Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
1.
Oncol Rep ; 15(2): 479-83, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16391872

RESUMO

We analyzed the morphological changes accompanying the development of cancer in the mouse forestomach. The main aim of the study was to evaluate whether cancer in this area of the stomach arises de novo or undergoes a series of precancerous changes. Tumors were induced by the 1,2-dimethylbenz(a)antracene (DMBA) at a total dose of 4 mg/mouse. The suspected areas of the stomach were studied morphologically in 79 mice. Benign tumors (squamous-cell papillomas) and malignant tumors (squamous-cell carcinomas) were found in 40 mice. Tumors arose in all cases together with differential changes in the forestomach epithelium. These changes were seen as irregular diffuse hyperplasia or focal proliferation, with or without differential signs of dysplasia. Destruction of the basal epithelial membrane indicated transformation of the process into malignant invasive carcinoma. Thus, in chemically induced cancer of the forestomach, squamous-cell carcinoma develops as the final stage of morphologically recognizable precancerous changes in the epithelial layer. De novo formation of such tumors in the forestomach was not observed.


Assuntos
Carcinoma de Células Escamosas/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Carcinógenos/toxicidade , Carcinoma de Células Escamosas/induzido quimicamente , Feminino , Hiperplasia/patologia , Camundongos , Neoplasias Gástricas/induzido quimicamente
2.
In Vivo ; 20(4): 543-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16900787

RESUMO

Two-year-old mice of the long-living transgenic mice of the alphaMUPA strain were previously found to show higher tumor resistance than the their initial wild-type (WT) strain (Tirosh, 2003). To better understand the mechanism underlying the differences in tumorigenesis rates between the two mouse lines, the rate of tumorigenesis and survival effects were studied in alphaMUPA mice and parental WT mice exposed to dimethylbenz(a)anthracene (DMBA). Each animal received three intragastric feedings of DMBA, each one week apart, at doses of 2, 1, and 1 mg dissolved in 0.2 ml corn oil; thus, the total amount of the carcinogen was 4 mg/mouse. Control mice received corn oil. The alphaMUPA mice exhibited distinctly higher survival rates in experimental chemically-induced tumorigenesis compared to their WT counterparts: 93% vs. 67%, p =2.7. The rate of tumorigenesis differed between the mouse lines (yield was 1.5 and 2.1), owing to a distinct tendency toward decreased tumor frequency in the skin and forestomach in the alphaMUPA mice. The experimental duration was also significantly higher for transgenic mice: 35.9 +/- 1.2 weeks compared to 30.5 +/- 1.3 weeks in WT mice, p <0.01. The lungs, forestomach and skin were target organs for the carcinogenic effect of DMBA. Our observations suggest that aging promotes the rate of spontaneous and induced tumorigenesis.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Carcinógenos/toxicidade , Longevidade , Neoplasias Experimentais/mortalidade , 9,10-Dimetil-1,2-benzantraceno/administração & dosagem , Administração Oral , Animais , Carcinógenos/administração & dosagem , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Transgênicos , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/patologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo
3.
In Vivo ; 20(2): 253-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16634527

RESUMO

The potential preventive effect of the synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on spontaneous tumorigenesis in mice was studied. One-year-old female C3H/He mice were kept for 6.5 months under standard conditions. Epitalon was injected at a dose of 0.1 microg, 5 times a week. Long-term exposure to Epitalon in small doses did not show any toxic effect. Treatment with Epitalon decreased the number of tumor-bearing mice with malignant tumors and prevented the development of metastases. Spontaneous tumors of the reproductive organs (mammary glands and ovaries) were predominant in both groups of mice (control and experimental). The mammary gland tumors were different variants of invasive ductal carcinomas. In the ovaries, granulosa-cell tumors were found. Tumors were in the minority in other organs and had benign characteristics. In control mice, metastases were found in 3 out of 9 tumor-bearing mice, all of them being from tumors of the reproductive organs. Treatment with Epitalon slowed down the development of metastases from spontaneous tumors, and no metastases were found in the experimental mice. These data highlight the antimetastatic effect of Epitalon as part of its oncostatic properties.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Neoplasias Mamárias Animais/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Neoplasias/tratamento farmacológico , Oligopeptídeos/farmacologia , Animais , Carcinoma Intraductal não Infiltrante/prevenção & controle , Carcinoma Intraductal não Infiltrante/secundário , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Animais/patologia , Neoplasias Mamárias Animais/prevenção & controle , Camundongos , Camundongos Endogâmicos C3H , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Neoplasias/patologia , Neoplasias/prevenção & controle
4.
Oncol Rep ; 14(5): 1317-21, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16211303

