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Sergi Serrano

Publications and source records attributed to Sergi Serrano.

At least 19 recordsLinked to original sources
PubMed2007

Human papillomavirus detection in urine samples: an alternative screening method.

OBJECTIVES: To investigate the usefulness of human papillomavirus detection in the urine of women with poor gynecologic attention. MATERIALS AND METHODS: Fifty urine and 50 cervical samples from 50 women were analyzed. Polymerase chain reaction was performed on these 100 samples using consensus primers and a low-density microarray-based method for human papillomavirus typing. RESULTS: The concordance of the results between both sample groups was 80%. In the urine samples, the sensitivity of polymerase chain reaction for high-grade squamous intraepithelial lesion was 100%, the specificity was 80%, the positive predictive value was 91%, and the negative predictive value was 100%. CONCLUSIONS: Human papillomavirus detection in urine samples may be used as an alternative screening method for women with poor gynecologic attention.

Adult↗
PubMed2006

Methotrexate resistance in vitro is achieved by a dynamic selectionprocess of tumor cell variants emerging during treatment.

Genetic instability leads to tumor heterogeneity, which in turn provides a source of cell variants responsible for drug resistance. However, the source of resistant cells during the process of acquired resistance is poorly understood. Our aim has been to characterize the mechanism by which acquired resistance to methotrexate emerges during the course of cancer cell treatment in vitro. We recently demonstrated that, in vitro, HT-29 colon cancer cells become transiently sensitive to methotrexate by depleting the extracellular milieu of survival factors; on the other hand, the cell population under treatment can reversibly adapt to grow below a critical cell density in the presence of the drug. Here, we show that this adapted cell population gives rise to permanent resistant populations through repeated cycles of cell death and growth. This increased cell turnover, but not merely cell proliferation, is required for the appearance of increasing degrees of stable resistance that are progressively selected by drug pressure. Such a process, taking place in multiple steps, is here designated "dynamic selection." The analysis of sensitive and resistant HT-29 cell populations revealed that methotrexate induces genomic instability--characterized by centrosome amplification and aberrant chromosome recombination--leading to a low-level amplification of the 5q chromosome arm as one of the earliest genetic events selected during treatment. Therefore, this model provides a mechanism by which a tumor cell population lacking resistant subpopulations before treatment is able to acquire the genetic changes required for stable drug resistance.

Cell Line, Tumor↗
PubMed2006

Aberrant nuclear BCL10 expression and lack of t(11;18)(q21;q21) in primary cutaneous marginal zone B-cell lymphoma.

Inhibition of apoptosis seems to play an important role in the pathogenesis of marginal zone lymphoma. Apoptosis regulator B-cell lymphoma 10 (BCL10) may show aberrant nuclear localization in some aggressive extracutaneous MALT lymphomas, often in association with a MALT1 gene t(11;18)(q21;q21) translocation. The possible occurrence of this association in primary cutaneous marginal zone lymphoma (PCMZL) remains insufficiently explored. The aim of this study was to evaluate BCL10 protein expression pattern and its possible relationship to the presence of t(11;18)(q21;q21) and other MALT1 gene abnormalities in PCMZL and to assess their clinical significance. The study included 42 consecutive PCMZL patients diagnosed on the basis of the World Health Organization/European Organization for the Research and Treatment of Cancer classification criteria. BCL10 expression was immunohistochemically evaluated in all cases, whereas t(11;18)(q21;q21) reverse transcriptase polymerase chain reaction amplification was performed on 21 samples. In addition, the presence of other MALT1 gene translocations was explored in 26 samples by interphase fluorescence in situ hybridization using a MALT1 locus-specific probe. We observed the presence of aberrant nuclear BCL10 expression in a significant number of PCMZL cases (36%, 15/42). This aberrant expression was significantly related to the development of extracutaneous disease. In contrast, neither the t(11;18)(q21;q21) translocation nor other MALT1 gene translocations could be demonstrated. t(11;18)(q21;q21), strongly linked to extracutaneous MALT lymphomas, does not seem to play a role in PCMZL. The participation of other MALT1 gene translocations in PCMZL pathogenesis seems also unlikely.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Study of chromosomal abnormalities in 11 cases of cervical dysplasia using comparative genomic hybridization on cotton-lint cervical samples.

