RESUMO
OBJECTIVES: Galectins are mediators that play an important role in the inflammatory response and in this study we analyzed the expression of Galectins (Gal) -1, -3 and -9 in biopsies of the gastric antrum of patients with upper gastrointestinal symptoms. METHODOLOGY: 44 patients with upper digestive tract symptoms were evaluated, and underwent Upper Digestive Endoscopy examination. Sections of the gastric antrum were fixed in buffered formaldehyde at 4% in order to perform the anatomopathological examination and immunohistochemical analysis for Galectins-1, -3 and -9 expression. Fresh sections of gastric antrum were used for DNA extraction and evaluation of Helicobacter pylori (H. pylori). P values<0.05 were considered statistically significant. RESULTS: Gal-1 was significantly more expressed on stroma than epithelium (p<0.0001), whereas Gal-3 and Gal-9 were more expressed on epithelium (p<0.0001). Gal-3 was found to be significantly higher in the stroma of patients with H. pylori infection, mainly on Cag-A positive H. pylori (p<0.0001). Gal-9 was down modulated in stroma of patients with chronic gastritis. CONCLUSION: Up modulation of Gal-3 expression was associated with H. pylori infection and down modulation of Gal-9 with the inflammatory process of chronic gastritis.
Assuntos
Células Epiteliais/química , Galectina 3/análise , Galectinas/análise , Mucosa Gástrica/química , Gastrite/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/isolamento & purificação , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Biópsia , Proteínas Sanguíneas , Doença Crônica , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Humanos , Imuno-Histoquímica , Células Estromais/química , Células Estromais/microbiologia , Células Estromais/patologiaRESUMO
INTRODUCTION AND OBJECTIVES: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. MATERIALS AND METHODS: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: a-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Era and ERß. RESULTS: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERa. CONCLUSIONS: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.
Assuntos
Adenocarcinoma/patologia , Células Epiteliais/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias da Próstata/patologia , Células Estromais/patologia , Actinas/análise , Adenocarcinoma/química , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Proteínas de Ligação a DNA/análise , Progressão da Doença , Células Epiteliais/química , Receptor alfa de Estrogênio/análise , Fator 2 de Crescimento de Fibroblastos/análise , Proteínas Ligadas por GPI/análise , Humanos , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/análise , Masculino , Metaloproteinase 2 da Matriz/análise , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/análise , Células-Tronco Neoplásicas/química , Neoplasias da Próstata/química , Células Estromais/química , Fatores de Transcrição/análise , Microambiente Tumoral , Vimentina/análiseRESUMO
ABSTRACT Introduction and Objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. Materials and Methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: α-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Erα and ERβ. Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERα. Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/patologia , Células Epiteliais/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias da Próstata/patologia , Células Estromais/patologia , Actinas/análise , Adenocarcinoma/química , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Progressão da Doença , Proteínas de Ligação a DNA/análise , Células Epiteliais/química , Receptor alfa de Estrogênio/análise , /análise , Proteínas Ligadas por GPI/análise , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/análise , /análise , Gradação de Tumores , Proteínas de Neoplasias/análise , Células-Tronco Neoplásicas/química , Neoplasias da Próstata/química , Células Estromais/química , Microambiente Tumoral , Fatores de Transcrição/análise , Vimentina/análiseRESUMO
Patterns of invasion and stromal response are understudied in vulvar squamous cell carcinoma. The aim of this study was to explore whether histologic features such as an infiltrative pattern of invasion and fibromyxoid stromal response (FMX-SR) are meaningful prognostic factors. We reviewed 143 vulvar squamous cell carcinoma resections and correlated patterns of invasion and stromal response with patient age, ethnicity, depth of invasion, tumor size, perineural invasion (S100/AE1/3 stain), lymph node involvement (LNI), extranodal extension, margin status, pathologic stage, and recurrence. Univariate analyses of continuous variables were performed using t tests, whereas Pearson χ tests were used for categorical variables. Logistic regression analyses examined the relationship between histopathologic characteristics and clinical outcomes. There was a statistically significant association between infiltrative tumors and an FMX-SR in comparison with noninfiltrative tumors (P<0.001). Tumors with FMX-SR were significantly more deeply invasive (P=0.0025) and more likely to have LNI (P=0.0364), extranodal extension (P=0.0227), and perineural invasion (P=0.0011) compared with tumors without FMX-SR. For cases with negative surgical margins, the association between tumors with FMX-SR and LNI was significantly strengthened (odds ratio=4.73, P=0.0042), even after adjustments for age, race, and depth of invasion (odds ratio=4.34, P=0.0154). The presence of both FMX-SR and an infiltrative pattern of invasion in tumors with negative margins was significantly associated with LNI (P=0.0235) and recurrence (P=0.0124). These results suggest that interactions between nerve, tumor, and stromal cells play a role in tumor progression and represent additional prognostic factors that help stratify those patients at highest risk for LNI, extranodal extension, and recurrence.
