Blood vessel density correlates with the effects of targeted intra-arterial carboplatin infusion with concurrent radiotherapy for squamous cell carcinomas of the oral cavity and oropharynx.

Our aim was first to evaluate the association between blood vessel density (BVD) and free platinum concentration in experimentally induced tumours in rabbits. We also investigated the association between tumour BVD and the clinical response of patients who had undergone targeted carboplatin intra-arterial (i.a.) chemoradiotherapy. VX2 carcinoma cells were transplanted into 46 inbred female Japanese white rabbits. In the i.a. group, carboplatin was infused into the lingual artery, and in the intravenous (i.v.) group, carboplatin was infused through the auricular vein. In the clinical study, we evaluated 19 patients with squamous cell carcinomas of the oral cavity and oropharynx, who had undergone targeted carboplatin i.a. chemoradiotherapy and had been administered i.a. tegafur/uracil chemotherapy before surgery. We quantified angiogenesis in both studies. Increased BVD was associated with a higher free platinum concentration in the tumour region in the i.a. group of rabbits. In the clinical study, using multivariate logistic regression analysis, only the BVD was related independently to the treatment effect. Therefore, BVD is a valid predictor of the effects of i.a. targeted carboplatin chemotherapy and concurrent radiotherapy for treating human oral and oropharyngeal squamous cell carcinomas.

Gene therapy for HIV-1 infection: are lethal genes a valuable tool?

At present, virus replication is quite efficiently blocked by highly active antiretroviral therapy (HAART). However current HAART therapies still have important limitations that compromise in the long term the health of the patient. This failure is due to the existence of viral sanctuaries of replication-competent HIV-1, which can persists for the whole life. Two main strategies of HIV-1 gene therapy have been tried. One is based in the rationale of killing the infected cells before the virus can produce infective particles and the other strategy is to protect the cell from the virus. The first strategy uses lethal genes that are expressed in response to the expression of a HIV-1 provirus. Although technical limitations and safety concerns have limited the use of this approach in the last years, recent development of efficient lentiviral vectors and the need of the elimination of the latently infected cells are reasons to reconsider and come back to use this approach. Elimination of latently infected cells would also represent a perfect complement of the HAART therapy and may represent a hope in the long term for the development of a real cure of this infection.

AUC of Calvert's formula in targeted intra-arterial carboplatin chemoradiotherapy for cancer of the oral cavity.

We investigated whether intra-arterial administration of carboplatin using Calvert's formula is useful for avoiding thrombocytopenia in targeted chemoradiotherapy in patients with squamous cell cancer of the oral cavity and oropharynx. Carboplatin was infused intra-arterially under digital subtraction angiography in 28 patients. In the first group of patients, the dose of carboplatin was calculated according to the body surface area (BS group). In the second group, the dose was calculated using Calvert's formula (AUC group). The value for AUC (area under concentration vs time curve; mg ml(-1) min(-1)) in the formula was set at 4.5. All patients received concurrent radiotherapy (30 Gy) and were given oral tegafur-uracil (UFT((R)), 400-600 mg day(-1)). The AUC group showed a significantly lower percentage platelet reduction than the BS group (49.0+/-22.0 vs 65.1+/-23.2%; P=0.045) and also tended to have a higher platelet nadir count (10.9+/-4.2 vs 8.4+/-5.8 x 10(4); P=0.27) without reducing the antitumour effect. The value of 4.5 for target AUC is recommended clinically. However, AUC of Calvert's formula could not predict thrombocytopenia associated with intra-arterial chemoradiotherapy due to the variability of the actual AUC.

Tratamiento de las pseudoartrosis y retardos de consolidación mediante ondas de choque extracorpóreas / Treatment of nonunion and delayed consolidation with extracorporeal shockwaves

Objetivo: Evaluar la efectividad de las ondas de choque extracorpóreas de alta energía en el tratamiento de las pseudoartrosis. Pacientes: Entre los años 1998 y 1999 se trataron 20 pseudoartrosis (19 pacientes). La edad media fue 42 años. El promedio de intervenciones antes del tratamiento con ondas de choque fue 1,3. Tras la aplicación de ondas de choque, los pacientes fueron inmovilizados con yeso si existía duda sobre la estabilidad de la fractura. El seguimiento medio de los pacientes fue 15 meses. Resultados: La consolidación se obtuvo en 10 pseudoartrosis (50 por ciento), detectando una tendencia para mayor riesgo de fracaso en pseudoartrosis de miembro superior respecto a miembro inferior (RR = 2,25; i.c.95 por ciento 0,92-5,50). Conclusiones: El tratamiento con ondas de choque es un método eficaz para el tratamiento de las pseudoartrosis. Aunque ha demostrado una tasa de éxitos moderada, es una técnica no invasiva, con pocas complicaciones, de escasa importancia, y no altera la reserva ósea o la cobertura de partes blandas, permitiendo así la aplicación de ulteriores tratamientos (AU)

Fas antigen expression and outcome of oral squamous cell carcinoma.

Paraffin sections of biopsy specimens obtained from 46 patients with oral squamous cell carcinomas were stained with both anti-peptide antibody against human Fas antigen and monoclonal mouse antibody against human proliferating cell nuclear antigen (PCNA). The patients received chemotherapy with a combination of carboplatin and peplomycin sulfate or mitomycin C and peplomycin sulfate before surgery. The relation between the expression of Fas antigen and the clinical features of each case was examined. The correlation between PCNA and Fas antigen expression was also studied. The mean PCNA labeling index of the 22 Fas-negative cases was 46.9%, which was significantly higher than that of the 24 Fas-positive cases (39.5%). Strong correlations were found between the expression of Fas antigen and the response to chemotherapy, tumor recurrence, and survival. The Fas-negative group had only a minor response to chemotherapy and a poor outcome, whereas the Fas-positive group had a better response to chemotherapy and a good outcome. Although lymph node metastasis was significantly related to survival, there was no correlation between Fas antigen expression and lymph node metastasis. The Kaplan-Meier survival curve of patients positive for Fas antigen was significantly better than that of patients negative for Fas antigen. Our results suggest that Fas antigen expression is an independent predictor of outcome whose usefulness should be evaluated in prospective studies.