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21.
Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type. 总被引:6,自引:0,他引:6
William D Foulkes Kelly Metcalfe Ping Sun Wedad M Hanna Henry T Lynch Parviz Ghadirian Nadine Tung Olufunmilayo I Olopade Barbara L Weber Jane McLennan Ivo A Olivotto Louis R Bégin Steven A Narod 《Clinical cancer research》2004,10(6):2029-2034
PURPOSE: BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied. EXPERIMENTAL DESIGN: ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America. There were 208 BRCA1 mutation carriers, 88 BRCA2 carriers, and 804 women without a known mutation. We stratified the patients by mutation status, grade, age, and histological type and calculated the percentage of ER-positive tumors within each stratum. RESULTS: BRCA1 mutation carriers were more likely to have ER-negative breast cancers than were women in other groups, after adjustment for age, grade, and histological subtype (P < 0.001). Only 3.9% of BRCA1-related breast cancers were ER-positive cancers occurring in women in their postmenopausal years. The direction and magnitude of the change in ER status with increasing age at diagnosis in BRCA1 carriers was significantly different from in BRCA2 carriers (P(intercept) = 0.0002, P(slope) = 0.04). Notably, changes in ER status with age at diagnosis for BRCA1 carriers and noncarriers were almost identical (P(slope) = 0.98). CONCLUSIONS: The strong relationship between the presence of a BRCA1 mutation and the ER-negative status of the breast cancers is neither a consequence of the young age at onset nor the high grade but is an intrinsic property of BRCA1-related cancers. The ER-negative status of these cancers may reflect the cell of origin of BRCA1-related cancers. 相似文献
22.
Hemoglobin and albumin adducts of benzene oxide among workers exposed to high levels of benzene 总被引:3,自引:0,他引:3
Yeowell-O'Connell K; Rothman N; Smith MT; Hayes RB; Li G; Waidyanatha S; Dosemeci M; Zhang L; Yin S; Titenko-Holland N; Rappaport SM 《Carcinogenesis》1998,19(9):1565-1571
Benzene oxide (BO) reacts with cysteinyl residues in hemoglobin (Hb) and
albumin (Alb) to form protein adducts (BO-Hb and BO-Alb), which are
presumed to be specific biomarkers of exposure to benzene. We analyzed
BO-Hb in 43 exposed workers and 42 unexposed controls, and BO-Alb in a
subsample consisting of 19 workers and 19 controls from Shanghai, China, as
part of a larger cross-sectional study of benzene biomarkers. The adducts
were analyzed by gas chromatography-mass spectrometry following reaction of
the protein with trifluoroacetic anhydride and methanesulfonic acid. When
subjects were divided into controls (n = 42) and workers exposed to < or
=31 (n = 21) and >31 p.p.m. (n = 22) benzene, median BO-Hb levels were
32.0, 46.7 and 129 pmol/g globin, respectively (correlation with exposure:
Spearman r = 0.67, P < 0.0001). To our knowledge, these results
represent the first observation in humans that BO-Hb levels are
significantly correlated with benzene exposure. Median BO-Alb levels in
these 3 groups were 103 (n = 19), 351 (n = 7) and 2010 (n = 12) pmol/g Alb,
respectively, also reflecting a significant correlation with exposure
(Spearman r = 0.90, P < 0.0001). The blood dose of BO predicted from
both Hb and Alb adducts was very similar. These results clearly affirm the
use of both Hb and Alb adducts of BO as biomarkers of exposure to high
levels of benzene. As part of our investigation of the background levels of
BO-Hb and BO-Alb found in unexposed persons, we analyzed recombinant human
Hb and Alb for BO adducts. Significant levels of both BO-Hb (19.7 pmol/g)
and BO-Alb (41.9 pmol/g) were detected, suggesting that portions of the
observed background adducts reflect an artifact of the assay, while other
portions are indicative of either unknown exposures or endogenous
production of adducts.
相似文献
23.
