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In this study we demonstrate that prothrombin activates the cell proliferation of the lung adenocarcinoma A549 cells. The A549 cell expresses factor Xa-like prothrombinase activity on its surface and prothrombin was converted to thrombin on the cell surface. Furthermore, thrombin induced the activation of PKC, increased [Ca2+]i and potentiated MAP kinase activity through thrombin receptor. The mitogenic activity of prothrombin and the conversion to thrombin were completely abolished by the synthetic coagulation factor Xa inhibitor, DX9065a. These findings suggest that DX9065a is an effective agent for a therapeutic strategy against cancer itself and prothrombotic complications associated with malignancy.

Mutations in p53, a tumor suppressor gene, are one of the most common genetic lesions of human cancers. The relationship between pS3 gene mutation and ultraviolet (UV) light has been demonstrated in skin cancers of sun-exposed sites. In this study, genomic DNA from 12 skin cancers was screened for mutations in exons 5 to 9 of this gene using the polymerase chain reaction — single strand conformation polymorphism (PCR-SSCP) analysis followed by DNA sequencing. DNA samples were obtained from 8 basal cell carcinomas (BCCs): 1 from an organoid nevus, 1 from a patient with basal cell nevus syndrome, 1 from a patient with xeroderma pigmentosum, and 1 from a recurrent and 4 from primary sporadic lesions on actinic damaged skin, and from 4 squamous cell carcinomas (SCCs): 1 from a burn scar, 1 from a patient with epidermodysplasia verruciformis, and 2 from actinic keratosis. Mutation of the p53 gene was detected in only 1 case of SCC which had arisen from actinic keratosis. The mutation occurred at codon 159 in exon S with a GCC to CCC base-pair substitution resulting in an amino acid change of alanine to proline. This mutation does not correspond to results of UV mutagenesis studies reported in the literature. Our findings imply that, although p53 gene mutation and UV exposure play an important role in the carcinogenesis of some skin cancers, they are not crucial, especially in skin cancers that develop from underlying skin disorders.

To investigate the effect of obesity and hypertension on left ventricular (LV) mass in children, we performed echocardiography and measured the height, weight, and blood pressure of 267 healthy children (145 boys and 122 girls) aged 12 years. The percentage of body fat was estimated using bioelectric impedance to derive the total adipose weight and lean body weight. End-diastolic measurements of LV parameters were obtained from M-mode echocardiograms. The LV mass was calculated by using the formula of Devereux et al. A strong positive correlation was demonstrated between non-normalized LV mass and height or other measures of body size. Systolic blood pressure was weakly correlated with non-normalized LV mass in boys. The impact of height on LV mass differed between boys and girls. Thus, different allometric formulas to normalize the LV mass for height were determined, using the height to the 3.1 and 1.9 powers for boys and girls, respectively. Regression analysis revealed that only total adipose weight affected the normalized LV mass, and that the effect of total adipose weight was greater in girls than in boys. The obese children had a significantly greater normalized LV mass than the nonobese children. The increase in the LV mass due to obesity appeared to be eccentric, because of the lack of an association between the indices of obesity and relative wall thickness. Our data indicate that appropriate normalization of LV mass is necessary for each study population, and that LV hypertrophy due to obesity begins in childhood.