Expresión de proteínas relacionadas con resistencia a múltiples drogas (MDR-Proteínas) y resistencia a la quimioterapia en el cáncer de pulmón / Expression of proteins related to multiple drug resistance (MDR-proteins) in chemotherapy-resistant lung cancer

Propósito: El objetivo de este estudio es analizar la expresión de proteinas transportadoras de fármacosy la resistencia a la quimioterapia en el cáncer de pulmón.Material y métodos: Se recogieron 147 muestras tumorales procedentes de 143 pacientes (35broncoscópicas y 112 quirúrgicas). Resultaron válidas para el estudio 101 muestras correspondientes a99 pacientes. Las muestras tumorales criocongeladas fueron sometidas a análisis inmunohistoquímicopara la detección de las tres MDR-proteínas, Pgp, Mrp1 y Lrp.Resultados: No expresaron ninguna proteína, 16 casos. Expresaron una sola proteína, 32 casos: 3Pgp, 11 Mrp1 y 18 Lrp=0. Expresaban dos proteínas, 34 casos: 24 Pgp y Lrp, 5 Mrp1 y Pgp, 5 Mrp1 yLrp=0. Expresaban las tres proteínas, 17 casos. No hemos detectado relación significativa entre laedad y la expresión de Pgp (p=0.74), Mrp1 (p=0.95), o Lrp (p=0.26). No observamos diferencias significativasentre sexos, tanto al analizar por el número (p=0.72), como por el tipo (p=0.39) de proteínasexpresadas de forma simultánea.Tampoco detectamos diferencias significativas entre los diferentesestadios tumorales, tanto para el número (p=0.55), como para el tipo (p=0.21) de MDR-proteínasexpresada. Tampoco encontramos diferencias significativas entre los diferentes grados histológicos,tanto para el número (p=0.59), como para el tipo (p=0.51) de MDR-proteínas expresadas simultáneamenteesadas simultáneamente. La tendencia de Pgp y Lrp a expresase asociadas ha resultado muysignificativa (p<0.01), no ocurrió lo mismo para la sociación Pgp y Mrp1 (p=0.18) o Mrp1 y Lrp(p=0.26).Conclusiones: Pgp se expresa fundamentalmente asociada a Lrp. Solamente la expresión de Pgpy el número de proteinas expresabas simultáneamente parece guardar relación con la respuesta a laquimioterapia

Purpose: To evaluate the expression of MDR-proteins in the response to lung cancerchemotherapy.Methods: 147 tumor samples were collected from 143 patients, 35 of which were obtained bybronchoscopy and 112 from surgery; 101 samples belonging to 99 patients were considered valid forthe study. The samples were cryopreserved and immunochemistry with monoclonal murine antibodiesused to determine the MDR-proteins Pgp, Mrp1 and Lrp.Results: No MDR-proteins were expressed in 16 cases. One MDR-protein was present in 32cases: Pgp in 3, Mrp1 in 11 and Lrp in 18. Two MDR-proteins were expressed in 34 cases: Pgp andLrp in 24, Mrp1 and Pgp in 5, and Mrp and Lrp in 5. All the three MDR-proteins were present in 17cases. No differences were observed considering age (Pgp, p = 0.74; Mrp1, p = 0.95; Lrp, p = 0.26).Neither sex produced changes when considering either number of MDR-proteins (p = 0.55) or types ofthem (p = 0.21). Significant differences of MRD-proteins were also lacking for number (p = 0.59) andtype (p = 0.51) in relation to the tumor histologic grade. The tendency to the simultaneous expressionof Pgp and Lrp was very significant (p < 0.01), while the simultaneous expression of Mrp1 and Lrpshowed to be no significant (p = 0.26).Conclussions: Pgp and Lrp are frequently expressed simultaneously. Only the expression of Pgpand the number of MDR-proteins expressed simultaneously seem to be related to response tochemotherapy

Expresión de proteínas relacionadas con resistencia a múltiples drogas (MDR-Proteínas) en el cáncer de pulmón / Expression of proteins related to multiple drug resistance (MDR-proteins) in lung cancer

• Introducción: La reducción en la acumulación intracelular de los fármacos, es uno de los mecanismosmás frecuentes de resistencia a los antineoplásicos. Las proteinas transportadoras de membrana juegan un papelesencial en este fenómeno.• Material y métodos: Se recogieron 147 muestras tumorales procedentes de 143 pacientes. De éstas,35 eran broncoscópicas y 112 quirúrgicas. Resultaron válidas para el estudio 101 muestras correspondientes a99 pacientes. Las muestras tumorales criocongeladas fueron sometidas a análisis inmunohistoquímico para ladetección de las tres MDR-proteínas, Pgp, Mrp1 y Lrp• Resultados: No expresaban ninguna proteína, 16 casos. Expresaban una sola proteína, 32 casos: 3 Pgp,11 Mrp1 y 18 Lrp=0. Expresaban dos proteínas, 34 casos: 24 Pgp y Lrp, 5 Mrp1 y Pgp, 5 Mrp1 y Lrp=0. Expresabanlas tres proteínas, 17 casos. No hemos detectado relación significativa entre la edad y la expresión dePgp (p=0.74), Mrp1 (p=0.95), o Lrp (p=0.26). No detectamos diferencias significativas entre sexos, tanto alanalizar por el número (p=0.72), como por el tipo (p=0.39) de proteínas expresadas de forma simultánea.Tampocodetectamos diferencias significativas entre los diferentes estadios tumorales, tanto para el número(p=0.55), como para el tipo (p=0.21) de MDR-proteínas expresada. Tampoco detectamos diferencias significativasentre los diferentes grados histológicos, tanto para el número (p=0.59), como para el tipo (p=0.51) deMDR-proteínas expresadas simultáneamente esadas simultáneamente.La tendencia de Pgp y Lrp a expresarse asociadas ha resultado muy significativa (p<0.01), no ocurrió lo mismopara la asociación Pgp y Mrp1 (p=0.18) o Mrp1 y Lrp (p=0.26).• Conclusiones: El cáncer de pulmón expresa con frecuencia MDR-proteínas.De las tres MDR-proteínasestudiadas, Pgp Mrp1 y Lrp, es Lrp la más frecuentemente expresada. Los adenocarcinomas expresan menosMrp1 que el resto de los tipos histológicos.Los carcinomas escamosos expresan menos Lrp que los adenocarcinomasy carcinomas indiferenciados de célula grande.Una proporción importante de pacientes expresan de formasimultánea más de una MDR-proteína. Los carcinomas escamosos, son los que con más frecuencia expresanPgp, Mrp1 y Lrp de forma simultánea. Pgp se expresa fundamentalmente asociada a Lrp

• Introduction: Lowering of intracellular drug deposition plays an important role in the resistance tochemotherapy of many neoplasms. MDR-proteins regulate the process.• Material and methods: 147 tumor samples were collected from 143 patients, 35 were obtained bymeans of bronchoscopy and 112 were surgical specimens; 101 samples from 99 patients were consideredcorrect for final analysis. Samples were cryopreserved and immuno-staining techniques used for MDRproteinscharacterization (Pgp, Mrp1, and Lrp). A monoclonal murine antibody to each was employed.• Results: 16 cases failed to express any of the three analysed MDR-proteins. One protein was expressedin 32 cases: 3 Pgp, 11 Mrp1, and 18 Lrp. The expression of two proteins was observed in 34 cases: 24 Pgp andLrp, 5 Mrp1 and Pgp, and 5 Mrp1 and Lrp. All the three proteins were expressed in 17 cases. No differenceswere found in the expression according to age: Pgp (p=0.74), Mrp (p=0.95) and Lrp (p=0.26). Sex showed nodifferences when considered either number (p=0.72) or type of proteins (p=0.39). No significative differenceswere found according to tumor stage analysing either number (p=0.55) or type (p=0.21) of expressed MRDproteins.Differences were also not observed in relation to histologic grade for number (p=0.59) or type(p=0.51) of expressed proteins.A tendency to the simultaneous expression of Pgp and Lrp was very significative (p<0.01). No similartendency was observed for the association of Mrp- Lrp (p=0.26) and Pgp-Mrp1 (p=0.18).• Conclussions: Lung cancer cells frequently express MDR-proteins. Lrp was the most frequently found inour series. Adenocarcinomas rarely express Mrp1 as compared with other histological classes. Squamous-cellcarcinomas express less Lrp than adenocarcinomas and large-cell undifferentiated carcinomas. The simultaneousexpression or more than two proteins was observed in a significant number of cases. Squamous-cell carcinomastend to express Pgp, Mrp1 and Lrp simultaneously. Pgp is ussually expressed associated to Lrp

Histiocitosis de células de Langerhans en vulva y hueso / Langerhans cell histiocytosis of the vulva and bone

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[Anatomopathologic and morphometric study of hepatocarcinoma]. / Estudio anatomopatológico y morfométrico del hepatocarcinoma.

UNLABELLED: Because of its great incidence and poor prognosis the hepatocarcinoma (HPC) has become a first line clinical challenge. This is the reason we have performed a descriptive anatomo-pathological analysis of our own cases and a study of the possible prognostic value of nuclear parameters. DESIGN: We have performed a retrospective study of 83 cases. We reviewed the clinical records and histologic preparations. METHODS: We analysed the following parameters: 1) Tumour site; 2) Association to cirrhosis; 3) Microscopic features (cellular type differentiation grade, peritumoral lymphocytic infiltration, architecture, mitotic index); 4) Metastatic frequency and location; 5) Morphometric nuclear parameters (area, perimeter, major diameter, major and minor axis, circle diameter, sphere volume, ellipse volume, shape factor. RESULTS: We highlight the following: 1) 50% of HPC associated to liver cirrhosis; 2) Ascites was more frequent in the tumours located in the right lobe or both lobes than in tumours affecting the left lobe (p < 0.005); 3) Macroscopically, the commonest type was the nodular one (47.8%); 4) Microscopically, the commonest findings were as follows: cellular type (93%); differentiation grade type II (61.4%); trabecular architecture (64.9%); lymphocytic infiltration grade I (57.9%); 5) Mean mitotic index was 16.3 m./high power field. 6) There were distant metastases in 81.1% and portal vein invasion in 44.6%. 7) The nuclear morphometric study did not support any influence on patients' survival. CONCLUSIONS: 1) This descriptive analysis allows a morphological data base that is very useful for subsequent morphological or prognostic studies. 2) Our data do not support any influence of nuclear parameters on patients' survival, although we cannot exclude some relation in a greater series.

Nuclear morphometry lacks prognostic value in squamous cell carcinoma of the oesophagus.

In order to determine the possible influence in oesophageal squamous cell carcinoma of nuclear measurements on patients' postoperative survival and on various histological tumour features, we performed a nuclear morphometry study on 53 patients (50 males, 3 females) with a mean age of 57.4 years (37-79). A statistical correlation was revealed between area, perimeter and diameter and the analysis was, therefore, performed only in terms of nuclear area. No influence of nuclear area on postoperative survival was observed. Nor was a relationship found between mean nuclear area and either involvement of the oesophageal wall or degree of histological differentiation. The tumours showing expansive growth had a larger mean nuclear area than those of the infiltrative growth type, although differences did not reach statistical significance. The nuclear area standard deviation (reflecting anisocytosis of the tumour) showed no correlation with survival. In conclusion, our data do not support that measurement of nuclear parameters by static methods is of any prognostic value in surgically-treated squamous cell carcinoma of the oesophagus.

Post-vagotomy variations of gastric mucosal mast cells in the rat.

The effects of the vagus and its action on the mucosal mast cells (MMC) of the secretory portion of the rat stomach are analyzed by observing the consequences caused by subdiaphragmatic truncal vagotomy on the MMC in terms of cell count and degranulation over a period of four months. Observations showed a gradual decrease in the number of mast cells/mm2, an increase in the percentage of MMC in a state of degranulation, but the same number of degranulated cells/mm2. This suggests that the vagus controls both numerically and functionally the MMC population in the secretory portion of the rat stomach.

[Gastric carcinoma in Cantabria: I. Incidence and distribution]. / Carcinoma gástrico en Cantabria: I. Incidencia y distribución.

We have proceeded to study the rate of incidence and distribution in Cantabria of six hundred and thirty two patients suffering from gastric carcinoma in a period of time ranging from 1970 to 1981. The rate of incidence being observed among this population amounts to 14.54, cases per one hundred thousand inhabitants and year between 1976-1981. This rate increases with age in women more than in men. We have also been able to see how those cases where the carcinoma has appeared at an early age, under thirty, concern females exclusively. Males have been affected by this pathology more than females in a proportion of 1.38:1. We have verified there exists a special geographical distribution of this kind of tumour in our region, being Reinosa the judicial district presenting the highest rate of incidence.

[Gastric carcinoma in Cantabria: II. Histopathological aspects]. / Carcinoma gástrico en Cantabria: II. Aspectos histopatológicos.

In this study we have proceeded to analyze the differences found in each histological type of gastric carcinoma according to age and sex, showing a predominance of tubular adenocarcinoma in advanced ages, affecting females, as an average, more than males. We have also found out how other histological types such as the signet ring cell adenocarcinoma tend to appear at an early age, concerning females preferably. We have also checked on the pathogenesis concerning the different histological types described by certain authors as to age and sex.

[Gastric carcinoma in Cantabria: III. Anatomo-pathological factors of prognostic significance]. / Carcinoma gástrico en Cantabria: III. Factores anatomo-patológicos de interés pronóstico.

In the present study, we have proceeded to analyze different anatomo-pathological parametres concerning 638 gastric carcinomas, for a twelve year period between 1970-1981, such as location and macroscopic aspect, tumoral extension and histological type, observing their prognosis in the case of curative surgery. We have also proceeded to analyze the rate of survival amounting to 5 years in all the patients being examined, depending on the therapeutical attitude in use. We then proceeded to compare our series with others already published, thus coinciding in the best prognosis as to tumoral location in antrum-pylorus with an ulcerated aspect, less depth as to intraparietal invasion, as well as an absence of ganglionar compromise and visceral metastasis. We also proceeded to analyze the rate of survival concerning the histological type, according to WHO classification.