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M Nistal

Publications and source records attributed to M Nistal.

At least 19 recordsLinked to original sources
PubMed2006

MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) represents the most frequent and therapy-refractive sub-class of lung cancer. Improving apoptosis induction in NSCLC represents a logical way forward in treating this tumor. Cisplatin, a commonly used therapeutic agent in NSCLC, induces activation of N-terminal-c-Jun kinase (JNK) that, in turn, mediates induction of apoptosis. In analysing surgical tissue samples of NSCLC, we found that expression of MKP1/CL100, a negative regulator of JNK, showed a strong nuclear staining for tumor cells, whereas, in normal bronchial epithelia, MKP1 was localized in the cytoplasm as well as in nuclei. In the NSCLC-derived cell lines H-460 and H-23, we found that MKP1 was constitutively expressed. Expressing a small-interfering RNA (siRNA) vector for MKP1 in H-460 cells resulted in a more efficient activation by cisplatin of JNK and p38 than in the parental cells, and this correlated with a 10-fold increase in sensitivity to cisplatin. A similar response was also observed in H-460 and H-23 cells when treated with the MKP1 expression inhibitor RO-31-8220. Moreover, expression of a siRNA-MKP2, an MKP1-related phosphatase, had no effect on H-460 cell viability response to cisplatin. Tumors induced by H-460 cells expressing MKP1 siRNA grew slower in nu(-)/nu(-) mice and showed more susceptibility to cisplatin than parental cells, and resulted in an impaired growth of the tumor in mice. On the other hand, overexpression of MKP1 in the H-1299 NSCLC-derived cell line resulted in further resistance to cisplatin. Overall, the results showed that inhibition of MKP1 expression contributes to a slow down in cell growth in mice and an increase of cisplatin-induced cell death in NSCLC. As such, MKP1 can be an attractive target in sensitizing cells to cisplatin to increase the effectiveness of the drug in treating NSCLC.

Adult↗
PubMed2006

The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane.

The oncogene BRAF(V600E) is the most frequent genetic event in papillary thyroid carcinoma (PTC) but its prognostic impact still remains to be elucidated. We evaluated a representative series of 67 individuals with PTC who underwent total thyroidectomy. BRAF-positive tumours correlated with early recurrences (32% vs 7.6%; P=0.02) during a median postoperative follow-up period of 3 years. Interestingly, within the recurrences, a significant majority had negative radioiodine ((131)I) total body scans, predicting a poorer outcome as treatment with (131)I is not effective. This last observation led us to investigate the role of BRAF(V600E) and the MEK-ERK pathway in thyroid dedifferentiation, particularly in Na(+)/I(-) symporter (NIS) impairment, as this thyroid-specific plasma membrane glycoprotein mediates active transport of I(-) into the thyroid follicular cells. A subset of 60 PTC samples was evaluated for NIS immunoreactivity and, accordingly, we confirmed a significant low NIS expression and impaired targeting to membranes in BRAF-positive samples (3.5% vs 30%; P=0.005). Furthermore, experiments with differentiated PCCl3 thyroid cells demonstrated that transient expression of BRAF(V600E) sharply impaired both NIS expression and targeting to membrane and, surprisingly, this impairment was not totally dependent on the MEK-ERK pathway. We have concluded that BRAF(V600E) is a new prognostic factor in PTC that correlates with a high risk of recurrences and less differentiated tumours due to the loss of NIS-mediated (131)I uptake.

Adenocarcinoma↗
PubMed2004

Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors.

Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHS-R), has been primarily linked to the central neuroendocrine regulation of GH secretion and food intake, although additional peripheral actions of ghrelin have also been reported. In this context, the expression of ghrelin and its cognate receptor has been recently demonstrated in rat testis, suggesting a role for this molecule in the direct control of male gonadal function. However, whether this signaling system is present in human testis remains largely unexplored. In this study we report the expression and cellular location of ghrelin and its functional receptor, the type 1a GHS-R, in adult human testis. In addition, evaluation of ghrelin and GHS-R1a immunoreactivity in testicular tumors and dysgenetic tissue is presented. The expression of the mRNAs encoding ghrelin and GHS-R1a was demonstrated in human testis specimens by RT-PCR, followed by direct sequencing. In normal testis, ghrelin immunostaining was demonstrated in interstitial Leydig cells and, at lower intensity, in Sertoli cells within the seminiferous tubules. In contrast, ghrelin was not detected in germ cells at any stage of spermatogenesis. The cognate ghrelin receptor showed a wider pattern of cellular distribution, with detectable GHS-R1a protein in germ cells, mainly in pachytene spermatocytes, as well as in somatic Sertoli and Leydig cells. Ghrelin immunoreactivity was absent in poorly differentiated Leydig cell tumor, which retained the expression of GHS-R1a peptide. In contrast, highly differentiated Leydig cell tumors expressed both the ligand and the receptor. The expression of ghrelin and GHS-R1a was also detected in dysgenetic Sertoli cell-only seminiferous tubules, whereas germ cell tumors (seminoma and embryonal carcinoma) were negative for ghrelin and were weakly positive for GHS-R1a. In conclusion, our results demonstrate that ghrelin and the type 1a GHS-R are expressed in adult human testis and testicular tumors. Overall, the expression of ghrelin and its functional receptor in human and rat testis, with roughly similar patterns of cellular distribution, is highly suggestive of a conserved role for this newly discovered molecule in the regulation of mammalian testicular function.

Adult↗
PubMed2003

New insights in beta-tubulin sequence analysis in non-small cell lung cancer.

Scarce data are available regarding the molecular mechanisms implicated in paclitaxel resistance. There is controversial data about beta-tubulin mutations role in paclitaxel resistance. We have conducted this trial to address the influence of beta-tubulin mutations in paclitaxel resistance in advanced non-small cell lung cancer (NSCLC). A group of 15 patients were biopsied and diagnosed of stages IIIB and IV NSCLC. Tumor specimens were used for DNA isolation and exon 4 of HM40 beta-tubulin isotype was amplified and automatically sequenced, using both intronic and exonic primers. Next, the chemotherapy schedule consisted of weekly paclitaxel (100 or 150 mg/m(2) x 6) followed 2 weeks later by cisplatin 100 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) on days 1 and 14, and vinorelbine 25 mg/m(2) on days 1 and 14, every 28 days. Using exonic primers, gene sequence alterations were found in 13/15 (87%) patients, including transitions (codons 180 and 182) and one silent transversion (codon 195). Also, three transversions (codons 231, 234, and 235) were found in all patients and controls. All alterations disappeared when sequenced with intronic primers. Our results suggest that point mutations demonstrated with exonic primers but not with intronic ones are probably due to beta-tubulin pseudogenes present in advanced NSCLC specimens. Even so, when these beta-tubulin pseudogenes are found there is a clear relation with clinical response. Although these changes could be relevant in paclitaxel resistance, this observation must be proven in future clinical trials to resolve "the tubulin dilemma".

Adenocarcinoma↗
PubMed2003

Adenomatous hyperplasia of the rete testis. A review and report of new cases.

Adenomatous hyperplasia of the rete testis (AHRT) is an uncommon benign lesion that preferentially involves the septal rete testis and mediastinal rete testis. It is usually an incidental finding in surgical specimens from cryptorchidism and testicular tumour. It can be found in autopsy specimens from patients dying with different chronic diseases and newborns with kidney diseases. Since its first description many articles have been published communicating new cases and putting forward some hypotheses on its aetiology and pathogenic mechanisms. Some authors suggest a role for hormonal changes, tumour invasion and action of chemical agents. We think that AHRT should be categorised into two main aetiological categories: congenital and acquired. The cases associated with different kidney and spermatic duct diseases, most cases associated with cryptorchidic testis and some cases associated with testicular germ cell tumour should be included in the congenital group. The remaining cases associated with chemical agents, some hormonal changes (i.e. androgen blockade) and most of the germ cell tumour cases can be considered as acquired AHRT. Differential diagnosis must be established mainly with metastatic adenocarcinoma of prostate to testis and primary adenocarcinoma of the rete testis. Pseudohyperplasia of the rete testis must also be considered in atrophic testes. Here we review the papers published on this subject and report our recent cases.

Adenocarcinoma↗
PubMed2002

[Bronchocentric granulomatosis and pulmonary hydatidosis].