Assuntos
Carcinoma de Células Escamosas/secundário , Fibroma/patologia , Nervos Periféricos/patologia , Células Estromais/patologia , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/cirurgia , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Fibroma/química , Fibroma/etnologia , Fibroma/cirurgia , Humanos , Modelos Logísticos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasia Residual , Razão de Chances , Nervos Periféricos/química , Estudos Retrospectivos , Fatores de Risco , Células Estromais/química , Fatores de Tempo , Resultado do Tratamento , Neoplasias Vulvares/química , Neoplasias Vulvares/etnologia , Neoplasias Vulvares/cirurgia , Adulto JovemRESUMO
Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma/química , Ácido Hialurônico/análise , Neoplasias Pulmonares/química , Escarro/química , Biópsia , Biomarcadores Tumorais/análise , Estudos de Casos e Controles , Carcinoma/patologia , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Pulmão/química , Pulmão/patologia , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Fumar/efeitos adversos , Células Estromais/química , Células Estromais/patologiaRESUMO
Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.
Assuntos
Carcinoma/química , Ácido Hialurônico/análise , Neoplasias Pulmonares/química , Escarro/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Carcinoma/patologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Pulmão/química , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Fumar/efeitos adversos , Estatísticas não Paramétricas , Células Estromais/química , Células Estromais/patologiaRESUMO
BACKGROUND: Very few studies have evaluated the expression of homeobox A10 (HOXA10) and steroid (estrogen and progesterone) receptors exclusively in deep endometriosis. Conclusions drawn from studies evaluating peritoneal and ovarian endometriosis are usually generalized to explain the pathogenesis of the disease as a whole. We aimed to evaluate the expression of HOXA10, estrogen receptor α (ER-α), progesterone receptor (PR), and PR-B in rectosigmoid endometriosis (RE), a typical model of deep disease. METHODS: We used RE samples from 18 consecutive patients to construct tissue microarray blocks. Nine patients each were operated during the proliferative and secretory phases of the menstrual cycle. We quantified the expressions of proteins by immunohistochemistry using the modified Allred score. RESULT: The HOXA10 was expressed in the stroma of nodules during the secretory phase in 5 of the 18 patients. Expression of ER-α (in 16 of 18 patients), PR (in 17 of 18 patients), and PR-B (17 of 18 patients) was moderate to strong in the glands and stroma of nodules during both phases. Expression of both PR (P = .023) and PR-B (P = .024) was significantly greater during the secretory phase. CONCLUSION: The HOXA10 is expressed in RE, where it likely imparts the de novo identity of endometriotic lesions. The ER-α, PR, and PR-B are strongly expressed in RE, which differs from previous studies investigating peritoneal and ovarian lesions. This suggests different routes of pathogenesis for each of the 3 types of endometriosis.
