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1.
Cir Esp ; 83(5): 252-5, 2008 May.
Article in Spanish | MEDLINE | ID: mdl-18448028

ABSTRACT

INTRODUCTION: The frequency of haemorrhoid disease and the deterioration in the quality of life in the immediate post-operative period has led to the appearance of new techniques in an attempt to obtain improve patient satisfaction. PATIENTS AND METHOD: A prospective study was carried out in which 50 consecutive patients with a diagnosis of Goligher grade III haemorrhoids were intervened. To perform the haemorrhoid dearterialisation, a device called THD R was used (designed by TKC SRL and distributed by Palex Medical). The technique consisted of, a reduction in arterial flow using ligation of the terminal branches above the anorectal ring, starting in the anterior position, it was carried out in a clockwise direction: 1, 3, 5, 7, 9, 11. Follow up was carried out at one week, 1 month, 3 months, 6 months and 1 year. RESULTS: We intervened 50 consecutive patients with a diagnosis of grade III haemorrhoids. The mean age was 45 years (range, 25-78). The surgical indication was, pain-discomfort, 40 (80%); bleeding, 35 (70%), prolapse 6 (12%). The procedure was always performed under local/regional anaesthesia. The mean duration of the procedure was 25 minutes (range, 20-35). Analgesia was required by 90% of the patients during the first 24 hours, decreasing to 15% for those who continued to require it until the third day and only 2 (4%) patients continued for one week. Pain was resolved 48 hours after surgery, in all patients who consulted for this reason, except for one patient (2.5%) who had a recurrence in the pain as well as in his prolapse. This meant that patients could re-start their daily living within 48-72 hours. CONCLUSIONS: Pending for randomised studies, we can say that in our experience, Doppler guided transanal haemorrhoidal dearterialisation is a technique that should be offered to the patient with haemor-rhoidal disease.


Subject(s)
Hemorrhoids/diagnostic imaging , Hemorrhoids/surgery , Ultrasonography, Doppler , Adult , Aged , Arteries/surgery , Female , Humans , Ligation/methods , Male , Middle Aged , Pain, Postoperative/psychology , Prospective Studies , Quality of Life/psychology
2.
Cir. Esp. (Ed. impr.) ; 83(5): 252-255, mayo 2008. ilus, tab
Article in Es | IBECS | ID: ibc-64333

ABSTRACT

Introducción. La frecuencia de la enfermedad hemorroidal y el deterioro de la calidad de vida durante el postoperatorio inmediato ha hecho que aparezcan nuevas técnicas para lograr una mayor satisfacción de los pacientes. Pacientes y método. Se realizó un estudio prospectivo en que, desde octubre de 2005 a septiembre de 2006, se intervino de forma consecutiva a 50 pacientes con diagnóstico de hemorroides de grado III de Goligher. Para la realización de la desarterialización hemorroidal se utilizó un dispositivo denominado THDR (diseñado por TKC SRL y distribuido por Palex Medical), la técnica consiste en la reducción del flujo arterial hemorroidal, mediante ligadura de ramas terminales de la arteria hemorroidal superior por encima de la línea dentada, comenzando en posición anterior y seguimos según las agujas del reloj: 1, 3, 5, 7, 9, 11. El seguimiento se realiza a la semana, al mes, 3 y 6 meses y 1 año. Resultados. Hemos intervenido a 50 pacientes de forma consecutiva con diagnóstico de hemorroides de grado III. La media de edad fue de 45 (intervalo, 25-78) años. La indicación de cirugía fue dolor-incomodidad en 40 (80%); sangrado en 35 (70%), y prolapso en 6 (12%). El procedimiento siempre fue realizado bajo anestesia locorregional. La duración media del procedimiento fue de 25 (intervalo, 20-35) min. El 90% de los pacientes precisó de analgesia durante las primeras 24 h, que disminuyó hasta un 15% los que la mantuvieron hasta el tercer día y sólo en 2 (4%) pacientes se mantuvo durante una semana. El dolor se resolvió a las 48 h de la cirugía en todos los pacientes que consultaron por este motivo, salvo en 1 (2,5%) paciente que presentó recidiva tanto del do- lor como de su prolapso. Esto permitió que los pacientes se incorporasen a su vida cotidiana en 48-72 h. Conclusiones. A la espera de estudios aleatorizados, podemos decir que en nuestra experiencia la desarterialización hemorroidal transanal guiada por Doppler es una técnica que se debe ofrecer al paciente con afección hemorroidal (AU)


