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1.
ANZ J Surg ; 94(6): 1071-1075, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38426382

RESUMO

BACKGROUND: In 2015 our centre introduced a nurse-led renal cell cancer follow-up protocol and clinic for patients who have undergone partial or radical nephrectomy for organ-confined kidney tumours. The main aims of this clinic were to improve healthcare efficiency and standardize follow-up processes. OBJECTIVES: The primary objective was to assess the effectiveness of a nurse-led renal cell cancer follow up clinic in regard to surveillance protocol compliance and the timely identification and appropriate management of recurrences. A secondary objective was to evaluate this locally developed follow up protocol against the current European Association of Urology (EAU) guidelines surveillance protocol. PATIENT AND METHODS: All patients who underwent a partial or radical nephrectomy between 2015 and 2021 at a single Western Australia institution for a primary renal malignancy were included. Data was collected from local clinical information systems and protocol adherence, recurrence characteristics and management were assessed. The current EAU guidelines were applied to the cohort to assess differences in risk-stratification and theoretical outcomes between the protocols. RESULTS: After a mean follow up period of 31.2 months (range 0-77 months), 75.5% (185/245) of patients had all follow up imaging and reviews within 1 month of the timeframe scheduled on the protocol. 17.1% (42/245) had a delay in their follow up of more than a month at some stage, 5.7% (14/245) did not attend for follow up but had documented attempts to facilitate their compliance, and 0.4% (1/245) were lost to follow up with no evidence of attempted contact. 15.5% (38/245) of patients had recurrence of malignancy detected during follow up and these were all discussed in a multi-disciplinary team (MDT) meeting. The recurrence rate was 2.5% (3/119) for low risk, 17.7% (14/79) for intermediate risk, and 44.7% (21/47) for high risk patients when they were re-stratified according to EAU risk categories. No recurrences were detected through ultrasound (USS) or chest x-ray (CXR) in this cohort and our protocol tended to place patients in higher risk-stratification groups as compared to current EAU guidelines. CONCLUSION: Nurse-led renal cell cancer follow up is a safe, reliable and effective clinical framework that has significant benefits in regard to resource utilization. USS and CXR are ineffective in detecting recurrence and Computerized tomography (CT) should be considered the imaging modality of choice for this purpose. The EAU surveillance protocol appears superior to our protocol, and we have therefore transitioned to the EAU guideline protocol going forward.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Recidiva Local de Neoplasia , Nefrectomia , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Masculino , Feminino , Nefrectomia/métodos , Pessoa de Meia-Idade , Idoso , Fidelidade a Diretrizes , Austrália Ocidental , Padrões de Prática em Enfermagem , Adulto , Idoso de 80 Anos ou mais , Seguimentos , Estudos Retrospectivos
2.
Oncogene ; 35(50): 6389-6402, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27157612

RESUMO

Using a 4-hydroxytamoxifen (4OHT)-inducible, conditional Sos1-null mutation, we analyzed wild-type (WT), single Sos1-KO, Sos2-KO and double Sos1/2 KO primary mouse embryonic fibroblasts (MEF) with an aim at evaluating the functional specificity or redundancy of the Sos1 and Sos2 alleles at the cellular level. The 4OHT-induced Sos1-KO and Sos1/2-DKO MEFs exhibited distinct flat morphology, enlarged cell perimeter and altered cytoskeletal organization that were not observed in the WT and Sos2-KO counterparts. The Sos1-KO and Sos1/2-DKO MEFs also displayed significant accumulation, in comparison with WT and Sos2-KO MEFs, of cytoplasmic vesicular bodies identified as autophagosomes containing degraded mitochondria by means of electron microscopy and specific markers. Cellular proliferation and migration were impaired in Sos1-KO and Sos1/2-DKO MEFs in comparison with WT and Sos2-KO MEFs, whereas cell adhesion was only impaired upon depletion of both Sos isoforms. RasGTP formation was practically absent in Sos1/2-DKO MEFs as compared with the other genotypes and extracellular signal-regulated kinase phosphorylation showed only significant reduction after combined Sos1/2 depletion. Consistent with a mitophagic phenotype, in vivo labeling with specific fluorophores uncovered increased levels of oxidative stress (elevated intracellular reactive oxygen species and mitochondrial superoxide and loss of mitochondrial membrane potential) in the Sos1-KO and the Sos1/2-DKO cells as compared with Sos2-KO and WT MEFs. Interestingly, treatment of the MEF cultures with antioxidants corrected the altered phenotypes of Sos1-KO and Sos1/2-DKO MEFs by restoring their altered perimeter size and proliferative rate to levels similar to those of WT and Sos2-KO MEFs. Our data uncover a direct mechanistic link between Sos1 and control of intracellular oxidative stress, and demonstrate functional prevalence of Sos1 over Sos2 with regards to cellular proliferation and viability.


