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1.
Int J Obstet Anesth ; 56: 103931, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37801899

RESUMO

European countries of "Eastern Block" origin took different healthcare and economic development trajectories after the Berlin Wall fell. Despite decreased maternal and neonatal mortality in the last two decades, healthcare disparities exist between the various countries. Minimum standards for obstetric anesthesia are not available for every maternity patient. Lack of equity in access to healthcare for maternity patients is multifactorial and includes differences in systems of care and health economics, and shortages of medical personnel. The war in Ukraine generates additional challenges for healthcare systems in the region, resulting from a significant increase in the number of refugees, some of whom are pregnant and require maternity services, including obstetric anesthesia and analgesia and maternal critical care. The next decade's challenges comprise the implementation of evidence-based medicine advances in the field of obstetric anesthesia and analgesia, and of maternal critical care at national levels, including access to neuraxial opioids, the broad implementation of enhanced recovery after cesarean section protocols, and more frequent use of labor epidural analgesia. Further, there needs to be improvement in medical education provided in the national language, so that healthcare providers, patients, and their families can build and provide a safe environment for maternity patients. In addition, better provision of services and access to healthcare providers who have been well trained and are dedicated to dealing with obstetric patients. These measures will hopefully enhance the quality of care for maternity patients, focusing on further reduction of maternal and neonatal morbidity and mortality, which is a priority and a highly desirable long-term outcome.


Assuntos
Analgesia Epidural , Anestesiologia , Trabalho de Parto , Serviços de Saúde Materna , Recém-Nascido , Gravidez , Feminino , Humanos , Cesárea , Dor
2.
Sci Rep ; 12(1): 7017, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488115

RESUMO

Hyperthermic intravesical chemotherapy (HIVEC)-whereby the bladder is heated to ± 43 °C during a chemotherapy instillation-can improve outcomes of non-muscle invasive bladder cancer (NMIBC) treatments. Experiments in animal models are required to explore new hyperthermia based treatments. Existing HIVEC devices are not suitable for rodents or large-scale animal trials. We present a HIVEC setup compatible with orthotopic rat models. An externally heated chemotherapeutic solution is circulated in the bladder through a double-lumen catheter with flow rates controlled using a peristaltic pump. Temperature sensors in the inflow channel, bladder and outflow channel allow temperature monitoring and adjustments in real-time. At a constant flow rate of 2.5 mL/min the system rapidly reaches the desired bladder temperature of 42-43 °C with minimal variability throughout a one-hour treatment in a rat bladder phantom, as well as in euthanised and live rats. Mean intraluminal bladder temperatures were 42.92 °C (SD = 0.15 °C), 42.45 °C (SD = 0.37 °C) and 42.52 °C (SD = 0.09 °C) in the bladder phantom, euthanised, and live rats respectively. Thermal camera measurements showed homogenous heat distributions over the bladder wall. The setup provides well-controlled thermal dose and the upscaling needed for performing large scale HIVEC experiments in rats.


Assuntos
Hipertermia Induzida , Neoplasias da Bexiga Urinária , Administração Intravesical , Animais , Feminino , Temperatura Alta , Humanos , Masculino , Ratos , Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico
3.
Eur Rev Med Pharmacol Sci ; 24(17): 8889-8892, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32964978

RESUMO

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a slowly growing cancer, which is the most common malignant tumor of the salivary glands. It is claimed that it is a non-inherited cancer. People with family history of ACC are reported extremely rarely. We present patients with suspected hereditary ACC. MATERIALS AND METHODS: Next generation sequencing (NGS) was performed for both RNA and DNA isolated from FFPE material. RESULTS: In DNA from tumor tissue we detected the mutation in MET gene, in exon 14 c.3029C>T (p.Thr1010Ile). It has never been proven that this mutation may play a role in the pathogenesis of ACC. The most important for our case report seems to be the patient's family history of cancer occurrence which indicates presence of familial cancer aggregation (familial cancer syndrome) and even familial lung cancer. CONCLUSIONS: ACC is extremely rare; it is difficult to observe a specific genetic pattern and NGS can provide a lot of information about the genetic causes of this disease. Our work shows that the MET p.Thr1010Ile mutation can be associated with the hereditary occurrence of ACC.


