RESUMEN

Exposure to ambient air pollution influences cardiovascular (CV) morbidity and mortality. The differential effects of changing particulate or gaseous air pollution on endothelial function in young healthy individuals remain unclear. The aim of this study was to evaluate the relationships between exposures to different pollutants and vascular function in a group of 39 young (33±11 years old) subjects with low CV risk. Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were performed, when air pollution reached highest levels (heating period) and repeated in a subgroup of 18 participants a few months later (just before the heating period starts). Daily mean concentrations of PM2.5 and PM10 were inversely correlated with FMD, and this relationship remained significant after adjusting for factors known to affect vascular dysfunction. Endothelial function did not differ between the two time points studied. However, we observed a strong inverse association between the change in the concentration of particulate matter (deltaPM2.5 and deltaPM10) and the change in FMD (deltaFMD) between the two visits (R= -0.65, p= 0.02; R= -0.64, p= 0.02, respectively). In summary, we provide evidence that the concentration of PM2.5 and PM10, but not SO2, NO, NO2, CO, or O3 is associated with impaired endothelial function in young, healthy individuals.

Asunto(s)

Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Adulto Joven , Adulto , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Factores Relajantes Endotelio-Dependientes , Vasodilatadores , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Material Particulado/efectos adversos , Material Particulado/análisis

RESUMEN

AIM OF THE STUDY: The analysis of prognostic factors and treatment outcomes in 106 patients with Stage I and II endometrial carcinoma (EC) treated between 1980 and 2005 in the Center of Oncology, Maria Sklodowska-Curie Memorial Institute, Kracow, Poland, who developed vaginal or pelvic recurrences. MATERIAL AND METHODS: The median age of patients was 61. Stage IB and IC of EC was diagnosed in 48 (45.3%) patients and Stage IIA and IIB in 58 (54.7%) patients. All patients were treated previously with surgery (TAH-BSO) and postoperative radiotherapy. There were 17 (16%) patients with vaginal vault recurrences, 30 (28.3%) with lower one-third vaginal recurrences, and 59 (55.7%) with pelvic recurrences. Palliative treatment (chemo- or hormonotherapy) or best supportive care only was undertaken in 53 (50.0%) patients. Radical treatment was conducted in 70.6% (12/17) of vault recurrences, 86.7% (26/30) of lower one-third vagina recurrences, and 25.4% (15/59) of pelvic recurrences, with surgery (4 patients), brachytherapy +/- chemotherapy (34 patients), and teleradiotherapy +/- chemotherapy (15 patients). RESULTS: The 5-year overall survival rate in the observed group was 17%. Five-year survival was 23.3% (14/60) for patients with KPS 60-70 vs 8.7% (4/46) with KPS 40-50, 25% (12/48) patients with Stage I EC vs 10.3% (6/58) with Stage II EC, and 34% (16/47) patients with vaginal recurrence vs 3.4% (2/59) with pelvic recurrences. CONCLUSIONS: In the analyzed group of 106 patients with Stage I and II EC, treated previously with surgery and postoperative radiotherapy, 5-year overall survival rate was low; in radically treated patients it was 42.1%, and 13.3% for vaginal and pelvis recurrences, respectively. Univariate analysis showed a statistically significant, unfavorable impact of KPS < 60, Stage II and recurrence pelvic. Cox multivariate analysis demonstrated that the only independent prognostic factor for 5-year overall survival was the site of recurrence.

Asunto(s)

Carcinoma Endometrioide/secundario , Neoplasias Endometriales/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Pélvicas/patología , Neoplasias Vaginales/secundario , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/terapia , Supervivencia sin Enfermedad , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/terapia , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Cuidados Paliativos , Neoplasias Pélvicas/diagnóstico , Neoplasias Pélvicas/mortalidad , Neoplasias Pélvicas/terapia , Polonia , Radioterapia Adyuvante , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias Vaginales/mortalidad , Neoplasias Vaginales/terapia

