CLINICAL ONCOLOGY

Author: LOSA GASPA FERRAN.
Year: 2002.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: HOSPITAL DE BELLVITGE.

Summary: INTRODUCTION tumors diagnosed from their metastases in those without identifying the primary tumor, despite a more or less comprehensive, it is known as metastatic cancer of unknown origin (CMOD). Those cases where, being the reason for a consultation metastases and origin is not clear prior to the initial visit, we labeled metastatic cancer presentation CPM. The study should be a diagnostic program explorations led to the identification of those cases that can benefit from special treatment, either by virtue of their primary tumor, as determined by individual prognostic factors. MATERIALS AND METHODS Between January 1992 and December 1997 were studied prospectively to those pacietnes (pts) entered with SCLC. Implemented in Studio Basic (EB) consisting of a medical history and complete physical examination, standard blood analysis with tumor markers and Rx chest. We considered the CM OD pts with EB negative, and they were treated Additional Study (EA): abdominal CT scan and mammography (women). The rest depts underwent follow-up. It realizón a uni and multivariate analysis for the identification of prognostic factors associated with survival. RESULTS included 234 pts. The EB was positive in 140 pts (59.8%). The EA identified the primary tumor in 24 cases, 8 considered treatable. The primary tumor was identified in 182 cases (77.8%). Lung cancer was the most common (40.1%), followed by prostate (6.4%), breast (5.1%) and ovary (4.7%). By histologías: adenocarcinoma well and moderándamente differential (55.6%), followed by carcinoma and adenocarcinoma undifferentiated (24.0%) and neuroendocrine carcinoma and small cell (10.7%). Univariate analysis and multivariate identified the primary tumor as vital prognostic factor. The other five independent prognostic variables in the multivariate analysis were age, performance status, location metastatic dominant, histology and treatment modality. The impact lymph node, pleural or peritoneal bone also obtained information unequivocal unamayor survival. CONCLUSIONS There is a need to discard through rapid diagnostic protocols, all those primary tumors are presented and disseminated in a manner which enjoy special treatments. Also, it must continue to identify those situations in which, although it has not been diagnosed with tumro primary, could receive effective treatments, or at least be candidates for clinical trials.

Author: JIMÉNEZ ANULA JUAN.
Year: 2002.
University: JAÉN [www.ujaen.es].
Place of defense: UNIVERSIDAD DE JAÉN.
Place of preparation: UNIVERSIDAD DE JAÉN.

Summary: INTRODUCTION: The cyclooxygenase (COX) is a key enzyme in the synthesis of prostaglandins, which have identified two isoforms: COX-Iy COX-2. The involvement of COX-2 in the oncogénesis colonic is supported by the overexpression of this enzyme in tumor cells, and the effects observed with the administration of fánnacos selective inhibitors of COX-2 in experimental models of colorectal cancer. OBJECTIVES: 10Investigar the expression of cyclooxygenase-2 (COX-2) in tumor cells from colorectal cancer and its relation to the clinical and histologic features of the tumor and 20 studying COX-2 as a prognostic factor of distance metastases and survival. PATIENTS and METHODS: We retrospectively studied in a series of 105 patients with sporadic colorectal cancer intervened in the Department of Surgery at the University Hospital "Princess of Spain" Jaén between the years 1991y 1997. Have been excluded from this series of patients presenting at diagnosis distance metastases and those with locally advanced cancers, which did not allow a radical resection of the tumor. We studied the following characteristics: sex, tumor location, TNM stage, histological type, histologic grade, and venous invasion invasion linrntica. The average time of follow-up was 54 months (range between 1and 126). Immunohistochemistry: immunohistochemical staining method were avidina-biotinaperoxidasa. The extent of staining was scored on Oa 4 and intensity Or 3. The expression was considered positive when the sum of the two numbers was greater than 2. Statistical Analysis: survival curves were constructed in accordance with the procedure and Kaplan-Meier curves in the comparison test was used log-rank. We calculated the rate ratio (RT) And he felt his confidence interval at 95% (lC 95%). In multivariate analysis using Cox regression. RESULTS: Expression of cyclooxygenase-2: The expression of COX-2 in tumor cells was considered positive in 38 cases (36.2%). There was a statistically significant relationship between the expression of cyclooxygenase-2 and sex, tumor location, tumor stage, histological type, histologic grade, invasion linrntica or venous invasion (p> O, 05). Recurrence tnmoral: In fourteen patients (13.3%) were diagnosed metastases distance. In multivariate analysis the expression of cyclooxygenase-2 is not significantly associated with remote metastases (HR = 0.36, 95% CI = 0.07-1.69). Survival: The median survival was 55 months. In the multivariate analysis COX-2 did not behave as an independent factor of risk of death (HR = 0.51, 95% CI = 0.22-1.21). Nor are significant differences when comparing survival curves associated with the expression of COX-2 (p = 0.25). CONCLUSIONS: la.La COX-2 was not significantly associated with the clinical and histologic features of the tumor. 28. COX-2 was not an independent prognostic factor for tumor recurrence and survival.

