Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Pharmacogenomics J ; 17(6): 506-514, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-27779244

RESUMO

To evaluate the predictive value of genes involved in resistance to platinum-taxane chemotherapy in patients with epithelial ovarian cancer (EOC). Microdissected formalin-fixed tumoral samples from 187 EOC patients' primary tumors (90 and 97 samples from matched patients in the experimental and validation sets, respectively) were analyzed. All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, UIMC1(RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) mRNA expression by quantitative real-time PCR. Most of the patients (172 out of 187) received front-line carboplatin-paclitaxel regimen. Expression levels were correlated with overall (OS) and progression-free (PFS) survival by multivariate analysis. Patients with high TXN and THBS1 expression presented longer PFS (P=0.001 and P<0.001, respectively) and OS (P=0.024 and P<0.001, respectively). High TXR1 expression was associated with decreased PFS (P<0.001) and OS (P<0.001). Multivariate analysis demonstrated that high PRR13/low THBS1 expression was an independent factor for decreased PFS (hazards ratio: 1.94; 95% confidence interval (CI): 1.48-2.92; P=0.008) and OS (hazard ratio: 3.89; 95% CI: 2.16-6.87; P<0.001), whereas low TXN expression was correlated with decreased PFS (hazard ratio: 1.44; 95% CI: 1.05-2.84; P=0.043) and OS (hazard ratio: 2.38; 95% CI: 1.78-2.77; P=0.009). These findings indicate that PRR13/THBS1 and TXN expression could be used for the prediction of resistance to treatment of EOC patients and, therefore, merit to be further evaluated.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Proteínas Repressoras/genética , Tiorredoxinas/genética , Trombospondina 1/genética , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Taxoides/administração & dosagem , Taxoides/uso terapêutico
2.
Br J Cancer ; 113(6): 914-20, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26325103

RESUMO

BACKGROUND: An everyday clinical practice dilemma in the 20-30% of metastatic colorectal cancer (CRC) patients that have not been operated on their primary tumour, is, under which specific histopathology and molecular circumstances, an endoscopic biopsy could be considered adequate to provide a representative RAS/BRAF molecular status to guide treatment. METHODS: A consecutive series of 193 paired biopsy and primary CRC tumour samples between August 2008 and 2010 available in the Department of Pathology archives, University Hospitals, KU Leuven were retrieved. For a pair to be included, in the endoscopic biopsy, 20% of invasive adenocarcinoma cells should be present and enough slides to yield an extracted DNA concentration of ⩾5 ng µl(-1), and no <2 ng µl(-1) should be available for cutting. Exons 2-4 KRAS/NRAS, BRAF, PIK3CA molecular evaluation was performed with RT-PCR and Sequenom. RESULTS: From 165 deemed adequate by the pathologist pairs, 85 (51.5%) were concordantly mutated in at least one of the tested genes, 70 (42.5%) were wt and 10 (6%) were discordant, harbouring a mutation in the primary and not in the endoscopic biopsy. In the re-evaluation, when more slides were cut per discordant pair, mutational status changed in two of the six discordantly KRAS-mutated pairs. A strong strength of agreement for both runs was observed (Cohen's kappa, k=0.877, P<0.001 and k=0.901, P<0.001, respectively) between the surgically acquired and the endoscopic biopsy specimens' evaluation. CONCLUSIONS: Based on our results, an endoscopic biopsy could provide an accurate mutational profile and become a justified alternative to a surgically removed primary tumour specimen, as long as specific histopathology criteria are met.


