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BACKGROUND Calprotectin (S100A8/A9 or myeloid-related protein 8/14) is a heterodimeric S100 complex expressed in leukocytes. Calprotectin participates in development of the inflammatory response by binding to receptors for advanced glycation end-products (RAGE) and Toll-like receptors (TLR). The clinical activity of systemic lupus erythematosus (SLE) is evaluated using the Systemic Lupus International Collaborating Clinics (SLICC) criteria and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This Polish single-center case-control study aimed to evaluate serum levels of calprotectin as a rapid diagnostic biomarker of SLE (59 patients with SLE were compared with 52 healthy controls). MATERIAL AND METHODS Calprotectin concentration was measured with the use of enzyme-linked immunosorbent assay (ELISA). The SLE activity of the patients was assessed by the SLEDAI scale. Statistical analysis of the results was carried out using MedCalc 15.8 software. P<0.05 was considered statistically significant. RESULTS A significantly higher concentration of calprotectin was found in the study group compared to the control group (medians: 3.11 vs 2.45 ng/ml; P=0.0013). We found that calprotectin has high sensitivity (89.83%) and specificity (53.85%) in differentiating between SLE patients and healthy volunteers. We found that calprotectin has very high sensitivity (100%) and specificity (82.46%) in detection of patients with moderate and severe SLE assessed using SLEDAI. CONCLUSIONS Consistent with previous studies, serum calprotectin level was revealed to have potential as a rapid diagnostic biomarker of disease activity in patients with SLE.
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Complejo de Antígeno L1 de Leucocito , Lupus Eritematoso Sistémico , Biomarcadores/sangre , Calgranulina A , Estudios de Casos y Controles , Humanos , Complejo de Antígeno L1 de Leucocito/sangre , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Polonia , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND Head and neck cancers (HNC) are the 7th most prevalent neoplasms in the world. In 50% of these patients, body weight loss and malnutrition are observed before the beginning of therapy. It is known that an important role in the pathomechanism of malnutrition and cachexia is played by the development of inflammation, degradation of muscle fibers, and browning of white adipose tissue (WAT). It was demonstrated that even a slight increase in irisin concentration leads to browning of WAT. MATERIAL AND METHODS The study group consisted of 50 patients with HNC. The nutritional status of the patients was assessed by the Nutritional Risk Score 2002 (NRS 2002) and Subjective Global Assessment (SGA) scales. Using bioelectrical impedance analysis (BIA), the parameters fat mass (FM) and fat-free mass (FFM) were obtained. RESULTS Higher irisin values (1.57 vs 1.18 [ng/ml], P=0.0004) were observed in patients with higher nutritional risk (≥3) evaluated according to the NRS scale. In patients assessed as B or C on the SGA scale, higher values of irisin concentration (1.38 vs 1.07 [ng/ml], P=0.0139) were noted. It was also observed that the level of irisin before treatment was negatively correlated (rho=-0.30, p=0.0350) with FM% and was positively correlated (rho=0.30, p=0.0340) with FFM% in BIA measurements performed after the 7th cycle of RTH. CONCLUSIONS Based on these results, we conclude that patients with malnutrition tend to have higher irisin values compared to normally nourished patients. A high level of irisin may be a useful marker of malnutrition in patients with HNC.
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Neoplasias de Cabeza y Cuello , Desnutrición , Biomarcadores , Impedancia Eléctrica , Fibronectinas , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Desnutrición/diagnóstico , Desnutrición/etiología , Evaluación Nutricional , Estado NutricionalRESUMEN
INTRODUCTION: Malnutrition is a frequently diagnosed condition in head and neck cancer (HNC) patients after radiation therapy (RTH). Malnutrition causes adipose tissue dysfunction associated with intensified lipolysis and disruption of the activity of mechanisms that protect adipose tissue against this process, which include the protective function of perilipin. MATERIAL AND METHODS: The purpose of this study was the evaluation of the predictive value of 13041A>G PLIN1 polymorphism in the development of malnutrition related to adipose tissue loss in a group of 80 patients with locally advanced HNC treated by means of radical radiation therapy. RESULTS: After the completion of RTH, men with AA genotype had significantly lower fat mass (FM compared to men with G haplotype; FM: 13.84 ± 6.36 kg and 19.06 ± 6.30 kg (p = 0.009). In consequence of RTH, the AA genotype carriers lost an average of 37.01% adipose tissue mass and patients with GA and GG genotypes lost 12.82 and 0.31% (p = 0.035), respectively. AA genotype was also associated with higher chance of ≥ 10%, ≥ 20% and ≥ 30% FM loss in the course of RTH (OR = 13.78; 5.78; 2.28). CONCLUSIONS: The evaluation of such molecular factors as SNP 13041A>G may have higher predictive value in the development of malnutrition associated with severe loss of fat mass than the subjective scales, e.g., SGA and NRS-2002. The presence of AA genotype on men with HNC before RTH may facilitate earlier nutritional intervention and supportive treatment aimed at limiting or preventing body mass and fat mass loss during the applied treatment.