RESUMEN

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is one of the most common causes of chronic morbidity and mortality. The "Burden of Obstructive Lung Disease" (BOLD) initiative was established as an international study collecting data about the prevalence of COPD. The Medical University of Hanover took part in this study collecting data representative for Germany. METHODS: 683 individuals aged = 40 years from the city and region of Hannover were included in the study. On the basis of standardized questionnaires data were collected on general health, physical and mental capability, smoking habits and occupational exposure to dust. All participants performed spirometry before and after inhalation of salbutamol. RESULTS: The prevalence of COPD, GOLD (Global Health Initiative on Obstructive Lung Disease) severity stage = I, was 13.2% (GOLD stage I: 7.4%; GOLD stage II: 5.0%, GOLD stage III or IV: 0.8%). There was a marked increase of the prevalence of COPD depending on age and smoking habits. The percentage of active smokers in the sample was 20.6 %. Among younger participants the percentage of female smokers was noticeable higher than in older subjects. Although clinical symptoms of COPD, GOLD stage = III correlated with disease severity, only persons with COPD reported reduced physical capability. CONCLUSION: COPD is a highly prevalent disease. With regard to the increasing life expectancy and the change of smoking habits of the population, a further increase of morbidity and mortality due to COPD must be expected, especially in women.

Asunto(s)

Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Fumar/epidemiología , Adulto , Factores de Edad , Anciano , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Calidad de Vida , Índice de Severidad de la Enfermedad , Factores Sexuales , Espirometría

RESUMEN

AIM OF THE STUDY: The objective was the analysis of prognostic factors and treatment outcomes of 104 patients with vulvar cancer, treated between 1990 and 2003 in the Center of Oncology, Maria Sklodowska-Curie Memorial Institute, Cracow, Poland. MATERIAL AND METHODS: The median age of patients was 67. Advanced disease (TNM III and IVA) was found in 54 (51.9%) patients and grade 2 and 2 in 50 (48.1%). Inguinal lymph nodes were clinically uni- or bilaterally involved in 40.4% of patients. Fifty-seven (54.8%) patients underwent radical vulvectomy with bilateral inguinal lymphadenectomy and 47 (45.2%) radical vulvectomy only. Cancer differentiation was well in 38 (36.2%) of patients, moderate in 38 (36.2%) and poor in 28 (36.6%). Adjuvant radiotherapy was applied in 30 (28.8%) cases. RESULTS: Five-year overall survival rate was observed in 44.4% of patients. Depending on TNM grade, 5-year OS rates were 61.4% for grade 1, 54.9% for grade 2, 40.1% for grade 3 and 13.3% for IVA. In patients aged < 70, 5-year OS rate was 54.7% compared to 30.5% for those > or = 70. Among patients with G1 cancer differentiation 64.4% survived five years, with G2 39.1% and with G3 24.9%, respectively. CONCLUSION: Univariate analysis revealed a statistically significant, unfavorable impact of age > or = 70, with G3 cancer differentiation, clinically confirmed inguinal lymph node involvement and TNM classification stage on 5-year overall survival. Cox multivariate analysis demonstrated that independent prognostic factors for 5-year survival were the age of the patient, clinical status of inguinal lymph nodes and TNM classification grade.

Asunto(s)

Carcinoma/cirugía , Neoplasias de la Vulva/cirugía , Anciano , Carcinoma/patología , Carcinoma/radioterapia , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática/patología , Estadificación de Neoplasias , Polonia , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Factores de Riesgo , Resultado del Tratamiento , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/radioterapia

RESUMEN

The aim of the present study was to examine the low-dose radiation response of human normal cells using the micronucleus assay. Skin fibroblasts and keratinocytes derived from 40 cervix cancer patients were studied. After in vitro gamma irradiation with single doses ranging from 0.05 to 4 Gy, the fraction of binucleated cells with micronuclei was assessed. For each patient, the Linear-Quadratic (LQ) model and the Induced-Repair (IR) model were fitted over the whole data set (0.05-4 Gy). In conclusion, the present study showed some evidence of low-dose hypersensitivity in the fibroblasts of two patients and in the keratinocytes of four of the forty patients studied.

Asunto(s)

Fibroblastos/efectos de la radiación , Queratinocitos/efectos de la radiación , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Modelos Biológicos , Tolerancia a Radiación/fisiología , Neoplasias del Cuello Uterino/patología , Células Cultivadas , Simulación por Computador , Daño del ADN , Relación Dosis-Respuesta en la Radiación , Medicina Basada en la Evidencia , Femenino , Rayos gamma , Humanos , Dosis de Radiación , Tolerancia a Radiación/efectos de la radiación , Valores de Referencia , Piel/citología , Piel/efectos de la radiación

RESUMEN

We identified 4316 unselected incident cases of early-onset breast cancers (<51 ears of age at diagnosis) in 18 Polish hospitals between 1996 and 2003. We were able to obtain a blood sample for DNA analysis from 3472 of these (80.4%). All cases were tested for the presence of three founder mutations in BRCA1. The proportion of cases with a BRCA1 mutation was 5.7%. The hereditary proportions were higher than this for women with breast cancer diagnosed before age 40 (9%), for women with cancer of medullary or atypical medullary histology (28%), for those with bilateral cancer (29%) or with a family history of breast or ovarian cancer (13%). It is reasonable to offer genetic testing to women with early-onset breast cancer in Poland.