Assuntos
Adenocarcinoma/genética , Colonoscopia/normas , Neoplasias Colorretais/genética , GTP Fosfo-Hidrolases/genética , Genes ras , Proteínas de Membrana/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/normas , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Análise Mutacional de DNA , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Reação em Cadeia da Polimerase em Tempo Real
3.
Ann Oncol ; 26(1): 126-132, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25361982

RESUMO

BACKGROUND: Although colon cancer (CC) with microsatellite instability (MSI) has a more favorable prognosis than microsatellite stable (MSS) CC, the impact varies according to clinicopathological parameters. We studied how MSI status affects prognosis in a trial-based cohort of stage II and III CC patients treated with 5-fluorouracil (5-FU)/leucovorin or FOLFIRI. MATERIALS AND METHODS: Tissue specimens of 1254 patients were tested for 10 different loci and were classified as MSI-high (MSI-H) when three or more loci were unstable and MSS otherwise. Study end points were overall survival (OS) and relapse-free survival (RFS). RESULTS: In stage II, RFS and OS were better for patients with MSI-H than with MSS CC [hazard ratio (HR) 0.26, 95% CI 0.10-0.65, P = 0.004 and 0.16, 95% CI 0.04-0.64, P = 0.01). In stage III, RFS was slightly better for patients with MSI-H CC (HR 0.67, 95% CI 0.46-0.99, P = 0.04), but the difference was not statistically significant for OS (HR 0.70, 95% CI 0.44-1.09, P = 0.11). Outcomes for patients with MSI-H CC were not different between the two treatment arms. RFS was better for patients with MSI-H than with MSS CC in the right and left colon, whereas for OS this was significant only in the right colon. For patients with KRAS- and BRAF-mutated CC, but not for double wild-type patients, RFS and OS were significantly better when the tumors were also MSI-H. An interaction test was statistically significant for KRAS and MSI status (P = 0.005), but not for BRAF status (P = 0.14). CONCLUSIONS: Our results confirm that for patients with stage II CC but less so for those with stage III MSI-H is strongly prognostic for RFS and OS. In the presence of 5-FU treatment, stage II patients with MSI-H tumors maintain their survival advantage in comparison with MSS patients and adding irinotecan has no added benefit. CLINICALTRIALS.GOV IDENTIFIER: NCT00026273.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/uso terapêutico , Instabilidade de Microssatélites , Repetições de Microssatélites/genética , Camptotecina/uso terapêutico , Quimioterapia Adjuvante , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Humanos , Leucovorina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle
4.
J BUON ; 18(1): 296-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23613423

RESUMO

At the beginning of the 20th century, Professor Jean-Louis Faure, one of the leading surgeons of the innovative Parisian Medical School, published an exhaustive work on uterine cancer. He was the first to perform in France the procedure of total abdominal hysterectomy by median section of the uterus contributing to the evolution of cancer surgery.


Assuntos
Pesquisa Biomédica/história , Histerectomia/história , Oncologia/história , Neoplasias Uterinas/história , Feminino , França , História do Século XIX , História do Século XX , Humanos , Neoplasias Uterinas/cirurgia
5.
J BUON ; 18(4): 1101-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24344048

RESUMO

In 1872, the Hungarian born dermatologist Moriz Kaposi that was practicing in Vienna first described a rare endemic disease that bears his name, among elderly persons of Central European or Mediterranean origin named "idiopathic multiple pigmented sarcoma of the skin". Ten years later the Italian dermatologist Tommaso de Amicis confirms Kaposi's findings. For more than a century the disease was known as a rare low grade malignancy till the 1980s AIDS epidemic.


Assuntos
Dermatologia/história , Sarcoma de Kaposi/história , Neoplasias Cutâneas/história , Áustria , Dermatologia/educação , Educação Médica/história , História do Século XIX , Humanos
6.
Br J Cancer ; 107(12): 1932-7, 2012 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-23169296

