Vascular endothelial growth factor-A and Poly(A) binding protein-interacting protein 2 expression in human head and neck carcinomas: correlation and prognostic significance

Vascular endothelial growth factor-A (VEGF-A) has been demonstrated to play an important role in tumour angiogenesis and to influence prognosis in many cancers. However its prognostic value in head and neck squamous cell carcinomas (HNSCCs) remains controversial. Therefore, we investigated the clinical relevance of VEGF-A expression in HNSCCs and analysed whether its expression was associated with PAIP2 protein levels, a VEGF-A mRNA-binding partner that strongly regulates VEGF-A expression in tissue culture. We determined the correlation of VEGF-A and PAIP2 protein levels, quantitatively evaluated in tumour tissue homogenates from 54 patients with HNSCC, to clinicopathological parameters. We showed that VEGF-A expression in HNSCC is correlated to the stage of tumour differentiation (P=0.050) and is an independent prognostic factor for progression-free survival (P=0.001) and overall survival (P=0.0004). In a pharynx carcinoma cell line, we demonstrated by RNA interference that VEGF-A expression is closely controlled by PAIP2. Moreover, in human HNSCCs, VEGF-A expression is significantly correlated to PAIP2 protein levels (P=0.0018). Nevertheless, PAIP2 expression is associated with neither clinicopathological factors nor patient's survival. Our data suggest that, in contrast to PAIP2 protein levels, which are unrelated to tumour prognosis, VEGF-A expression could serve as a prognostic marker in head and neck cancer and may be helpful for targeted therapies

Ternary combination of irinotecan, fluorouracil-folinic acid and oxaliplatin: results on human colon cancer cell lines

A marked antitumour efficacy is currently obtained by oxaliplatin (LOHP)–fluorouracil (FU)–folinic acid (FA) combination and by CPT11–FU–FA combination. Logically, the triple association LOHP, CPT11 and FUFA will be soon tested in cancer patients. The aim of the present study was to compare two schedules combining SN38 (the active metabolite of CPT11, irinotecan) with FU–FA and LOHP. The two schedules differed by the SN38 position. The relative contribution of each drug in the resulting global cytotoxicity was evaluated. Two human colon cancer cell lines were used (WIDR and SW620 both p53 mutated). LOHP plus FA were applied for 2 h, just before a 48 h FU exposure. The SN38 sequence was applied for 24 h, starting either 48 h before LOHP-FA (schedule A), or just after LOHP-FA exposure (schedule B). Cytotoxicity was assessed by the 3-(4,5-demethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test and drug interactions were analysed according to the Chou and Talalay method, based on the computation of a combination index (CI). The SN38 position significantly induces a shift from additivity-antagonism when SN38 was applied after LOHP, towards additivity-synergism when SN38 was applied first (P = 0.03). The relative contribution (RC) of each drug in the overall cytotoxicity of the triple combination was defined as the drug concentration giving 50% cell lethality (IC 50) of the double association without that drug divided by the IC 50 of the triple association. Whatever the SN38 position, the larger contribution was made by LOHP (median RC = 2.4) and the smaller by SN38 (median RC = 1.1). In addition, the contribution of FUFA was improved when SN38 was applied first (median RC = 2.2) as compared to the opposite schedule (median RC = 1.2). Results were in agreement between the two explored cell lines. The present data should be taken into account when establishing the rationale of future trials combining CPT11, LOHP and FU–FA. © 2001 Cancer Research Campaign http://www.bjcancer.co

Actividad fungicida / fungistática in vitro del fosfito de manganeso contra hongos patógenos habitantes del suelo con soja

Carmona, Marcelo Aníbal. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Vegetal. Cátedra de Fitopatología. Buenos Aires, Argentina.Simonetti, Ester. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola. Buenos Aires, Argentina.Ravotti, Maximiliano Ezequiel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Vegetal. Cátedra de Fitopatología. Buenos Aires, Argentina.Scandiani, M. M. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Referencia de Micología (CEREMIC). Rosario, Argentina.Luque, A. G. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Referencia de Micología (CEREMIC). Rosario, Argentina.Formento, Angela Norma. Instituto Nacional de Tecnología Agropecuaria (INTA). Centro Regional Buenos Aires Norte. Estación Experimental Agropecuaria Delta del Paraná (EEA Delta del Paraná). Buenos Aires, Argentina.Sautua, Francisco J. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Vegetal. Cátedra de Fitopatología. Buenos Aires, Argentina.265-269Soybean root and stem rots caused by soil - borne pathogens are diseases commonly found in soybean fields, and one of the most important causes of crop losses. In the present study, the mycelial sensitivity of Fusarium virguliforme, F. tucumaniae, Sclerotinia sclerotiorum and Macrophomina phaseolina was evaluated on potato dextrose agar media (25 mL) supplemented with different concentrations of manganese phosphite (MnPhi) diluted in water (0, 25, 37.5, 50, 100, 200, 300, 400, 500, 800 and 1000 μg/mL). Mycelial growth sensitivity was analyzed using logarithmic linear regression analysis. The MnPhi concentration needed to inhibit 50% of the mycelial growth (IC50) ranged from 105 μg/mL (Fusarium spp.) to 409 μg/mL (M. phaseolina). Sclerotia were completely inhibited at 500 μg/mL. The results of our study represent the first report on the direct in vitro fungicidal/fungistatic action of MnPhi against fungi that are causal agents of soil - borne diseases