BACKGROUND An accurate staging system is crucial for cancer management. Evaluations for continual suitability and improvement are needed as staging and treatment methods evolve. METHODS This was a retrospective study of 1609 patients with nasopharyngeal carcinoma investigated by magnetic resonance imaging, staged with the 7th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system, and irradiated by intensity-modulated radiotherapy at 2 centers in Hong Kong and mainland China. RESULTS Among the patients without other T3/T4 involvement, there were no significant differences in overall survival (OS) between medial pterygoid muscle (MP)±lateral pterygoid muscle (LP), prevertebral muscle, and parapharyngeal space involvement. Patients with extensive soft tissue involvement beyond the aforementioned structures had poor OS similar to that of patients with intracranial extension and/or cranial nerve palsy. Only 2% of the patients had lymph nodes>6cm above the supraclavicular fossa (SCF), and their outcomes resembled the outcomes of those with low extension. Replacing SCF with the lower neck (extension below the caudal border of the cricoid cartilage) did not affect the hazard distinction between different N categories. With the proposed T and N categories, there were no significant differences in outcome between T4N0-2 and T1-4N3 disease. CONCLUSIONS After a review by AJCC/UICC preparatory committees, the changes recommended for the 8th edition include changing MP/LP involvement from T4 to T2, adding prevertebral muscle involvement as T2, replacing SCF with the lower neck and merging this with a maximum nodal diameter>6 cm as N3, and merging T4 and N3 as stage IVA criteria. These changes will lead not only to a better distinction of hazards between adjacent stages/categories but also to optimal balance in clinical practicability and global applicability.

Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles in mammalian embryogenesis. Nevertheless, it has long been recognized that overexposure to vitamin A or retinoic acid causes widespread teratogenesis in rodents as well as humans. Although it has a short half-life, exposure to high levels of retinoic acid can disrupt development of yet-to-be formed organs, including the metanephros, the embryonic organ which normally differentiates into the mature kidney. Paradoxically, it is known that either an excess or a deficiency of retinoic acid results in similar malformations in some organs, including the mammalian kidney. Accordingly, we hypothesized that excess retinoic acid is teratogenic by inducing a longer lasting, local retinoic acid deficiency. This idea was tested in an established in vivo mouse model in which exposure to excess retinoic acid well before metanephric rudiments exist leads to failure of kidney formation several days later. Results showed that teratogen exposure was followed by decreased levels of Raldh transcripts encoding retinoic acid-synthesizing enzymes and increased levels of Cyp26a1 and Cyp26b1 mRNAs encoding enzymes that catabolize retinoic acid. Concomitantly, there was significant reduction in retinoic acid levels in whole embryos and kidney rudiments. Restoration of retinoic acid levels by maternal supplementation with low doses of retinoic acid following the teratogenic insult rescued metanephric kidney development and abrogated several extrarenal developmental defects. This previously undescribed and unsuspected mechanism provides insight into the molecular pathway of retinoic acid-induced teratogenesis.

No abstract

No abstract

The present study describes the sequential ultrastructural changes in the apoptotic cells of the rat ventral and dorsal prostates during the early period of 1-3 days postcastration. The major morphological changes include: (1) condensation of heterochromatin along the nuclear envelope and fragmentation into crescent-shaped micronuclei; (2) formation of membrane-bound cytoplasmic spherical bodies, which contain various organelles and micronuclei, within the apoptotic cells; (3) formation of non-membrane-bound autolytic vacuoles by autolysis of cytoplasm; (4) focal rupture of outer mitochondrial membrane; and (5) phagocytosis of the fragmented cytoplasmic spherical bodies and apoptotic cells by macrophages. The occurrence of both cytoplasmic apoptotic bodies and autolytic vacuoles in apoptotic cells suggests that the cytoplasm of the apoptotic cells could be destroyed by different means. The responsiveness of different prostatic lobes to androgen withdrawal and the time course of the transitory apoptotic activity in different lobes were analyzed by counting the indices of the TUNEL-labeled apoptotic cells against the postcastration periods. The results showed that the ventral lobe responded more rapidly to castration than the lateral and dorsal lobes. The dorsal lobe was the slowest in response to castration among the three lobes. Analysis of protease activities by zymography has identified two Ca(2+)-independent proteases of apparent MW 20 and 24 kDa (expressed in both ventral and dorsolateral lobes), and one Ca(2+)-dependent protease of MW 66.5 kDa (expressed only in the dorsolateral lobe) which became activated at day 3 postcastration. Their expression patterns were different from that of CPP-3 in the castrated prostates, suggesting that the activated proteases were enzymes other than CPP-3. The association of their highest activities with the maximum apoptotic activity at day 3 postcastration and also their loss of activity at day 15 suggest that these protease activities might be related to apoptosis or glandular involution.