RESUMEN
Las células madre de origen mesenquimal (CMM) suscitan un interés especial debido a sus propiedades regenerativas, antiinflamatorias, antiapoptóticas, contra el estrés oxidativo, antitumorales o antimicrobianas. Sin embargo, su implementación en clínica se topa con inconvenientes de la terapia celular como la incompatibilidad inmunológica, la formación de tumores, la posible transmisión de infecciones, la entrada en senescencia celular y la difícil evaluación de seguridad, dosis y potencia; así como complejas condiciones de almacenamiento, elevado coste económico o uso clínico poco práctico. Considerando que los efectos positivos de las CMM se deben, en gran medida, a los efectos paracrinos mediados por el conjunto de sustancias que segregan (factores de crecimiento, citoquinas, quimiocinas o microvesículas), la obtención in vitro de esos productos biológicos posibilita una medicina regenerativa libre de células sin los inconvenientes de la terapia celular. No obstante, esa nueva innovación terapéutica implica retos, como el reconocimiento de la heterogeneidad biológica de las CMM y la optimización y estandarización de su secretoma (AU)
Stem cells of mesenchymal origin (MSC) arouse special interest due to their regenerative, anti-inflammatory, anti-apoptotic, anti-oxidative stress, antitumor or antimicrobial properties. However, its implementation in the clinic runs into drawbacks of cell therapy (immunological incompatibility, tumor formation, possible transmission of infections, entry into cellular senescence, difficult evaluation of safety, dose and potency; complex storage conditions, high economic cost or impractical clinical use). Considering that the positive effects of MSC are due, to a large extent, to the paracrine effects mediated by the set of substances they secrete (growth factors, cytokines, chemokines or microvesicles), the in vitro obtaining of these biological products makes possible a medicine cell-free regenerative therapy without the drawbacks of cell therapy. However, this new therapeutic innovation implies challenges, such as the recognition of the biological heterogeneity of MSC and the optimization and standardization of their secretome (AU)
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Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Trasplante de Células Madre Mesenquimatosas/tendencias , Medicina Regenerativa/métodos , Medicina Regenerativa/tendenciasRESUMEN
Stem cells of mesenchymal origin (MSC) arouse special interest due to their regenerative, anti-inflammatory, anti-apoptotic, anti-oxidative stress, antitumor or antimicrobial properties. However, its implementation in the clinic runs into drawbacks of cell therapy (immunological incompatibility, tumor formation, possible transmission of infections, entry into cellular senescence, difficult evaluation of safety, dose and potency; complex storage conditions, high economic cost or impractical clinical use). Considering that the positive effects of MSC are due, to a large extent, to the paracrine effects mediated by the set of substances they secrete (growth factors, cytokines, chemokines or microvesicles), the in vitro obtaining of these biological products makes possible a medicine cell-free regenerative therapy without the drawbacks of cell therapy. However, this new therapeutic innovation implies challenges, such as the recognition of the biological heterogeneity of MSC and the optimization and standardization of their secretome.
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Medicina , Células Madre Mesenquimatosas , Humanos , Tratamiento Basado en Trasplante de Células y Tejidos , Células Madre , Medicina RegenerativaRESUMEN
Toll-like receptors (TLRs) have achieved an extraordinary amount of interest in cancer research due to their role in tumor progression. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4, 7 and 9 in cutaneous malignant melanoma (CMM). The expression levels of TLR3, 4, 7 and 9 were analyzed in tumors from 30 patients with CMM. The analysis was performed by immunohistochemistry, and the results were correlated with various clinicopathological findings and with relapse-free survival. Our results indicate that there was a wide variability in the immunostaining score values for each receptor. Positive staining for TLRs was generally found in tumor cells, especially for TLR4 and TLR9. Nevertheless, a significant percentage of tumors also showed TLR4 expression in mononuclear inflammatory cells (62.1 %) and in fibroblast-like cells (34.5 %). Our results showed no significant association between score values for each TLR and clinicopathological characteristics of patients. However, our results demonstrated that high TLR4 expression was significantly associated with a shortened relapse-free survival (p = 0.001). Therefore, TLR4 expression may be a new prognostic factor of unfavorable evolution in cutaneous malignant melanoma.
