RESUMO
The molecular profile of a tumor is associated with its histological type and can be used both to study the mechanisms of tumor progression and to diagnose it. In this work, changes in the lipid profile of a malignant breast tumor and the adjacent tissue were studied. The potential possibility of determining the histological type of the tumor by its lipid profile was evaluated. Lipid profiling was performed by reverse-phase chromato-mass-spectrometric analysis the tissue of lipid extract with identification of lipids by characteristic fragments. Potential lipid markers of the histological type of tumor were determined using the Kruskal-Wallis test. Impact of lipid markers was calculated by MetaboAnalyst. Classification models were built by support vector machines with linear kernel and 1-vs-1 architecture. Models were validated by leave-one out cross-validation. Accuracy of models based on microenvironment tissue, were 99% and 75%, accuracy of models, based on tumor tissue, were 90% and 40% for the positive ion mode and negative ion mode respectively. The lipid profile of marginal (adjacent) tissue can be used for identification histological types of breast cancer. Glycerophospholipid metabolism pathway changes were statistically significant in the adjacent tissue and tumor tissue.
Assuntos
Neoplasias da Mama , Lipidômica , Humanos , Feminino , Neoplasias da Mama/patologia , Lipídeos/análise , Espectrometria de Massas , Biomarcadores , Microambiente TumoralRESUMO
Research of cancer progression mechanisms and their impact on metabolism of tumor cells and tumor microenvironment cells is an important element in drug development for cancer target therapy. In this study, changes in tumor tissue and margin tissue lipid profiles, were associated with the following clinical and morphological characteristics: tumor size, cancer stage, multifocalite, tumor grade, number of lymph node metastasis, Nottingham prognostic index, total malignancy score, level of Ki67 protein. Lipid profiling was performed by reverse-phase chromato-mass spectrometry analysis of lipid tissue extract with lipid identification by characteristic fragments. In the lipid profile of tumor tissue 13 characteristic lipids were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Eight of 13 belonged to phosphatidylcholines. In lipid profile of tumor microenviroment tissue 13 lipid features were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Four of 13 belonged to oxidized lipids, 4 lipid features belonged to sphingomyelins, four of 13 belonged to phosphatidylethanolamines. The tumor microenvironment tissue lipid profile correlated with tumor size, cancer stage, tumor grade, number of axillary metastases, Nottingham prognostic index. The tumor tissue lipid profile correlated with tumor size, tumor grade, total malignant score, and number of axillary metastases.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/metabolismo , Feminino , Humanos , Lipidômica , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Microambiente TumoralRESUMO
Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene - p=0.009 (AUC (95%CI) = 0.76 (0.59-0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6-0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.
Assuntos
Neoplasias da Mama , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Metilação de DNA , Feminino , Humanos , Metástase Linfática , Fenobarbital , Receptores de Estrogênio/metabolismoRESUMO
BACKGROUND: It is shown that each type of human malignancies has a unique set of expressed miRNAs, and tumor-specific miRNAs in biological tissues of a patient are stable. The aim of this study was to determine the differences in the expression of miRNAs in tumor tissue of invasive breast carcinoma compared to normal tissue, as well as to analyze the variable expression of miRNAs in molecular genetic subtypes of breast cancer. METHODS: We determined differences in mRNA expression in 35 biopsies of tumor tissue of various molecular genetic subtypes of breast cancer and 35 biopsies of adjacent conventionally normal breast tissue by RT-PCR in real time. We assessed the expression levels of miRNA-21, 221, 222, 155, 205, 20a , 