Bronchocentric granulomatosis is a non-specific necrotizing granulomatous reaction in the bronchi and bronchioles. In asthmatic patients, bronchocentric granulomatosis is considered a hypersensitivity reaction to intrabronchial fungi. However, in non-asthmatic patients the possible etiology has not been identified. We report the case of a 46-year-old woman with bronchocentric granulomatosis associated with pulmonary hydatidosis. The likely immuno-pathogenic mechanisms leading to bronchial lesions are briefly discussed.

Bronchi↗
PubMed2001

Lipomembranous fat necrosis in three cases of testicular torsion.

AIMS: To describe for the first time a lesion termed lipomembranous fat necrosis (LFN) in three patients with spermatic cord torsion. METHODS AND RESULTS: We reviewed 386 testes and their epididymides and spermatic cords which had been removed for testicular infarction. For the three cases showing LFN, a battery of histochemical tests (including periodic acid-Schiff (PAS), orcein, Sudan black and Perls stains) was applied and clinical histories and laboratory data were also investigated. Findings were similar in the three specimens. The testes showed a central group of necrotic seminiferous tubules which were surrounded by granulation tissue consisting of macrophages, multinucleated giant cells, lymphocytes, plasma cells and fibrous connective tissue at the periphery of the lesion. The spermatic cord showed thrombosed veins surrounded by fat necrosis showing cystic cavities which were bounded by wavy hyaline membranes. These stained with Sudan black, PAS (before and after diastase digestion) and orcein and presented yellowish-green autofluorescence. CONCLUSIONS: Lipomembranous fat necrosis of the spermatic cord is a distinctive entity which seems to be related to spermatic cord torsion and the differential diagnosis of which should be established with regard to the presence of parasites, sclerosing lipogranuloma and granuloma evoked by rupture of a testicular prosthesis.

Adipose Tissue↗
PubMed2001

Androgen receptor expression in sertoli cells as a function of seminiferous tubule maturation in the human cryptorchid testis.

Androgen receptor (AR) immunohistochemistry was performed in an archival collection of adult human cryptorchid testes to determine whether AR cellular distribution and intensity of immunostaining were functions of the severity of cellular dysgenesis. The seminiferous tubule histology of cryptorchid testes collected from adults is marked by three specific patterns. 1) Seminiferous tubules are characterized as maintaining focal areas of germinal cell differentiation (albeit incomplete) that are interspersed with 2) tubules composed of Sertoli cells only, these latter cells being principally of the adult type, although dysgenetic and immature Sertoli cells may also be detected. 3) In contrast, there is a class of tubule that is characterized as being composed exclusively of Sertoli cells that are extremely dysgenetic in appearance. The majority of adult-type Sertoli cells found in the first types of tubules exhibited either robust or moderate AR staining intensity. Peritubular cells of these tubules also expressed a similar AR staining intensity. In contrast, in the more dysgenetic and immature type Sertoli cells found in the second type of tubules, the intensity of AR staining was significantly less, if not missing altogether. Finally, in the most dysgenetic tubules, Sertoli cell AR staining was never detected. To our knowledge, this is the first report in the literature that addresses the intensity of AR immunostaining in Sertoli cells of cryptorchid testes. The results presented herein are consistent with the interpretation that the intensity of AR staining in Sertoli cells diminishes as a function of the severity to which the cells are afflicted within a cryptorchid testis and that focal absence of AR expression in Sertoli cells correlates with a lack of local spermatogenesis in the tubules.

Adolescent↗
PubMed2001

Thoracic duct cyst presenting as an hour-glass shaped mass in the left supraclavicular area: case report.

Thoracic duct cyst presenting as an hour-glass shaped mass in the left supraclavicular area: case report. Thoracic duct cysts are a very rare entity in the head and neck pathology. We present a case of a 52 year-old man, who was referred to our service, complaining by a 30 days left cervical mass, with no other symptoms. A 6 cm cystic mass was revealed after ultrasonography and CT. Needle aspiration confirmed the presence of lymph in the cyst. The treatment was simple excision. Special care was taken to ligate the connected lymphatic vessels.

Clavicle↗
PubMed2000

Correlation between testicular biopsies (prepubertal and postpubertal) and spermiogram in cryptorchid men.

