RESUMO
BACKGROUND: Identifying protein interfaces can inform how proteins interact with their binding partners, uncover the regulatory mechanisms that control biological functions and guide the development of novel therapeutic agents. A variety of computational approaches have been developed for predicting a protein's interfacial residues from its known sequence and structure. Methods using the known three-dimensional structures of proteins can be template-based or template-free. Template-based methods have limited success in predicting interfaces when homologues with known complex structures are not available to use as templates. The prediction performance of template-free methods that only rely only upon proteins' intrinsic properties is limited by the amount of biologically relevant features that can be included in an interface prediction model. RESULTS: We describe the development of an integrated method for protein interface prediction (ISPIP) to explore the hypothesis that the efficacy of a computational prediction method of protein binding sites can be enhanced by using a combination of methods that rely on orthogonal structure-based properties of a query protein, combining and balancing both template-free and template-based features. ISPIP is a method that integrates these approaches through simple linear or logistic regression models and more complex decision tree models. On a diverse test set of 156 query proteins, ISPIP outperforms each of its individual classifiers in identifying protein binding interfaces. CONCLUSIONS: The integrated method captures the best performance of individual classifiers and delivers an improved interface prediction. The method is robust and performs well even when one of the individual classifiers performs poorly on a particular query protein. This work demonstrates that integrating orthogonal methods that depend on different structural properties of proteins performs better at interface prediction than any individual classifier alone.
Assuntos
Algoritmos , Proteínas , Sítios de Ligação , Bases de Dados de Proteínas , Ligação Proteica , Conformação Proteica , Proteínas/químicaRESUMO
BACKGROUND: The effect of histology-based treatment regimen on diffuse gastric adenocarcinoma has not been evaluated in clinical trials. This international phase III trial evaluated the efficacy and safety of S-1 (a contemporary oral fluoropyrimidine)/cisplatin versus 5-fluorouracil (5-FU)/cisplatin in chemotherapy-naïve patients with diffuse-type adenocarcinoma involving the gastroesophageal junction or stomach. PATIENTS AND METHODS: Eligibility criteria included untreated, measurable, advanced diffuse adenocarcinoma confirmed by central pathology and performance status of 0-1. Patients were randomized (2 : 1) to receive S-1/cisplatin or 5-FU/cisplatin. Primary end point was overall survival (OS), and secondary end points were progression-free survival, time to treatment failure, overall response rate, and safety. A multivariable analysis was also carried out. RESULTS: Overall, 361 patients were randomized (S-1/cisplatin, n = 239; 5-FU/cisplatin, n = 122); half (51%) were men, and median age was 56.0 years. In each group, median number of treatment cycles per patient was 4 (range, S-1/cisplatin: 1-20; 5-FU/cisplatin: 1-30), and dose intensity was >95%. OS was not different in the two groups {median OS with S-1/cisplatin, 7.5 [95% confidence interval (CI): 6.7, 9.3]; 5-FU/cisplatin, 6.6 [95% CI: 5.7, 8.1] months; hazard ratio, 0.99 [95% CI: 0.76, 1.28]; P = 0.9312}. Overall response rate was significantly higher in the S-1/cisplatin than 5-FU/cisplatin group (34.7% versus 19.8%; P = 0.01), but progression-free survival and time to treatment failure were not different. Safety was similar between the 2 groups; however, fewer patients treated with S-1/cisplatin than 5-FU/cisplatin had ≥1 grade 3/4 treatment-emergent adverse event or ≥1 adverse event resulting in treatment discontinuation. One treatment-related death occurred in each group. Slow accrual led to early termination. CONCLUSIONS: These data suggest that S-1/cisplatin and 5-FU/cisplatin are similar in efficacy and safety in untreated patients with advanced diffuse adenocarcinoma of the gastroesophageal junction or stomach. The primary end point was not met. CLINICALTRIAL.GOV REGISTRATION NUMBER: NCT01285557.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Fluoruracila/administração & dosagem , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem , Adenocarcinoma/patologia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Combinação de Medicamentos , Junção Esofagogástrica/patologia , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Gástricas/patologia , Análise de SobrevidaRESUMO
An analysis of results of 498 patients with malignant pleural effusion was made. All patients were divided into three groups depending on methods of treatment: in the first group of patients the puncture of pleural cavity and the evacuation of liquid were made against the background of complex treatment; in the second group of patients the thoracocentesis and suspension induction were performed; in the third group the video thoracoscopy was carried out. In an assessment of each method of treatment, the researchers came to the conclusion that in case when the patient had the sufficient functional capabilities, the doctors should give preference to the thoracoscopy operations and in case of severe somatic status the doctors should give preference to the drainage of pleural cavity with release from exudates and with subsequent introduction of talc as the most effective sclerosing agent.