Author: DIAZ LANCIEGO ANGEL MANUEL.
Year: 2003.
University: EXTREMADURA [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.

Summary: In an area of high obviousness and high agragación family has described the polumorfisma essemáticos (YP, A) (ml and m2), GSTM1 (GSTM1-0) and GSTT1 (GSTT1-0) in patients with reviewing and lungs asociandolos among themselves clinical variables, antropometrícos, labor and toxicological and nutritional, social and genetros and according to the varibles histológia of lung cancer.

Author: CIRUELOS GIL EVA M..
Year: 2003.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA, UNIVERSIDAD COMPLUTENSE.

Summary: Cancer is a major health problem at present. Because of its incidence and prevalence, it is necessary to develop new strategies in their treatment, as is the discovery of new drugs derived from natural resources. Aplidine is derived from the marine tunicate Aplidinum albicnas, drugs that has proved a potent antitumor activity in preclinical models. In this PhD thesis presents the results of two Phase I studies performed with Aplidine. The survey was administered to Aplidine in intravenous infusion of 24 hours and weekly schedule with a week of rest for every 4. The initial dose and dose escalation was based on certain lethal dose in preclinical studies and toxicities that happened along the study. The recommended dose in this scheme of management for future phase II studies was 3.75 mg/m3, and the dose limiting toxicities were kind of muscle and liver. In study B, the administration Aplidine took place in the 3 hour intravenous infusion every two weeks. The initial dose was based on data obtained in the study A, and the escalation of dose toxicities that appeared over the study. The recommended dose for this scheme was 5 mg/m2, and the dose limiting toxicities were kind of kidney, liver and muscle. We found some evidence of drug activity in patients suffering from medullary thyroid carcinoma, neuroendocrine tumors and melanoma, basically. It can be concluded that Aplidine drug is a potential anti-tumor activity, simple operation in clinical practice and good toxicity profile. At this time there is an agenda for development of the drug in phase II studies in various tumors.

Author: DÍAZ ANGEL MANUEL.
Year: 2003.
University: EXTREMADURA [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.

Author: PASAMONTES PINGARRON JUAN ANTONIO.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: MEDICINA.

Summary: This work Doctoral Thesis aims to show the usefulness of the Positron Emission Tomography (PET 18F-FDG) in the diagnosis of tumor recurrence in patients with a history of head and neck cancer, which before the suspected recurrence both clinical data and / or physical exploratory patient, as well as proof of conventional image (Rx, CT and MRI) are negative or indeterminate. It also seeks to assess the impact of clinical PET 18F-FDG, describing the changes made in the diagnostic and therapeutic management of patients. It proceeded to conduct a meta-analysis of the literature on this subject and then compare the results from this study with those obtained in our patients. It selected a group of 54 patients, who had conducted 60 studies PET 18F-FDG, and analyzed the criterion validity of this technique, based on the criteria of Evidence Based Medicine (MBE). This yielded parameters Sensitivity, specificity, positive and negative Predictive Value, calculating the odds ratio and likelihood ratios, as well as to calculate the cutoff point in the summary ROC curve. It was able to establish the impacton the PET 18F-FDG in the management of patients applying criteria described by Hicks and tamibén as its effectiveness, according to the levels set by Fryback and Thornbury. Finally, these results were compared with those obtained for the meta-analysis of the literature, concurring in demonstrating the utility of PET 18F-FDG in the diagnosis of suspected reucrrencia tumor in head and neck cancers.

Author: CANDIOTA SILVEIRA ANA PAULA.
Year: 2004.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: ESCUELA DE POSTGRADO.

Summary: The human brain tumors are relatively common in the elderly. His correct diagnosis is of great importance to ensure therapeutic procedures or adequate clinical decision. The nuclear magnetic resonance spectroscopy in vivo is a tool for noninvasive diagnosis with great potential in front of the suspected lesion intracerebral. It can be purchased at the same exploration MRI with a small increase in time. The high-resolution spectroscopy has been widely used in the analysis of metabolites and excerpts from tumor biopsies or body fluids for better resolution and separation of the molecular components of the sample. This thesis deals with the analysis in vivo and in vitro spectral patterns of human brain tumors and tamibén injury císticas associated with these tumors. The analysis of in vivo spectra has used the methodology of spectral pattern recognition. The study of injuries císticas, we have developed an automatic classifier based on spectral patterns in vivo to distinguish between malignant lesions, benign and abscesses. Liquids císticos have been studied chemically. Siálico acid were detected and hexurónico often present in macromolecular components of extracellular matrix. We have done extractions metabolites solubes in perchloric acid (PCA) to observe the spectral pattern. The main results of this section are that the signal observed in vivo at 2.03 ppm, usually attributed to N-acetil aspartate, relate primarily to a macromolecular possibly acid siálico associated protein. We analyzed patterns in vivo model and solutions to field clinical (1.5 Teslas) and myo-inositol glycine, given its importance in the gradation of tumors astrocíticos and discrimination in other tumors as hemangiopericitomas and meningiomas, and has been designed a calibration curve with solutions model to determine the relative amounts of each in the spectrum in vivo. This will enable comparison of these values with those obtained in the analysis of biopsies in vitro. In this section, it was found that the relative amount of myo-inositol decreases with increasing tumor grade. We have also arisen, in the analysis of spectral patterns to field clinical, experimental formulas discriminatory (Classifiers), as based on mio-inositol/glicina and lipids to discriminate glioblastomas metastasis with an improvement of discrimination by some 22% of cases of glioblastoma. The in vitro analysis has been made by extracting soluble metabolites PCA with subsequent evaluation of spectral pattern by statistical analysis to detect metabolites useful in the types of discrimination are difficult to differentiate tumor in screening in vivo. In addition, there have been preliminary tests of spectral pattern recognition in vitro. We have obtained evidence to understand the differences observed in vivo. Finally, the detection of contraciones of glycine in vivo tumors astrocíticos low-grade, lower than that obtained in vitro, suggesting a restriction on mobility of glycine in the tissue intact, possibly because of its association with cellular macromolecules. In addition, this thesis deals with the collaboration in the development of a tool to aid in the diagnosis of brain tumors, based on NMR spectral patterns of 1H, image analysis by resonances, and pathological data anatomías cl 8 ínicos, 3eb associated with the project INTERPRET (International Network for Pattern Recognition of Tumors using Magnetic Resonance, http://carbon.uab.es/INTERPRET). This tool is in the process of certification industry and is undergoing evaluation in several clinical centers.