Assuntos
Proliferação de Células , Fibroblastos/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Proteína SOS1/fisiologia , Animais , Antioxidantes/farmacologia , Adesão Celular , Movimento Celular , Sobrevivência Celular , Células Cultivadas , Dano ao DNA , Camundongos , Transdução de Sinais , Proteínas Son Of Sevenless/fisiologia
3.
Hernia ; 18(2): 185-92, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23180147

RESUMO

INTRODUCTION: In inguinal hernia repair, many complications are due to mesh fixation technique. Therefore, new types of atraumatic methods of fixation have been proposed. In this article, we present the results of a prospective multicentric parallel randomized controlled trial aiming to compare two mesh fixation techniques: fibrin sealant (QUIXIL(®), Omrix Biopharmaceuticals S.A., Belgium) and Lichtenstein technique. METHOD: Adult patients with primary uncomplicated inguinal hernia were randomized in two groups: fibrin sealant group (FSG) and Lichtenstein group (LTG). The two groups underwent a follow-up of 15 months. Operative time is the primary outcome. Intraoperative and postoperative outcomes were analyzed. Moreover, a differential cost analysis was performed. Patients and evaluators (with exception of the surgeon who treated the patient) were blinded. RESULTS: A total of 102 patients, 50 in FSG and 52 in LTG, were enrolled from January 2009 to June 2010, and two patients were lost to follow-up at the twelfth month. No significant differences in baseline and clinical characteristics were observed in the two groups. Operative time was longer in LTG (median/ interquartile range: 35 min/30-42.5 min vs. 31 min/28-35 min; effect size: 0.65/95% CI 0.50-0.91; p < 0.05). No differences in intraoperative complications were observed. No significant differences were observed in early complication rate (RR = 0.62; p > 0.05). Numbness rate was lower in the FSG at 1 week (RR = 0.43; p < 0.01) and at 1 month (RR = 0.17; p < 0.05). No significant differences were observed after 6 months. Postoperative pain was lower in the FSG at 1 week (0/0-1 vs. 1/0-2; p < 0.05) and at 1 month (0/0-0 vs. 0/0-1; p < 0.05). Pain disappeared in all patients after 6 months. Analgesic assumption rate was lower in the FSG (RR = 0.42; p < 0.05). Twenty per cent of FSG and 9.62% of LTG patients were discharged within 12 h; 78% of FSG and 90.38% of LTG patients were discharged within 24 h. The only one recurrence we observed was in FSG group. About costs, although fibrin sealant needed for one mesh fixation is about 10 times more costly than the needed sutures, the total costs of the two procedures did not change significantly. This was mainly due to reduction in operative time. CONCLUSIONS: The use of fibrin sealant determined a significant reduction in short-term numbness rate and postoperative pain. There was no relevant difference in total costs per patient between the two procedures.


Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Telas Cirúrgicas , Análise Custo-Benefício , Feminino , Adesivo Tecidual de Fibrina/economia , Herniorrafia/economia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Medição da Dor , Dor Pós-Operatória , Estudos Prospectivos , Telas Cirúrgicas/economia , Resultado do Tratamento
4.
Oncogene ; 32(11): 1441-51, 2013 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-22641220