Introduction. The frequency of haemorrhoid disease and the deterioration in the quality of life in the immediate post-operative period has led to the appearance of new techniques in an attempt to obtain improve patient satisfaction. Patients and method. A prospective study was carried out in which 50 consecutive patients with a diagnosis of Goligher grade III haemorrhoids were intervened. To perform the haemorrhoid dearterialisation, a device called THDR was used (designed by TKC SRL and distributed by Palex Medical). The technique consisted of, a reduction in arterial flow using ligation of the terminal branches above the anorectal ring, starting in the anterior position, it was carried out in a clockwise direction: 1, 3, 5, 7, 9, 11. Follow up was carried out at one week, 1 month, 3 months, 6 months and 1 year. Results. We intervened 50 consecutive patients with a diagnosis of grade III haemorrhoids. The mean age was 45 years (range, 25-78). The surgical indication was, pain-discomfort, 40 (80%); bleeding, 35 (70%), prolapse 6 (12%). The procedure was always performed under local/regional anaesthesia. The mean duration of the procedure was 25 minutes (range, 20-35). Analgesia was required by 90% of the patients during the first 24 hours, decreasing to 15% for those who continued to require it until the third day and only 2 (4%) patients continued for one week. Pain was resolved 48 hours after surgery, in all patients who consulted for this reason, except for one patient (2.5%) who had a recurrence in the pain as well as in his prolapse. This meant that patients could re-start their daily living within 48-72 hours. Conclusions. Pending for randomised studies, we can say that in our experience, Doppler guided transanal haemorrhoidal dearterialisation is a technique that should be offered to the patient with haemor-rhoidal disease (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Hemorrhoids/complications , Hemorrhoids/diagnosis , Hemorrhoids/surgery , Arteries/surgery , Echocardiography, Doppler , Proctoscopy/methods , Proctoscopy , Postoperative Care/methods , Hemorrhoids/epidemiology , Prospective Studies , Ambulatory Surgical Procedures
3.
Psicooncología (Pozuelo de Alarcón) ; 4(1): 121-132, jun. 2007. tab
Article in Spanish | IBECS | ID: ibc-95088

ABSTRACT

El objetivo del presente estudio es evaluar la calidad de vida, el estado emocional y la satisfacción percibida con el tratamiento y con el equipo médico en una muestra de pacientes con cáncer colorrectal intervenidos mediante cirugía laparoscópica. La muestra está constituida por 35 pacientes y las variables objeto de estudio fueron: a) sociodemográficas: edad y género; b) calidad de vida (EORTC QLQ C-30); c) ansiedad y depresión (HADS); d) satisfacción con el tratamiento y con el equipo médico (escala categórica). Los resultados obtenidos muestran que las dimensiones de calidad de vida global, función física, rol, emocional, cognitivas y social son altamente satisfactorias, no obstante muchos pacientes muestran síntomas de fatiga, nausea y dolor. En cuanto la ansiedad y depresión las puntuaciones en el HADS son bajas: media de 4,57 y 3,38 respectivamente. El 19% de la muestra se puede considerar caso clínico de depresión y el 29% de ansiedad. La satisfacción percibida es alta, más del 50% de los pacientes se considera muy o totalmente satisfechos. Se puede concluir que los pacientes de cáncer colorrectal necesitan una atención integral para mejorar la calidad de vida y el estado emocional, ya que el mero paso de tiempo no produce una recuperación, sino que se precisa de una intervención psicológica, que ha de aplicarse desde el inicio del tratamiento medico para optimizar la calidad asistencial (AU)


