RESUMO
p53 wild-type is a tumor suppressor gene involved in DNA gene transcription or DNA repair mechanisms. When damage to DNA is unrepairable, p53 induces programmed cell death (apoptosis). The mutant p53 gene is the most frequent molecular alteration in human cancer, including breast cancer. Here, we analyzed the genetic alterations in p53 oncogene expression in 55 patients with breast cancer at different stages and in 8 normal women. We measured by ELISA assay the serum levels of p53 mutant protein and p53 antibodies. Immunohistochemistry and RT-PCR using specific p53 primers as well as mutation detection by DNA sequencing were also evaluated in breast tumor tissue. Serological p53 antibody analysis detected 0/8 (0%), 0/4 (0%) and 9/55 (16.36%) positive cases in normal women, in patients with benign breast disease and in breast carcinoma, respectively. We found positive p53 mutant in the sera of 0/8 (0.0%) normal women, 0/4 (0%) with benign breast disease and 29/55 (52.72%) with breast carcinoma. Immunohistochemistry evaluation was positive in 29/55 (52.73%) with mammary carcinoma and 0/4 (0%) with benign breast disease. A very good correlation between p53 mutant protein detected in serum and p53 accumulation by immunohistochemistry (83.3% positive in both assays) was found in this study. These data suggest that detection of mutated p53 could be a useful serological marker for diagnostic purposes.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Mutação , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Carcinoma in Situ/sangue , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteína Supressora de Tumor p53/sangue , Proteína Supressora de Tumor p53/imunologiaRESUMO
Uracil and tegafur (in a molar ratio of 4:1 [UFT]) has proven activity against breast cancer and is delivered in an easy-to-administer oral formulation. Orzel, which combines UFT with the oral biomodulator, calcium folinate, may provide even greater antitumor efficacy against breast cancer. Here, we describe the preliminary results of this phase II trial investigating the feasibility of 250 mg/m2/day of UFT plus 45 mg/day of oral calcium folinate administered to highly pretreated patients with advanced breast cancer. The results indicate a highly tolerable regimen and an overall response rate of 27.8% in a group of poor-prognosis patients. These findings warrant continued investigation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Leucovorina/administração & dosagem , Administração Oral , Idoso , Neoplasias da Mama/patologia , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Tegafur/administração & dosagem , Resultado do Tratamento , Uracila/administração & dosagemRESUMO
INTRODUCTION: Neonatal hemochromatosis is a disease that starts in utero, characterized by severe fibrosis or cirrhosis and siderosis of the liver and other organs without affecting the mononuclear fagocytic system. The most important clinical features are severe hepatic failure at birth and hypoglycemia. The diagnosis is made excluding other diseases more frequently seen in the neonatal period and with at least two of the clinicopathologic criteria delineated by Knisely. METHODS: A retrospective analysis of the autopsies of newborn done at the Department of Pathology of the Hospital de Pediatría, C.M.N. SXXI, IMSS, a tertiary care facility in the period 1989 from 1997. Those cases with primarily hepatic disease as the main diagnosis were chosen. The degree of siderosis was determined cualitatively. The amount of Fe and copper in the liver and spleen in samples fixed in formalin was obtained using X ray fluorescence in the Instituto Nacional de Investigaciones Nucleares, two control cases were also tested. RESULTS: Only four out of 210 autopsies of newborn babies were found to have hepatic disease as a main diagnosis but without an etiology determined. In three of such cases the diagnosis of neonatal hemochromatosis was made. All patients were male with ages six, 29 and 36 days, one with Down's syndrome. The ratio of iron deposits in liver/spleen in hemochromatosis' cases was higher to 1.5 in the liver in contrast to the two control cases. CONCLUSIONS: These cases showed the utility of the autopsy in establishing the adequate diagnosis in three cases of neonatal hemochromatosis. The importance of establishing an accurate diagnosis is to recognize it as an entity with a lethal course, that can be potentially managed with liver transplant as well as genetic counseling to the family. A remarkable finding in the study of these cases was the ratio of iron concentration in the liver and spleen that allowed to discard other causes of siderosis. To our knowledge this finding has never been recorded.
