Nasopharyngeal carcinoma in the young: a combined M.D. Anderson and Stanford experience.

From 1956 to 1988, 57 children and young adults (age 4-21 years) with a diagnosis of nasopharyngeal carcinoma were treated at The University of Texas M.D. Anderson Cancer Center (42 patients) and Stanford University Medical Center (15 patients). The male to female ratio was 2:1. Forty-three patients had lymphoepithelioma, seven had undifferentiated neoplasms, and seven had squamous cell carcinoma. Two patients had Stage III disease and the remainder had Stage IV disease at the time of presentation. All patients were treated with primary radiotherapy, and 14 patients also had chemotherapy with combinations of the following drugs: dactinomycin, doxorubicin, bleomycin, cisplatin, cyclophosphamide, fluorouracil, methotrexate, and vincristine. Twenty-six patients are alive 6 to 178 months from the first day of treatment (median 93 months). The 5- and 10-year actuarial survival rates are 51% and 36%, respectively, and the corresponding disease specific survival rates were 51% and 51%. There were no recurrences after 42 months. The patterns of failure were as follows: distant metastasis only, 21 patients; locoregional metastasis only, 1; both, 5. Distant metastases most commonly occurred in bones, lungs, liver, and mediastinal lymph nodes. Chronic treatment-related morbidity was encountered in a significant number of long term survivors. Trends in the data not reaching statistical significance suggest a more favorable prognosis for a) females, b) patients less than or equal to 15 years of age, c) lymphoepithelioma or undifferentiated histologies, d) stages T3-4 NO-1 vs T1-2 N2-3 vs T3-4 N2-3, e) primary tumor dose greater than or equal to 65 Gy and f) patients who received chemotherapy.

Interaction of glucosyltransferase with the cell surface of Streptococcus mutans.

The partially purified glucosyltransferase (GTF) fraction synthesizing primarily water-insoluble glucans, GTF-A, and the homogeneous fraction synthesizing water-soluble glucans, GTF-B, were utilized to assess the binding of GTF activity to the cell surface of Streptococcus mutans GS-5. Growth of the cells in either Todd-Hewitt broth or a chemically defined medium did not appear to affect the ability of the cells to bind either enzyme fraction. Heat inactivation of the cells did not singificantly reduce the interaction of the enzymes with the cells. Cell surface glucan molecules appear to be involved in GTF binding to the cells because: (i) dextranase or alpha-1,3-glucanase treatment of the cells markedly reduced enzyme binding; (ii) the inclusion of soluble dextrans in the binding assays reduced both GTF-A and GTF-B binding to the cells; and (iii) pretreatment of the cells or the GTF-B fraction with soluble dextrans before binding significantly reduced enzyme binding to the cells. In addition, enzyme binding appears to require a cell surface protein component because Pronase, but not trypsin, treatment of cells reduced enzyme binding. Furthermore, the removal of a portion of the cell surface GTF-glucan complex with 3 N NaCl appears to provide additional binding sites for the enzymes. These results are interpreted in terms of the mechanism of the conversion of extracellular GTF to the cell-associated form.

Interaction of Streptococcus mutans glucosyltransferases with antibodies.

1) The GTF-A and GTF-B activities of serotype (c), (e), and (f) organisms are antigenically more closely related to each other than to the comparable enzymes from organisms of the other four S. mutans serotypes. 2) The adherence-inhibiting antibody in anti-GTF-A appears to be mediated against a heat sensitive cell surface antigen of S. mutans - most likely GTF activity. However, unequivocal proof of this conclusion awaits the preparations of homogeneous GTF-A preparations.

Molecular basis for the different sucrose-dependent adherence properties of Streptococcus mutans and Streptococcus sanguis.

The enzymatic and adherence properties of Streptococcus mutans GS5 and S. sanguis ST3, both isolated from human carious lesions, have been compared. During growth in sucrose media, S. mutans GS5 adheres to smooth surfaces approximately three times more effectively than dose S. sanguis ST3. However, strain ST3 does not display sucrose-dependent adherence under nongrowth conditions, whereas strain GS5 displays significant adherence. Although both organisms synthesize both water-soluble and -insoluble glucans, the glucosyltransferases from S. mutans GS5 synthesize much more adherent glucan molecules than do the comparable enzymes from S. sanguis ST3. Both cell types bind exogenous glucosyltransferases synthesized by strain ST3 equally well, whereas cells of strain GS5 bind the comparable enzyme fraction that it synthesizes to a greater degree than do cell of S. sanguis ST3. However, in contrast to the results with cells of S. mutans GS5, the absorption of the glucosyltransferase activity synthesized by S. mutans GS5 to the surface of S. sanguis ST3 results in low levels of subsequent sucrose-dependent adherence. These results are discussed in terms of the molecular basis for the sucrose-dependent adherence of the oral streptococci to smooth surfaces.

Immunological relationships between glucosyltransferases from Streptococcus mutans serotypes.

Partially purified glycosyltransferase enzymes for Streptococcus mutans GS-5 (serotype c) have been utilized to prepare antibodies directed against the soluble glucan-synthesizing activity, GTF-B, and the insoluble-soluble glucan synthetic activity, GTF-A. Anti-GTF-A inhibited insoluble glucan formation catalyzed by the extracellular enzymes from strains GS-5 and FA-1 (serotype b) to a much greater extent than that of strains HS-6 (serotype a) or OMZ-176 (serotype d). This antibody fraction also inhibited both the cell-associated glucosyltransferase activities as well as the sucrose-mediated adherence of cells to glass surfaces by strains GS-5 and FA-1 but not that of strains HS-6 and OMZ-176. Anti-GTF-B inhibited soluble glucan formation catalyzed by the extracellular enzymes of strains GS-5 but not that of strain HS-6, FA-1, or OMZ-176. However, this antibody fraction did not strongly inhibit either the cell-associated glycosyltransferase activity or cellular adherence of any of the four strains. These results with body antibody fractions were also correlated with the ability of the antibodies to agglutinate the cells and form precipitin bands after immunodiffusion with the extracellular enzymes. Antibody prepared against the homogeneous soluble glucan-synthesizing enzyme demonstrated similar effects to the anti-GTF-B fraction. These results are discussed in terms of the antigenic relationships existing between the glucosyltransferases from different serotypes of S. mutans.

Differential inhibition of Streptococcus mutans in vitro adherence by anti-glucosyltransferase antibodies.

Antibodies prepared against an insoluble-soluble glucan-synthesizing fraction significantly inhibited in vitro adherence of Streptococcus mutans, whereas antibodies directed against a soluble glucan-synthesizing fraction were much less inhibitory.