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Biomarcadores de Tumor/análisis , Melanoma/inmunología , Neoplasias Cutáneas/inmunología , Receptor Toll-Like 3/análisis , Receptor Toll-Like 4/análisis , Receptor Toll-Like 7/análisis , Receptor Toll-Like 8/análisis , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Melanoma/mortalidad , Melanoma/patología , Melanoma/terapia , Persona de Mediana Edad , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Adulto JovenRESUMEN
Urothelial bladder cancer represents a heterogeneous disease with divergent pathways of tumorigenesis. Tumor invasion and progression are a multifactorial process promoted by microenvironmental changes that include overexpression of matrix metalloproteinases (MMPs). Recent data clearly challenge the classic dogma that MMPs promote metastasis only by modulating the remodeling of extracellular matrix. Indeed, MMPs have also been attributed as an impact on tumor cell behavior in vivo as a consequence of their ability to cleave growth factors, cell surface receptors, cell adhesion molecules, and chemokines/cytokines. Levels of the different MMPs can be measured in several sample types, including tissue, blood (serum and plasma), and urine, and using different methodologies, such as immunohistochemistry, real-time PCR, western and northern blot analyses, enzyme-linked immunosorbent assay, and zymography. Several MMPs have been identified as having potential diagnostic or prognostic utility, whether alone or in combination with cytology. Although MMP inhibitors have shown limited efficacy, advances in the understanding of the complex physiologic and pathologic roles of MMPs might permit the development of new MMP-specific and tumor-specific therapies. In this paper we update the understanding of MMPs based on a systematic PubMed search encompassing papers published up to December 2011.
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BACKGROUND: Toll-like receptors (TLRs) have achieved an extraordinary amount of interest in inflammatory diseases due to their role in the inflammatory activation. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive the inflammatory response and activate the adaptive immune system. AIMS: The aim of this study was to investigate and compare the expression and clinical relevance of TLRs and interleukins in pediatric and adult celiac disease (CD), defined as intolerance to dietary proteins found in wheat, barley, and rye. METHODS: The expression levels of TLR3, TLR4, and TLR7, interleukins, and different transcription factors were analyzed on duodenal biopsies from ten children and 31 adults with CD, and 21 duodenal controls biopsies without CD (ten children and 11 adults). The analyses were performed by immunohistochemistry and real-time PCR. RESULTS: There were no significant differences in the studied parameters between adults and children. TLR4 expression level was increased twofold in CD specimens compared to controls. CD patients with high levels of TLR4 also showed high levels of interleukins (IL1, IL6, IL8, and IL17) as well as transcription factors (IRAK4, MyD88, and NF-κB). CONCLUSIONS: TLR4 expression is associated with CD independently of age at diagnosis. Pediatric patients and adult patients have a similar inflammatory profile, making it possible to treat both with the same immunological therapy in the future.
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Enfermedad Celíaca/metabolismo , Duodeno/metabolismo , Interleucinas/metabolismo , Receptores Toll-Like/metabolismo , Adulto , Estudios de Casos y Controles , Enfermedad Celíaca/patología , Niño , Femenino , Humanos , Inflamación/genética , Inflamación/metabolismo , Interleucinas/genética , Masculino , ARN/genética , ARN/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Toll-Like/genéticaRESUMEN
BACKGROUND: Extracellular matrix metalloproteases (MMPs) have raised an extraordinary interest in cancer research because of their potential role in basal membrane and extracellular matrix degradation, consequently facilitating tumour invasion and metastases development. METHODS: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs 1, 2, 7, 9, 11, 13, 14, and their tissue inhibitors, TIMPs 1, 2 and 3. More than 2600 determinations on cancer specimens from 133 patients with clinically localised prostate carcinoma, 20 patients with prostatic intraepithelial neoplasia and 50 patients with benign prostate hyperplasia and controls, were performed. RESULTS: When compared with benign pathologies, prostate carcinomas had higher expression of all MMPs and TIMPs. Dendogram shows a first-order division of tumours into two distinct MMPs/TIMPs molecular profiles, one of them with high MMPs/TIMs expression profile (n=70; 52.6%). Tumours with high expression of MMP-11 or -13, or cluster thereof, were significantly associated with higher probability of biochemical recurrence. CONCLUSION: The expression of MMPs and TIMPs seems to have an important role in the molecular biology of prostate carcinomas, and their expression by tumours may be of clinical interest to used as indicators of tumour aggressiveness.
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Adenocarcinoma/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasia Intraepitelial Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Adenocarcinoma/secundario , Anciano , Biomarcadores de Tumor/metabolismo , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Pronóstico , Hiperplasia Prostática/patología , Neoplasia Intraepitelial Prostática/patología , Neoplasias de la Próstata/patología , Tasa de Supervivencia , Análisis de Matrices TisularesRESUMEN
PURPOSE: Metalloproteases (MMPs) and their tissue inhibitors of metalloproteases (TIMPs) are involved in several key aspects of tumoral growth, invasion and metastasis. The purpose of this study was to characterize on how the different histological types of breast cancer differ in the expression of several components of this enzymatic system. METHODS: An immunohistochemical study was performed in 50 ductal, 23 lobular, 14 mucinous, 7 tubular, 4 papillary and 5 medullary invasive carcinomas, using tissue arrays and specific antibodies against 7 MMPs and 3 tisullar TIMPs. Staining results were categorized by means of a specific software program (score values). RESULTS: Carcinomas of the ductal type showed higher score values for MMPs and TIMPs than the other histological types; whereas mucinous carcinomas had lower scores values for expressions of the majority of these proteins. Stromal fibroblasts were more frequently positive for MMP-1, -7 and -13 and TIMP-1 and -3, when present in carcinomas of the ductal type than in other histological types of breast carcinomas. Stromal mononuclear inflammatory cells were more frequently positive for MMP-1 and TIMP-3, but more often negative for MMP-7, -9 and -11, when located in carcinomas of the ductal type than in other histological types of breast carcinomas. CONCLUSIONS: We found variations in MMP/TIMP expressions among the different histological subtypes of breast carcinomas suggesting differences in their tumor pathophysiology.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Metaloproteasas/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Carcinoma Medular/metabolismo , Carcinoma Medular/patología , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Matrices TisularesRESUMEN
BACKGROUND: Several studies have suggested the significance of some metalloproteases in the malignant behaviour of hepatocellular carcinoma. AIMS: To evaluate the liver expression of MMPs and their tissular inhibitors in patients with HCC. METHODS: An immunohistochemical study using tissue microarrays on samples obtained from 30 HCC patients, with antibodies against MMPs (1, 2, 7, 9, 11, 13 and 14) and TIMPs (1, 2 and 3) was performed. Results were correlated with various clinico-pathological findings and with overall survival. RESULTS: MMP-1 is mainly expressed by stromal cells, and MMP-13, TIMP-1 and TIMP-2 by inflammatory cells. A positive correlation between MMP-1 expression and larger size tumours (p<0.01) was found. Increased TIMP-2 expression was associated with higher preoperative serum levels of alpha-fetoprotein (p<0.01). Unsupervised hierarchical clustering for total score values designated two groups, one of them characterised by high MMPs and TIMPs expressions, including 21 cases (70%) for tumour cell clustering, 5 cases for fibroblasts (16.6%) and 6 cases for inflammatory cells (20%). All patients showing elevated MMPs and TIMPs expression in stromal cells presented a poor prognosis (p<0.05). CONCLUSIONS: High liver MMPs and TIMPs expressions in peritumour stromal cells are related to a poorer prognosis in HCC.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Anciano , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Hígado/citología , Hígado/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Células del Estroma/metabolismo , Análisis de SupervivenciaRESUMEN
An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 5,000 determinations on cancer specimens from 124 patients with invasive breast cancer were performed at the center of the tumor and the invasive front. Immunostaining for MMPs/TIMPs by fibroblasts was evaluated. To identify specific groups of tumors with distinct expression profiles, the data obtained from both fibroblast populations were analyzed by unsupervised hierarchical cluster analysis. Intratumor stromal fibroblasts more frequently showed expression of MMP-2, -7, and -14, and TIMP-3, but less frequently of MMP-9 than fibroblasts at the invasive front. Multivariate analysis showed that a high profile of MMPs and TIMPs staining in both fibroblast populations was the most potent predictor factor of distant metastases, whereas a low staining profile in fibroblasts was associated with a low risk of metastases.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/enzimología , Fibroblastos/enzimología , Metaloproteinasas de la Matriz/biosíntesis , Inhibidores Tisulares de Metaloproteinasas/biosíntesis , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Análisis por Conglomerados , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Invasividad Neoplásica/patología , Pronóstico , Células del Estroma/enzimología , Análisis de Matrices TisularesRESUMEN
An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and -14, tissular inhibitors of metalloproteinase (TIMP)-1, -2 and -3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast were performed. To identify specific groups of tumours with distinct expression profiles the data were analysed by unsupervised hierarchical cluster analysis by each cellular type. We did not find well-defined cluster of cases for tumour cells or fibroblastic cells. However, for mononuclear inflammatory cells the dendogram shows a first-order division of the tumours into two distinct MMP/TIMP molecular profiles, designated group 1 (n=89) and group 2 (n=42). Matrix metalloproteinase-7, -9, -11, -13 and -14, and TIMP-1 and -2, were identified as showing significant high expression in group 2 compared with group 1. Multivariate analysis demonstrated that clustering for mononuclear inflammatory cells was the most potent independent factor associated with distant relapse-free survival (group 2: 5.6 (3.5-9.6), P<0.001). We identify a phenotype of mononuclear inflammatory cells infiltrating tumours, which is associated with the development of distant metastasis. Therefore, this finding suggests that these host inflammatory cells could be a possible target for inhibition of metastasis.
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Neoplasias de la Mama/enzimología , Carcinoma Ductal/enzimología , Carcinoma Ductal/secundario , Leucocitos Mononucleares/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Biomarcadores de Tumor/metabolismo , Western Blotting , Neoplasias de la Mama/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Leucocitos Mononucleares/inmunología , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Tasa de Supervivencia , Análisis de Matrices Tisulares/métodosRESUMEN
AIMS: To evaluate the expression of androgen receptors (AR) and two androgen-induced proteins [apolipoprotein D (ApoD) and pepsinogen C (PepC)] in ductal carcinoma in situ (DCIS) of the breast. METHODS AND RESULTS: AR, ApoD and PepC expression was examined in 28 cases of pure DCIS and in 31 cases of DCIS adjacent to invasive carcinoma of the breast using immunohistochemical methods and then correlated with the architectural subtype, the degree of differentiation and the ostrogen receptor (ER)/progesterone receptor (PgR)/HER-2 status. We found no significant differences between pure DCIS and DCIS adjacent to invasive breast cancer regarding the percentage of positive cases for ApoD (64.3% versus 54.8%), PepC (42.9% versus 48.4%), ER (64.3% versus 58.1%), PgR (60.7% versus 58.1%) and HER-2 (39.3% versus 67.7%). However, there was a significantly higher percentage of AR+ DCIS among those adjacent to invasive carcinomas of the breast than among pure DCIS lesions (93.5% versus 60.9%) (P = 0.009). AR expression did not correlate with architectural subtype, degree of differentiation, or ER/PgR/HER-2/ApoD/PepC status, in cases of pure DCIS, nor in DCIS adjacent to invasive carcinoma of the breast. CONCLUSIONS: AR expression may represent an independent predictive factor in DCIS of the breast.
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Apolipoproteínas D/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Glicoproteínas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Pepsinógeno C/metabolismo , Receptores Androgénicos/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS: We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specific antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitative score based on their intensity, and the percentage of immunostained cells was measured. RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.
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Apolipoproteínas D/análisis , Carcinoma Hepatocelular/química , Glicoproteínas/análisis , Neoplasias Hepáticas/química , Hígado/química , Proteínas de Transporte de Membrana/análisis , Receptores Androgénicos/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Adulto , Anciano , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases.
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Neoplasias de la Mama/enzimología , Carcinoma Ductal/enzimología , Metaloproteinasas de la Matriz/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Anciano , Neoplasias de la Mama/patología , Carcinoma Ductal/patología , Femenino , Humanos , Inmunohistoquímica , Isoenzimas/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Matrices Tisulares/métodosRESUMEN
PURPOSE: we investigated by immunohistochemistry the pepsinogen C (pepC) expression in uveal melanomas and analyzed the possible relationship to clinicopathological parameters and prognostic significance. METHODS: We studied 22 patients who had undergone enucleation of the eyeball or local tumor resection for uveal melanoma. The specimens were immunostained for pepC on formalin-fixed, paraffin-embedded sections. Sex, age, tumor location, histological type, local invasion, postoperative treatment and metastasis were evaluated. RESULTS: Eleven tumors (50%) were positive for pepsinogen C. The percentage of pepC-positive tumors was significantly higher in uveal melanomas with scleral invasion than in those without scleral invasion (p < 0.01). PepC expression was significantly associated with a shortened overall survival (p < 0.05). CONCLUSIONS: Our results show that pepsinogen C may be expressed by uveal melanoma and suggest that this protein could be considered as a new, unfavorable prognostic factor in these tumors.
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Melanoma/metabolismo , Melanoma/patología , Pepsinógeno C/metabolismo , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Hyaluronan a high-molecular weight glycosaminoglycan, is considered to be involved in the growth and progression of malignant tumours. The objective of this work was to evaluate the cytosolic hyaluronan content in gastric cancer cells, its possible relationship with clinicopathological tumour parameters and its potential prognostic significance. METHODS: Cytosolic hyaluronan levels were examined utilizing immunoenzymatic techniques in 129 patients with gastric cancer. The mean follow-up period for these patients was 28 months. RESULTS: Cytosolic hyaluronan levels ranged widely in tumours as well as in adjacent mucosal samples (median (range) 2822 (50-24,523) versus 3650 (507-20,782) ng/mg protein). Statistical analysis showed that tumour hyaluronan levels correlated significantly with patient's sex and the presence of lymphatic invasion. In addition, high tumour hyaluronan levels were significantly associated with shorter overall survival period (p<0.05). CONCLUSIONS: Our results suggest that high tumoral cytosolic hyaluronan levels are associated with lesions of unfavorable outcome in gastric cancer patients. Thus, hyaluronan may provide additional prognostic information to that given by other biochemical markers currently used in gastric cancer.