Asunto(s)

Proteína BRCA1/biosíntesis , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Genes BRCA1 , Predisposición Genética a la Enfermedad , Mutación , Adulto , Neoplasias de la Mama/metabolismo , Análisis Mutacional de ADN , Femenino , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Polonia , Estudios Prospectivos

RESUMEN

OBJECTIVES: To analyze the results of treatment of 70 patients with stage III and IV ovarian cancer after second look laparotomy with negative findings and to identify causes of failure and prognostic factors. MATERIALS AND METHODS: Between 1985 and 1998, seventy patients with ovarian cancer stage III and IV were treated with surgery and at least six courses of chemotherapy with cisplatin doxarubicin and cyclophosphamide. Then a second look laparotomy was performed. RESULTS: The actuarial survival rate without evidence of disease was 50% at 5 years. Locoregional failure was observed in 31 patients (88%) and distant metastases in 9, but they were the sole reason for unsuccessful treatment in only 4 (12%). Adverse prognostic factors were: grade 3 differentiation, primary stage IIIC and IV, and residual infiltration exceeding 2 cm after first laparotomy. CONCLUSION: Our results are comparable with reports in the literature. The actuarial survival rate without evidence of disease at 5 years in patients with advanced ovarian cancer after second look negative laparotomy is 50%.

Asunto(s)

Laparotomía , Recurrencia Local de Neoplasia , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Segunda Cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Factores de Tiempo

RESUMEN

BACKGROUND: Cancer patients of the Department of Internal Medicine (Cancer Research) of the Essen University Medical School (Tumor Clinics), Germany, were examined and questioned with the aim of identifying those who run a high risk of deep vein thrombosis (DVT). PATIENTS AND METHODS: Between September 2002 and April 2003, cancer therapy and DVT risk factors of 507 cancer patients (53% males, 47% females, mean age 56+/-12 years) were documented. During a mean follow-up of 8+/-5 months, 60 patients (12%) suffered from new venous thromboembolic events (VTE): 28 at the lower limb, 25 at the upper limb and 13 pulmonary embolisms. RESULTS: The following factors were considered as predictive for an increased VTE risk: inpatient treatment (P<0.0001), prior DVT in medical history (P=0.0275), DVT in family (P=0.0598), chemotherapy (P=0.0080), fever (P=0.0093) and CRP (P<0.001). After combining factors in one variable (number of factors) the predicted VTE risk increased with the number of factors in both outpatients (OR 1.85, 95% CI 1.18-2.88, P=0.0071) and inpatients (OR 2.34, 95% CI 1.63-3.36, P

Asunto(s)

Neoplasias/complicaciones , Tromboembolia/etiología , Trombosis de la Vena/etiología , Anticoagulantes/uso terapéutico , Antineoplásicos/efectos adversos , Proteína C-Reactiva/análisis , Femenino , Fiebre/complicaciones , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Medición de Riesgo , Factores de Riesgo , Tromboembolia/prevención & control , Trombosis de la Vena/prevención & control

RESUMEN

AIM: To present our experience regarding the efficiency of treatment in patients with uterine-confined endometrial cancer. PATIENTS AND METHODS: 775 patients with uterine-confined endometrial cancer (UCEC) were treated between July 1985 and June 2000 in the Krakow Branch of Sklodowska Memorial Institute. RESULTS: Among the 775 patients, 5-year disease-free survival was observed in 82.8% patients; 96% patients with low risk of disease recurrence, 93.6% patients with intermediate risk and 78.3% patients with high risk survived five years with no evidence of disease. In the group with a high-risk disease recurrence rate, 5-year disease-free survival was statistically higher among patients treated with adjuvant brachytherapy plus external beam radiotherapy (EBRT) in comparison to patients treated with adjuvant brachytherapy (BRT) alone (82.4% vs 72.1%). CONCLUSIONS: The recommended treatment in patients with high and moderate differentiation of UCEC with FIGO Stage IA is surgery alone. Surgery with adjuvant EBRT in the group of patients with intermediate risk of cancer recurrence allows over 90% of patients to be cured. In the group of patients with a high risk of disease recurrence adjuvant BRT with EBRT is statistically more efficient in comparison to BRT alone.