The aim of this study is to evaluate quality of life, emotional state and satisfaction perceived with the treatment and the medical team in a simple of colorrectal cancer patients in which has been carried laparoscopic surgery. The sample is constituted by 35 patients and the variables objects of study were a) sociodemographics: age and sex; b) quality of life EORTC QLQ C-30); c) anxiety and depression (HADS); d) satisfaction with the treatment and the medical team (categorical scale). The obtained results show that dimensions of global quality of life, physical function role, emotional, cognitive and social are highly satisfactory, despite many patients show fatigue, nauseous, and pain symptoms. In reference to the anxiety and depression scores in the HADS are low: mean: 4,57 and 3,38 respectively, 19% of the sample can be considered clinical case of depression and 29% of anxiety. The perceived satisfaction is elevated, more than 50% of the patients were considered very or totally satisfied. It is concluded that the colorectal cancer patients need and integral attention in order to improve the quality of life and the emotional state, because the mere step of time does not produce a recovery. A psychological intervention is necessary to optimize the welfare quality. This intervention should be applied since the start of the medical process (AU)


Subject(s)
Humans , Colorectal Neoplasms/psychology , Laparoscopy/psychology , Affective Symptoms/epidemiology , Patient Satisfaction , Quality of Life
4.
Hepatogastroenterology ; 54(73): 315-9, 2007.
Article in English | MEDLINE | ID: mdl-17419282

ABSTRACT

BACKGROUND/AIMS: The aim of the present work is to clarify the role of metalloproteinase-9 and its inhibitor in the evolution of gastric cancer after surgical resection. METHODOLOGY: We have studied 44 gastric cancer patients submitted to surgery. There were 13 proximal tumors, 16 located in the middle third and 15 in the distal one. Overall survival was 26% at 6 years. Metalloproteinase-9 and tissue inhibitor of metalloproteinase concentrations were investigated by means of ELISA in frozen samples of tumoral and normal gastric mucosa. RESULTS: Mean concentration of metalloproteinase-9 in tumoral tissue was 42 ng/mg of total protein, and this value was 6.9 times greater than the mean concentration in non-tumoral tissue. Cancer tissue also expressed higher levels of TIMP-1, 7.25 versus 4.39 ng/mg of protein. Higher levels of metalloproteinase expression in tumoral tissue, greater [metalloproteinase in tumor]/[metalloproteinase in non-tumor] ratio and greater [metalloproteinase]/[inhibitor] ratio in tumor cells, were all of them statistically related to a worse prognosis when T1 and T2 tumors were considered. CONCLUSIONS: The expression of metalloproteinase-9 or its inhibitor is related to a more aggressive phenotype of gastric cancer.


Subject(s)
Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , Matrix Metalloproteinase 9/metabolism , Stomach Neoplasms/metabolism , Tissue Inhibitor of Metalloproteinase-1/metabolism , Adenocarcinoma/mortality , Aged , Enzyme-Linked Immunosorbent Assay , Female , Gastric Mucosa/metabolism , Humans , Male , Prognosis , Stomach Neoplasms/mortality , Survival Analysis
5.
Oncol Rep ; 17(1): 217-23, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17143501

ABSTRACT

Our main aim consists of investigating the clinical usefulness of gelatinases and their tissue inhibitors in non-small cell lung cancer (NSCLC). Thus, we have analysed in 111 NSCLCs, levels and activity of MMP-2, MMP-9, TIMP-1 and TIMP-2, by Enzymoimmunoassay and Gelatine zymography, respectively. Our data revealed higher MMP-2 net activity in the NSCLC population analyzed in this study, this parameter showing a significant association with the TNM stage of tumours (P=0.002). Moreover, MMP-9 levels were significantly associated with poor clinical evolution of patients (P=0.02). Also, disease-free survival time was higher for patients whose tumours showed TIMP-1 increased levels (P=0.04). Of interest, Cox multivariate analysis revealed that TIMP-1 levels can be considered as an independent prognostic factor in NSCLC. Relative Risk (RR) to tumour relapse was more than two times lower for patients showing high TIMP-1 levels (RR=0.420, P=0.041). Therefore, according to our results, we conclude that MMP-9 and TIMP-1 levels of synthesis could be useful for the selection of patients with potentially unfavourable clinical evolution in order to establish adjuvant therapy protocols. Among these parameters, TIMP-1 level evaluation emerges as the main factor to predict the clinical outcome of patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Immunoenzyme Techniques , Lung Neoplasms/enzymology , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging
6.
Psicooncología (Pozuelo de Alarcón) ; 3(2/3): 407-422, dic. 2006. tab
Article in Es | IBECS | ID: ibc-055875