RESUMO

BACKGROUND: We conducted an open-label, pilot phase II trial to evaluate the efficacy and safety of FOLFOXIRI plus cetuximab as first-line treatment of patients with metastatic colorectal cancer (mCRC). METHODS: Thirty patients with KRAS wild-type mCRC, <70 years and with performance status 0-1 were included in the trial. RESULTS: Complete and partial responses were observed in 4 (13.3%) and 17 (56.7%) patients, respectively (overall response rate (ORR)=70%; 95% confidence interval (CI): 53.6%-86.4%); 8 patients (26.7%) had stable disease and 1 had progressive disease. The median time to tumour progression was 10.2 months (95% CI: 7.1-13.4) and the overall median survival time was 30.3 months (95% CI: 18.8-41.9). Secondary R0 resection was performed in 11 (37%) patients. Grade 3 or 4 diarrhoea and neutropenia were observed in 16 (53%) and 7 (23.3%) patients, respectively, and febrile neutropenia observed in 2 (6.6%) patients. Neurotoxicity grade 2 or 3 was reported in 7 (23.3%) and in 2 (6.7%) patients, respectively, and grade 3 rush was reported in 1 patient. CONCLUSION: The FOLFOXIRI/cetuximab combination presented increased activity in terms of response rate and R0 secondary liver metastases resection, and merits further investigation, especially in patients with initially unresectable disease confined to the liver.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas ras/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorretais/metabolismo , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Hepatectomia , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Projetos Piloto , Proteínas Proto-Oncogênicas p21(ras) , Resultado do Tratamento
7.
J BUON ; 17(3): 446-51, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23033279

RESUMO

The diagnosis of metastatic cancer in peritoneal fluid is of great importance for the patient and the attending physician. A cytopathologist's responsibility is twofold: (1) to accurately identify malignant cells; (2) to interpret tumor type and if possible the site of its origin even in the absence of complete clinical history of other clues. The difficulty in the diagnosis of metastatic neoplasms in peritoneal fluid is due to 2 factors: (1) abnormal mesothelial cells or macrophages may simulate cancer cells, or may conceal tumor cells; and (2) peritoneal fluid constitutes a natural and hitherto inadequately explored medium of cell culture, in which neoplastic cells may proliferate free of the boundaries imposed upon them by the framework of organs and tissues. Immunocytochemistry (ICC) and molecular techniques are essential to establish an accurate diagnosis. From a great many points of view malignant peritoneal fluid is suitable for continuous study of cancer cells, thus providing knowledge about biologic aspects of human solid tumors.


Assuntos
Ascite/patologia , Neoplasias Peritoneais/secundário , Ascite/etiologia , Líquido Ascítico/patologia , Humanos , Neoplasias Peritoneais/diagnóstico
8.
J BUON ; 16(2): 215-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21766488

RESUMO

PURPOSE: Continuous administration of oral vinorelbine, given 3 times a week (metronomic), is feasible and exceptionally well tolerated at doses up to 50 mg with clinical activity against refractory tumors. In this phase II study oral metronomic vinorelbine and bevacizumab were evaluated as salvage therapy in women with pretreated metastatic breast cancer (MBC). METHODS: Patients received oral vinorelbine (50 mg 3 times a week) and bevacizumab (10 mg/kg) biweekly in cycles of 28 days. The primary endpoint was objective response rate (ORR). A preplanned analysis was performed when the first 13 patients were evaluated for tumor response. RESULTS: One patient (7.7%) achieved partial response (PR) and 6 (46.1%) stable disease (SD). The combination was very well tolerated but, as per protocol, the study was closed prematurely due to lack of efficacy. CONCLUSION: The combination of oral metronomic vinorelbine and bevacizumab has good tolerance but minimal activity in terms of objective responses in pretreated patients with MBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Bevacizumab , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina
9.
ESMO Open ; 6(6): 100306, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773904

RESUMO

The current state of the SARS-CoV-2 pandemic is an equilibrium between expanding vaccine coverage on the one hand, and emergence of variants of concern which compromise vaccine effectiveness and enhance viral transmission on the other. Inequity in vaccine distribution, primarily an ethical issue, challenges this equilibrium, as industrialized countries prepare to administer a third booster dose to their population. Solid tumor cancer patients typically respond well to initial full vaccination and someone could argue that they should not be prioritized for an adjuvant third dose, since protection from severe disease has largely been achieved with the two-dose regimen. Nevertheless, their immune status is dynamic and not all of them exhibit an adequate immune response. A booster third dose is necessary for the inadequate responders, while it will result in better protection of all patients from mild disease as well, which if presented could have ominous consequences due to their overall frailty, and their need to adhere to strict therapeutic schemes. International scientific and public health communities should develop approaches that allow for wide immediate vaccination coverage of the developing world, in parallel with administration of adjuvant doses to solid tumor cancer patients (and other at-risk categories) of the developed nations, in order to avoid prolonging the pandemic, which will be prospectively against cancer patients' best interest.