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Tejido Adiposo/fisiopatología , Neoplasias de Cabeza y Cuello/radioterapia , Desnutrición/genética , Perilipina-1/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Perilipina-1/farmacología , Polimorfismo de Nucleótido SimpleRESUMEN
Brain-derived neurotrophic factor (BDNF) is a protein with a potent influence on several aspects of neuronal and blood vessel functions. However, its prognostic potential and functional role in multiple myeloma (MM) remain largely unknown. In this study, we investigated the influence of BDNF on the risk of chemotherapy-induced peripheral neuropathy (CIPN) and clinical outcome. Study group consisted of 91 newly-diagnosed MM patients treated with bortezomib and/or thalidomide-based chemotherapy. Detection of BDNF in serum was performed using ELISA. Polyneuropathy was assessed according to the CTCAE Criteria v5. We observed that BDNF concentration correlated with the severity of polyneuropathy (P = 0·0463). Higher BDNF values were noted in patients who responded to treatment (P = 0·0326), and BDNF proved to be a useful marker to predict lack of response after eight cycles of treatment (sensitivity - 100%, specificity - 61·5%, P = 0·0142). Moreover this marker showed significant diagnostic usefulness in diagnosis of CIPN (sensitivity - 76%, specificity - 71·43%; area under the curve (AUC)= 0·77, 95%, confidence interval (CI): 0·64-0·88; P < 0·0001). Low BDNF was an independent, unfavourable prognostic factor associated with reduced overall survival (OS) (hazard ratio (HR) = 2·79, P = 0·0470). In conclusion, BDNF level may play a prognostic role and constitute a useful biomarker in predicting CIPN in MM patients.
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Biomarcadores de Tumor/sangre , Bortezomib , Factor Neurotrófico Derivado del Encéfalo/sangre , Mieloma Múltiple , Polineuropatías , Talidomida , Adulto , Anciano , Anciano de 80 o más Años , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Polineuropatías/sangre , Polineuropatías/inducido químicamente , Polineuropatías/mortalidad , Tasa de Supervivencia , Talidomida/administración & dosificación , Talidomida/efectos adversosRESUMEN
Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are considered as laboratory markers of inflammation. They can be potentially useful in predicting the course of multiple neoplasms including selected hematological cancers. The aim of the study was to assess the value of NLR and PLR in predicting the effects of therapy and prognosis in multiple myeloma patients treated with thalidomide-based regimen. The study group consisted of 100 patients treated with the first line CTD (cyclophosphamide, thalidomide, and dexamethasone) chemotherapy. The NLR and PLR were calculated before treatment. High NLR was observed in patients with higher stage of the disease, with poor performance status, hypercalcemia, and high CRP. High PLR was associated with low BMI and high CRP. In patients with high NLR, significantly shorter PFS was observed (17 vs. 26 months, p = 0.0405). In addition, high values of NLR and PLR were associated with significantly shorter OS (38 vs. 79 months, p = 0.0010; 40 vs. 78 months, p = 0.0058). Summarizing, NLR and PLR have a significant independent prognostic value for multiple myeloma patients. Furthermore, the NLR can be a predictive marker for the outcome of thalidomide-based chemotherapy.
