ONCOLOGY

Author: VILLANUEVA ALVAREZ ASUNCIÓN.
Year: 2003.
University: MÁLAGA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA UNIVERSIDAD DE MÁLAGA.

Summary: Based on previous studies, we designed this research work which consists in the administration of low-dose cisplatin (in the form of monoquimioterapia concominante radiotherapy) demonstrated an increase in survival compared to radiotherapy alone and administration of an accelerated radiotherapy with overlay or "concomitant boost" to administer two sessions a day only in the final stage of treatment, gaining better control found in the schedules accelerated or hiperfraccionados, but at least, with less toxicity late and less overhead for radiotherapy services involved the hiperfraccionamiento conventional. We start with the objectives of assessing the feasibility and tolerance of treatment, to find a tolerable toxicity and to explore the patterns of response and the impact on the overall survival, relapse-free and free of progression. Have been studied, in the period between January 2000 and September 2002 a total of 92 patients, predominantly male, with an average age of 58 years, with an ECOG between 0 and 1. The histology has been the dominant being the oropharynx epidermoid tumor location more frequent. Regarding the estadiaje, we found that the majority of patients have a stadium loco-regional advanced, with a 77% of cases stadiums IV. The overall average survival of all patients was analyzed from 23.89 months, with a probability of superviencia accumulated to 2 years of 49.3%, the disease-free interval in patients who obtain an RC was 26.35 months with a probability of econtrarse relapse-free of 66.9% and an average duration of treatment response at the global nature of the series of 20.7 months with a probability of being free of progression of 51%. In the univariate analysis there has been a statistically significant relationship in terms of overall survival with the cytological degree of differentiation, with the overall stadium, with lymph node involvement and the type of response. Of these factors, the multivariate analysis confirmed its significance degree of histological differentiation as a prognostic factor in the survival before applying the treatment, and what kind of response after treatment and the variable relapse or progression of the disease. The probability of relapse or progression is associated with hemoglobin levels, the overall stadium and the type of response. In analyzing through logistic regression model the factors that most influence the achievement of a complete response after treatment, we note that only tends to the stadium overall significance. We can say in general that the prognostic factors identified in our series match those in the literature, maintaining the toxicity within an acceptable range and reflecting survival parallel to that of other published papers that employ radioquimioterapia simultaneously.

Author: CAMACHO ROVIRA EMMA.
Year: 2003.
University: BARCELONA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA CUNIV.DE BARCELONA.

Summary: In this thesis elaborates knowledge of the molecular alterations involved in protogÃÂ © nesis of LCM, travÃÂ © s study gene involved in the regulaciÃÂ ³ n the progress of the cell cycle, particularly at points of control.Los data show that alterations in the ATM gene are a fenÃÂ ³ meno frequent, apariciÃÂ charges early in the encogÃÂ © nesis of LCM and co a clear influence on the generaciÃÂ charges of desecrilibrios cromosonicos in tumors vaciante clÃÂ ¡music. Regarding the possible influence alterations of ATM and other genes in the same vÃÂa of trasduciÃÂ charges of seÃÂ ± ales As CHK9, CHR2 and p53 in predisposiciÃÂ ³ n genÃÂ © rich development meoplasias hematologÃÂcas asociadaa to LCM, could not be excluded due to pequeÃÂ ± or tamaÃÂ ± or mostral analizado.Finalmente will analyze the pesencia of genetic alterations genes HMPS1 and AuroraA, observandose a soje frecuencio these alterations consÃÂ ³ micas type nÃÂ fourth merico or amenploidÃÂa in LCM.AsÃÂ, has found a viriante gene Aurora A significantly sobrereprentado in tumor samples, which could relate to the predisposiciÃÂ charges to the development of such tumors.

Author: CAMPO BALSA M. TERESA DEL.
Year: 2003.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: HOSPITAL LA PAZ.