Assuntos
COVID-19 , Neoplasias , Vacinas , Humanos , Neoplasias/epidemiologia , SARS-CoV-2 , Eficácia de Vacinas
10.
ESMO Open ; 6(5): 100254, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34481329

RESUMO

BACKGROUND: The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. RESULTS: High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. CONCLUSIONS: The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Inflamação , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos
11.
Br J Cancer ; 102(12): 1762-8, 2010 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-20485284

RESUMO

BACKGROUND: The significance of BRAF mutations, microsatelite instability (MSI) status and cyclin D1 expression in patients with metastatic colorectal cancer (mCRC) was evaluated. METHODS: Primary tumours from 144 patients treated for mCRC were assessed for BRAF (V600E) mutation, MSI status and cyclin D1. The data were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: BRAF mutations were detected in 10 (out of 22, 45%) patients with MSI-H tumours compared with 2 (out of 122, 1.6%) in those with microsatellite stable tumours (P<0.001). The presence of BRAF mutations was correlated with cyclin D1 overexpression (7 out of 26 patients, 58% vs 5 out of 118 patients, 14%; P=0.001). Patients with BRAF-mutated primary tumours had a significantly decreased PFS (2.7 vs 9.8 months; P<0.001) and median OS (14 vs 30 months; P<0.001) than patients with wild-type (wt) tumours. Patients with MSI-H and BRAF-mutated tumours experienced significantly lower PFS (3.1 vs 11.4 months; P=0.008) and OS (14.5 vs 35.5 months; P=0.004) than patients with MSI-H and BRAF wt tumours. Similarly, BRAF mutations and cyclin D1 overexpression were correlated with decreased PFS (3.1 vs 8.6 months; P=0.03) and OS (17.8 vs 39.2 months; P=0.01). CONCLUSION: BRAF V600E mutations are associated with MSI-H status and cyclin D1 overexpression and characterize a subgroup of patients with poor prognosis.


Assuntos
Neoplasias Colorretais/genética , Ciclina D1/metabolismo , Instabilidade de Microssatélites , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico
12.
Br J Cancer ; 101(3): 465-72, 2009 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-19603024

RESUMO

BACKGROUND: We address the prognostic and predictive value of KRAS, PIK3CA and BRAF mutations for clinical outcomes in response to active agents in the treatment of metastatic colorectal cancer (mCRC). METHODS: We determined KRAS, BRAF and PIK3CA mutations in tumours from 168 patients treated for mCRC at two institutions. All patients received 5-FU-based first-line chemotherapy and treatment outcome was analysed retrospectively. RESULTS: KRAS, BRAF and PIK3CA mutations were present in 62 (37%), 13 (8%) and 26 (15%) cases, respectively. Multivariate analysis uncovered BRAF mutation as an independent prognostic factor for decreased survival (hazard ratio (HR) 4.0, 95% confidence interval (CI) 2.1-7.6). In addition, patients with BRAF-mutant tumours had significantly lower progression-free survival (PFS: HR 4.0, 95% CI 2.2-7.4) than those whose tumors that carried wild-type BRAF. Among 92 patients treated using chemotherapy and cetuximab as salvage therapy, KRAS mutation was associated with lack of response (P=0.002) and shorter PFS (P=0.09). BRAF (P=0.0005) and PIK3CA (P=0.01) mutations also predicted reduced PFS in response to cetuximab salvage therapy. CONCLUSIONS: These results underscore the potential of mutational profiling to identify CRCs with different natural histories or treatment responses. The adverse significance of BRAF mutation should inform patient selection and stratification in clinical trials.