125b and 200a. RESULTS: A significant increase in the level of expression of the oncogenic miRNA-20a (p=0.000141) and miRNA-221 (p=0.037777) in the triple negative cancer in comparison with the luminal A and luminal B/HER2/neu-negative breast cancer subtypes was established. Assessment of significance of the results was conducted using ROC analysis. For miRNA-221 AUC value was 0.772, for miRNA-20a AUC value was 0.949. The obtained results suggest the possibility of using the levels of miRNA-21, 155, 205, 125b expression in tumor tissue to assess a malignant potential of a breast carcinoma. The levels of expression of oncogenic miRNA-221 and miRNA-20a are increased in TNBC compared with luminal A and luminal B/HER2/neu-negative breast cancer subtypes, supporting the characteristic of TNBC as the most aggressive subtype of breast cancer. MiRNA-20a is a marker of TNBC compared with luminal subtypes of breast cancer. MICRO ABSTRACT: To identify markers for breast cancer with triple-negative phenotype, we evaluated expression levels of siRNA-21, 221, 222, 155, 205, 20a, 125b, 200a and 146b in the tumor tissue of 35 patients by RT-PCR. AUC value equal to 0.949 in the ROC-analysis allows us to recommend the miRNA-20a as a marker of triple negative breast cancer to differentiate it from the luminal subtypes.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias da Mama/diagnóstico , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Transcriptoma , Carga TumoralRESUMO
It was retrospectively analyzed clinicopathological features of 529 breast cancer patients treated at the Ulyanovsk Oncology Center. Of 529 patients 235 (44.4%) had at least one positive axillary lymph node. Tumor size (p = 0,0005), histological grade (p = 0004), lymphovascular invasion (p < 0,0001), HER2-status (p = 0,014) and total score of malignancy (p < 0,0001) were significant independent predictors for lymph nodes metastases. By univariate and multivariate regression analysis it was created the graphic variant of nomogram which could predict the risk of lymph nodes metastases in breast cancer patients. An area under ROC-curve in our nomogram reached 0,737 that demonstrated high prediction level of accuracy of the developed model. Thus new nomogram is a useful tool in planning axillary surgery in breast cancer patients.
Assuntos
Neoplasias da Mama/diagnóstico , Linfonodos/patologia , Metástase Linfática/diagnóstico , Nomogramas , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Receptor ErbB-2/análise , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Vasculares/secundárioRESUMO
Informative capacity analysis of immunohistochemistry (IHC) and flow cytometry (FCM) in the assessment of estrogen receptor α (ERα) expression in breast cancer tissue was performed. Similar frequencies of expression were shown by both methods: 27% of ERα-negative and 73% ERα-positive cases. However, IHC evaluation detected low levels in only 20% of ERα-positive cases, whereas low levels of ERα detected by FCM were 2 times more often (48%). Moreover, FCM revealed positive expression (23-60%) in 33% of IHC ERα-negative cases. Among IHC ER-positive cases, zero ERα expression was detected by FCM in 12.5%. The approaches to minimize errors in routine clinical determination of the estrogen receptor status were proposed.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Receptor alfa de Estrogênio/metabolismo , Biomarcadores Tumorais/genética , Receptor alfa de Estrogênio/genética , Feminino , Citometria de Fluxo , Humanos , Imuno-HistoquímicaRESUMO
Among 894 patients with acute destructive cholecystitis complicated by peritonitis there were 478 patients with slight clinical symptoms of peritonitis. In 125 of these patients (26.1%) the clinical symptoms of peritonitis were completely absent, extremely slight manifestations being observed in 353 patients (73.9%). The percentage of patients with acute destructive cholecystitis having slight clinical symptoms of peritonitis was considerably higher in elderly and senile patients (72.3%) than in the group of young patients (27.7%). The slight clinical symptoms of this complication was observed more often in patients with a local peritonitis.