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Adenocarcinoma/clasificación , Ácido Hialurónico/análisis , Recurrencia Local de Neoplasia , Neoplasias Gástricas/química , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Citosol/química , Femenino , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Análisis de SupervivenciaRESUMEN
PURPOSE: we investigated by immunohistochemistry the pepsinogen C (pepC) expression in uveal melanomas and analyzed the possible relationship to clinicopathological parameters and prognostic significance. METHODS: We studied 22 patients who had undergone enucleation of the eyeball or local tumor resection for uveal melanoma. The specimens were immunostained for pepC on formalin-fixed, paraffin-embedded sections. Sex, age, tumor location, histological type, local invasion, postoperative treatment and metastasis were evaluated. RESULTS: Eleven tumors (50%) were positive for pepsinogen C. The percentage of pepC-positive tumors was significantly higher in uveal melanomas with scleral invasion than in those without scleral invasion (p<0.01). PepC expression was significantly associated with a shortened overall survival (p<0.05). CONCLUSIONS: Our results show that pepsinogen C may be expressed by uveal melanoma and suggest that this protein could be considered as a new, unfavorable prognostic factor in these tumors. (Int J Biol Markers 2004; 19: 240-4).
RESUMEN
BACKGROUND: The protein encoded by the c-erbB-2 gene is a membrane receptor expressed in a variety of solid human cancers and directly related to poor prognosis. The objective of this work was to evaluate the clinical value of the quantification of membranous oncoprotein levels in gastric cancer. MATERIALS AND METHODS: Membranous c-erbB-2 levels were examined by means of a sandwich immunoenzymatic assay in 82 patients with gastric cancer. The median follow-up period for these patients was 16 months. In addition, c-erbB-2 expression was analyzed by immunohistochemistry in 57 gastric carcinomas. RESULTS: Membranous c-erbB-2 levels ranged widely in the studied tumors (44-112,000 NHU/mg protein). Median c-erbB2 content was significantly higher in intestinal-type tumors than in diffuse-type tumors (p = 0.01). In addition, high levels of c-erbB-2 were significantly associated with shorter relapse-free survival and overall survival in patients with resectable gastric carcinomas (p = 0.01 and p = 0.04, respectively). However, the correlation between immunohistochemistry and ELISA determinations did not reach statistical significance. CONCLUSION: Our results suggest a potential prognostic value of membranous c-erbB-2 quantification by immunoenzymatic assay in gastric cancer. However, its possible role in the selection of patients with a view to the possible introduction of Herceptin as a novel drug against gastric cancer is at present uncertain.
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Membrana Celular/metabolismo , Receptor ErbB-2/biosíntesis , Neoplasias Gástricas/metabolismo , Anciano , Supervivencia sin Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoensayo , Inmunohistoquímica , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Factores de TiempoRESUMEN
BACKGROUND: The Trefoil Factor 1 (TFF1/pS2), a peptide consisting of 60 amino acids, is the most abundant estrogen-induced messenger RNA in MCF-7 breast cancer cells and is also expressed by colorectal carcinomas. The objective of this work was to evaluate the cytosolic TFF1 content in colorectal carcinomas, its possible relationship with estrogen and progesterone receptors as well as with clinicopathological tumor parameters, and its potential prognostic significance. METHODS: Cytosolic TFF1 levels were examined by immunoradiometric assay in 178 patients with resectable colorectal cancer. The mean follow-up period was 32 months. RESULTS: There was a wide variability of cytosolic TFF1 levels in tumor-surrounding mucosa samples (0.09-42.5 ng/mg protein) as well as in tumors (0.01-270 ng/mg protein). Comparison of paired mucosa and carcinoma samples showed significantly higher TFF1 levels in tumors (mean: 17.1 ng/mg protein) than in mucosa samples (10 ng/mg protein) (p = 0.027). TFF1 levels were significantly higher in mucosa samples surrounding distal colon and rectal tumors (p = 0.0001) and in tumor samples obtained from older patients (p = 0.007). However, there were no significant differences in tumor TFF1 levels with respect to clinicopathological parameters such as the patient's sex, tumor location, stage, histological grade, ploidy, S-phase, or tumor estrogen and progesterone receptors. In addition, there was no significant relationship between tumor TFF1 levels and disease outcome. CONCLUSIONS: TFF1 may play an as yet undetermined role in the tumorigenesis of colorectal carcinomas. However, cytosolic levels of TFF1 do not seem to have any prognostic significance in colorectal carcinomas.