Summary: INTRODUCTION In many Consensus Conference on Prevention, dignóstico and treatment of Osteoporosis states that since childhood, have an adequate intake of calcium and vitamin D is crucial for the development of optimal peak bone mass and to preserve the same through of life. The Osteoporosis is defined as a transtorno currently characterized by skeletal disorder of the bone resistance that predisposes an increased risk of fracture. Some randomized and controlled in the long term has found a significant decrease in the frequency of fractures after receiving vitamin D3 with or without calcium. Some authors also found a correlation between the serum concentration of calcidiol and bone mineral density (BMD). The optimal value of calcidiol serum is undefined, and in recent years it is considering not only the deficiency of vitamin D (calcidiol serum lower 10 ng / mL), but also insufficient (calcidiol minor 15 or 20 ng / mL) . In Europe it has been observed that in the Mediterranean countries is a higher prevalence of vitamin D deficiency in the Nordic countries, which could be due to different health policy management sumplementos vitamin D in these countries. Today we find an open debate on the need to manage sumplementos vitamin D in these countries. Today we find an open debate on the need to administer vitamin D supplements, and in particular about its indication of certain population groups and on which would be the optimal dosing regimen. The hypothesis was this Doctoral Thesis value if a posbile deficit of vitamin D in our population senile and postmenopaúsica might entail the need to administer vitamin D supplements to compensate for their natural sources and inadequate and / or to optimize bone physiology. Thus, our objectives were: 1-To study the influence of vitamin D in osteoporosis complicated for the elderly, assessing the concentrations of metabolites of vitamin D (calcidiol and calcitriol) and PTH in elderly hip fracture and without it V belonging to the area of Madrid. 2-To assess the levels of calcidiol serum with a BMD in postmenopausal lowered and its possible influence on the development of osteopoenia and postmenopausal osteoporosis. 3-Evaluate the prevalence of vitamin D deficiency in postmenopausal women belonging to a query reumtatológica Area V Madrid, and its relationship with BMD. 4-Check if found vitamin D deficiency in postmenopausal women and elderly hip fracture reversed after administration of vitamin D supplements, evaluating the effectiveness of different patterns of administration. PATIENTS AND METHODS We conducted four procolos study: * Protocol I: Prospective study conducted at the time of minimum solar irradiance deemed to 58 fracture patients caderaa and older than 70 years, attending emergency Traumagológicas Hospital La Paz and exclusion criteria cosistentes in pathology and / or therapeutic puderan affect bone metabolism. At the same time it was considered a control group of 39 elderly without hip fracture and similar criteria, and a control group of healthy adults to compare biochemical parameters. In patients with fractures and deficient in vitamin D (Calcidiol infieror to 10 ng / mL) were given vitamin D supplements 8 3: 1 two 120th is the clash of 200,000 IU of calcidiol followed by 400 IU / day of vitamin D3 for one year. * Protocol II; cross-sectional study of 150 postmenopausal women (with natural menopause toward since at least 2 years) who went to an outpatient Rheumatology Hospital La Paz and had a decreased BMD (Z-score of BMD at the lumbar lower 0) with exclusion criteria similar to the protocol I. It was also a control group of 25 women premenopaúsicas with normal BMD (Z-core greater =) and exclusion criteria similar. * Protocol III: prospective study conducted at the time of minimum solar irradiance deemed to 171 postmenopausal women (from natural menopause for at least 2 years) who came in a row to a search of the area Rheumatology V Madrid and exclusion criteria similar to previous products. * Protocol IV; prospective study of 82 postmenopausal women (60 of them coming from the protocol III and other similar characteristics) of a search of the area Rheumatology V Madrid, calcidioil less than 10 ng / mL and exclusion criteria of the protocol III. The group of patients were randomly distributed into two groups of features similar age and the prevalence of osteoporosis who were given two different patterns of vitamin D supplementation: A-Group 1:800 IU / day of vitamin D3 (along with 1000 mg of calcium daily). B-Group 2: A single dose of 80,000 IU of calcidiol followed a pattern similar to that of group 1. In all study protocols (except 1) was performed bone densitometry (at the lumbar spine and hip). The analytical methods included calcidiol, calcitriol and PTH (through methods for radioactive isotopes). And the statistical methods included in the multiple regression analysis by the method of successive steps and partnership linear Mantel (made in the protocol III). The most important results are summarized in the conclusions. The conclusions of the thesis were: 1 - The elderly population studied area belonging to V Madrid presents a very high prevalence of inadequacy and deficiency of vitamin D, decreased levels of calcitriol and secondary hyperparathyroidism. 2 - The elderly hip fracture have a higher failure (prevalence of 100%) and higher vitamin D deficiency (91%) than the elderly without fracture of the same age (90% and 70% shortfall deficiency) not dependent on PTH. 3-In the postmenopausal population from outpatient visits within the area V Madrid, we see a high prevalence of decreased serum levels of calcidiol, a 64% mujres postmenopausal with insufficient vitamin D and a 36% deficient in vitamin D. 4 - The postmenopausal women with a bone mineral density decreased presents levels calcidiol lower than women with normal bone density. 5-In postmenopausal women there is a positive correlation between serum concentrations of calidiol and bone mineral density in the lumbar spine, expand such correlation with the hip in women older than 60 years. 6 - The population postmenopausal objetivamos that when the calcidiol serum is less than 15 ng / mL, there is a positive relationship between calcidiol and bone mineral density in the hip not dependent on PTH. 7-Although the two patterns of supplementation of vitamin D daily in postmenopausal women deficient in this vitamin used in the study increased the levels of calcidiol only prescription with a dose of shock of 80,000 IU calcidiol followed by 800 IU vitamin D3, achieved during 3 months to overcome the deficiency of vitamin D in all women, it would be advisable doses with high cyclical pattern of vitamin D in populations deficient in the vitamin. 8-It concludes that seems to be taking the necessary health policies for the administration of vitamin D supplements in populations at risk for developing osteoporosis as is the population postmenopausal.

Author: GORDILLO CHAVES JUAN.
Year: 2003.
University: EXTREMADURA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Author: MALENO JIMÉNEZ ISABEL.
Year: 2003.
University: GRANADA.
Place of defense: HOSPITAL UNIVERSITARIO VIRGEN DE LAS NIEVES - GRANADA.
Place of preparation: HOSPITAL UNIVERSITARIO VIRGEN DE LAS NIEVES. GRANADA.

