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1.
Anal Chem ; 94(25): 8928-8936, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35713244

RESUMO

We present a novel combination of a metal oxide laser ionization mass spectrometry imaging (MOLI MSI) technique with off-line lipid derivatization by ozone for the detection of fatty acids (FA) and their carbon-carbon double bond (C═C) positional isomers in biological tissues. MOLI MSI experiments were realized with CeO2 and TiO2 nanopowders using a vacuum matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometer in the negative mode. The catalytic properties of these metal oxides allow FA cleavage from phospholipids under UV laser irradiation. At the same time, fragile ozonides produced at the sites of unsaturation decomposed, yielding four diagnostic ions specific for the C═C positions. Advantageously, two MOLI MSI runs from a single tissue sprayed with the metal oxide suspension were performed. The first run prior to ozone derivatization revealed the distribution of FAs, while the second run after the reaction with ozone offered additional information about FA C═C isomers. The developed procedure was demonstrated on MSI of a normal mouse brain and human colorectal cancer tissues uncovering the differential distribution of FAs down to the isomer level. Compared to the histological analysis, MOLI MSI showed the distinct distribution of specific FAs in different functional parts of the brain and in healthy and cancer tissues pointing toward its biological relevance. The developed technique can be directly adopted by laboratories with MALDI TOF analyzers and help in the understanding of the local FA metabolism in tissues.


Assuntos
Ácidos Graxos , Ozônio , Animais , Carbono/química , Ácidos Graxos/análise , Lasers , Camundongos , Óxidos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
2.
Vnitr Lek ; 66(7): 26-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380131

RESUMO

The aim of this retrospective study is to evaluate our experience with diagnostic and therapeutic endoscopic retrograde cholangiopancreaticography (ERCP) in patients after choledochoduodenoanastomosis. METHODS: The study took 20 years (November 1994 - December 2014). Three patients after choledochoduodenoanastomosis who had symptoms of biliary obstruction were retrospectively evaluated. In all cases, a standard therapeutic videolateroscope was used to perform ERCP. PATIENTS AND RESULTS: We achieved ERCP in these 3 patients with choledochoduodenoanastomosis 100% cannulation success rate - 3 out of 3 patients. This was 100% success rate of diagnostic ERCP. In all of these patients, ERCP was found - both stenosis of the natural mouth of the Vater papilla, stenosis of choledochoduodenoanastomosis, and suprastenotic distal choledocholithiasis. In all patients with the above-described ERCP pathology, endoscopic treatment was initiated immediately after diagnostic ERCP, consisting of standard endoscopic papillotomy of the stenotic Vater papilla, balloon dilatation of choledochoduodenoanastomosis stenosis, and endoscopic extraction of suprastenotic distal choledocholithiasis. In total, therapeutic ERCP was completely successful in all 3 patients out of 3 (100%) who had initially started endoscopic treatment. There were no complications in our group of 3 patients. CONCLUSION: In ERCP in patients after choledochoduodenoanastomosis, we achieved 100% success of both diagnostic and therapeutic ERCP in all of our 3 patients.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Colestase , Cateterismo , Humanos , Estudos Retrospectivos , Esfinterotomia Endoscópica , Resultado do Tratamento
3.
Chem Rev ; 116(3): 771-85, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26761074

RESUMO

After a brief survey of conventional radical polymerization of alkenes, we review their Li(+) catalyzed radical polymerization and their controlled radical polymerization. Emphasis is on homopolymerization, but related copolymerization of less activated monomers is mentioned as well.