Comparative genomic hybridization (CGH) allows the analysis of chromosomal imbalances without requiring cell cultures and is more reliable than conventional cytogenetic studies for detecting gains, losses, and amplified regions. To perform CGH on cervical lesions, some authors obtain the tumoral DNA from frozen or paraffin-embedded biopsies. Others use laser microdissected material from paraffin-embedded samples, followed by degenerate oligonucleotide primer-polymerase chain reaction (DOP-PCR). In all these cases, surgery is required to obtain the sample. In our study, we obtained DNA from a cotton-lint cervical sample obtained from the pathological zone using a colposcopy technique. Chromosomal alterations were found in 9 (81%) of the 11 cases analyzed. The most frequent alterations affected the 3p12, 4q25, 5q15 approximately q21, and 18p11 regions. Satisfactory results have been observed when the cotton-lint cervical sample has been used as the source for obtaining DNA. In the laboratory, the manipulation of this type of sample obtained by a noninvasive system is much simpler, easier, and faster than the obtained with a conventional biopsy.

Chromosome Aberrations↗
PubMed2006

Detection of abnormalities of PRV-1, TPO, and c-MPL genes detected by fluorescence in situ hybridization in essential thrombocythemia.

No specific diagnostic markers have been described in essential thrombocythemia (ET). PRV-1 (polycythemia rubra vera-1), TPO (thrombopoietin), and c-MPL (myeloproliferative leukemia virus oncogene) genes are candidate ET molecular markers because of their implication in the pathogenesis of ET. We have studied the status of PRV-1, TPO, and c-MPL genes in 30 ET patients by a fluorescence in situ hybridization (FISH) technique using three noncommercial, locus-specific probes for PRV-1 (BAC RP11-160A19, located at 19q13.2), TPO (BAC RP11-45NP16, located at 3q27), and c-MPL (BAC RP11-297L5, located at 1p34). FISH study showed no PRV-1, TPO, and c-MPL cytogenetic abnormalities in any of the analyzed cases. Our results suggest a lack of structural and numerical rearrangements (deletions, translocations, or amplifications) of PRV-1, TPO, and c-MPL genes in ET patients.

Autoantigens↗
PubMed2006

Translocation t(9;14)(p13;q32) in cases of splenic marginal zone lymphoma.

Translocation t(9;14)(p13;q32) involving PAX5 and IGH genes was first described in lymphoplasmacytic lymphoma. New data suggest that this translocation is not restricted to a specific morphologic subtype but occurs in other B-cell lymphomas. We present three cases with a diagnosis of splenic marginal zone lymphoma and t(9;14) confirmed by fluorescent in situ hybridization.

Aged↗
PubMed2005

Identification of male cardiomyocytes of extracardiac origin in the hearts of women with male progeny: male fetal cell microchimerism of the heart.

BACKGROUND: Fetal progenitor cells may cross the placenta during pregnancy, persist for decades in the maternal bloodstream, and find a microenvironment conducive to colonization in a variety of maternal solid organs. Whether extracardiac fetal progenitors are present in the heart of women with male issue is unknown. METHODS: The hearts from 2 non-pregnant women who had given birth to 2 and 3 male children, respectively, were studied. Myocardial specimens from 2 men and 2 women (without history of pregnancies) were used as controls. Real time polymerase chain reaction was performed to amplify the SRY gene located at the Y chromosome. Fluorescence in situ hybridization (FISH) with probes specific for X and Y chromosomes was combined with alpha-actin immunohistochemistry to identify cardiac muscle cells. Histocompatibility studies were conducted in both patients and their male relatives. RESULTS: The SRY gene was amplified in the myocardium of both patients. FISH analysis showed clear evidence of male cells with the typical cardiomyocyte phenotype within the myocardium. X- and Y-chromosome bodies in the nuclei were found in 0.25% and 0.20% of cells, respectively. Increased human leukocyte antigen compatibility was observed between patients and their sons. CONCLUSIONS: This study identified male cardiomyocytes of extracardiac origin, presumably fetal, in the hearts of 2 women with male progeny. Fetal progenitor cells may colonize the heart and under appropriate microenvironmental stimuli, differentiate into cardiomyocytes.