Summary: INTRODUCTION The molecules of the MHC class I are glycoproteins that appear on the membrane of the majority of nucleated cells. The genes that encode are located on the short arm of chromosome 6 (region of HLA class I) and chromosome 15 (gene of B2m). His expression on the surface of cells in combination with the antigen allows recognition by T lymphocytes There has been alterations in the expression of HLA class I molecules of different tumors that can be generated by different molecular alterations. MATERIALS AND METHODS We analyzed 95 carcinoma of the colon, 70 laryngeal and 50 adenocarcinomas kidney of these, 45 were clear cell type and 5 type cromófobo. Using the technique of microdisección, which allows us to obtain DNA of the tumor cells in histological cuts, we have made analysis of microsatellites, to detect the presence of lost heterocigosidad (LOH) of the HLA molecules. We have studied the frequency of LOH of the B2m using 2 markers and a centromérico telomérico to another gene, as well as the region 6p21.3 using 7 markers to identify those tumors that have submitted loss heterocigosidad (LOH) in the HLA region. It also includes a marker for 6q, to indicate where they might presume the existence of a monosomia this chromosome. In tumors that had LOH in the HLA region subsequently was conducted tipaje genomic for determining haplotype lost. RESULTS We found that some 40% of the tumors of the colon, 41% of the tumors of the larynx, 9% of renal tumors type cells and a 20% clear of the type cromófobo showed LOH of the B2m. Likewise, 40% of the tumors of the colon, 54% of tumors laringeos, 6% of renal tumors of clear cell type and 60% of the types cromófobo showed LOH of the HLA region. The haplotype lost could be given in cases that presented a total loss allele in the analysis of microsatellites. In carcinoma of the colon and larynx, which previously had been studied by inmunohistología alterations in the expression of HLA molecules, to reference results of the analysis of microsatellites with inmunohistológicos to define more precisely the frequency of HLA different phenotypes. By combining both techniques, the loss of an HLA haplotype (phenotype II), the phenotype was much more common in tumors of the colon (28%) and in those of the larynx (34%), mainly due to be added to this phenotype large number of cases that had been considered phenotype IV (loss alelicas) in the study inmunohistológico. In 26% of the tumors of the colon and in 23% of tumors laringeos, there was no alteration in the expression of HLA class I molecules The presence of LOH of the B2m not related to the presence of any particular alteration in the expression of HLA molecules. The availability of data concerning loss of expression determined by inmunohistología different HLA alleles those who have joined the loss of genomics, we have analyzed the frequency with which they will lose different HLA alleles. We found that tumors of the colon, the alleles HLA-A29 and HLA-B44 lost more frequently and allele HLA-A24 less frequently than the rest (statistically significant difference). While in tumors of the larynx single allele HLA-B44 faded more frequently. Finally, we analyzed whether there is a relationship between the results of our study and data clínico - patológicos or aggressiveness of tumor progression. We found that tumors of the colon, is rHLA-A29 was related to the advanced tumor stage (Duke D) and the presence of metastasis at a distance (M1). And be HLA-B44 with 8 presenc b52 ia metastasis distance. In laryngeal tumors, we found statistically significant relationship between the presence of LOH in the HLA region and the presence of alterations in the expression of HLA molecules in tumor location, so that those who had tumors location transglotica, these alterations were being in those rare tumor localization glotica. In renal tumors were found statistically significant relationship between the presence of LOH in the HLA region and the subtype. DISCUCIÓN The combination of the study inmunohistológico and analysis of microsatellites has enabled us to make a new approximation of the frequency at which the various alterations in the expression of HLA antigens (phenotypes) in the tumors studied. The detection of LOH at 6p21 is of great significance since it could mean a selective advantage for tumor growth by allowing the escape delas tumor cells to recognition by CTLs. In addition, the band 6p21 where HLA genes are located harbors genes encoding cytokines such as tumor necrosis factor and linfotocinas alpha and beta, which have effects in vitro cytostatics lines of melanoma and therefore this could be implicated in the regulation tumor growth. The loss of an HLA haplotype might arise at random in the clonal tumor that progress, therefore did not require a inmuinoselección upon, but would be an added advantage for the tumor to escape system inmuinitario to reduce the chances of antigenic recognition. In cancer treatment, being developed in recent years different immunization protocols using tumor-specific peptides presented by HLA class I molecules to generate a response by cytotoxic T lymphocytes Determine the loss of expression of HLA class I alleles can be very important to select the best scheme to stimulate a response immunotherapeutic anti-lymphocyte CD8. Most of the peptides antigéneticos that have been described are presented by HLA-A2, the most frequent allele in the population caucasoide. We have found that this rarely allele is lost in tumors studied, making it the allele of choice for use in tumor peptides based therapies and the search for new tumor antigens presented by HLA-A2.