Increased aneusomy and long arm deletion of chromosomes 5 and 7 in the lymphocytes of Chinese workers exposed to benzene 总被引:4,自引:1,他引:4
Zhang L; Rothman N; Wang Y; Hayes RB; Li G; Dosemeci M; Yin S; Kolachana P; Titenko-Holland N; Smith MT 《Carcinogenesis》1998,19(11):1955-1961
Two of the most common cytogenetic changes in therapy- and chemical-
related leukemia are the loss and long (q) arm deletion of chromosomes 5
and 7. The detection of these aberrations in lymphocytes of individuals
exposed to potential leukemogens may serve as useful biomarkers of
increased leukemia risk. We have used a novel fluorescence in situ
hybridization (FISH) procedure to determine if specific aberrations in
chromosomes 1, 5 and 7 occur at an elevated rate in the blood cells of
workers exposed to benzene. Forty-three healthy workers exposed to a wide
range of benzene concentrations (median 31 p.p.m., 8 h time-weighted
average) and 44 unexposed controls from Shanghai were studied. Whole blood
was cultured and metaphase spreads were harvested at 72 h. Benzene exposure
was associated with increases in the rates of monosomy 5 and 7 but not
monosomy 1 (P < 0.001, P < 0.0001 and P = 0.94, respectively) and
with increases in trisomy and tetrasomy frequencies of all three
chromosomes. Long arm deletion of chromosomes 5 and 7 was increased in a
dose-dependent fashion (P = 0.014 and P < 0.0001) up to 3.5-fold in the
exposed workers. These results demonstrate that leukemia-specific changes
in chromosomes 5 and 7 can be detected by FISH in the peripheral blood of
otherwise healthy benzene-exposed workers. We suggest that aberrations in
chromosomes 5 and 7 may be useful biomarkers of early biological effect for
benzene exposure.
相似文献
24.
Michael WT Chao David Byram Richard Bell Rodney Bond Steven Vaughan Roger McLennan Michael Lim-Joon Morikatsu Wada David Joseph 《Journal of Medical Imaging and Radiation Oncology》1998,42(1):47-51
Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months’duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71 % and 79%, respectively. 相似文献
25.
Background : Dry eye is a common complication of LASIK surgery. Our clinical impression was that post‐LASIK dry eye was more problematic for our Asian patients. The aim of this study was to determine if dry eye after LASIK is more prevalent, more sustained and more severe in Asian eyes compared with Caucasian eyes. Methods : This study was based on a retrospective analysis of a clinical database. Data (n = 932 eyes, 932 patients) was collected before and after (week 2 and months 1, 3 and 6) LASIK surgery. Patients were defined as Asian if both parents were of East Asian ethic origin. Assessments included dry eye symptoms, ocular surface staining, tear volume, tear secretion, tear film stability and corneal sensation. Results : Asian eyes had greater ocular surface staining, poorer tear film stability and lower tear volume before LASIK and at all times after LASIK. Dry eye symptoms occurring ‘often or constantly’ were more prevalent at all time points after LASIK in Asian eyes. Chronic dry eye persisting six months or more after LASIK was diagnosed in 28 per cent of Asian eyes and 5 per cent of Caucasian eyes (p < 0.001). Asian patients with chronic dry eye were predominantly female, reported dry eye symptoms, had greater ocular surface staining and lower tear secretion, stability and volume before surgery. After LASIK, Asian eyes had a slower return to pre‐operative values for ocular surface staining, tear volume and corneal sensation. Discussion : The risk of chronic dry eye after LASIK was significantly higher in Asian eyes. Contributing factors could include racial differences in eyelid and orbital anatomy, tear film parameters and blinking dynamics and higher attempted refractive corrections in Asian eyes. 相似文献
26.
Wesley H. Self MD MPH Joyce Mickanin MSN RN Carlos G. Grijalva MD MPH Freda H. Grant MT ASCP Michelle C. Henderson MSN RN Glenda Corley MT ASCP D. Glen Blaschke II MD Candace D. McNaughton MD MPH Tyler W. Barrett MD MSCI Thomas R. Talbot MD MPH Barbara R. Paul MD 《Academic emergency medicine》2014,21(3):274-282
27.
28.
Gregory Welter PE BCEE Myra Socher BS EMT/P Patricia Needham MT HEM Steve Bieber MS MPA Heidi Bonnaffon MS 《Journal of healthcare risk management》2013,32(4):5-14
The purpose of this article is to outline the criticality of water supply in sustained operations of healthcare facilities, particularly during community emergencies, and to advocate for enhanced cross‐sector support from the water utilities in meeting this need. Information and ideas presented here were developed in the course of a regional project sponsored by the Metropolitan Washington Council of Governments (MWCOG) for development of emergency water supply operations plans for critical water uses in the Washington, DC, area. 相似文献
29.