4.
Vnitr Lek ; 63(9): 572-579, 2017.
Artigo em Tcheco | MEDLINE | ID: mdl-29120653

RESUMO

Thyroid carcinoma (TC) represents 1-2 % of all human tumors, and is the seventh most common tumor. Women are in large majority among new patients. For women, this is the fifth most common tumor. In the Czech Republic, 1 143 new cases of TC were diagnosed in 2015. It is the tumor with the highest increase in incidence. Among newly diagnosed tumors, most of those are differentiated thyroid gland carcinomas (DTCs) originating from follicular thyroid cells. These tumors are follicular and papillary carcinomas and Hurthle carcinoma, accounting for 95 % of new cases. Due to the great progress in treatment, the prognosis is most commonly good for these tumors. Treatment is more difficult for other types of tumors. Anaplastic thyroid cancer (representing less than 1 % of thyroid tumors) is a rare form of thyroid cancer that is very malignant. Also found in the thyroid gland is Euro-C-cell tumor, which originates in C cells. This is the so-called medullary thyroid carcinoma, which is less common (5 % of all thyroid carcinomas). It emerges from the parapolyclic neuroendocrine cells of the thyroid gland. This tumor often metastasizes to the cervical lymph nodes, and frequently occurs in distant bone, liver and lung metastases. In 2015, in this publication we published an article: Thyroid gland carcinomas, current therapeutic procedures. This article was devoted to the diagnosis of thyroid carcinoma and individual treatment procedures. In this article, we look at differentiated thyroid carcinomas (DTCs), especially current opinions on the treatment of low-risk carcinomas.Key words: differentiated thyroid cancer - radioidine - targeted therapy.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Estadiamento de Neoplasias , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia
5.
Tumour Biol ; 37(8): 10723-9, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26873484

RESUMO

The MYB gene codes for the c-Myb transcription factor maintaining proliferation of colon epithelial progenitors, thus controlling colon development and homeostasis. This gene is overexpressed in early phases of colorectal cancer (CRC) tumorigenesis. The aim of this study was to examine the expression of c-Myb in CRC tissue samples both at the messenger RNA (mRNA) and protein levels and to evaluate their associations with clinicopathological characteristics in a group of 108 CRC patients. Statistically significant negative association was found between the frequency of the c-Myb-positive tumor cells assessed by immunohistochemistry and the presence of distant metastases (p < 0.01) but not tumor differentiation, tumor stage, lymph node involvement, vascular invasion, tumor localization, age, and gender of the patients. Although the c-Myb protein level in the tumor tissue correlated with its mRNA level, no significant association between MYB mRNA and any clinicopathological characteristics was observed. We conclude that albeit overexpression of c-Myb is considered as an important factor contributing to early phases of CRC tumorigenesis, it may later have negative effect on tumor cell dissemination as observed recently in breast cancer as well. Further studies are required to explain the role of c-Myb during formation of CRC distant metastases.


Assuntos
Adenocarcinoma/secundário , Neoplasias Colorretais/genética , Genes myb , Proteínas de Neoplasias/biossíntese , Proteínas Proto-Oncogênicas c-myb/biossíntese , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Neoplasias Colorretais/patologia , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-myb/genética , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese
6.
Vnitr Lek ; 62(9 Suppl 3): 115-120, 2016.
Artigo em Tcheco | MEDLINE | ID: mdl-27734703

RESUMO

Incidence of differentiated thyroid carcinomas, especially papillary carcinomas, in recent decades worldwide increase. This is especially the detection of small tumor sizes up to two centimeters. Causes of the increase of these cancers are either increased number of thyroid investigations, but also the actual increase of this disease. The subject of expert discussion on this topic is mainly assessment of the severity of newly diagnosed tumors, the choice of treatment strategy and choice of follow-up of patients. Given that a large part of tumor detected in an early stage and due to the success of the current treatment options for the prognosis of thyroid cancer is usually good. Despite the large increase of the incidence, mortality for this type of cancer, in countries with good individualized treatment, decreases. We present a review of literature on the topic.Key words: thyroid carcinoma - post-operation monitoring - radioiodine - stratification of the risk of relapse.


Assuntos
Carcinoma/terapia , Radioisótopos do Iodo/uso terapêutico , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Assistência ao Convalescente , Carcinoma/epidemiologia , Carcinoma Papilar , Detecção Precoce de Câncer , Intervenção Médica Precoce , Humanos , Incidência , Prognóstico , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/epidemiologia
7.
Vnitr Lek ; 62(9 Suppl 3): 40-44, 2016.
Artigo em Tcheco | MEDLINE | ID: mdl-27734690

RESUMO

Thyroid cancer is the main endocrine malignancy. Its incidence is steadily growing and what is alarming is its increase in children and adolescent population. Pediatric thyroid carcinomas differ from the adult ones in phenotype as well as in genetics. These carcinomas tend to be clinically more aggressive, with more frequent local and distant metastases. However, their long-term prognosis is better in comparison with the adult thyroid cancers. Due to the rarity of the disease, there is lack of data on genetic changes in this age group. Knowledge on the genetic background of thyroid cancer in children will help to precise diagnosis and prognosis of the disease and to personalized treatment.Key words: adolescents - carcinoma - gene - genetics - children - mutation - next generation sequencing - thyroid.