Assuntos
Drenagem/métodos , Derrame Pleural Maligno/terapia , Pleurodese/métodos , Toracoscopia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Pleural , Estudos Retrospectivos , Soluções Esclerosantes/administração & dosagem , Talco/administração & dosagem , Resultado do TratamentoRESUMO
Generally recognized factor, which complicates the course of sepsis, is the development of hypercoagulation syndrome. The increase of thrombin coagulation indicates on the elevation of risk of thrombus formation in microcirculation vessels, which could cause the formation of multiple organ failure. The thrombin generation assay is a new method of the evaluation of homeostasis system status. The test reflects the fermentation activity of thrombin and shows the functional condition, which arises in the interaction of procoagulant and anticoagulant. The diagnosis of generalized peritonitis had 30 patients (18 men and 12 women, aged 61+/-18,3 years) and they were included in the research. It was shown, that the use of thrombin generation assay in patients with the abdominal sepsis could give the well-timed analysis of hypercoagulation changes and the assessment of protein C system investment in the thrombin generation.
Assuntos
Testes de Coagulação Sanguínea/métodos , Peritonite/complicações , Sepse , Trombina , Trombofilia , Adulto , Idoso , Coagulação Sanguínea , Feminino , Hemostasia , Humanos , Masculino , Pessoa de Meia-Idade , Peritonite/sangue , Medição de Risco/métodos , Sepse/sangue , Sepse/etiologia , Trombina/análise , Trombina/metabolismo , Trombofilia/diagnóstico , Trombofilia/etiologiaRESUMO
On the basis of an analysis of results of treatment of 123 patients by different methods of pleurodesis the authors have shown advantages of the method of videothoracoscopy.
Assuntos
Derrame Pleural Maligno/terapia , Pleurisia/terapia , Pleurodese/métodos , Cirurgia Torácica Vídeoassistida/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/complicações , Pleurisia/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The means for using prophylactic measures for prevention of the development of the adhesion process in the abdominal cavity are divided by the authors into two groups: for primary and secondary prophylactics. The mechanism of action of means for primary prophylactics is directed to restoration of the peritoneum mesothelium and its function; secondary prophylactics--to prevention of adhesions of scarry regenerated leaves of the parietal and visceral peritoneum. The findings are analyzed. The authors give recommendations for using means against adhesions. The necessity to choose the means for prophylactics depending on the state of the abdominal cavity is grounded (first operation or reoperation, planned or emergency operation). On the basis of the personal experience the authors recommend measures of the primary and secondary prophylactics of the adhesion process.
Assuntos
Doenças Peritoneais/terapia , Peritônio/cirurgia , Aderências Teciduais/terapia , Humanos , Doenças Peritoneais/prevenção & controle , Doenças Peritoneais/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controleRESUMO
Abdominal sepsis (AS) is a systemic inflammatory reaction of organism in response to the development of infectious process in organs of the abdominal cavity. The course of AS is complicated by hypercoagulation syndrome which facilitates progression of endogenous intoxication. The investigation included 26 patients (14 men and 12 women, mean age 65.5 +/- 16.4 years) with AS. The test of thrombin generation (TTG) used in patients with AS allows assessment of changes in the hemostasis system and control of the heparin dose. It was established that TTG revealed elevated endogenous thrombin potential of blood practically in all patients with AS. In the patients given 25 000 IU of heparin the TTG indices showed a reliably decreased endogenous thrombin potential and peak thrombin concentration as compared with a group of patients given 10 000 IU of heparin.