Assuntos
Endometriose/metabolismo , Endométrio/química , Receptor alfa de Estrogênio/análise , Proteínas de Homeodomínio/análise , Receptores de Progesterona/análise , Doenças Retais/metabolismo , Doenças do Colo Sigmoide/metabolismo , Análise Serial de Tecidos , Adulto , Endometriose/patologia , Endometriose/fisiopatologia , Endométrio/patologia , Endométrio/fisiopatologia , Células Epiteliais/química , Feminino , Proteínas Homeobox A10 , Humanos , Imuno-Histoquímica , Ciclo Menstrual , Doenças Retais/patologia , Doenças Retais/fisiopatologia , Doenças do Colo Sigmoide/patologia , Doenças do Colo Sigmoide/fisiopatologia , Células Estromais/químicaRESUMO
OBJECTIVE: To evaluate p27 protein expression in the endometrium of women with endometriosis. DESIGN: Transversal case-control study. SETTING: Endometriosis Unit, Federal University of São Paulo, Brazil. PATIENT(S): Thirteen patients with stage I/II endometriosis, five with stage III/IV endometriosis, and 11 control subjects. INTERVENTION(S): Endometrial biopsies were obtained from patients with proven endometriosis and women without disease at laparoscopy. P27 protein was immunolocalized in the biopsy tissues and quantified by light microscopy. MAIN OUTCOME MEASURE(S): Immunostaining scores of glandular and stromal cells in endometrial biopsies obtained from patients with confirmed endometriosis compared with those of healthy control women with normal pelvis at laparoscopy. The staining scores of stage I/II and stage III/IV patients and of both patient groups and the control group were compared. RESULT(S): The level of p27 protein expression observed in the control group, both in the stroma and in the endometrial glands, was significantly different from that observed in the endometriosis patient groups. Significant differences in p27 protein expression levels in the glandular epithelium and stroma were not observed among groups of patients with endometriosis. CONCLUSION(S): The decreased level of p27 protein in the endometrium of women with endometriosis suggests that cell cycle alterations in the endometrial mucosa may be involved in the pathogenesis of this disease.
Assuntos
Endometriose/metabolismo , Endométrio/química , Peptídeos e Proteínas de Sinalização Intracelular/análise , Biópsia , Estudos de Casos e Controles , Inibidor de Quinase Dependente de Ciclina p27 , Regulação para Baixo , Endometriose/patologia , Endométrio/patologia , Células Epiteliais/química , Feminino , Humanos , Imuno-Histoquímica , Laparoscopia , Índice de Gravidade de Doença , Células Estromais/químicaRESUMO
The aim of the present study was to monitor endometrial distribution and concentrations of oestrogen receptors alpha (ER alpha) and progesterone receptors (PR) by immunohistochemistry in Nelore cows (Bos taurus indicus) during the oestrous cycle. Blood samples were collected for progesterone measurement and endometrial samples were taken from the uterine horn contra lateral to the corpus luteum in 16 cows at days 0 (ovulation), 5, 9, 13 and 19 of the oestrous cycle. Immunostaining evaluation for ER alpha and PR in the glandular epithelium and uterine stroma was performed by two methods: positive nuclei counting and staining intensity of the nuclei. Specific positive staining reactions for both receptors were limited to cell nuclei and they were not identified in the cytoplasm. The proportion of ER alpha positive nuclei had a temporal variation throughout the oestrous cycle in both cell types evaluated and was higher in uterine stroma than the glandular epithelium (p < 0.05). The greatest proportion of ER alpha stained nuclei was observed at oestrus and during the initial and mid luteal phase (days 5, 9 and 13) (p < 0.05) in the glandular epithelium and at days 0, 5 and 9 in the uterine stroma (p < 0.01). The proportion of PR positive nuclei remained constant throughout the entire oestrous cycle for both cell types evaluated (p > 0.05). A higher proportion of PR positive nuclei was measured in the uterine stroma compared with the glandular epithelium (p < 0.05). Intensity of staining for ER alpha and PR varied throughout the oestrous cycle (p < 0.01). There was a higher staining intensity at days 0 and 5 in the stroma for ER alpha (p < 0.01) and PR (p < 0.01) and in the glandular epithelium at days 0, 5, 9 and 13 for ER alpha (p < 0.01) and at days 0, 5 and 9 for PR (p < 0.01) when compared with the other evaluated days. These data demonstrate that ER alpha and PR expression varied throughout the oestrous cycle in Nelore cows, in general with highest concentrations at oestrus and the lowest during the luteal phase. This is similar to patterns observed in Bos taurus taurus.