Author: MARTÍN MALAVÉ FERNANDO.
Year: 2004.
University: MÁLAGA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: We have appreciated the factors clinico-patológicos most important prognostic (eg, age, histologic type, tumor estadificación, surgical treatment, extending pre-treatment metastases ,...), individually (descriptive) and trying to demonstrate the importance of each one of these parameters in relation to overall survival, after nine years of monitoring, to identify those who define, more significant -independiente and objectively the risk of mortality. In addition, we intend to evaluate the quality of care in patients by studying delays consultation, diagnostic and therapeutic. 1 a) The RHT the University Teaching Hospital in Malaga. Virgin of VICtoria "- created it 14 years, has proved a useful tool for information on patients with cancer of the uterus: number, age distribution and origin of the diseased . also obtained data on the quality of care in gynecological oncology activity at the center: the degree of certainty of the diagnosis of cancer, histological type, estadificación / extension tumor and the treatment applied. 2) In our center, we see a high tumor incidence of cervical stadiums in non-invasive, which affect mostly young and still a population of childbearing age. We believe that these results are a reflection of greater awareness of women gynecological preventive recognition. Endometrial cancer is a malignancy that affected primarily to women older than 65 years and, while not currently have efficient methods for early detection of the disease, most of the malignancies included in our series were limited to the uterine body, it in other words, they were stage 1. 4 a) The study of delays for consultation, diagnosis and treatment implementation translate existing difficulties, both by the patients and the health care system, to assess the initial symptoms of a malignant tumor, which affects, sometimes crucially, prognosis and treatment of the tumor. In cancer of cervix and endometrium, the average of three to four months in the delayed consultation, approximately two and a half months in establishing a diagnosis and two months in the implementation of treatment indicate that the level of education health and accessibility to the health system are upgradable, while it is acceptable delay in diagnosis and treatment. 5 a) At present, the data is more sensitive to the advances in the diagnosis and treatment applied is an assessment of the likelihood of survival, as this parameter summarized the effectiveness of assistance to the patients and response to different treatments, as well as prevention activities implemented. In our study, we see that overall survival after nine years of follow-up, both at the invasive cancer of cérvi in endometrial tumors is close to 80%. However, to stratify patients -atendiendo especially the stadium clínicopatológico- note that the stadiums IV, survival, and at two years was only 50% in patients with cervical cancer and 22% of cancer endometrium. 6 a) After the completion of this study, we recommend for the registration of gynecological cancer, incorporating proactively in the road data collection, new parameters recognized and associated with the etiology of injuries, for example, the association between infection (confirmed) human papillomavirus and cervical carcinomas. 7 a) It is necessary to emphasize the great imprecision exists in certain collected data on clinical findings, as well as, low uniformity of the protocols used and the terminology used in coding and estadificación. This is a major obstacle, sometimes decisive 8 to ll 30e evar research retrospectives, such relevance for therapeutic and prognostic evaluation of cancer.

Author: LÓPEZ DÍAZ ANDRÉS CARLOS.
Year: 2004.
University: MÁLAGA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Given the interest aroused ovarian cancer in our midst, and providing the data registry Hospital HCUM we ask this work with the following objectives: a) To determine the incidence of ovarian cancer hospital, from the year 1993, in this area health. B) Evaluate the importance of the parameters clínico - patológicos conventional (ie, age, parity, location, stadium histopalológico) in ovarian cancer. C) To assess the survival of patients with ovarian cancer, the eight-year follow-up. According to the characteristics of the tumor, the extent of the disease at diagnosis. Applied therapy. D) To assess the quality assistance 'in ovarian cancer patients, using indicators such as intervals consultation, diagnosis and treatment. 1 a) With this work of ovarian cancer, conducted in the area of registration Hospital of the University Teaching Hospital tumors "Our Lady of Victory" Malaga, it becomes apparent that, in addition to the limitations inherent in any study relrospectivo rearlZado cases they have been diagnosed and / or treated by different professionals, we find difICultades who rely on the information contained in the stories clinics. And so, in tumors of the series studied, it has been impossible to assess, among others parameters demonstrated prognostic relevance, such as the size of residual tumor after the first intervention and the extent citohistológico. 2 a) In our environment, and during the years studied, there was a progressive increase in the frequency of cancer ovaoo: whereas in the year 1993 it accounted for 2.12% of tumors in women and only 0.81% of total registered neoplasms, in 1999 this pathology was already 3.7% of female cancers and 1.6% of all cases. 3 a) ovarian cancer, is a pathology that it is diagnosed at advanced stages and that affects primarily women over the age of forty, postmenopausal, with children and no history with cancer. 4 a) An analysis of the survival shows that, after five years after diagnosis, there is even applying existing methods for treating a notable decrease in the probability of overall survival, ranging from almost 60% to less than 40% the 5 Y9 years of follow-up, respectively. 5 a) In our study, the variables that negatively influenced the supefVivencia were having more than 65 years and the spread of the disease at diagnosis, specifically Stadium IVde FIGO and the presence of metastasis. 6 a) It should be emphasized the impact that implies, in determining the survival oncological patients who are wrongly classified, and histological surgically. In this series, have encountered problems stemming from poor uniformity in terminology used for histological classification and the need to peñeccionamiento process estadiflCaCión post-tumor. 7 a) The fact that patients with ovarian cancer do not attend the first consultation until after-al menos seventy days after the appearance of the first symptom, the delay of less than a month in establishing a diagnosis and about twenty days in the treatment, which reaffirms the symptoms of ovarian cancer is insidious and that the accesibBidad the health system of patients from our environment is satisfactory. 8 a) Although there precísan greater guarantees on the quality of care data recorded, we believe the statistical monitoring of ovarian cancer medíante dynamics Hospital tumor registry, which now represents a valuable tool, both for assistance as for the investigation of this important disease neopren 8 lásica. <296 / b>

Author: GARCÍA DE LA CRUZ GEMMA.
Year: 2004.
University: AUTÓNOMA DE BARCELONA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: ESCUELA DE POSTGRADO.