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Plaquetas/metabolismo , Linfocitos/metabolismo , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Neutrófilos/metabolismo , Talidomida/uso terapéutico , Anciano , Plaquetas/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Recuento de Linfocitos/métodos , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Neutrófilos/efectos de los fármacos , Recuento de Plaquetas/métodos , Pronóstico , Tasa de Supervivencia/tendencias , Talidomida/farmacología , Resultado del TratamientoRESUMEN
PURPOSE: Radiotherapy (RTH) usually combined with chemotherapy (C-RTH) is the main method of treatment in head and neck cancer (HNC). The most common complication of RTH is oral mucositis (OM). At a certain stage of RTH, it occurs in almost all patients, often lead to discontinuation of treatment. Tumour necrosis factor alpha (TNF-α) is a cytokine secreted during inflammatory process accompanying RTH and the development of cancer itself. Single nucleotide polymorphism (SNP) of the TNF-α promoter region can potentially affect the function or expression of this cytokine, and thus modulate the risk of occurrence and intensity of OM and shortening of overall survival (OS). METHODS: The study group consisted of 62 patients with HNC in whom intensity-modulated radiation therapy (IMRT) technique was applied. The plasma TNF-α level was assessed using the ELISA Kit. Genotyping was performed using a real-time PCR method. RESULTS: HNC patients with the CC genotype of TNF-α (- 1211 T > C) have higher TNF-α plasma concentrations than those with T allele (10.70 vs 9.62 ng/ml). Patients with the 3rd degree of OM have significantly higher TNF-α levels after 5th (10.40 vs 9.45 ng/ml) and 7th (10.32 vs 9.60 ng/ml) week of RTH. CC genotype was related to a higher risk of 3rd degree OM development in the last weeks of RTH (5th, OR = 7.33; 7th, OR = 23.15). CONCLUSIONS: High TNF-α plasma concentration and CC genotype of TNF-α are related to the higher risk of more severe OM in patients irradiated due to HNC. High TNF-α plasma concentration and CC genotype of TNF-α are independent prognostic factors for patients subjected to RTH due to HNC.
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Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Radioterapia de Intensidad Modulada/métodos , Estomatitis/etiología , Factor de Necrosis Tumoral alfa/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Thalidomide is commonly used in treatment of multiple myeloma (MM). This study aimed to analyse the influence of clinical and molecular factors - single nucleotide polymorphisms (SNPs) of the CRBN gene: rs6768972 and rs1672753, on the risk of adverse effects (AEs) of thalidomide-based chemotherapy in patients with MM. The study group included 82 patients receiving CTD (thalidomide, cyclophosphamide, dexamethasone) as first line treatment. The intensity of haematological and non-haematological AEs was assessed according to the Common Terminology Criteria for Adverse Events v4.03. Multivariate analysis showed that patients with the CRBN CC genotype (rs1672753) had more than a 14-fold higher risk of peripheral polyneuropathy compared to patients with other variants of the investigated SNP [odds ratio (OR) = 14·29]. Carriers of this genotype were burdened with significantly (about 17-fold) higher risk of diarrhoea during treatment (OR = 16·67). The presence of CRBN AA (rs6768972) or TT (rs1672753) genotypes was associated with about 333-fold and 250-fold lower risk of constipation in the course of therapy (OR = 0·003; OR = 0·004, respectively). Selected CRBN SNPs may be useful in assessing the probability of AEs in the form of peripheral polyneuropathy and gastrointestinal motility disorders associated with the use of thalidomide in patients with MM.
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Inmunosupresores/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Talidomida/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Enfermedades del Sistema Nervioso Periférico/mortalidad , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Tasa de Supervivencia , Talidomida/administración & dosificaciónRESUMEN
Introduction: Direct parameters resistance (R), reactance (Xc), phase angle (PA), capacitance of membrane (Cm), and impedance ratio (Z200/Z5)) determined by bioelectrical impedance analysis (BIA) detect changes in tissue electrical properties and have been found to be a marker of cell membrane function in various diseases. Materials and Method: The cross-sectional study was conducted to investigate whether direct bioimpedance parameters differ in a group of heart failure (HF) patients divided on the basis of the New York Heart Association (NYHA) functional classes I-II and III-IV. BIA was evaluated in 100 patients with HF treated in Clinic of Cardiology and Internal Medicine, Department of Cardiology, Military Hospital, Lublin. Results: In men, lower PA values (p = 0.01), Xc (p < 0.01), Cm (p = 0.02), and higher values of the Z200/Z5 ratio (p < 0.01) were observed in patients classified into NYHA groups III and IV in comparison to those with lower stages of disease. Similar correlations were noted in women (only Cm differences were insignificant). In addition, in men, C-Reactive Protein (CRP) correlated negatively with PA (p < 0.01), Xc (p < 0.01), and Cm (p < 0.01) and positively with the Z200/Z5 index (p < 0.01). There were no similar correlations observed in women. Conclusion: Patients with advanced CHF have altered electrical values. Changes in electrical values may directly reflect tissues as well as the whole-body condition.