RESUMO

Previously, we showed that the 66 and 51 kDa soluble tumor-associated antigens (sTAAs) have distinct suppressive effects on chemically induced mammary cancer in rats, both alone and in combination with the hormone-related anticancer drug tamoxifen. Here, we describe the effects of both sTAA and tamoxifen on the histological structure of ovaries in mammary tumor-bearing 30- to 34-week-old rats. Central ovary sections were pooled, the number of the healthy and degenerated follicles were counted, and the size of the corpora lutea was estimated. In follicular development primordial, primary, preantral and antral stages were recognized. Only healthy follicles with visible nuclei were counted. Follicular degeneration was estimated as the number of atretic follicles with follicular remnants. Treatment with tamoxifen alone or in combination with sTAA significantly increased the number of primordial follicles and atretic follicles in the ovaries, and promoted the formation of small follicular cysts. Total area of the corpora lutea decreased. sTAA participated in this process by increasing apoptosis in degenerated follicles.


Assuntos
Antígenos de Neoplasias , Antineoplásicos Hormonais/farmacologia , Neoplasias Mamárias Animais/fisiopatologia , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Tamoxifeno/farmacologia , Animais , Apoptose , Feminino , Folículo Ovariano/patologia , Ratos , Ratos Wistar
5.
Oncol Rep ; 14(6): 1625-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16273267

RESUMO

In our previous studies, we showed that soluble tumor-associated antigens (sTAA) of 66 kDa and 51 kDa have distinct tumor-preventive effects on chemically induced mammary cancer in rats and are able to repair the damage caused by tumorigenesis in its early stages. In the present study, we investigated whether these proteins can prevent the development of chemically induced tumors in mice. The study was performed on C3H/He mice which have the ability to develop many spontaneous tumors with age. Forty-four, 6-week-old mice were exposed twice at a 2-week interval to the carcinogen 9,10-dimethyl-1,2-benz(alpha)anthracene (DMBA), at a dose of 2 mg/mouse administered intragastrically. Two months later, the mice were divided into two groups. One group received sterile saline twice a week at a dose of 0.2 ml/mouse, intraperitoneally (i.p.). The other group received sTAA twice a week at a dose of about 10 microl in 0.2 ml of sterile saline/mouse, i.p. Periodically, all mice were checked for the presence of tumors. The experiment was terminated at week 35. Vaccination with sTAA increased the time of involvement of mice in the experiment, prevented the tumorigenic effect of DMBA, and inhibited further development of existing tumors.


Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Neoplasias Experimentais/imunologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Antígenos de Neoplasias/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/prevenção & controle , Camundongos , Camundongos Endogâmicos C3H , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/prevenção & controle , Neoplasias Ovarianas/induzido quimicamente , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/prevenção & controle , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/prevenção & controle , Fatores de Tempo , Neoplasias Uterinas/induzido quimicamente , Neoplasias Uterinas/imunologia , Neoplasias Uterinas/prevenção & controle
6.
Oncol Rep ; 13(4): 585-8, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15756427

RESUMO

This study examined whether soluble 66 and 51 kDa tumor-associated antigens (sTAA), isolated from the serum of rats with mammary cancer, possess specific suppressive effects on chemically-induced mammary tumorigenesis in syngeneic counterparts. Dimethylbenzanthracene (DMBA, 10 mg/rat, two administrations) was used to induce mammary tumors in 8-week-old Sprague Dawley rats. After the appearance of numerous tumors, preparations of sTAA (50 to 60 microg/rat in 0.5 ml sterile PBS) obtained from breast cancer patients (heterologous sTAA) or from syngeneic mammary tumor-bearing rats (syngeneic sTAA) were administered weekly for 12 weeks. The following groups of mammary tumor-bearing rats were studied: groups 1 and 3, control rats treated with saline; group 2, rats treated with heterologous sTAA; and group 4, rats treated with syngeneic sTAA. The experiment was terminated when tumors in 50% of the rats became ulcerous. The treatment with both types of sTAA significantly decreased, compared to controls and initial values, the yield and total area of the tumors. We conclude that syngeneic sTAA have tumor-suppressive properties, which are very similar to those in heterologous sTAA.