Author: JIMENO DOÑAQUE JOSÉ M..
Year: 2004.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: ET-743 represents an illustration of a new chemical entity with marine-derived anti-tumor activity in patients with mesenchymal tumors resistant to conventional therapy. The experimental approach of this work part of mechanistic aspects that demonstrate an impact on pharmacodynamic processes transcript as a unique relationship between the functionality of the DNA repair machinery (FRA) Yla sensitivity to the compound in experimental models of solid tumors. This correlation (more efficient repair of DNA nucleotide excision and increased sensitivity to ET-743) is the opposite to apply to other drugs that interact with DNA and therefore provides a model characterization of susceptibility / resistance ET -743 in the clinical arena. In addition to data from the phase 11pivotal in patients with soft tissue sarcoma relapsed or resistant to conventional therapies show that the drug of marine origin is capable of inducing objective response and long-term tumor control in a clinically relevant proportion of patients. The clinical sensitivity to ET-743 gives extreme differences in natural history (survival) among patients sensitive vs. resistant to the drug. This evidence anticipates the possibility of identifying molecular markers correlated with the clinical response to ET-743 and formed the basis for implementing a pilot project in two segments of research aimed at identifying molecular markers of response / resistance to propose models of treatment measure. The first segment of the pilot study is based on the characterization of the genetic expression profiles (PEG) basal and dynamic (after exposure to pharmacologic concentrations of ET-743) in a panel of cell lines of human sarcomas explantadas of patients not treated with chemotherapy conventional. The data generated using the cDNA Oncochip @ microarray show that from the point of view molecular ET-743 acts as a non-specific inhibitor of the transcription. Additionally, we have identified a number of genes (related to processes of binding to DNA, proteins and the impact on the machinery of the transcript) correlated with resistance or sensitivity to the drug. This model represents a paradigm for validation studies in patients candidates to be treated with ET-743. The second segment pilot has characterized FRA in a group of 45 patients with sarcoma advanced pretratado and have received ET-743 as rescue therapy. There were correlated using tumor samples fixed in paraffin, the polymorphisms of genes repairers ERCCl and XPD and the levels of mRNA ERCCl, XPD and BRCAl. The results show a concentration of objective response in patients homozygous carriers of the polymorphisms not mutants XPD. Levels of mRNA high ERCCl and XPD are correlated with disease-free survival at 6 months higher levels BRCAl low correlate with a response rate of progression-free survival and survival superiors.

Author: ESCUIN BORRÀS DANIEL.
Year: 2004.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of preparation: ESCUELA DE POSTGRADO.

Author: URBERUAGA PASCUAL ALEJANDRO.
Year: 2004.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGÍA.
Place of preparation: UPV/EHU.

Summary: The medulobastoma is the most common malignant brain tumor in the pediatric age. After analyzing so restrospective 79 patients under 18 years of age diagnosed with medulobastoma in 9 centers oncologia pediatrica of Spanish territory during the period between the years 1980 and 2001, we have found to be independent prognostic factors for the type and extent of surgery tumor necrosis. In our opinion, these characteristics and aided the nuclear pleomorphism and intratumoral vascularity (both parameters showed a statistical significance), in addition to the stadium M classification Chang, we can plan the treatment of these patients.

Author: NAVARRO FERRANDO JOSÉ TOMÁS.
Year: 2004.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: ESCUELA DE POSTGRADO.