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Impedancia Eléctrica , Sistema de Conducción Cardíaco/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Enfermedad Crónica , Estudios Transversales , Femenino , Corazón/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , PoloniaRESUMEN
In response to various stimuli, neutrophils and eosinophils can release neutrophil extracellular traps (NET) consisting of proteolytic enzymes, DNA and other components of the cell nucleus. The NETosis process has been characterized as a mechanism of programmed cell death, which leads to chromatin decondensation and disintegration of organelles, followed by lysis of the cell membrane. In recent years the significant role of neutrophils in the pathogenesis of cancer has been highlighted. The presence of two subpopulations of TAN with different phenotypes and functions - acting antitumor "N1" and the pro-cancerous "N2" - has been discovered. By the release of cytokines and chemokines neutrophils may affect angiogenesis and contribute to escape of tumor cells from immune surveillance. Interactions between cells and the microenvironment are of vital importance both for the preservation of homeostasis in normal tissue and tumor growth. They affect the initiation of disease progression and prognosis. The impact of NETosis on the process of metastasis is evaluated in the context of the functions of the individual components of the NET (MMP-9, CG, NE). Furthermore, presumably the pro- or anti-tumor effect of NETosis depends on many factors including the status of the immune system or tumor microenvironment. Probably the cancer cells can be captured by the NET microenvironment in the same manner as microorganisms. However, the high concentration of proteins released during NETosis can induce their proliferation and inhibit apoptosis, thus promoting tumor growth. A better understanding of NETosis function in tumor progression may lead to the emergence of new prognostic factors and targets for therapy in many types of cancer.
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Trampas Extracelulares/metabolismo , Neoplasias/metabolismo , Neutrófilos/metabolismo , Muerte Celular , Cromatina/metabolismo , Citocinas/metabolismo , ADN/metabolismo , Humanos , Invasividad Neoplásica/inmunología , Metástasis de la Neoplasia , Neoplasias/inmunología , Neutrófilos/inmunologíaRESUMEN
Introduction: Multiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related adverse events. Methods: We conducted a prospective observational study with 81 newly diagnosed MM patients, analyzing serum cytokine levels using the multiplex cytometric bead assay (CBA) flow cytometry method. The study used non-parametric and multivariate analysis to compare cytokine levels with treatment-induced toxicities, including lymphopenia, infections, polyneuropathy, and neutropenia. Results: Our findings revealed significant associations between cytokine levels and specific toxicities. IL-8 levels were lower in patients with lymphopenia (p=0.0454) and higher in patients with infections (p=0.0009) or polyneuropathy (p=0.0333). VEGF concentrations were notably lower in patients with neutropenia (p=0.0343). IL-8 demonstrated an 81% sensitivity (AUC=0.69; p=0.0015) in identifying infection risk. IL-8 was an independent predictor of lymphopenia (Odds Ratio [OR]=0.26; 95% Confidence Interval [CI]=0.07-0.78; p=0.0167) and infection (OR=4.76; 95% CI=0.07-0.62; p=0.0049). High VEGF levels correlated with a 4-fold increased risk of anemia (OR=4.13; p=0.0414). Conclusions: Pre-treatment concentrations of IL-8 and VEGF in serum can predict hematological complications, infections, and polyneuropathy in patients with newly diagnosed MM undergoing chemotherapy. They may serve as simple yet effective biomarkers for detecting infections, lymphopenia, neutropenia, and treatment-related polyneuropathy, aiding in the personalization of chemotherapy regimens and the mitigation of treatment-related risks.
