scholarly journals Serum levels and tumour expression of leptin and leptin receptor as promising clinical biomarkers of specific feline mammary carcinoma subtypes

2020 ◽  
Author(s):  
Andreia Gameiro ◽  
Catarina Nascimento ◽  
Ana Catarina Urbano ◽  
Jorge Correia ◽  
Fernando Ferreira
Keyword(s):  
Mammary Carcinoma ◽  
Leptin Receptor ◽  
Elevated Serum ◽  
Serum Levels ◽  
Her2 Positive ◽  
Nutritional Disorder ◽  
Serum Leptin ◽  
Luminal B ◽  
Clinical Biomarkers ◽  
Feline Mammary Carcinoma

AbstractObesity is a risk factor for human breast cancer, being associated with increased serum levels of leptin. In cat, although obesity is a common nutritional disorder, the role of leptin and its receptor in mammary carcinoma is unknown. In this study, serum levels of leptin and leptin receptor (ObR) were evaluated in 58 cats with mammary carcinoma and compared with healthy controls by ELISA, as tumour expression by immunohistochemistry. Results showed that the free leptin index is decreased in cats with mammary carcinoma (p=0.0006), particularly for those with luminal B and HER2-positive disease that showed significantly lower serum leptin levels (p<0.0001 and p<0.005, respectively). Serum leptin levels above 4.17 pg/mL were associated with ulcerating tumours (p=0.0005) and shorter DFS (p=0.0217). Elevated serum ObR levels were found in all cats with mammary carcinoma (p<0.0001), with levels above 16.89 ng/mL being associated with smaller tumours (p=0.0118), ER-negative status in HER2-positive tumours (p=0.0291) and increased serum levels of CTLA-4 (p=0.0056), TNF-α (p=0.0025), PD-1 (p=0.0023) and PD-L1 (p=0.0002). In tumour samples, leptin was overexpressed in luminal B and triple-negative carcinomas (p=0.0046), whereas ObR was found overexpressed in luminal B samples (p=0.0425). Altogether, our results reinforce the importance of feline mammary carcinoma in comparative oncology.

scholarly journals Serum and Tissue Expression Levels of Leptin and Leptin Receptor Are Putative Markers of Specific Feline Mammary Carcinoma Subtypes

2021 ◽  
Vol 8 ◽  
Author(s):  
Andreia Gameiro ◽  
Catarina Nascimento ◽  
Ana Catarina Urbano ◽  
Jorge Correia ◽  
Fernando Ferreira
Keyword(s):  
Mammary Carcinoma ◽  
Leptin Receptor ◽  
Elevated Serum ◽  
Disease Free Survival ◽  
Serum Levels ◽  
Her2 Positive ◽  
Serum Leptin ◽  
Expression Levels ◽  
Luminal B ◽  
Feline Mammary Carcinoma

Obesity is an established risk factor for breast cancer in post-menopausal women, being associated with elevated serum levels of leptin. Although overweight is a common condition in cat, the role of leptin and its receptor in feline mammary carcinoma remains unsettled. In this study, serum leptin and leptin receptor (ObR) levels were investigated in 58 cats with mammary carcinoma and compared with those of healthy animals, as were the expression levels of leptin and ObR in tumor tissues. The results showed that the Free Leptin Index is significantly decreased in cats with mammary carcinoma (p = 0.0006), particularly in those with luminal B and HER2-positive tumors, and that these animals also present significantly lower serum leptin levels (p &lt; 0.0001 and p &lt; 0.005, respectively). Interestingly, ulcerating tumors (p = 0.0005) and shorter disease-free survival (p = 0.0217) were associated to serum leptin levels above 4.17 pg/mL. In contrast, elevated serum ObR levels were found in all cats with mammary carcinoma (p &lt; 0.0001), with levels above 16.89 ng/mL being associated with smaller tumors (p = 0.0118), estrogen receptor negative status (p = 0.0291) and increased serum levels of CTLA-4 (p = 0.0056), TNF-α (p = 0.0025), PD-1 (p = 0.0023), and PD-L1 (p = 0.0002). In tumor samples, leptin is overexpressed in luminal B and triple-negative carcinomas (p = 0.0046), whereas ObR is found to be overexpressed in luminal B tumors (p = 0.0425). Altogether, our results support the hypothesis that serum levels of leptin and ObR can be used as biomarkers of specific feline mammary carcinoma subtypes, and suggests the use of leptin antagonists as a therapeutic tool, reinforcing the utility of the cat as a cancer model.

scholarly journals VISTA Is a Diagnostic Biomarker and Immunotherapy Target of Aggressive Feline Mammary Carcinoma Subtypes