Assuntos
Carcinoma/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Carcinoma/epidemiologia , Carcinoma/metabolismo , Criança , Feminino , Patrimônio Genético , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Incidência , Masculino , Mutação , Prognóstico , Análise de Sequência de DNA , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/metabolismo
8.
Cas Lek Cesk ; 154(1): 11-3, 2015.
Artigo em Tcheco | MEDLINE | ID: mdl-25994822

RESUMO

Anal fissure is one of the very frequent and painful proctologic diseases. Linear ulcer is situated in the anal canal and extending from the dentate line to the margin of the anus. Fissure can cause pain and bleeding. Diagnosis is made from the history and local inspection. Acute anal fissure should be treated conservatively - increased fibre and fluid intake, warm baths, local anaesthetic ointment, alternatively with nitrates and if all else fails by botulinum toxin. Treatment of chronic fissure will start conservatively but operative options are necessary in many cases.


Assuntos
Fissura Anal/diagnóstico , Fissura Anal/terapia , Canal Anal/cirurgia , Terapia Combinada , Humanos
9.
Vnitr Lek ; 61(7-8): 655-9, 2015.
Artigo em Tcheco | MEDLINE | ID: mdl-26375692

RESUMO

Thyroid cancer is one of the worlds fastest growing tumor incidences. The number of new cases has particularly increased in differentiated papillary thyroid carcinoma. In the Czech Republic it is documented that the incidence of thyroid cancer continues to grow, since 1980 has increased four times. The Czech Republic has a higher incidence than most other European countries and at the same time is a country with average and declining mortality from this disease. This review summarizes the known risk factors that may contribute to the formation and rise of thyroid carcinomas.


Assuntos
Neoplasias da Glândula Tireoide/epidemiologia , Carcinoma/epidemiologia , Carcinoma Papilar , República Tcheca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Fatores de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia
10.
Vnitr Lek ; 61(9): 769-77, 2015 Sep.
Artigo em Tcheco | MEDLINE | ID: mdl-26465275

RESUMO

INTRODUCTION: The incidence of well-differentiated low-risk thyroid cancer have increased globally over the last three decades. Thyroid cancer treatment relates to a suitable surgical procedure and the use of adjuvant radio-iodine therapy in selected patients. Evaluation of prognostic factors and risk stratification are critical for determining appropriate treatment. Survival of patients with low-risk thyroid cancer is excellent. Appropriate choice of medical treatment resulted in full recovery in most patients. Relapse risk increases with the size of the primary tumor, along with the findings of the risk factors in men. METHODS AND RESULTS: Our study included a total of 1 980 patients in whom were diagnosed T1a and T1b tumors between the years 2003 to 2012. The population included 1 675 women (84.6 %) of average age of 45.22 years and 305 men (15.4 %) of average age of 50.0 years. The bulk of the file represented papillary carcinomas (1 868; 94.4 %), and smaller group of follicular carcinomas (112; 5.6 %). Patients were divided into four groups according to tumor size. Patients were evaluated according to risk factors: unifocality no other risk factors, multifocality - more bearings in thyroid tumor, metastases in regional lymph nodes, distant metastases or combination of risk factors. Group A: In the monitored set of 678 patients with papillary and follicular microcarcinoma up to 5 mm, during histological input, the findings revealed one bearing (unifocal type of cancer) in 566 patients. Multifocality was found in 112 patients, local nodal metastasis were demonstrated in 24 cases and pulmonary metastasis was discove-red in 1 case. Group B: In this group there were 576 study patients with papillary and follicular microcarcinoma size of 5-10 mm. Histological findings were captured input one bearing carcinoma in 434 patients, 142 patients with multifocality, in 53 cases of local nodal metastasis, and 1 case of bone metastases. Group C: In this group there were 467 study patients with papillary and follicular microcarcinoma size 10-15 mm. The histological initial finding captured unifocal type of cancer in 344 patients, multifocality in 123 patients, in 45 cases local metastases and in 3 cases of pulmonary metastases. Group D: 259 patients were monitored in this group with breast size 16-20 mm. At the initial finding was captured one bearing cancer in 188 patients, multifocality in 71 patients, in 24 cases evidence of local metastases and 2 patients had a case of distant lung metastases. In patients in whom risk factors were found, radioiodine treatment was indicated. This included 744 patients. In this group of patients after a year or more, relapse was observed in 74 patients (9.94 %). In 1 236 patients who did not undergo radioiodine treatment, there was a relapse in 49 patients (3.96 %). CONCLUSION: Based on our analysis, it is necessary to stratify the risk of relapse according to risk factors. In case of missed radioiodine therapy in patients with low-risk cancer without confirmed risk factors, it is also necessary to have regular clinical, laboratory and ultrasound examination. It is important to distinguish patients with risk factors that may contribute to disease recurrence. Only in this way, on one hand we prevent excessive treatment of patients with low-risk thyroid cancer which leads to increased cost of health care, and on the other hand prevent reduced level of care for patients with an increase in relapses.


Assuntos
Adenocarcinoma Folicular/terapia , Adenocarcinoma Papilar/terapia , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Papilar/epidemiologia , Adenocarcinoma Papilar/patologia , Adulto , Idoso , Terapia Combinada , Estudos Transversais , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Prognóstico , Fatores de Risco , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia
11.
Lancet Oncol ; 15(6): 648-55, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24745698

RESUMO

BACKGROUND: The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. METHODS: This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. FINDINGS: 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent. INTERPRETATION: The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasia Endócrina Múltipla Tipo 2a/complicações , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Feocromocitoma/cirurgia , Adolescente , Neoplasias das Glândulas Suprarrenais/etiologia , Neoplasias das Glândulas Suprarrenais/mortalidade , Adrenalectomia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/mortalidade , Feocromocitoma/etiologia , Feocromocitoma/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Endocr Relat Cancer ; 30(12)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37882481

RESUMO

Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes. The importance of characterizing RET fusion-positive tumors has recently increased due to the possibility of targeted treatment. The aim of this study was to identify RET fusion-positive thyroid tumors, correlate them with clinicopathological features, compare them with other mutated carcinomas, and evaluate long-term follow-up of patients. The cohort consisted of 1564 different thyroid tissue samples (including 1164 thyroid carcinoma samples) from pediatric and adult patients. Samples were analyzed for known driver mutations occurring in thyroid cancer. Negative samples were subjected to extensive RET fusion gene analyses using next-generation sequencing and real-time PCR. RET fusion genes were not detected in any low-risk neoplasm or benign thyroid tissue and were detected only in papillary thyroid carcinomas (PTCs), in 113/993 (11.4%) patients, three times more frequently in pediatric and adolescent patients (29.8%) than in adult patients (8.7%). A total of 20 types of RET fusions were identified. RET fusion-positive carcinomas were associated with aggressive tumor behavior, including high rates of lymph node (75.2%) and distant metastases (18.6%), significantly higher than in NTRK fusion, BRAF V600E and RAS-positive carcinomas. Local and distant metastases were also frequently found in patients with microcarcinomas positive for the RET fusions. 'True recurrences' occurred rarely (2.4%) and only in adult patients. The 2-, 5-, 10-year disease-specific survival rates were 99%, 96%, and 95%, respectively. RET fusion-positive carcinomas were associated with high invasiveness and metastatic activity, but probably due to intensive treatment with low patient mortality.


Assuntos
Carcinoma , Neoplasias da Glândula Tireoide , Adolescente , Humanos , Adulto , Criança , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Câncer Papilífero da Tireoide , Mutação , Prognóstico , Proteínas Proto-Oncogênicas c-ret/genética
13.
Cas Lek Cesk ; 151(10): 472-5, 2012.
Artigo em Tcheco | MEDLINE | ID: mdl-23256632

RESUMO

The paper presents a case of 51 years old patient suffering from repetitive upper intestinal tract bleedings following several months after uncomplicated laparoscopic cholecystectomy for acute cholecystitis. After a difficult diagnostic algorithm the diagnosis is set as a right hepatic artery pseudoaneurysm fistulating into the cystic duct stump. Several attempts of intraarterial embolisation (coiling) were done with only temporary effect. Finally an open surgical procedure with transligation of the aneurysm was performed with an immediate and definitive effect. No clinical signs of bleeding appeared within 6 months after the procedure. Key words: haemobilia, hepatic artery pseudoaneurysm, complication of cholecystectomy, coiling.


Assuntos
Falso Aneurisma/complicações , Fístula Biliar/complicações , Colecistectomia Laparoscópica/efeitos adversos , Ducto Cístico/lesões , Hemorragia Gastrointestinal/etiologia , Artéria Hepática , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva
14.
Case Rep Gastroenterol ; 16(2): 526-534, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157607

RESUMO

At the time of the current COVID-19 pandemic, on a daily basis, we encountered patients suffering from various manifestations of this infection. The most common are respiratory symptoms. Many of the patients require acute hospital care, and a smaller group of them are hospitalized in intensive care units. A subset of these critically ill patients demonstrates clinically remarkable hypercoagulability and thus a predisposition to venous and arterial thromboembolism, manifested by thrombotic events ranging from acute pulmonary embolism and splanchnic vascular ischemia to extremity ischemia. The article describes a case of a patient with COVID-19 pneumonia complicated by massive bleeding into the gastrointestinal tract due to ischemic enterocolitis in connection with COVID-19 infection.

15.
Biomed Pharmacother ; 153: 113465, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076577

RESUMO

Drug efficacy determined in preclinical research is difficult to transfer to clinical practice. This is mainly due to the use of oversimplified models omitting the effect of the tumor microenvironment and the presence of various cell types participating in the formation of tumors in vivo. In this study, we used robust three-dimensional models including spheroids grown from colon cancer cell lines and organotypic cultures prepared from the colorectal carcinoma tissue to test novel therapeutic strategies. We developed a multi-modal approach combining brightfield and fluorescence microscopy for evaluating drug effects on organotypic cultures. Combined treatment with 5-fluorouracil and disulfiram/copper efficiently eliminated cancer cells in these 3D models. Moreover, disulfiram/copper down-regulated the expression of markers associated with 5-fluorouracil resistance, such as thymidylate synthase and CD133/CD44. Thus, we propose combined therapy of 5-fluorouracil and disulfiram/copper for further testing as a treatment for colorectal carcinoma. In addition, we show that organotypic cultures are suitable models for anti-cancer drug testing.


Assuntos
Neoplasias Colorretais , Fluoruracila , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Cobre/farmacologia , Cobre/uso terapêutico , Dissulfiram/farmacologia , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Esferoides Celulares/patologia , Microambiente Tumoral
16.
Front Psychol ; 13: 804753, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548549

RESUMO

Basic motor competencies (BMC) are a prerequisite for children to be physically active, participate in sports and thus develop a healthy, active lifestyle. The present study provides a broad screening of BMC and associations with age, sex, body mass index (BMI) and extracurricular physical activity (PA) in 10 different European countries. The different country and regional contexts within Europe will offer a novel view on already established BMC associations. The cross-sectional study was conducted in 11 regions in 10 European countries in 2018. The motor competence areas, object movement (OM) and self-movement (SM), were assessed using the MOBAK-1-2 test instrument in 3758 first and second graders (age: M = 6.86 ± 0.60 years; 50% girls) during Physical Education classes. Children were questioned about their extracurricular PA and age. Their body weight and height were measured in order to calculate BMI. Statistical analyses included variances and correlations. The results showed significant differences in BMC levels between countries (OM: F = 18.74, p < 0.001, η2 = 0.048; SM: F = 73.10, p < 0.001, η2 = 0.163) whereas associations between BMC and correlates were similar. Boys performed significantly better in OM while girls performed better in SM. Age was consistently positively related to OM and SM with older children reaching higher levels of BMC than younger ones. While participation rates for extracurricular PA differed widely, participation in ball sports was correlated with OM and SM. Participation in individual sports showed a significant association with SM. In summary, BMC levels of children seem to depend on where they live and are strongly related to their participation in extracurricular PA. Therefore, education and health policies, in order to enhance motor competence development and PA participation, are recommended. Further research on country-specific Physical Education frameworks and their influence on BMC will provide more insights into structural factors and cultural characteristics of BMC development. On a school level, support tools and educational materials for teachers about BMC may enable children to achieve a basic level of motor competencies through Physical Education, contributing to lifelong participation in PA.

