Effectiveness of the angiogenesis inhibitor TNP-470 in reducing the growth of human neuroblastoma in nude mice inversely correlates with tumor burden.

Angiogenesis plays an important role in the growth and metastasis of malignant tumors. We have previously reported that in children with neuroblastoma (NB), tumor vascularity directly correlates with metastatic disease, MYCN amplification, and poor outcome. The angiogenesis inhibitor TNP-470 has been shown to reduce the rate of NB growth in rodents with macroscopic tumors without ultimately impacting survival. To investigate whether TNP-470 could more effectively inhibit NB growth in animals with a low tumor burden, we treated 30 nude mice with minimal disease with this angiogenesis inhibitor (supplied by TAP Pharmaceuticals, Inc.). Therapy was initiated before tumors were clinically evident after s.c. inoculation of 5 x 10(6) cells from the MYCN-amplified NB cell line NBL-W-N. TNP-470 was administered 3 days/week, and after 12 weeks of treatment, 53% of the treated mice remained tumor free, whereas 100% of the control mice developed tumors (P < 0.0001). To further assess the relationship between the efficacy of TNP-470 treatment and tumor burden, TNP-470 was also administered s.c., 3 days/week, to mice with clinically evident small (<400 mm3; n = 15) and large (>400 mm3; n = 11) tumors. For animals with small tumors, the mean rate of growth was significantly decreased in the treated mice compared to the controls (P = 0.02). In contrast, there was no difference in the mean rate of tumor growth between animals with large tumors treated with TNP-470 and controls (P = 0.64). Our studies demonstrate that the effectiveness of TNP-470 inversely correlates with tumor burden. We speculate that TNP-470 may most effectively inhibit NB tumor growth in children with a low tumor burden.

Revision of neoclassical facial canons in young adult Afro-Americans.

The validity of seven neoclassical facial canons was tested in 100 young, adult, Afro-American (A-A) males and females, and the results were compared with 103 North American Caucasians, producing the first reliable information about the differences of facial proportions in the two populations. Although the canons should not be regarded as strict directives in reconstructive and esthetic surgery, the data obtained from the study offered the first information about the facial proportion qualities of Afro-Americans in relation to the white population. In the absence of a detailed facial proportion study in A-As, the findings in canons can assist in planning the surgery. Comparison of the two populations revealed that the three sections of the facial profile were not equal in either population. In an A-A sample it showed the prevalence of the long lower face height also in relation to the height of the forehead. In horizontal canons of the orbital regions, the similarity between the two populations was demonstrated by the great frequency of intercanthal spaces to be wider than the length of the palpebral fissures [1]. The facial canons, including the nose width, relatively wider [2] in A-A than in white subjects, prompted the difference between A-A and Caucasians in frequency and degree in the dominant canon variations. The greater inclination of the nasal bridge than that of the medial longitudinal axis of the ear was a very frequent canon variation in both populations. Generally, the frequency of valid canons was greatly surpassed by their variations.

Surface anatomy of the face in Down's syndrome: linear and angular measurements in the craniofacial regions.

Measurements (23 projective linear, 2 angular) taken in the 6 craniofacial regions of 127 patients with Down's syndrome showed that 63.1% (1,836 of 2,908) were within normal limits and 36.9% (1,072) were outside them. Abnormal measurements were subnormal in 90.8% (973) and supernormal in 9.2% (99). All statistical summaries were based on z scores (adjusting for age and sex differences) classified into a small number of ranges to yield a simplified frequency distribution for each measurement. The purpose of the study was to identify the measurements closest to normal and those indicating the most severe degrees of sub- or supernormality. Approximately a quarter of normal measurements were classified as optimal, and half the subnormal or supernormal measurements were classified as severe. Intercanthal width had the highest frequency of optimal measurements (93.7%, 119 of 127), head circumference the smallest (28.6%, 36 of 126). Knowledge of the frequency of extreme abnormalities in the craniofacial regions will help during visual examination of patients with Down's syndrome. This study found the highest percentage of severely subnormal measurements in the orbital region (57.8%, 74 of 128) and the smallest in the labio-oral region (32.7%, 16 of 49). The measurement with the highest proportion of severely subnormal to all subnormal values was the palpebral fissure length (68%, 51 of 75), and the nose width had the smallest proportion (14.3%, 1 of 7).