Cardiomyopathy, Dilated↗
PubMed2005

Large cell lymphoma-like reaction in a cervical polyp.

BACKGROUND: Inflammatory lesions of the uterine cervix are very common, and although lymphomas in this location are rare, the differential diagnosis between both diseases must be considered in some cases and may be difficult to achieve. CASE: A 37-year-old woman in good health with a cervical polyp, showing a lymphoma-like reaction with blastic appearance, which was initially interpreted as a diffuse large-cell lymphoma. The immunohistochemical and molecular studies showed the reactive origin of the lesion. CONCLUSIONS: Immunohistochemical and molecular biology studies may be useful to dilucidate the reactive or neoplastic origin of these lesions.

Adult↗
PubMed2005

Bone histomorphometry in 22 male patients with normocalciuric idiopathic osteoporosis.

Osteoporosis is associated with increased bone resorption together with a decrease in bone formation. In women, there is an increase of resorption surfaces and in the number of osteoclasts. These changes, however, are not found in males. This purpose of this study was to examine clinical, laboratory, and histomorphometric data in a series of 22 male patients with primary osteoporosis and normocalciuria undergoing transiliac bone biopsy. All of them gave written informed consent for bone biopsy. Automated biochemical profile, urinary calcium excretion, and bone marker assays were performed. Histomorphometric studies were carried out in transiliac bone biopsies obtained with a Bordier-Lepine needle with previous tetracycline labeling. The histomorphometric values of cancellous bone showed significantly lower values of bone volume and values of osteoid surface (OS/BS) and osteoblast surface (Ob.S/BS), and a modest increase in osteoid thickness (O.Th) without changes in the mineralization lag time or eroded surface in patients compared with controls. In cortical bone, there was a low cortical volume (Ct.V/TV) and cortical width (Ct.Wi) in patients compared with controls, without differences in cortical porosity (Po.V/TV). These results suggest that normocalciuric idiopathic osteoporosis in men is characterized by decreased cancellous osteoblasts and bone turnover.

Adult↗
PubMed2005

Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease.

RATIONALE: Oxidative stress is involved in the skeletal muscle dysfunction observed in patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that the diaphragms of such patients might generate greater levels of oxidants than those neutralized by antioxidants. OBJECTIVES: To assess the levels of both oxidative and nitrosative stress and different antioxidants in the diaphragms of those patients, and to analyze potential relationships with lung and respiratory muscle dysfunctions. METHODS AND MEASUREMENTS: We conducted a case-control study in which reactive carbonyl groups, hydroxynonenal-protein adducts, antioxidant enzyme levels, nitric oxide synthases, and 3-nitrotyrosine formation were detected using immunoblotting and immunhistochemistry in diaphragm specimens (thoracotomy) obtained from six patients with severe COPD, six patients with moderate COPD, and seven control subjects. MAIN RESULTS: Diaphragms of patients with severe COPD showed both higher protein carbonyl groups and hydroxynonenal-protein adducts than control subjects. When only considering patients with COPD, negative correlations were found between carbonyl groups and airway obstruction, and between hydroxynonenal-protein adducts and respiratory muscle strength. Although diaphragmatic neuronal nitric oxide synthase did not differ among the three groups and no inducible nitric oxide synthase was detected in any muscle, muscle endothelial nitric oxide synthase was lower in patients with severe COPD than in control subjects. Muscle nitrotyrosine levels were similar in both patients with severe COPD and control subjects. CONCLUSIONS: This study shows that oxidative stress rather than nitric oxide is likely to be involved in the respiratory muscle dysfunction in severe COPD.