Assuntos
Bovinos , Endométrio/química , Prenhez/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Células Estromais/química , Animais , Receptor alfa de Estrogênio/análise , Receptor alfa de Estrogênio/metabolismo , Estro , Feminino , Imuno-Histoquímica/métodos , Imuno-Histoquímica/veterinária , Hibridização In Situ/métodos , Hibridização In Situ/veterinária , Gravidez , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Distribuição TecidualRESUMO
OBJECTIVE: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary tumour, classified as low, intermediate and high grade. Myofibroblasts are the main stromal component and are included as prognostic factor in some tumours. The aim of this study was to evaluate the myofibroblasts in the stroma of MEC with possible relationship to malignancy grading. METHODS: Twenty-five cases of MEC (six low grade, 11 intermediate grade, four high grade and four metastasis) were stained for vimentin, desmin and smooth muscle actin (SMA) for the identification of myofibroblasts. Transforming growth factors (TGFbeta1 and TGFbetaRII) were also assessed in our study. RESULTS: Myofibroblasts were present in all cases, in amounts varying according to histological grading. TGFbeta1 was positive in squamous cells of intermediate grade tumours, and in the stroma of only four cases. TGFbetaRII was positive in most squamous and intermediate cells, regardless of malignancy grading. CONCLUSIONS: Our study showed that the analysis of neoplastic stroma must be added to the studies of neoplastic cells to draw a better picture leading to tumour diagnosis and prognosis.
Assuntos
Carcinoma Mucoepidermoide/patologia , Fibroblastos/patologia , Neoplasias das Glândulas Salivares/patologia , Actinas/análise , Actinas/biossíntese , Carcinoma Mucoepidermoide/química , Carcinoma Mucoepidermoide/metabolismo , Desmina/análise , Desmina/biossíntese , Fibroblastos/química , Fibroblastos/metabolismo , Humanos , Imuno-Histoquímica , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/biossíntese , Prognóstico , Proteínas Serina-Treonina Quinases , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/análise , Receptores de Fatores de Crescimento Transformadores beta/biossíntese , Neoplasias das Glândulas Salivares/química , Neoplasias das Glândulas Salivares/metabolismo , Células Estromais/química , Células Estromais/metabolismo , Células Estromais/patologia , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta/biossíntese , Fator de Crescimento Transformador beta1 , Vimentina/análise , Vimentina/biossínteseRESUMO
The female prostate has aroused scientific interest because it is subjected to the same diseases compromising the male prostate during aging. The objective of this work was to characterize structurally, cytochemically, and ultrastructurally the tissue compartments of the normal adult female prostate of Meriones unguiculatus gerbils. The morphological analyses showed that the gerbil's female prostate is constituted of a cluster of glands and ducts inserted in a musculofibrous stroma. The alveolar epithelium is differentiated and consisted of basal proliferating cells, intermediary cells, and secretory cells. The secretory cells are the most numerous cell type and continuously secrete glycoproteins. The basal cells are the source of the secretory cells and they are then responsible for the alveolus renovation. The prostatic stroma is abundant and rich in elastic and collagen fibers, which are closely associated with smooth muscle cells and fibroblasts. The results showed that the gerbil's female prostate shows morphological and ultrastructural homology to the human female prostate (Skene's gland), and despite being a small organ, it is a mature and physiologically active gland.
Assuntos
Genitália Feminina/anatomia & histologia , Gerbillinae/anatomia & histologia , Próstata/anatomia & histologia , Animais , Epitélio/anatomia & histologia , Epitélio/ultraestrutura , Feminino , Genitália Feminina/citologia , Histocitoquímica , Humanos , Masculino , Próstata/citologia , Células Estromais/química , Células Estromais/ultraestruturaRESUMO
Proteoglycan and glycosaminoglycan content was analyzed in a model of rat mammary carcinoma to study the roles of these compounds in tumorigenesis. Hyaluronic acid and proteoglycans bearing chondroitin and/or dermatan sulfate chains were detected in solid tumors obtained after subcutaneous inoculation of Walker 256 rat carcinoma cells. About 10% of sulfated glycosaminoglycan chains corresponded to heparan sulfate. The small leucine-rich proteoglycan, decorin, was identified as one of the proteoglycans, in addition to others of higher molecular weight, by cross-reaction with an antiserum raised against pig laryngeal decorin and by N-terminal amino acid sequencing. Decorin was separated from other proteoglycans by hydrophobic chromatography and its complete structure was determined. It has a molecular weight of about 85 kDa and a dermatan chain of 45 kDa with 4-sulfated disaccharides. After degradation of the glycosaminoglycan chain, three core proteins of different molecular weight (36, 46 and 56 kDa) were identified. The presence of hyaluronic acid and decorin has been reported in a variety of tumors and tumor cells. In the Walker 256 mammary carcinoma model, hyaluronic acid may play an important role in tumor progression, since it provides a more hydrated extracellular matrix. On the other hand, decorin, which is expressed by stromal cells, represents a host defense response to tumor growth.
