Investigation of the role of the amino acid residue at position 230 for catalysis in monomeric carbonyl reductase 3.

Monomeric carbonyl reductase 3 (CBR3) is a member of the short-chain dehydrogenase/reductase family. CBR3 exhibits much lower activity than monomeric carbonyl reductase 1 (CBR1) in humans and Chinese hamsters although they are highly homologous to each other in amino acid sequence levels. In the present study, we first cloned the CBR3 gene of rat origin (rCBR3), and characterized its enzymatic activity. rCBR3 also exhibited a limited catalytic efficiency similarly to the other CBR3 orthologues of humans and Chinese hamsters. Among the CBR3 orthologues, the human enzyme showed considerably lower activity. Compared with the amino acid sequences of CBR1 and CBR3 among humans, rats, Chinese hamsters, and mice, the tryptophan residue at position 230 is highly conserved while human CBR3 possesses rigid amino acid, proline, at that position instead. Thus, the Trp-230 was expected to be one of the important residues for catalysis since it locates in the hinge region at the substrate-binding loop. The substitution of tryptophan for proline in hCBR3 failed to affect the enzymatic characteristics. Similarly, the substitution of proline for tryptophan in either Chinese hamster CBR3 (CHCR3) or rCBR3 showed no significant change in the catalytic properties. These results suggest that limited catalytic efficiency of carbonyl reductase activity of CBR3 is a common property among animal species, and the substitution of the amino acid residue at position 230 alone has no apparent impact on their enzymatic activities.

Impact of lymph node metastasis on the pattern of failure and survival in oral carcinomas.

BACKGROUND: Carcinomas of the oral cavity present a high risk for neck metastases that decrease the disease control and survival. METHODS: A total of 106 patients with squamous cell carcinoma of the oral cavity who had metastatic neck nodes were studied. The impact of neck metastasis and treatment modalities on outcome was assessed. RESULTS: Thirty-eight patients developed neck recurrence or distant metastasis. The 5-year survival, neck recurrence-free, and distant metastases-free rates were 56%, 84%, and 77%, respectively. Univariate analyses showed extranodal spread (ENS), number of positive nodes, and adjuvant chemotherapy were predictors for survival. In multivariate analysis, ENS and postoperative radiotherapy were of borderline significance. There was no prognostic factor for neck control. The presence of ENS and lower levels of positive nodes and no chemotherapy were associated with high distant failure rates. CONCLUSIONS: To prevent distant metastases, patients with ENS should be considered for adjuvant chemotherapy.

Squamous cell carcinomas of the mandibular alveolus: analysis of prognostic factors.

BACKGROUND: To assess the effect of clinicopathologic factors on local tumor control and survival in patients with mandibular alveolar carcinoma. METHODS: Fifty patients with mandibular alveolar carcinoma treated surgically were included in this study. There were 3 patients with T1, 25 with T2, 5 with T3, and 17 with T4 disease. Clinical evidence of bone invasion was noted in 47 patients. A hemi- or segmental mandibulectomy was performed on 37 patients, whereas 10 patients had a marginal mandibulectomy. The impact of clinicopathologic variables on local tumor control and patient survival was assessed by univariate analysis. Variables included T and N stage, dental extraction, treatment modality, tumor differentiation, nodal status, surgical margin, and bone invasion. RESULTS: Eleven patients (22%) develop recurrent disease, including 8 local recurrences, 1 neck, and 2 distant metastases. Overall, the 5-year actuarial rates of local control and disease-specific survival were 85 and 73%, respectively. Most local recurrences after surgical treatment were caused by inadequate resection margins. When resection margins were negative, the survival and local control rate were significantly better than when there were positive resection margins (survival, 91 vs. 11%; local control, 100 vs. 49%; p < 0.01). Neither T and N stages, clinical stage, tumor differentiation, dental extraction, bone invasion, extent of bone resection, nor treatment modality influenced outcome. CONCLUSIONS: The status of surgical margins was of major importance for the outcome of patients with gingival carcinoma of the mandible.