Aged↗
PubMed2005

Polysomy of chromosome 17 in breast cancer tumors showing an overexpression of ERBB2: a study of 175 cases using fluorescence in situ hybridization and immunohistochemistry.

INTRODUCTION: One of the most common genetic aberrations associated with breast cancer is the amplification and overexpression of the ERBB2 proto-oncogene located at chromosome 17, bands q12-21. The amplification/overexpression occurs in 25 to 30% of all breast cancers. In breast cancer, aneusomy of chromosome 17, either monosomy or polysomy, is frequently observed by conventional cytogenetics and fluorescence in situ hybridization (FISH). The aim of this study was to discover whether or not numerical aberrations on chromosome 17 have a correlation to the amplification or overexpression of the ERBB2 gene and to analyze their clinical implications in subgroups showing 2+ or 3+ positive scores by immunohistochemistry (IHC). METHODS: We used FISH on a series of 175 formalin-fixed paraffin-embedded breast carcinomas to detect ERBB2 amplification, using a dual-probe system for the simultaneous enumeration of the ERBB2 gene and the centromeric region of chromosome 17, as well as using IHC to detect overexpression. We analyzed clinical and pathological variables in a subgroup of patients with 2+ and 3+ IHC scores (147 patients), to describe any differences in clinicopathological characteristics between polysomic and non-polysomic cases with the use of the chi2 test. RESULTS: We found 13% of cases presenting polysomy, and three cases presented monosomy 17 (2%). According to the status of the ERBB2 gene, instances of polysomy 17 were more frequently observed in non-amplified cases than in FISH-amplified cases, suggesting that the mechanism for ERBB2 amplification is independent of polysomy 17. Polysomy 17 was detected in patients with 2+ and 3+ IHC scores. We found that nodal involvement was more frequent in polysomic than in non-polysomic cases (P = 0.046). CONCLUSIONS: The determination of the copy number of chromosome 17 should be incorporated into the assesment of ERBB2 status. It might also be helpful to differentiate a subgroup of breast cancer patients with polysomy of chromosome 17 and overexpression of ERBB2 protein that probably have genetic and clinical differences.

Breast Neoplasms↗
PubMed2005

Insertion (8;11) in a renal oncocytoma with multifocal transformation to chromophobe renal cell carcinoma.

We report the case of a 43-year-old male with multiple tumor foci showing microscopic features of chromophobe renal carcinoma (ChRCC) arising in an oncocytoma. Conventional cytogenetics of fresh tumor cells and fluorescence in situ hybridization (FISH) revealed the following abnormal karyotype: 46,XY,der(8)ins(8;11)(p?;q13),der(11)ins(8;11)inv(11)(q12?p15) with CCND1 (11q13) rearrangement. To our knowledge, chromosome 8 has not been reported as a partner involved in structural rearrangements of 11q13 in oncocytomas. FISH in paraffin tissue sections revealed a rearrangement of CCND1 (11q13) in the oncocytoma cells. The multiple foci of chromophobe carcinoma presented multiple copies of CCND1, suggesting that they represented a transformation from oncocytoma into ChRCC. There was immunohistochemical overexpression of CCND1 in both oncocytoma and chromophobe carcinoma cells. In this case, the correlation of the microscopic findings with changes in CCND1 gene associated to CCND1 overexpression in both components suggest that the ChRCC would have originated from the preexisting oncocytoma. It is not possible to detect, by cytogenetic techniques alone, if the ChRCC component have also the CCND1 rearrangement in addition to the detected polysomy. FISH techniques on paraffin tissue sections may help to identify genetic aberrations such as CCND1 rearrangement in order to establish a diagnosis of oncocytoma.