Summary: Lymphomas are the second most common malignancy that affects patients infected with the inmnodeficiencia human virus (HIV). From the calving of highly active antiretroviral therapy (HAART), the prognosis of patients infected with HIV has changed, and there has been a decrease in the incidence of opportunistic infections and certain malignancies. The widespread use of HAART has been determined that the prognostic factors for patients with lymphoma associated with HIV infection are more related to the lymphoma that with the virus. When starting the Doctoral Thesis raised the following assumptions: * The international prognostic index for patients with lymphomas not hodgkinianos (NHL) and Hodgkin's lymphoma (LH), which had no immunosuppression, can be applied to patients with lymphoma associated with the infection with HIV. * The HAART can modify the characteristics clilnicobiológicas of lymphomas associated with the HIV infection, as patients receiving treatment aimed at restoring immunity. * The HAART may improve response to chemotherapy and survival in patients with lymphoma associated with HIV infection. * The potential beneficial effect of HAART on the response to treatment and survival of patients with lymphoma can be restricted to patients who respond to that treatment. The main conclusions of the Doctoral Thesis are: * At the time of HAART, the NHL associated with HIV infection were diagnosed in patients with an older, a higher percentage of women and with figures of CD4 more a high serum LDH figures higher. * In the era of HAART, patients with LH associated with HIV infection have an AIDS test advanced in a lower proportion of cases. They noted an increase in the incidence of variety nodular sclerosis and a decrease of lymphocytic depletion over the period pre-TARGA. * The HAART is an independent prognostic factor for obtaining a complete response, overall survival and disease-free survival in patients with NHL associated with HIV infection treated with CHOP, and in patients with LH associated with the HIV infection. * Patients with NHL and HIV infection receiving HAART and CHOP virologic response and present, have a probability of overall survival higher.

Author: TELLERIA GARAY NAIARA.
Year: 2004.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: THE METASTASIS IS THE MAIN CAUSE OF DEATH BY CANCER, AFECTANDO TO A 60% OF PATIENTS WITH CANCER. THERE ARE FACTORS ENABLING THE TUMOR AND OTHER OF MICROAMBIENTE TUMORAL WHICH CONTRIBUTES TO INCREASE CAPACITY METASTATICA OF THE CELLS OF MELANOMA B16. BUT WITHOUT SUCCESS HAS TRIED TO IDENTIFY GENES AND PROTEINS REGULATING THE BEHAVIOR METASTATICO OF TUMORS MALIGNOS. THIS INFORMATION PROPORCIONARIA MARKERS FOR PREDECIR THE PRONOSTICO OF CANCER AND ABOUT THE MOLECULAS REGULATING THE METASTASIS COULD HAVE IMPLICATIONS TERAPEUTICAS. THIS PROJECT IS PLANTEO TO IDENTIFY THE PURPOSE OF THE PROFILE OF EXPRESSION GENICA THAT CONTAINED IN THE TUMOR CELLS OF AN EXPERIMENTAL METASTATICO WHEN HE BRINGS HIS LEVEL OF STRESS OXIDATIVO AFTER INHIBICION ITS MACHINERY ANTIOXIDANTS ENDOGENA, OR AS CONSECUENCA OF FACTORS OXIDANTES EXOGENOS. THE RESULTS OBTAINED DEMUESTRAN THAT CHANGES INTRACELULARES OF GSH PARTNERS TO GROWTH IN VITRO OF MELANOMA DETERMINING DIFFERENT PATTERNS TRANSCRIPCIONALES EXPRESSION GENICA IN RESPONSE TO STRESS OXIDATIVO ENDOGENO And EXOGENO. THESE PATTERNS ARE CORRELACIONAN WITH INCREASES ESTADISTICAMENTE SIGNIFICANT IN THE ABILITY TO GENERATE METASTASIS HEPATICAS OF CELL TUMORALES MANTENIDAS IN THESE CONDITIONS. ANALYZING THE GENES FACED DISORDERS TRANSCRIPCIONALES CURRENT MODEL FOR ACTIVATION PROMETASTATICA OF MELANOMA BY STRESS OXIDATIVO DEMUESTRA THE APPARITION IN CELLS OF MELANOMA OF A FACILITY ENTRAMADO MOLECULAR IN ELQ EU IS ARMONIZAN SIMULTANEAMENTE MECHANISMS OF FUNCTIONAL PROLIFERATION, INVASION, ANGIOGENESIS, PROTECTION REDOX. ESCAPE INMUNE, INFLAMACION And ACCESSION INTERCELULAR. EVEN MORE, THE TRANSCRIPTOMAS THAT CARACTERIZAN THE ACTIVATION PROMETASTATICA OF MELANOMA B16 BY STRESS OXIDATIVO, ENDOGENO And EXOGENO, CONSTITUTE NEW FOR FUNCTIONAL FOR DISCRIMINATION FARMACOGENOMICA OF AGENTS WITH THE ABILITY SPECIFIED FOR INHIBIR BEHAVIOR METASTATICO OF MELANOMA.

Author: PAREDES LARIO ALFREDO.
Year: 2004.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGIA.
Place of preparation: FACULTAD DE MEDICINA Y ODONTOLOGIA.

