scholarly journals Anthracycline-induced cardiotoxicity: molecular and genetic predictors for risk assessment

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Grakova ◽  
S.N Shilov ◽  
E.N Berezikova ◽  
A.A Popova ◽  
M.N Neupokoeva ◽  
...  

Abstract Objective The objective of this study was to evaluate the role of molecular and genetic biomarkers in the development of anthracycline-induced cardiotoxicity in women with breast cancer at the 12 months after polychemotherapy. Methods A total of 176 women, median age of 45,0 [42,0; 50,0] years with breast cancer without cardiovascular diseases who received anthracycline antibiotics as part of polychemotherapeutic treatment were enrolled in the study. Two-dimensional transthoracic echocardiography and 6-minute walk test were performed at baseline and at the 12 months after polychemotherapy. Serum levels of NT-proBNP, sFas-L were measured using an enzyme immunoassay after polychemotherapeutic treatment. Evaluation of gene polymorphisms of p53 protein (polymorphic marker-Arg72Pro exon 4, rs1042522) and nitric oxide synthase (NOS3, Glu298Asp, rs1799983) were carried out by polymerase chain reaction at baseline. Results After the 12 months of polychemotherapy all patients had breast cancer remission and were divided into 2 groups: group 1 (n=52) comprised patients with anthracycline-induced cardiotoxicity, group 2 (n=124) comprised those without it. After polychemotherapeutic treatment the median value of NT-proBNP in group 1 was higher (p<0,00001) by 52,4% than in group 2 (113 [101,8; 126,15] pg/mL and 53,8 [43,4; 63,0] pg/mL, respectively). The median value of sFas-L in group 1 was higher (p<0,00001) by 44,3% than in group 2 (125,3 [111,85; 133,95] pg/mL and 69,8 [59,8; 77,6] pg/mL, respectively). Based on ROC-analysis, sFas-L concentration of 95.8 pg/mL (sensitivity of 92.2%, specificity of 92.1%, and AUC=0,951; p=0,0001) and NT-proBNP concentration of 71.5 pg/mL (sensitivity of 99.9%, specificity of 91.9%, and AUC=0,951; p=0,0001) were identified as a cut-off values predicting the development of anthracycline-induced cardiotoxicity. The development of anthracycline-induced cardiotoxicity in women with breast cancer at the 12 months after polychemotherapy significantly was related to the presence of T/T genotype of NOS3 gene (OR = 3,059; p=0,018) and with Arg/Arg genotype of p53 protein gene (OR = 2,972; p=0,001). While, the presence of Pro/Pro the Pro53 gene genotype of p53 protein gene was related to the absence of anthracycline-induced cardiotoxicity. Conclusion Our data suggest that evaluation of polymorphisms gene of p53 (rs1042522) and NOS3 (rs1799983) can be recommended before polychemotherapy in women with breast cancer for the risk assessment of anthracycline-induced cardiotoxicity. The serum levels of NT-proBNP and sFas-L after polychemotherapy may be considered as non-invasive biomarkers for prediction of the development of anthracycline-induced cardiotoxicity in women with breast cancer during the 12 months after polychemotherapy. Funding Acknowledgement Type of funding source: None