Asunto(s)

Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Braquiterapia , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/cirugía , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Radiografía , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , Medición de Riesgo , Resultado del Tratamiento

RESUMEN

Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors.

Asunto(s)

Neoplasias de la Mama/genética , Proteínas de Ciclo Celular/genética , Genes BRCA1 , Proteínas Nucleares/genética , Proteínas Serina-Treonina Quinasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Neoplasias de la Mama/epidemiología , Quinasa de Punto de Control 2 , Femenino , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Polonia/epidemiología , Prevalencia , Riesgo , Medición de Riesgo

RESUMEN

BACKGROUND: A common missense variant of the CDKN2A gene (A148T) predisposes to malignant melanoma in Poland. An association between malignant melanoma and breast cancer has been reported in several families with CDKN2A mutations, OBJECTIVE: To determine whether this variant also predisposes to breast cancer. METHODS: Genotyping was undertaken in 4209 cases of breast cancer, unselected for family history, from 18 hospitals throughout Poland and in 3000 controls. RESULTS: The odds ratio (OR) associated with the CDKN2A allele for women diagnosed with breast cancer before the age of 50 was 1.5 (p = 0.002) and after age 50 it was 1.3 (p = 0.2). The effect was particularly strong for patients diagnosed at or before the age of 30 (OR = 3.8; p = 0.0002). CONCLUSIONS: CDKN2A appears to be a low penetrance breast cancer susceptibility gene in Poland. The association should be confirmed in other populations.

Asunto(s)

Neoplasias de la Mama/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Genes p16 , Predisposición Genética a la Enfermedad , Variación Genética , Adulto , Alelos , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Polonia , Riesgo

RESUMEN

ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3+ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1+, 2+ or 3+) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1+ were grouped together with tumours showing staining categories 2+ and 3+. CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(-) group (P=0.022) and with disease-free survival (DFS) in the TP53(+) group (P=0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(-)/ERBB2(+) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53(+)/ERBB2(+) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Receptor ErbB-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anticuerpos Monoclonales , Epítopos/inmunología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Neoplasias Ováricas/inmunología , Pronóstico , Receptor ErbB-2/inmunología

RESUMEN

Presented study evaluates biologically effective dose (BED) in patients receiving low-medium dose-rate (LDR/MDR) brachytherapy (BRT) plus external beam radiotherapy (XRT) based on tumor cell proliferation values in cancer of the cervix patients. This study includes 229 patients treated entirely by radiotherapy at the Centre Oncology in Krakow. Doses to Point A were estimated for total treatment for each brachytherapy insertion. BED3 were calculated for reference points in the rectum. The linear quadratic equation was used to calculate BED, which is proportional to log cell kill, and the normalized total dose (NTD), that is, equivalent to a 2 Gy fraction schedule. In BEDs 10 calculation overall treatment time for each patient. Tumor proliferation rate was based on Bromodeoxyuridine labeling index (BrdUrdLI) assessed on biopsy material before beginning the radiotherapy. Total BED at those points was summed for each patient. The medium overall treatment time was 90 days (range 30--210). The mean calculated total BED for point A for tumour and "early reactions" was equal to 104.0 Gy10 and 229.0 Gy3 for the rectum, equivalent to NTD=86.6 Gy and 137.4 Gy in 2 Gy fractions, respectively. Kaplan-Meier analysis revealed that age >50 years, higher than mean BRBEDs and totBEDs doses, gaps in treatments shorter than 40 days and disease free survival (DFS) was significant prognostic factor for overall survival. In the multivariate Cox anaysis age >50 years, BRBED10 >77 Gy and gaps ?40 days appeared to be significant for overall survival. None of the examined parameters was significant for tumor control. However, patients age and shorter gaps in the treatment were predictive for DFS.

