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P L Fernández

Publications and source records attributed to P L Fernández.

At least 19 recordsLinked to original sources
PubMed2006

Fibrous Histiocytoma-like Spindle-Cell Proliferation in the Nipple After Body-Piercing.

We report the case of a 19-year-old pregnant woman who presented with a nipple tumor. The lesion consisted in a spindle-cell proliferation with histologic features similar to those of fibrous histiocytoma, with a highly vascularized stroma. Although it showed low mitotic activity, scattered marked atypical cells with prominent nucleoli were identified, thus raising concern about the benign nature of the tumor. Immunohistochemical evaluation revealed that the spindle cells were diffusely positive for vimentin, focally positive for CD68, and negative for all the other tested antibodies. The patient had a total excision of the lesion and she is free of disease after 30 months. To our knowledge this is the first reported case of a lesion of this type in the nipple after body-piercing.

Adult↗
PubMed2005

Activation of nuclear factor-kappaB in human prostate carcinogenesis and association to biochemical relapse.

Nuclear factor (NF)-kappaB/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-kappaB/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-kappaB active state. Nuclear localisation of NF-kappaB was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-kappaB was detected in 57 (66.3%) specimens, and nuclear NF-kappaB (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-kappaB staining was not correlated (P=0.19). By univariate analysis, nuclear localisation of NF-kappaB was associated with biochemical relapse (P=0.0009; log-rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P=0.02), Gleason score (P=0.03) and nuclear NF-kappaB (P=0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-kappaB/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-kappaB is an independent prognostic factor of biochemical relapse in prostate cancer.

Adenocarcinoma↗
PubMed2005

Clinical axillary recurrence after sentinel node biopsy in breast cancer: a follow-up study of 220 patients.

PURPOSE: The aim of this study was to evaluate the frequency of false-negative (FN) sentinel node procedures in patients with breast cancer and the subsequent clinical outcome in such patients. METHODS: A total of 325 breast cancer patients underwent sentinel lymph node biopsy at our institution between June 1998 and May 2004. A 2-day protocol was used to localise the sentinel node with the injection of 99mTc-nanocolloid. There were two phases in the study: the learning phase (105 patients) and the application phase (220 patients). In the learning phase, a complete lymphadenectomy was always performed. In the application phase, sentinel nodes were studied intraoperatively and lymphadenectomy was performed when considered warranted by the pathological intraoperative results. RESULTS: The median follow-up duration in the 220 patients studied during the application phase was 21.2 months (range 4-45 months). In this phase a total of 427 sentinel nodes were obtained (range 1-5 per patient, median 1.99), with 66 positive sentinel nodes in 56 patients (26%). The lymphadenectomies performed were also positive in 25% of cases (14 patients). We observed a total of two false-negative sentinel lymph node results (3.45%). One of them was found during the surgical excision of non-sentinel nodes, and the other presented as an axillary recurrence 17 months postoperatively (1.72% clinical false-negative rate). The latter patient died 1 year after the first recurrence. CONCLUSION: After a median follow-up of 21.2 months we observed only one clinical recurrence among 220 patients. Our results indicate that adequate local control is achieved by application of the sentinel node protocol.

Adult↗
PubMed2004

Natural gamma radiation map (MARNA) and indoor radon levels in Spain.

During the last decade, the Department of Applied and Medical Physics has been involved in the development of a radiation protection programme. In the framework of this programme, measurements of indoor radon, principally, have been carried out nationwide. Geometric mean radon concentrations of 45 Bq m(-3) in the whole country and 130 Bq m(-3) in the high natural radiation area have been estimated. On the other hand, the so-called MARNA Project is developed into the framework of an agreement subscribed between the Spanish Nuclear Safety Council (CSN) and the National Uranium (ENUSA), the first phase of which has been the elaboration of the Natural Gamma Radiation Map of Spain on the scale of 1:1,000,000 using radiometric data generated in the 30 years of the lifetime of the ancient National Uranium Exploration and Investigation Plan mainly through airborne, carborne, and by foot surveys, within the MARNA Project itself. The lowest averaged dose rate from external gamma radiation (19.3 nGyh(-1)) was found in carbonate bedrock and the highest (87.7 nGyh(-1)) was found in granite and clay bedrock. This paper summarizes the main results obtained from the measurements performed in both projects, with special interest in those concerning the correlation between the data reported in order to conclude about the potential benefit of the MARNA maps in the definition of affected areas in the country.

Air Pollution, Indoor↗
PubMed2004

Conversion factors for external gamma dose derived from natural radionuclides in soils.

Field in situ gamma radiation exposure rates and laboratory measured radioactivity contents of 1500 Spanish soils were compared. The main objective was to determine if published theoretically derived conversion factors would yield accurate quantitative activity concentration (Bq kg(-1)) for the data carried out in different surveys developed by our laboratory during the last ten years. The in situ external gamma dose rate results were compared to laboratory gamma analysis of soils samples gathered from each site, considering the concentrations of seven radionuclides: 40K, 214Pb, 214Bi, 212Bi, 212Pb, 208Tl and 228Ac. The coefficient of correlation found between these variables indicate a good relationship. A discussion of the factors contributing to the uncertainties as well as measurement procedure are also given in this paper.

Environmental Monitoring↗
PubMed2001

Expression of cathepsins B and S in the progression of prostate carcinoma.

Cathepsins B and S (CatB, CatS) are lysosomal cysteine proteases which, among other functions, appear to play a role in cancer progression in different tumor models due to their matrix-degrading properties. To investigate their possible involvement in the development of prostate carcinoma, we immunohistochemically analyzed CatB and CatS in 38 primary human prostatic adenocarcinomas, as well as concomitant high-grade prostatic intra-epithelial neoplasia, nodular hyperplasia and normal tissue. CatB expression was observed in 28 (74%) and CatS in 32 (84%) carcinomas, being concomitant in 24 cases (63%). High-grade intra-epithelial neoplasia expressed CatB in 20/23 cases (87%), and a similar result was obtained for CatS, with expression of both coinciding in 18 cases (78%). In non-neoplastic tissue, strong expression of both proteases was observed in macrophages, inflamed glands and transitional metaplasia, whereas atrophic glands and basal cells of normal glands displayed intense CatB positivity. We conclude that CatB and CatS are often expressed together in neoplastic prostatic cells from pre-invasive to invasive and clinically detectable stages, suggesting a putative role in local invasion, though other functions cannot be ruled out.

Adenocarcinoma↗
PubMed2001

Tissue macroarrays ("microchops") for gene expression analysis.

We describe a simple system of tissue arraying with multiple tissue fragments obtained with a biopsy punch from selected areas of paraffin blocks. The new blocks thus constructed allow multiple tissue sections in which the uniform shape of the fragments coupled with a geometrical display and a significant amount of tissue per case allows a dependable, cost-effective way to screen tumors or other kinds of tissues with techniques such as immunohistochemistry. This system avoids the disadvantages of previous laborious methods of tissue arraying, such as expensive equipment and scarce tissue sampling, and it can be implemented in any institution with minimal cost and elaboration.

DNA, Neoplasm↗
PubMed2001

Differential expression of cdc25 cell-cycle-activating phosphatases in human colorectal carcinoma.

cdc25 is a family of cell-cycle phosphatases that activate the cyclin-dependent kinases. cdc25A and B, but not C, have oncogenic potential in vitro. In this study, we analyzed the possible implication of cdc25 genes in the progression of colorectal tumors. RNA and DNA were extracted from 34 paired tumor and normal colorectal tissues and examined by Northern blot, RT-PCR, and Southern blot, respectively. Protein expression was analyzed by Western blot in a subset of normal and tumor samples. The expression levels were correlated with the clinicopathologic characteristics and survival of the patients. cdc25B mRNA was overexpressed in 19 carcinomas (56%). A significant correlation was observed between high cdc25B mRNA levels and the relapse-free, overall, and cancer-related survival of the patients. The cdc25B2 splicing variant was detected in 27 carcinomas (79%) but only in 9 normal samples (26%) and was associated with the grade of the differentiation of the tumors. cdc25A mRNA was overexpressed in four tumors (12%) and cdc25C1 mRNA was overexpressed in nine tumors (26%). A new cdc25C2 splicing variant lacking exon 4 and 5 was identified in all of the tumors and in 56% of the normal samples. No amplifications or gene rearrangements of these genes were detected. In conclusion, these findings indicate that cdc25 isoforms and splicing variants are differentially regulated in colorectal carcinomas and may participate in the development of these tumors. Additionally, the correlation between cdc25B mRNA levels and the survival of the patients also suggest that the cdc25B isoform may be involved in the progression of the disease.

Adult↗
PubMed2000

cdc25a and the splicing variant cdc25b2, but not cdc25B1, -B3 or -C, are over-expressed in aggressive human non-Hodgkin's lymphomas.

cdc25 is a family of phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and -B, but not -C, have been shown to have oncogenic potential. Three different splicing variants of the cdc25B gene, cdc25B1, -B2 and -B3, have also been identified. Experimental studies suggest that cdc25B2 may be more active in vivo than cdc25B3 and -B1, but the relative expression of these splicing variants in human tumors is not known. In this study, we have analyzed the expression of cdc25A, -B1, -B2, -B3 and -C mRNA in 9 non-neoplastic lymphoid samples, 89 non-Hodgki&ngrave;s lymphomas and 9 hematological cancer cell lines by semi-quantitative RT-PCR. cdc25A, -B and -C protein expression was examined by Western blot. Normal peripheral blood lymphocytes and reactive tissues expressed cdc25B1 and -B3 mRNA and very low or undetectable levels of cdc25A, -B2 and -C. High levels of cdc25A and cdc25B2 were found in 35% and 39% of the tumors, respectively, and they were more frequently observed in aggressive than in indolent lymphomas. cdc25B1 and -B3 splice variants were detected in virtually all tumors, and no significant differences were found between high- and low-grade lymphomas. cdc25A and -B protein expression was also higher in aggressive than in indolent lymphomas. cdc25C expression was relatively low in virtually all cases. In conclusion, these findings suggest that cdc25A and -B2, but not cdc25B1, -B3 and -C, are over-expressed in a relatively large number of malignant lymphomas and may participate in the pathogenesis of aggressive variants.

Blotting, Western↗
PubMed2000

INK4a/ARF locus alterations in human non-Hodgkin's lymphomas mainly occur in tumors with wild-type p53 gene.

INK4a/ARF locus codes for two different proteins, p16(INK4a) and p14(ARF), involved in cell cycle regulation. p14(ARF) is considered an upstream regulator of p53 function. To determine the role of these genes in the pathogenesis of human non-Hodgkin's lymphomas we have analyzed exon 1beta, 1alpha, and 2 of the INK4a/ARF locus and p53 gene aberrations in 97 tumors previously characterized for p16(INK4a) alterations. p53 alterations were detected in four of 51 (8%) indolent lymphomas but in 15 of 46 (33%) aggressive tumors. Inactivation of p14(ARF) was always associated with p16(INK4a) alterations. Exon 1beta was concomitantly deleted with exon 1alpha and 2 in eight tumors. One additional lymphoblastic lymphoma showed deletion of exon 1alpha and 2 but retained exon 1beta. No mutations were detected in exon 1alpha and 1beta in any case. Two of the three mutations detected in exon 2 caused a nonsense mutation in the p16(INK4a) reading frame and a missense mutation in the ARF reading frame involving the nucleolar transport domain of the protein. The third mutation was a missense mutation in the p16(INK4a) reading frame, but it was outside the coding region of p14(ARF). Aggressive lymphomas with p14(ARF) inactivation and p53 wild type showed a significantly lower p53 protein expression than tumors with no alteration in any of these genes. In this series of tumors, inactivation of the INK4a/ARF locus mainly occurred in tumors with a wild-type p53 gene because only two lymphomas showed simultaneous aberrations in these genes. Tumors with concomitant alterations of p16(INK4a) and p14(ARF)/p53 genes seem to exhibit a worse clinical behavior than lymphomas with no alterations or isolated inactivation of any of these genes. These findings indicate that p14(ARF) genetic alterations occur in a subset of aggressive NHLs, but they are always associated with p16(INK4a) aberrations. Concomitant disruption of p16(INK4a) and p14(ARF)/p53 regulatory pathways may have a cooperative effect in the progression of these tumors.

Carrier Proteins↗
PubMed2000

HPLC determination of catechins and caffeine in tea. Differentiation of green, black and instant teas.

A simple and fast high performance liquid chromatographic method for five catechins and caffeine using an ODS column and a water-acetonitrile-formic acid mobile phase system was developed. The catechins (epicatechin, catechin, epigallocatechin, epigallocatechin gallate, epicatechin gallate) and caffeine were separated by an acetonitrile gradient within 20 min. The detection limit of the method was approximately 10 ng for all the compounds (by injecting 10 microL). Several green, black and instant teas were analysed using this method. By using the studied compounds as chemical descriptors, linear discriminant analysis was performed and complete differentiation of the green, black and instant teas was achieved.

Caffeine↗
PubMed2000

Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase, creatine kinase and enolase activity and isoenzymes in breast carcinoma.

We have compared the levels of phosphoglycerate mutase (EC 5.4.2.1), 2,3-bisphosphoglycerate phosphatase (EC 3.1.3.13), creatine kinase (EC 2.7.3.2) and enolase (EC 4.2.1.11) activities and the distribution of their isoenzymes in normal breast tissue and in breast carcinoma. Tumour tissue had higher phosphoglycerate mutase and enolase activity than normal tissue. Creatine kinase activity was higher in seven out of 12 tumours. In contrast 2,3-bisphosphoglycerate phosphatase activity was lower. Phosphoglycerate mutase, enolase and 2,3-bisphosphoglycerate phosphatase presented greater changes in the oestrogen receptor-negative/progesterone receptor-negative breast carcinomas than in the steroid receptor-positive tumours. Determined by electrophoresis, type BB phosphoglycerate mutase, type BB creatine kinase and alpha alpha-enolase were the major isoenzymes detected in normal breast tissue. Types alpha gamma and gamma gamma enolase, types MB and MM phosphoglycerate mutase were detected in much lower proportions. In tumours a decrease of phosphoglycerate mutase isoenzymes possessing M-type subunit and some increase of enolase isoenzymes possessing gamma-type subunit was observed. No detectable change was observed in the creatine kinase phenotype.

Breast Neoplasms↗
PubMed1999

Disregulation of p16MTS1/CDK4I protein and mRNA expression is associated with gene alterations in squamous-cell carcinoma of the larynx.

To determine the relationship between p16MTS1/CDK4I expression, gene inactivation and 9p21 loss of heterozygosity (LOH) in the development of laryngeal carcinomas, we have examined p16MTS1/CDK4I protein and mRNA expression in a series of 7 normal and 36 tumoral tissues, and the presence of gene alterations and 9p21 LOH. Fifteen tumors (42%) showed low levels of pl6MTS1/CDK4I protein expression (similar to normal samples), 7 carcinomas (19%) expressed higher levels, and no protein expression was seen in 14 tumors (39%). No gene alterations were detected in 11 of the 15 tumors (73%) with protein levels similar to normal tissues. Most of the cases with absence of protein expression (86%) had gene alterations. Of the 7 tumors with protein over-expression, 4 showed frameshift or point mutations (2 cases each). mRNA analysis showed pl6MTS1/CDK4I -gene expression in 12 of 17 carcinomas examined. Gene alterations were detected in 9 of the 12 mRNA-positive tumors and in 2 of the 5 negative carcinomas. Concordant expression of p16alpha and p16beta transcripts was observed in all tumors. 9p21 LOH was detected in 23 carcinomas, 18 of which (78%) showed associated p16MTS1/CDK4I -gene alterations. These results indicate that disregulation of p16MTS1/CDK4I protein and mRNA expression is a frequent phenomenon in laryngeal carcinomas commonly associated with gene alterations and 9p21 LOH. The relative number of discrepancies between protein and mRNA expression and the presence of genetic alterations indicate that a comprehensive study of the gene including all these parameters may be necessary to assess the role of this gene in the pathogenesis of such tumors.

Amino Acid Substitution↗
PubMed1999

Expression of p27/Kip1 is down-regulated in human prostate carcinoma progression.

p27(Kip1) is a cyclin-dependent kinase inhibitor whose down-regulation has been observed in several tumour models, including breast, colorectal, and gastric carcinomas. The purpose of this study was to assess p27(Kip1) protein expression in normal and benign prostatic epithelia as well as the possible existence of abnormalities in prostate carcinoma progression. p27(Kip1) expression was immunohistochemically analysed in 51 normal tissue samples, 11 nodular hyperplasias (NH), 22 high-grade prostatic intraepithelial neoplasias (PIN), 56 localized prostate adenocarcinomas, and 19 metastases. Immunoblotting was performed in ten cases. Normal prostate epithelium and NH showed diffuse and intense p27(Kip1) nuclear expression in most cases. A significant p27(Kip1) down-regulation was observed in many carcinomas when compared with benign epithelium. Forty-seven cases (84 per cent) were low p27(Kip1) expressors (<50 per cent positive cells) and nine cases (16 per cent) were high p27(Kip1) expressors. p27(Kip1) down-regulation was also consistently seen in PIN. Fourteen out of 19 metastases (74 per cent) were low p27(Kip1) expressors. Six metastatic samples had their corresponding primary tumour analysed and three cases showed decreased expression in the metastasis. It is concluded that p27(Kip1) is constitutively expressed in normal and benign prostatic tissue. This expression is clearly down-regulated in neoplastic progression from the preinvasive lesions through invasive carcinoma and metastases and this therefore occurs in early stages of neoplastic transformation.

Adenocarcinoma↗
PubMed1999

c-myc mRNA expression and genomic alterations in mantle cell lymphomas and other nodal non-Hodgkin's lymphomas.