Adenoma, Oxyphilic↗
PubMed2005

Clonal proliferation of cyclin D1-positive mantle lymphocytes in an asymptomatic patient: an early-stage event in the development or an indolent form of a mantle cell lymphoma?

Mantle cell lymphoma (MCL) is a B-cell neoplasm with a relatively aggressive clinical course. There is a very small subgroup of patients who present with atypical lymphocytes in peripheral blood, with or without lymphocytosis, lymphadenopathy, or splenomegaly, and with an indolent clinical course. They frequently show mutated IgV(H) genes and CD5 negativity. We report an asymptomatic elderly patient who presented with a single submandibular lymphadenopathy. The biopsy showed immunophenotype and t(11;14)(q13;q32) consistent with MCL. The abnormal lymphoid population was also detected in peripheral blood and bone marrow. The patient has remained asymptomatic for 5 years without receiving any therapy. It is uncertain whether these cases represent an early-stage event in the development or an indolent form of MCL. The existence of such asymptomatic patients with an indolent clinical course should induce a strict clinical judgment in terms of therapeutic decisions.

Aged↗
PubMed2005

CD20-negative T-cell-rich B-cell lymphoma as a progression of a nodular lymphocyte-predominant Hodgkin's lymphoma treated with rituximab: a molecular analysis using laser capture microdissection.

Rituximab is a chimeric anti-CD20 monoclonal antibody. It has shown efficacy in patients with B-cell non-Hodgkin lymphoma and also in CD20-positive Hodgkin lymphoma. Recently, CD20-negative tumors have been described after Rituximab therapy. We report a 34-year-old man with a history of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), treated with different chemotherapy regimens, including anthracyclines and Rituximab. After 4 years in complete remission, he developed a CD20-negative T-cell-rich B-cell lymphoma (TCRBCL) presenting as multiple lung lesions. This case shows the difficulties in the diagnosis of CD20-negative lymphomas when the number of tumor cells is low and when they are found in a predominant T-cell context. Using anti-CD79a as a B-cell marker is mandatory to overcome the difficulties in identifying these tumors. Moreover, this case illustrates the usefulness of laser capture microdissection to obtain purified cell populations for molecular studies in lymphomas with relative paucity of tumor cells, as well as the need to analyze different IgH gene regions to decrease the rate of false-negative results in PCR clonality studies.

Adult↗
PubMed2005

Comparative genomic hybridization analysis of cutaneous large B-cell lymphomas.

The aim of the present study was to identify genetic aberrations in a series of patients with cutaneous large B-cell lymphoma (LBCL) using comparative genomic hybridization (CGH). Eighteen consecutive patients with primary (13 patients) (PCLBCL) and secondary (five patients) (SCLBCL) cutaneous large B-cell lymphoma were included in the study. Nine cases corresponded to PCLBCL leg type and four cases primary cutaneous follicle centre-cell lymphoma (PCFCL). Chromosomal imbalances (CIs) were detected in 14 of 18 samples (77.8%). All of nine cases with PCLBCL leg type and two of four cases with PCFCL showed CIs (100% and 50%, respectively). Regarding SCLBCL, in three of five cases (60%), CIs were detected. The most frequently detected gains involved 2q, 5q, 3 and 7q and amplifications affected 18, 12 and 13. Frequent losses were found in 17p. In PCLBCL leg type, the most frequent gains involved 2q and 7q, amplifications were localized in chromosomes 12, 13 and 18 and losses affected chromosomes 17p and 19. In PCFCL, gains located in 3q, 4 and 7q were found. Our study seems to confirm clear-cut differences between primary cutaneous LBCL and nodal diffuse LBCL, and it suggests the presence of genotypic differences between cases of PCLBCL leg type and cases of PCFCL.

Adult↗