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5559
Author(s):  
Andreia Gameiro ◽  
Catarina Nascimento ◽  
Jorge Correia ◽  
Fernando Ferreira
Keyword(s):  
Mammary Carcinoma ◽  
Triple Negative ◽  
Serum Levels ◽  
Luminal A ◽  
Her2 Positive ◽  
Feline Mammary Carcinoma ◽  
Tnf Α ◽  
Control Tumor ◽  
Immunotherapy Target ◽  
Tumor Expression

Feline mammary carcinoma (FMC) is a common neoplasia, showing aggressive clinicopathological features, without viable therapeutic options. The study of tumor microenvironment has gained importance, due to the ability to control tumor progression by regulating the immune response. Considering the lack of knowledge, feline serum VISTA levels from cats with mammary carcinoma were compared with healthy controls, and with serum levels of PD-1/PD-L1, CTLA-4, LAG-3, IL-6, and TNF-α. In parallel, VISTA tumor expression was evaluated in FMC samples. The obtained data revealed that serum VISTA levels were significantly higher in cats presenting HER2-positive (p = 0.0025) or triple-negative subtypes (p = 0.0019), with higher serum levels in luminal A (p = 0.0025) correlated to the presence of metastasis (p = 0.0471). Furthermore, in HER2-positive or triple-negative tumors, correlations were obtained between serum VISTA levels and the serum levels of the above-mentioned molecules. In tumors, VISTA expression revealed a stronger intensity in cancer cells, when compared to TILs (p < 0.0001). Stratifying the samples by subtypes, a higher number of VISTA-positive TILs was observed in the HER2-positive subtype, compared with triple-negative tumors (p = 0.0138). In conclusion, results support the development of therapeutic strategies for HER2-positive and triple-negative FMC subtypes, reinforcing the use of cats as a human oncology model.

scholarly journals Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis

2022 ◽  
Vol 12 ◽  
Author(s):  
Yoshimasa Imoto ◽  
Shigeharu Ueki ◽  
Yukinori Kato ◽  
Kanako Yoshida ◽  
Taiyo Morikawa ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Elevated Serum ◽  
Serum Levels ◽  
Histological Evaluation ◽  
Dependent Manner ◽  
Epithelial Surface ◽  
Serum Leptin

Background: Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated.Objective: To determine whether the serum levels of leptin are altered in patients with ECRS.Methods: In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient’s serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin in vitro to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression.Results: The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (p &lt; 0.0001 vs. ECRS; p &lt; 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (p &lt; 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, p &lt; 0.01) and the number of eosinophils in NPs (r = 0.5109, p &lt; 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, p &lt; 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established in vitro from NPs in a leptin receptor-dependent manner (p &lt; 0.05).Conclusion: Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs.

scholarly journals PD-1 and PD-L1 are diagnostic biomarkers and PD-L1 a promising therapeutic target in HER2-positive and triple negative normal-like feline mammary carcinoma subtypes

2020 ◽  
Author(s):  
Catarina Nascimento ◽  
Ana Catarina Urbano ◽  
Andreia Gameiro ◽  
João Ferreira ◽  
Jorge Correia ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mammary Carcinoma ◽  
Triple Negative ◽  
Strong Positive Correlation ◽  
Her2 Positive ◽  
Diagnostic Biomarkers ◽  
Mammary Carcinomas ◽  
Tumor Subtypes ◽  
Promising Therapeutic Target ◽  
Feline Mammary Carcinoma

AbstractTumor microenvironment has gained great relevance due to its ability to regulate distinct checkpoints mediators, orchestrating tumor progression. In order to understand the role of the PD- 1/PD-L1 axis in cats with mammary carcinoma, serum PD-1 and PD-L1 levels were compared with healthy controls and with serum CTLA-4 and TNF-α levels. PD-1 and PD-L1 expression was evaluated in TILs and cancer cells, as the presence of somatic mutations. Results showed that serum PD-1 and PD-L1 levels were significantly higher in cats with HER2-positive (p=0.017; p=0.032) and triple negative (TN) normal-like mammary carcinomas (p=0.004; p=0.015). Besides, cats presenting these tumor subtypes showed a strong positive correlation between serum PD-1, PD-L1, CTLA-4 and TNF-α levels. In tumors, PD-L1 expression in cancer cells was significantly higher in HER2-positive samples than in TN normal-like tumors (p=0.010), as the percentage of PD-L1-positive TILs (p=0.038). Results from the PD-L1 gene sequencing identified two heterozygous mutations in exon 4 (A245T, 3.8%; V252M, 42.3%) and one in exon 5 (T267S, 3.8%). In summary, results support that serum PD-1 and PD-L1 levels can be used as diagnostic biomarkers of HER2-positive and TN normal-like feline mammary carcinomas and suggest that the development of monoclonal antibodies may be a good therapeutic strategy.