Assuntos
Heparina/administração & dosagem , Sepse/tratamento farmacológico , Trombina/metabolismo , Abdome , Idoso , Anticoagulantes/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Sepse/sangue , Trombina/efeitos dos fármacos , Resultado do TratamentoRESUMO
An analysis of results of treatment of 112 patients with metastases of intrapulmonary colorectal carcinoma (CRC) for the period from 1990 to 2006 has shown that cytoreductive opera tions for excision of the metastases are an effective method of treatment of this category of patients which allows a two times increased survival median as compared with analogous index in the group of patients exposed to palliative chemotherapy. Palliative chemotherapy fails to have statistically significant influence to survival of patients who have ablated intrapulmonary CRC metastases in the volume of complete cytoreduction.
Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Pneumonectomia/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/secundário , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias , Prognóstico , Modelos de Riscos Proporcionais , Taxa de SobrevidaRESUMO
Results of treatment of 51 patients with intrapulmonary metastases of renal cancer were analyzed. Surgical interventions in volume of complete cytoreduction were made in 31 of them. All the patients were followed-up after operations at the period from 3 through 68 months. A multi-factor analysis has shown that surgical metastasectomy gives reliably better results of treatment of patients with disseminated renal cancer. Regressive analysis in the group of operated patients has shown that involvement of the lymph nodes of the bronchopulmonary group and mediastinum gave reliably worse results of treatment of this group of patients.
Assuntos
Neoplasias Renais/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Metastasectomia/métodos , Cuidados Paliativos/métodos , Pneumonectomia/métodos , Adulto , Idoso , Biomarcadores Tumorais , Antígeno Carcinoembrionário/sangue , Interpretação Estatística de Dados , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/fisiopatologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
PURPOSE: Leptomeningeal disease (LMD) is a rare but deadly complication of cancer in which the disease spreads to the cerebrospinal fluid and seeds the meninges of the central nervous system (CNS). Craniospinal irradiation (CSI) involves treatment of the entire CNS subarachnoid space and is occasionally used as a last-resort palliative therapy for LMD. METHODS: This review examined literature describing the role of CSI for LMD from solid and hematologic malignancies in adults. A search for studies published until September 1, 2020 was conducted using PubMed database. RESULTS: A total of 262 unique articles were identified. Thirteen studies were included for analysis in which a total of 275 patients were treated with CSI for LMD. Median age at time of irradiation was 43 years, and most patients had KPS score of 70 and higher. The most common cancers resulting in LMD were acute lymphocytic leukemia, breast cancer, and acute myelogenous leukemia. Median CSI dose was 30 Gy and 18% of patients were treated with proton radiation. 52% of patients had stable-to-improved neurologic symptoms. Median overall survival for the entire cohort was 5.3 months. Patients treated with marrow-sparing proton radiation had median OS of 8 months. The most common treatment toxicities were hematologic and gastrointestinal events. CONCLUSIONS: Despite advances in systemic and radiation therapies, LMD remains a devastating end-stage complication of some malignancies. Treatment-related toxicities can be a significant barrier to CSI delivery. In select patients with LMD, marrow-sparing proton CSI may provide safer palliation of symptoms and prolong survival.
Assuntos
Radiação Cranioespinal , Neoplasias Meníngeas/radioterapia , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Avaliação de Estado de Karnofsky/estatística & dados numéricos , Leucemia Mieloide Aguda/patologia , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/secundário , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Dosagem RadioterapêuticaRESUMO
The authors propose an individual decision on the character of treatment: strangulated intestinal obstruction should be operated immediately after making the diagnosis; treatment of adhesive intestinal obstruction should be started with conservative methods. Successful treatment, depending on the anamnesis and state of the patient, allows planned total enterolysis or conservative treatment of the peritoneal commissures. If the conservative treatment is not a success, the patients should be operated after normalization of homeostasis, and better in day time. Laparoscopic adhesiolysis in such category of patients is not indicated.
Assuntos
Obstrução Intestinal/cirurgia , Intestino Delgado/cirurgia , Laparotomia/métodos , Guias de Prática Clínica como Assunto , Idoso , Feminino , Seguimentos , Humanos , Prevenção SecundáriaRESUMO
The intracardiac characteristics were studied in 100 patients prior to a removal of varicose veins by surgical or screrotherapeutic methods using US methods. An analysis of these characteristics has shown that investigation of the diastolic function of the heart ventricles is the most demonstrative one. The function of one or two ventricles was shown to worsen with age having negative influence on the venous system of lower extremities which can cause the appearance of varicose veins or their progression thus increasing the stage of chronic venous insufficiency, the appearance of recurrent varicosity after its removal.