Assuntos
Carcinoma Adenoide Cístico/genética , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas Proto-Oncogênicas c-met/genética , Neoplasias das Glândulas Salivares/genética , Carcinoma Adenoide Cístico/diagnóstico por imagem , DNA de Neoplasias/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias das Glândulas Salivares/diagnóstico por imagem , Tomografia Computadorizada por Raios X
4.
Eur Rev Med Pharmacol Sci ; 23(9): 3857-3866, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31115013

RESUMO

OBJECTIVE: Lung cancer (LC) is diagnosed mostly in advanced, non-operable stage, with poor prognosis. The analysis of microRNAs may be a useful tool for early and non-invasive detection of cancer. Dicer and Drosha are enzymes with an essential role for microRNA biogenesis. The aim of our study was to analyze the expression of miRNA-27a-3p, miRNA-31, miRNA-182, miRNA-195 with the ability to reciprocal regulation of Dicer and Drosha expression in lung cancer patients. PATIENTS AND METHODS: The relative expression of microRNAs was detected by qPCR in plasma of 160 LC patients. The U-Mann Whitney test was used to compare the relative expression between particular groups of lung cancer patients and healthy individuals. The diagnostic value of microRNAs examination was analyzed using a receiver operating curve. RESULTS: We demonstrated that the plasma levels of miRNA-27, miRNA-31 and miRNA-182 were significantly higher and miRNA-195 significantly lower in the whole group of LC patients and in patients with early stages of NSCLC, in comparison with healthy donors. ROC analysis showed that four studied microRNAs have a potential diagnostic value for early stages of NSCLC with AUC=0.95 for miRNA-27a (94% sensitivity and 81% specificity, p=0.0001), 0.71 for miRNA-31 (73% sensitivity and 61% specificity, p=0.001) 0.77 for miRNA-182 (70% sensitivity and 79% specificity, p=0.0001) and 0.82 for miRNA-195 (74% sensitivity and 80% specificity, p=0.0001). CONCLUSIONS: We have proved that the expression of miRNA-27a-3p, miRNA-31, miRNA-182, and miRNA-195 in patients with LC is different from the expression of these molecules in healthy people. The examination of these microRNAs in plasma could be used in non-invasive lung cancer diagnosis.


Assuntos
RNA Helicases DEAD-box/genética , Neoplasias Pulmonares/diagnóstico , MicroRNAs/metabolismo , Ribonuclease III/genética , Idoso , Área Sob a Curva , RNA Helicases DEAD-box/metabolismo , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Curva ROC , Ribonuclease III/metabolismo , Sensibilidade e Especificidade
5.
Artigo em Inglês | MEDLINE | ID: mdl-29687446

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become the treatment of choice for severely hypothermic patients in cardiac arrest or acute cardiac failure. Highly specialized ECMO centres have been established, however, no centre has ever reported the costs of extracorporeal rewarming. The aim of this study was to assess the costs of the treatment of patients in Swiss Stage III and IV rewarmed with veno-arterial ECMO. METHODS: A retrospective exploratory cohort study analysed twenty-nine consecutive patients treated for hypothermia in the Severe Accidental Hypothermia Centre in Cracow, Poland. The main outcome parameters were the overall and specific costs of the ICU treatment of patients rewarmed with veno-arterial ECMO. The secondary outcome parameter was cost utility, determined by the costs involved for every year of life gained. Costs were processed using the bottom-up method and classified into six categories. Survivors were followed up after 1 year. RESULTS: The mean cost of VA-ECMO was $5133 USD, which equalled 35% of all ICU expenditures ($14 668 USD). One year after discharge, 13 of 29 patients were still alive (45%). The overall gain of life of the thirteen 1-year survivors was 28 years, while the mean cost related to treatment with VA-ECMO for each year of life gained was 1138 USD. CONCLUSIONS: In this study, the costs of VA-ECMO rewarming and intensive care treatment per patient were substantially lower than in other studies reporting ECMO and intensive care treatment of other causes.

6.
RSC Adv ; 8(34): 19237, 2018 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-35543966

RESUMO

[This corrects the article DOI: 10.1039/C7RA01678F.].