RESUMO

Ewing sarcoma (ES) is an aggressive bone and soft tissue tumor of children and young adults in which finding effective new targeted therapies is imperative. Here, we report an in-depth preclinical study of the investigational cullin-RING ubiquitin ligase (CRL) inhibitor MLN4924 in ES, as we have recently demonstrated the implication of a CRL component in the ES pathogenesis. First, our results support a high sensitivity of ES cells to MLN4924 growth inhibition both in vitro (14 ES cell lines tested, median IC50=81 nM) and in tumor xenografts (tumor regression achieved with 60 mg/kg BID, subcutaneously, n=9). Second, we report a dual mechanism of action of MLN4924 in ES cells: while a wide range of MLN4924 concentrations (∼30-300 nM) trigger a G2 arrest that can only be rescued by WEE1 kinase inhibition or depletion, saturating doses of the drug (>300 nM) cause a delay in S-phase progression concomitant with unbalanced CDK2-Cyclin E and CDK2-Cyclin A relative levels (accumulation of the first and depletion of the latter). The aberrant presence of CDC6 in the nucleus at late S-phase cell cycle stage confirmed the loss of CDK2-Cyclin A-specific functions. Remarkably, other mechanisms explored (P27 accumulation and DNA damage signaling pathways) were found unable to explain MLN4924 effects, strengthening the specificity of our findings and suggesting the absence of functionality of some CRL substrates accumulated in response to MLN4924. This study renders a rationale for clinical trials and contributes molecular mechanisms for a better understanding of this promising antitumoral agent.


Assuntos
Neoplasias Ósseas/patologia , Proteínas de Ciclo Celular/metabolismo , Ciclopentanos/farmacologia , Proteínas Nucleares/metabolismo , Proteínas Tirosina Quinases/metabolismo , Pirimidinas/farmacologia , Fase S/efeitos dos fármacos , Sarcoma de Ewing/patologia , Animais , Antineoplásicos/farmacologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , RNA Interferente Pequeno/farmacologia , Fase S/genética , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Rev Esp Enferm Dig ; 92(1): 13-26, 2000 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-10749594

RESUMO

OBJECTIVE: To retrospectively review a series of 12 patients operated on in our department for stromal tumor of the stomach. Clinical and morphological data, and the patients' postoperative course, were analyzed. METHODS: Medical records for 12 patients (mean age 63.3 years) were retrospectively reviewed to obtain data on clinical presentation, diagnosis and treatment. Surgical morbidity and mortality were analyzed. A pathologist reviewed the resected specimens to determine the morphological factors of prognostic value. The biological nature of the tumor was reclassified based exclusively on mitotic index, and all tumors were staged according to the TGM system. Recurrence and survival rates were also calculated. RESULTS: The most frequent clinical presentation was abdominal pain and gastrointestinal bleeding. The most sensitive diagnostic methods were computerized tomography and echographic endoscopy. Operability and resectability rates were 100% and 91.6% respectively. Local resection was done in 5 patients, partial gastrectomy in 5, and extended total gastrectomy in 1. Histologically, 6 cases were muscular tumors (2 leiomyomas, 3 low-grade leiomyosarcomas and 1 high-grade leiomyosarcoma), 2 were gastrointestinal autonomic nerve (GAN) tumors, and 4 were pure stomal tumors. The morbidity rate was 33.3% and the mortality rate was 8.3% (1 patient). All patients were followed up: 1 patient each died after 9 months and 4 years, 1 developed liver metastases after a disease-free interval of 14 months, and the other 9 patients were still alive and free of disease after intervals ranging from 4 months to 7 years. CONCLUSIONS: Stromal tumors include a group of tumors which may present muscular differentiation (the most frequent type), neural differentiation (GAN tumors) or no differentiation at all (pure stromal tumors). The mitotic index is the most valid parameter to determine biological nature, considering that classification as a benign tumor requires the total absence of mitoses. Treatment was mostly surgical, and local resection with adequate safety margins was effective. Prognosis was relatively good, but long-term follow-up is needed to assess the malignant potential of these tumors.


Assuntos
Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Seguimentos , Gastrectomia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Estômago/patologia , Neoplasias Gástricas/classificação , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia
9.
Rev. esp. enferm. dig ; 92(1): 13-26, ene. 2000.
Artigo em Es | IBECS | ID: ibc-14085