Assuntos
Coração/fisiologia , Varizes/fisiopatologia , Adulto , Idoso , Ecocardiografia Doppler , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Prognóstico , Função Ventricular/fisiologia , Adulto JovemRESUMO
The authors made an analysis of the results of treatment of 924 patients with non-small cell lung cancer, operated in the volume of pneumonectomy during 1990-2007 years and developed a method of complete suturing the mediastinum wound in order to isolate the bronchus stump from the free pleural cavity and prevention of the development of a bronchopleural fistula.
Assuntos
Fístula Brônquica/etiologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Carcinoma de Pequenas Células do Pulmão/cirurgia , Adulto , Idoso , Fístula Brônquica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Tamponamento Cardíaco , Traumatismos Cardíacos , Ferimentos por Arma de Fogo/complicações , Arritmias Cardíacas/etiologia , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/cirurgia , Drenagem/métodos , Armas de Fogo , Traumatismos Cardíacos/complicações , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/fisiopatologia , Traumatismos Cardíacos/cirurgia , Hemostasia Cirúrgica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The authors investigated the dependence of increasing serum oncomarkers CEA, Cyfra-21, NSE, TU M2-PK on survival in 739 patients with nonsmall cell lung cancer. The tests for the determination of the content of CEA, Cyfra-21, NSE in blood serum have low sensitivity and are of little use for the diagnosis of lung cancer. The tests because of their simplicity and low cost can be used for the detection of groups of patients with preliminarily diagnosed nonsmall cell lung cancer needing additional methods of examination for more exact staging of the disease and exclusion of remote metastases and more active using adjuvant method of treatment. The use of tumor pyruvate kinase can be perspective for clinical oncopulmonology. However, due to its low specificity, further experiences are required for using this oncomarker in the group of patients with nonsmall cell lung cancer.
Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Queratina-19/sangue , Neoplasias Pulmonares/sangue , Fosfopiruvato Hidratase/sangue , Piruvato Quinase/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Ensaio Imunorradiométrico , Medições Luminescentes , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PrognósticoRESUMO
Biomechanical parameters of the white line in health, in postoperative ventral hernias, in midline hernias and diastasis recti abdominis were studied on a special stand. It was noted that the elasticity modulus of the white line in the transverse direction is more than that in the longitudinal direction. The white line tissue strength in patients with midline hernia was 46.5% less as compared with the normal line. The greatest strength and transfer appeared with the elliptical opening stretched along the white line as compared with the round form of the opening.
Assuntos
Parede Abdominal/fisiopatologia , Hérnia Ventral/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Parede Abdominal/cirurgia , Fenômenos Biomecânicos , Feminino , Hérnia Ventral/fisiopatologia , Humanos , Masculino , Resultado do TratamentoRESUMO
The authors present results of investigation of the state of microbiocenosis of the intestine and immune status of organism of 139 patients after emergency operations on the gastro-intestinal tract organs. Disbiosis and reduced indices of the immune system in the postoperative period was a cause of using biocenosis sparing treatment resulting in stabilization of microecology of the gastro-intestinal tract, higher colonization resistance and general reactivity of organism.
Assuntos
Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/cirurgia , Trato Gastrointestinal/microbiologia , Imunidade Celular , Probióticos/uso terapêutico , Contagem de Colônia Microbiana , Feminino , Seguimentos , Gastroenteropatias/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/cirurgia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A method of treatment of the abdominal cavity in peritonitis patients has been developed which promotes early regeneration of the peritoneum mesothelium, fibrinolysis, recovery of functions of the abdominal cavity and thus preventing formation of the adhesion process in the abdominal cavity. Effectiveness of the method was experimentally confirmed in rabbits and used in 126 patients with different forms of peritonitis. A comparison of methods of traditional treatment of peritonitis in 120 patients and that with using the developed method has shown advantages of the latter one.