Asunto(s)

Carcinoma/radioterapia , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/radioterapia , Carcinoma/patología , Supervivencia sin Enfermedad , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología

RESUMEN

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

Asunto(s)

Carcinoma/tratamiento farmacológico , Carcinoma/genética , Proteínas de Ciclo Celular/biosíntesis , Ciclinas/biosíntesis , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis , Proteínas Supresoras de Tumor/biosíntesis , Adulto , Anciano , Carcinoma/patología , Proteínas de Ciclo Celular/análisis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Ciclinas/análisis , Inhibidores Enzimáticos , Femenino , Genes Supresores de Tumor , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/patología , Pronóstico , Proteínas Proto-Oncogénicas c-myc/análisis , Estudios Retrospectivos , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/análisis , Proteínas Supresoras de Tumor/análisis

RESUMEN

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatin-based chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P=0.005) or the only (in FIGO IIIC, P=0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(-) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P=0.047) and by BCL2 expression in the TP53(-) group (P=0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P=0.049); its loss was found with advancing FIGO stage (P=0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Regulación Neoplásica de la Expresión Génica , Quinasas de Proteína Quinasa Activadas por Mitógenos/biosíntesis , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Proteínas Serina-Treonina Quinasas/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis , Adulto , Anciano , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , MAP Quinasa Quinasa 1 , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/análisis , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Serina-Treonina Quinasas/análisis , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Análisis de Regresión , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/análisis , Proteína X Asociada a bcl-2

RESUMEN

The prognostic significance of apoptotic (AI) and mitotic (MI) indices, and the ratio of these parameters (AI/MI), MIB-1 labeling index (MIB-1LI) and proliferation pattern was studied in 130 (FIGO stage IB-IIIB) squamous cervical cancer patients before radiotherapy. Also the influence of the patients age and tumors pathological features (stage, grade, degree of keratinization) and DNA ploidy on the biological parameters were analysed. AI and MI were assessed on histological sections stained with hematoxylin and eosin, and the MIB-1LI on specimens stained with rabbit anti-human Ki-67 antibody (DAKO Ltd). Sections stained with MIB-1 antibody were used for assessment of the tumor proliferation pattern. The median age of the patients was 55 years (29-80). The median values for MIB-1LI, AI, MI, AI/MI, were: 52.3%, 1.1%, 1.5, and 0.9, respectively. In the univariate analysis median values for cut-off points were used for MIB-1LI, and AI, however, for other parameters significant cut-off points have been chosen. For MI it was 2.6 and for the AI/MI ratio 0.7. The median time of follow-up was 29 months, with a range of 2-145 months. The univariate analysis showed that tumor stage (p=0.7009), grade (p=0.6660) and AI (p=0.9378) had negligible influence on patients survival. However, MI >2.6 (p=0.0442), AI/MI

Asunto(s)

Apoptosis , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Mitosis , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/radioterapia , Carcinoma de Células Escamosas/metabolismo , ADN de Neoplasias/análisis , Supervivencia sin Enfermedad , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Pronóstico , Dosificación Radioterapéutica , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias del Cuello Uterino/metabolismo

RESUMEN

PURPOSE: In a prospective randomized trial, our aim was to evaluate and compare the tolerance and efficacy of postoperative radiotherapy and chemotherapy in the treatment of early ovarian cancer. MATERIAL AND METHODS: Between 1990 and 1996, 150 patients with ovarian cancer stage IA, IB grades G2-3, and all patients classified IC and IIA, who did not have evidence of residual disease after surgery, were randomized to two treatment branches: radiotherapy or chemotherapy (CH). In the radiotherapy branch (76 patients), a whole abdomen irradiation of 30 Gy in 24 fractions over 5 weeks, with a pelvic boost to 50 Gy, was delivered. In the chemotherapy branch (74 patients), there were six series of polychemotherapy separated with 3-weeks interval. In each series patients received association of cisplatin (50 mg/m2, d1), adriamycin (50 mg/m2, d1) and cyclophosphamide (500 mg/m2, d1). RESULTS: The tolerance of the treatment was good and comparable in both groups. In the radiotherapy branch, three late grade G3 intestinal complications were observed (three bowel obstructions, which required surgery in two cases). The actuarial survival rate without evidence of disease was 81% at 5 years for both groups. In our series we found that histological grade had the strongest influence on survival prognosis; it was the only significant factor in a multivariate analysis. Patients with grade G3 tumors had the worst survival. CONCLUSION: These data suggest that efficacy of postoperative radiotherapy and chemotherapy administered to our patients with early ovarian cancer gave approximately identical results.