Cyclin D1 is a weak oncogene that cooperates with c-myc activation in the development of B cell lymphomas in transgenic animals. Cyclin D1 is constantly overexpressed in human mantle cell lymphomas (MCL). However, the status of c-myc gene in these tumors is not known. We have examined the c-myc mRNA expression and genomic alterations, including mutational analysis of exon 1, intron 1, and exon 2 regulatory elements, in a series of 33 MCL, 22 typical and 11 blastoid variants. In addition, c-myc alterations were also examined in 56 nodal non-Hodgkin's lymphomas (NHL). c-myc mRNA overexpression was found in 38% (11/29) of MCL with a slightly higher frequency in blastoid variants (5/10, 50%) than in typical cases (6/19, 31%). Genetic alterations were only found in one blastoid MCL showing a three-fold c-myc gene amplification. In other nodal NHL, c-myc overexpression was found in 24% (7/29) of indolent tumors but in 70% (19/27) of aggressive variants. c-myc Genetic alterations detected in these cases were gene rearrangement and hypermutations in one Burkitt's lymphoma, and individual point mutations in intron 1 or exon 2 in 1/19 (5%) indolent and 7/16 (44%) aggressive variants. These results indicate that c-myc is overexpressed in a subset of MCL, but structural gene alterations are less frequent than in other nodal NHL.

Blotting, Southern↗
PubMed1998

cdc25 cell cycle-activating phosphatases and c-myc expression in human non-Hodgkin's lymphomas.

cdc25A, cdc25B, and cdc25C are a family of human phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and cdc25B have been shown to have oncogenic potential, and they have been identified as transcriptional targets of c-myc. To determine the role of cdc25 genes in the pathogenesis of human lymphomas and their possible correlation with c-myc deregulation, we have analyzed the expression of cdc25A, cdc25B, and cdc25C and c-myc genes in a series of 63 non-Hodgkin's lymphomas and 8 nonneoplastic lymphoid tissues. The mRNA levels of the three phosphatases in the nonneoplastic tissues were negative or negligible. cdc25B overexpression was detected in 35 tumors (56%). This overexpression was more frequently found in aggressive (81%) than in indolent lymphomas (36%; P < 0.01). cdc25B overexpression was also significantly associated with a higher proliferative activity of the tumors. No cdc25B gene amplification or rearrangements were detected by Southern blot analysis. A biallelic EcoRI polymorphism of cdc25B gene was identified with a similar distribution in patients with lymphoma and in a normal population. cdc25A was overexpressed in three aggressive lymphomas. No detectable cdc25C mRNA levels were seen in any of the tumors. c-myc was overexpressed in 43% of tumors, and it correlated significantly with the presence of cdc25B up-regulation. Twenty-six of 35 (74%) lymphomas with high levels of cdc25B mRNA also showed c-myc overexpression, whereas 27 of 28 (96%) tumors without detectable or with very low cdc25B expression also had undetectable c-myc levels (P < 0.0001). In addition, a significant linear correlation was found between the cdc25B and c-myc mRNA levels (r = 0.575, P < 0.001). These findings suggest that cdc25B overexpression in non-Hodkin's lymphoma may participate in the pathogenesis of aggressive variants, and it may cooperate with c-myc oncogene in the development of these tumors.

Blotting, Northern↗
PubMed1998

p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma.

p21WAF1/Cip1 is an inhibitor of cdk/cyclin complexes, and thus regulates the cell cycle. p21 is also related to cell differentiation and is regulated by wild-type p53, although p53-independent regulatory pathways have been proposed. In order to analyse p21 expression as well as its relationship with p53 in human breast cancer, an immunohistochemical analysis was undertaken of 77 breast carcinomas, 16 of them with an in situ component; 30 adjacent normal tissue samples; and five non-neoplastic specimens. Forty-four infiltrating carcinomas (57 per cent) were p21-positive. Expression of p21 was also observed in pre-invasive lesions, whereas normal ducts were negative or focally and weakly positive. p21 expression was associated with high histological grade (II + III) (P = 0.017) and poor tubule formation (P = 0.002), and was significantly less frequent in lobular carcinomas (P = 0.0001). p21 positivity also correlated with increased proliferation, but this seemed to be dependent on the histological grade. Twenty carcinomas (26 per cent) showed p53 overexpression, but this was not associated with p21 negativity, suggesting the existence of p53-independent mechanisms for p21 regulation in vivo. Cyclin D1CCND1 expression was analysed in the same series and an association between p21 and cyclin D1 expression was found, since 23 of 26 cyclin D1-positive carcinomas were p21-positive (P < 0.001 ...). In conclusion, p21 is frequently overexpressed in breast carcinomas and this occurs in the early stages of neoplastic progression. This overexpression seems to be independent of p53 status and might be involved in cyclin D1 modulation.

Blotting, Western↗