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
K Kopeva ◽  
EV Grakova ◽  
SN Shilov ◽  
EN Berezikova ◽  
AA Popova ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Objective. To evaluate prognostic role of molecular (endothelin-1, soluble Fas-L, NT-proBNP, interleukin-1β, TNF-α) and genetic factors (gene polymorphisms of endothelial NO synthase NOS3 (rs1799983), endothelin-1 receptor type A (EDNRA, C + 70G, rs5335), NADPH oxidase (C242T, rs4673), p53 protein (polymorphic marker-Arg72Pro exon 4, rs1042522), nitric oxide synthase (NOS3, Glu298Asp, rs1799983), Caspase 8 (CASP8, rs3834129 and rs1045485), interleukin-1β gene (Il-1β, rs1143634), TNF-α gene (rs1800629), superoxide dismutase-2 gene (SOD2, rs4880), glutathione peroxidase-1 gene (GPX1, rs1050450) in development of endothelial dysfunction and anthracycline-induced cardiotoxicity (AIC) in women without cardiovascular diseases (CVD). Methods. A total of 176 women, median age of 45.0 [42.0; 50.0] years with breast cancer and without CVD who received anthracycline antibiotics as part of chemotherapy (CT) were enrolled in the study. Two-dimensional transthoracic echocardiography was performed at baseline and at the 12 months after chemotherapy. Serum levels of molecular biomarkers were measured using an enzyme immunoassay baseline, right after chemotherapy and at 12 months after chemotherapy. Evaluation of gene polymorphisms was carried out by PCR at baseline. Results. After the 12 months of chemotherapy all patients had breast cancer remission and were divided into 2 groups: group 1 (n = 52) comprised patients with AIC, group 2 (n = 124) comprised those without it. The baseline levels of all biomarkers did not differ. After completion of chemotherapy the concentrations of endothelin-1, sFas-L statistically increased only in group 1. The levels of the NT-proBNP, TNF-α and interleukin-1β in both groups were normal before the initiation and after completion of CT. However, at 12 months after CT in the group with developed AIC, the levels of these biomarkers exceeded normal concentration for HF. Based on ROC-analysis, the levels of sFas-L ≥95.8 pg/mL (AUС=0.951; р=0.001), NT-proBNP ≥71.5 pg/mL (AUС=0.951; р=0.0001), and endothelin-1 ≥9.0 pg/mL (AUC = 0.7; p < 0.001) at the end of chemotherapy were identified as a cut-off values predicting development of AIC during 12 months after CT. The development of AIC was significantly related to the presence of Arg/Arg genotype of p53 protein gene (OR = 2.972; p = 0.001), T/T genotype of the NOS3 rs1799983 gene (OR = 3.059, p = 0.018), T/T genotype of the NADPH oxidase gene rs4673 (OR = 2.753, p = 0.008). Other gene polymorphisms did not differ between groups. Conclusion. Our data suggest that evaluation of polymorphisms gene of p53 (rs1042522), NOS3 (rs1799983) and NADPH oxidase gene (rs4673) can be recommended before chemotherapy in women with breast cancer and without cardiovascular disease for the risk assessment of AIC. The serum levels of NT-proBNP, endothelin-1, sFas-L after chemotherapy may be considered as non-invasive biomarkers for prediction of AIC development during the 12 months after chemotherapy.


2018 ◽  
pp. 168-172
Author(s):  
Kasra Karvandian ◽  
Jayran Zebardast ◽  
Nazila Zolfaghari Borra

Background: There are various factors affecting the effectiveness of the treatment of breast cancer patients. Although the disease pathology, along with surgery and other therapeutic modalities, plays the principal role in patient outcomes, anesthesia still plays an important role in the success of treatment. This study was designed to show the effects of anesthetic plans on risk classification and assessment in breast cancer surgeries. Methods: Two hundred sixty patients receiving different types of breast cancer surgery for therapeutic and reconstructive purposes were enrolled in this study. They were divided into three groups according to the anesthesia risk assessment. Group 1 consisted of low-risk patients (ASA I) who received small surgeries such as lumpectomy. Patients with intermediate risk of anesthesia (ASA II) or those who underwent breast cancer and axillary surgery with overnight admission (ASA I or II) were considered as group 2. Group 3 comprised the patients with higher risk for anesthesia (ASA class III) regardless of the surgery type or those in any ASA class who were about to undergo advanced and prolonged surgeries such as breast reconstruction with free or pedicle flaps. Results: Two hundred sixty-eight surgical interventions were done in 260 patients. There were 106, 107, and 47 patients in groups 1, 2, and 3, respectively. In group 1, five patients out of 106 were admitted in the hospital for 24 hours after surgery and the remaining 101 patients were discharged from the hospital in a few hours after the operation when they were fully conscious and could tolerate the diet completely. All 107 patients in group 2 were admitted in the hospital for a few days after the operation, though the vast majority of them (98 patients) discharged from the hospital the day after surgery. In the last group, 6 out of 47 patients showed the signs of surgical complications such as partial flap ischemia in the postoperative period, mostly after TRAM or DIEP flap breast reconstruction surgery. Conclusion: The findings of this study support the idea that breast surgeries can be done in an ambulatory situation with no considerable risk. In contrast, all medical and anesthetic considerations should be taken into account in more complex surgeries, especially when they are applied in high-risk patients.