Assuntos
Neoplasias da Mama/química , Carcinoma 256 de Walker/química , Proteínas de Neoplasias/análise , Proteoglicanas/análise , Animais , Decorina , Eletroforese em Gel de Ágar , Eletroforese em Gel de Poliacrilamida , Proteínas da Matriz Extracelular , Glicosaminoglicanos/análise , Ácido Hialurônico/análise , Masculino , Ratos , Ratos Sprague-Dawley , Células Estromais/químicaRESUMO
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the major cytokines involved in control of haemopoiesis both in bone marrow and in extramedullar sites. Its biological activity depends upon the composition and physicochemical properties of the microenvironment provided by the supporting stroma. GM-CSF activity is modulated and controlled by the stromal heparan-sulphate proteoglycans, but their optimal interaction occurs only at low pH. We questioned whether the microenvironment organisation of the interface between stroma and haemopoietic cells provides such conditions. We studied myeloid progenitor proliferation in contact with bone marrow-derived and extramedullar stromas using electron microscopy and selective labelling of pericellular components. We present evidence that, upon interaction, the two cell types reorganise their interface both in shape and molecular composition. Haemopoietic cells extend projections that considerably increase the area of intercellular contact, and stromal cells form lamellipodia and carry out a redistribution of membrane-associated sialylated glycoconjugates and proteoglycans. Such rearrangements lead to extensive capping of negatively charged molecules at the interface between the supporting stroma and the haemopoietic cells, leading potentially to a local decrease in pH. Our results indicate that the distribution of negative charges at the cellular interface may be responsible for the selectivity of cell response to GM-CSF.
Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Mielopoese/fisiologia , Animais , Divisão Celular/fisiologia , Linhagem Celular , Extensões da Superfície Celular/ultraestrutura , Células Cultivadas , Técnicas de Cocultura , Células do Tecido Conjuntivo/fisiologia , Ferritinas/análise , Fibroblastos/citologia , Fibroblastos/fisiologia , Glicocálix/química , Glicocálix/ultraestrutura , Glicosaminoglicanos/análise , Glicosaminoglicanos/isolamento & purificação , Glicosaminoglicanos/fisiologia , Concentração de Íons de Hidrogênio , Indóis/análise , Camundongos , Camundongos Endogâmicos C3H , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Microscopia de Contraste de Fase , Células Progenitoras Mieloides/química , Células Progenitoras Mieloides/fisiologia , Células Progenitoras Mieloides/ultraestrutura , Ácido N-Acetilneuramínico/metabolismo , Neuraminidase/metabolismo , Compostos Organometálicos/análise , Ligação Proteica , Proteoglicanas/análise , Proteoglicanas/fisiologia , Pseudópodes/ultraestrutura , Rutênio Vermelho/análise , Rutênio Vermelho/farmacologia , Espalhamento de Radiação , Células Estromais/química , Células Estromais/fisiologia , Células Estromais/ultraestruturaRESUMO
Histoarchitectural changes of the uterine cervix allow its successful adaptation to different physiological conditions. In this study, we evaluated cell turnover in each cellular compartment of the uterine cervix in association with steroid hormone receptor expression in order to establish the range of physiological changes. Proliferation, apoptosis, and progesterone receptor (PR) and estrogen receptor alpha (ERalpha) expression were evaluated in cycling, pregnant, and postpartum rats. In estrus and diestrus II, ERalpha and PR expression exhibited variations according to the region evaluated. Proliferation and apoptosis showed a reciprocal pattern, the epithelium being the region with higher cell turnover. High apoptotic index (AI) in estrus was associated with the lowest ERalpha and the highest PR scores. During pregnancy, proliferation of the epithelium was the predominant event and AI was low. On Postpartum Day 1 (PPD1), proliferation decreased while apoptosis increased. As described for the estrous cycle, during pregnancy and PPD1, AI and ERalpha were negatively correlated. In the fibroblastic stroma, low proliferation was observed throughout pregnancy; however, there was a net increase in cell number because very few cells underwent apoptosis. No difference in ERalpha was observed in fibroblastic cells during pregnancy and postpartum; however, a great decrease of this receptor in the epithelial compartment was observed after delivery. Unlike cervical epithelium, PR was highly expressed in stromal cells. At term, a dramatic increase in epithelial PR was observed. While epithelial PR remained high on PPD1, a decrease was observed in muscle stroma. These results show that, in all stages studied, 1) ERalpha and PR have different patterns of expression with differential responses to signals that modulate proliferation and/or apoptosis depending on the cellular compartment, and 2) even though the epithelium is the region with the highest cell turnover, the fibroblastic and muscle stroma are active regions that have their own patterns of behavior.