Assuntos
Colecistite/complicações , Peritonite/diagnóstico , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Colecistite/diagnóstico , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Peritonite/classificação , Peritonite/etiologiaAssuntos
Síndrome de Esmagamento , Desastres , Adolescente , Adulto , Armênia , Síndrome de Esmagamento/diagnóstico por imagem , Síndrome de Esmagamento/terapia , Feminino , Humanos , Oxigenoterapia Hiperbárica , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo , Cintilografia , Desintoxicação por Sorção , Fatores de TempoRESUMO
Experience in examination of 221 patients with postoperative cholangiolithiasis is discussed. Analysis of the results of instrumental examination ERPCG to surpass all the existing methods of diagnosis of stones in the bile ducts in informativeness and safety. A diagnostic algorithm of examination is suggested by means of which the necessary tactical problems connected with the forthcoming operation were solved in 98.2% of cases.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Colelitíase/diagnóstico por imagem , Colelitíase/cirurgia , Cálculos Biliares/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Colecistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , RecidivaAssuntos
Colecistite/complicações , Peritonite/etiologia , Doença Aguda , Idoso , Colecistectomia , Colecistite/diagnóstico , Colecistite/cirurgia , Diagnóstico Diferencial , Emergências , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Masculino , Pessoa de Meia-Idade , Peritonite/diagnóstico , Peritonite/cirurgia , Cuidados Pós-Operatórios/métodosRESUMO
The authors analysed the results of examination and treatment of 399 elderly and old-aged patients in the period between 1971 and 1981. At that time cholangitis was managed in 146 (36.6%) patients mainly by surgical intracavitary operations, in 21.2% with a fatal outcome. The results showed the high risk of surgical methods for treatment of cholangitis. Since 1982 the authors have introduced into every-day practice endoscopic methods for the management of this disease. It was found that endoscopic papillosphincterotomy (EPST) is the most physiological and safe method for the treatment of choledocholithiasis, stenosis of the major duodenal papilla, and acute cholangitis. EPST undertaken in 253 (63.4%) patients ensured adequate decompression of the bile ducts in 187 (73.9%) of them and facilitated removal of cholangitis and recovery. With the use of EPST in the treatment of acute cholangitis not only was the number of surgical operations on patients of the older age group reduced, but the mortality decreased to 5.5% (which was 3.9 times lower than the mortality in management of cholangitis by surgical operations).
Assuntos
Ampola Hepatopancreática/cirurgia , Colangite/cirurgia , Coledocostomia/métodos , Ducto Colédoco/cirurgia , Esfinterotomia Endoscópica/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-IdadeRESUMO
The dynamics of some oxygenating pulmonary function (OPF) indices has been studied in 33 patients with coronary cardiac disease and rheumatic lesions of cardiac valves 4-6 hours after surgery in response to a single hyperbaric oxygenation (HBO) session (1.5 ata, 45 min) in the immediate postoperative period. It is found that in the presence of slight or, on the contrary, pronounced arterial hypoxemia, no significant negative OPF changes were observed. At the same time, a temporary increase in the alveolo-arterial gradient has been found in some patients. The comparison of data on the systemic blood flow with the OPF indices permits suggesting the prevalent role of the membrane component in a PaO2 decrease in patients after using assisted circulation.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Hemodinâmica/fisiologia , Oxigenoterapia Hiperbárica , Hipóxia/terapia , Troca Gasosa Pulmonar/fisiologia , Adulto , Circulação Assistida , Doença das Coronárias/sangue , Doença das Coronárias/complicações , Doença das Coronárias/cirurgia , Doenças das Valvas Cardíacas/sangue , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/cirurgia , Humanos , Hipóxia/etiologia , Período Intraoperatório , Pessoa de Meia-Idade , Período Pós-Operatório , Cardiopatia Reumática/sangue , Cardiopatia Reumática/complicações , Cardiopatia Reumática/cirurgia , Fatores de TempoRESUMO
Results of treatment of 284 patients operated upon for diffuse peritonitis are presented. The assessment is given of the significance of detoxication methods--forced fractionated peritoneal dialysis and washing of the abdominal cavity in treatment of diffuse peritonitis and their influence upon the outcome of the disease.
Assuntos
Peritonite/terapia , Desintoxicação por Sorção/métodos , Doença Aguda , Adulto , Apendicectomia , Apendicite/complicações , Apendicite/cirurgia , Terapia Combinada , Humanos , Pessoa de Meia-Idade , Peritonite/etiologiaRESUMO
Data of 205 patients with recurrent (48) and residual (157) choledocholithiases are presented. In most observations postoperative cholelithiasis proceeded by the type of chronic intermittent obturation of bile ducts. Highly effective method of diagnosing recurrent and residual calculi is thought to be the endoscopic retrograde pancreatocholangiography, best results of the treatment being obtained after the endoscopic papillosphincterotomy which should be used as the operation of choice.