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Quimiocina CCL2 , Interleucina-8 , Mieloma Múltiple , Factor A de Crecimiento Endotelial Vascular , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Factor A de Crecimiento Endotelial Vascular/sangre , Interleucina-8/sangre , Pronóstico , Quimiocina CCL2/sangre , Interleucina-6/sangre , Estudios Prospectivos , Adulto , Anciano de 80 o más Años , Citocinas/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Multiple myeloma (MM) is a hematological neoplasm of the early precursor of B-cells. The most characteristic symptoms observed during MM include hypocalcemia, anemia, bacterial infections, and renal damage. Nutritional disorders, especially malnutrition, are noted in about 35-71% of MM patients. Interleukin 1 beta (IL-1ß) is a proinflammatory cytokine responsible for muscle atrophy and lipolysis during malnutrition and cachexia. This study aimed to evaluate the usefulness of the IL1B single-nucleotide polymorphism (SNP) (rs1143634) and plasma concentration of IL-1ß in the assessment of the risk of nutritional disorders and prognosis in patients with MM. METHODS: In our study, 93 patients with the de novo MM were enrolled. The real-time PCR with specific TaqMan probes method was used in genotyping. The IL-1ß ELISA kit was used to determine IL-1ß concentration in plasma samples. RESULTS: Patients with the CC genotype, compared to the carriers of the other variants of the IL1B, demonstrated significantly higher concentrations of IL-1ß in plasma (7.56 vs. 4.97 pg/mL), a significantly higher risk of cachexia (OR = 5.11), and a significantly higher risk of death (HR = 2.03). Moreover, high IL-1ß plasma level was related to a significantly higher risk of cachexia (OR = 7.76); however, it was not significantly associated with progression-free survival (PFS) or overall survival (OS). CONCLUSIONS: Determination of the IL1B SNP (rs1143634) and plasma concentration of IL-1ß may be useful in the assessment of the risk of cachexia and prognosis in patients with MM.
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Multiple myeloma (MM) is the second most common hematologic malignancy in the world and accounts for 15% of primary hemocytopathies, with an ever-increasing number of new cases. It is asymptomatic in 30% of instances; hence, the determination of highly sensitive and specific markers is necessary to make a proper diagnosis. In the last 20 years, miRNAs, involved in regulating the expression of genes responsible for cell proliferation and differentiation, including tumor cells, have been identified as potential diagnostic and prognostic markers. The main aim of the following review was to outline the role of miRNAs in the diagnosis and prognosis of MM, considering their role in the pathogenesis of the disease and identifying their target genes and pathways. For this purpose, publications dating from 2013-2023 have been reviewed. Based on the available data, it is concluded that non-coding RNAs including miRNAs could be potential markers in MM. Furthermore, they may serve as therapeutic targets for certain drugs.
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Multiple myeloma (MM) is the second most common hematological neoplasm. Cytokines, chemokines, and their receptors, induced by the microenvironment of MM, participate in tumor growth, the attraction of leukocytes, cell homing, and bone destruction. This study aimed to assess the correlation between the pretreatment serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), angiogenic chemokine monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) and the clinical outcomes and survival of patients newly diagnosed with MM. The study group consisted of 82 individuals. The IL-8 concentration was significantly positively correlated with the age of onset (p = 0.007), the International Staging System (ISS) stage (p = 0.03), the Eastern Cooperative Oncology Group (ECOG) performance status (p < 0.001), the degree of anemia before treatment (p < 0.0001), the degree of kidney disease (p < 0.001), and VEGF (p = 0.0364). Chemotherapy responders had significantly lower concentrations of IL-8 (p < 0.001), IL-6 (p < 0.001), and VEGF (p = 0.04) compared with non-responders. Patients with treatment-induced polyneuropathy had significantly higher levels of IL-8 (p = 0.033). Patients with a high level of IL-6 had a 2-fold higher risk of progression-free survival (PFS) reduction (17 vs. 35 months; HR = 1.89; p = 0.0078), and a more than 2.5-fold higher risk of overall survival (OS) reduction (28 vs. 78 months; HR = 2.62; p < 0.001). High levels of IL-6, IL-8, and VEGF demonstrated significant predictive values for some clinical conditions or outcomes of newly diagnosed MM patients. Patients with an early response to chemotherapy had a significantly lower concentration of these cytokines. A high pretreatment IL-6 concentration was an independent negative prognostic marker for newly diagnosed MM patients.
