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BACKGROUND/AIM: The role of single nucleotide polymorphisms (SNPs) in the frequency and intensity of chemotherapy-induced nausea and vomiting (CINV) in women with breast cancer (BC) is unclear. The primary purpose of this study was to compare/evaluate the effect of SNP-guided antiemetic treatment versus standard CINV treatment. PATIENTS AND METHODS: A randomised, factorial, phase II multicentre study design was used. Women planned for neoadjuvant or adjuvant chemotherapy with epirubicin, cyclophosphamide and fluorouracil (FEC /EC, with or without fluorouracil) for BC were randomised to SNP-guided antiemetic treatment (based on the results of SNP analyses) versus standard CINV treatment. Blood samples were taken before the treatment was initiated. Patient-reported data on CINV (during 10 days from onset of cancer treatment) and health-related quality of life (HRQoL), were collected before and after the first cancer treatment. RESULTS: A total of 188 women were included. Overall, nausea was reported by 86% (n=129) of the patients during the ten-day period from the start of cancer treatment. The SNP genotype studied varied. In FAS-CD95, the genotypes AG and GG were overrepresented; in RB1-LPAR6, GG was overrepresented, and in CCL2, both AA and GG were overrepresented. We found no statistically significant difference in CINV between SNP-guided antiemetic treatment versus standard CINV treatment. CONCLUSION: SNP-guided antiemetic treatment could be as effective as standard treatment. SNP-guided antiemetic treatment of CINV is possibly useful in detecting patients with a higher or lower risk for CINV and thus may help in avoiding over-treatment with toxic components. CINV negatively affects the HRQL.
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Antieméticos , Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/induzido quimicamente , Polimorfismo de Nucleotídeo Único , Qualidade de Vida , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Fluoruracila/efeitos adversos , Antineoplásicos/uso terapêutico , Receptores de Ácidos LisofosfatídicosRESUMO
Background: Sleep disruption is known to be highly prevalent in cancer patients, aggravated during oncological treatment and closely associated with reduced quality of life, therapeutic outcome and survival. Inflammatory factors are associated with sleep disruption in healthy individuals and cancer patients, but heterogeneity and robustness of inflammatory factors associated with sleep disruption and how these are affected by oncological therapy remain poorly understood. Furthermore, due to the complex crosstalk between sleep-, and therapy-associated factors, including inflammatory factors, there are currently no established biomarkers for predicting sleep disruption in patients undergoing oncological therapy. Methods: We performed a broad screen of circulating biomarkers with immune-modulating or endocrine functions and coupled these to self-reported sleep quality using the Medical Outcomes Study (MOS) sleep scale. Ninety cancer patients with gastrointestinal, urothelial, breast, brain and tonsillar cancers, aged between 32 and 86 years, and scheduled for adjuvant or palliative oncological therapy were included. Of these, 71 patients were evaluable. Data was collected immediately before and again 3 months after onset of oncological therapy. Results: Seventeen among a total of 45 investigated plasma proteins were found to be suppressed in cancer patients exhibiting sleep disruption prior to treatment onset, but this association was lost following the first treatment cycle. Patients whose sleep quality was reduced during the treatment period exhibited significantly increased plasma levels of six pro-inflammatory biomarkers (IL-2, IL-6, IL-12, TNF-a, IFN-g, and GM-CSF) 3 months after the start of treatment, whereas biomarkers with anti-inflammatory, growth factor, immune-modulatory, or chemokine functions were unchanged. Conclusion: Our work suggests that biomarkers of sleep quality are not valid for cancer patients undergoing oncological therapy if analyzed only at a single timepoint. On the other hand, therapy-associated increases in circulating inflammatory biomarkers are closely coupled to reduced sleep quality in cancer patients. These findings indicate a need for testing of inflammatory and other biomarkers as well as sleep quality at multiple times during the patient treatment and care process.
