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The authors performed a cross-sectional study to evaluate associations between blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead and measures of neurobehavioral and peripheral nervous system function among 803 lead-exposed workers and 135 unexposed controls in South Korea. The workers and controls were enrolled in the study between October 1997 and August 1999. Central nervous system function was assessed with a modified version of the World Health Organization Neurobehavioral Core Test Battery. Peripheral nervous system function was assessed by measuring pinch and grip strength and peripheral vibration thresholds. After adjustment for covariates, the signs of the beta coefficients for blood lead were negative for 16 of the 19 tests and blood lead was a significant predictor of worse performance on eight tests. On average, for the eight tests that were significantly associated with blood lead levels, an increase in blood lead of 5 microg/dl was equivalent to an increase of 1.05 years in age. In contrast, after adjustment for covariates, tibia lead level was not associated with neurobehavioral test scores. Associations with DMSA-chelatable lead were similar to those for blood lead. In these currently exposed workers, blood lead was a better predictor of neurobehavioral performance than was tibia or DMSA-chelatable lead, mainly in the domains of executive abilities, manual dexterity, and peripheral motor strength.

BackgroundIn the postgenome era, a prediction of response to treatment could lead to better dose selection for patients in radiotherapy. To identify a radiosensitive gene signature and elucidate related signaling pathways, four different microarray experiments were reanalyzed before radiotherapy.ResultsRadiosensitivity profiling data using clonogenic assay and gene expression profiling data from four published microarray platforms applied to NCI-60 cancer cell panel were used. The survival fraction at 2 Gy (SF2, range from 0 to 1) was calculated as a measure of radiosensitivity and a linear regression model was applied to identify genes or a gene set with a correlation between expression and radiosensitivity (SF2). Radiosensitivity signature genes were identified using significant analysis of microarrays (SAM) and gene set analysis was performed using a global test using linear regression model. Using the radiation-related signaling pathway and identified genes, a genetic network was generated. According to SAM, 31 genes were identified as common to all the microarray platforms and therefore a common radiosensitivity signature. In gene set analysis, functions in the cell cycle, DNA replication, and cell junction, including adherence and gap junctions were related to radiosensitivity. The integrin, VEGF, MAPK, p53, JAK-STAT and Wnt signaling pathways were overrepresented in radiosensitivity. Significant genes including ACTN1, CCND1, HCLS1, ITGB5, PFN2, PTPRC, RAB13, and WAS, which are adhesion-related molecules that were identified by both SAM and gene set analysis, and showed interaction in the genetic network with the integrin signaling pathway.ConclusionsIntegration of four different microarray experiments and gene selection using gene set analysis discovered possible target genes and pathways relevant to radiosensitivity. Our results suggested that the identified genes are candidates for radiosensitivity biomarkers and that integrin signaling via adhesion molecules could be a target for radiosensitization.

PurposeWe aimed to assess prognostic value of metastatic pelvic lymph node (mPLN) in early-stage cervical cancer treated with radical surgery followed by postoperative chemoradiotherapy. Also, we sought to define a high-risk group using prognosticators for recurrence.Materials and MethodsA multicenter retrospective study was conducted using the data from 13 Korean institutions from 2000 to 2010. A total of 249 IB-IIA patients with high-risk factors were included. We evaluated distant metastasis-free survival (DMFS) and disease-free survival (DFS) in relation to clinicopathologic factors including pNstage, number of mPLN, lymph node (LN)ratio (number of positive LN/number of harvested LN), and log odds of mPLNs (log(number of positive LN+0.5/number of negative LN+0.5)).ResultsIn univariate analysis, histology (squamous cell carcinoma [SqCC] vs. others), lymphovascular invasion (LVI), number of mPLNs (≤ 3 vs. > 3), LN ratio (≤ 17% vs. > 17%), and log odds of mPLNs (≤ ‒0.58 vs. > ‒0.58) were significant prognosticators for DMFS and DFS. Resection margin involvement only affected DFS. No significant survival difference was observed between pN0 patients and patients with 1-3 mPLNs. Multivariate analysis revealed that mPLN > 3, LVI, and non-SqCC were unfavorable index for both DMFS (p < 0.001, p=0.020, and p=0.031, respectively) and DFS (p < 0.001, p=0.017, and p=0.001, respectively). A scoring system using these three factors predicts risk of recurrence with relatively high concordance index (DMFS, 0.69; DFS, 0.71).ConclusionmPLN > 3 in early-stage cervical cancer affects DMFS and DFS. A scoring system using mPLNs > 3, LVI, and non-SqCC could stratify risk groups of recurrence in surgically resected early-stage cervix cancer with high-risk factors.

Results: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R 2 ‫؍‬ 0.05, P ‫؍‬ 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P ‫؍‬ 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P ‫؍‬ 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk ‫؍‬ 4.0, P ‫؍‬ 0.03).Conclusions: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.

BACKGROUND The objective of this study was to determine whether cyclooxygenase‐2 (COX‐2) overexpression was an indicator of prognosis in patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IIB uterine cervical carcinoma who underwent radiation and concurrent chemotherapy. METHODS Seventy‐five patients with FIGO Stage IIB squamous cell carcinoma (SCC) of the uterine cervix who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996 were divided into two groups according to their COX‐2 level in an immunohistochemical study: the COX‐2 negative group (n = 54 patients) and the COX‐2 positive group (n = 21 patients). The clinicopathologic features, patterns of treatment failure, and survival data for patients in the COX‐2 positive group were compared with data from the patients in the COX‐2 negative group. Univariate and multivariate analyses were performed to determine the prognostic factors that influenced patient survival. RESULTS In the immunohistochemical study, COX‐2 overexpression was observed in approximately 30% of patients with FIGO Stage IIB SCC of the uterine cervix. With delayed regression to the initial treatment, the treatment failure rate of patients in the COX‐2 positive group was much higher compared with the treatment failure rate of patients in the COX‐2 negative group. The higher incidence of central failure and lymph node failure for patients in the COX‐2 positive group was statistically significant (48% for the COX‐2 positive group vs. 13% for the COX‐2 negative group). However, there was no difference in the incidence of hematogenous metastases between the two groups (5% for the COX‐2 positive group vs. 7% for the COX‐2 negative group). In addition, increased COX‐2 expression in tumor cells also was correlated with a shorter interval to tumor recurrence (median interval to recurrence, 9 months in the COX‐2 positive group vs. 26 months in the COX‐2 negative group). Compared with patients in the COX‐2 negative group, patients in the COX‐2 positive group had lower overall actuarial and disease free survival rates (overall 5‐year actuarial survival rates: 56% for the COX‐2 positive group vs. 94% for the COX‐2 negative group; P = 0.003). Univariate and multivariate analyses showed that COX‐2 overexpression was an independent prognostic factor that surpassed other well‐known clinicopathologic parameters. CONCLUSIONS COX‐2 overexpression can be used as a potent molecular risk factor in patients with FIGO Stage IIB SCC of the uterine cervix who are treated with radiotherapy and concurrent chemotherapy. Cancer 2002;95:531–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10684

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IMPORTANCEThe benefit of internal mammary node irradiation (IMNI) for treatment outcomes in node-positive breast cancer is unknown.OBJECTIVE To investigate whether the inclusion of IMNI in regional nodal irradiation improves disease-free survival (DFS) in women with node-positive breast cancer.