Summary: This study investigated the action modular diets hiperlipídicas polyunsaturated n-6 (corn oil) and monounsaturated No-9 (virgin olive oil) on mammary carcinogenesis in an experimental model induced by DMBA. The analysis of the parameters of carcinogenesis revealed the stimulating effect of the high lipid content of polyunsaturated n-6 in the diet. On the other hand, emerged the protective role of the diet. On the other hand, emerged the protective role of dietary hiperlipídica olive on the breast cancer trial. The results showed that the ratio between the levels of mRNA for c-erB1 for the entire receiver EGFR and levels of mRNA for this truncated receptor increased in tumors groups diet hiperlipídica corn and diminished in the oil. However, the lipids in the diet would not have acted in mammary tumors either by direct action on the EGFR through changes in the activity of it, or by increasing its ligand. The diet of olive tended to decrease the levels of mRNA and protein c-erbB2/neu, although activity levels of the protein were not affected by dietary lipids, regardless of the type. Moreover, in considering the point mutation condom 61 activation of c-Ha-ras1 were obtained results consistent with a modulatory effect of dietary lipids: stimulator, primarily on cell carriers of the mutation, in the case of corn oil , and potentially inhibitor mainly on the cells without the mutation of ras, in the case of virgin olive oil. The fat in the diet did not affect the mRNA expression of c-Ha-ras1 or protein p21Ras. However, the diet rich in olive oil significantly decreased the activity of Ras. This decrease was not associated with a decreased activity of MAPK. Furthermore, we investigated the possible influence of lipids in the diet on the expression of genes involved in cell differentiation. The results showed that the fat in the diet, regardless of the type, increase the mRNA of beta-actina, but do not alter levels of the protein. This fact could be related to an effect of these lipids on ZBP-1, one of the proteins involved in the translation of beta-actina. Moreover, in analyzing the possible effect on the expression of alpha and beta-caseína, results surgirieron that deregulated expression of these proteins in breast tumors not be a good indicator of the state of differentiation of the tumor or changes on this exercise lipids in the diet. In addition, lipids in the diet, especially the diet of olive oil, tended to reduce the levels of expression of the protein antiapoptótica survivina. Finally, we analyzed the influence of lipids on the expression of mRNA of differentially expressed genes found by diet of corn oil in a previous job at it. While lipid No-9 did not affect the expression of alfa-2u globulin submaxillary, H19 and VDUP1, lipids n-6 decreased these levels, which would be associated with more aggressive behavior of tumors of this gr 8 upo. Tam 3aa well analyzed the expression of transferrin, found a trend to greater expression in groups of olive oil, despite the fact that the expression of this gene that appears linked to greater proliferation.

Author: SANCHO PARDO GEMMA RAMONA.
Year: 2004.
University: AUTÓNOMA DE BARCELONA.
Place of defense: FACULTAD DE MEDICINA (HOSPITAL DE SANT PAU).
Place of preparation: ESCUELA DE POSTGRADO.