2020 ◽  
pp. 75-80
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  

The objective: was to evaluate the efficacy of the first line chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Materials and methods. Open randomized study was performed including 122 patients with metastatic TNBC. The efficacy and safety of the first line chemotherapy of regimens АТ (n=59) – group 1, patients received doxorubicine 60 мг/м2 and paclitaxel 175 мг/м2 and ТР (n=63) – group 2, patients received paclitaxel 175 мг/м2 and carboplatin AUC 5 were evaluated. Results. The median duration of response was 9.5 months (4.5–13.25 months) in patients received AT regimen and 8.5 months (4.7–12.25 months), in TP regimen; no statistically significant differences were observed, р=0.836. The median progression free survival was 7 months (95% CI 5–26 months) in group 1 and 7.5 months (95% CI 6–35 months) in group 2, p=0.85. Both chemotherapy regimens (AT and TP) had mild or moderate toxicity profiles (grade 1 or 2 in most patients). No significant difference in gastrointestinal toxicity was observed. The incidence of grade 3–4 neutropenia was higher in patients of group 2 (TP regimen): 42.8% versus 27% (р<0.05). Conclusions. Both regimens of chemotherapy (AT and TP) are appropriate to use in the first line setting in patients with metastatic TNBC. Key words: metastatic triple negative breast cancer, chemotherapy, progression free survival, chemotherapy toxicity.


Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 185-192
Author(s):  
Deniz Öğütmen Koç ◽  
Hande Sipahi ◽  
Cemile Dilşah Sürmeli ◽  
Mustafa Çalık ◽  
Nilgün Bireroğlu ◽  
...  

AbstractIn Coronavirus disease 2019 (COVID-19), it is important to evaluate disease activity and investigate possible biomarkers. Therefore, in this study, we investigated the relationship between disease activity and serum levels of possible immune activation marker neopterin in patients with COVID-19. The study enrolled 45 patients (23 females, 51.1%) treated for COVID-19. The patients were divided into two groups according to their clinical presentation: those who recovered quickly (Group 1) and those who worsened progressively (Group 2). The neopterin and C-reactive protein levels were high in all patients on admission. In Group 1, neopterin concentrations and serum neopterin/creatinine ratios were significantly higher on admission compared to Day 14 of the disease, whereas in Group 2, levels were significantly higher at Day 14 of the disease than on admission. Neopterin levels at admission were significantly higher in Group 1. The serum neopterin concentrations at admission were markedly higher in patients with a derived neutrophil–lymphocyte ratio (dNLR) > 2.8 compared to those with a dNLR ≤ 2.8 (p < 0.05). Serum neopterin levels can be used as a prognostic biomarker in predicting disease activity in COVID-19.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1328.1-1328
Author(s):  
R. Assandri ◽  
G. Martellosio ◽  
A. Montanelli

