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1.
Cardiovasc Diabetol ; 17(1): 15, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343259

RESUMO

BACKGROUND: Increased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats. METHODS: Six-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test. RESULTS: Body weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups. CONCLUSION: Apocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.


Assuntos
Acetofenonas/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Sequestradores de Radicais Livres/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Estreptozocina , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Catalase/sangue , Colágeno , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Glutationa Peroxidase/sangue , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Masculino , NADPH Oxidases/metabolismo , Ratos Wistar , Superóxido Dismutase/sangue
2.
Cardiovasc Diabetol ; 15(1): 126, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27585437

RESUMO

PURPOSE: Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM). METHODS: Male SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann-Whitney. RESULTS: Echocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups. CONCLUSION: Apocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.


Assuntos
Acetofenonas/farmacologia , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/prevenção & controle , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Catalase/metabolismo , Colágeno Tipo III/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Glutationa Peroxidase/metabolismo , Hipertensão/complicações , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/metabolismo , Masculino , Contração Miocárdica/efeitos dos fármacos , Miocárdio/patologia , Ratos Endogâmicos SHR , Estreptozocina , Função Ventricular Esquerda/efeitos dos fármacos
3.
J Diabetes Res ; 2015: 457848, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26509175

RESUMO

UNLABELLED: We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary diabetes (DM-Sed), and exercised diabetes (DM-Ex). Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV) papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73 ± 0.49; C-Ex: 5.67 ± 0.53; DM-Sed: 6.41 ± 0.54; DM-Ex: 5.81 ± 0.50 mm; P < 0.05 DM-Sed vs C-Sed and DM-Ex). Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. CONCLUSION: Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.


Assuntos
Diabetes Mellitus Experimental/terapia , Miocárdio/metabolismo , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/fisiologia , Remodelação Ventricular/fisiologia , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Terapia por Exercício , Coração/fisiopatologia , Masculino , Ratos , Ratos Wistar
4.
Nanoscale ; 7(22): 10218-32, 2015 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-25990927

RESUMO

Electrodeposited nano-hydroxyapatite (nHAp) is more similar to biological apatite in terms of microstructure and dimension than apatites prepared by other processes. Reinforcement with carbon nanotubes (CNTs) enhances its mechanical properties and increases adhesion of osteoblasts. Here, we carefully studied nHAp deposited onto vertically aligned multi-walled CNT (VAMWCNT) scaffolds by electrodeposition and soaking in a simulated body fluid (SBF). VAMWCNTs are porous biocompatible scaffolds with nanometric porosity and exceptional mechanical and chemical properties. The VAMWCNT films were prepared on a Ti substrate by a microwave plasma chemical vapour deposition method, and then oxidized and exfoliated by oxygen plasma etching (OPE) to produce graphene oxide (GO) at the VAMWCNT tips. The attachment of oxygen functional groups was found to be crucial for nHAp nucleation during electrodeposition. A thin layer of plate-like and needle-like nHAp with high crystallinity was formed without any need for thermal treatment. This composite (henceforth referred to as nHAp-VAMWCNT-GO) served as the scaffold for in vitro biomineralization when soaked in the SBF, resulting in the formation of both carbonate-rich and carbonate-poor globular-like nHAp. Different steps in the deposition of biological apatite onto VAMWCNT-GO and during the short-term biomineralization process were analysed. Due to their unique structure and properties, such nano-bio-composites may become useful in accelerating in vivo bone regeneration processes.


Assuntos
Durapatita/química , Nanocompostos/química , Nanotubos de Carbono/química , Óxidos/química , Alicerces Teciduais/química , Técnicas Eletroquímicas
5.
Bone Marrow Transplant ; 31(9): 809-12, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12732889

RESUMO

The majority of patients with hepatitis A have a benign course, but some may develop fulminant hepatitis and hematological complications. Peripheral stem cell transplantation (PSCT) is associated with loss of immunity. There are no data regarding loss of HAV antibodies (anti-HAV) after PSCT. We retrospectively evaluated the persistence of anti-HAV in a nonvaccinated population that underwent PSCT. Serum detection of anti-HAV was determined before and after PSCT using a qualitative commercially available enzyme immunoassay. From January 1997 to March 2001, 136 (68%) of 201 patients tested (+) for anti-HAV prior to PSCT. Subsequent investigation of anti-HAV was possible in 36 of these patients at a median of 12 months after PSCT. The median age of patients was 47 years old; they had diagnoses of hematological malignancies (33) and solid tumors (three), and underwent autologous (31) and allogenic (five) PSCT. A total of 31 (86%) of 36 patients remained anti-HAV (+) and five (14%) became (-) after PSCT. The variables age, sex, diagnosis, type of PSCT, time of testing, and number of CD34 cells infused were not predictors of loss of anti-HAV. In conclusion, 14% of 36 nonvaccinated anti-HAV (+) patients lost their antibodies at a median of 12 months after PSCT.