Summary: Prostate cancer is the most common cancer in men and third leading cause of cancer death in Spain. The natural history of this tumor is uncertain and radical prostatectomy is still the treatment of choice in the stadiums located. Minor radiotherapy is a curative treatment alternative to prostatectomy and the treatment of choice in locally advanced tumors. The best known of the prognostic factors can be individualized and optimize treatments with radiotherapy. PATIENTS AND METHODS have been 981 patients with localized prostate cancer treated with external beam radiation with radical intent at the Hospital de la Santa Creu i Sant Pau in the period 1979-1999. Only 16% of cases are considered radiotherapy as a treatment of first choice. Average age: 68.5 years. Venue: 24% T1; 45% T2, 29% T3, 1% T4 and 1% N +. In 12% is unknown Gleason: 13% Gleason minor 4.60% lower 7 and 15% lower 7. A 17% of patients without initial PSA; 4% lower than 4 ng / ml 32% 4-10ng/ml; 24% higher 10-20 ng / ml and 23% increased 20 ng / ml. Risk Group: 20% low, 28% intermediate, 27% and 25% high not classifiable. A 58% performed endocrine therapy associated, and 3% had done previously radical prostatectomy. 30% of patients were treated with cobaltoterpia and 70% of 18 MV photons. In 907 patients was conducted elective pelvic irradiation. Dolsis half run in prostate: 70 Gy. In 673 patients have been able to gauge control biochemical agree with the definition proposed by the ASTRO. For the assessment of toxicity have been used scales of the RTOG. RESULTS * Response radiotherapy: 18% did not respond to radiotherapy. There is a statistically significant difference between the average value of PSA nadir of the group of patients who had biochemical failure and the group of patients free of judgment biochemist (1.12 vs. 0.65 ng / ml), if only treated with radiotherapy (1.57 vs. 1.12 ng / ml , p less 0,001) whether endocrine therapy associated (0.94 vs. 0.32 ng / ml, p less 0,001). A PSA nadir greater 1ng/ml is associated with more likely to have biochemical failure (p = 0.013), increased risk of disease progression (OR = 2.57, p = 0.001) and an increased risk of dying from prostate cancer ( p = 0.001). Patients who achieved a PSA nadir faster during the first year after radiotherapy, had a higher risk of biochemical progression and / or clinic that patients in whom the PSA decreased slowly (41% vs. 24%, p = 0.001) * biochemical failure: 27%; prognostic factors: age (p = 0.010), stage (p = 0.001), Gleason (p = 0.003), dose (p less 0,001) and PSA nadir less 1 ng / ml (p = 0.033). Some 39% of patients with biochemical failure presented clinical progression vs. an 8% of patients free of biochemical failure (p less 0,001). * Local Recurrence: 10.4%: prognostic factors: stage (p = 0.005) and dose (p = 0.05). * Metastases: 11%; prognostic factors: age (p = 0.046), Gleason (p = 0.006), stage (p less 0,001), dose (p00.009), PSA nadir less 1 ng / ml (p less 0,001), biochemical failure (p less 0,001), local recurrence (0,009). * Acute toxicity lesser degree 2: 66%: The use of cobalt therapy (p = 0.014) and pelvic irradiation (p = 0.019) were significantly associated with an increase in acute toxicity. * Chronic toxicity greater degree 2:22.8%. Prognostic factors: having presented acute toxicity (p less 0,001), an RTU (p = 0.009) and pelvic irradiation elective (0,041). The RTU prostate is associated with an increased toxicity Urinary chronic, but regardless of the existence 8 of this 90b background, the incidence of urethral stricture and incontinence remains low (less 1%). The administration of endocrine therapy is associated with erectile dysfunction. * GS 84% 5 years, 51% at 10 years and 38% at 15 years. The only variable associated with a lower overall survival with statistical significance is not reaching a nadir PSA less 1 ng / ml. * SVCE 93% at 5 years, 68% at 10 years and 57% at 15 years. The stadium has been confirmed as a powerful prognostic factor for death from prostate cancer, in conjunction with the dose and the PSA nadir. * SVLEC 77% at 5 years and 58% at 10 years. * SVLFB was 72.6% at 5 and 10 years. * SVLP is 58% at 5 years and 30% at 10 years. In about 50% of cases the cause of death was prostate cancer (9%). Mortality from prostate cancer is related in the first instance Stadium tumor (20% in stadiums T3-T4 vs. 3.8% in stadiums T1-T2). Only 1 patient the cause of death was associated with toxicity by radiotherapy. CONCLUSION External beam radiation is a curative treatment of localized prostate cancer (disease-free survival biochemical and / or clinic from 58% at 5 years and 30% at 10 years) with an acceptable toxicity. The clinical and dose radiotherapy are prognostic factors which are strongly associated with the progression of the disease. Knowledge of the prognostic factors and their use in the valoraicón individualized for each patient, the introduction and development of techniques RTC-3D, escalating doses and partnership rational systemic treatments will improve the outcome.

Author: SERRANO BLANCH RAQUEL.
Year: 2004.
University: CÓRDOBA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The development of molecular biology of cancer in recent years, has allowed us to identify changes in specific genes and their products that could be useful clinically. In colorectal carcinoma and other types of tumors, there is a defining component gene, mutations and / or molecular abnormalities found are many and its appearance can not only relate to one of them. In the cell cycle are the end point of many of these changes occur in tumorigenesis. Changes at the level of membrane receptors, cytosolic proteins responsible for the transmission of signals or level cycle itself, producing a disregulación in proliferación-apoptosis, determinandola emergence of enfermedadescomo cancer. The alterations of oncogenes and proteins involved in cell cycle, have been shown by different diagnostic techniques, including immunohistochemistry. The functional change any of these genes has been linked at least in theory, with disease progression, as well as the likelihood of response to treatment. However, when it has tried to apply this conocimientodel cell cycle into clinical practice the results have been mixed. The study of different alterations in isolation without taking into account the one hand, at what point in the cell cycle occurs alteration and on the other hand, the relationship between the different proteins involved in the same limit greatly the chances that the study unaúnica alteracióntenga some valorcomo factor pronósticoo predictivode respuestaal treatment. In this paper:-review the importance of factors clínico - patológicos and molecular alterations at the level of cell cycle, apoptosis and proliferation in relacióna the predicciónde the evolution colorectal cancer-studying the usefulness of a new technique, matrices quilt Tissue Microarrays "(MEAs), which through immunohistochemistry analizala expression of many proteins; - Finally, we applied a new methodology for analyzing data.