Assuntos
Colelitíase/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças dos Ductos Biliares/diagnóstico , Doenças dos Ductos Biliares/etiologia , Doenças dos Ductos Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica , Colecistectomia , Colelitíase/etiologia , Colelitíase/cirurgia , Feminino , Cálculos Biliares/diagnóstico , Cálculos Biliares/etiologia , Cálculos Biliares/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Recidiva , Reoperação , Esfincterotomia Transduodenal , SíndromeRESUMO
The article analyses 610 patients with acute cholecystitis complicated by circumscribed peritonitis which determines the results of surgical treatment in many patients. The clinical manifestations of circumscribed peritonitis complicating destructive cholecystitis are discussed. It is shown that laparoscopy plays a role in the early diagnosis of atypical or asymptomatic course of this complication, particularly in elderly and old-aged patients. Data on the surgical treatment of acute cholecystitis complicated by localized circumscribed and ++non-circumscribed peritonitis are presented. The authors show the possibility of choosing the optimal operation--laparoscopic drainage of the gallbladder and abdominal cavity--in the first stage of treatment of patients with phlegmonous cholecystitis and localized ++non-circumscribed peritonitis in the presence of serious concomitant diseases.
Assuntos
Colecistite/cirurgia , Peritonite/cirurgia , Doença Aguda , Adulto , Idoso , Colecistectomia , Colecistite/complicações , Colecistite/diagnóstico , Drenagem , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Peritonite/diagnóstico , Peritonite/etiologia , Cuidados Pós-OperatóriosRESUMO
An experience with repeated examinations of 656 patients operated upon for bile calculi is presented. It was shown that the estimation of long-term results of surgical treatment of choledocholithiasis should be performed on the basis of common criteria three years after operation by complex use of clinical, laboratory, X-ray and endoscopic methods of examination. Debatable questions associated with the interpretation of special examinations and their influence on the clinical estimation of long-term results are elucidated.
Assuntos
Ducto Colédoco/cirurgia , Cálculos Biliares/cirurgia , Colangiografia , Colangiopancreatografia Retrógrada Endoscópica , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/fisiopatologia , Cálculos Biliares/diagnóstico , Cálculos Biliares/fisiopatologia , Humanos , Autoavaliação (Psicologia) , Inquéritos e Questionários , Fatores de TempoAssuntos
Colecistite/cirurgia , Peritonite/cirurgia , Idoso , Colecistectomia , Colecistite/complicações , Colecistite/diagnóstico , Drenagem , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Lavagem Peritoneal , Peritonite/diagnóstico , Peritonite/etiologia , Cuidados Pós-OperatóriosRESUMO
The authors analyse the late results of surgical treatment of 463 patients who underwent operation for stones in the bile ducts. The late results were found to be determined by the character of the affection of the bile excreting system and the rational choice of the operative method. The indications and contraindications for various methods of treating cholelithiasis were determined more precisely from study of the late results.
Assuntos
Ducto Colédoco/cirurgia , Cálculos Biliares/cirurgia , Adulto , Idoso , Ampola Hepatopancreática/cirurgia , Coledocostomia/métodos , Ducto Colédoco/fisiopatologia , Drenagem/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Técnicas de Sutura , Fatores de TempoRESUMO
The paper describes a morphologic picture of changes in eye tissues of rabbits in transconjunctival scleral action on the ciliary body by means of krypton laser (wavelength--647.1 nm) working in a continuous regime. The applications were located 1.0-1.5 mm from the limbus with energy--0.8--3.0 Wt, exposition time--2.0 sec., spot diameter--1000 mcm. The degree of necrosis of ciliary epithelium and atrophy of ciliary processes are directly dependent on the dose of action. Thus, the greatest part of laser radiation with 647.1 nm wavelength is absorbed at the level of the ciliary body. In perspective, this can lead to development of new methods for treatment of some eye diseases, such as glaucoma, tumors of the uveal tract, etc.