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Background: Head and neck squamous cell carcinoma (HNSCC) is a disease involving genetic and lifestyle risk factors such as smoking or high-risk papillomavirus (HR-HPV) infections.Objective: This study analyzed 92 single nucleotide polymorphisms (SNPs) associated with smoking and HPV on HNSCC cancer risk and survival among HNSCC patients.Material and methods: Eighty-six HNSCC patients (48 non-smoking and 38 smoking) were consecutively included.Results: Differences were detected in the analysis of survival and SNP genotypes located in the CXCR2 and COMT. Five SNPs in genes PRKDC, TGFb, XRCC1, Cyp2A6 and CTLA4 were found to be different when comparing SNP genotypes in all patients and all controls as a risk of HNSCC. When comparing SNP genotypes among smoking patients and smoking controls, six SNPs in the genes PFR1, IL10, CCL4, IL6, Ku70, and PRF1 were detected. When comparing SNP genotypes, nine SNPs in CHRNA3, PRKDC, CHARNA5, IFN-γ, ESR1, XRCC1, Cyp2A6, CTLA4, and COMT were different in non-smoking patients and non-smoking controls. No association was found between SNP distribution or patient survival and the impact of HR-HPV.Conclusions: The SNPs differed between smokers and non-smokers and could indicate a possible interaction between genetics and smoking. This could play an important role in a better understanding of the pathogenesis of HNSCC.
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Carcinoma de Células Escamosas , Fumar Cigarros , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Polimorfismo de Nucleotídeo Único , Neoplasias de Cabeça e Pescoço/genética , Antígeno CTLA-4/genética , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas/genética , Interleucina-10/genética , Interleucina-6/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genéticaRESUMO
For the women breast cancer (BC) patients included in this retrospective study, the first line of systemic treatment in adjuvant modality for breast cancer (BC) after surgery was fluorouracil, epirubicin and cyclophosphamide (FEC). The aim of our investigation was to analyze the prognostic biomarkers for relapse and death of patients eight to ten years after chemotherapy in association with nausea and vomiting. METHOD: This retrospective study included 114 patients treated between 2010 and 2013. Blood samples for Single Nucleotide Polymorphism (SNP) analysis before the chemotherapy treatment were collected. The medical records were used to determine relapses and death. RESULTS: Sixteen percent relapsed and 9 % died during the follow-up period. SNPs located in the genes ESR and CASP9 were associated with both relapse and death. CONCLUSIONS: Relapse and death were at a relative moderate level and consistent with other studies. Two SNPs in the Estrogen hormone receptor gene ESR1 and the apoptosis execution gene Caspases 9 (Casp9) were found to be associated with a higher risk of relapse and death. These findings suggest the possible value of blood biomarkers in the selection of individual treatments in the clinical setting.
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Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Polimorfismo de Nucleotídeo Único/genética , Assistência ao Convalescente , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Sleep is a basic need that is frequently set aside in modern societies. This leads to profound but complex physiological maladaptations in the body commonly referred to as circadian disruption, which recently has been characterized as a carcinogenic factor and reason for poor treatment outcomes, shortened survival, and reduced quality of life in cancer patients. As sleep and circadian physiology in cancer patients spans several disciplines including nursing science, neurology, oncology, molecular biology and medical technology, there is a lack of comprehensive and integrated approaches to deal with this serious and growing issue and at best a fractionated understanding of only part of the problem among researchers within each of these segments. Here, we take a multidisciplinary approach to comprehensively review the diagnosis and impact of sleep and circadian disruption in cancer patients. We discuss recent discoveries on molecular regulation of the circadian clock in healthy and malignant cells, the neurological and endocrine pathways controlling sleep and circadian rhythmicity, and their inputs to and outputs from the organism. The benefits and drawbacks of the various technologies, devices, and instruments used to assess sleep and circadian function, as well as the known consequences of sleep disruption and how sleep can be corrected in cancer patients, will be analyzed. We will throughout the review highlight the extensive crosstalk between sleep, circadian rhythms, and metabolic pathways involved in malignancy and identify current knowledge gaps and barriers for addressing the issue of sleep and circadian disruption in cancer patients. By addressing these issues, we hope to provide a foundation for further research as well as better and more effective care for the patients in the future.
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Relógios Circadianos , Neoplasias , Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Humanos , Qualidade de Vida , Sono/fisiologiaRESUMO
INTRODUCTION: It has been suggested that age could influence the treatment-induced side effects and survival time of cancer patients. The influence of age on blood-based biomarkers, acute radiation skin reactions (ARSRs), and survival time of breast cancer patients was analysed. MATERIALS AND METHODS: Two hundred ninety-three individuals, 119 breast cancer patients, and 174 healthy blood donors were included. RESULTS: Before radiotherapy (RT), decreased levels of lymphocytes, interleukin 2, platelet-derived growth factors, and tumour necrosis factor but increased levels of monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, C-reactive protein, and macrophage inflammatory protein 1b (MIP1b) were detected in the patient group. All of the patients developed ARSRs and intensity of ARSRs was inversely related to the MIP1b level before RT. Fifteen out of 119 (13%) patients deceased during follow-up time. No influence of age (≤50 compared to >50 years) on survival time was detected (p = 0.442). Tumour recurrence, found in 11 out of 119 (9%) patients, had impact on survival time of these patients (p < 0.001). CONCLUSIONS: The level of circulating MIP1b before RT was associated with intensity of ARSRs. Tumour recurrence, but not age, was associated with poor survival time. Analysis of circulating MIP1b was low cost, rapid, and could be done in routine laboratory facility. Since RT almost always induces ARSRs, the possibility of using MIP1b as a prognostic biomarker for ARSRs is of interests for further investigation.