Background:Systemic Lupus Erythematosus (SLE) is an autoimmune disease that involves several molecular patterns with a wide spectrum of clinical manifestations and symptoms. Inflammation and related pathway play a role in SLE pathogenesis. The pentraxin superfamily including long and short pentraxin, C Reactive Protein CRP, Serum amyloid A (SAA), Pentraxin 3 (PTX3) are key components of innate immune system and induce a variety of inflammation associated pathway. However Literature provides several evidences that CRP serum levels not correlated with clinical and immunological manifestations. This situation affected clinical practice and the patient follow up. PTX3 have been identified as a component of inflammatory status in several autoimmune conditions. SAA is an acute phase protein secreted in large quantity during inflammation.Objectives:We want to evaluated SAA, PTX3 and CRP concentrations, their correlation between SLE Disease Activity Index (SLEDAI), that including complement fractions C3, C4.Methods:We enrolled fifty patients that fulfilled the SLE American College of Rheumatology criteria and fifty healthy subjects. The SLE disease activity was classified with the SLEDAI (0 to 12). Patients were divided into two groups according to SLEDAI score: inactive group (Group 1, 25 patients, 50%: SLEDAI < 4) and active group (Group 2, 25 patients, 50%: SLEDAI 5 to 12). PTX3 concentration was measured by a sandwich ELISA kit (Hycult) with 2.8 ng/mL cut-off point. SAA concentration was detected by nephelometry performed on a BN ProSpec System (Siemens, Germany), with assay kit based on polyclonal antibodies (Siemens Healthcare Diagnostics Products, Germany, 6.5 mg/L cut-off point). High sensitive CRP concentrations were determined using the ci8200 platform (Abbott Laboratories Chicago, Illinois).Results:Plasma PTX3 and serum SAA levels was significantly higher in SLE patients than in the healthy subjects (PTX311.5 ± 7.3 ng/mL vs 2.3 ± 1.1; p < 0.001; SAA: 87 ±77 mg/L vs 2.6±2.5; p < 0.001). These differences were not evident in CRP levels (8.5 ± 7.8 mg/L vs 6.2± 2.5). Considering two groups, there were statistical differences in PTX3 level (Group 2: 14.9 ± 12 ng/mL vs Group 1: 2.16 ±0.5 ng/mL, p<0,05) and SAA concentration (Group 2: 114 ± 89 ng/mL vs Group 1: 3.6 ±1.7 ng/mL, p<0,05) but not in CRP concentration (Group 2: 11.5 ± 8.4 mg/L vs Group 1: 9.5 ±3.5). There was a significantly negative correlation between C3, C4 fractions, PTX3 and SSA levels (respectively r = −0.74, p=<0.05, and r = −0.79, p<0.05). No statistical correlation were appeared between C3, C4 fractions and CRP serum levels (r= −0,12., p= 0.82, and r= −0.18, p= 0,21). We noted a positive significant correlation between SLEDAI, PTX3 and SAA concentration (r = 0.79, p < 0.05, 0.83, p < 0.05, respectively) an increase in PTX3 and SAA levels followed the lupus flare and symptoms. No significant correlation appeared between SLEDAI and CRP (r= 0.15, p=0.89)Conclusion:PTX3 and SAA concentration was significantly higher in SLE patients than the healthy control subjects and their levels reflected disease activity. We showed a direct correlation between PTX3 and SAA. In SLE patients PTX3 and SAA concentrations were correlated with SLEDAI. We suggest an integrate viewpoint in witch SAA and PTX3 may play a role as a biomarker of disease activity, with synergic work during SLE events. Evidences suggested that PTX3 and SAA could trigger the same molecular pathway, by TLR4, via NF-kB.References:[1]Assandri R, Monari M Montanelli A. Pentraxin 3 in Systemic Lupus Erithematosus: Questions to be Resolved, Translational Biomedicine (2015)Disclosure of Interests:None declared


1994 ◽  
Vol 22 (3) ◽  
pp. 171-176 ◽  
Author(s):  
N-A Ankrah ◽  
T Rikimaru ◽  
F A Ekuban ◽  
M M Addae

Cysteine, methionine, vitamin A, β-carotene and glutathione (GSH) are known to protect body tissues against oxidative damage and inflammation but their value as protection against liver inflammation in tropical areas has received little attention. Blood levels of these nutrients were measured in Ghanaian volunteers with (Group 2) or without (Group 1) increased lipid peroxidation and signs of liver inflammation, as indicated by blood malonic dialdehyde, serum α1-antitrypsin and triglyceride levels, and the α1-acid glycoprotein: pre-albumin ratio. Serum levels of cysteine and blood glutathione were significantly lower ( P < 0.02) in group 2 than in group 1 volunteers. In contrast, serum levels of methionine, vitamin A and β-carotene were similar in both groups. Deficits in cysteine and glutathione may increase the risk of liver toxicity from oxidants in Ghanaians.