17.
Hepatogastroenterology ; 58(106): 275-80, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21661381

RESUMO

BACKGROUND/AIMS: The aim of this retrospective study is to follow the main parameters such as the success of performing diagnostic endoscopic retrograde cholangiopancreatography (ERCP) and to determine the effectiveness and morbidity of therapeutic ERCP. METHODOLOGY: The study of the group took 12 years (January 1997-December 2008). The paper assesses in retrospect 138 patients who underwent laparoscopic cholecystectomy (LCE). Signs leading to the suspicion of possible biliary complications (BC) after previous LCE appeared in these patients in the postoperative period, indicating the performance of ERCP. RESULTS: Diagnostic ERCP was successful in all 138 patients (i.e. in 100% of cases). There were normal ERCP results in 8 patients and pathological results in the sense of some of the BC in the remaining 130 patients. Endoscopic therapy was performed after diagnostic ERCP in 115 of 130 patients with proved BC. Therapeutic ERCP was absolutely successful in altogether 111 of 130 patients (85.38%) with BC after LCE. CONCLUSIONS: The success rate of therapeutic ERCP in our group was 85.38%. Morbidity in relation to therapeutic ERCP was 4.2%. ERCP appears to be highly effective diagnostic and primarily therapeutic method in solving BC after LCE.


Assuntos
Doenças dos Ductos Biliares/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomia Laparoscópica/efeitos adversos , Adulto , Idoso , Doenças dos Ductos Biliares/terapia , Coledocolitíase/diagnóstico , Coledocolitíase/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Cancers (Basel) ; 13(8)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923728

RESUMO

Chromosomal rearrangements of NTRK genes are oncogenic driver mutations in thyroid cancer (TC). This study aimed to identify NTRK fusion-positive thyroid tumors and to correlate them with clinical and pathological data and determine their prognostic significance. The cohort consisted of 989 different TC samples. Based on the detected mutation, samples were triaged, and those that were positive for a BRAF, HRAS, KRAS, NRAS, RET, RET/PTC or PAX8/PPARγ mutation were excluded from further analyses. NTRK fusion gene testing was performed in 259 cases, including 126 cases using next-generation sequencing. NTRK fusion genes were detected in 57 of 846 (6.7%) papillary thyroid carcinomas and in 2 of 10 (20.0%) poorly differentiated thyroid carcinomas. A total of eight types of NTRK fusions were found, including ETV6/NTRK3, EML4/NTRK3, RBPMS/NTRK3, SQSTM1/NTRK3, TPM3/NTRK1, IRF2BP2/NTRK1, SQSTM1/NTRK1 and TPR/NTRK1.NTRK fusion-positive carcinomas were associated with the follicular growth pattern, chronic lymphocytic thyroiditis and lymph node metastases. NTRK1-rearranged carcinomas showed a higher frequency of multifocality and aggressivity than NTRK3-rearranged carcinomas. Tumor size, presence of metastases, positivity for the NTRK3 or NTRK1 fusion gene and a late mutation event (TERT or TP53 mutation) were determined as factors affecting patient prognosis. NTRK fusion genes are valuable diagnostic and prognostic markers.

19.
Cell Rep ; 35(2): 108982, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33852837

RESUMO

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.


Assuntos
Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Pirróis/farmacologia , Tiazóis/farmacologia , Proteína Supressora de Tumor p53/genética , Animais , Antineoplásicos/síntese química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Doxorrubicina/farmacologia , Descoberta de Drogas , Sinergismo Farmacológico , Feminino , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Ligação Proteica , Pirróis/síntese química , Tiazóis/síntese química , Proteína Supressora de Tumor p53/agonistas , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Thyroid ; 30(12): 1771-1780, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32495721

RESUMO

Background: Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods: The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results: A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types of RET, NTRK3, ALK, NTRK1, BRAF, and MET fusions were found, of which five novel, TPR/RET, IKBKG/RET, BBIP1/RET, OPTN/BRAF, and EML4/MET, rearrangements were identified and a CUL1/BRAF rearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were the RET fusions, followed by NTRK3 fusions. RET fusions were associated with more frequent lymph node and distant metastases and psammoma bodies, and NTRK3 fusions were associated with the follicular variant of PTC. Conclusions: Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.


Assuntos
Biomarcadores Tumorais/genética , Fusão Gênica , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-ret/genética , Receptor trkA/genética , Receptor trkC/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Fatores Etários , Criança , Feminino , Rearranjo Gênico , Predisposição Genética para Doença , Humanos , Masculino , Fenótipo , Mutação Puntual , Prognóstico , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Adulto Jovem
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