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

Positive Selection Shaped the Convergent Evolution of Independently Expanded Kallikrein Subfamilies Expressed in Mouse and Rat Saliva Proteomes

We performed proteomics studies of salivas from the genome mouse (C57BL/6 strain) and the genome rat (BN/SsNHsd/Mcwi strain). Our goal was to identify salivary proteins with one or more of three characteristics that may indicate that they have been involved in adaptation: 1) rapid expansion of their gene families; 2) footprints of positive selection; and/or 3) sex-limited expression. The results of our proteomics studies allow direct comparison of the proteins expressed and their levels between the sexes of the two rodent species. Twelve members of the Mus musculus species-specific kallikrein subfamily Klk1b showed sex-limited expression in the mouse saliva proteomes. By contrast, we did not find any of the Rattus norvegicus species-specific kallikrein subfamily Klk1c proteins in male or female genome rat, nor transcripts in their submandibular glands. On the other hand, we detected expression of this family as transcripts in the submandibular glands of both sexes of Sprague-Dawley rats. Using the CODEML program in the PAML package, we demonstrate that the two rodent kallikrein subfamilies have apparently evolved rapidly under the influence of positive selection that continually remodeled the amino acid sites on the same face in the members of the subfamilies. Thus, although their kallikrein subfamily expansions were independent, this evolutionary pattern has occurred in parallel in the two rodent species, suggesting a form of convergent evolution at the molecular level. On the basis of this new data, we suggest that the previous speculative function of the species-specific rodent kallikreins as important solely in wound healing in males be investigated further. In addition to or instead of that function, we propose that their sex-limited expression, coupled with their rapid evolution may be clues to an as-yet-undetermined interaction between the sexes