Summary: The majority of patients with lung cancer are often resistant to chemotherapy. In experimental studies with cultured cells, the expression of specific transport proteins, known as "proteins associated with resistance to multiple drugs or MDR-proteínas", conferring resistance to multiple antineoplastic drugs. In this Doctoral Thesis, by immunohistochemical methods, we studied the expression of three of these proteins (Pgp, Mrp1 and Lrp), in samples tumor criocongeladas of 99 patients with lung cancer without prior chemotherapy: 93 carcinomas cell non-small (49 scaly, 37 adenocarcinomas, 7 cél. big 3 carcinomas small cell, 3 other histologías). Our results reveal an important expression of the three MDR-proteínas, with a 64%, 49% and 38% of patients expressing Lrp, Pgp and Mrp1 respectively, and 66% of them expressing simultaneously over a MDR-proteína. We found no differences in expression in relation to clinical variables such as age, stage, grade of differentiation histological or survival, but there are variations among different histological types, stressing a low expression of Mrp1 in adenocarcinomas (p = 0.000) . Proteins Pgp and Lrp often expressed partner ((p = 0.000). Patients expressing simultaneously Pgp and Mrp1 respond to chemotherapy significantly lower (p = 0.0

Author: MUÑOZ MADERO VICENTE.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: MEDICINA.
Place of preparation: FAC. DE MEDICINA.

Summary: INTRODUCTION The present thinking in the surgical treatment of breast cancer, leads to embark on an attempt to complete rehabilitation of the patient, based on the prevention of sequels and the conservation or plastic breast reconstruction, as well as conservative treatment in the armpit. But the main goal remains the disease control oncology, whose persistence is due to three biological phenomena. Recidiva-metástasis, instability tissue oncogenética and residual disease unnoticed. Seeking to establish a guide for action in this regard, we undertake, in accordance with the method of Browman action based on the existing knowledge and its development with a parallel task of auditing. PATIENTS AND METHODS Following technical procedures, with adequate scientific evidence of suitability, existing knowledge and appeared in the development of our work, we operate within a multidisciplinary coordination effort, 243 patients with different procedures oncoplásticos conservatives and reconstructivos. Periodically perform an evaluation oncology (locoregional recurrence, metastasis and cancer mortality) and aesthetics (size, symmetry and projection) introducing changes that this audit and knowledge appeared advised. Finally, we performed a multivariate analysis, including as dependent variables, recurrence, metastasis and mortality as covariates, different circumstances between the clinical and biological stresses that the type of surgery. RESULTS 7 patients developed recidíva local 21 metastatic disease and 15 died of neoplastic progression to relapse and metastasis, had the statistical significance permeation linfovascular for death, in addition to the clinical diagnosis. The procedures with a better cosmetic result and recent developments were lumpectomy, mamoplastia and TRAM flap reconstruction. CONCLUSION It is possible to carry out conservative surgery and oncoplástica grandular and nodal accordance with the principles of radical cancer without prejudice to the outcome of controlling cancer.

Author: CANTALEJO LÓPEZ M. ANGELES.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA U.C.M..

Summary: The quality of life following the treatment of any type of cancer occurred during childhood is of increasing importance because the number of survivors is increasing, but a proportion of these survivors may present side effects long-term treatment found one of the first places growth, reason for our study. It appreciate retrospect, the loss of stature and variations in velocity, weight, body mass index and growth hormone in the diagnosis, treatment and evaluation so in 100 patients diagnosed at age 18 years in Section Onco- Pediatric Hematology Hospital Gregorio Maranon in Madrid. All were free of disease and the time elapsed since the end of treatment was over one year. Of these 53 were women and 47 men. The greatest loss of stature with statistical significance takes place between diagnosis and evaluation (p wiggle 0,001). The hardest hit have been children under 3 years. The Lymphomas show a loss of stature significant (p less 0.05), as well as Óseos tumors (p less 0.01), from the diagnostic evaluation. Patients receiving combination therapies, C + + RT QT and QT + RT are presented lost height significant (p less 0,001). The increase in the growth rate in the general population from the diagnostic evaluation was +1.01 ESU (p less 0,001). The largest of 10 years had a larger increase at that time and those treated with QT (p less 0.01) and C + QT (p less 0.05). The 41.8% of the 43 patients studied introduced deficit Growth hormone more involvement in children under 3 years and in those receiving radiotherapy on central nervous system. We conclude that patients most affected by the treatment antineoplasico are: children under 3 years, tumors and lymphomas Óseos and those who received combination therapy. This suggests the need for long-term follow-ups to collect and study groups multicentre to allow the number of patients arriving at meaningful conclusions.

Author: RODRÍGUEZ DÍAZ JUAN CARLOS.
Year: 2004.
University: OVIEDO [www.uniovi.es].
Place of defense: FACULTAD DE MEDICINA DE OVIEDO.
Place of preparation: UNIVERSIDAD DE OVIEDO.