ABSTRACT

El cáncer de pulmón es, en la actualidad, la primera causa de muerte por cáncer en el hombre y la segunda en la mujer. Además la tasa de incidencia y mortalidad por carcinoma pulmonar sigue aumentando en la población mundial. La resección quirúrgica, si es factible, es el tratamiento de elección. Sin embargo, la cirugía constituye una fuente de estrés psicológico elevado tanto para el paciente como para sus familiares. En el presente trabajo se expone el protocolo de evaluación e intervención psicosocial desarrollado en pacientes intervenidos por cáncer de pulmón en la Unidad de Cirugía Torácica del Hospital Clínico San Carlos de Madrid, con el objetivo de contribuir a la reducción del estrés psicológico y el malestar emocional y mejora de la calidad de vida de estos pacientes


At present, lung cancer is the most common cause of death worldwide from cancer in men and the second among women. Moreover, lung cancer shows an increasing rate of incidence and mortality among the world’s population. Surgical resection, if feasible, is the treatment of choice. However, surgical treatment can cause a great amount stress, both for patients and their families. To reduce psychological and emotional distress and improving quality of life, psychosocial evaluation and intervention should begin prior to the surgical procedure and continue through the postsurgical period. In this paper, the psychosocial evaluation and intervention protocol developed in the Thoracic Surgery Unit of the Hospital Clínico San Carlos of Madrid is presented


Subject(s)
Humans , Social Support , Lung Neoplasms/surgery , Stress, Psychological/prevention & control , Quality of Life , Postoperative Complications/psychology , Clinical Protocols , Lung Neoplasms/psychology
7.
J Hepatobiliary Pancreat Surg ; 13(2): 167-71, 2006.
Article in English | MEDLINE | ID: mdl-16547680

ABSTRACT

Epithelioid hemangioendothelioma (EH) is a rare tumor of vascular origin, which occurs at sites such as soft tissues, liver, or lung, and has a highly unpredictable malignant potential. It is an intermediate entity between well-differentiated hemangioma and angiosarcoma. We present two cases of this rare disease in which the tumor was detected fortuitously and the definitive diagnosis was based on histological evidence. Both our cases are highly illustrative of the two ways in which hepatic EH can present (nodular or diffuse) and of its diagnostic and therapeutic management. Neoplastic cells expressed the factor VIII-related antigen, CD31 or CD34. Treatment was surgical resection in one patient and liver transplant in the other. Although EH of the liver has a better prognosis than other hepatic neoplasms, conservative treatment is not recommended. Our cases highlight the importance of a histological diagnosis to avoid it being mistaken for another entity.


Subject(s)
Hemangioendothelioma, Epithelioid/pathology , Hemangioendothelioma, Epithelioid/surgery , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Liver Transplantation , Adult , Diagnosis, Differential , Female , Humans , Middle Aged
8.
Cancer ; 106(3): 541-51, 2006 Feb 01.
Article in English | MEDLINE | ID: mdl-16388518

ABSTRACT

BACKGROUND: Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status. METHODS: Ninety-one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric-repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors. RESULTS: Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P=0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P=0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P=0.04; relative risk, 6.48). Among patients with tumors classified as telomerase-positive, telomere length ratios (the ratio of tumor tissues to normal tissues)

Subject(s)
Carcinoma/genetics , Colorectal Neoplasms/genetics , Telomerase/metabolism , Telomere/ultrastructure , Telomeric Repeat Binding Protein 1/biosynthesis , Aged , Carcinoma/metabolism , Carcinoma/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Prognosis , Risk Factors , Survival Analysis
9.
Cir. Esp. (Ed. impr.) ; 78(5): 293-302, nov. 2005. ilus
Article in Es | IBECS | ID: ibc-041645

ABSTRACT

En el trabajo se analizan las figuras de los profesores universitarios que desde 1911 pertenecieron a uno de los pilares básicos en el desarrollo de la cirugía torácica española. Es el momento en que existe cierta lucha entre la cirugía general y la especializada, que será salvado si se admite la especialización tras un período de formación en el tronco. A la Universidad no se le debe negar el gran mérito de haber formado a cirujanos íntegros con un amplio bagaje general que luego optarían por una especialidad. En el trabajo, se glosan las figuras de los profesores Ricardo Lozano Monzón, Francisco Martín Lagos, José Gascó, Benjamin Narbona, Carlos Carbonell Antolí, Rafael Vara López, Alfonso de la Fuente Chaos y José M. Beltrán de Heredia, con su formación previa, sus correspondientes precursores y sus respectivas escuelas. También se analizan la "praxis" docente y quirúrgica, y la labor científica. Se esboza la escritura de un próximo trabajo basado en la contribución valenciana a la especialidad de cirugía torácica general (AU)