RESUMO

OBJETIVO: el propósito del estudio es una revisión retrospectiva de una serie de 12 tumores estromales gástricos intervenidos en nuestro servicio, analizando tanto sus datos clínicos como sus características morfológicas y valorando el tratamiento quirúrgico y la evolución de los pacientes. PACIENTES Y MÉTODOS: se revisan las historias clínicas de todos los pacientes obteniendo datos de presentación clínica, diagnóstico y tratamiento; se analiza morbilidad y mortalidad. Paralelamente se revisan las piezas de anatomía patológica estudiando factores morfológicos de valor pronóstico y reclasificando el carácter biológico de los tumores en base exclusivamente al índice mitótico. Se estadifica la serie según el sistema TGM. Se analiza la tasa de recurrencia y supervivencia. RESULTADOS: la edad media de los pacientes fue de 63,3 años. La forma más frecuente de presentación clínica fue el dolor abdominal y la hemorragia digestiva. Los métodos diagnósticos más sensibles fueron CT y ecoendoscopia. La operabilidad fue del 100 por ciento y la resecabilidad del 91,6 por ciento, se realizó resección local en cinco pacientes, gastrectomía parcial en cinco casos y una gastrectomía total ampliada. Histológicamente seis casos fueron tumores musculares (dos leiomiomas, tres leiomiosarcomas de bajo grado y un leiomiosarcoma de alto grado), hubo dos tumores GAN y cuatro estromales puros. La morbilidad fue del 33,3 por ciento y la mortalidad del 8,3 por ciento (un caso). El seguimiento se llevó a cabo en el 100 por ciento de los casos: dos pacientes fallecieron (a los nueve meses y a los cuatro años respectivamente), un paciente desarrolló metástasis hepáticas (tras un intervalo libre de 14 meses) y el resto están vivos y libres de enfermedad con un rango entre cuatro meses y siete años. CONCLUSIONES: los tumores estromales incluyen un grupo de tumores que pueden presentar diferenciación muscular (los más frecuentes), diferenciación neural (tumores GAN) o ninguna diferenciación (tumores estromales puros). El índice mitótico es el criterio diferencial más válido para determinar su carácter biológico, considerándose que el criterio de benignidad exige la ausencia total de mitosis. El tratamiento se basa fundamentalmente en la cirugía, siendo suficiente la resección local con márgenes de seguridad. El pronóstico es relativamente bueno, siendo necesarios seguimientos a largo plazo para controlar la expresión de su potencia maligno (AU)


Assuntos
Pessoa de Meia-Idade , Adulto , Idoso , Idoso de 80 Anos ou mais , Masculino , Feminino , Humanos , Estômago , Estudos Retrospectivos , Biópsia , Gastrectomia , Seguimentos , Gastroscopia , Neoplasias Gástricas , Estadiamento de Neoplasias
11.
Surgery ; 124(1): 57-64, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9663252

RESUMO

BACKGROUND: Surgical excision of liver tumors represents the only curative treatment for primary and metastatic liver malignancies. It has been suspected that hepatectomy may stimulate growth of microscopic tumors. To determine whether local or systemic factors after hepatectomy are responsible for enhancement of tumor growth, the effects of hepatectomy on the experimental growth of liver or pulmonary tumors were examined. METHODS: One hour after injection of 10(6) Morris hepatoma cells into either the portal or femoral vein, which produces isolated liver and lung tumors, respectively, animals were randomized to undergo 0%, 30%, or 70% partial hepatectomy (PH). RESULTS: Animals that underwent portal injection of tumor had significantly increased liver tumor burden after PH (sham, 25 +/- 7 vs PH, 94 +/- 17; p < 0.01), whereas animals that underwent femoral injection had no change in lung tumor burden after PH. PH was associated with significantly increased levels of transforming growth factor-alpha, transforming growth factor-beta, and basic fibroblast growth factor in the liver but not in the lung. CONCLUSIONS: Changes in liver cytokine-growth factor activation may contribute to enhanced tumor growth in the liver after hepatectomy.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia/métodos , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Pulmonares/patologia , Animais , Carcinoma Hepatocelular/metabolismo , Fator 2 de Crescimento de Fibroblastos/sangue , Fator 2 de Crescimento de Fibroblastos/metabolismo , Injeções Intravenosas , Fígado/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Transplante de Neoplasias , Neoplasias Experimentais/patologia , Ratos , Ratos Endogâmicos BUF , Fator de Crescimento Transformador alfa/sangue , Fator de Crescimento Transformador alfa/metabolismo , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta/metabolismo
12.
Surgery ; 121(6): 625-32, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9186462