Summary: REASONS AND OBJECTIVES The catepsina D is a protein that proteolytic has often been implicated as a prognostic factor in breast cancer primary. The present study analyzed, using a method of analysis immune radiometric concentrations cytosolic intratumorales of the protein in breast cancer primary, their relationship with clinical and pathological parameters of the tumor and its prognostic significance in a wide range of patients breast cancer. Methods The study included 1033 patients diagnósticadas of invasive breast carcinoma. The catepsina D was determined cytosol of the samples using a method inmunoradiométrico that determined the various forms of catepsina (52K, 48K and 34K). Assessing the time disease-free survival and overall was conducted on a group of 1003 patients with no evidence of metastasis at the time of initial diagnosis. The mean follow-up period was 54 months. RESULTS levels catepsina D tumors showed a wide variation (n = 1033; median 41; interval 0,9-2504; pmol / mg protein). In addition, levels of captesina D were significantly higher in breast tumors than in non-neoplastic tissue adjacent (n = 10,10,4 (4,2-38,5) pmol / mg protein, p = 0.00009 ). Statistical analysis also showed that the levels of catepsina D were significantly higher in tumors larger (t2-T4) than in those smaller (T1) (p = 0017), those with lymph node involvement compared to tumors without lymph node involvement (p = 0004). Levels of catepsina D were also significantly higher in tumor histological type of ductal tumors than in other histological types (p = 0001), as well as for those with a lesser degree of differentiation with respect to well-differentiated tumors ( p increased 0.01). Tumors aneuoploides showed levels catepsina D significantly higher than diploid tumors (p = 0.02). Also of catepsina D levels were significantly higher in tumors with RE / PR negative than in those who were negative for these recipients (p = 0011 & p = 0004 respectively). The multivariate analysis showed that high catepsina D (highest 59 pmol / mg protein) were significantly associated with a shorter overall survival in all patients with breast cancer and in the subgroup of patients who had lymph node involvement (p less 0 , 05). Conclusions This study suggests that levels intratumorales high catepsina D can identify a subgroup of patients with breast cancer who show a high risk of death as a result of tumor progression.

Author: ARAQUE ARROYO PATRICIA.
Year: 2004.
University: GRANADA [www.ugr.es].
Place of defense: DEPARTAMENTO DE NUTRICIÓN Y BROMATOLOGÍA.
Place of preparation: FAUCLTAD DE FARMACIA.

Summary: The study population consisting of a homogeneous group of patients affected breast cancer in early stages of the disease, treated surgically, presents an exposure to organochlorine pesticides classified as xenoestrógenos bioaccumulative, which can be defined as important both for the frequency of waste identified by concentrations found. The frequency of accumulation in the body fat of pesticides analyzed in this study were, in descending order, as follows: p, p'DDE (100%), HCB (98%), lindane (91.5%), or , p'OOT and endosulfán-I (85.7%), endrin (83.7%), methoxychlor (81, 7%), dieldrin (79.6%) and vinclozolina (73.5%). The most abundant pesticide found in the adipose tissue breast proved p, p'ODE (arithmetic mean, 382.83 ng / g fat), followed by the following compounds: HCB (151.42 ng / g fat); or, p'OOO (108.58 ng / g fat), endosulfán-diol (51.72 ng / g fat), endrin (50.89 ng / g fat) and vinclozolina (42.69 ng / g fat). The largest age of the patients at the time of recruitment, the countryside, dedication to agriculture, greater parity and lactation longer associated with exposure to organochlorine pesticides with the greatest impact. The estimate of the combined effect of xenoestrógenos by far the burden actual total estrogen (CETE), has revealed the extent of public exposure to them. Thus, the average values of estrogenicidad of chromatographic fractions alpha and beta were 335 and 331, 9 pM estradiol equivalents per gram of fat (arithmetic mean), with a percentage of positivídad of 72.2 and 94.4%, respectively. The antitumor treatment to the patients who underwent exercise seems certain modifications on the estrogenicidad fat, so that the extent of CETE fractions for the alpha and beta, estimated at the time of surgical intervention (geometric mean, 13.07 and 17, 13 pM Eeq this, adiollg lipid) became 148.88, 158.86 Y80, 82 pM Eeq estradiol / g lipid fractions for alpha (p greater 0, OO1) and 174,71241,72 And 126.21 pM Eeq estradiol / g lipido for fractions beta (p greater O, O01) at 6, 12 and 18 months into the antineoplastic therapy. The repeated measures the levels of waste xenoestrógenos biacumulables in breast and abdominal adipose tissue and peripheral blood have identified a pattern of biological behavior common to most pesticides investigated. After more than three months of treatment in place, there is a drop in levels of the compounds bioacumulados in fat which is reflected in the concomitant decrease circulating levels of these compounds. In the particular case of organochlorine more abundant, patients younger, urban habitat, with high level of education, who have been pregnant and who have received chemotherapy before and after surgery, had a significant decrease in the mean values p, p'DDE which went from 291.3 in the speech to 136.1 ng / g fat in adipose tissue to the 18-month follow-up (medías geométrícas). Patients in the study who received chemotherapy prior to surgery had levels of organochlorine pesticides at the time of recruitment significantly lower than those who were not subject to the same (geometric mean, P, p'DDE, 202.6 vs. 309.5 riglg fat), suggesting an effect of certain systemic treatment on bioeliminación of xenoestrógenos. Those patients progressed, on the other hand, during the 18-month follow-up in a particular place therein greater drop in the levels of organochlorine than in the rest of the series 8 of estu 9fa gave. Patients included in the study were treated with chemotherapy and postoperative radiotherapy showed a significant fall (Factor 3, in the case of p, p'DOE), statistically significant, the average concentrations of pesticides group OOT. Falling levels of pesticide tissue correlated with serum levels of the same, so that the ratio of the concentrations of p, p'DDE in adipose tissue and peripheral blood estimated at follow-up, ranged from the value 3, 22 / 3.90 (chemotherapy / radiotherapy) at the time of the intervention and 2.64 / 3.39 to 18 months follow-up. In both situations (chemotherapy / radiotherapy) observed a minimum value (2.16 / 2.37) within three months of starting treatment. This reflects, in our view, the relative increase in the values of pesticide circulating in early established antitumor therapy and suggests the early mobilization of the same fatty deposits has proved the striking discrepancy between the estimated exposure as measured by determining the actual total burden estrogen (CETE) and the quantification of residual organochlorine pesticides. Indeed, the trends in the temporary change during follow-up were opposed and the factors that conditioned the first lacked importance in defining the second. Thus, the patients who had a significant increase in the estrogenicidad of alpha fraction, from 6 months follow-up, were younger than 65 years not commented contact with pesticides and treated with adjuvant and neoadjuvant chemotherapy, and patients who showed a significant increase in the values of estrogenicidad of beta fraction were those who spoke have been pregnant, not having had contact with pesticides, presenting a BMI under 29.6 at the time of surgery and had been treated with chemotherapy and adjuvant conflicting situations on what measure of organochlorine pesticide residue suggests.

Author: MELGUIZO BÉJAR AMOR.
Year: 2004.
University: ZARAGOZA [www.unizar.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: INTRODUCTION The CECC is a set of rules aimed at preventing Europe's population, was drafted in 1986 by a committee of experts oncologists representatives of the then 12 member countries. The latest revision has been undertaken in the year 2003, with its field of 25 member countries. The opinion of the experts is that if people follow these standards, a significant decreasing mortality from cancer. The ASSUMPTIONS work is that the CECC is little known by the people and lifestyles that are sparsely recommends followed by youth. The knowledge of the situation would allow us to establish possible intervention measures. A descriptive study was designed observational type cross, made through health survey. The universe of the study were students enrolled in the first class at the University of Zaragoza in the 2000-2001 academic year and attending class (N = 8188), it took a sample of 600 students, through random sampling with afijación proportional, as the number of students enrolled in the various Colleges and Schools. As Instrument used a questionnaire based on those commissioned by the European Commission Eurobarometer, expanding with questions of development itself. We personally filled out by students, while maintaining anonymity. Pilot study: January 2001. Data collection: the second half of April 2001. OBJECTIVES Analyze knowledge and attitudes about cancer prevention. To assess the spread and impact of the councils of the CECC in students. Knowing lifestyles of the students who have been linked to cancer. Knowing the views regarding EU action in the fight against cancer. MAIN RESULTS collected 578 valid questionnaires from students of Zaragoza, Huesca, Teruel and La Almunia. The consumption of fruits and vegetables is very low. More than 30% drink alcohol at high-ranking one or two days a week. They are the 34.1% current smokers and want to quit smoking or minus 81%. Different motives, circumstances and methods that have been used to try to stop smoking, and exposure to environmental tobacco. The 56.9% believe that the authorities must take an active role in overcoming the problem of smoking. Students have confusing information on the action of fotoprotectores and on the signs that can help early detection of cancer. The 89.9% does not know the existence of the European Code Against Cancer. The 87.9% believed that the European Union should be responsible for the prevention of cancer, compared with 11.9% who say it is a matter of each member country. CONCLUSIONS would interest the spread of the councils of the European Code Against Cancer among university students, especially those actions to control smoking, encouraging the consumption of fresh fruits and vegetables, use and dissemination of fotoprotectores councils early detection. It would be of interest to the creation of a page on the Internet or institutional portal of the European Union on cancer in different languages, with information aimed at professionals, patients and the various population groups. It would be of interest to know these views in other populations, especially young people from other backgrounds. Following our review of the issue, we concluded that we should raise the desirability of recovering or push for a European integrated action to combat cancer. INTRODUCTION The CECC is a set of rules aimed at preventing Europe's population, was drafted in 1986 by a committee of experts oncologists representatives of the then 12 member countries. The latest revision has been undertaken in the year 2003, with its field of 25 member countries. The opinion of the experts is that if people follow these standards, a significant decreasing mortality from cancer. The ASSUMPTIONS work is that the CECC is little known by the pop 8 ation and e71 lifestyles are recommended sparsely followed by youth. The knowledge of the situation would allow us to establish possible intervention measures. A descriptive study was designed observational type cross, made through health survey. The universe of the study were students enrolled in the first class at the University of Zaragoza in the 2000-2001 academic year and attending class (N = 8188), it took a sample of 600 students, through random sampling with afijación proportional, as the number of students enrolled in the various Colleges and Schools. As Instrument used a questionnaire based on those commissioned by the European Commission Eurobarometer, expanding with questions of development itself. We personally filled out by students, while maintaining anonymity. Pilot study: January 2001. Data collection: the second half of April 2001. OBJECTIVES Analyze knowledge and attitudes about cancer prevention. To assess the spread and impact of the councils of the CECC in students. Knowing lifestyles of the students who have been linked to cancer. Knowing the views regarding EU action in the fight against cancer. MAIN RESULTS collected 578 valid questionnaires from students of Zaragoza, Huesca, Teruel and La Almunia. The consumption of fruits and vegetables is very low. More than 30% drink alcohol at high-ranking one or two days a week. They are the 34.1% current smokers and want to quit smoking or minus 81%. Different motives, circumstances and methods that have been used to try to stop smoking, and exposure to environmental tobacco. The 56.9% believe that the authorities must take an active role in overcoming the problem of smoking. Students have confusing information on the action of fotoprotectores and on the signs that can help early detection of cancer. The 89.9% does not know the existence of the European Code Against Cancer. The 87.9% believed that the European Union should be responsible for the prevention of cancer, compared with 11.9% who say it is a matter of each member country. CONCLUSIONS would interest the spread of the councils of the European Code Against Cancer among university students, especially those actions to control smoking, encouraging the consumption of fresh fruits and vegetables, use and dissemination of fotoprotectores councils early detection. It would be of interest to the creation of a page on the Internet or institutional portal of the European Union on cancer in different languages, with information aimed at professionals, patients and the various population groups. It would be of interest to know these views in other populations, especially young people from other backgrounds. Following our review of the issue, we concluded that we should raise the desirability of recovering or push for a European integrated action to combat cancer.

Author: DUARTE RUIZ BLANCA.
Year: 2004.
University: ZARAGOZA [www.unizar.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The oral cancer is a growing health problem and common. However, this is a disease that still attracts little attention from epidemiologists. The fact that there was no relevant studies on the disease, has motivated this study. It wants to determine the epidemiological profile of the patient with squamous cell carcinoma of tongue in the Autonomous Community of Aragon, for that defining characteristics geneales typical and the most common clinical behavior of the same disease in the area indicated.

Author: JORDÀ RAMOS MIREIA.
Year: 2005.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: UNIVERSITAT AUTÒNOMA DE BARCELONA.
Place of preparation: IDIBELL-INSTITUT DE RECERCA ONCOLÒGICA (IRO).

Summary: The carcinomas are tumors of epithelial origin and constitute approximately 90% of human tumors. The tumor progression involves several stages: growth of the primary tumor, local invasion, intravasation, extravasation and proliferation of tumor cells in a new body which forms a secondary tumor or metastasis. These are precisely metastases the leading cause of death for cancer patients. The invasion local carcinomas requires the loss of expression or function of the adhesion molecule cadherina E, which is considered an invasion suppressor. Additionally, the process of invasion is often accompanied by the loss of other epithelial markers, the markers mesenquimáticos acquisition and the increase in migratory and invasive properties. These changes have significant parallels with the phenotypic conversion that occurs in some processes of embryonic development and is called transition epitelio-mesénquima (TEM). The main mechanism involved in the silencing of the cadherina E is the transcriptional repression, and have recently been characterized several transcription factors that through their interaction with the boxes E (sequence CANNTG) promoter of cadherina E repress expression: Snail, Slug, E47, Twist, ZEB-1 and ZEB-2. The stable expression of Snail or E47 in epithelial MDCK cells induces a complete TEM process, but did not know the mechanism. Many of the alterations that occur in the TEM can be explained as a consequence of the suppression of the cadherina E, but other cellular events, independent of the cell dissociation, would also contribute to the initiation and completion of the process. For this reason, in this thesis has done an analysis of differential gene expression through RAP-PCR and of cDNA microarrays to identify genes involved in the process of TEM induced Snail or E47. We have found genes that code for proteins related to various cellular functions such as cell cycle, apoptosis, or metabolic signaling, but the group is the majority of genes involved in migration and invasion (Accession cellular cytoskeleton, extracellular matrix (ECM) and proteases MEC). This study also shows that in MDCK cells induces programs is partly genetic and partly specific common after the stable expression of Snail or E47, supporting a differential role of these two repressors in tumor progression and invasion. In addition, we have studied the mechanism of transcriptional activation of the metaloproteasa MMP-9 and the transcription factor Id-1 whose expression is activated in the TEM induced by Snail cook for E47. In the case of MMP-9, activation-induced Snail and E47 is indirect and mediated by other transcription factors such as Ets-1 and SP1 join the proximal region of its promoter into a multiplex, and NFkB/p65 that is interacts with a more distal region. In the case of Id-1, transcriptional activation is regulated mainly through the second box E promoter human interacts with E47. Concerning Snail, we were unable to confirm whether binds directly to this element or induces the expression d another transcription factor can join. In addition it is also important to the GC box adjacent to recruit Sp1. In both cases, the activation is regulated by the way Erk / MAPK (activated by Snail and E47) phosphorylated at least Sp1.