Author: HERNÁNDEZ MONTERO ELENA.
Year: 2004.
University: ZARAGOZA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Study restrospectivo on a homogeneous sample itself and treated equally affects cancer epidermoid faringo-laríngeo locally advanced stage III and IV receiving treatment following schedule: three cycles of induction chemotherapy followed by quimio-radioterapia concomitant response in the event higher than 80%, or rescue surgical case. We conducted a descriptive analysis of the sample and a study of fctores forecasts Check the following: * The classic prognostic factors remain valid in cancer faringo-laríngeo treaty combination. * Comorbidity is an independent prognostic factor for overall survival, overall and specific disease-free, making a contribution novel application of this index in head and neck cancer in our country, with determination required in the future in addition to the TNM system. * The percentage decrease in hemoglobin greater than 75% of baseline, is an independent prognostic factor for disease-free survival. This finding is also a new contribution of our study, pointing to the correction of this factor as a possibility for better resutlados in loco-regional control and preservation of organ. * The response to induction chemotherapy is an independent prognostic factor for overall survival, overall and specific disease-free, thus confirming the ability of induction chemotherapy for selecting patients for further treatments, as well as optimize the results of the quimio-radioterapia concomitant later. * The systematic identification of the factors p53 and Ki-67 is not justified, not to make any forecast information in our series.

Author: ALÉS PAVÓN INÉS.
Year: 2005.
University: SEVILLA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA DE LA UNIVERSIDAD DE SEVILLA.

Summary: INTRODUCTION: Breast cancer in men is rare, accounting for only 1% of all breast cancers, both women and men, which affects more late diagnosis and prognosis clouds. Materials and METHOD: There is a retrospective study of data collection in the province of Seville, in the period from December 1981 to December 1996, through the revision of 32 clinical protocols of Surgery Services and / or the Oncology Hospitals: HUV Rocio, HUV Macarena and HUV Valme. RESULTS: The mean age of presentation was 58.13 years, and there are no substantial differences between the left or right breast to the frequency of malignancy, its location being predominantly retroareolar. The painless tumor was the first symptom onset in 56.25% of cases. The average time elapsed since the onset of the first symptoms until the patient consultation was 25.75 months. The average delay from diagnosis to treatment was 1.27 months. FNAB was practiced in 65.6% of cases, being positive in almost all. Tumor markers are practiced in 24 patients, being increased in 16 of them. The result of the predominant pathological anatomy was infiltrating ductal carcinoma, and surgical treatment was more common type Patey mastectomy. There was local recurrence in 50% of cases and survival at 2 years was higher than 50%. CONCLUSIONS: There is very useful conducting FNAB, CT, ultrasound breast, bone scan, tumor markers and hormone receptors as part of the study protocol for these patients. Coinciding with the literature consulted, highlighted the dominance of infiltrating ductal carcinoma on any other type of tumor, as well as the surgical technique, the most practiced mastectomy rate Patey. Survival at two years, agreed to study in other series, exceeding 50% may decrementarse whether the study should be extended to ten years. A protocol should be established for the study unified diagnostic estadiaje, surgical treatment and follow-up for these patients.

Author: Villanueva de la Torre Maria Teresa.
Year: 2005.
University: AUTÓNOMA DE BARCELONA.
Place of defense: Hospital Vall d'Hebron.
Place of preparation: Institut de Recerca. Hospital Vall d'Hebron.

Summary: A substantial number of transmembrane proteins from the cell surface suffered a cut proteolítico leading to the release of their extracellular domain. This process, known as "shedding" remodels the surface of cells and regulates the function of a number of transmembrane proteins that include growth factors, cytokines, adhesion molecules, recipients of growth factors and cytokines. During the eighties and nineties it became clear that the role played metaloproteasas dependent zinc in carrying out most, if not all, the process of shedding described as inhibitors metaloproteasas block this process in an effective manner. Years later identified the first metaloprotease, a member of the subfamily ADAM, which is responsible for cutting proteolítico a transmembrane protein, cytokine TNF-alpha, so this protease was called ADAM 17 or TACE (Tumor necrosis factor converting enzyme ). The phenotype of mice TACE Zn / Zn shows that TACE is essential in the development of these animals and the use of fibroblasts derived from them showed that not only is responsible for the shedding of TNF-alpha but the shedding of a large number of proteins transmembrane function and structures quite different. Given this range of substrates, including the family of ligands EGF, it is reasonable to guess that the activity of TACE will be under strict control to prevent unwanted proteólisis and activation of specific receptors. However, little is known about the mechanisms responsible for regulation of the activity of TACE. TACE is a transmembrane protein type I (with the region amino-terminal in the area extracellular / intraluminal) containing the following domains identifiable: signal peptide, prodominio, catalytic domain or metaloproteasa, domain desintegrina, domain rich cisteínas, similar domain at the epidermal growth factor (EGF-like), transmembrane domain and cytosolic domain. It is synthesized in the form of cimógeno stable inactive form (proTACE) with prodominio inhibiting domain metaloproteasa. As proTACE progresses through the secretory route their prodominio is removed. The proproteínas convertasas type Furina have been described as proteases involved in the prosecution of some ADAMs. Since its identification, TACE has been subjected to intense studies. However, other important aspects of the biology of TACE remain unresolved characterize. Particularly, it is not known how TACE select its substrates and at what level regulating their activity. Because TACE is responsible for the release of growth factors soluble receptor ligands of EGFR family, various evidence indicates the involvement of TACE in processes such as differentiation, proliferation and migration, which is closely related to tumor progression. The elucidation of the mechanisms that control the expression and activity of TACE remains outstanding and is critical for the control of this pathological situation. In this work we have characterized a functional knockout mutant cell line for TACE. By using this cell line, we studied the role of cytosolic domain of TACE in regulating its activity induced intracellular activators, concluding that this is not essential in the modulation of the catalytic activity of TACE. This suggests that the activity of TACE is controlled by a complex mechanism that has enveloped another factor that once stimulated intracellular form, active TACE in its extracellular region.