RESUMO

BACKGROUND: The role of liver resection for hepatic metastases from noncolorectal, nonneuroendocrine (NCNN) cancers is unknown. This study examines a large, single institutional experience of hepatic resection for NCNN metastases. METHODS: Records of 96 patients who underwent liver resection for metastatic NCNN cancer from 1980 to 1995 at a single institution were reviewed. Survival after liver resection in this cohort of patients is reported, and factors predictive of survival are analyzed. RESULTS: Resection was performed for liver metastases from genitourinary primary tumors (n = 34), soft tissue primary tumors (n = 41), and metastases from other primary cancers (n = 21). Extent of liver resection included wedge (n = 32), lobectomy (n = 44), and extended hepatic lobectomy (n = 20). No operative deaths occurred. Overall survival rate after resection at 1, 3, and 5 years was 80%, 45% and 37%, respectively (median survival, 32 months), with 12 actual 5-year survivors. There was no difference in survival according to the type of liver resection, bilateral versus unilateral disease, or resection of extrahepatic disease. Disease-free interval of less than 36 months before discovery of liver metastases, curative resection, and primary tumor group (genitourinary was greater than soft tissue, which was greater than gastrointestinal) were predictors of a significantly better survival by multivariate analysis. CONCLUSIONS: Primary tumor type, disease-free interval, and curative resection predict those patients who benefit from hepatic resection. Hepatic resection for patients with NCNN metastasis has value in carefully selected patients.


Assuntos
Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
13.
World J Surg ; 21(3): 323-9, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9015179

RESUMO

The objective of this study was to determine the prognostic information provided by flow cytometric DNA analysis in non-small-cell lung cancer. Lung samples of 132 consecutive patients submitted to surgery were prospectively processed. When no aneuploid populations were detected in fresh frozen samples, the process continued as a second step in paraffin-embedded tissue, consuming all the tumor available. The influence of ploidy on the postoperative outcome was studied by both a univariate and a multivariate analysis. Aneuploidy was found in 81 patients (61.4%). Fourteen patients showed no aneuploidy in fresh frozen samples; and only after further analysis in paraffin-embedded tissue was abnormal DNA detected. Overall, the 36-month survival was 69% for the diploid group and 24% for the aneuploid group (p = 0.0006). Including subjects submitted to complete tumor removal (stages I, II, and IIIA) in a multivariate analysis adjusted for TNM stage and histologic type, bearers of aneuploid tumors exhibited a higher risk of relapse (hazard ratio 2.65; CI 95% 1.5-4.66;p = 0.004) or death (hazard ratio 2.17; CI 95% 1.08-4.39;p = 0.032) than patients with diploid tumors. DNA ploidy resulted an independent prognostic factor of survival and tumor relapse in completely resected non-small-cell lung cancer. Sequential analysis of fresh and paraffin-embedded samples can help avoid the bias due to intratumoral DNA content heterogeneity. DNA ploidy could be an useful parameter in any future multifactorial analysis of outcome in such tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA de Neoplasias/análise , Neoplasias Pulmonares/genética , Aneuploidia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Diploide , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo
14.
J Surg Res ; 63(2): 452-6, 1996 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-8661241

RESUMO

Transplantation of normal or ex vivo modified hepatocytes holds promise in therapy of a variety of diseases. In order to investigate hepatocyte trafficking, and specifically to determine whether the route, method of delivery, or other host factors may affect hepatocyte sequestration in the liver, 51chromium- and 111indium-labeled hepatocytes were transplanted into allogeneic hosts. Systemic injection of hepatocytes into the femoral vein resulted in sequestration mainly in the lungs (30 +/- 4%) whereas sequestration in the liver amounted to only 5 +/- 1%. Portal injection resulted in a dramatic increase in the liver sequestration (52 +/- 4%) and a reduction in the lung (2 +/- 1%, P < 0.05 vs systemic injection). Nevertheless, nearly half of portally injected hepatocytes came to rest in other organ sites. Partial hepatectomy prior to transplantation did not change the total hepatocyte sequestration in the liver or the organ specific activity. A remote site of inflammation, in the form of a turpentine abscess, also did not alter the pattern of hepatocyte trafficking. Isolated perfusion of the liver with labeled hepatocyte, however, significantly increased the sequestration of hepatocytes at this organ (control, 52 +/- 4%; isolated perfusion, 71 +/- 9%; P < 0.05). In the delivery of potentially toxic gene products for therapy, isolated perfusion of the target organ appears to provide the greatest likelihood of restricting expression of potentially toxic gene products to the target organ.