Assuntos
Apoptose , Divisão Celular , Colo do Útero/química , Colo do Útero/citologia , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Animais , Diestro , Células Epiteliais/química , Células Epiteliais/citologia , Receptor alfa de Estrogênio , Estro , Feminino , Período Pós-Parto , Gravidez , Ratos , Ratos Wistar , Células Estromais/químicaRESUMO
Environmental estrogens (xenoestrogens) are chemicals that bind to estrogen receptor, mimic estrogenic actions, and may have adverse effects on both human and wildlife health. Bisphenol A (BPA), a monomer used in the manufacture of epoxy resins and polycarbonate has estrogenic activity. In male rodents prenatal exposure to BPA resulted in modifications at the genital tract level. Our objective was to examine the effects of in utero exposure to low, environmentally relevant levels, of the xenoestrogen BPA on proliferation and differentiation of epithelial and stromal cells on the prepubertal rat ventral prostate. To characterize the periductal stromal cells phenotype the expression of vimentin and smooth muscle alpha-actin was evaluated. Androgen receptor (AR) and prostatic acid phosphatase (PAP) expression were also evaluated in epithelial and stromal compartments. Prenatal exposure to BPA increases the fibroblastic:smooth muscle cells ratio and decreases the number of AR-positive cells of periductal stroma of the ventral prostate. In contrast, no differences in AR expression were observed in epithelial cells between control and BPA-treated groups. No changes in proliferation patterns were observed in epithelial and stromal compartments; however, the expression of PAP was diminished in prostate ductal secretory cells of rats in utero exposed to BPA. Our results suggest that prenatal exposure to BPA altered the differentiation pattern of periductal stromal cells of the ventral prostate. These findings are significant in light of the data on human prostate cancers where alterations in the stroma compartment may enhance the invasive and/or malignant potential of the nascent tumor.
Assuntos
Estrogênios não Esteroides/administração & dosagem , Fenóis/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal , Próstata/citologia , Próstata/efeitos dos fármacos , Fosfatase Ácida/análise , Actinas/análise , Animais , Compostos Benzidrílicos , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Epiteliais/química , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Receptor alfa de Estrogênio , Estrogênios não Esteroides/efeitos adversos , Feminino , Masculino , Fenóis/efeitos adversos , Gravidez , Próstata/fisiologia , Ratos , Ratos Wistar , Receptores Androgênicos/análise , Receptores de Estrogênio/análise , Células Estromais/química , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Vimentina/análiseRESUMO
BACKGROUND: Prostaglandin-E(2) and platelet-activating factor (PAF) are embryonic-derived signals that time embryo passage into the uterus in the mare and hamster respectively. PAF-like activity is detectable in the spent media of preimplantation human embryos and it has been suggested that PAF may be the embryonic signal that controls embryo transport to the uterus in our species. The actions of PAF are regulated at the level of its synthesis and degradation as well as the expression of a specific cell surface receptor (PAFr). The enzyme PAF acetylhydrolase (PAF-AH) degrades PAF. This study was undertaken to examine whether or not PAFr and PAF-AH are expressed in the human Fallopian tube and to identify the cell types in which they are expressed. METHODS: The presence of PAFr mRNA in tissue extracts was investigated using reverse transcription-polymerase chain reaction. We amplified the predicted amplicon for PAFr mRNA from RNA samples extracted from Fallopian tubes. The expression of PAF-AH was detected by Western blot and the localization of PAFr and PAF-AH proteins was detected by immunohistochemistry. RESULTS: Utilizing antibodies against PAFr and PAF-AH, co-localization of the two proteins in the epithelium and stromal cells were demonstrated. CONCLUSIONS: These observations show that the human Fallopian tube expresses PAFr and PAF-AH at a location compatible with the proposed paracrine role of early embryo-derived PAF.