7.
Clin. transl. oncol. (Print) ; 19(12): 1447-1453, dic. 2017. tab
Artigo em Inglês | IBECS | ID: ibc-168906

RESUMO

Purpose. RT-PCR technique has showed a promising value as pre-screening method for detection of mRNA containing abnormal ALK sequences, but its sensitivity and specificity is still discussable. Previously, we determined the incidence of ALK rearrangement in CNS metastases of NSCLC using IHC and FISH methods. Materials. We evaluated ALK gene rearrangement using two-step RT-PCR method with EML4-ALK Fusion Gene Detection Kit (Entrogen, USA). The studied group included 145 patients (45 females, 100 males) with CNS metastases of NSCLC and was heterogeneous in terms of histology and smoking status. Results. 21% of CNS metastases of NSCLC (30/145) showed presence of mRNA containing abnormal ALK sequences. FISH and IHC tests confirmed the presence of ALK gene rearrangement and expression of ALK abnormal protein in seven patients with positive result of RT-PCR analysis (4.8% of all patients, 20% of RT-PCR positive patients). RT-PCR method compared to FISH analysis achieved 100% of sensitivity and only 82.7% of specificity. IHC method compared to FISH method indicated 100% of sensitivity and 97.8% of specificity. In comparison to IHC, RT-PCR showed identical sensitivity with high number of false positive results. Conclusion. Utility of RT-PCR technique in screening of ALK abnormalities and in qualification patients for molecularly targeted therapies needs further validation (AU)


No disponible


Assuntos
Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/secundário , Reação em Cadeia da Polimerase em Tempo Real/métodos , Imuno-Histoquímica/métodos , Rearranjo Gênico/genética , Linfoma Anaplásico de Células Grandes/genética
9.
Scand J Immunol ; 86(3): 130-134, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28675453

RESUMO

Lung cancer (LC) is the most common cause of cancer death in the world. A great challenge in treating NSCLC is the discovery of advanced, molecular tools to diagnose the disease in early stages as well as the development of immunotherapy. MicroRNAs are regulatory molecules (~20 nt in length) with the ability to regulate the expression of genes. The recently described PD-1 and PD-L1 molecules have great importance for potential use in immunotherapy of many cancers. These molecules are associated with immune checkpoints and provide an opportunity for the treatment of advanced NSCLC patients with synthetic monoclonal antibodies. PD-L1 expression is strictly associated with microRNA function in lung cancer cells. The group of microRNAs related to PD-L1 includes, among others, miR-200, miR-197 or miRNA-34. Expression of these molecules may be useful in lung cancer diagnosis, qualification to anti-PD-1 or anti-PD-L1 antibody therapy and could be a potential therapeutic target. However, studies on PD-L1-related microRNAs are necessary to develop advanced targeted molecular therapies.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/metabolismo , Imunoterapia/tendências , Neoplasias Pulmonares/imunologia , MicroRNAs , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/terapia , Ativação Linfocitária , Terapia de Alvo Molecular , Receptor de Morte Celular Programada 1/metabolismo , Evasão Tumoral
10.
Clin Transl Oncol ; 19(12): 1447-1453, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28534101

RESUMO

PURPOSE: RT-PCR technique has showed a promising value as pre-screening method for detection of mRNA containing abnormal ALK sequences, but its sensitivity and specificity is still discussable. Previously, we determined the incidence of ALK rearrangement in CNS metastases of NSCLC using IHC and FISH methods. MATERIALS: We evaluated ALK gene rearrangement using two-step RT-PCR method with EML4-ALK Fusion Gene Detection Kit (Entrogen, USA). The studied group included 145 patients (45 females, 100 males) with CNS metastases of NSCLC and was heterogeneous in terms of histology and smoking status. RESULTS: 21% of CNS metastases of NSCLC (30/145) showed presence of mRNA containing abnormal ALK sequences. FISH and IHC tests confirmed the presence of ALK gene rearrangement and expression of ALK abnormal protein in seven patients with positive result of RT-PCR analysis (4.8% of all patients, 20% of RT-PCR positive patients). RT-PCR method compared to FISH analysis achieved 100% of sensitivity and only 82.7% of specificity. IHC method compared to FISH method indicated 100% of sensitivity and 97.8% of specificity. In comparison to IHC, RT-PCR showed identical sensitivity with high number of false positive results. CONCLUSION: Utility of RT-PCR technique in screening of ALK abnormalities and in qualification patients for molecularly targeted therapies needs further validation.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias do Sistema Nervoso Central/secundário , Rearranjo Gênico , Receptores Proteína Tirosina Quinases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Quinase do Linfoma Anaplásico , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias do Sistema Nervoso Central/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
11.
Int J Hyperthermia ; 33(4): 419-427, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28100096

RESUMO

Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells (CSCs), is considered to be of particular significance for tumour initiation, progression and metastasis. CSCs are considered in particular to be therapy-resistant and may drive disease recurrence, which positions CSCs in the focus of anti-cancer research, but successful CSC-targeting therapies are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising radiation and chemotherapy are least effective. Second, hyperthermia can modify factors that are essential for tumour survival and growth, such as the microenvironment, immune responses, vascularisation and oxygen supply. Third, hyperthermia targets multiple DNA repair pathways, which are generally upregulated in CSCs and protect them from DNA-damaging agents. Addition of hyperthermia to the therapeutic armamentarium of oncologists may thus be a promising strategy to eliminate therapy-escaping and -resistant CSCs.

12.
J Dent Res ; 96(4): 430-436, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27941125

RESUMO

Cellular adhesion is essential for successful integration of dental implants. Rapid soft tissue integration is important to create a seal around the implant and prevent infections, which commonly cause implant failure and can result in bone loss. In addition, soft tissue management is important to obtain good dental aesthetics. We previously demonstrated that the salivary peptide histatin 1 (Hst1) causes a more than 2-fold increase in the ability of human adherent cells to attach and spread on a glass surface. Cells treated with Hst1 attached more rapidly and firmly to the substrate and to each other. In the current study, we examine the potential application of Hst1 for promotion of dental implant integration. Our results show that Hst1 enhances the attachment and spreading of soft tissue cell types (oral epithelial cells and fibroblasts) to titanium (Ti) and hydroxyapatite (HAP), biomaterials that have found wide applications as implant material in dentistry and orthopedics. For improved visualization of cell adhesion to Ti, we developed a novel technique that uses sputtering to deposit a thin, transparent layer of Ti onto glass slides. This approach allows detailed, high-resolution analysis of cell adherence to Ti in real time. Furthermore, our results suggest that Hst1 has no negative effects on cell survival. Given its natural occurrence in the oral cavity, Hst1 could be an attractive agent for clinical application. Importantly, even though Hst1 is specific for saliva of humans and higher primates, it stimulated the attachment and spreading of canine cells, paving the way for preclinical studies in canine models.


Assuntos
Adesão Celular/efeitos dos fármacos , Implantes Dentários , Durapatita/química , Histatinas/farmacologia , Titânio/química , Animais , Células Cultivadas , Cães , Fibroblastos/citologia , Gengiva/citologia , Humanos , Camundongos , Microscopia de Fluorescência , Propriedades de Superfície
13.
Clin. transl. oncol. (Print) ; 18(10): 1039-1043, oct. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-155968

RESUMO

Background: The mitogen-activated protein kinases 1 and 2 (MEK1, MEK2) are fundamental partners in the RAS-RAF-MEK-ERK pathway that is involved in regulation of cell proliferation, differentiation and survival. Downregulation of the MEK cascades has been implicated in acquiring of the malignant phenotype in various cancers. Somatic mutations in MEK1 gene (substitutions K57N, Q56P, D67N) were described in < 1 % of non-small cell lung cancer (NSCLC) and they were more commonly reported in adenocarcinoma patients with current or former smoking status. Materials and methods: In the following study, we assessed the MEK1 gene mutations in 145 FFPE tissue samples from central nervous system (CNS) metastases of NSCLC using HRM-PCR and ASP-qPCR techniques. The studied group was heterogeneous in terms of histopathology and smoking status. The prevalence of the MEK1 gene mutation was correlated with the occurrence of mutations in KRAS, EGFR, DDR2, PIK3CA, NRAS, HER2, AKT1 and PTEN genes. Results: Using HRM and ASP-qPCR methods we identified one (0.7 %; 1/145) MEK1 substitution (Q56P) in CNS metastases of NSCLC. The mutation was identified in a single, 50-year-old, current smoking men with adenocarcinoma (1.25 %; 1/80 of all adenocarcinomas). Conclusions: According to the current knowledge, the incidence of MEK1 gene mutation in CNS metastatic lesion of NSCLC is the first such report worldwide. The analysis of gene profile in cancer patients may extend the scope of molecularly targeted therapies used both in patients with primary and metastatic tumors of NSCLC (AU)


No disponible


Assuntos
Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Neoplasias do Sistema Nervoso Central/patologia , Metástase Neoplásica/patologia , Proteína Quinase 1 Ativada por Mitógeno/análise
14.
Clin. transl. oncol. (Print) ; 18(9): 915-924, sept. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-155506

RESUMO

Purpose: Chemotherapy with platinum compounds and gemcitabine is frequently used in first-line treatment of advanced non-small cell lung cancer (NSCLC) patients in which tyrosine kinase inhibitors (EGFR or ALK) cannot be administered. Unfortunately, less than half of the patients achieve the benefit from chemotherapy. Gemcitabine is an analog of deoxycytidine (pyrimidine antimetabolite) with antitumor activity. The excess of deoxycytidine synthesized by RRM1 enzyme activity may be a cause of competitive displacement of gemcitabine, which reduces the efficacy of this cytostatic. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) of the RRM1 promoter (-37C[A, -524C[T) and the effectiveness of first-line chemotherapy based on platinum compounds and gemcitabine in NSCLC PATIENTS: PATIENTS AND METHODS: SNPs were determined by SNaPshot PCR in DNA isolated from peripheral blood of 91 NSCLC PATIENTS: RESULTS: The median progression-free survival (PFS) was significantly longer in carriers of AA (-37C[A) as well as CC (-524C[T) genotype of RRM1 compared to patients with other genotypes (10.5 vs 3.5 months, p = 0.0437; HR = 2.17, 95 % CI 1.02-4.62 and 10.5 vs 3.5 months, p = 0.0343; HR = 2.12, 95 % CI 1.06-4.27). In addition, the CC genotype carriers (-37C[A) showed a significant increase in the risk of shortening overall survival (OS) in comparison to patients with AA or AC genotypes (9.5 vs 18 months, p = 0.0193; HR = 2.13, 95 % CI 1.13-4.03). CONCLUSIONS: Presence of rare AA (-37C[A) and CC (-524C[T) genotypes of the RRM1 may be favorable predictive factors for chemotherapy with platinum compounds and gemcitabine in NSCLC patients


No disponible


Assuntos
Humanos , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , /análise , Compostos de Platina/uso terapêutico , Nucleosídeos/uso terapêutico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Polimorfismo Genético
15.
Clin. transl. oncol. (Print) ; 18(4): 398-404, abr. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-150455

RESUMO

Introduction: The possibility of detection of suppressor genes methylation in circulating free DNA (cf-DNA) of cancer patients and the lack of methylation in healthy individuals makes this epigenetic alternation an ideal diagnostic marker of neoplastic processes. Moreover, hypermethylation in several genes promoter was described as a biomarker of lung cancer. Methylation in the gene encoding doublecortin-like kinase 1 (DCLK1) is observed in patients with colorectal cancer and cholangiocarcinoma. However, there are no studies concerning DCLK1 methylation in lung cancer patients. The aims of the study was to evaluate the frequency of DCLK1 promoter methylation in cf-DNA of lung cancer patients and of healthy persons as well as the usefulness of this test for predicting the lung cancer course. Materials and methods: DCLK1 methylation status was evaluated in DNA isolated from peripheral blood plasma from 65 lung cancer patients and 95 healthy individuals. After DNA bisulfitation, DCLK1 methylation was determined using the qMSP-PCR technique. Moreover, the presence of DCLK1 methylation was correlated with the overall survival (OS) probability of lung cancer patients. Results: DCLK1 promoter methylation was detected in 32 lung cancer patients (49.2 %) and 8 healthy individuals (8.4 %). The methylation of the region before transcription start site (TSS) and the region after TSS of DCLK1 gene was detected in 28 and 11 patients, respectively. In seven cases (10.8 %), the DCLK1 promoter methylation in both regions was reported simultaneously. The methylation was observed slightly frequently in patients with small cell lung cancer (75 % of SCLC patients). The median overall survival of patients with DCLK1 promoter methylation was lower than that of patients without DCLK1 gene modification (p = < 0.001, HR = 4.235). Conclusions: The evaluation of DCLK1 promoter region methylation may be useful in both early diagnosis and prediction of the course of lung cancer (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metilação , Metilação/efeitos da radiação , Metilação de DNA/genética , Metilação de DNA/efeitos da radiação , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/genética , Poluição por Fumaça de Tabaco/efeitos adversos , Fumar/efeitos adversos , Fumar/patologia , MicroRNAs/genética
17.
Clin Transl Oncol ; 18(10): 1039-43, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26860843

RESUMO

BACKGROUND: The mitogen-activated protein kinases 1 and 2 (MEK1, MEK2) are fundamental partners in the RAS-RAF-MEK-ERK pathway that is involved in regulation of cell proliferation, differentiation and survival. Downregulation of the MEK cascades has been implicated in acquiring of the malignant phenotype in various cancers. Somatic mutations in MEK1 gene (substitutions K57N, Q56P, D67N) were described in <1 % of non-small cell lung cancer (NSCLC) and they were more commonly reported in adenocarcinoma patients with current or former smoking status. MATERIALS AND METHODS: In the following study, we assessed the MEK1 gene mutations in 145 FFPE tissue samples from central nervous system (CNS) metastases of NSCLC using HRM-PCR and ASP-qPCR techniques. The studied group was heterogeneous in terms of histopathology and smoking status. The prevalence of the MEK1 gene mutation was correlated with the occurrence of mutations in KRAS, EGFR, DDR2, PIK3CA, NRAS, HER2, AKT1 and PTEN genes. RESULTS: Using HRM and ASP-qPCR methods we identified one (0.7 %; 1/145) MEK1 substitution (Q56P) in CNS metastases of NSCLC. The mutation was identified in a single, 50-year-old, current smoking men with adenocarcinoma (1.25 %; 1/80 of all adenocarcinomas). CONCLUSIONS: According to the current knowledge, the incidence of MEK1 gene mutation in CNS metastatic lesion of NSCLC is the first such report worldwide. The analysis of gene profile in cancer patients may extend the scope of molecularly targeted therapies used both in patients with primary and metastatic tumors of NSCLC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias do Sistema Nervoso Central/genética , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/genética , MAP Quinase Quinase 1/genética , Mutação/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias do Sistema Nervoso Central/secundário , Detecção Precoce de Câncer/métodos , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real
18.
Clin. transl. oncol. (Print) ; 18(2): 125-131, feb. 2016. tab
Artigo em Inglês | IBECS | ID: ibc-148216

RESUMO

Introduction. Platinum-based chemotherapy and 3rd generation drugs is still the main treatment option for advanced non-small cell lung cancer (NSCLC) patients without activating EGFR mutations or ALK rearrangements. However, the side effects associated with cytostatics are well known. Changes in the genes (e.g. single nucleotide polymorphisms, SNPs) encoding proteins regulating DNA repair or cell division could potentially influence on both the susceptibility of cancer cells to chemotherapy, and the occurrence of toxicities. Materials and methods. In presented study, the relationship between the fourteen SNPs in nine DNA repair and cell division regulating genes: ERCC1, XPD, XPA, XPC, XRCC1, XPG, RRM1, BRCA1, STMN1 and the toxicity of first-line chemotherapy in NSCLC patients were investigated. SNPs were determined by SNaPshot PCR® in DNA isolated from peripheral blood of 55 NSCLC patients treated with platinum compound and vinorelbine. The toxicity of therapy was evaluated according to the Common Toxicity Criteria (CTC) Version 4.03. Results. The odds ratio (OR) of severe haematological toxicity was significantly lower in carriers of the T allele of XRCC1 gene (1196A > G, OR = 0.22, 95 % CI: 0.06-0.82, p = 0.018) and higher in the carriers of the T allele (2704C > A) of XPC gene (OR: 7.50, 95 % CI: 0.89-63.17, p = 0.036) compared to the remaining patients. Risk of severe hepatotoxicity was significantly lower in carriers of the C allele of STMN1 (−2166T > C, OR = 0.09, 95 % CI: 0.01-1.12, p = 0.025) than in patients with T allele of this gene. In carriers of G allele (2251A > C, OR: 0.24, 95 % CI: 0.07-0.81, p = 0.017) and T (934G > A, OR: 0.26, 95 % CI: 0.07-0.90, p = 0.029) of XPD gene, risk of severe nephrotoxicity was significantly lower than in other patients. Conclusions. Selected SNPs of genes encoding DNA repair enzymes and cell division regulation proteins could be useful biomarkers for prediction of platinum and vinorelbine-based chemotherapy toxicity in patients with advanced NSCLC (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/métodos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Trato Gastrointestinal/metabolismo , Preparações Farmacêuticas/administração & dosagem , Terapêutica/métodos , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Estudos Retrospectivos , Trato Gastrointestinal/anormalidades , Preparações Farmacêuticas , Terapêutica/instrumentação
19.
Clin. transl. oncol. (Print) ; 18(1): 33-39, ene. 2016. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-148049

RESUMO

Purpose. Second-line chemotherapy of advanced non-small cell lung cancer (NSCLC) with docetaxel or pemetrexed allows to achieve objective response rate only in 5-10 % of patients. Recent studies have shown that single nucleotide polymorphisms (SNPs) in genes encoding proteins which regulate dynamics of microtubules may be considered as predictive factors of response to taxane-based chemotherapy. STMN1 gene encodes stathmin 1, which plays role in cell division by regulation of microtubules epolarisation, and this process may be associated with taxanes’ effectiveness. Materials and methods. Using HRM-PCR technique, we evaluated the −2166C>T SNP of STMN1 gene in DNA from peripheral blood leucocytes of 54 advanced NSCLC patients treated in second-line monotherapy with docetaxel or paclitaxel. Results. Patients with TT genotype of STMN1 gene demonstrated significantly longer progression-free survival (PFS) and the lower risk of early disease progression after second-line treatment compared to patients with other STMN1 genotypes (median PFS: 7 and 2 months; p = 0.0154; HR = 0.371; 95 % CI 0.184-0.743). Early disease progression during second-line chemotherapy was significantly more frequently observed in patients with CC genotype of STMN1 in contrast to patients with presence of T allele (median PFS: 2 and 4 months; p = 0.0385; HR = 1.776; 95 % CI 0.905-3.445). Conclusion. Only selected NSCLC patients could benefit from second-line chemotherapy. Therefore, investigations of novel predictive molecular factors for proper qualification of patients to second-line taxane-based chemotherapy are justified. Studied SNP of STMN1 gene may have potential predictive role in such therapy (AU)


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Assuntos
Humanos , Masculino , Feminino , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/métodos , Nucleotídeos/administração & dosagem , Nucleotídeos/metabolismo , Buffy Coat/citologia , Buffy Coat/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Sobrevivência/fisiologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/classificação , Nucleotídeos/farmacologia , Buffy Coat/classificação , Buffy Coat/fisiologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Sobrevivência/psicologia , Estudos Retrospectivos
20.
Clin Transl Oncol ; 18(1): 33-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26148901

RESUMO

PURPOSE: Second-line chemotherapy of advanced non-small cell lung cancer (NSCLC) with docetaxel or pemetrexed allows to achieve objective response rate only in 5-10 % of patients. Recent studies have shown that single nucleotide polymorphisms (SNPs) in genes encoding proteins which regulate dynamics of microtubules may be considered as predictive factors of response to taxane-based chemotherapy. STMN1 gene encodes stathmin 1, which plays role in cell division by regulation of microtubules depolarisation, and this process may be associated with taxanes' effectiveness. MATERIALS AND METHODS: Using HRM-PCR technique, we evaluated the -2166C>T SNP of STMN1 gene in DNA from peripheral blood leucocytes of 54 advanced NSCLC patients treated in second-line monotherapy with docetaxel or paclitaxel. RESULTS: Patients with TT genotype of STMN1 gene demonstrated significantly longer progression-free survival (PFS) and the lower risk of early disease progression after second-line treatment compared to patients with other STMN1 genotypes (median PFS: 7 and 2 months; p = 0.0154; HR = 0.371; 95 % CI 0.184-0.743). Early disease progression during second-line chemotherapy was significantly more frequently observed in patients with CC genotype of STMN1 in contrast to patients with presence of T allele (median PFS: 2 and 4 months; p = 0.0385; HR = 1.776; 95 % CI 0.905-3.445). CONCLUSION: Only selected NSCLC patients could benefit from second-line chemotherapy. Therefore, investigations of novel predictive molecular factors for proper qualification of patients to second-line taxane-based chemotherapy are justified. Studied SNP of STMN1 gene may have potential predictive role in such therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Estatmina/genética , Taxoides/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Progressão da Doença , Docetaxel , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do Tratamento
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