Assuntos
Formação de Anticorpos , Anticorpos Anti-Hepatite A/sangue , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Neoplasias Hematológicas/terapia , Humanos , Imunização , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Soroepidemiológicos , Transplante Autólogo , Transplante Homólogo
6.
J Chromatogr B Analyt Technol Biomed Life Sci ; 771(1-2): 303-28, 2002 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-12016006

RESUMO

Hepatocellular carcinoma (HCC or hepatoma) is the most common primary cancer of the liver. Persistent viral infection by the hepatic B or C virus is probably the most important cause of HCC worldwide. It is responsible for approximately one million deaths each year, predominantly in the underdeveloped and developing countries, but its incidence is also on the rise in the developed countries. For most patients suffering from HCC, long-term survival is rare, as they are presented late and are often unsuitable for curative treatment. Thus there is great interest to identify novel HCC diagnostic markers for early detection of the disease, and tumour specific associated proteins as potential therapeutic targets in the treatment of HCC. Proteome analyses of HCC cell lines and liver tumour tissues should facilitate the screening and discovery of these HCC proteins. The creation of a comprehensive HCC proteome database would be an important first step towards achieving this goal. This review presents an update of the two-dimensional electrophoresis proteome database of the cell line, HCC-M, which is also now freely accessible through the World Wide Web at http://proteome.btc.nus.edu.sg/hccm/.


Assuntos
Carcinoma Hepatocelular/metabolismo , Bases de Dados de Proteínas , Neoplasias Hepáticas/metabolismo , Proteoma , Eletroforese em Gel Bidimensional , Humanos
7.
Breast Cancer Res Treat ; 48(2): 135-47, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9596485

RESUMO

Human mammary carcinoma xenografts (MCF-7) growing in nude mice were treated with natural interferon alpha (n-IFN-alpha) alone or conjugated to a humanized monoclonal antibody (MoAb) anti-breast mucin (HuBrE-3vl) or to irrelevant human IgG1kappa. The IFN and the conjugates were administered as 20 intra-lesional (i.l.) injections to 1 of 2 xenografts in each mouse, or i.p. The growth inhibitory effects of HuBrE-3vl/nIFN-alpha were significantly greater than those of nIFN-alpha used as a single agent or conjugated to HuIgG1kappa. These effects occurred locally in the tumors receiving i.l. injections and systemically, although to a slightly lesser extent, in the noninjected tumors of mice treated i.l. and in the xenografts of mice treated i.p. Biodistribution studies showed that the uptake of 125I-HuBrE-3vl/nIFN-alpha by the tumors 24 hours after i.l. or s.c. injection was greater than that of 125I-HuIgG1kappa/nIFN-alpha, 125I-nIFN-alpha alone, or by normal tissues, documenting a tumor targeting effect and favorable tumor:normal tissues (T:NT) ratios. The targeting effects and the resulting tumor growth inhibition were favored by the IFN-mediated up-regulation of the HuBrE-3vl reactive antigen, which was more prominent after 3 weeks of treatment with HuBrE-3vl/nIFN-alpha. These results were superior to those we obtained previously with nIFN-alpha conjugated to another MoAb of the same group (Mc5). These studies point out the potential usefulness of HuBrE-3vl/nIFN-alpha for the local and systemic treatment of breast cancer lesions by providing a means of delivering high doses of IFN to the tumors while minimizing the amount of IFN binding to normal tissues.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Neoplasias da Mama/terapia , Carcinoma/terapia , Imunoconjugados/uso terapêutico , Interferon-alfa/administração & dosagem , Animais , Anticorpos Monoclonais/análise , Disponibilidade Biológica , Neoplasias da Mama/patologia , Carcinoma/patologia , Sistemas de Liberação de Medicamentos , Feminino , Interferon-alfa/farmacocinética , Interferon-alfa/uso terapêutico , Camundongos , Camundongos Nus , Distribuição Tecidual
8.
Ann Thorac Surg ; 61(2): 692-5, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8572789