Assuntos
Neoplasias Colorretais/genética , Mutação , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Cetuximab , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Valor Preditivo dos Testes , Prognóstico , Proteínas Proto-Oncogênicas p21(ras) , Terapia de Salvação
14.
J BUON ; 12(2): 197-202, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17600872

RESUMO

PURPOSE: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of weekly high dose 5-fluorouracil (5FU) continuous infusion and leukovorin (LV) alternatively combined with oxaliplatin and irinotecan in patients with advanced tumors of the gastrointestinal (GI) tract. PATIENTS AND METHODS: Patients received a fixed dose of LV (500 mg/m(2)) over 2 h infusion on weeks 1 to 4 and escalated doses of: oxaliplatin (starting dose 65 mg/m(2): 120 min i.v. infusion on weeks 1 and 3); irinotecan (starting dose 80 mg/m(2); 90 min i.v. infusion on weeks 2 and 4) and 5FU (starting dose 1500 mg/m(2); 22 h continuous i.v. infusion, on weeks 1 to 4), in cycles of 5 weeks. DLTs were evaluated during the fi rst cycle. RESULTS: Twenty-eight patients were treated on 8 dose levels and all but two patients received the regimen at least as second-line treatment. The DLT level was reached at the oxaliplatin dose of 90 mg/m(2), irinotecan dose of 110 mg/m(2), LV dose of 500 mg/m(2) and 5FU dose of 1750 mg/m(2); the recommended MTDs were 85 mg/m(2) for oxaliplatin, 110 mg/m(2) for irinotecan, 1750 mg/m(2) for 5FU and 500 mg/m(2) for LV. Grade 3 or 4 diarrhea and grade 3 nausea/vomiting were the dose-limiting events. Diarrhea was the most common toxicity of the regimen, occurring in 12 (42.8%) patients. Hematological toxicity was mild and there were no treatment- related deaths. CONCLUSION: This weekly regimen showed a favorable toxicity profile and merits further investigation in patients with advanced/metastatic tumors of the GI tract.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/análogos & derivados , Fluoruracila/administração & dosagem , Neoplasias Gastrointestinais/tratamento farmacológico , Leucovorina/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Esquema de Medicação , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Irinotecano , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina
15.
Oncology ; 71(3-4): 197-203, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17641541

RESUMO

PURPOSE: The study aimed to determine the maximum tolerated doses (MTDs) and identify the dose-limiting toxicities of the biweekly administration of pemetrexed plus gemcitabine in patients with solid tumors. PATIENTS AND METHODS: Patients with advanced malignancies were treated with escalated doses of gemcitabine and pemetrexed (starting doses 1,250 and 300 mg/m(2), respectively) both given on days 1 and 15 in cycles of 4 weeks. RESULTS: Forty-one patients were treated at 7 dose levels. The MTD was reached at the dose of 1,750 mg/m(2) for gemcitabine and 450 mg/m(2) for pemetrexed. Dose-limiting events were grade IV neutropenia, febrile neutropenia and treatment delay due to grade III hematological toxicities. One partial response in a pretreated patient with ovarian cancer was observed, while 4 other patients experienced stable disease. CONCLUSIONS: The biweekly administration of gemcitabine plus pemetrexed at the recommended MTDs is safe, well tolerated and demonstrates antitumor activity which merits further evaluation in phase II studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Glutamatos/administração & dosagem , Guanina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Pemetrexede , Gencitabina
16.
Anticancer Res ; 25(4): 2743-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16080520

RESUMO

BACKGROUND: Tumor angiogenesis is considered a multi-pathway process, while p21(WAF1/CiP1) is a CDK inhibitor involved in cell division and survivaL Herein the tumor environment effect on endothelial p21(WAF1/Cip1) expression is examined. MATERIALS AND METHODS: The EA.hy 926 endothelial cell line and tumor-conditioned medium (TCM) from the MDA-MB-468 breast cancer cell line were used. Endothelial cells grown alone and in TCM were immunostained for p21(WAF1/Cip1) and analyzed by RT-PCR Forty-four cases of breast cancer and forty-three cases of normal breast tissue were immunostained for p21(WAF1/Cip1). RESULTS: Endothelial p21(WAF1/Cip1) is transcriptionally down-regulated under the influence of TCM. Moreover, it seems that breast cancer tumor endothelium does not express p21(WAF1/Cip1). CONCLUSION: P21(WAF1/Cip1) plays a major role in angiogenesis, since tumor cells seem to down-regulate endothelial p21(WAF1/Cip1), compared to endothelial cells grown in serum-free medium. The verification of the tissue culture experiment results by immunohistochemistry on tissue sections indicates p21(WAF1/Cip1) as a target of modern molecular therapy.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Ciclo Celular/biossíntese , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Processos de Crescimento Celular/fisiologia , Linhagem Celular , Linhagem Celular Tumoral , Meios de Cultivo Condicionados , Inibidor de Quinase Dependente de Ciclina p21 , Regulação para Baixo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Humanos , Imuno-Histoquímica , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Transcrição Gênica
17.
J Invest Dermatol ; 115(4): 719-25, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10998150