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BACKGROUND: The KIAA1524 gene encodes an oncoprotein, CIP2A, which inhibits the phosphorylation of the Akt kinase B, stabilizes the c-Myc protein, and, through that, promotes cancerogenesis. An increase in CIP2A expression has been observed in numerous solid tumors and hematologic malignancies, including multiple myeloma (MM). The aim of our study was to evaluate the clinical impact of the functional single nucleotide polymorphisms (SNP) of the KIAA1524 gene (rs2278911, 686C > T) in MM patients. METHODS: The study group consisted of 128 patients with de novo MM. EDTA venous blood samples were collected prior to the treatment. The SNPs were analyzed by Real-Time PCR with the use of specific Taqman probes. RESULTS: Multivariable analysis revealed that variables independently associated with shorter progression-free survival (PFS) included thrombocytopenia, delTP53 and IGH/CCND1 translocation and the TT genotype of the KIAA1524 gene (686C > T) (median PFS: 6 vs. 25 months; HR = 7.18). On the other hand, autologous haematopoietic stem cell transplantation (AHSCT) was related to a lower risk of early disease progression. Moreover, light chain disease, International Staging System (ISS) 3, poor performance status, hypoalbuminemia, IGH/FGFR3 translocation and the TT genotype of the KIAA1524 gene (686C > T) were independent prognostic factors associated with shorter overall survival (OS) (median OS: 8 vs. 45 months; HR = 7.08). CONCLUSION: The evaluation of the SNP 686C > T of the KIAA1524 gene could be used as a diagnostic tool in MM patients at risk of early disease progression and death.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Genotipo , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Mieloma Múltiple/terapiaRESUMEN
According to the World Health Organization, in 2018, cancers, along with over 18 million new cases and over 9.5 million deaths remained one of the main causes of mortality globally. Cancer-cachexia, also called wasting syndrome is a complex, multifactorial disorder characterized by progressive skeletal muscle mass loss, with or without adipose tissue atrophy. It is considered as a state of cancer-related malnutrition (CRM) accompanied by inflammation, that is irreversible despite the introduction of nutritional support. Indication of markers of pre-cachectic state seems to be urgently needed. Moreover, such markers have also potential to be used in the assessment of the effects of anti-cachexia treatment, and prognosis. miRNAs are non-coding RNA molecules that are about 20-30 nucleotides long. Single miRNA has the potential to control from few dozen to several hundred different genes. Despite the fact, that the number of miRNAs keep growing. we are making steady progress in establishing regulatory targets and their physiological levels. In this review we described the current knowledge on the impact of miRNAs on processes involved in cancer cachexia development: inflammation, adipose tissue remodelling, and loss of muscle mass both in animal models and the human cohorts. The available studies suggest that miRNAs, due to their properties, e.g., the possibility of regulating even hundreds of different genes, signalling pathways, and biological processes by one molecule, but also due their stability in biological material, the fact, that the change in their level reflects the disease status or the response to the applied treatment, they have great potential to be used as valuable biomarkers in the diagnosis, treatment, and prognosis of cancer cachexia.
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Introduction: Every year over 25 million women worldwide experience menopause symptoms. Menopause leads to the occurrence and intensification of many psychological and somatic disorders including body composition change. Myostatin may play a crucial role in the remodeling of muscle and fat tissue. The aim of the study was to determine the relationship between the level of body fat and the concentration of myostatin protein in serum of peri- or postmenopausal women. Material and methods: The study included 300 Caucasian women (in perimenopause or postmenopause). Detailed data were collected at a single time point from all enrolled women. The data included: age, body mass index, hormone replacement therapy and body fat. Measurements of adipose tissue were performed using electronic skinfold calipers. Serum levels of myostatin were determined using a Human Myostatin ELISA Kit. Results: The mean myostatin concentration in blood serum was 6.58 ±3.59 ng/ml. The mean percentage of body fat was 32.7 ±6.3 (range: 16.1-50.7). The percentages of women in particular groups of body fat level (I, II, III, IV and V) were 1.7%, 11%, 35.3%, 30.7% and 21.3% respectively. Myostatin level in blood serum was significantly lower (median concentrations: 5.5 vs. 7.0 ng/ml, p = 0.0269) in subjects with higher body fat (groups IV and V) compared to those classified as having a normal or low level of body fat (groups I-III). Myostatin was an independent predictive factor of the occurrence of high body fat (p = 0.0463). Conclusions: Decreased level of myostatin is related to higher level of body fat in peri- and postmenopausal women.
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Background: Malnutrition is a nutritional disorder observed in 52% of patients with head and neck cancer (HNC). Malnutrition is frequently related to the increased level of proinflammatory cytokines. In turn, ongoing inflammation is associated with increased catabolism of skeletal muscle and lipolysis. Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine that plays a pivotal role in the development of malnutrition and cachexia in cancer patients. The aim of the study was to assess the relationship between a functional single-nucleotide polymorphism (SNP) −610 T > G (rs4149570) of the TNFRSF1A gene and the occurrence of nutritional disorders in patients subjected to RT due to HNC. Methods: The study group consisted of 77 patients with HNC treated at the Oncology Department of the Medical University in Lublin. Genotyping of the TNFRSF1A gene was performed using capillary electrophoresis (Genetic Analyzer 3500). Results: Multivariable analysis revealed that the TT genotype of the TNFRSF1A gene (−610 T > G) was an independent predictor of severe malnutrition (odds ratioOR = 5.05; p = 0.0350). Moreover, the TT genotype of this gene was independently related to a higher risk of critical weight loss (CWL) (OR = 24.85; p = 0.0009). Conclusions: SNP (−610 T > G) of the TNFRSF1A may be a useful marker in the assessment of the risk of nutritional deficiencies in HNC patients treated with intensity-modulated radiotherapy (IMRT).