Author: FIGUERAS I AMAT AGNÈS.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAT DE MEDICINA HOSPITAL CLÍNIC.
Place of preparation: FACULTAT DE MEDICINA HOSPITAL CLÍNIC.

Author: PEREZ DE ANDRES MARTIN.
Year: 2005.
University: SALAMANCA.
Place of defense: CENTRO DE INVESTIGACION DEL CANCER.
Place of preparation: FACULTAD DE MEDICINA.

Author: MARTÍN VEGAS FELIPE.
Year: 2006.
University: EXTREMADURA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Each year, nearly 1.000,000 people develop colorectal cancer in the world, and about 500,000 patients die, is the third most common cancer and the fourth most common cause of cancer deaths worldwide. The glutathione (GSH) has long been described only as a reactive defensive against the toxic action of xenobiotics and as a prototype antioxidant. However, more recent studies have also indicated the ability of GSH-their catabolitos- promote oxidative processes, for participation in mediated reactions metal ions eventually leading to the formation of reactive species of oxygen and free radicals, showing their role as prooxidante. The glutathione S-transferasas (GSTs) are a family of enzymes dimérica detoxification of Phase II enzymes that catalyze the transfer or GSH conjugation of a large variety of compounds electrofílicos. Numerous studies have linked genetic polymorphisms in GSTs with the emergence of various diseases such as lung cancer, breast cancer, colorectal cancer or neurodegenerative diseases. In this study we wanted to study the polymorphism of the subclasses GSTA1, GSTM1, GSTM3, GSTT1 and GSTP1 with colorectal cancer to get to know whether these enzymes promote or prevent the onset of the disease. We have conducted the study in healthy subjects and patients with colorectal cancer.

Author: TAPIA LALIENA MARÍA ÁNGELES.
Year: 2006.
University: BARCELONA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: 1-Role of NF-B in the cellular response to chemotherapy. The family of transcription factors NF-kB (p65/Rel-A, p105-p50/NF-B1, p100-p52/NF-B2, c-Rel, RelB) regulates the expression of genes involved in several related processes cancer, as cell cycle progression, migration, adhesion and cell apoptosis, but its role in cell survival signals what it really means to develop quimioresistencia. In order to advance our knowledge about their role in quimioresistencia, a lso objectives of this thesis has been to characterize the expression of the protein in the cell lines via NF-kB in breast cancer, prostate and lung and their relationship the different response to chemotherapy current -doxorubicina, bortezombib, PS-1145, Docetaxel and Cisplatin. NF subunits in this process through RNA interference (siRNA). In conclusion, inhibition of NF-B sensitizes cell lines studied treatment with doxorubicin and docetaxel, implying directly to the protein p65, p52, c-Rel and NEMO in tumor resistance to chemotherapy, but not subunit RelB . These results show that selective inhibition of the road canonical NF-kB activation is sufficient to enhance the anti-tumor effects of these drugs. 2-effects of proteasome inhibitor bortezomib in lines of breast cancer. Bortezomib (Velcade, PS - 341) is a new selective and reversible inhibitor of the proteasome, whose activities include the stabilization of cell cycle regulatory proteins, inhibiting the activation of nuclear factor Kappa-B (NF-kB), induction apoptosis, the annulment of the resistance mediated Bcl-2 and inhibition of angiogenesis. In addition, bortezomib has a wide range of antitumor activity and increases the activity of many conventional chemotherapy. It has recently been approved for the treatment of refractory multiple myeloma and is in clinical development for many types of tumors, including breast cancer. In this second part of the thesis has analyzed the effects of bortezombi in cell viability and in various pathways of signal transduction in a panel of cell lines of breast cancer. Overall, the results obtained relate the answer to bortezomib with the basal activity of the proteasome and its impact on routes transucción signals can be relevant to help design combinations of treatments.

Author: SECADES VAZQUEZ PABLO.
Year: 2006.
University: OVIEDO.
Place of defense: SALA DE GRADOS. FACULTAD DE BIOLOGIA.
Place of preparation: INSTITUTO UNIVERSITARIO DE ONCOLOGIA DEL PRINCIPADO DE ASTURIAS.