The Potential for Midtreatment Albumin-Bilirubin (ALBI) Score to Individualize Liver Stereotactic Body Radiation Therapy.

PURPOSE: Our individualized functional response adaptive approach to liver stereotactic body radiation therapy (SBRT) with assessment of indocyanine green (ICG) retention at baseline and midtreatment to detect subclinical changes in liver function, permitting dose adjustment, has decreased toxicity while preserving efficacy. We hypothesized that assessment of the albumin-bilirubin (ALBI) score at baseline and midtreatment would allow for more practical identification of patients at risk for treatment-related toxicity (TRT). METHODS AND MATERIALS: Patients with hepatocellular carcinoma were treated on 3 prospective institutional review board-approved trials using baseline and midtreatment ICG to deliver individualized functional response adaptive liver SBRT. Patients received 3 or 5 fractions, with fraction 3 followed by a 1-month treatment break. TRT was a ≥2-point rise in Child-Pugh score within 6 months of SBRT. Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for assessment of TRT. Area under the receiver operating curve was used to compare predictive ability across models. RESULTS: In total, 151 patients underwent 166 treatments. Baseline Child-Pugh class and ALBI grade were A (66.9%), B (31.3%), or C (1.8%) and 1 (25.9%), 2 (65.7%), or 3 (8.4%), respectively. Thirty-five patients (20.3%) experienced TRT. On univariate analysis, baseline ALBI (OR, 1.8; 95% CI, 1.24-2.62; P = .02), baseline ICG (OR, 1.66; 95% CI, 1.17-2.35; P = .04), and change in ALBI (OR, 3.07; 95% CI, 1.29-7.32; P = .003) were associated with increased odds of TRT. ALBI-centric models performed similarly to ICG-centric models on multivariate analyses predicting toxicity (area under the receiver operating curve of 0.79 for both). In a model incorporating baseline and midtreatment change in ALBI and ICG, both ALBI values were statistically significantly associated with toxicity, whereas ICG values were not. CONCLUSIONS: Incorporation of midtreatment change in ALBI in addition to baseline ALBI improves the ability to predict TRT in patients with hepatocellular carcinoma receiving SBRT. Our findings suggest that functional response adaptive treatment could be implemented in a practical manner because the ALBI score is easily obtained from standard laboratory values.

Cervical mucins carry alpha(1,2)fucosylated glycans that partly protect from experimental vaginal candidiasis.

Cervical mucins are glycosylated proteins that form a protective cervical mucus. To understand the role of mucin glycans in Candida albicans infection, oligosaccharides from mouse cervical mucins were analyzed by liquid chromatography-mass spectrometry. Cervical mucins carry multiple alpha(1-2)fucosylated glycans, but alpha(1,2)fucosyltransferase Fut2-null mice are devoid of these epitopes. Epithelial cells in vaginal lavages from Fut2-null mice lacked Ulex europaeus agglutinin-1 (UEA-I) staining for alpha(1-2)fucosylated glycans. Hysterectomy to remove cervical mucus eliminated UEA-I and acid mucin staining in vaginal epithelial cells from wild type mice indicating the cervix as the source of UEA-I positive epithelial cells. To assess binding of alpha(1-2) fucosylated glycans on C. albicans infection, an in vitro adhesion assay was performed with vaginal epithelial cells from wild type and Fut2-null mice. Vaginal epithelial cells from Fut2-null mice were found to bind increased numbers of C. albicans compared to vaginal epithelial cells obtained from wild type mice. Hysterectomy lessened the difference between Fut2-null and wild type mice in binding of C. ablicans in vitro and susceptibility to experimental C. albicans vaginitis in vivo. We generated a recombinant fucosylated MUC1 glycanpolymer to test whether the relative protection of wild type mice compared to Fut2-null mice could be mimicked with exogenous mucin. While a small portion of the recombinant MUC1 epitopes displayed alpha(1-2)fucosylated glycans, the predominant epitopes were sialylated due to endogenous sialyltransferases in the cultured cells. Intravaginal instillation of recombinant MUC1 glycanpolymer partially reduced experimental yeast vaginitis suggesting that a large glycanpolymer, with different glycan epitopes, may affect fungal burden.

Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation.

BACKGROUND/AIMS: Neoplasia-related alterations in cell surface alpha(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-beta signaling gene Smad3 (Madh3) were tested for alpha(1,2)fucosylated glycan expression. METHODS: Ulex europaeus agglutinin-I (UEA-I) lectin staining, fucosyltransferase gene Northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. RESULTS: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express alpha(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of alpha(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3-targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knockout mice, UEA-I lectin staining was eliminated from colon and colon tumors; however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. CONCLUSIONS: In this model of colorectal cancer, cell surface alpha(1,2)fucosylation does not affect development of colon tumors.