RESUMO

Basal cell carcinoma of the skin is the most common neoplasia in humans. Previous studies have shown the existence of allelic imbalance (loss of heterozygosity and microsatellite instability) in BCC on several human chromosomes. Chromosome region 9p21-p22 harbors the CDKN2a/p16INK4a, p19ARF, and p15INK4b tumor suppressor genes. To determine the contribution of these genes to the development of basal cell carcinomas we looked for evidence of allelic imbalance in 67 sporadic basal cell carcinoma specimens from Greek patients and screened 28 of them presenting loss of heterozygosity at 9p21-p22 for germline mutations in p16INK4a and p19ARF genes. Chromosome regions 17q21 and 17p13 were also screened for allelic imbalance in all the 67 basal cell carcinoma specimens. Overall, 69% (46 of 67) of the specimens displayed loss of heterozygosity in at least one microsatellite marker, whereas only six of the 67 (9%) exhibited microsatellite instability. For the 9p21-p22 locus the overall frequency of loss of heterozygosity reached 55% (37 of 67) and is the highest reported. The overall frequency of loss of heterozygosity for the 17q21 locus is 34% (22 of 64) and for the 17p13 locus is 11% (seven of 65). Two of the 28 loss of heterozygosity positive cases were heterozygous for a previously described polymorphism, Ala148Thr, in exon 2 of the CDKN2a gene. This is the first demonstration of polymorphism in the CDKN2a gene in human basal cell carcinomas. No sequence variation in exon 1beta of the p19ARF gene was found. Our results provide evidence of a significantly high occurrence of loss of heterozygosity for the 9p21-p22 locus; however, lack of p16INK4a/p19ARF mutation suggests that these genes seem not to be implicated by mutational inactivation in the development of basal cell carcinoma. Other(s), yet unidentified, tumor suppressor gene(s) located in this locus may be related to this specific type of skin cancer.


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/genética , Proteínas de Transporte/genética , Cromossomos Humanos Par 9 , Perda de Heterozigosidade , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Genes Supressores de Tumor/genética , Grécia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo Genético
18.
Anticancer Res ; 23(5b): 4339-45, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14666649

RESUMO

BACKGROUND: Approximately 20% of patients with breast cancer present with locally advanced disease without distant metastases. This phase II double-center trial aimed at investigating the activity of epirubicin (Farmorubicin)--mitoxantrone (Onkotrone/Novantrone) combination as first-line intra-arterial chemotherapy (IAC) in locally advanced breast cancer patients. PATIENTS AND METHODS: Thirty-six patients with locally advanced disease and no prior exposure to anthracyclines received the following regimen: epirubicin (Farmorubicin) 30 mg/mq and mitoxantrone (Onkotrone/Novantrone) 10 mg/mq by IAC short infusion on day 1, every 3 weeks for up to six cycles. Prior to IAC an arteriogram of subclavian, internal mammary and lateral thoracic arteries was obtained in all patients, followed by infusion of a blue dye solution into the arteries to determine the most appropriate vessel that supplies the tumor area. RESULTS: Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 25 patients (70%; 95%CI, 62% to 80%): 3 CR, 22 PR. Although three of the patients showed complete tumor regression, operative removal or toilet mastectomy became feasible in 25 patients since tumor shrinkage ranged over 75%. A total of 25 mastectomies were carried out for 36 patients. Four patients had bulky tumors (> 13 cm tumor diameter), while 8 patients had ulcerated tumors, two of which presented with complete infiltration of normal breast tissue. The median time to progression and median overall survival were 11 and 27 months, respectively. The time to local response was 3 weeks and time to mastectomy was 9 weeks. Transient neurological disorders developed in six patients and skin chemical burns with painful inflammatory reactions were encountered in ten patients. No systemic toxicity was observed in terms of bone marrow depression and hair loss. No cardiotoxicity was observed. In all specimens necrosis was reported (complete 3 cases, partial 16 and minimal 6). CONCLUSION: A combination of epirubicin (Farmorubicin) and mitoxantrone (Onkotrone/Novantrone) as IAC appears to be a safe and well tolerated treatment for locally advanced breast cancer without clinical evidence of distant metastases. When combined with surgery it offers interesting results in terms of local control and allows a high rate of mastectomies in otherwise inoperable cases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/cirurgia , Cateteres de Demora , Terapia Combinada , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Infusões Intra-Arteriais , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos
19.
Am Surg ; 66(8): 728-31, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10966027

RESUMO

The purpose of this study is to report the results of a tension-free repair technique using expanded polytetrafluoroethylene Gore-Tex Mycro Mesh in patients with inguinal hernias. Over 3 years, 104 patients have undergone the aforementioned procedure for 118 hernias (85 indirect and 33 direct) in our clinic. Ninety-three of the patients were operated for the first time, whereas the remainder of them were operated for hernia recurrence. Fourteen patients had bilateral hernias, and six had incarcerated ones. The median patient's age was 53 years. Eighty-three patients were operated under general and 21 under local or epidural anesthesia. One hundred and two patients were offered a one-day surgery procedure, but three were readmitted with wound infection. Two of these patients were conservatively cured, and the third was submitted to mesh removal. Two patients developed hematoma in the scrotum and were discharged a week later after the absorption of the hematoma. All of the patients except the one who was submitted to mesh removal returned to normal life within a week after the operation. During the follow-up period, none of our patients experienced hernia recurrence. Our results are in accordance with those of the world literature. We perform the tension-free hernia repair by using the expanded polytetrafluoroethylene mesh in our patients because we believe it is a safe procedure without significant postoperative morbidity and with no hernia recurrences.


Assuntos
Hérnia Inguinal/cirurgia , Politetrafluoretileno/uso terapêutico , Próteses e Implantes , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Técnicas de Sutura
20.
Am Surg ; 66(7): 679-82, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10917481

RESUMO

Repairing an incisional ventral hernia is a major challenge for a surgeon. The high recurrence rates observed during hernia repair by tissue approximation led to development of tension-free procedures by using prosthetic materials. The purpose of this study is to report the results of a tension-free repair technique using expanded polytetrafluoroethylene Gore-Tex Dual Mesh (Gore-Tex Soft Tissue Patch, W.L. Gore and Associates Inc, Flagstaff, AZ) in patients with primary or recurrent incisional ventral hernias. Over 3 years, 52 patients with incisional hernias have undergone this procedure in our clinic. Fourteen of them had recurrent hernias which had been primarily repaired by Mayo hernioplasty. Six of our patients had irreducible hernias preoperatively. Twenty-five patients had hernias on midline incisions, and the rest of them had hernias on transverse abdominal incisions. The median patient age was 65 years, and all were operated on under general anesthesia. The majority of the patients had 4 to 6 days of hospitalization. A subcutaneous seroma developed in eight patients. They all were treated by multiple paracentesis. Four of our patients experienced wound infection and were treated by mesh removal. None of the patients presented with cardiovascular or pulmonary complications. During the follow-up period, no other hernia recurrence, except the cases with mesh removal, has been noticed. The tension-free incisional hernia repair using expanded polytetrafluoroethylene mesh is, to our experience, a safe and easy procedure with no major morbidity or recurrence.


Assuntos
Hérnia Ventral/etiologia , Hérnia Ventral/cirurgia , Politetrafluoretileno , Telas Cirúrgicas , Procedimentos Cirúrgicos Operatórios/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA