Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin

The purpose of this study was to evaluate by a retrospective analysis of 53 patients the efficacy of chemotherapy combining etoposide and cisplatin in the treatment of neuroendocrine tumours. The regimen was a combination of etoposide 100 mg m–2 day–1 for 3 days and cisplatin 100 mg m–2 on day 1, given by 2-h intravenous infusion, administered every 21 days. Twelve patients had a well-differentiated and 41 a poorly differentiated neuroendocrine tumour. Toxicity of treatment was assessed in 50 patients and efficacy in 52 patients. Among the 11 patients with a well-differentiated tumour evaluable for tumoural response, only one (9.4%) had a partial response for 8.5 months. Forty-one patients with a poorly differentiated tumour showed an objective response rate of 41.5% (four complete and 13 partial responses); the median duration of response was 9.2 months, the median overall survival 15 months and the median progression-free survival 8.9 months. Haematological grade 3–4 toxicity was observed in 60% of the cases with one treatment-related death, digestive grade 3–4 toxicity in 40% and grade 3 alopecia was constant. No severe renal, hearing and neurological toxicities were observed (grade 1 in 6%, 14%, 72% respectively and no grade >1). We confirm that poorly differentiated neuroendocrine tumours are chemosensitive to the etoposide plus cisplatin combination. However, the prognosis remains poor with a 2-year survival lower than 20% confirming that new therapeutic strategies have to be developed. © 1999 Cancer Research Campaig

Mechanism of trifluorothymidine potentiation of oxaliplatin-induced cytotoxicity to colorectal cancer cells

Oxaliplatin (OHP) is an anticancer agent that acts by formation of Platinum-DNA (Pt-DNA) adducts resulting in DNA-strand breaks and is used for the treatment of colorectal cancer. The pyrimidine analog trifluorothymidine (TFT) forms together with a thymidine phosphorylase inhibitor (TPI) the anticancer drug formulation TAS-102, in which TPI enhances the bioavailability of TFT in vivo. In this in vitro study the combined cytotoxic effects of OHP with TFT were investigated in human colorectal cancer cells as a model for TAS-102 combinations. In a panel of five colon cancer cell lines (WiDr, H630, Colo320, SNU-C4 and SW1116) we evaluated the OHP-TFT drug combinations using the multiple drug–effect analysis with CalcuSyn software, in which the combination index (CI) indicates synergism (CI<0.9), additivity (CI=0.9–1.1) or antagonism (CI>1.1). Drug target analysis was used for WiDr, H630 and SW1116 to investigate whether there was an increase in Pt-DNA adduct formation, DNA damage induction, cell cycle delay and apoptosis. Trifluorothymidine combined with OHP resulted in synergism for all cell lines (all CI<0.9). This was irrespective of schedule in which either one of the drugs was kept at a constant concentration (using variable drug ratio) or when the two drugs were added in a 1 : 1 IC50-based molar ratio. Synergism could be increased for WiDr using sequential drug treatment schedules. Trifluorothymidine increased Pt-DNA adduct formation significantly in H630 and SW1116 (14.4 and 99.1%, respectively; P<0.05). Platinum-DNA adducts were retained best in SW1116 in the presence of TFT. More DNA-strand breaks were induced in SW1116 and the combination increased DNA damage induction (>20%) compared with OHP alone. Exposure to the drugs induced a clear cell-cycle S-phase arrest, but was dose schedule and cell line dependent. Trifluorothymidine (TFT) and OHP both induced apoptosis, which increased significantly for WiDr and SW1116 after TFT–OHP exposure (18.8 and 20.6% respectively; P<0.05). The basal protein levels of ERCC1 DNA repair enzyme were not related to the DNA damage that was induced in the cell lines. In conclusion, the combination of TFT with the DNA synthesis inhibitor OHP induces synergism in colorectal cancer cells, but is dependent on the dose and treatment schedule used

Avaliação da qualidade de frutos de café atacados por Ceratitis capitata (Wiedemann, 1824) (Diptera: Tephritidae) Evaluation of the quality of coffee fruit attacked by Ceratitis capitata (Wiedemann, 1824) (Diptera: Tephritidae)

Foram usadas plantas de Coffea arabica L., variedade Catuaí Vermelho, localizadas no Campus da Escola Superior de Agricultura "Luiz de Queiroz" - USP, Piracicaba,SP, para avaliação dos danos que Ceratitis capitata (Wied., 1824) pode causar aos frutos do cafeeiro. Os resultados mostraram que o ataque de C. capitula não causou queda prematura dos frutos, mas aumentou a queda de cerejas e foram encontradas, fortes evidências, com base na atividade da enzima polifenol oxidase e lixiviação de potássio, que cerejas atacadas podem produzir bebida de café de qualidade inferior.<br>The present work was carried out using trees of Coffea arabica L. variety Red Catuaí grown at Escola Superior de Agricultura "Luiz de Queiroz" - Campus of the University of São Paulo, Piracicaba,SP. The objective was to estimate damages that Ceratitis capitata (Wied., 1824) can cause to coffee fruits. The results showed that C.capitata did not cause premature fruit fall, but it increased berry fall. The activity of the enzyme polyphenol oxidase and potassium lixiviatiou give strong evidences that atacked coffee beans produce coffee beverage of inferior quality

Transport and retention of microparticles in packed sand columns at low and intermediate ionic strengths: experiments and mathematical modeling

Functional relationships correlating particle filtration coefficients and porewater ionic strength are herein proposed and validated, based on deposition experiments of micrometer-sized particles onto siliceous sand. Experiments were conducted using one-dimensional laboratory columns and stable monodisperse aqueous suspensions of negatively charged latex particles with a mean size of 1.90 lm. The role of ionic strength was systematically investigated and six different monovalent salt concentrations (1, 3, 10, 30, 100, 300 mM) were employed by addition of sodium chloride to the aqueous solution. A mathematical advection-dispersiondeposition transport model was adopted assuming that attachment and detachment of particles in the porous medium are concurrent mechanisms of particle filtration, and including a Langmuir-type blocking function to account for availability in deposition sites. The system of equations modeling colloid transport was solved numerically. Attachment rate and detachment rate coefficients were thereby determined for each employed ionic strength, as well as a blocking coefficient in the form of a maximum particle concentration in the solid phase. Therefore, functional relationships expressing the dependence of these coefficients on ionic strength were proposed, based on literature findings and present experimental observations. The existence of a critical salt deposition concentration (and release concentration) separating a favorable attachment (and detachment) regime from an unfavorable condition is assumed. In respect to the blocking coefficient, a power-law dependence on ionic strength is hypothesized. The proposed functional relationships proved adequate to reproduce the coefficient trends extrapolated from data fitting by the transport model. They may represent a powerful tool to describe and predict microparticle mobility in saturated porous media if embedded a priori in the related mathematical transport model