The present article analyzes the figures of the university professors who, from 1911, formed part of one of the basic pillars in the development of "Spanish Thoracic Surgery". At that time, there was a certain amount of infighting between general and specialized surgery, which was resolved by allowing specialization after a period of training in general surgery. Universities should not be denied the great merit of having produced well-trained surgeons with a broad general foundation who would later choose a specialty. The figures of Ricardo Lozano Monzón, Francisco Martín Lagos, José Gascó, Benjamín Narbona, Carlos Carbonell Antolí, Rafael Vara López, Alfonso de la Fuente Chaos and José M. Beltrán de Heredia with their previous training, corresponding precursors and respective schools are described. Their teaching, surgical practice, and scientific activity are also described. A future article based on the contribution of Valencia to the specialty of general thoracic surgery is also outlined (AU)


Subject(s)
Thoracic Surgery/education , Thoracic Surgery/history , Thoracic Surgery/methods , Education/methods , General Surgery/education , General Surgery/history , Thoracic Surgery/classification , Thoracic Surgery/organization & administration , Thoracic Surgery/trends , General Surgery , General Surgery/methods , General Surgery/organization & administration
10.
Cytokine ; 31(3): 213-26, 2005 Aug 07.
Article in English | MEDLINE | ID: mdl-15950486

ABSTRACT

An inflammatory etiopathogeny can be suggested in portal hypertensive enteropathy since infiltration of the intestinal wall by mononuclear cells has been described in this condition. This work was carried out with the intention of shedding light on this matter. Male Wistar rats were divided into 4 control groups and 4 groups with partial portal vein ligation at 1, 2, 3 and 15 months. TNF-alpha, IL-1beta and IL-10 were quantified in liver and ileum by ELISA. CO and NO were measured in splanchnic and systemic vein by spectrophotometry and Griess reaction, respectively. Expression of constitutive and inducible isoforms of NO and HO were assayed by Western blot in liver and ileum. An increased hepatic release of proinflammatory mediators (TNF-alpha, IL-1beta and NO) associated with intestinal release of anti-inflammatory mediators (IL-10, CO) occurs in an early evolutive phase (1 month) of experimental portal hypertension. On the contrary, in the long-term (15 months), the increase in the intestinal release of proinflammatory mediators (TNF-alpha, IL-1beta) is associated with an increase in the hepatic release of anti-inflammatory mediators (IL-10, CO). These results suggest that experimental prehepatic portal hypertension presents changes in the serum and tissular (liver and small bowel) concentrations of mediators which are considered as pro- and anti-inflammatory.


Subject(s)
Hypertension, Portal/pathology , Ileum/pathology , Liver/pathology , Animals , Carbon Monoxide/blood , Collateral Circulation , Heme Oxygenase (Decyclizing)/biosynthesis , Hypertension, Portal/blood , Hypertension, Portal/physiopathology , Ileum/enzymology , Ileum/metabolism , Inflammation/blood , Inflammation/physiopathology , Inflammation/prevention & control , Liver/enzymology , Liver/metabolism , Male , Mesenteric Veins/pathology , Mesenteric Veins/physiopathology , Nitric Oxide/blood , Nitric Oxide Synthase/biosynthesis , Nitric Oxide Synthase/metabolism , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism
11.
Cir Esp ; 78(5): 293-302, 2005 Nov.
Article in Spanish | MEDLINE | ID: mdl-16420845

ABSTRACT

The present article analyzes the figures of the university professors who, from 1911, formed part of one of the basic pillars in the development of "Spanish Thoracic Surgery". At that time, there was a certain amount of infighting between general and specialized surgery, which was resolved by allowing specialization after a period of training in general surgery. Universities should not be denied the great merit of having produced well-trained surgeons with a broad general foundation who would later choose a specialty. The figures of Ricardo Lozano Monzón, Francisco Martín Lagos, José Gascó, Benjamín Narbona, Carlos Carbonell Antolí, Rafael Vara López, Alfonso de la Fuente Chaos and José M. Beltrán de Heredia with their previous training, corresponding precursors and respective schools are described. Their teaching, surgical practice, and scientific activity are also described. A future article based on the contribution of Valencia to the specialty of general thoracic surgery is also outlined.