Twenty-one young men who underwent testicular biopsy and orchidopexy in infancy consulted owing to infertility and had biopsies again. The first and second biopsy specimens from these patients were compared by means of a semiquantitative study of the seminiferous tubules to evaluate the evolution of germ cells and to correlate these data with spermatozoon numbers. The infant testes showing lesions were classified into 3 types according to the mean tubular diameter and tubular fertility index: (1) slight lesions, (2) marked germinal hypoplasia, and (3) severe germinal hypoplasia. In the adult testes, spermatogenesis was evaluated by calculating the average numbers of spermatogonia, primary spermatocytes, young spermatids, and mature spermatids. These testes were classified as (1) normal; (2) having lesions in the adluminal compartment; (3) having lesions in the basal compartment; and (4) mixed atrophy. The number of differentiated spermatids was correlated with the expected number of spermatozoa in the ejaculate by a power regression curve. The observation of certain histologic lesions in the seminiferous tubules was assumed to indicate excretory duct obstruction: ectasia, indented outline of the seminiferous epithelium, intratesticular spermatocele, apical cytoplasmic vacuolation of Sertoli cells, and mosaic distribution of testicular lesions. There was a correlation between the prepubertal lesions and the degree of spermatogenesis in postpubertal biopsy specimens. The evolution of the 40 testes without regard to their location in infancy (cryptorchid or scrotal) was as follows. The 14 infant testes with a normal histologic pattern (5 testes) or minor lesions (9 testes) evolved to testes with lesions of the adluminal compartment (8 testes), mixed atrophy (4 testes), or lesions of the basal and adluminal compartments (2 testes). The 6 testes with marked germinal hypoplasia evolved to testes with mixed atrophy. The 20 testes with severe germinal hypoplasia evolved to testes with mixed atrophy (17 testes), Sertoli-cell-only tubules (2 testes), or lesions in the basal compartment (1 testis). In the 9 patients with a histologic pattern of obstruction bilaterally (6 men) or unilaterally (3 men), the expected number of spermatozoa according to the correlation curve was much higher than the actual number in the spermiogram. This means that the testes of many azoospermic men produce spermatozoa, and this finding corroborates the importance of testicular biopsy in infertility studies.

Adult↗
PubMed2000

Bilobectomy and amphotericin B in a case of endobronchial mucormycosis.

Lung mucormycosis is a rare fungal infection that has been described mainly in oncologic and diabetic patients. We here report the case of an endobronchial lesion caused by this fungus in an immunocompetent person. Prompt diagnosis, and therapy with Amphotericin B and surgery, permitted the complete resolution.

Aged↗
PubMed2000

[Scrotal invasive angiomyofibroblastoma. First reported case].

OBJECTIVE: To report a case of locally invasive angiomyofibroblastoma of the scrotum. To our knowledge, this is the first case of invasive scrotal angiomyofibroblastoma reported in the literature. METHODS: A case of invasive angiomyofibroblastoma of the scrotum is presented. The literature is reviewed with special reference to the etiopathogenesis, clinical features, diagnosis and treatment of this rare soft tissue tumor. RESULTS/CONCLUSIONS: The case described herein shows that angiomyofibroblastoma can be invasive.

Aged↗
PubMed1999

Testicular biopsy. Contemporary interpretation.

Biopsy of the testis is not universally accepted in contrast with biopsies of other organs. The pathologist studies and reports on the pathophysiology of the testicular biopsy specimen. Methodology requires the inclusion of qualitative and quantitative studies, the evaluation of the lesion's evolution (prognosis), and, often, therapeutic advice regarding treatment. Cooperation between pathologists and clinicians optimizes the utility of the biopsy for the patient.

Atrophy↗
PubMed1999

Testicular biopsy in patients with obstructive azoospermia.