Assuntos
Antígenos de Neoplasias/biossíntese , Imunoterapia Ativa/métodos , Neoplasias Mamárias Animais/induzido quimicamente , Neoplasias Mamárias Animais/prevenção & controle , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/prevenção & controle , 9,10-Dimetil-1,2-benzantraceno , Animais , Antígenos de Neoplasias/imunologia , Carcinógenos/farmacologia , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
7.
Int J Mol Med ; 16(1): 127-33, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15942689

RESUMO

The role of protein components of the secretory immune system (SIS), such as the polymeric immunoglobulin receptor/secretory component (pIgR/SC), immunoglobulins (Igs) and joining (J) chain, in human intrauterine development was reviewed. These components are already present in 3.5- to 4-week-old embryos, and found in all tissues and organs of epithelial origin. The SIS is made up of two parts: the SIS of mucous membranes and their derivatives (mucosal or secretory immune system), and the SIS of barrier structures (barrier immune system). During organogenesis, SC disappears from the cells of organs that lose their exocrine Ig-secretion function, such as the hypophysis, pancreatic islands and adrenal glands. In cells and tissues of mesenchymal origin, SC is absent from the start, i.e. during their initial development. As examples of the barrier immune system, blood-tissue and tissue-tissue barriers, such as the chorion of the placenta, the epithelium of the choroid plexuses in the brain, as well as other barrier structures to Ig transfer were considered. Besides the SC and J chain, Fc receptors, cellular and tissue structures participate in this process. Three stages were described in Ig transfer: i) passing from the maternal blood into intervillous spaces and the trophoblast, ii) shifting in the intravillous stroma and its cells, and iii) excretion into embryonic (fetal) blood through the endothelium of the trophoblastic villous capillaries. Igs of maternal origin, mainly IgG and least abundant IgA, pass through the placental barrier in healthy embryos. Following a massive antigenic attack, the increased exocrine secretion of IgG, IgA, and IgM to a lesser extent, are already seen in embryos, reflecting increased functional activity of the SIS. Thus, in human intrauterine development, the SIS is a very early immune defensive system, which presents and acts before the appearance of the common lymphoid system.


Assuntos
Embrião de Mamíferos/embriologia , Embrião de Mamíferos/imunologia , Imunidade nas Mucosas/imunologia , Placenta/imunologia , Útero/imunologia , Útero/patologia , Feminino , Humanos , Imunoglobulinas/imunologia , Imunoglobulinas/metabolismo , Útero/metabolismo
8.
Int J Mol Med ; 16(3): 401-7, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16077946

RESUMO

We studied the effect of ascending infections of the birth canal on the transport of maternal immunoglobulins (Igs) through the placental barrier in humans. The study was performed on 41 human placentas obtained from embryos (n=21) and fetuses (n=20) who had died from different causes, including those connected with ascending infections of the birth canal, and seven placentas obtained after normal delivery at term. Different morphological and immunohistochemical methods were used. The transfer of Igs through the placental barrier is a complex process that involves tissues (trophoblast, stroma of the trophoblastic villi, and capillaries), cells (monocytes and erythroblasts) and molecular components (at least six types of transfer receptors and biologically active components). We found that the intensification of transfer of different types of maternal Igs (IgG, IgA, IgM) is accompanied by certain morphological and functional changes in the placental barrier. In normal development without infection, the transfer of IgG is steady and the process most intensive, while the transfer of IgA was evaluated in 75% of the cases, and of IgM in only 10%. Inflammation of the birth canal was accompanied by an increase in the transport of IgG in early embryogenesis, which was maintained throughout intrauterine development. In cases with moderate infection, transfer of IgG and IgA was found in all cases studied, while transfer of IgM was seen in 45% of the cases. In cases with massive infection, transfer of all three types of Igs was seen, the most intensive being of IgG and the least of IgM. Ascending infection of the birth canal changes dramatically the transport of Igs through the placenta and can be dangerous and even fatal for the embryo or fetus.


Assuntos
Imunoglobulinas/metabolismo , Inflamação/metabolismo , Placenta/metabolismo , Doença Aguda , Antígenos CD/análise , Feminino , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Imuno-Histoquímica , Infecções/metabolismo , Infecções/fisiopatologia , Inflamação/fisiopatologia , Placenta/irrigação sanguínea , Placenta/química , Gravidez , Transporte Proteico , Receptores Fc/análise , Fatores de Tempo , Trofoblastos/química , Trofoblastos/metabolismo
9.
In Vivo ; 19(3): 591-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15875781

RESUMO

The soluble p51 antigen alone, or in combination with the soluble p66 (as a preparation of the soluble tumour-associated antigens, sTAA) was shown to be useful in both cancer detection, prevention and therapy. CANCER DETECTION: In colon cancer patients with recurrent cancer, the blood level of p51 increased whereas the blood level of p66 did not change. The correlation and regression coefficients between the serum level of p51 protein and the progress in colon cancer were 0.48 and 0.88, respectively. In patients with melanoma, development of metastases significantly increased the blood levels of p51. The method was shown to be highly sensitive (92 to 96%) and moderately specific (42 to 65%) for the detection of different types of cancer, such as of the colon, uterus, ovary and breast, as well as melanoma. CANCER PREVENTION AND THERAPY: This was performed using a preparation of both p66 and p51 antigens. sTAA have both tumour-preventive and tumour-suppressive effects on chemically-induced cancers of the colon, skin and mammary glands in rats and mice. sTAA promote suppression of rat mammary tumours by different anticancer drugs, such as cyclophosphamide, tamoxifen and 5-fluorouracil. This effect was shown to be connected with activation of the host's immune system, especially that which is responsible for the activity of T and B lymphocytes. CONCLUSION: We propose the follow-up of cancer patients in order to verify, as early as possible, recurrent cancer and perform preventive therapy of suspect cancer patients with their own sTAA as a kind of autoimmunotherapy. Moreover, in combination with anticancer drugs, sTAA may serve as a new tool in prevention of the toxic side-effects of chemotherapy.


