The presence of hypoxia in tumours results in the overexpression of certain genes, which are controlled via the transcription factor HIF-1. Hypoxic cells are known to be radioresistant and chemoresistant, thus, a reliable surrogate marker of hypoxia is desirable to ensure that treatment may be rationally applied. Recently, the HIF-1-regulated proteins Glut-1 and CAIX were validated as intrinsic markers of hypoxia by comparison with pO 2 measured using oxygen electrodes. We compare the expression of Glut-1 and CAIX with the binding of the bioreductive drug hypoxia marker pimonidazole. Pimonidazole was administered to 42 patients with advanced carcinoma of the cervix, 16 hr before biopsy. Sections of single or multiple biopsies were then immunostained for Glut-1 and CAIX, and the area of staining scored by eye, using a "field-by-field" semi-quantitative averaging system. Using 1 biopsy only, Glut-1 (r ‫؍‬ 0.54, p ‫؍‬ <0.001) correlated with the level of pimonidazole binding, and Glut-1 and CAIX expression also correlated significantly (r ‫؍‬ 0.40, p ‫؍‬ <0.009). Thus, our study has shown that HIF-1 regulated genes have potential for future use as predictors of the malignant changes mediated by hypoxia, and warrant further investigation as indicators of response to cancer therapy.

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Purpose: Hypoxia-inducible factor (HIF)-1␣ expression was studied retrospectively in locally advanced carcinoma of the cervix in relation to other methods for measuring/assessing tumor hypoxia and outcome after radiotherapy.Experimental Design: HIF-1␣ expression was examined in formalin-fixed tumor biopsies using a semiquantitative scoring system and correlated with measurements of hypoxia obtained using oxygen electrodes, pimonidazole staining, and carbonic anhydrase 9.Results: High HIF-1␣ expression showed a weak correlation with low pO 2 (r ‫؍‬ ؊0.26; P ‫؍‬ 0.030; n ‫؍‬ 72). Weak significant correlations were found between HIF-1␣ and pimonidazole staining (r ‫؍‬ 0.34; P ‫؍‬ 0.040; n ‫؍‬ 36) and carbonic anhydrase IX (r ‫؍‬ 0.27; P ‫؍‬ 0.001; n ‫؍‬ 160). There was no relationship with surviving fraction at 2 Gy. The relationship between HIF-1␣ expression and radiotherapy outcome was examined in 99 patients. HIF-1␣ expression did not correlate with disease stage, grade, tumor size, and patient age. HIF-1␣ alone was not a significant prognostic factor for disease-free survival, metastasis-free survival, or local recurrence-free survival. High HIF-1␣ expression tended to be associated with poor outcome in small tumors but good outcome in large tumors, with statistically significant interactions between HIF-1␣ and tumor size for survival (P ‫؍‬ 0.046) and local control (P ‫؍‬ 0.009).Conclusions: In this study, HIF-1␣ had no prognostic significance in locally advanced carcinoma of the cervix. The possible switch in large tumors for an association between high HIF-1␣ expression and good outcome might relate to tumor size-related changes in the balance of genes up-regulated by HIF-1␣. Whereas angiogenesis-promoting genes might be preferentially up-regulated in small tumors, proapoptotic genes might be induced in large tumors. This hypothesis needs testing in future work.

Carbons are versatile and diverse materials that have numerous applications across energy and environmental sciences. Carbons with a graphitic structure are particularly appealing due to their high chemical stability, large...

Qualitative and quantitative measures of the Aufwuchs (scum flora) on artificial substrates in situ were used to evaluate the effects of grazing by freshwater pulmonate snails in a shallow pond in southeastern Michigan . Grazer densities of-216 snails/ M 2 marked reduced standing crop so that after 45 days grazed substrata had 6 .46 mg dry weight, 604 µg C and 4.18 µg chlorophyll a as compared to controls with 30 .62 mg dry weight, 3699 µg C and 6 .29 µg chlorophyll a, all on a per dm 2 basis .Grazing did not change carbon per mg dry matter but caused significant increases in both µg chlorophyll a (control, 0 .2o6 ; and grazed, 0.649 µg chlorophyll a/ mg dry weight, P < o .o1) and nitrogen (control, 8 .3 ; and grazed, 24 .2 µg N/ mg dry weight, P < 0.00,) after 45 days . Both abundance and diversity of the attached community was reduced by grazing from 24 taxa and 80,889 individuals/ cm2 on control to 8 taxa and Sot individuals/ cm 2 on grazed substrates . Mean productivity of the Aufwuchs was significantly (P