scholarly journals Influence of the presence of OB-Re on leptin radioimmunoassay

2001 ◽  
Vol 168 (1) ◽  
pp. 79-86 ◽  
Author(s):  
T Murakami ◽  
S Otani ◽  
T Honjoh ◽  
T Doi ◽  
K Shima
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Serum Levels ◽  
Mouse Serum ◽  
Serum Leptin ◽  
Mouse Placenta ◽  
Pregnant State

Leptin, a hormone derived from adipose tissue, regulates energy homeostasis and body weight. In the mouse, serum leptin levels, when measured by radioimmunoassay (RIA), increase by a factor of more than 50 times during pregnancy, compared with those in the non-pregnant state. It is well known that mouse placenta produces the secretory isoform of the leptin receptor, OB-Re. In order to investigate the issue of whether serum leptin levels are actually increased during pregnancy or whether the increased OB-Re concentration plays a role in this phenomenon, serum leptin levels were determined by the immunoprecipitation of leptin using anti-leptin antibody, and were found to be increased only by about ten times during pregnancy. To investigate the influence of OB-Re on leptin measurement by the RIA procedure, serum leptin levels were measured by the RIA after the addition of OB-Re to the serum. The apparent values of leptin levels increased in parallel with the amount of OB-Re added to the serum. Leptin levels, as determined by the RIA, might therefore provide artificially high values when serum levels of the secretory form of OB-R are high, in cases, for example, such as the last period of pregnancy in mice.

Leptin deficiency enhances sensitivity to endotoxin-induced lethality

1999 ◽  
Vol 276 (1) ◽  
pp. R136-R142 ◽  
Author(s):  
Raffaella Faggioni ◽  
Giamila Fantuzzi ◽  
Cem Gabay ◽  
Arthur Moser ◽  
Charles A. Dinarello ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Serum Levels ◽  
Interferon Γ ◽  
Serum Glucose ◽  
Serum Leptin ◽  
Inflammatory Protein ◽  
Increased Sensitivity ◽  
Necrosis Factor

Leptin is induced by lipopolysaccharide (LPS) and cytokines. We investigated the role of leptin in LPS-induced toxicity using leptin-deficient ( ob/ ob) and leptin receptor-deficient ( db/ db) mice. Sensitivity to LPS-induced mortality is significantly greater in ob/ obmice compared with their own lean littermates but not in db/ dbmice. LPS reduced serum glucose in both ob/ oband db/ dbmice but induced corticosterone only in db/ dbmice. Despite the very high basal levels of serum leptin in db/ dbmice, a twofold increase in serum leptin levels was observed after LPS in both db/ dbmice and their lean littermates. No differences were detected in LPS-induced serum levels of interleukin (IL)-1β, tumor necrosis factor, macrophage inflammatory protein-1α, and interferon-γ in ob/ obmice compared with their own littermates. In contrast, a blunted induction of IL-10 and IL-1 receptor antagonist (IL-1Ra) was observed in ob/ obmice compared with their littermates. In vitro, leptin induced IL-1Ra production and upregulated the IL-1Ra induction by LPS in macrophages. Moreover, treatment with leptin reversed the increased sensitivity to LPS-induced lethality found in ob/ obmice. These results suggest that leptin participates in the host response to inflammation by modulating the host immune and cytokine responses after LPS.

scholarly journals Increased Expression of the Leptin Gene in Adipose Tissue of Patients with Chronic Kidney Disease–The Possible Role of an Abnormal Serum Fatty Acid Profile

Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 98
Author(s):  
Justyna Korczyńska ◽  
Aleksandra Czumaj ◽  
Michał Chmielewski ◽  
Maciej Śledziński ◽  
Adriana Mika ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Elevated Serum ◽  
Serum Levels ◽  
Mrna Levels ◽  
Serum Fatty Acid ◽  
Serum Leptin

Chronic kidney disease (CKD) is associated with an increased level of leptin and an abnormal fatty acid (FA) profile in the serum. However, there are no data on the associations between them, and the reason for increased serum levels in patients with CKD is not well elucidated. Recently, we found that a CKD-related abnormal FA profile caused significant changes in the expression of genes involved in lipid metabolism in hepatocytes. The aim of this study was to examine whether leptin gene expression in subcutaneous adipose tissue (SAT) of patients with CKD may contribute to increased serum levels of this adipokine and whether the abnormal serum FA profile observed in CKD patients has an impact on leptin gene expression in adipocytes. The FA profile was measured in serum samples from patients with CKD and controls by GC–MS. The relative mRNA levels of leptin were measured in SAT by Real-Time PCR. Moreover, the effect of the CKD-related abnormal FA profile on leptin gene expression was studied in in vitro cultured 3T3-L1 adipocytes. Patients with CKD had higher concentrations of serum leptin than controls and higher expression level of the leptin gene in SAT. They also had increased serum monounsaturated FAs and decreased polyunsaturated FAs. The incubation of adipocytes with FAs isolated from CKD patients resulted in an increase of the levels of leptin mRNA. Increased leptin gene expression in SAT may contribute to elevated concentrations of these adipokine in patients with CKD. CKD-related alterations of the FA profile may contribute to elevated serum leptin concentrations in patients with CKD by increasing the gene expression of this adipokine in SAT.

