The γ-H2AX foci as an indicator for double-stranded DNA breaks and response to ongoing chemotherapy in breast cancer women: a pilot study.

OBJECTIVE: The double-stranded breaks (DSBs) of the DNA can predispose to cancer development. The γH2AX foci have been proposed for prediction of tumor growth and response to radiotherapy. We aimed to evaluate the γ-H2AX foci as an indicator for DSBs and response to ongoing chemotherapy in breast cancer women. PATIENTS AND METHODS: Twenty-nine (29) breast cancer women, scheduled for adjuvant chemotherapy were included in this pilot study after obtaining written informed consent and approval of the study by the WKMU ethics committee. Participants received adjuvant chemotherapy, according to the treatment protocol of the Republic of Kazakhstan. A peripheral blood sample was collected from each studied participant for analysis of the γ-H2AX foci in the participants' lymphocytes using the immunofluorescent staining kit. Data of the Fluorescein isothiocyanate (FITC) rupture, and Adenomatous Polyposis Coli (APC) repair channels were analyzed to evaluate the γ-H2AX foci as an indicator for DSBs, and response to ongoing chemotherapy. RESULTS: About 10.3% (3/29) of the studied breast cancers were luminal A, 72.4% (21/29) were luminal type B, 13.8% (4/29) were basal-like, and 3.5 (1/29) were HER2 positive. The FITC rupture channel during the ongoing chemotherapy showed significantly decreased foci intensity means (p=0.0075), and significantly increased colocalization (p=0.02). The APC repair channels during the ongoing chemotherapy showed significantly increased nuclei intensity (p=0.046), foci overall (p=0.0007), clusters (p=0.002), foci mean (p<0.0001), and foci mean + clusters (p=0.0003). It also showed significantly increased clusters positive cells (p<0.0001), foci low intensity (p<0.0001), foci low intensity + clusters (p=0.0003), and clusters of low-intensity positive cells (p=0.002). CONCLUSIONS: The γ-H2AX foci, the changes in the FITC rupture, and APC repair channels can serve as real-time indicators for the response to ongoing chemotherapy in breast cancer women. The γ-H2AX foci as an indicator for DSBs/repair pathway, and for the response to ongoing chemotherapy in breast cancer should be evaluated in further studies.

The relation between vitamin D and the adolescents' mid-luteal estradiol and progesterone.

OBJECTIVE: The aim of this study was to detect the effect of vitamin D (Vit. D) intake on the mid-luteal estradiol (E2), and progesterone (P), and the relation between vit. D, and the adolescents' mid-luteal E2, and P. PATIENTS AND METHODS: Eighty-five (85) adolescents were recruited for this cohort study after obtaining informed consent. After a detailed history and clinical examination, the body mass index (BMI) of the studied participants was calculated, followed by pelvic sonography to exclude any pelvic pathology. Participants' blood samples were collected on days 21-22 of the menstrual cycle (mid-luteal) to measure the thyrotropin (TSH) (i.e., to exclude hypothyroidism), prolactin (i.e., to exclude hyperprolactinemia), glycosylated hemoglobin (HbA1C), (i.e., to exclude diabetes), E2, P, and 25(OH)D.  Participants received 50,000 IU of vit. D weekly for two months, and on the 3rd month, the mid-luteal E2, P, and 25(OH)D were measured. The mid-luteal E2, P, and 25(OH)D were compared before and after the vit. D intake to detect the effect of vit. D intake (50,000 IU weekly for 2 months) on the mid-luteal E2 and P (primary outcome). Additionally, the relations between vit. D and the adolescents' mid-luteal E2 and P were detected as secondary outcomes using the correlation analysis (Pearson's correlation). RESULTS: The mid-luteal E2 and P statistically decreased from 109.3±15.7 pg/mL and 9.8±1.01 ng/mL, respectively to 40.7±10.52 pg/mL, and 5.2±0.73 ng/mL, respectively, after vit. D intake (p=0.00015; 95% CI: 64.5, 68.6, 72.7, and p=0.0016; 95% CI: 4.3, 4.6, 4.87, respectively). Significant negative correlations between the 25(OH)D, and both the mid-luteal E2 (r -0.661; p<0.00001), and P (r -0.521; p<0.00001) were detected in this study. CONCLUSIONS: The mid-luteal E2 and P statistically decreased after vit. D intake (50,000 IU of vit. D weekly for 2 months). Significant negative correlations between the 25(OH)D, and both the mid-luteal E2 and P were detected in this study. The relation between vit. D and ovarian steroids, and the effect of vit. D intake on ovarian steroids need further larger studies.