Subject(s)
Thoracic Surgery/history , Faculty, Medical/history , History, 20th Century , Schools, Medical/history , Spain
13.
Int J Oncol ; 24(2): 349-55, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14719111

ABSTRACT

Inactivation of p16 has been reported as one of the more frequent events in human carcinogenesis. In order to contribute to the knowledge of the impact of p16 silencing by promoter methylation, we have investigated p16 expression and inactivation of p16 by methylation in two of the major types of human cancer, non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). p16 expression was evaluated by Western blot, and p16 promoter methylation by a methylation-specific PCR procedure (MSP). Clinical correlations were established using the chi-square test, and distributions of disease-free survival (DFS) were estimated with the Kaplan-Meier method. Analyses for p16 revealed that 61.22% (60 of 98) of NSCLCs, and 32.9% (26 of 79) of CRCs here considered, lacked p16 expression. Moreover, 36.7% (22/60) of the non-small cell lung tumours without p16 expression showed p16 promoter methylation, detecting a significant correlation between p16 methylation and the histological subtype of squamous cell carcinomas (SCC) (P=0.04). With respect to CRCs, p16 promoter methylation was observed in 26.9% of tumours that lacked p16 expression (7/26), all tumours studied showing partial methylation. Survival studies demonstrated a clear correlation between p16 negative expression and poor prognosis in NSCLC patients. Moreover, we found a trend toward poor clinical evolution in the group of patients with tumours showing total p16 methylation, in NSCLC, without statistically significant differences in CRC. In conclusion, our results indicate that p16 alterations constitute a major molecular abnormality in NSCLC with a considerable prognosis impact, promoter methylation being an important mechanism involved in p16 silencing. In CRC, however, p16 promoter methylation could be considered as a less definitive molecular factor without prognostic implication, since partial methylation constitutes a prevalent mechanism.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Colorectal Neoplasms/genetics , Gene Silencing , Genes, p16 , Lung Neoplasms/genetics , Promoter Regions, Genetic , Aged , Blotting, Western , DNA Methylation , Disease-Free Survival , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Prognosis , Time Factors
14.
Cancer Res ; 62(13): 3855-60, 2002 Jul 01.
Article in English | MEDLINE | ID: mdl-12097300

ABSTRACT

Colorectal cancers from the mutator phenotype pathway display distinctive pathological features and confer a lesser aggressiveness than colorectal adenocarcinomas originated by the suppressor pathway. The goal of this work was to test whether tumors developed through the mutator pathway could show a decrease in matrix metalloproteinase (MMP) activity. We evaluated levels and activity of gelatinase A (MMP-2) and gelatinase B (MMP-9), as well as stromelysin-1 (MMP-3) expression in 101 sporadic colorectal tumors in consideration of the microsatellite instability (MSI) status of the groups. Gelatinases were analyzed by ELISA and zymography. The MMP-3 study was performed by real-time quantitative PCR. MMP-9 total levels were significantly higher in MSI-H tumors. However, levels of the active MMP-9 form were significantly much lower in this group of tumors. Data from real-time quantitative PCR indicated that levels of MMP-3 for MSI-L/MSS tumors were much higher as compared with those observed in MSI-H cancers (P = 0.033). Moreover, all MSI-H tumors showed nucleotide insertions and/or deletions in MMP-3 promoter. These mutations were not observed in the group of MSI-L/MSS tumors. Our data indicate that the MMP-3 promoter constitutes a novel target of the defective mismatch repair machinery in sporadic colorectal tumors, resulting in a dramatic decrease in the levels of the active MMP-9 form, which may result in a lessened capacity for invasion.