Assuntos
Neoplasias/terapia , Fosfoproteínas/análise , Transativadores/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Proteínas de Ligação a DNA , Feminino , Genes Supressores de Tumor , Humanos , Neoplasias/diagnóstico , Neoplasias/prevenção & controle , Fosfoproteínas/sangue , Valores de Referência , Transativadores/sangue , Fatores de Transcrição , Proteínas Supressoras de Tumor , Neoplasias Uterinas/diagnóstico
10.
In Vivo ; 19(3): 563-6, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15875777

RESUMO

The relationship between the rate of household low-frequency electromagnetic fields (EMF) and incidences of mammary tumors was studied in 1290 clinical case-records of female patients aged 60 and more over a period of 26 years, based on the materials of the Edith Wolfson Medical Center, Israel. The studied material was divided into two groups, each corresponding to a period of 13 years. Group I included patients with mammary tumors under observation from 1978 to 1990, who rarely used EMF-generating appliances. Group II consisted of patients being under observation in the period between 1991 and 2003, characterized by much more extensive use of personal computers (more than 3 hours a day), mobile telephones, television sets, air conditioners and other household electrical appliances generating EMF. 200,527 biopsy and surgery samples were analyzed. Mammary tumors were found in 2824 women (1.4%), of which 1290 cases (45.6%) were observed in elderly women. Most of the observed tumors--1254 (97.2%)--were epithelial neoplasms. Mammary tumors were found in 585 elderly women in Group I and 705 women in Group II. The case records of these patients showed that 114 elderly women (19.5%) in Group I and 360 (51.1%) in Group II were regularly exposed to EMF (mostly from personal computers) for at least 3 hours a day (chi2=57.2, p<0.001). There was a statistically significant influence of EMF on the formation of all observed epithelial mammary tumors in Group II. This influence is most evident for invasive ductal carcinomas, which was the commonest form of cancer in elderly women.


Assuntos
Poluição do Ar em Ambientes Fechados , Neoplasias da Mama/epidemiologia , Campos Eletromagnéticos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal/epidemiologia , Carcinoma Ductal/patologia , Feminino , Humanos , Israel/epidemiologia , Prontuários Médicos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/patologia
11.
Oncol Rep ; 10(6): 2059-61, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14534743

RESUMO

In this communication, we report for the first time, that immunization of cancer patients with autologous soluble tumor-associated antigens (sTAA) isolated from their own serum prevents the toxic side effects of chemotherapy, improves the patients' clinical status, and has therapeutic effects without chemotherapy. In 2001 and 2002, two cancer patients were treated, during chemotherapy, with autologous sTAA. Another benign tumor-bearing patient was treated with a medicinal herb and autologous sTAA. Doses for subcutaneous injections varied between 2.5 and 3 mg of sTAA in 0.5 ml of sterile distilled water. Injections were performed twice a week or at weekly intervals. In each case, the clinical status of the patient became more stable and healthier. Toxic side effects caused by chemotherapy decreased or even disappeared. No additional toxic side effects were observed after vaccination with sTAA. In the studied cases, a polyp disappeared and a metastatic brain tumor began to encapsulate. No metastases were seen in the case with colon adenocarcinoma. We concluded that vaccination of patients with autologous sTAA prevents the toxic side effects of chemotherapy in cancer patients and improves their clinical status. In the case with the benign tumor, this vaccination activated the host's immune system, prevented progress of the disease and even promoted tumor disappearance. We suggest that immunotherapy with autologous sTAA provides significant clinical benefits in cancer patients and appears to be an important new adjuvant treatment of cancer.


Assuntos
Adjuvantes Farmacêuticos/uso terapêutico , Antígenos de Neoplasias/biossíntese , Antineoplásicos/farmacologia , Vacinas Anticâncer , Imunoterapia Ativa/métodos , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Colo Sigmoide/cirurgia , Doenças do Colo/terapia , Feminino , Humanos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Pólipos/terapia , Doenças Vaginais/terapia
12.
Oncol Rep ; 12(6): 1329-33, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15547759

RESUMO

We showed previously that soluble tumor-associated antigens (sTAA) isolated from breast cancer patients could suppress chemically-induced tumorigenesis in rats in comparison to the effect of commercial human albumin (CHA). Herein we analyze the possible mechanism of those findings. The following groups of mammary tumor-bearing rats were used in the studies: i) control rats treated with saline; ii) rats treated with CHA; and iii) rats treated with human sTAA. Different zones of the spleen, regional lymph nodes and tumors and their cellular content (B and T cells) were analyzed using the methods of morphometry and immunohistochemistry. Treatment of tumor-bearing rats with CHA resulted in a significant decrease in the size of the germinal center of the follicles. The number of B lymphocytes in the mantle layer of the follicles, the marginal zone and red pulp decreased significantly. The number of CD8+ T cells also decreased in the marginal zone and red pulp, whereas the number of CD4+ T cells increased in the periarterial lymph sheath (PALS) and the red pulp. Reaction of the spleen to vaccination with sTAA manifested in a significant increase in the size of most areas of the white pulp and in the number of B lymphocytes. In lymph nodes from control rats or those treated with CHA, CD8+ lymphocytes mainly accumulated in the paracortical zone. In rats treated with sTAA, CD8+ lymphocytes accumulated also in the medulla. The number of CD4+ T cells in these rats sharply increased and accumulated mainly in the medulla around the vessels. The total number of lymphocytes was changed differently in different areas of tumors (peripheral vs. at depth). The number of CD8+ cells significantly increased at depth of tumors, and also the ratio in the number of these cells at depth of tumors compared to a periphery increased. No difference was found in response of lymph cells to different types of treatment. All findings indicated a strict antitumor effect of vaccination with the sTAA, which prevents the development of insufficiency of the immune system when an intensive immune reaction takes place.


Assuntos
Albuminas/farmacologia , Antígenos de Neoplasias/farmacologia , Linfócitos B/efeitos dos fármacos , Vacinas Anticâncer/imunologia , Neoplasias Mamárias Experimentais/imunologia , Linfócitos T/efeitos dos fármacos , Animais , Linfócitos B/imunologia , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/imunologia , Linfócitos T/imunologia
13.
Oncol Rep ; 11(2): 487-91, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14719088

RESUMO

This study examined whether the soluble 66- and 51 kDa tumor-associated antigens (sTAA), isolated from the serum of breast cancer patients, possess specific suppressive effects on chemically-induced rat mammary tumorigenesis in comparison to commercial human albumin. Dimethylbenzanthracene (DMBA, 10 mg/rat, 2 administrations) was used to induce mammary tumors in 8-week-old Sprague Dawley rats. After the appearance of many large tumors, preparations of sTAA (50-60 micro g/rat in 0.5 ml sterile PBS) or commercial human albumin (HA, in the same doses as sTAA) were administered weekly, for 10-14 more weeks. The following groups of mammary tumor-bearing rats were studied: i) control non-treated rats, ii) rats treated with HA, iii) rats treated with sTAA. The experiment was terminated when tumors in 70% of the rats became ulcerous. The treatment with sTAA significantly decreased, compared to controls, the yield and total area of the tumors. In rats treated with sTAA, the appearance of new tumors stopped at week 5 as compared to week 7 in rats treated with HA and week 10 in control rats. In rats treated with sTAA, the time of appearance of ulcerous tumors increased to 8 weeks, as compared to 6 weeks in controls and in rats treated with HA. Duration of the experiment increased from 11 weeks in controls to 12 weeks in rats treated with HA and to 14 weeks in rats treated with sTAA. We conclude that sTAA have tumor-suppressive properties, which are well-defined if the treatment is begun on small tumors.


Assuntos
Antígenos de Neoplasias/isolamento & purificação , Antígenos de Neoplasias/uso terapêutico , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/prevenção & controle , Albumina Sérica/uso terapêutico , 9,10-Dimetil-1,2-benzantraceno , Animais , Anticarcinógenos/uso terapêutico , Feminino , Humanos , Neoplasias Mamárias Experimentais/induzido quimicamente , Peso Molecular , Ratos
14.
Oncol Rep ; 12(1): 181-5, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15201981

RESUMO

We analyzed the role of T- and B-lymphocytes in the antitumor effects of the anticancer drug tamoxifen and soluble tumor-associated antigens (sTAA) on rat mammary carcinogenesis. Studies were performed on the spleen from the following groups of mammary tumor-bearing rats. i) Rats in group 1 were not exposed to DMBA and served as age-related controls. Rats in other groups were exposed to DMBA and received different types of treatment; ii) rats in group 2, received no additional treatment, and served as carcinogen-related controls; iii) rats in group 3 were treated with the commercial hormone-dependent anticancer drug tamoxifen by weekly subcutaneous (s.c.) injections of 10 mg dissolved in 0.5 ml distilled water per rat; iv) rats in group 4 were vaccinated s.c. weekly with a preparation of sTAA (50 micro l/rat) dissolved in 0.5 ml of phosphate-buffered saline; v) rats in group 5 were treated with tamoxifen and were also vaccinated with a preparation of sTAA. Different zones of the spleen were measured and their T- and B-cell contents were analyzed immunohistochemically. The treatment with tamoxifen significantly increased the total number of lymphocytes in the follicles, PALS (periarterial lymph sheath) and red pulp relative to all other groups. The combined treatment with tamoxifen and sTAA increased the areas of white pulp, the PALS, and marginal zone. The number of B-cells was higher in the marginal zone of spleens from age-related controls, as well as from rats treated with sTAA and those treated with tamoxifen and sTAA. The number of CD4+ lymphocytes in the PALS was higher in rats treated with sTAA and tamoxifen, and notably so in those treated with sTAA alone. The number of CD8+ lymphocytes was significantly lower in the PALS of spleens from all tumor-bearing rat groups compared to the unexposed age-related control rats. We suggest that the tumor-suppressive effect of sTAA and tamoxifen is accompanied by the activation of B- and T-lymphocyte production.


Assuntos
Antígenos de Neoplasias/uso terapêutico , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/patologia , Baço/imunologia , Linfócitos T/imunologia , Tamoxifeno/uso terapêutico , Animais , Feminino , Neoplasias Mamárias Experimentais/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
15.
Oncol Rep ; 9(5): 977-80, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12168058

RESUMO

The aim of this study was to evaluate the possible role of apoptosis-related proteins (ARP: Fas and Fas ligand, bcl-2, p53) in the progress of tumorigenesis in breast cancer. Epithelial tumor cells and lymphocytes were analyzed immunohistochemically for the rate of lymphoid infiltration and presence of ARP in 50 human breast tumors of different types. The tumors included: i) fibrocystic disease (n=12); ii) benign fibroadenoma (n=11); iii) carcinoma in situ (n=8); iv) invasive ductal carcinoma with high lymphoid infiltration (n=12); and v) invasive ductal carcinoma with lymphoid depletion (n=7). Both fibrocystic disease and fibroadenomas had low amounts of lymphocytes and very little lymphoid infiltration. In cancer in situ, expansion of lymphoid infiltrates and increased density of lymphocytes resulted in a rise in the total number of lymphocytes, reflecting intensification of the immune response. In carcinomas with high lymphoid infiltration, a significant increase in the number of Fas and FasL and p53-positive cells was found. The number of bcl-2-positive tumor cells in these tumors was not changed, whereas the number of bcl-2-positive lymphocytes decreased. In carcinomas with lymphoid depletion, the opposite picture was found as a result of deep subcompensation of the lymph system. ARP are present in a significantly higher number of lymphocytes than of the epithelial tumor cells. This indicates that the cells initiating apoptosis in tumors are themselves damaged by the process. The intense apoptosis in lymphocytes in malignant tumors may be one of the reasons for the progress of breast tumors.


Assuntos
Neoplasias da Mama/metabolismo , Glicoproteínas de Membrana/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Receptor fas/biossíntese , Apoptose , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/sangue , Carcinoma Intraductal não Infiltrante/metabolismo , Progressão da Doença , Células Epiteliais/metabolismo , Proteína Ligante Fas , Feminino , Fibroadenoma/sangue , Fibroadenoma/metabolismo , Humanos , Imuno-Histoquímica , Linfócitos/metabolismo , Glicoproteínas de Membrana/sangue , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Fatores de Tempo , Proteína Supressora de Tumor p53/sangue , Receptor fas/sangue
16.
Int J Mol Med ; 9(4): 425-30, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11891540

