Potential Molecular Cross Talk Among CCR5 Pathway Predicts Regorafenib Responsiveness in Metastatic Colorectal Cancer Patients.

BACKGROUND: Genetic variants in the CCL5/CCR5 pathway have been shown to predict regorafenib efficacy in patients with metastatic colorectal cancer (mCRC). This study investigated the biological role of CCL4 and CCL3 gene polymorphisms in patients with refractory mCRC treated using regorafenib. PATIENTS AND METHODS: We analyzed the genomic DNA extracted from mCRC patients receiving regorafenib. Serum factor levels at baseline, day 21, and progressive disease (PD) were measured using ELISA. RESULTS: Decreased CCL4 levels at day 21 or increased CCL3 levels at PD were associated with better clinical outcomes. In patients with any CCL5 rs2280789 G allele, CCL3 significantly increased between BL and day 21 compared with the A/A variant (72.7% vs. 23.1%, p=0.006), but CCL4 decreased (31.8% vs. 69.2%, p=0.043). CONCLUSION: Increased CCL3 and decreased CCL4 seen in specific genotypes may serve as potential biomarkers of regorafenib in mCRC patients.

[Multiplex fluorescence PCR for detection of Y Chromesome microdeletions].

OBJECTIVE: Detection of azoospermia factor (AZF) microdeletions on the Y chromosome is one of the auxiliary strategies recognized at home and abroad for the examination of male infertility. Traditional PCR gel electrophoresis fails to meet the clinical needs due to its shortcomings. The purpose of this study was to explore the feasibility of multiplex fluorescence PCR in the detection of AZF microdeletions. METHODS: We collected samples of Y chromosomal AZF microdeletions from 238 patients with azoospermia or oligozoospermia and 62 normal males, identified the 14 short tandem repeat (STR) loci in the AZF region of the Y chromosome by multiplex PCR gel electrophoresis and multiplex fluorescence PCR, and analyzed the consistency in the results of the two methods by Kappa test. RESULTS: There was a perfect consistency between multiplex PCR gel electrophoresis and multiplex fluorescence PCR in the detection rate of the STR loci in the 300 samples. Kappa test showed both P and Kappa values to be 1 for the 6 loci in the AZFa, AZFb and AZFc regions of the Y chromosome, with no statistically significant difference between the two methods. CONCLUSIONS: Multiplex fluorescence PCR can save a lot of time, reduce workload and improve laboratory efficiency and therefore is preferable to multiplex PCR gel electrophoresis in detecting Y chromosome microdeletions.

Indirect validation of benzene exposure assessment by association with benzene poisoning.

We present a validation study of a quantitative retrospective exposure assessment method used in a follow-up study of workers exposed to benzene. Assessment of exposure to benzene was carried out in 672 factories in 12 cities in China. Historical exposure data were collected for 3179 unique job titles. The basic unit for exposure assessment was a factory/work unit/job title combination over seven periods between 1949 and 1987. A total of 18,435 exposure estimates was developed, using all available historical information, including 8477 monitoring data. Overall, 38% of the estimates were based on benzene monitoring data. The highest time-weighted average exposures were observed for the rubber industry (30.7 ppm) and for rubber glue applicators (52.6 ppm). Because of its recognized link with benzene exposure, the association between a clinical diagnosis of benzene poisoning and benzene exposure was evaluated to validate the assessment method that we used in the cohort study. Our confidence in the assessment method is supported by the observation of a strong positive trend between benzene poisoning and various measures, especially recent intensity of exposure to benzene.

Cohort study among workers exposed to benzene in China: I. General methods and resources.

Benzene is recognized internationally as a leukemogen, but the available data to clarify dose-response relationships and examine risks of malignancies other than leukemia are sparse. A collaborative study was therefore carried out to expand on a previous retrospective cohort mortality study of Chinese benzene-exposed workers. Methods and resources used in the 16-year follow-up of 74,828 benzene-exposed and 35,805 unexposed workers employed for any length of time during 1972-1987 in 712 factories in 12 cities in China are described. Details are provided of the study organization, assessment of benzene exposures since 1949, characterization of factories and workers by exposure status, city, and sex, identification and confirmation of cancers and other deaths, and quality control procedures. The distinguishing features of the study are discussed in relation to earlier cohort studies, and study limitations as well as strengths are presented.

Cohort study among workers exposed to benzene in China: II. Exposure assessment.

This report describes a retrospective exposure assessment method used in a follow-up mortality study of workers exposed to benzene. The approach quantified historical exposure to benzene in a multi-industry, multicenter cohort, involving 672 factories in 12 cities in China. Historical exposure data were collected to obtain exposure information related to 1,427 work units (departments) and 3,179 unique job titles from benzene-producing or -using factories in which written records and other data sources were evaluated. The basic unit for exposure assessment was a factory/work unit/job title combination which was considered separately during each of seven calendar-year time periods between 1949 and 1987 for a total of 18,435 exposure assignments. Historical information collected to estimate exposure included benzene monitoring data; lists of raw materials and factory products, and the percentage of benzene in each; the total amount and dates of use of benzene or benzene-containing materials; use of engineering controls and personal protective equipment; and other available exposure information. Overall, 38% (ranging from 3% for the earliest periods to 67% for the last period) of the estimates were based primarily on benzene monitoring data. In the absence of job-specific benzene monitoring data for a given calendar period, measurement results or exposure estimates for similar jobs and/or other calendar periods were used in conjunction with other exposure information to derive estimates. Estimated exposure levels are presented by industries and occupations. The highest average exposures during 1949-1987 were observed for the rubber and plastic industry (30.7 ppm), and for rubber glue applicators (52.6 ppm).

Gender differences in hematopoietic and lymphoproliferative disorders and other cancer risks by major occupational group among workers exposed to benzene in China.

Gender differences in risk for leukemia and other selected and combined disease categories were examined by major occupational category for 74,828 benzene-exposed workers compared to 35,805 unexposed workers from 12 cities in China. No significant differences in the relative risks for total mortality and cancer mortality were found between female and male benzene-exposed workers, although risks tended to be somewhat higher among male than among female employees. Both female and male workers in several occupational categories had notably increased risks for all hematopoietic and lymphoproliferative (HLP) malignant and nonmalignant disorders combined and for total leukemia. Variation in risk for HLP disorders by occupational category was observed in both genders, with highest risks for male and female chemical manufacturing workers, female nonproduction employees, and male printers. However, the numbers of leukemia and other HLP malignancies in each category were small. The findings suggest that both female and male benzene-exposed workers in several occupational categories experience excess leukemia and other HLP disorders with relatively minor gender differences. Although this population is one of the largest cohorts of benzene-exposed workers studied to date, evaluation of the observed variation in risk for HLP neoplasms among the occupational groups for workers of each gender is limited by the small numbers of these relatively rare malignancies.