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MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16-3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie-Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high ß2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20-7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients.
Asunto(s)
Antineoplásicos , MicroARN Circulante , Hipoalbuminemia , MicroARNs , Mieloma Múltiple , Antineoplásicos/uso terapéutico , Biomarcadores , Bortezomib/uso terapéutico , Humanos , Hipoalbuminemia/complicaciones , Hipoalbuminemia/tratamiento farmacológico , MicroARNs/sangre , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Pronóstico , Talidomida/uso terapéuticoRESUMEN
Nutritional deficiencies, including malnutrition and its irreversible type cachexia, are often observed in patients with head and neck cancer (HNC). Among the various factors contributing to the occurrence of these disorders, inflammation seems to be crucial. The potential regulatory properties of miR-511-3p, e.g., post-translational alteration of expression of genes with protein products that are involved in inflammation, may be related to nutritional deficiencies observed in HNC patients. Therefore, the aim of our study was to assess the correlation between pretreatment miR-511-3p expression and nutritional status in patients undergoing radiotherapy (RT) due to HNC. In our retrospective study, 60 consecutively admitted patients treated with intensity-modulated radiotherapy (IMRT) due to advanced HNC were enrolled. The analysis of miR-511-3p expression was performed using real-time PCR. Significantly higher expression of miR-511-3p was observed in well-nourished patients compared to patients with moderate or severe malnutrition (p = 0.0001). Pretreatment expression of miR-511-3p may be a useful biomarker of nutritional deficiencies in patients subjected to IMRT due to HNC.
RESUMEN
(1) Introduction: Autoimmune hepatitis (AIH) is a chronic disease. A persistent autoimmune reaction in the liver is significantly related to the systemic inflammatory response. Extended Inflammation Parameters (EIP) can be used to assess the activation of immune cells such as activated neutrophils (NEUT-RI and NEUT-GI) and activated lymphocytes (RE-LYMP and AS-LYMP) in the phase of active inflammation. The role of the systemic inflammatory response markers should also be emphasised, especially: NLR, PLR, and RLR, which have recently been widely studied as markers in autoimmune skin diseases or liver diseases. (2) Materials and Methods: The study included 30 patients with AIH and 30 healthy volunteers. The parameters of the EIP group (RE-LYMP, AS-LYMP, NEUT-RI, NEUT-GI), calculated haematological indices Red Blood Cell Distribution Width-to-Platelet Ratio (RPR), Mean Platelet Volume-to-Platelet Ratio (MPR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Red Blood Cell Distribution Width-to-Lymphocyte Ratio (RLR), and selected blood morphological and biochemical indices were analysed. The aim of the study was to assess the usefulness of the EIP and systemic inflammatory response markers in the diagnostics of AIH. (3) Results: Compared to the controls, the patients with AIH showed significantly higher EIP values: NEUT-RI (48.05 vs. 43.30), NEUT-GI (152.65 vs. 147.40), RE-LYMP (0.07 vs. 0.03), and the inflammatory response markers: MPR (0.05 vs. 0.04), RPR (0.07 vs. 0.05), and NLR (2.81 vs. 1.42. Among the examined markers, EIP has significant diagnostic potential: NEUT-RI (AUC = 0.86), NEUT-GI (AUC = 0.80), and RE-LYMP (AUC = 0.78), and so do calculated haematological indices, i.e., MPR (AUC = 0.75), PLR (AUC = 1.00), and RLR (AUC = 1.00) Moreover, the importance of NEUT-GI (AUC = 0.89), MPR (AUC = 0.93), PLR (AUC = 0.86), RPR (AUC = 0.91), and FIB-4 (AUC = 0.83) in the detection of liver fibrosis in the course of AIH has also been proven. (4) Conclusions: EIP and systemic inflammatory response markers may turn out to be useful in detecting AIH and in looking for features of already developed liver cirrhosis in its course.