The present report studies the testicular biopsy lesions (histologic and semiquantitative) in a series of 48 patients with obstructive azoospermia of known etiology (vasectomy, congenital absence of vas deferens, herniorrhaphy, hydrocelectomy, Young's syndrome, and ejaculatory duct obstruction) in order to establish objective testicular data that permit the pathologist to diagnose an obstructive process, which should not be mistaken with a primary testicular lesion. The semiquantitative study included determinations of the average numbers of spermatogonia, primary spermatocytes, young spermatids (Sa + Sb), and differentiated spermatids (Sc + Sd). According to this study, the testes were classified into the following groups: (1) normal testes whose germ cell numbers were within normal limits (27 testes); (2) testes with lesions in the adluminal compartment; these lesions comprise two subgroups: (2a) late sloughing of primary spermatocytes (both spermatid types were greatly reduced in number while the other germ cell types were in normal numbers) (45 testes); and (2b) early sloughing of primary spermatocytes (normal spermatogonial number, reduced number of spermatocytes, and scanty spermatids) (9 testes); and (3) lesions in the basal compartment; these lesions comprise two subgroups: (3a) pure hypospermatogenesis (a proportionate decrease in the numbers of all germ cell types) (8 testes); and (3b) hypospermatogenesis associated with sloughing of primary spermatocytes (decreased numbers of all germ cell types with a very scanty number spermatids) (4 testes). Two testes appeared hyalinized and one testis was removed owing to cryptorchidism. The most frequent testicular lesion observed (alteration in the adluminal compartment of seminiferous tubules) seems to be related to the increase in hydrostatic pressure in the tight compartment formed by seminiferous tubules, rete testis, efferent ducts, the epididymal duct, and the initial portion of the vas deferens. The severity of the lesions is probably related to the cause and span of the obstruction. In addition, two azoospermic men without obstructive azoospermia and whose testicular biopsy study revealed meiotic anomalies (with the subsequent bad prognosis) were also studied for comparison. The semiquantitative study of these patients permitted the differential diagnosis between two lesion types. Testes with meiotic anomalies had a disproportionately elevated number of primary spermatocytes, and an extremely low number of young spermatids.

Adult↗
PubMed1999

Extracapsular spread and desmoplastic pattern in neck lymph nodes: two prognostic factors of laryngeal cancer.

The influence of extracapsular spread (ECS) and a desmoplastic pattern (DP) of metastatic cervical lymph nodes in patients with laryngeal cancer is presented. The study includes 128 patients surgically treated between 1984 and 1992 for squamous cell carcinoma of the larynx with pathologically proven lymph node metastasis. The results were studied from 2 major standpoints: survival and recurrence. The 3-year survival rates were as follows: patients without ECS 73.4%, and with ECS 28.9% (p < .001); patients without a DP 76.9%, and with a DP 43.3% (p < .03). Also, the 3-year recurrence rates in the neck showed significant differences: patients without ECS 10.7%, and with ECS 49.6% (p < .001); patients without a DP 10%, and with a DP 31.6% (p = .1142). Postoperative radiotherapy did not appear to improve the outcome.

Actuarial Analysis↗
PubMed1999

Androgen receptor distribution in adult human testis.

The distribution of the androgen receptor (AR) in archival human testes was determined immunocytochemically using an affinity-purified peptide-specific rabbit antibody, PG21, and employing a modified biotin-streptavidin-immunoperoxidase method that incorporated a biotin amplification step. In combination with microwave epitope retrieval, the biotin amplification step increased the sensitivity of the immunostaining assay approximately 20-fold. Thus, the useful range at which PG21 rendered a robust, specific immunostaining signal without also increasing nonspecific background was extended dramatically. Broadening the useful range of the PG21 antibody made it possible to resolve the relative amounts of immunopositive AR in different cell types of the human testis. At a high PG21 concentration, for example, all AR-positive cells exhibited a robust immunostaining intensity, but it was not possible to distinguish between nuclei exhibiting either high or moderate immunostaining intensities. In contrast, as the concentration of PG21 was decreased, distinct populations of testicular cells exhibited differential AR immunostaining intensities in their nuclei. AR immunostaining of Sertoli cell nuclei was present at low PG21 concentrations at which no immunostaining of peritubular myoid cells or Leydig cells could be detected. In turn, AR immunostaining of peritubular myoid cells was detected at PG21 concentrations that did not immunostain Leydig cells. Moreover, within the seminiferous epithelium, Sertoli cell nuclear AR staining intensity was less at stages V and VI of the cycle of the seminiferous epithelium than that at stage III, and stage III staining intensity was greater than that at stages I and II. This AR immunostaining pattern in human Sertoli cell nuclei as a function of the cycle of the seminiferous epithelium is reminiscent of the pattern observed in rodent species. Finally, no AR immunostaining of germ cells was observed at any of the PG21 concentrations examined.

Aged↗