Asunto(s)

Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/radioterapia , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/cirugía , Cuidados Posoperatorios , Estudios Prospectivos

RESUMEN

The prognostic importance of various pretherapeutic and therapeutic factors was analysed in a group of 413 cervical cancer patients with stage IIB (183 pts) and IIIB (230 pts) treated with radical radiotherapy, which consisted of external irradiation and intracavitary brachytherapy. Univariate analysis of pretherapeutic factors revealed the prognostic significance of patient age, history of abortion, stage, haemoglobin and hematocrit levels. Five-year overall survival rate in stage IIB patients was 51%, in stage IIIB 40% and the respective rates for local control at each stage were 61%, and 46%. Univariate analysis of therapeutic factors showed that survival and local control rates increased with the dose, but a significant difference was found only in the case of a paracentral (point A) dose. In a multivariate analysis only patient age, abortions, and clinical stage appeared to have a significant and independent impact on survival. Linear regression analysis results indicated that prolongation of treatment time between 33 and 108 days caused a loss of local control of 0.36% per day.

Asunto(s)

Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Modelos Lineales , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología

RESUMEN

PURPOSE: Proliferative rate and DNA ploidy status were evaluated by flow cytometry in cervical cancer patients, prior to radiotherapy, to assess their importance as prognostic factors to predict survival rates. MATERIAL AND METHODS: Between 1987 and 1995, a total of 260 patients with squamous cell carcinoma (SCC) of the cervix, FIGO stages IB-IIIB were analysed. Tumour samples were incubated with bromodeoxyuridine (BrdUrd) in vitro to measure their total labelling index (totLI) and LI (totLI for diploid and anLI for aneuploid tumours). Proliferation was also assessed by S-phase fraction (SPF) analysis of the DNA profile. Patients had intracavitary therapy (three applications, each of 16 Gy to point A) and XRT of 40-50 Gy given over 4-5 weeks. RESULTS: The cervical tumours were characterized by a high proliferation rate which varied within each clinical stage of disease. The totLI ranged from 1.1 to 33.1% with median value of 9.6% whilst the LI ranged from 1.1 to 37.1% with a median value of 10.9%. Univariate analysis identified patient's age (cut-offpoint < or = 50&greater; years) and to a lesser extent proliferation (cut-off point, median totLI=9.6%) as significant prognostic factors for 5-year survival. The median survival time for younger patients ( < or = 50 years) with tumours of low proliferation (totLI < or = 9.6%) tumours was 17.5 months compared with 56 months in the faster proliferating tumours (P=0.0354). In the older patient sub-group, proliferation rate had no influence on survival. The median LI value was not a useful parameter in survival. Cox multivariate analysis showed that patient age ( < or = 50 years) and low proliferation of the tumour cells (totLI < or = 9.6) were unfavourable prognostic factors for cervical cancers treated with radiotherapy. DNA ploidy was not significant in this series. CONCLUSIONS: These data suggest that further improvements in therapy might be gained by selection of alternative treatments strategies such as neoadjuvant chemotherapy or radiation sensitizers in younger patients with more slowly proliferating tumours.

Asunto(s)

Carcinoma de Células Escamosas/patología , Neoplasias del Cuello Uterino/patología , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Aneuploidia , Antimetabolitos , Braquiterapia , Bromodesoxiuridina , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Ciclo Celular , División Celular/efectos de la radiación , ADN de Neoplasias/efectos de la radiación , Diploidia , Femenino , Citometría de Flujo , Predicción , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Dosificación Radioterapéutica , Fase S , Tasa de Supervivencia , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/radioterapia

RESUMEN

Thirty-two patients with adenocarcinoma of the fallopian tube, treated between 1975 and 1990, were studied. Thirteen patients had stage I disease, 9 stage II, and 10 stage III. All patients underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy, and subcolic omentectomy. All patients received postoperative primary whole abdominal external beam radiotherapy. Seventeen patients (53.1%) of the treated group survived NED for at least 5 years. Survival was 76.9% for stage I, 55.6% for stage II, and 20% for stage III. In the Cox multivariate analysis, two variables were independently related to survival: stage of disease and size of residual disease after surgery. Postoperative teleradiotherapy was totally ineffective in gross residual (>2 cm in diameter) disease (0% 5-year NED survivors) and not effective enough in small residual disease (<2 cm in diameter) (33% 5-year NED survivors). Despite postoperative whole abdominal external beam radiotherapy, 3 patients with microscopic, 4 with small, and 4 with gross residual disease did fail within the peritoneal cavity.

Asunto(s)

Adenocarcinoma/radioterapia , Neoplasias de las Trompas Uterinas/radioterapia , Irradiación de Hemicuerpo , Abdomen , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Neoplasias de las Trompas Uterinas/mortalidad , Neoplasias de las Trompas Uterinas/patología , Neoplasias de las Trompas Uterinas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Cuidados Posoperatorios , Estudios Retrospectivos , Tasa de Supervivencia