Assuntos
Hemocromatose/congênito , Cobre/análise , Síndrome de Down/complicações , Edema/etiologia , Evolução Fatal , Fibrose , Hemocromatose/complicações , Hemocromatose/diagnóstico , Hemocromatose/patologia , Humanos , Lactente , Recém-Nascido , Ferro/análise , Icterícia Neonatal/etiologia , Fígado/química , Fígado/patologia , Masculino , Pâncreas/patologia , Estudos Retrospectivos , Baço/química , Baço/patologia , Glândula Tireoide/patologiaRESUMO
La eyaculación precoz es muy frecuente, pero sólo consultan aquellos hombres que lo sienten como problema. Los inhibidores de la recaptacción de Serotonina actuan a nivel de la vesícula sináptica impidiendo la recaptación del neurotransmisor, permitiendo así una mayor utilización por la neurona sináptica
Assuntos
Humanos , Masculino , Adulto , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Paroxetina/farmacologia , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Ejaculação , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Paroxetina , Paroxetina/efeitos adversosRESUMO
From March 1991 to October 1992, 41 patients with advanced non-small cell lung cancer (NSCLC) (20 stage IIIB and 21 stage IV) received a regimen consisting of cisplatin (CP) 100 mg/m2 i.v. days 1 and 8, and dipyridamole (DPD) 100 mg p.o. 75 minutes before CP, and then at hours 6, 12, and 18 as first-line chemotherapy. Cycles were repeated every 28 days for a total of 3. Median age was 56 years (range: 40-70). All patients had a performance status 0 to 1 and a weight loss < or = 10%. Squamous-cell carcinoma was diagnosed in 19 patients; adenocarcinoma in 16, and large-cell carcinoma in 6. A total of 37 patients were fully evaluable for response, whereas 39 were assessable for toxicity. No complete responses were observed: 5 patients (14%) achieved partial response; 23 patients (62%) showed no change, and progressive disease was observed in 9 (24%). The median time to treatment failure was 4 months, whereas median survival was 8 months. The average dose intensity received at the end of the third course of therapy was 46 mg/m2/week. There were no drug-related deaths. Toxicity was mild to moderate, with a high incidence of ototoxicity (54%) and emesis (67%). In conclusion, these results failed to demonstrate any significant advantage from a high-dose CP regimen modulated by DPD in patients with advanced NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Dipiridamol/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Carcinoma Pulmonar de Células não Pequenas/secundário , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Dipiridamol/administração & dosagem , Dipiridamol/efeitos adversos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: A phase II trial was performed to evaluate the efficacy and toxicity of vinorelbine (VNB) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS: Between August 1991 and February 1993, 45 patients with metastatic breast cancer were entered onto the study. Therapy consisted of VNB 30 mg/m2 diluted in 500 mL of normal saline administered as a 1-hour intravenous infusion. Injections were repeated weekly until evidence of progressive disease (PD) or severe toxicity developed. RESULTS: One patient was considered not assessable for response. An objective response (OR) was observed in 18 of 44 patients (41%; 95% confidence interval, 26% to 56%). Three patients (7%) had a complete response (CR) and 15 (34%) had a partial response (PR). The median time to treatment failure for the entire group was 6 months (range, 1 to 15), and the median duration of response was 9 months (range, 1 to 15). The median survival duration has not been reached yet. There were no treatment-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (78%) and was grade 3 or 4 in 16 (36%). Phlebitis was observed in 19 of 29 patients (66%) who did not have central implantable venous systems. Fifteen patients (33%) developed peripheral neurotoxicity. Myalgia occurred in 20 patients (44%). CONCLUSION: VNB is an active drug against metastatic breast cancer with moderate toxicity, which justifies further evaluation in association with other agents.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Antineoplásicos/efeitos adversos , Argentina , Neoplasias da Mama/patologia , Carcinoma/secundário , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , VinorelbinaRESUMO
PURPOSE: A phase II trial was performed to evaluate the efficacy and toxicity of a combination of ifosfamide (IFX) and mitoxantrone (MXN) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS: Between January 1990 and August 1991, 48 patients with metastatic breast cancer were entered onto the study. Therapy consisted of IFX 2 g/m2 given as a 1-hour intravenous (IV) infusion on days 1 to 3; mesna 400 mg/m2 as an IV bolus immediately before and 4 hours after IFX administration and 2,000 mg orally 8 hours after IFX administration on days 1 to 3; and MXN 12 mg/m2 as an i.v. bolus on day 3. Cycles were repeated every 21 days until progressive disease (PD) or severe toxicity developed. RESULTS: One patient was considered not assessable for response. Objective regression (OR) was observed in 28 of 47 patients (60%; 95% confidence interval, 46% to 74%). Six patients (13%) had a complete response (CR) and 22 (47%) had a partial response (PR). The median time to treatment failure for the whole group was 9 months (range, 1 to 28); median survival was 19 months (range, 2 to 28). There were no treatment-related deaths. The limiting toxicity was myelosuppression. Leukopenia occurred in 37 patients (77%) and was grade 3 or 4 in 19 patients (40%). Nausea and vomiting were observed in 38 patients (80%), mucositis in 16 patients (33%), and grade 2 hematuria in two patients (4%). Eight patients (16%) developed mild neurotoxicity. CONCLUSION: The combination of IFX plus MXN is an active regimen against metastatic breast cancer with moderate toxicity that deserves further evaluation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Carcinoma/secundário , Esquema de Medicação , Feminino , Humanos , Ifosfamida/administração & dosagem , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Análise de Sobrevida , Resultado do TratamentoRESUMO
One hundred and twenty-five previously untreated patients bearing metastatic or advanced recurrent (inoperable) colorectal carcinoma and measurable disease were prospectively randomized. Those in arm A received 5-fluorouracil (5-FU), 1,200 mg/m2 i.v. infusion over 2 h, while those in arm B received methotrexate (MTX), 200 mg/m2 i.v. (push injection), followed 20 h later by 5-FU, 1,200 mg/m2 i.v. infusion over 2 h, plus calcium leucovorin (LV), 25 mg i.m. every 6 h for eight doses beginning 24 h after MTX administration. Cycles were repeated every 15 days. All patients receiving treatment were evaluable for toxicity and survival, and 118 patients were evaluable for response. The objective regression rate (complete plus partial response) was 12% (7 of 58) in arm A and 28% (17 of 60) in arm B (p = 0.049). No change was observed in 24% (14 of 58) in arm A and in 35% (21 of 60) in arm B (p = 0.28), while progressive disease was registered in 64% (37 of 58) and 37% (22 of 60) in arms A and B, respectively (p = 0.006). Median duration of response was 3 months in arm A and 5 months in arm B (p = 0.39). The median survival was 8.3 months in arm A and 11.2 months in arm B (p = 0.25). No statistically significant differences were found when objective regression and survival were related to site of primary tumor, performance status, and number of involved organs. There were two drug-related deaths in arm B due to severe myelosuppression followed by mucositis and sepsis. Of nonhematologic toxicities, diarrhea was more frequently observed in arm B, as were mucositis and infectious complications. Our results indicate that the sequential schedule MTX-5-FU-LV with 20-h intervals between MTX and 5-FU is superior in terms of objective regression to 5-FU alone given at the dose and schedule used in the present study. However, MTX-5-FU-LV did not have a significant impact on survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/mortalidade , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Taxa de SobrevidaRESUMO
The medical records of 510 patients with metastatic breast cancer were retrospectively reviewed. Seventy-seven patients with metastases confined to skeleton and 73 patients bearing visceral-only disease were identified. All patients had a disease-free interval greater than or equal to 6 months and received systemic therapy with any of the following modalities: chemotherapy, hormonotherapy, or chemohormonotherapy. The clinical features, response to treatment, and survival were analyzed and compared for both groups. Median survival of patients with osseous metastases was 28 months, while it was 13 months for those patients with a visceral pattern (p less than 0.001). Response rates to first and second line systemic therapy for both metastatic patterns showed no significant differences, suggesting a similar degree of sensitivity or resistance in both groups. Objective regression to first therapy was 45% in the group with bony disease and 41% among patients with visceral involvement; median duration of response was 16 months and 13 months, respectively. In both groups progressive disease conserved the original metastatic pattern in most patients. We conclude that although a superiority in survival was evident for the osseous metastatic pattern, for these patients efforts should be made to select the least aggressive therapy in order to avoid excessive toxicity. Further studies are needed to confirm our findings.
Assuntos
Adenocarcinoma/secundário , Neoplasias Ósseas/secundário , Neoplasias da Mama , Vísceras , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.