Assuntos
Embrião de Mamíferos/fisiologia , Tubas Uterinas/química , Fosfolipases A/genética , Fator de Ativação de Plaquetas/fisiologia , Glicoproteínas da Membrana de Plaquetas/genética , Receptores de Superfície Celular , Receptores Acoplados a Proteínas G , Útero , 1-Alquil-2-acetilglicerofosfocolina Esterase , Western Blotting , Epitélio/química , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Fosfolipases A/análise , Glicoproteínas da Membrana de Plaquetas/análise , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/químicaRESUMO
We report a small, well-demarcated stromal tumor of the gallbladder in a 69-year-old woman. The tumor and associated cholelithiasis led to chronic cholecystitis symptoms. The wall of the gallbladder contained a 2.4-cm hypocellular nodule composed of bland spindle-shaped cells that were immunoreactive for vimentin, CD34, and CD117. With the latter antibody, which stains interstitial cells of Cajal (ICC), the neoplastic cells appear fusiform with elongated bipolar projections or dendritic-like cytoplasmic projections. The gallbladder wall adjacent to the tumor contained numerous CD117-positive cells in close contact with the normal smooth muscle cells, whereas two of 10 gallbladders with minimal chronic cholecystitis showed only a few CD117-positive cells. These findings provide evidence that this stromal tumor of the gallbladder shows ICC differentiation similar to some stromal tumors of the gut. The presence of numerous ICC in the uninvolved gallbladder wall suggests that this tumor might have evolved through hyperplasia of ICC.
Assuntos
Neoplasias da Vesícula Biliar/patologia , Plexo Mientérico/patologia , Neurilemoma/patologia , Células Estromais/patologia , Idoso , Antígenos CD34/análise , Biomarcadores Tumorais/análise , Colecistite/etiologia , Colecistite/patologia , Colelitíase/complicações , Colelitíase/patologia , Feminino , Neoplasias da Vesícula Biliar/química , Neoplasias da Vesícula Biliar/complicações , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Técnicas Imunoenzimáticas , Plexo Mientérico/química , Proteínas de Neoplasias/análise , Neurilemoma/química , Neurilemoma/complicações , Neurilemoma/cirurgia , Proteínas Proto-Oncogênicas c-kit/análise , Células Estromais/química , Vimentina/análiseRESUMO
The objective of the present study was to evaluate the cyclic changes and regional localization of immunoreactive c-fos and prolactin (PRL) in the human endometrium, using immunohistochemistry. Immunoreactive PRL was found in the epithelium of 9.1% of the proliferative specimens and in 55.6% of the secretory specimens (p < 0.05, Fisher's exact test). In the endometrial stroma, immunoreactive PRL was present in 9.1 and 66.7% of the proliferative and secretory samples, respectively (p < 0.01). Immunoreactive c-fos predominated in the stroma and was identified in 54.5% of the specimens in the proliferative phase, but in only 7.1% of those in the secretory phase (p < 0.05). The progesterone/estradiol ratio was lower in the patients expressing immunoreactive c-fos (median = 13.1 ng/ml) compared to those who did not (median = 84.5 ng/ml, p < 0.05). We conclude that immunoreactive c-fos is found mostly in stromal cells during the proliferative phase of the menstrual cycle, and is sharply reduced during the secretory phase, when the endometrium is under progesterone stimulation - attested by PRL production.
Assuntos
Endométrio/química , Ciclo Menstrual , Prolactina/análise , Proteínas Proto-Oncogênicas c-fos/análise , Adulto , Epitélio/química , Estradiol/análise , Feminino , Humanos , Imuno-Histoquímica , Progesterona/análise , Células Estromais/químicaRESUMO
The authors investigate the differences between the angiogenesis that occurs in malignant and benign breast tumours (10 specimens of invasive ductal carcinoma and 10 specimens of fibroadenoma) as well as in the adjacent breast stroma of these women highlighting the microvessels by staining their endothelial cells for factor VIII immunohistochemically. The number of vessels counted in invasive ductal carcinoma was significantly higher than the number of vessels counted in fibroadenoma and in the adjacent breast stroma. There was no difference between the number of vessels counted in the fibroadenoma and its adjacent stroma. Even though the patients with invasive ductal carcinoma showed a adjacent stroma with a higher number of vessels, the difference was not significant when compared with the adjacent stroma obtained from patients with fibroadenoma.