RESUMO

We have shown previously that soluble low-molecular-mass tumor-associated antigens (sTAA) promote the anti-tumor effect of the anticancer drug cyclophosphamide (CPA) on rat mammary carcinogenesis. In this study, we analyzed the possible mechanism underlying this phenomenon. Studies were performed on tumors obtained from the following groups of mammary tumor-bearing rats: i) control rats, ii) rats treated with sTAA, iii) rats treated with CPA, iv) rats treated with CPA and sTAA. All analyzed tumors represented different types of invasive duct carcinomas. The rate of lymphoid infiltration and T cell content (CD4+ and CD8+ cells) of tumors were analyzed immunohistochemically. In parallel, mitotic index was evaluated in tumor cells. In tumor-bearing rats, high lymphoid proliferation was found at the periphery of tumors, and to a lesser extent deep inside the tumors. In control tumors, CD4+ T cell content was very low whereas CD8+ cells were highly abundant, especially at the tumor periphery. Treatment with sTAA significantly increased the total number of lymph cells and the number of CD8+ lymphocytes inside the tumors. Cytoplasmic vacuolization, decreased mitotic index and various degrees of fibrosis were the most distinct changes in tumors treated with CPA alone. CPA also sharply decreased the activity of all lymph cells studied, especially of CD4+ lymphocytes which could no longer be observed following this treatment. The combined treatment of CPA and sTAA increased the number of lymph cells, although they did not reach control levels. Inhibition of mainly CD4+ lymphocyte synthesis of CPA was confirmed by the low CD4/CD8 ratio, which increased slightly after the combined treatment with CPA and sTAA. Findings in the present study demonstrate that vaccination with sTAA actively promotes the generation of the host's antitumor immune response.


Assuntos
Antígenos de Neoplasias/imunologia , Antineoplásicos Alquilantes/farmacologia , Ciclofosfamida/farmacologia , Imunoterapia , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/terapia , Linfócitos T/imunologia , Animais , Antígenos de Neoplasias/farmacologia , Antineoplásicos Alquilantes/imunologia , Relação CD4-CD8 , Ciclofosfamida/imunologia , Citotoxicidade Imunológica/efeitos dos fármacos , Feminino , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Mamárias Experimentais/patologia , Ratos , Ratos Sprague-Dawley , Linfócitos T/efeitos dos fármacos
17.
Int J Mol Med ; 10(4): 517-21, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12239604

RESUMO

We showed in a previous study that soluble low-molecular-mass tumor-associated antigens (sTAA) promote the anti-tumor effect of the anticancer drug cyclophosphamide (CPA) on rat mammary carcinogenesis. In this report, we analyzed the possible mechanism underlying this phenomenon. Studies were performed on the bone marrow and thymus from the following groups of rats: i) control rats, ii) rats treated with sTAA, iii) rats treated with CPA, iv) rats treated with CPA and sTAA. The cellular content of the bone marrow and thymus (CD4+ and CD8+ lymphocytes) was analyzed morphometrically and immunohistochemically. In the bone marrow, CPA caused significant substitution of cellular components with fatty tissue whereas sTAA repaired this process. We found that CPA affects mainly the process of myelogenesis whereas sTAA protect the production of lymphocytes. In the thymus, CPA alone or in combination with sTAA repaired the inhibition effect of DMBA on synthesis of CD4+ and CD8+ thymocytes. sTAA further increased the amount of CD8+ T lymphocytes in the medulla of the thymus. Data in the literature as well as the findings presented here demonstrate that the tested treatment, including vaccination with sTAA, actively promotes the generation of the host's antitumor immune response.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Biomarcadores Tumorais/farmacologia , Ciclofosfamida/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/imunologia , Animais , Medula Óssea/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Ratos , Timo/citologia , Timo/efeitos dos fármacos , Timo/imunologia
18.
Int J Mol Med ; 10(6): 773-8, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12430006

RESUMO

We studied whether feeding pregnant female rats different high fat diets affects structural zones in the spleen and lymph nodes, involved in production of T and B cells, as well as cell kinetics and apoptosis in some offspring with mammary glands tumors. Rat mothers were fed either a 7% or 15% corn-oil or a 7% or 15% olive-oil diet. At four weeks of age, female offspring (n=10-15 per group) were transferred to 7% corn oil diet. Five-week old offspring were exposed twice to the carcinogen, dimethylbenz(a)antracene (10 mg/rat/week). Three months later, tumors were counted and sized, and samples from the spleen, axillary lymph nodes and tumors collected for immunohistochemical analyses. Feeding the mothers with both the 7% and 15% olive-oil diets significantly increased the number of tumor-free rats in offspring. Tumors were characterized with active mitosis, intensive lymphoid infiltration inside a knot and high rates of apoptosis, particularly in tumors obtained from rats whose mothers were fed the 15% olive-oil diet. In the spleen, the 15% olive-oil diet significantly increased the areas of the follicles and germinal centers but only in tumor-free rats. In tumor-bearing rats, areas of germinal centers increased compared to the 7% olive-oil diet. The 15% olive-oil diet increased all areas of the lymph nodes in tumor-free rats, while in tumor-bearing rats, this diet increased the areas of the cortex and mantle layer. We conclude that exposure to various diets in utero and during lactation affects the immune system. In addition, the promotion of apoptosis may play a key role in the mechanisms involved in the transplacental effects on mammary tumor development as seen using a 15% olive-oil diet, similar to the high fat diets of Mediterranean countries.