Assuntos
Transplante de Células , Fígado/fisiologia , Animais , Veia Femoral , Hepatectomia , Injeções Intravenosas , Células de Kupffer/fisiologia , Fígado/citologia , Masculino , Perfusão , Veia Porta , Ratos , Ratos Endogâmicos F344
15.
Eur J Cancer ; 32A(7): 1171-8, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8758249

RESUMO

To assess any synergistic stimulatory effect in vivo of Interleukin 3 (IL-3) and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) upon white cell and platelet counts, toxicity and antitumour effect, we conducted this phase I study. IL-3 0.25, 0.5 or 5 micrograms/kg/day for 1, 4 or 7 days was given by continuous intravenous (i.v.) infusion to 35 patients with advanced malignancy. 21 of the 35 patients also received sequential or overlapping treatment with continuous i.v. infusion of GM-CSF 1 or 3 micrograms/kg/day for up to 10 days. Monotherapy with IL-3 producted significant dose related increases in platelets and white cell counts. Combinations of IL-3 and GM-CSF also produced increases in white cell counts, but these were no greater than would be expected following GM-CSF treatment alone. There was a trend for platelets to increase more in patients receiving IL-3 and GM-CSF than those receiving IL-3 alone, but this did not reach statistical significance. In general, IL-3 and combinations of IL-3 and GM-CSF were well tolerated and the most common side-effect was fever. A maximum tolerated dose was not reached and antitumour effects were not seen. Future studies using combinations of IL-3 5 micrograms/kg/day and GM-CSF 3 micrograms/kg/day may help to define the optimal therapeutic regimen.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Interleucina-3/uso terapêutico , Neoplasias/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Exame de Medula Óssea , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Hemoglobinas/metabolismo , Humanos , Infusões Intravenosas , Interleucina-3/efeitos adversos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Contagem de Plaquetas , Proteínas Recombinantes/uso terapêutico
16.
Br J Cancer ; 73(10): 1248-54, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8630287

RESUMO

Risk of death and risk of recurrence in 108 potentially curable non-small-cell lung cancer patients were analysed with respect of TNM stage, histological type and carcinoembryonic antigen (CEA), CA125 antigen and squamous cell carcinoma antigen (SCC) levels in serum and cytosol. CA125 and CEA levels were closely related to outcome figures. Multivariate analyses indicated that TNM stage and histological type had the best predictive power, but serum and cytosolic CA125 and serum CEA contained additional, independent prognostic information. Predictive information drawn from serum and cytosolic levels proved mutually complementary. We conclude that CA125 and CEA complement TNM classification and histological type for the purpose of quantifying risk of death or recurrence.


Assuntos
Antígenos de Neoplasias/metabolismo , Antígeno Ca-125/metabolismo , Antígeno Carcinoembrionário/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Serpinas , Adenocarcinoma/diagnóstico , Adenocarcinoma/imunologia , Adenocarcinoma/cirurgia , Idoso , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Análise de Sobrevida
17.
Cancer ; 77(6): 1066-72, 1996 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-8635125

RESUMO

BACKGROUND: The use of new prognostic factors as guidelines for the indication of treatment ancillary to surgery has been advocated for patients with nonsmall cell lung carcinoma (NSCLC). This article is an analysis of the prognostic information derived from determination of tumor-tissue cytosolic concentration of CA 125 tumor-associated antigen (CA 125), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC) in patients with NSCLC. METHODS: Tumor samples were obtained from 97 patients who successfully underwent surgery for NSCLC with curative intent. CA 125 and CEA were determined by enzyme immunoassay. SCC was determined by radioimmunoassay. The relationship between the tumor-tissue marker level and survival or likelihood of disease free survival was analyzed. RESULTS: Thirty-month survival post-treatment in patients registering CA 125 levels less than 26 U/mg was 68%, versus 30% among patients with levels of CA 125 greater tha 26 U/mg (P < 0.005). For SCC, these values were 57% and 39%, respectively (P = 0.07). No significant difference was seen for CEA (60% versus 44%; P = 0.3). Patients whose tumors had CA 125 levels lower than cutoff recorded a disease free survival rate of 61% versus 29% (P < 0.001); with SCC, likelihood of remaining free of tumor recurrence was 55% versus 34% (P < 0.05). Again, no significant difference was seen for CEA (49% versus 45%; P = 0.5). For CA 125 and SCC, the relationship between marker level and outcome held only with the most favorable histologic types. For CA 125 however, this relationship also held for Stage I tumors (P < 0.005). CONCLUSIONS: Ascertainment of concentrations of CA 125 and SCC in tumor tissue is useful parameter in the determination of postoperative prognosis for patients with NSCLC.