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Proteínas Adaptadoras de Transdução de Sinal/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Recidiva Local de Neoplasia/mortalidade , Radiodermite/sangue , Radiodermite/etiologia , Radioterapia Adjuvante/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias da Mama/radioterapia , Proteína C-Reativa/análise , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Contagem de Linfócitos , Linfócitos/metabolismo , Pessoa de Meia-Idade , Monócitos , Neutrófilos/metabolismo , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: Cigarette smoke is suggested to be a risk factor for coronary artery disease (CAD), urinary bladder cancer (UBCa) or lung cancer (LCa). However, not all heavy smokers develop these diseases and elevated cancer risk among first-degree relatives suggests an important role of genetic factor. METHODS: Three hundred and ten healthy blood donors (controls), 98 CAD, 74 UBCa and 38 LCa patients were included in this pilot study. The influence of 92 single nucleotide polymorphisms (SNPs) and impact of cigarette smoking were analysed. RESULTS: Out of 92 SNPs tested, differences in distribution of 14 SNPs were detected between controls and patient groups. Only CTLA4 rs3087243 showed difference in both CAD and UBCa patient group compared to control group. Stratified by smoking status, the impact of smoking was associated to frequencies of 8, 3 and 4 SNPs in CAD, UBCa, LCa patients, respectively. None of these 92 SNPs showed a statistically significant difference to more than one type of disease among smoking patients. In non-smoking patients, 7, 3 and 6 SNPs were associated to CAD, UBCa, LCa, respectively. Out of these 92 SNPs, CTLA4 rs3087243 was associated to both non-smoking CAD and UBCa. The XRCC1 rs25487 was associated to both non-smoking UBCa and LCa. CONCLUSION: SNPs might be important risk factors for CAD, UBCa and LCa. Distribution of the SNPs was specific for each patient group, not a random event. Impact of cigarette smoking on the disease was associated to the specific SNP sequences. Thus, smoking individuals with SNPs associated to risk of these serious diseases is an important target group for smoking cessation programs.
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Fumar Cigarros/genética , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Smoking induces inflammation and an immune response. A cancer-related inflammatory response has been seen in smoking and nonsmoking head and neck squamous cell carcinoma (HNSCC) patients. OBJECTIVES: The aim of this study was to analyze the possible separated effects of smoking or HNSCC on 18 inflammatory or immune regulatory biomarkers. METHODS: Fifty-one nonsmoking and 36 smoking pretreated HNSCC patients and 101 nonsmoking and 39 smoking controls were included in this study. The levels of 18 inflammatory or immune regulatory biomarkers were analyzed. A multivariable linear regression model was used to predict the impact of smoking and HNSCC on the levels of the biomarkers. RESULTS: Smoking had the highest impact on total WBC, IFN-γ, and MCP-1 levels. The highest impact of HNSCC was found on neutrophils, neutrophil-to-lymphocyte ratio, HsCRP, MIP-1b, and TNF-α levels. CONCLUSION: IdentifyingHNSCC or smoking-related inflammatory biomarkers might contribute to the understanding of the immune response in HNSCC patients. This study could provide information of inflammatory biomarkers in HNSCC patients.
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Biomarcadores/sangue , Fumar Cigarros , Mediadores da Inflamação/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Fumar Cigarros/efeitos adversos , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Carga Tumoral , Adulto JovemRESUMO
Improving the efficiency of waste-to-energy combined heat and power plants increases their production of both electricity and heat. Economic evaluation of such improvements enables adequate decisions to be made between the various alternatives with respect to economic viability of the plant. In this study, the cost and profitability of different modifications to improve efficiency in a waste-to-energy plant are considered: these include the re-arrangement of air heaters, the introduction of a reheater, flue gas condensation (FGC) and an integrated gasification-combustion process. The base case and the modifications are evaluated and compared when operating either as a combined heat and power plant or as a power plant. Modelling, simulation and cost estimations were performed with the Aspen Plus software. Although the integrated gasification-combustion technology with FGC has the highest exergy efficiency, its higher capital cost is greater than all of the other alternatives. Modification 6, which involves both re-arrangement and changing the air heating medium has the lowest capital cost with respect to enhancing exergy efficiency. Modifications 1 and 7, involving FGC, are the best alternatives for the capital cost per total unit of revenue generated. These modifications not only provides the highest heat production but also the highest net present value (NPV). The base case and the modifications investigated all have positive NPV, indicating that a waste-to-energy combined heat and power plant is an attractive investment. However, an increase of about 122% in the gate fees would be required for a system with only electricity production to be profitable.
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Eliminação de Resíduos , Análise Custo-Benefício , Eletricidade , Temperatura Alta , Centrais ElétricasRESUMO
BACKGROUND/AIM: Adjuvant radiotherapy (RT) damages multiple layers of skin, muscle, blood vessels and blood cells that are included within the RT area. Indirect, bystander systemic effects could also develop in cells not directly hit by radiation. MATERIALS AND METHODS: Ninety-three female patients recovering from breast cancer surgery and 82 female healthy blood donors were analyzed. For identification of systemic adaptive and innate immune response, rapid and low-cost blood-based biomarkers were assayed. RESULTS: Post-operated breast cancer patients had a decreased number of circulating adaptive immune response cells but increased number of circulating immunosuppressive myeloid subpopulations. RT decreased the number of T-cells and platelets without influencing the number of immunosuppressive myeloid subpopulations. Alterations in the number and phenotypes of T-cell subpopulations were associated with SNPs. CONCLUSION: The combination of RT and immunotherapy might provide optimal treatment for cancer patients.
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Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Imunidade Celular/genética , Imunidade Celular/efeitos da radiação , Contagem de Leucócitos , Fenótipo , Polimorfismo de Nucleotídeo Único , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Estudos de Casos e Controles , Feminino , Humanos , Imunidade Inata , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Radioterapia Adjuvante , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Independently of tumour and treatment modulation, the host immune response status plays an important role in the clinical outcome of patients with cancer. The influence of single nucleotide polymorphisms (SNPs) and adjuvant radiotherapy (RT) on the systemic immune response status of patients with breast cancer was investigated. MATERIALS AND METHODS: Eighty-six female patients recovering from breast cancer surgery were investigated. As a control cohort, 82 healthy female blood donors were used. Blood-based SNPs, plasma C-reactive protein (CRP), cytokines and chemokines were analyzed for this purpose. RESULTS: Independently of tumour stage and hormone receptor status, dysregulation of plasma CRP, chemokine (C-C motif) ligand 4 (CCL4) and interleukin 2 (IL2), but not CCL5, CCL2, platelet-derived growth factor, IL6, IL10, IL12, interferon-gamma or tumour necrosis factor alpha were detected in the patients when compared to controls. The extent of alteration in plasma levels of CRP and IL2 patients was significantly associated with SNPs in CRP rs1800947 and IL2 rs6822844, respectively. These SNPs had no influence on the levels of corresponding plasma biomarkers in the healthy controls. Adjuvant RT reduced plasma CRP and CCL5 levels in patients with regards to CRP rs1800947CC, CCL5 rs2107538GG and CCL5 rs2280789AA sequences. CONCLUSION: Dysregulation of immune responses, as indicated by plasma levels of CRP, CCL4 and IL2 were found in patients with breast cancer despite the removal of the tumour mass. The benefit of adjuvant RT, as indicated by reduced plasma amounts of inflammatory protein CRP and chemokine CCL5 were based on the SNPs of the patients. Analyses of blood-based SNPs, plasma CRP, IL2 and CCL5 are low cost, rapid and can be carried out using general laboratory facilities while requiring only a peripheral blood sample. The possibility of using these blood-based biomarkers as an indicator of patient immune status for selection of individual patient treatment warrants further investigation.
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Neoplasias da Mama , Proteína C-Reativa/análise , Citocinas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Proteína C-Reativa/genética , Citocinas/genética , Feminino , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Radioterapia AdjuvanteRESUMO
BACKGROUND: Cigarette smoke induces inflammation and remodels immune response. Genetic and epigenetic alterations might be involved in the pathogenesis of smoking related diseases. In this study, we investigated the effect of smoking on systemic inflammation biomarkers and epigenetic changes at microRNA (miRNA) expression level. We also examined if the levels of inflammatory biomarkers were associated with selected single nucleotide polymorphisms (SNPs). METHOD: From 39 smokers and 101 non-smokers, levels of total white blood cells (WBCs) and its subpopulations, plasma cytokines/chemokines/proteins and miRNAs were analysed. For three biomarkers, C-reactive protein (CRP), MCP-1 and IFN-γ that were affected by smoking, the influence of SNPs was analyzed. RESULT: Elevated levels of total WBCs, neutrophils, monocytes, lymphocytes, CRP, MCP-1, IFN-γ and lower levels of miR-21 were detected in smokers. The elevated levels of IFN-γ in smokers was only statistically significantly associated with rs2069705 AG/GG SNP-genotype. CONCLUSIONS: A lower level of oncomir miRNA-21 and a higher level of immune modelling cytokine IFN-γ detected in smokers could be a protective immune response to cigarette smoke. The higher level of IFN-γ in smokers with a specific SNP genotype also suggests that a genetic interaction with smoking might predict the pathobiology of smoking related disease.
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Biomarcadores/sangue , Fumar Cigarros/sangue , Interferon gama/sangue , MicroRNAs/sangue , Adulto , Idoso , Proteína C-Reativa/metabolismo , Quimiocina CCL2/sangue , Fumar Cigarros/efeitos adversos , Epigênese Genética/efeitos dos fármacos , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Inflamação/sangue , Inflamação/patologia , Leucócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , FumantesRESUMO
Adverse skin reactions during radiotherapy (RT) are common. The aim of this study was to explore whether genetic variation might be linked to acute radiation skin reactions (ARSR). MATERIALS AND METHODS: One hundred and nineteen women undergoing adjuvant RT for breast cancer were included. The symptoms of itching, burning and irritation were self-reported twice using the visual analogue scale. Assessments used the Radiation Therapy Oncology Group scoring system for acute RT skin reaction (RTOG scale). Blood-based single nucleotide polymorphism (SNP) analysis was performed. Thirty SNPs of well-defined functional genes were investigated. RESULTS: All women were assessed with ARSR. After RT, the women self-reported itching (n=97), burning (n=64) and irritation (n=96). Two SNPs in X-Ray Repair Cross Complementing 2 gene (XRCC2) rs2040639 and interferon gamma (IFNG) rs2069705 genes were found to be associated with ARSR. CONCLUSION: An association between two SNPs and ARSR was found. The possibility of using these SNPs as prognostic biomarkers for ARSR as tools to improve the care of patients needs further investigation.
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Neoplasias da Mama/radioterapia , Proteínas de Ligação a DNA/genética , Interferon gama/genética , Polimorfismo de Nucleotídeo Único , Radiodermite/diagnóstico , Radiodermite/genética , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Prognóstico , Radioterapia Adjuvante/efeitos adversosRESUMO
Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important, because not all smokers develop smoking-related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty-four healthy blood donors were recruited, 31 of whom were current smokers and 33 were never-users of tobacco products, references. Compared to references, the smokers showed significantly increased levels of circulating total white blood cells, lymphocytes, monocytes, neutrophils, basophils and C-reactive protein (CRP). Smokers also more frequently exhibited circulating cell phenotypes that are associated with an immunocompromised state: CD8dim cells in the lymphocyte group, CD13+ CD11+ , CD13+ CD14+ , CD13+ CD56+ cells in the monocyte group and CD13+ CD11+ , CD13+ CD56+ cells in the neutrophil group. We observed an interaction among SNPs, smoking status and some of the studied biomarkers. The average plasma CRP level was significantly higher among the smokers, with the highest level found among those with the CRP rs1800947 CC genotype. Additionally, an increased CD8+ GZB+ cells in the CD8dim group were found among smokers with the GZB rs8192917 AA genotype. Thus, smoking appears to be associated with systemic inflammation and increased levels of circulating immunosuppressive cells. The extent of these effects was associated with SNPs among the smokers. This observation may contribute to a better understanding of the genetic susceptibility of smoking-related disease and the variations observed in clinical outcomes.