1993 ◽  
Vol 4 (1) ◽  
pp. 81-90
Author(s):  
D J Leehey ◽  
B I Braun ◽  
D A Tholl ◽  
L S Chung ◽  
C A Gross ◽  
...  

A randomized, controlled clinical trial was performed to determine whether individualized dosing by use of Bayesian pharmacokinetic modeling could decrease nephrotoxicity accosted with aminoglycoside therapy. Two hundred forty-three patients receiving aminoglycosides for suspected or proven infection were randomly assigned to one of three groups: usual physician-directed dosing (Group 1), pharmacist-assisted dosing (Group 2), or pharmacist-directed dosing (Group 3). Dosing in Groups 2 and 3 was based on a Bayesian pharmacokinetic dosing program, whereas Group 1 served as the control group. Individualized dosing resulted in higher mean postinfusion (peak) serum aminoglycoside levels, higher ratios of mean peak level to minimum inhibitory concentration (peak/MIC ratios), and a trend toward lower trough serum levels. Milligrams per dose were higher and number of doses per day was lower in the pharmacist-dosed groups. However, the incidence of nephrotoxicity (> or = 100% increase in serum creatinine) was not different among the three groups (16, 27, and 16% in Groups 1, 2, and 3, respectively). Similarly, severity of toxicity was not affected by the dosing intervention. Risk factors for toxicity included duration of therapy, shock, treatment with furosemide, older age, and liver disease. After controlling for these factors, the dosing intervention still had no effect on nephrotoxicity. It was concluded that Bayesian pharmacokinetic dosing did not decrease the risk of nephrotoxicity associated with aminoglycoside therapy.


2014 ◽  
Vol 23 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Adriana Cavasi ◽  
Eduard Cavasi ◽  
Mircea Grigorescu ◽  
Adela Sitar-Taut

Background & Aims: ProBNP is a sensitive marker of cardiac dysfunction. We assessed the concentration of circulating NT-proBNP in patients with liver cirrhosis in various stages of the disease and its correlation with markers of cardiac and renal dysfunction and with markers of liver disease severity.Patients and methods: A number of 88 patients with liver cirrhosis were included in the study, divided into 3 groups: group 1 - 18 control patients without ascites; group 2 - 35 non-azotemic patients with ascites; group 3 - 35 patients with hepatorenal syndrome. The cardiac dysfunction was assessed by measuring the NT-proBNP serum levels and the QTc interval. The markers of renal dysfunction were the estimated glomerular filtration rates - formulas involving creatinine and serum cystatin C. The Child-Pugh score was used to assess the liver disease severity.Results: The median NT-proBNP serum levels significantly increased in patients with advanced liver cirrhosis (group 3: 960 fmol/ml and group 2:  660 fmol/ml) as compared to group 1 (435 fmol/ml) (p<0.05). A significant direct correlation was found between the NT-proBNP concentration and the QTc interval (r=0.540, p<0.001). The NT-proBNP levels also correlated with the Child-Pugh score (r=0.501, p<0.01), proving the link between the cardiac dysfunction and the liver disease severity. The cardio-renal interrelation is supported by the relationship between the NT-proBNP concentration and the estimated clearances.Conclusion: The high NT-proBNP levels in patients with advanced cirrhosis indicate the presence of cardiac dysfunction, which has a role in the pathogenesis of the hepatorenal syndrome.Abbreviations: DP: diastolic pressure; GFR: glomerular filtration rate; HRS: hepatorenal syndrome; MAP:mean arterial pressure; NT-proBNP: N-terminal fragment of the prohormone B-type natriuretic peptide; proBNP: prohormone brain natriuretic peptide; SBP: spontaneous bacterial peritonitis; SP: systolic pressure; TIPS: tranjugular intrahepatic portosystemic shunt.