Assuntos
Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Antígeno Ca-125/análise , Antígeno Carcinoembrionário/análise , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Citosol/química , Neoplasias Pulmonares/mortalidade , Serpinas , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico
19.
Arch Bronconeumol ; 30(6): 282-6, 1994.
Artigo em Espanhol | MEDLINE | ID: mdl-8087386

RESUMO

In this study we determined the concentration of epidermic growth factor receptors (EGFr) in non-small cell carcinoma of the lung (NSCCL) and analyzed its relation to the anatomical, pathological and clinical factors of these neoplasms. The concentration of EGFr in 62 tumor tissue samples was 9.9 +/- 14 fmol/mg, higher than that found in 14 tissue samples from cases of spontaneous pneumothorax (3.9 +/- 3.6 fmol/mg) (p = 0.005). EGFr concentration in lung tissue with no signs of neoplasm was 6.5 +/- 10 fmol/mg. In 21 (33%) cases of NSCCL the concentration exceeded the normal threshold of 10 fmol/mg. EGFr concentration was higher in cases of epidermoid carcinoma than in other tissue samples (p = 0.042). No significant association was found between EGFr levels and status of tumor node metastasis, degree of differentiation and mitotic index. The probability of remaining free of tumor recurrence and of survival after 24 months among patients whose tumoral EGFr concentration was below 10 fmol/mg was 34 and 40%, respectively. The rates for patients with concentrations that exceeded the threshold were 20% (p = 0.32) and 25% (p = 0.26), respectively. The results seem to indicate that the study of EGFr concentration alone does not yield practically important information for the management of patients with NSCCL who have undergone surgery. The concentration of EGFr marks degree of differentiation in NSCCL and has prognostic implications derived from its association with other factors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/química , Receptores ErbB/análise , Neoplasias Pulmonares/química , Adenocarcinoma/química , Adenocarcinoma/patologia , Idoso , Carcinoma de Células Grandes/química , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Recidiva Local de Neoplasia , Pneumotórax/diagnóstico , Prognóstico
20.
Cancer ; 73(9): 2305-11, 1994 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-8168034

RESUMO

BACKGROUND: The cytosolic content of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC), CA 125, and CA 50 antigens in non-small cell lung cancer (NSCLC) is analyzed in this study. The aim was to ascertain the relationship between tumor marker content and the clinicopathologic aspects of this neoplasm. METHODS: Lung tissue samples were obtained at the time of surgery from 75 patients with NSCLC patients (samples of tumor and unaffected tissue) and 29 subjects with idiopathic pneumothorax. All determinations were performed on cytosols obtained from lung specimens. CEA and CA 125 were determined by enzyme immunoassay, SCC antigen by radioimmunoassay, and CA 50 by fluoroimmunoassay. Tumor marker content was analyzed by TNM stage, histologic type, tumor grade, and number of atypias. RESULTS: The concentration of the four markers was significantly higher in cytosol obtained from neoplastic tissue. Frequency of elevated levels of CEA was higher in adenocarcinoma (87% cases expressing high levels of the marker), SCC antigen in epidermoid carcinoma (65% expressing high levels), and CA 125 in large cell carcinomas (100% expressing high levels). No association was found between TNM stage and cytosol concentration for any of the four markers. CEA exhibited significantly greater concentration in well differentiated tumors, whereas this was true of CA 125 in poorly differentiated tumors. CA 125 content was higher in tumors with more atypia. CONCLUSIONS: Cytosolic quantification of tumor markers may be an adjuvant mechanism to evaluate histologic subtypes of non-small cell lung cancer and identification of tumors with poorly differentiated features.


Assuntos
Antígenos de Neoplasias/análise , Antígenos Glicosídicos Associados a Tumores/análise , Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/análise , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Serpinas , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adulto , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Citosol/imunologia , Feminino , Humanos , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pneumotórax/imunologia , Pneumotórax/patologia , Curva ROC
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