RESUMO

BACKGROUND: Anecdotal reports of allergic and anaphylactic reactions after aprotinin therapy have raised concern that its repeat use may be associated with substantial morbidity. METHODS: To address this concern, we reviewed our experience with all patients who underwent implantation of a left ventricular assist device and subsequent cardiac transplantation with perioperative use of aprotinin. RESULTS: Twenty-three patients received full-dose aprotinin during left ventricular assist device implantation and subsequent cardiac transplantation. All patients tolerated primary exposure to aprotinin without complication. One episode of anaphylaxis after secondary exposure was treated with rapid institution of cardiopulmonary bypass. Although renal dysfunction was observed shortly after cardiac transplantation in 30.4% of patients, the effect was transient and occurred in the presence of cyclosporine. The one perioperative death after secondary exposure was unrelated to bleeding complications. No clinically evident thromboembolic events were documented. CONCLUSIONS: Primary and secondary exposure to aprotinin during operation with cardiopulmonary bypass is associated with limited intraoperative blood use, a low incidence of transient renal dysfunction and anaphylaxis, a rare need of reoperation for bleeding, and no clinical thromboembolic events.


Assuntos
Aprotinina/efeitos adversos , Transplante de Coração , Coração Auxiliar , Adulto , Aprotinina/administração & dosagem , Perda Sanguínea Cirúrgica , Ponte Cardiopulmonar , Ciclosporina/administração & dosagem , Esquema de Medicação , Transfusão de Eritrócitos , Feminino , Humanos , Hipotensão/induzido quimicamente , Testes de Função Renal , Masculino , Hemissuccinato de Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Troca Plasmática , Transfusão de Plaquetas , Medicação Pré-Anestésica , Reoperação
9.
J Interferon Cytokine Res ; 15(10): 839-48, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8564705

RESUMO

The potentiating effects of human recombinant tumor necrosis factor-alpha (rTNF-alpha) on the antitumor actions of recombinant interferon-gamma (rIFN-gamma) and of natural interferons alpha and gamma combined (nIFN-alpha/nIFN-gamma) were studied on human breast cancer xenografts growing bilaterally in nude mice. The cytokines were injected singly or in combination in one of the two tumors of each mouse to study local effects while the opposite tumor was left undisturbed to evaluate systemic effects. The tumors received 20 intralesional injections (four cycles of 5 daily injections each). In injected tumors the best results were obtained with nIFN-alpha/nIFN-gamma supplemented with rTNF-alpha. The responses were dose dependent, resulting in complete regression of 9 of 9 tumors with rTNF-alpha used at the dose of 5 micrograms per injection, of 6 of 8 tumors at the dose of 2.5 micrograms, and of 4 of 8 tumors at the dose of 0.5 microgram. Mostly mild to moderate partial responses were seen in the other groups. The systemic effects on the contralateral tumors were significantly less than the local effects on the corresponding tumors. Histologically, responding tumors showed reactive fibrosis and inflammatory cell infiltration. No vascular alterations were seen, presumably because of the immunodeficiency of nude mice. It was concluded that the potentiation of the antitumor actions of IFNs by rTNF-alpha was effective at the local but not at the systemic level.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Animais , Neoplasias da Mama/patologia , Sinergismo Farmacológico , Feminino , Humanos , Interferon Tipo I/uso terapêutico , Interferon gama/uso terapêutico , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Especificidade da Espécie , Transplante Heterólogo , Fator de Necrose Tumoral alfa/uso terapêutico
10.
Cancer Invest ; 13(2): 165-72, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7874570

RESUMO

Two groups of patients with disseminated breast carcinomas who had failed radiotherapy, chemotherapy, and hormonotherapy were treated with natural interferon alpha (nIFN-alpha) alone or in combination with nIFN-gamma delivered in cycles of 10-12 intralesional (i.l.) injections to recurrent and metastatic lesions. In group, I, 16 skin lesions in 12 patients received nIFN-alpha alone resulting in 7 complete regressions verified histologically (CR), 7 partial regressions (PR), and no regressions (NR) in 2. Group II included 4 patients in whom 7 cutaneous recurrences were treated with nIFN-alpha/nIFN-gamma (5 CR, 2 PR), 2 were injected with nIFN-alpha alone (1 CR, 1 PR), and 1 received nIFN-gamma alone (PR). Two additional patients in group II were given i.l. injections of nIFN-alpha/nIFN-gamma to lymph node metastases (1 CR, 1 PR). Clinical toxicity was experienced by 5 of 12 patients in group I and by all the patients in group II and was controlled in most instances by antipyretics. Systemic antitumor effects were not appreciable clinically. Nevertheless, noninjected lesions exposed only to systemic levels of IFNs, when studied immunohistochemically, displayed an immunological response similar to that of IFN-injected lesions, although less intense. Therefore, IFNs can be useful in controlling locoregional recurrences of breast cancer even in patients who are not responding to other forms of therapy. Furthermore, in addition to the local antitumor actions, they appear to be capable of eliciting systemic immunological effects.


Assuntos
Neoplasias da Mama/patologia , Carcinoma/secundário , Carcinoma/terapia , Interferon-alfa/uso terapêutico , Interferon gama/uso terapêutico , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/terapia , Neoplasias da Mama/terapia , Carcinoma/patologia , Feminino , Humanos , Imuno-Histoquímica , Injeções Intralesionais , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Interferon gama/administração & dosagem , Interferon gama/efeitos adversos , Indução de Remissão , Neoplasias Cutâneas/patologia
13.
Breast Cancer Res Treat ; 25(3): 265-76, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8369527

RESUMO

An immunoconjugate composed of natural interferon alpha (nIFN alpha) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN alpha/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN alpha/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN alpha on the injected tumors. Further enhancement was obtained when nIFN gamma or nIFN gamma together with Mc5 (at a dose 10 times larger than that present in nIFN alpha/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of 125I-nIFN alpha/Mc5 by the tumors was greater and its elimination slower than for 125I-nIFN alpha alone or conjugated to irrelevant mouse IgG1. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alpha alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.


Assuntos
Antígenos de Neoplasias/imunologia , Antígenos Glicosídicos Associados a Tumores , Neoplasias da Mama/terapia , Carcinoma/terapia , Imunotoxinas/uso terapêutico , Interferon-alfa/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Carcinoma/imunologia , Carcinoma/patologia , Divisão Celular/efeitos dos fármacos , Estudos de Viabilidade , Feminino , Humanos , Interferon-alfa/farmacocinética , Interferon gama/uso terapêutico , Camundongos , Camundongos Nus , Índice Mitótico , Transplante Heterólogo , Células Tumorais Cultivadas
14.
Cancer Res ; 52(17): 4571-81, 1992 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-1355007

RESUMO

Cutaneous recurrences of breast carcinomas were treated with 10 i.l. injections of nIFNs alpha and gamma delivered in combination (7 lesions) or singly (11 with nIFN-alpha, one with nIFN-gamma). Histologically confirmed complete regressions occurred in 5 of 7 lesions treated with nIFN-alpha/nIFN-gamma and in 5 of 11 recurrences injected with nIFN-alpha alone. In all cases specimens were obtained before and after therapy. In addition, in some cases (4 treated with nIFN-alpha/nIFN-gamma, 2 with nIFN-alpha, one with nIFN-gamma) multiple recurrences were injected simultaneously and were excised 24 h after 1, 3, and 10 injections and 21 days after completion of therapy. The main findings observed in the treated lesions undergoing complete and partial regressions included: (a) inhibition of mitotic activity and up-regulation of antigenic expression (mammary epithelial membrane antigen, intercellular adhesion molecule 1, HLA-DR) by the carcinoma cells; (b) activation of macrophages and dendrocytes with marked expression of HLA-DR and HLA-A,B,C; (c) infiltration of the dermis and tumors by activated T-lymphocytes (CD3+, CD4+, CD8+); (d) questionable participation by B-lymphocytes and natural killer cells; (e) activation of endothelium with enhancement of antigenic expression (intercellular adhesion molecule 1, HLA-DR), procoagulant activity, and vascular permeability. The responses elicited by nIFN-alpha/nIFN-gamma were greater than those caused by either IFN used alone. It appears that in these patients the IFNs exerted an antiproliferative action and potentiated a cell-mediated immunological response liminally present in the neoplastic tissues prior to therapy.


Assuntos
Neoplasias da Mama/terapia , Carcinoma/terapia , Interferon-alfa/administração & dosagem , Interferon gama/administração & dosagem , Neoplasias Cutâneas/secundário , Administração Cutânea , Vasos Sanguíneos/citologia , Moléculas de Adesão Celular/análise , Antígenos HLA/análise , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular , Células de Langerhans/citologia , Linfócitos/citologia , Macrófagos/citologia , Glicoproteínas de Membrana/análise , Mucina-1 , Receptores de Interleucina-2/análise , Recidiva , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
15.
J Interferon Res ; 8(5): 679-90, 1988 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3148672

RESUMO

Natural interferons (nIFNs) -alpha and -gamma were used to treat nude mice bearing bilateral xenografts of human breast cancer cells (MCF-7 and BT 20). The IFNs were administered singly or in combination by means of intralesional (i.l.) or intraperitoneal (i.p.) injections. In the animals treated intralesionally 1 of the 2 tumors was injected to study the local therapeutic effects, while the contralateral one was left undisturbed and used to assess systemic effects. Treatment of MCF-7 tumors with i.l. injections of nIFN-alpha and nIFN-gamma combined resulted in complete regression of the injected tumors in 8 of 20 mice treated for 2 weeks and in 10 of 10 mice of an additional group treated for 4 weeks. The corresponding contralateral tumors showed complete regression in 2 mice treated for 4 weeks and partial responses in the others. Incomplete responses were also observed when the IFNs were used singly or when they were delivered intraperitoneally. Similarly, in BT 20 xenografts the best results were obtained with i.l. injections of the 2 IFNs combined, but no complete regressions were achieved. These experiments provide further evidence for a synergistic interaction of nIFN-alpha and nIFN-gamma in vivo and indicate that the potentiated antitumoral activity is greater when these interferons are administered i.l.


Assuntos
Neoplasias da Mama/terapia , Interferon Tipo I/uso terapêutico , Interferon gama/uso terapêutico , Animais , Quimioterapia Combinada , Humanos , Interferon Tipo I/administração & dosagem , Interferon gama/administração & dosagem , Camundongos , Camundongos Nus , Transplante de Neoplasias , Transplante Heterólogo
17.
J Interferon Res ; 8(2): 207-15, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3379324

RESUMO

The effects of intralesional injections of human natural and recombinant interferons-alpha (nIFN-alpha and rIFN-alpha A) were studied in nude mice bearing bilateral xenografts of human mammary carcinoma cells (BT 20, MCF-7). One tumor of each animal received intralesional injections, while the contralateral tumor was left undisturbed. Thus, the injected tumors were subjected to the local action of the IFNs whereas the opposite ones were exposed to the systemic effects of the IFNs seeping into the subcutaneous tissue following the intratumoral injection. When used singly these IFNs exerted an inhibitory effect on the growth of both injected and contralateral tumors, but failed to cause complete regression. Many of the cells of treated BT 20 xenografts showed significant morphological alterations (increased cell volume and nuclear pleomorphism) as compared to the untreated controls. Morphological alterations in MCF-7 tumors were difficult to assess because of the inherent pleomorphism of these cells. The immunoreactivity of BT 20 and MCF-7 tumors to monoclonal antibodies directed against milk fat globule proteins and against HLA antigens was not appreciably affected by treatment with these IFNs. This study confirms that intralesional injections of human IFNs-alpha partially inhibit the growth of human breast cancer xenografts, probably through a direct effect on the carcinoma cells. Under the present experimental conditions, the intralesional and the subcutaneous routes of administration appear to offer comparable antitumor effectiveness.


Assuntos
Neoplasias da Mama/terapia , Interferon Tipo I/farmacologia , Animais , Anticorpos Monoclonais , Neoplasias da Mama/patologia , Feminino , Humanos , Interferon Tipo I/administração & dosagem , Camundongos , Camundongos Nus , Transplante de Neoplasias , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Transplante Heterólogo
18.
Am J Surg Pathol ; 11(12): 943-50, 1987 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2825550

RESUMO

Immunostaining of estrogen receptor was carried out on paraffin sections of breast carcinomas using an anti-estrophilin monoclonal antibody (D75P3 gamma) and the avidin-biotin technique. The tumors were fixed in Bouin's solution or in formalin for varying periods of time at room temperature or at 4 degrees C. Best results were obtained following fixation in Bouin's at room temperature or in formalin at 4 degrees C. The staining was localized in the nuclei of carcinoma cells and was heterogeneous in intensity and extent. Prolonged fixation resulted in decreased immunoreactivity and in the appearance of nonspecific cytoplasmic and background staining. The estrogen receptor immunostaining on paraffin sections was found to be in concordance with that on frozen sections (Abbott ER-ICA) and with the steroid-binding assay (dextran-coated charcoal) in over 90% of the cases. This method is of easy and rapid execution and yields reliable and reproducible results.


Assuntos
Anticorpos Monoclonais , Neoplasias da Mama/análise , Carcinoma/análise , Proteínas de Transporte/imunologia , Receptores de Estrogênio/análise , Idoso , Carcinoma Intraductal não Infiltrante/análise , Feminino , Humanos
19.
Cancer Res ; 46(8 Suppl): 4303s-4307s, 1986 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2425948

RESUMO

Estrogen receptor (ER) was detected in frozen sections of 36 breast carcinomas using an antiestrophilin monoclonal antibody according to an immunocytochemical technique elaborated and made available by Abbott Laboratories in the form of a kit (ER-immunocytochemical assay monoclonal). Immunostaining was confined to the nuclei of the carcinoma cells. In all positive specimens, nuclei with different staining intensities were present in addition to a variable number of unstained nuclei, presumably because of functional heterogeneity. Of the 36 carcinomas, 27 displayed positive immunostaining, 4 had no staining, and in 5 the staining was borderline. All specimens were assayed for ER content by the dextran-coated charcoal (DCC) technique. When the DCC values were compared with the results of immunostaining it was found that 4 tumors were negative and 27 were positive by both techniques, whereas of 5 cases with borderline staining 3 were negative by DCC and 2 had low DCC values. These correlations proved to be highly significant (P much less than 0.001). The number of stained nuclei (extent of staining) related to the DCC status in a significant manner (P less than 0.01), whereas the intensity of staining did not (P greater than 0.10). These results indicate that immunocytochemical visualization of ER using Abbott's "ER-Immunocytochemical Assay Monoclonal" kit is an easy, reproducible, and reliable technique.


Assuntos
Neoplasias da Mama/análise , Carcinoma/análise , Proteínas de Transporte/análise , Receptores de Estrogênio/análise , Idoso , Núcleo Celular/análise , Carvão Vegetal , Dextranos , Feminino , Congelamento , Histocitoquímica , Humanos , Pessoa de Meia-Idade , Receptores de Estrogênio/imunologia , Coloração e Rotulagem
20.
Educ Med Salud ; 19(2): 209-26, 1985.
Artigo em Espanhol | MEDLINE | ID: mdl-3928329

RESUMO

This paper offers a quantitative evaluation of the scientific information produced in Brazil on several endemic diseases: Chagas' disease, schistosomiasis, leishmaniasis, leprosy, malaria and filariasis. The source of data was the Index Medicus Latino Americano (IMLA), and the published scientific information was analyzed in general and specifically, by type of disease and year of publication. The indexed production of articles on the material of the Latin American countries as a whole increased from 3,506 articles in 1978 to 5,528 in 1982 (for an increase of 52.7%), whereas that of Brazil alone rose from 1,781 to 2,531 (an increase of 42.1%) during the same period. The output of articles on endemic diseases totaled 703 papers (6.3% of the total indexed production). Of this total, 441 (62.7%) was on applied research and 262 (37.3%) were on basic research, and these proportions held relatively constant. Chagas' disease and schistosomiasis accounted for 75.2% of that total over the period considered. The production of papers on the diseases of interest grew 79.2%, at the same rate as that of all biomedical information published in Brazil over the period. An equilibrium was reached between the numbers of basic and applied papers. The analysis also identified the core of Brazilian periodicals that most frequently publish information on those endemics. It was also found that a large proportion of articles by Brazilian authors are published in journals of international circulation, and the foreign journals that publish papers by researchers in Brazil were identified.


Assuntos
Serviços de Informação , Brasil , Doença de Chagas , Filariose , Humanos , Sistemas de Informação , Leishmaniose , Malária , Publicações Periódicas como Assunto , Esquistossomose
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