Author(s):  
Osman Erdogan ◽  
Alper Parlakgumus ◽  
Ugur Topal ◽  
Kemal Yener ◽  
Umit Turan ◽  
...  

Aims: Mucinous, medullary, and papillary carcinomas are rarely encountered types of breast cancer. This study aims to contribute to the literature by comparing the clinical and prognostic features and treatment alternatives of rare breast carcinomas. Study Design: Thirty-four patients with rare breast cancer out of a total of 1368 patients who underwent surgery for breast cancer in our clinic between January 2011 and December 2020 were included in the study. Methodology: The patients were assigned into three groups, i.e., medullary carcinoma group (Group 1), mucinous carcinoma group (Group 2) and papillary carcinoma group (Group 3). Demographic and clinical features, treatment modalities used, surgical approaches, pathological features of tumors and survival were compared between the groups. Results: Thirty-four patients were included in the study. The mean age of the patients in Group 3 was higher, though it was not statistically significant. Modified radical mastectomy was more frequently performed in all the groups. The number of the lymph nodes removed through axillary dissections and the number of the positive lymph nodes were similar in all the groups. The tumors in all the groups were also of comparable sizes (30 mm in Group 1, 42.5 mm in Group 2 and 30 mm in Group 3; p:0.464). Estrogen receptors were negative in a significantly higher rate of Group 1(66.7% of Group 1, p<0,001). A significantly higher rate of Group 1 received postoperative chemotherapy (93,3% of Group 1,p:0.001), but the rate of the patients receiving hormonotherapy in this group was significantly lower (26.7% of Group, p<0,001). The patients with medullary cancer had significantly longer survival than those with mucinous cancer and those with papillary cancer (76.2 in Group 1, 54.5 in Group 2 and 58.4 in Group 3; p:0.005). Conclusion: While rare subtypes of breast carcinoma did not affect opting for surgical treatment, selection of oncological therapy was affected depending on the hormone receptor status of these tumors. The long-term survival differed between rare breast tumors. In view of the unique clinical pictures of the tumors, the patients should be evaluated individually, and the evaluation should be associated with theevidence-based principles available for more common breast carcinomas.


2010 ◽  
Vol 8 (4) ◽  
pp. 414-418 ◽  
Author(s):  
Darcielle Bruna Dias Elias ◽  
Rivelilson Mendes de Freitas ◽  
Romélia Pinheiro Gonçalves ◽  
Hemerson Yuri Ferreira Magalhães ◽  
Jacqueline Holanda de Sousa ◽  
...  

ABSTRACT Objective: To determine the serum levels of malondialdehyde and nitrite in patients with sickle cell anemia treated or not with hydroxyurea in outpatient's setting. Methods: Of the 65 patients with sickle cell anemia selected for the study, 51 were not treated with hydroxyurea (Group 1), 14 made chronic use of hydroxyurea (Group 2) and 20 individuals had no hemoglobinopathies (Control Group). Results: The Control Group had a lower and more homogeneous concentration of malondialdehyde levels as compared to the other groups. The results of Groups 1 and 2 showed increased values of malondialdehyde levels when compared to the Control Group. Considering the values of Groups 1 and 2, there were no significant changes in the malondialdehyde levels. There was no significant difference in the serum levels of nitrite between the groups. Group 2 presented a statistically significant correlation between serum malondialdehyde levels and the clinical variables investigated. In turn, Group 1 showed correlation only with occurrence of three or more vaso-occlusive crises. There was no correlation between nitrite levels and the clinical variables. Conclusion: The results revealed that during the pathogenesis of sickle cell anemia, an increase in lipid peroxidation was observed. On the other hand, no changes in oxidative parameters were detected during treatment with hydroxyurea, probably due to the short period of treatment of the patients studied.


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