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Antihistamines and Ovarian Cancer Survival: Nationwide Cohort Study and in Vitro Cell Viability Assay.

ABSTRACT: Antihistamines with cationic amphiphilic drug (CAD) characteristics induce cancer-specific cell death in experimental studies. Epidemiologic evidence is, however, limited. In a Danish nationwide cohort of ovarian cancer patients diagnosed during 2000-2015 (n?=?5075), we evaluated the association between filled antihistamine prescriptions and cancer mortality. We used Cox regression models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for ovarian cancer mortality. In an in vitro cell viability assay, we evaluated cell death in three ovarian cancer cell lines after treatment with clinically relevant doses of eight antihistamines. In our cohort study, CAD antihistamine use (?1 prescription; n?=?133) was associated with a hazard ratio of 0.63 (95% CI = 0.40 to 0.99) compared to use of non-CAD antihistamines (n?=?304), and we found a tendency toward a dose-response association. In our cell viability assay, we found consistent and dose-dependent cytotoxicity for all CAD but not non-CAD antihistamines. In this nationwide cohort study, use of antihistamines with CAD characteristics is associated with a prognostic benefit in ovarian cancer patients.

SUBMITTER: Verdoodt F

PROVIDER: S-EPMC7492759 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Antihistamines and Ovarian Cancer Survival: Nationwide Cohort Study and in Vitro Cell Viability Assay.

Verdoodt Freija F Dehlendorff Christian C Jäättelä Marja M Strauss Robert R Pottegård Anton A Hallas Jesper J Friis Søren S Kjaer Susanne K SK

Journal of the National Cancer Institute 20200901 9

Antihistamines with cationic amphiphilic drug (CAD) characteristics induce cancer-specific cell death in experimental studies. Epidemiologic evidence is, however, limited. In a Danish nationwide cohort of ovarian cancer patients diagnosed during 2000-2015 (n = 5075), we evaluated the association between filled antihistamine prescriptions and cancer mortality. We used Cox regression models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for ovarian cancer mortality. In an in v ...[more]

PMID: 31688928

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Project description:This study evaluated in vitro cell viability by the colorimetric MTT stands for 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay compared to image analysis by CellProfiler® software.Hepatoma (Hepa-1c1c7) and fibroblast (L929) cells were exposed to isolated substances, camptothecin, lycorine, tazettine, albomaculine, 3-epimacronine, trispheridine, galanthine and Padina gymnospora, Sargassum sp. methanolic extract, and Habranthus itaobinus Ravenna ethyl acetate in different concentrations. After MTT assay, cells were stained with Panotic dye kit. Cell images were obtained with an inverted microscope equipped with a digital camera. The images were analyzed by CellProfiler®.No cytotoxicity at the highest concentration analyzed for 3-epimacronine, albomaculine, galanthine, trispheridine, P. gymnospora extract and Sargassum sp. extract where detected. Tazettine offered cytotoxicity only against the Hepa1c1c7 cell line. Lycorine, camptothecin, and H. itaobinus extract exhibited cytotoxic effects in both cell lines. The viability methods tested were correlated demonstrated by Bland-Atman test with normal distribution with mean difference between the two methods close to zero, bias value 3.0263. The error was within the limits of the confidence intervals and these values had a narrow difference. The correlation between the two methods was demonstrated by the linear regression plotted as R2.CellProfiler® image analysis presented similar results to the MTT assay in the identification of viable cells, and image analysis may assist part of biological analysis procedures. The presented methodology is inexpensive and reproducible.In vitro cell viability assessment with MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay may be replaced by image analysis by CellProfiler®. The viability methods tested were correlated demonstrated by Bland-Atman test with normal distribution with mean difference between the two methods close to zero, bias value 3.0263. The correlation between the two methods was demonstrated by the linear regression plotted as R2. Abbreviations: HPLC: High pressure liquid chromatography MTT: (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide).

Project description:BackgroundPrior reports on a possible female survival advantage in both surgical and nonsurgical cohorts of patients with lung cancer are conflicting. Previously reported differences in survival after lung cancer surgery could be the result of insufficient control for disparities in risk factor profiles in men and women.Research questionDo women who undergo pulmonary resections for lung cancer have a better prognosis than men when taking a wide range of prognostic factors into account?Study design and methodsWe performed a nationwide population-based observational cohort study analyzing sex-specific survival after pulmonary resections for lung cancer. We identified 6356 patients from the Swedish National Quality Register for General Thoracic Surgery and performed individual-level record linkage to other national health-data registers to acquire detailed information regarding comorbidity, socioeconomic status, and vital status. Inverse probability of treatment weighting was used to account for differences in baseline characteristics. The association between female sex and all-cause mortality was assessed with Cox regression models, and flexible parametric survival models were used to estimate the absolute survival differences with 95% CIs. We also estimated the difference in restricted mean survival time.ResultsWe observed a lower risk of death in women compared with men (hazard ratio, 0.73; 95% CI, 0.67-0.79). The absolute survival difference at 1, 5, and 10 years was 3.0% (95% CI, 2.2%-3.8%), 10% (95% CI, 7.0%-12%), and 12% (95% CI, 8.5%-15%), respectively. The restricted mean survival time difference at 10 years was 0.84 year (95% CI, 0.61-1.07 years). The findings were consistent across several subgroups.InterpretationWomen who underwent pulmonary resections for lung cancer had a significantly better prognosis than men. The survival advantage was evident regardless of age, common comorbidities, socioeconomic status, lifestyle factors, physical performance, type and extent of surgery, tumor characteristics, and stage of disease.Trial registryClinicalTrials.gov; No.: NCT03567538; URL: www.clinicaltrials.gov.

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Antihistamines and Ovarian Cancer Survival: Nationwide Cohort Study and in Vitro Cell Viability Assay.

Publications

Antihistamines and Ovarian Cancer Survival: Nationwide Cohort Study and in Vitro Cell Viability Assay.

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