A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling

This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m−2 plus doxorubicin 60 mg m−2 (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m−2 plus cisplatin 70 mg m−2 (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with ⩾73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy

Phase I/II trial of doxorubicin and fixed dose-rate infusion gemcitabine in advanced soft tissue sarcomas: a GEIS study

The aim of the study was to determine the dose-limiting toxicity and maximum tolerated dose of a first-line combination of doxorubicin and gemcitabine in adult patients with advanced soft tissue sarcomas and to explore its activity and toxicity, and the presence of possible interactions between these agents. Patients with measurable disease were initially treated with doxorubicin 60 mg m−2 by i.v. bolus on day 1 followed by gemcitabine at 800 mg m−2 over 80 min on days 1 and 8, every 21 days. Concentrations of gemcitabine and 2′,2′-difluorodeoxyuridine in plasma, and gemcitabine triphosphate levels in peripheral blood mononuclear cells were determined during 8 h after the start of gemcitabine infusion. Myelosuppression and stomatitis were limiting toxicities, and the initial dose level was applied for the Phase II trial, where grade 3–4 granulocytopenia occurred in 70% of patients, grade 3 stomatitis in 46% and febrile neutropenia in 20%. Objective activity in 36 patients was 22% (95% CI: 9–35%), and a 50% remission rate was noted in leiomyosarcomas. Administration of doxorubicin preceding gemcitabine significantly reduced the synthesis of gemcitabine triphosphate. Clinical activity, similar to that of single-agent doxorubicin, and the toxicity encountered do not justify further studies with this schedule of administration

Agroforesterie et services écosystémiques en zone tropicale

Respectueux de l’environnement et garantissant une sécurité alimentaire soutenue par la diversification des productions et des revenus qu’ils procurent, les systèmes agroforestiers apparaissent comme un modèle prometteur d’agriculture durable dans les pays du Sud les plus vulnérables aux changements globaux. Cependant, ces systèmes agroforestiers ne peuvent être optimisés qu’à condition de mieux comprendre et de mieux maîtriser les facteurs de leurs productions. L’ouvrage présente un ensemble de connaissances récentes sur les mécanismes biophysiques et socio-économiques qui sous-tendent le fonctionnement et la dynamique des systèmes agroforestiers. Il concerne, d’une part les systèmes agroforestiers à base de cultures pérennes, telles que cacaoyers et caféiers, de régions tropicales humides en Amérique du Sud, en Afrique de l’Est et du Centre, d’autre part les parcs arborés et arbustifs à base de cultures vivrières, principalement de céréales, de la région semi-aride subsaharienne d’Afrique de l’Ouest. Il synthétise les dernières avancées acquises grâce à plusieurs projets associant le Cirad, l’IRD et leurs partenaires du Sud qui ont été conduits entre 2012 et 2016 dans ces régions. L’ensemble de ces projets s’articulent autour des dynamiques des systèmes agroforestiers et des compromis entre les services de production et les autres services socio-écosystémiques que ces systèmes fournissent

A pathological study of experimental long-standing Schistosoma bovis infection in sheep

6 pages, 2 figures, 1 table.-- PMID: 9839209 [PubMed].The pathological response of sheep to two dose levels (400 or 10,000 cercariae) of Schistosoma bovis was evaluated 24 weeks after infection. The results confirmed that a single low or high dose causes lesions in the liver and intestine, and that the lungs, lymph nodes, pancreas and abomasum are affected in sheep given a single high dose. In addition, the study showed that pathological changes (mainly a granulomatous inflammatory reaction) were induced not only by eggs but also by adult worms, and that their severity was in general related to the dose of S. bovis. Hoeppli reaction product, observed on the surface of adult schistosomes in some parasitic granulomas, showed no immunoreaction for IgG, IgA or IgM.Peer reviewe

Local immune response to experimental ovine dicrocoeliosis

1 page.-- Contributed to: VIII European Multicolloquium of Parasitology (Warszawa, Poland, Sep. 2000).-- Published by: Acta ParasitologicaTo investigate the phenotypic expression of inflammatory cells in liver and hepatic lymph nodes of lambs experimentally infected with Dicrocoelium dendriticum.(Study supported by the CICYT: AGF92-0588, AGF96-0416).Peer reviewe

Comparison of histopathological lesions induced by single and double infection with Fasciola hepatica and Schistosoma bovis in sheep

2 pages.-- Contributed to: Abstracts of the 13th European Congress on Veterinary Pathology (Edinburgh, Gran Bretaña, Sep, 1995).Cross-resistance between Fasciola hepatica and Schistosoma bovis has previously been demonstrated in calves and sheep. Both parasites are common in some regions of Spain and natural infections are frequently diagnosed...Peer reviewe

Immunohistochemical study in experimental ovine dicrocoeliosis

1 page.-- Contributed to: 18th International Conference of the World Association for the Advancement of Veterinary Parasitology (Stresa, Italia, Aug 26-30, 2001).Study supported by CICYT (AGF96-04l6, IFD97-1313- C02).Peer reviewe

Lesiones hepáticas en corderos infectados experimentalmente con Dicrocoelium dendriticum

Trabajo presentado al V Congreso Ibérico de Parasitología (Évora, Portugal, octubre de 1997).Se ha realizado un estudio histopatológico del hígado de corderos infectados experimentalmente con metacercarias del Digenea Dicrocoelium dendriticum (Rudolphi, 1819), Looss, 1899. Para ello se utilizaron 32 corderos de raza churra, de 4 meses de edad al comienzo del experimento.Estudio financiado por la CICYT, Proyectos n° AGF92-0588 y u° AGF96-0416Peer reviewe