scholarly journals Polymorphisms of Leptin (-2548 G/A) and Leptin Receptor (Q223R) Genes in Iranian Women with Breast Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Reza Mahmoudi ◽  
Bahareh Noori Alavicheh ◽  
Mohammad Amin Nazer Mozaffari ◽  
Mohammad Fararouei ◽  
Mohsen Nikseresht
Keyword(s):  
Breast Cancer ◽  
Significant Contribution ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Serum Levels ◽  
Serum Leptin ◽  
Increased Risk ◽  
Pcr Rflp ◽  
The Mean ◽  
Larger Sample

Recent studies have shown that polymorphisms in leptin and leptin receptor genes are associated with increased risk for breast cancer. This study aimed at investigating -2548 G/A polymorphism in leptin gene and Q223R polymorphism in leptin receptor gene in patients with breast cancer. The study included 45 women with breast cancer and 41 healthy women. PCR-RFLP was used to determine the genotype of the subjects in terms of -2548 G/A polymorphism in leptin gene and Q223R polymorphism in leptin receptor gene. Serum levels of leptin were also measured by ELISA. For -2548 G/A polymorphism, the genotypes were homozygous AA (OR = 1.13;p=0.8) and heterozygous GA (OR = 0.41;p=0.2) and for Q223R polymorphism, the genotypes were homozygous RR (OR = 6.7;p=0.09) and heterozygous QR (OR = 8.3;p=0.06). The mean serum level of leptin was 33.22 ± 21.35 ng/mL in patients and 29.49 ± 23.27 ng/mL in the normal participants (p=0.3). Although, despite the magnitude of the associations, the results suggested no statistically significant contribution of -2548 G/A polymorphism (in leptin gene), Q223R polymorphism (in leptin receptor gene), and serum leptin levels in predicting the risk of breast cancer, further studies with larger sample size are suggested.

Abstract 14316: Diurnal Variation of the Macrophage Expressed Gene-1 Inflammatory Marker in the Timing of Sudden Cardiac Arrest

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sharma Kattel ◽  
Hardik Bhatt ◽  
Shirley Xu ◽  
Jibran Mirza ◽  
Saraswati Pokharel ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Diurnal Variation ◽  
Troponin I ◽  
Inflammatory Marker ◽  
Tertiary Care ◽  
Sudden Cardiac Arrest ◽  
Elevated Serum ◽  
Serum Levels ◽  
Clinical Biomarkers ◽  
Myocardial Infraction

Background: In the last decade, inflammatory biomarkers have been implicated in out of hospital sudden cardiac arrest (OH-SCA). However, the role of diurnal variation in these inflammatory markers in relation to the timing of OH-SCA is unknown. Here we report an increased macrophage-expressed gene-1 (MPEG-1) expression, an evolutionary conserved protein with membrane attack complex domain, in relation to the timing of OH-SCA and survival after resuscitation. Objectives: To examine the relationship between the circulating MPEG-1protein levels and the timing of OH-SCA. Methods: We prospectively enrolled 144 subjects from 4 different tertiary care centers who were successfully resuscitated from OH-SCA. The timing of OH-SCA and other clinical parameters were obtained from medical record review. Serum levels of a novel biomarker, MPEG-1, and other conventional clinical biomarkers including troponin-I and CK-MB were measured in the blood samples obtained within the 6 hours of OH-SCA. Results: Approximately 32% of the sudden cardiac arrest happened in the morning hours ( 5AM- 12PM ). The higher incidence of the OH-SCA occurring in morning hours correlated with elevated serum MPEG-1 levels as shown in figure 1 . In 71% of the OH-SCA, the etiology was of cardiac in nature, of which 32% were from acute myocardial infraction. At the end of the hospital stay, 46% of the patients had died. Conclusions: This study suggests that the diurinal variation in the propensity to develop OH-SCA is associated with elevated serum levels of MPEG-1. Further research examining this novel biomarkers in larger cohorts can form the basis for accurate and timely risk-prediction.

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