Concentration-Dependent, Size-Independent Toxicity of Citrate Capped AuNPs in Drosophila melanogaster

The expected potential benefits promised by nanotechnology in various fields have led to a rapid increase of the presence of engineered nanomaterials in a high number of commercial goods. This is generating increasing questions about possible risks for human health and environment, due to the lack of an in-depth assessment of the physical/chemical factors responsible for their toxic effects. In this work, we evaluated the toxicity of monodisperse citrate-capped gold nanoparticles (AuNPs) of different sizes (5, 15, 40, and 80 nm) in the model organism Drosophila melanogaster, upon ingestion. To properly evaluate and distinguish the possible dose- and/or size-dependent toxicity of the AuNPs, we performed a thorough assessment of their biological effects, using two different dose-metrics. In the first approach, we kept constant the total surface area of the differently sized AuNPs (Total Exposed Surface area approach, TES), while, in the second approach, we used the same number concentration of the four different sizes of AuNPs (Total Number of Nanoparticles approach, TNN). We observed a significant AuNPs-induced toxicity in vivo, namely a strong reduction of Drosophila lifespan and fertility performance, presence of DNA fragmentation, as well as a significant modification in the expression levels of genes involved in stress responses, DNA damage recognition and apoptosis pathway. Interestingly, we found that, within the investigated experimental conditions, the toxic effects in the exposed organisms were directly related to the concentration of the AuNPs administered, irrespective of their size

Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study.

International audienceBACKGROUND: The role of chemoradiation with systemic chemotherapy compared with chemotherapy alone in locally advanced pancreatic cancer (LAPC) is uncertain. PATIENTS AND METHODS: One hundred and nineteen patients with LAPC, World Health Organization performance status of zero to two were randomly assigned to either the induction CHRT group (60 Gy, 2 Gy/fraction; concomitant 5-fluorouracil infusion, 300 mg/m(2)/day, days 1-5 for 6 weeks; cisplatin, 20 mg/m(2)/day, days 1-5 during weeks 1 and 5) or the induction gemcitabine group (GEM: 1000 mg/m(2) weekly for 7 weeks). Maintenance gemcitabine (1000 mg/m(2) weekly, 3/4 weeks) was given in both arms until disease progression or toxicity. RESULTS: Overall survival was shorter in the CHRT than in GEM arm [median survival 8.6 (99% confidence interval 7.1-11.4) and 13 months (8.7-18.1), P = 0.03]. One-year survival was, respectively, 32% and 53%. These results were confirmed in a per-protocol analysis for patients who received 75% or more of the planned dose of radiotherapy. More overall grades 3-4 toxic effects were recorded in the CHRT arm, both during induction (36 versus 22%) and maintenance (32 versus 18%). CONCLUSION: This intensive induction schedule of CHRT was more toxic and less effective than gemcitabine alone

Locally advanced unresectable pancreatic cancer: Induction chemoradiotherapy followed by maintenance gemcitabine versus gemcitabine alone: Definitive results of the 2000-2001 FFCD/SFRO phase III trial

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Multicentre randomised phase III trial comparing Tamoxifen alone or with Transarterial Lipiodol Chemoembolisation for unresectable hepatocellular carcinoma in cirrhotic patients (Fédération Francophone de Cancérologie Digestive 9402)

International audienceThe FFCD 9402 multicentre phase III trial was designed to compare the effects of the combination of Transarterial Lipiodol Chemoembolisation (TACE) and tamoxifen with tamoxifen alone on overall survival and quality of life in the palliative treatment of hepatocellular carcinoma with cirrhosis. From 1995 to 2002, 138 patients were randomised between the two groups. One hundred and twenty three patients were eligible including 61 in the Tamoxifen group and 62 in the TACE group. Baseline characteristics were similar: Child-Pugh class A: 70%, alcoholic cirrhosis: 76%, Okuda stage I: 71%, multinodular tumour: 70% and segmental portal vein thrombosis: 10%. At 2 years, the overall survival was 22% and 25% in the Tamoxifen and TACE groups (P = .68), respectively. Multivariate analysis identified four independent prognostic factors for survival: α-fetoprotein (AFP) &gt; 400 ng/mL (P = .008), abdominal pain (P = .011), hepatomegaly (P = .023) and Child-Pugh score (P = .032). The Spitzer Index level assessing the quality of life during follow-up did not differ between the two groups (P = .70). Amongst patients with stage Okuda I, the 2-year overall survival was 28% in the Tamoxifen group and 32% in the TACE group (P = .58). In this subgroup, two prognostic factors were statistically significant for survival: AFP &gt; 400 ng/mL (P = .004) and Spitzer Index (P = .013) as shown by multivariable analysis.In conclusion, this study suggests that TACE improves neither the survival nor the quality of life in patients with HCC and cirrhosis.</p

[Locally advanced unresectable pancreatic cancer: Induction chemoradiotherapy followed by maintenance gemcitabine versus gemcitabine alone: Definitive results of the 2000-2001 FFCD/SFRO phase III trial].

International audiencePURPOSE: To compare chemoradiation with systemic chemotherapy to chemotherapy alone in locally advanced pancreatic cancer. PATIENTS AND METHODS: One hundred and nineteen patients with locally advanced pancreatic cancer, with World Health Organization performance status of zero to two were randomly assigned to either the induction chemoradiation group (60 Gy, 2 Gy/fraction; concomitant 5-fluoro-uracil infusion, 300 mg/m(2) per day, days 1-5 for 6 weeks; cisplatin, 20 mg/m(2) per day, days 1-5 during weeks 1 and 5) or the induction gemcitabine group (GEM: 1000 mg/m(2) weekly for 7 weeks). Maintenance gemcitabine (1000 mg/m(2) weekly, 3/4 weeks) was given in both arms until disease progression or toxicity. RESULTS: Overall survival was shorter in the chemoradiation than in the gemcitabine arm (median survival 8.6 [99% confidence interval 7.1-11.4] and 13 months [8,9,9-18], p=0.03). One-year survival was, respectively, 32 and 53%. These results were confirmed in a per-protocol analysis for patients who received 75% or more of the planned dose of radiotherapy. More overall grades 3-4 toxic effects were recorded in the chemoradiation arm, both during induction (36 versus 22%) and maintenance (32 versus 18%). CONCLUSION: This intensive induction schedule of chemoradiation was more toxic and less effective than gemcitabine alone