Subject(s)
Adenocarcinoma/genetics , Colorectal Neoplasms/genetics , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 9/metabolism , Microsatellite Repeats/genetics , Mutation , Adenocarcinoma/enzymology , Adenocarcinoma/pathology , Base Sequence , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/pathology , DNA, Neoplasm/genetics , Enzyme Activation/genetics , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 3/biosynthesis , Molecular Sequence Data , Neoplasm Staging , Promoter Regions, Genetic
15.
Oncogene ; 21(19): 3089-94, 2002 May 02.
Article in English | MEDLINE | ID: mdl-12082541

ABSTRACT

We report the genomic organization of a novel human gene mapped to chromosome 6p21, encoding a putative glycosylphosphatidylinositol (GPI) anchored protein containing a MAM (meprin, A5 antigen, protein tyrosine phosphatase mu) domain, that we have termed as GPIM (GPI and MAM) protein. GPIM gene consists of an 8.9 kb transcript composed of 17 coding exons spanning about 65.5 kb of genomic DNA. The deduced polypeptide consists of 955 amino acids and exhibits structural features found in different types of cell adhesion molecules (CAMs), such as the presence of immunoglobulin domains, the presence of a MAM domain or the capacity to anchor to the cell membrane by a GPI motif. Expression analysis in normal human tissues revealed that this gene is expressed as a 5 kb and 9.5 kb mRNA. Furthermore, the smaller transcript is highly expressed in some human cancer cell lines, as well as in different primary tumors (lung, colon, uterus, stomach and breast). Interestingly, the gene was higher expressed in several tumor tissues analysed as compared to their corresponding normal tissues. Thus, GPIM is a novel gene codifying a protein with structural features characteristics of some CAMs, which might be involved in the tumor progression.


Subject(s)
Cell Adhesion Molecules/genetics , Chromosomes, Human, Pair 6/genetics , Genes , Neoplasm Proteins/genetics , Neoplasms/genetics , Amino Acid Sequence , Animals , Base Sequence , Cattle , Cell Adhesion Molecules/biosynthesis , Cell Adhesion Molecules/chemistry , DNA, Neoplasm/genetics , Disease Progression , Expressed Sequence Tags , Female , GPI-Linked Proteins , Gene Expression , Glycosylphosphatidylinositols/metabolism , Humans , Male , Mice , Molecular Sequence Data , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/chemistry , Neoplasms/metabolism , Neoplasms/pathology , Neural Cell Adhesion Molecules , Organ Specificity , Protein Structure, Tertiary , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Sequence Homology, Nucleic Acid , Tumor Cells, Cultured/metabolism
16.
J Clin Oncol ; 20(1): 254-62, 2002 Jan 01.
Article in English | MEDLINE | ID: mdl-11773177

ABSTRACT

PURPOSE: Telomerase activity and p16 expression can be considered two of the most important molecular markers implicated in tumorigenesis. Our main aim was to study the cooperative role of both molecular alterations in the prognosis of patients surgically resected for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We have determined telomerase activity and p16 expression in a series of 98 prospectively collected NSCLC specimens obtained from patients who had undergone surgery without other treatment. Telomerase activity was investigated by a telomeric repeat amplification protocol enzyme-linked immunosorbent assay-based procedure, and p16 expression was examined by Western blot. Associations with survival were evaluated. RESULTS: Positive results for telomerase activity were found in 82% of the cases, and this variable correlated with poor differentiation and recurrence of tumors. Lack of p16 expression was observed in 61% of tumors, and a significant association with tumor recurrence was also observed. By univariate analysis, both negative telomerase activity and p16-positive expression were significantly correlated with a better prognosis. Moreover, statistics for equality of survival distributions for telomerase, adjusted for p16, indicated a positive interaction between both parameters. For telomerase-positive tumors, p16 expression emerged as a significant independent protective variable, as indicated by Cox multivariate analysis (relative risk [RR], 0.214; P =.014). This protective effect was maintained only for stage I and II tumors (RR, 0.108; P =.046). CONCLUSION: These results suggest that the combined telomerase activity and p16 expression analyses may be of prognostic importance in NSCLC, especially for patients affected by stage I and II tumors.


Subject(s)
Biomarkers, Tumor/biosynthesis , Carcinoma, Non-Small-Cell Lung/genetics , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , Lung Neoplasms/genetics , Telomerase/biosynthesis , Aged , Analysis of Variance , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/surgery , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/surgery , Male , Middle Aged , Prognosis , Proportional Hazards Models , Prospective Studies , Risk , Spain , Survival Rate
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