Assuntos
Apoptose/fisiologia , Gorduras na Dieta/metabolismo , Linfonodos/metabolismo , Neoplasias Mamárias Animais/metabolismo , Baço/metabolismo , Animais , Óleo de Milho/metabolismo , Feminino , Cinética , Neoplasias Mamárias Animais/patologia , Neoplasias Mamárias Animais/prevenção & controle , Azeite de Oliva , Óleos de Plantas/metabolismo , Gravidez , Ratos
19.
Int J Mol Med ; 12(5): 797-801, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14533012

RESUMO

This study examined whether the soluble 66 and 51 kDa tumor-associated antigens (sTAA) could promote suppression by the anticancer drug 5-fluorouracil (5-Fu) of chemically induced mammary tumorigenesis, and which, if any, morphological changes in the immune organs accompany this treatment. Dimethylbenzanthracene (DMBA, 8 mg/rat, twice) was used to induce mammary tumors. After the appearance of many large tumors, the preparations of sTAA and 5-Fu, alone or in combination, were administered in weekly doses, for 4 weeks. The following groups of mammary tumor-bearing rats were studied: 1) control non treated rats, 2) rats treated with sTAA, 3) rats treated with 5-Fu, 4) rats treated with 5-Fu and sTAA. The experiment was terminated when tumors in 70% of control rats became ulcerous. Treatment with sTAA alone significantly decreased tumor yield and their total area relative to controls. Both of these parameters showed an even larger significant decrease after treatment with 5-Fu, and the most marked decrease was obtained after the combined treatment with 5-Fu and sTAA. Results demonstrated that not only do sTAA have tumor-suppressive properties, they also enhance the anticancer effects of 5-Fu and prevent its toxic side effects. Morphologically, the treatment with sTAA was manifested in a significant increase in the size of the spleen follicles and mantle layer compared to control rats with large tumors. The treatment with 5-Fu decreased the sizes of almost all areas of the spleen compared to control rats, whereas the combined treatment with 5-Fu and sTAA increased all these parameters to the levels found in rats treated with sTAA alone. The total areas of the cortex and paracortex in the lymph nodes increased after treatment with sTAA. Treatment with 5-Fu alone resulted in a significant decrease of these areas which, as seen in the spleen, increased after combined treatment with 5-Fu and sTAA. Similar changes were seen in the areas of the separate lymph node zones. We concluded that the addition of sTAA to conventional tumor chemotherapy regimens has a remarkable synergistic effect on mammary tumors leading to curative antitumor responses of the host's immune organs.


Assuntos
Antígenos de Neoplasias/administração & dosagem , Antígenos de Neoplasias/uso terapêutico , Fluoruracila/uso terapêutico , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/patologia , Animais , Antígenos de Neoplasias/farmacologia , Feminino , Fluoruracila/farmacologia , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Ratos , Ratos Sprague-Dawley , Solubilidade , Baço/efeitos dos fármacos , Baço/patologia
20.
Int J Mol Med ; 14(1): 35-42, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15202014

RESUMO

The role of joining (J) chain, one of the protein components of the secretory immune system (SIS), in the immune reactions of the human embryo and fetus was analyzed on the basis of data from the literature and our previous studies. All organs and structures, including extra-corporeal ones, of 18 embryos (4-8 weeks of development) and 45 fetuses (9-38 weeks) were studied using methods of pathomorphology, immunohistochemistry and morphometry. This approach enabled us to analyze the problem in the whole organism throughout its embryonic and fetal development. J chain, as well as polymeric immunoglobulin (Ig) receptor-secretory component (pIgR/SC) and Igs, are already widely distributed in 4-week-old embryos before the appearance of the common immune system. The whole complex of protein components of the SIS was seen in mucous layers, and in blood-tissue and tissue-tissue barrier structures. Therefore, we can consider two parts of the SIS: mucosal and barrier. Already in embryos, an increase in the functional activity of the SIS following massive antigenic attack in cases of acute chorioamnionitis reflects the increased exocrine secretion of Igs. The J chain appears to participate in the endocytosis but not exocytosis of Igs. J chain and Igs, but not pIgR/SC, were present in cells of the heart, endocrine glands, gonads and some other organs. The exocrine secretion of Igs, the main function of the SIS, is absent in these organs, and, they are therefore, not considered part of the SIS.


Assuntos
Desenvolvimento Embrionário/imunologia , Desenvolvimento Fetal/imunologia , Sistema Imunitário/metabolismo , Cadeias J de Imunoglobulina/metabolismo , Imunoglobulinas/metabolismo , Humanos , Cadeias J de Imunoglobulina/análise , Organogênese/imunologia , Transporte Proteico , Componente Secretório/análise , Componente Secretório/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA