remain poorly investigated. Herein, we investigated the phenotypical features of a cohort of plasmacytoid UC (n = 32) by comparison to a control group of conventional high-grade UC with matched clinicopathological characteristics (n = 30). Methods: Histopathological analysis included the following antibodies: p63, GATA3, CK5/6, CK20 and HER2. In addition, the density of intra-tumor CD8+ lymphocytes, and PD-L1 expression in tumor (TC) and immune cells (IC) were evaluated. Clinical data were collected. Results: Plasmacytoid UC expressed GATA3 (97% vs 86% p = 0.18), CK20 (59% vs 36% p = 0.08) markers and showed a significantly higher rate of HER2 overexpression (2+ and 3+ score: 25% vs 0%, p < 0.01) compared to controls. A significantly lower expression of CK5/6 (22% vs 56%, p < 0.05) and p63 (41% vs 80%, p < 0.05) was observed in plasmacytoid UC compared to controls. The density of tumor-infiltrating CD8+ cells was similar between plasmacytoid and conventional UC (p = 0.5). PD-L1 expression on IC was similar compared to conventional UC (p = 0.3). Overall survival at 5 years was significantly lower among patients with plasmacytoid UC compared to patients with conventional UC (p = 0.02). Conclusions: Together, our study demonstrated that plasmacytoid UC belong to the luminal subtype and display a rather inflamed microenvironment similar to conventional UC. These data support the inclusion of plasmacytoid variant of UC in clinical trials evaluating immune checkpoint inhibitors monotherapy or combination immunotherapeutic strategies.

Dendrobium officinalis Flower Improves Learning and Reduces Memory Impairment by Mediating Antioxidant Effect and Balancing the Release of Neurotransmitters in Senescent Rats

2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Brain Aging ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Histopathological Analysis ◽  
Hippocampal Damage ◽  
Common Belief ◽  
Mao B ◽  
Positive Effects ◽  
The Brain

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.

Atezolizumab-induced myositis and myocarditis in a patient with metastatic urothelial carcinoma

2020 ◽  
Vol 13 (12) ◽  
pp. e236357
Author(s):  
Mary Sessums ◽  
Siva Yarrarapu ◽  
Pramod K Guru ◽  
Devang K Sanghavi
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Basic Knowledge ◽  
Malignant Neoplasms ◽  
Diverse Range ◽  
History Of ◽  
Metastatic Urothelial Carcinoma ◽  
Acute Hypercapnic Respiratory Failure

Immune checkpoint inhibitors have revolutionised cancer therapy in the past decade. Although they have been indicated to treat a diverse range of malignant neoplasms, they are also associated with various immune-related adverse effects. We report the case of a 74-year-old man with a history of urothelial carcinoma who had atezolizumab-induced myocarditis and myositis resulting in acute hypercapnic respiratory failure, despite the discontinuation of atezolizumab and aggressive treatment with corticosteroids. This case highlights the importance of a multidisciplinary approach for early diagnosis and treatment of immune-related adverse events. Physicians must be aware of the risks associated with immune checkpoint inhibitors and have a basic knowledge regarding their management.

scholarly journals Effect of a single or two doses of an anti-GnRH vaccine on testicle morpho-functional characteristics in Nelore bulls

2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Emanuel M. Doroteu ◽  
Joao H. M. Viana ◽  
Jair A. Ferreira Junior ◽  
Juliana T. A. Macedo ◽  
Rodrigo A. Oliveira ◽  
...  
Keyword(s):  
Bos Taurus ◽  
Active Immunization ◽  
Control Group ◽  
Histopathological Analysis ◽  
Sample Collection ◽  
Functional Characteristics ◽  
Scrotal Circumference ◽  
Bos Taurus Indicus ◽  
Boost Dose ◽  
And Control

AbstractThe aim of this study was to compare testicle morpho-functional characteristics in bulls undergoing a single or two immunizations against GnRH. Nelore (Bos taurus indicus) bulls were randomly allocated into three experimental groups: G1 (n=12), a single 400 μg dose of anti-GnRH vaccine on day 0; G2 (n=11), a first 400 μg dose of anti-GnRH vaccine on day 0 followed by a second (boost) dose 30 days later; and control group (CG, n=12), 1 mL saline 0.9% at day 0. Every 30 days, from day 0 until slaughter at day 90, the bulls were weighed and underwent testicular biometry, semen collection and analysis, and blood sample collection for testosterone measurement. Immediately after slaughter, the testicles were removed and transport at 15°C to the laboratory for histopathological analysis. There was a decrease in testicular height (P=0.0476), width (P=0.0021), and in scrotal circumference (P=0.0001), after either a single (G1) or two (G2) immunizations against GnRH. Both G1 and G2 had lower testosterone concentrations than CG from day 60 on (P<0.01), but in G2, it was also lower than in G1 at day 90 (P=0.0006). All sperm parameters were affected by active immunization against GnRH (P<0.05), and in G2, averages were lesser (P<0.05) than in G1 from day 60 on. No signs of seminiferous tubule degeneration were found in any sample from the CG, contrasting with 75.0% and 100.0% of the samples from G1 and G2, respectively. In summary, immunocastration affected testicle morpho-functional characteristics in bulls in a time- and dose-dependent way.

565 A novel long-acting interleukin-7 agonist, NT-I7, increases cytotoxic CD8+ T cells and enhances survival in mouse glioma models

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A599-A599
Author(s):  
Subhajit Ghosh ◽  
Ran Yan ◽  
Sukrutha Thotala ◽  
Arijita Jash ◽  
Anita Mahadevan ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Standard Of Care ◽  
Control Group ◽  
Cervical Lymph Nodes ◽  
Cd8 Cells ◽  
Interleukin 7 ◽  
Long Acting

BackgroundRadiation (RT) and temozolomide (TMZ), which are standard of care for patients with glioblastoma (GBM), can cause prolonged severe lymphopenia. Lymphopenia, in turn, is an independent risk factor for shorter survival. Interleukin-7 (IL-7) is a cytokine that is required for T cell homeostasis and proliferation. IL-7 levels are inappropriately low in GBM patients with lymphopenia. NT-I7 (efineptakin alfa) is a long-acting recombinant human IL-7 that supports the proliferation and survival CD4+ and CD8+ cells in both human and mice. We tested whether NT-I7 rescues treatment-induced lymphopenia and improves survival.MethodsImmunocompetent C57BL/6 mice bearing two intracranial glioma models (GL261 and CT2A) were treated with RT (1.8 Gy/day x 5 days), TMZ (33 mg/kg/day x 5 days) and/or NT-I7 (10 mg/kg on the final day of RT completion). We profiled the CD3, CD8, CD4, FOXP3 cells in peripheral blood over time. We also immunoprofiled cervical lymph nodes, bone marrow, thymus, spleen, and the tumor 6 days after NT-I7 treatment. Survival was monitored daily.ResultsMedian survival in mice treated with NT-I7 combined with RT was significantly longer than RT alone (GL261: 40d vs 34d, p<0.0021; CT2A: 90d vs 40d, p<0.0499) or NT-I7 alone (GL261: 40d vs 24d, p<0.008; CT2A: 90d vs 32d, p<0.0154). NT-I7 with RT was just as effective as NT-I7 combined with RT and TMZ in both GL261(40d vs 47d) and CT2A (90d vs 90d). Cytotoxic CD8+ T cells were increased in both peripheral blood (0.66 x 105 to 3.34 x 105; P≤0.0001) and tumor (0.53 x 103 to 1.83 x 103; P≤0.0001) in mice treated with NT-I7 when compared to control. Similarly, NT-I7 in combination with RT increased the CD8+ T cells in peripheral blood (0.658 x 105 to 1.839 x 105 P≤0.0001) when compared to RT alone. There were decreases in tumor infiltrating FOXP3+ T-reg cells in mice treated with NT-I7 (1.9 x 104 to 0.75 x 104 P≤0.0001) and NT-I7 + RT (1.9 x 104 to 0.59 x 104 P≤0.0001) when compared to the control group without NT-I7. In addition, NT- I7 treatment increased CD8+ T cells in thymus, spleen, and lymph nodes.ConclusionsNT-I7 enhances cytotoxic CD8+ T lymphocytes systemically and in the tumor microenvironment, and improves survival. A phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).

scholarly journals Development of secondary urothelial carcinoma following complete response to immune checkpoint inhibitors

2021 ◽  
pp. 101762
Author(s):  
Jean-Michel Lavoie ◽  
Gillian Vandekerkhove ◽  
Andrew J. Murtha ◽  
Gang Wang ◽  
Alexander W. Wyatt ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Complete Response

scholarly journals Correlation ofA2bARandKLF4/KLF15with Obesity-Dyslipidemia Induced Inflammation in Uygur Population

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Cuizhe Wang ◽  
Xiaodan Ha ◽  
Wei Li ◽  
Peng Xu ◽  
Yajuan Gu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Normal Control Group ◽  
Expression Level ◽  
Control Group ◽  
Mrna Expression Level ◽  
Key Genes ◽  
Visceral Adipose ◽  
Lower Expression ◽  
Uygur Population

In this paper, the researchers collected visceral adipose tissue from the Uygur population, which were divided into two groups: the normal control group (NC,n=50, 18.0 kg/m2≤ BMI ≤ 23.9 kg/m2) and the obese group (OB,n=45, BMI ≥ 28 kg/m2), and then use real-time PCR to detect the mRNA expression level of key genes involved in inflammation signaling pathway. The findings suggest that, in obese status, the lower expression level ofA2bAR,KLF4, andKLF15of visceral adipose tissue may correlate with obese-dyslipidemia induced inflammation in Uygur population.

scholarly journals Astragalus Polysaccharide Injection (PG2) Normalizes the Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Lung Cancer Receiving Immunotherapy

2021 ◽  
Vol 20 ◽  
pp. 153473542199525
Author(s):  
Shih Ming Tsao ◽  
Tz Chin Wu ◽  
JiZhen Chen ◽  
Feichi Chang ◽  
Thomos Tsao
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Treatment Initiation ◽  
Checkpoint Inhibitors ◽  
Neutrophil To Lymphocyte Ratio ◽  
Advanced Lung Cancer ◽  
Control Group ◽  
Lymphocyte Ratio ◽  
Astragalus Polysaccharide

Objectives: The neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in patients with cancer receiving immunotherapy. Recent studies have shown that a high NLR was associated with a poor response and decreased survival. However, there is no intervention to reverse abnormally high NLR and improve clinical outcomes. Astragalus polysaccharide injection (PG2) is an immunomodulatory therapy for cancer-related fatigue. This study aimed to examine whether PG2 might normalize the NLR and affect the overall survival of patients with lung cancer treated with immunotherapy. Materials and Methods: We retrospectively examined the medical records of patients with lung cancer treated with immune checkpoint inhibitors (ICIs) between October 1, 2015 and November 30, 2019. All patients received ICI combination chemotherapies, and some similarly received PG2 (Control vs PG2). The NLR was assessed before treatment and 6 weeks after ICI initiation, and the survival data was collected at least 4 years after treatment initiation for the first enrolled patient. Results: Fifty-three patients were included. Six weeks after ICI initiation, 91.3% of the patients in the PG2 group exhibited a predefined “Decrease or no change” in the NLR, which was 28% higher than that in the Control group (63.3%) ( P = .028). The NLR significantly decreased by 31.60% from baseline in the PG2 group ( P = .012), whereas it increased by 5.80% in the Control group ( P = .572). Six weeks after ICI treatment initiation, both groups had a median NLR of 3.73, and the overall survival was also similar (PG2 vs Control, 26.1 months vs 25.4 months, respectively); however, the PG2 group had a higher median baseline NLR than the Control group (PG2 vs Control, 4.51 vs 2.81, respectively). Conclusion: This study demonstrated that PG2 could normalize the NLR in patients with lung cancer receiving ICI combination treatments.

Effect of Granulocyte Colony-Stimulating Factor Combined with Erythropoietin on Chronic Granulocytic Leukemia with Anemia and Its Effect on Nutritional Status

2021 ◽  
Vol 7 (5) ◽  
pp. 3150-3154
Author(s):  
GeLe Tong ◽  
Liusha Xu ◽  
Yanqi Leng ◽  
Pang Wu
Keyword(s):  
Nutritional Status ◽  
Immune Function ◽  
Control Group ◽  
Observation Group ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Chronic Granulocytic Leukemia ◽  
Cd8 Cells ◽  
Stimulating Factor ◽  
Granulocytic Leukemia

Objective: To investigate the clinical effect of granulocyte colony-stimulating factor combined with erythropoietin on chronic granulocytic leukemia with anemia and its effect on nutritional status. Methods: 60 patients of chronic granulocytic leukemia of our hospital with anemia induced by maintenance chemotherapy were randomly divided into two groups. Patients in the control group received routine treatment, while patients in the observation group received basal treatment with granulocyte colony-stimulating factor and erythropoietin. The nutritional status before and after treatment as well as the immune function and the incidence of blood transfusion and adverse events were compared between the two groups. Results: There was no significant difference in hemoglobin, hematocrit, nutritional status and immune function between the two groups before treatment (P>0.05). Those after treatment were significantly higher than that before treatment (P<0.05). After treatment, the percentage of CD4* cells in the control group was significantly higher than that before treatment (P<0.05), but the percentage of CD8* cells and CD47/CD8* cells did not change significantly (P>0.05). After treatment, the concentrations of IgA, IgM and IgG in the observation group were significantly higher than those before treatment (P<0.05), but only the concentrations of IgA and IgM in the control group were significantly higher than those in the observation group after treatment (P<0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group. Conclusion: Granulocyte colony-stimulating factor combined with erythropoietin can effectively correct anemia, improve nutritional status and improve immune function in patients with chronic myelogenous leukemia.

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