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Hospedeiro Imunocomprometido/genética , Mediadores da Inflamação/sangue , Inflamação/genética , Polimorfismo de Nucleotídeo Único , Fumar/efeitos adversos , Biomarcadores/sangue , Proteína C-Reativa/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Granzimas/sangue , Granzimas/genética , Voluntários Saudáveis , Humanos , Inflamação/sangue , Inflamação/imunologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Perforina/sangue , Perforina/genética , Fenótipo , Fatores de Risco , Fumar/sangue , Fumar/genética , Fumar/imunologiaRESUMO
Head and neck (H&N) cancer is an aggressive disease and the incidence has increased in younger population worldwide. Tumour TNM staging is the main basis for treatment decision despite significant variation in clinical outcome. Survival time of these patients has marginally improved during the last 30 years. Various biomarkers with cumbersome analysis, high cost, time consumption and requirement of special laboratory facilities have been investigated. However, none of these biomarkers have been shown to be suitable to use for individual H&N cancer patient treatment selection in the clinic. For practical use in clinical settings, the given biomarkers must be simple to analyse, rapid, cost effective and available in routine laboratories. With this intension, we suggested the combination of standard TNM staging and biomarkers associated with inflammation such as neutrophils, neutrophil to lymphocyte ratio, plasma C-reactive protein or plasma tumour necrosis factor alpha (TNFa) and single-nucleotide polymorphism in TNFa rs1800629 using blood-based analysis. The optimal treatment outcome of H&N cancer by using combination of TNM stage and these blood-based biomarkers for individual patient selection need further investigation.
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Biomarcadores Tumorais/sangue , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Humanos , Estadiamento de Neoplasias , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVE: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients. METHODS: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study. RESULTS: Ten SNPs were associated with H&N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNFα) rs1800629 could have an influence on cancer risk, tumor recurrence as well as survival. CONCLUSION: Genetic variation of the TNFα rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of H&N cancer patients.
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Neoplasias de Cabeça e Pescoço/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Feminino , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Women receiving FEC (5 fluorouracil, epirubicin and cyclophosphamide) chemotherapy (CT) for breast cancer (BC) often experience side effects such as nausea and vomiting. Individual variations of side effects occur in patients despite similar cancer therapy. The purpose of this study was to investigate a possible genetic background as a predictor for individual variations in nausea induced by CT. METHODS: 114 women were included in the study. All women received adjuvant CT for BC. Self-reported nausea and vomiting was recorded in a structured diary over ten days following treatment. Blood samples were collected before the treatment and used for the detection of 48 single nucleotide polymorphisms (SNPs) in 43 genes. SNPs from each individual woman were analyzed for their relation to the patient-reported frequency and intensity of nausea and vomiting. RESULTS: Eighty-four percent (n = 96) of the women reported acute or delayed nausea or combined nausea and vomiting during the ten days following CT. Three out of the forty-eight SNPs in the following genes: FAS/CD95, RB1/LPAR6 and CCL2 were found to be associated with a risk of nausea. CONCLUSION: SNPs in the FAS/CD95, RB1/LPAR6 and CCL2 genes were found to be associated with nausea among women treated with adjuvant FEC for BC. SNPs analysis is fast and cost effective and can be done prior to any cancer therapy. The association between individual SNPs and severe side effects from FEC may contribute to a more personalized care of patients with BC.
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PURPOSE: Tumor TNM staging is the main basis for prognosis and treatment decision for head and neck squamous cell carcinoma (HNSCC) despite significant heterogeneity in terms of outcome among patients with the same clinical stage. In this study, a possible role of plasma interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) as biomarkers for survival of HNSCC patients was investigated. METHODS: In this prospective study, plasma levels of IL-2, IL-6, GM-CSF, TNF-α and CRP in patients (n = 100) and controls (n = 48) were analyzed. RESULTS: Significantly elevated levels of CRP and TNF-α (p < 0.001) were found in the patients. Combination of upregulated CRP and TNF-α in the patient plasma was significantly related to shorter patient survival, independent of clinical stage. CONCLUSIONS: Our findings indicate that CRP and TNF-α might be suitable as biomarkers in combination with tumor TNM staging for predicting survival and individualized treatment of HNSCC patients. Plasma CRP and TNF-α analysis are simple, rapid, cost effective and suitable for clinical practice.
Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/mortalidade , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/mortalidade , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Interleucina-2/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Análise de SobrevidaRESUMO
This paper briefly describes waste treatment trends in Sweden and describes an example of state-of-the-art treatment in a local integrated waste treatment system (Borås). The focus is on treatment of household waste, to illustrate what can be done to establish a sustainable waste treatment system with high recovery of materials and energy. The various processes have resulted in a low amount of landfilled household waste, and high proportions of recovered energy and materials. Heat, electricity, vehicle fuel and fertilizers, metals and construction materials are recovered from the local waste in Borås, with less than 4% of domestic waste being sent to landfill.