cholecalciferol and Carcinoma

Topics: Bone Diseases; Calcium; Carcinoma; Cholecalciferol; Chromatin; Dihydroxycholecalciferols; Ergocalciferols; Homeostasis; Humans; Hydroxycholecalciferols; Intestinal Diseases; Intestinal Mucosa; Kidney; Kidney Diseases; Liver; Liver Diseases; Parathyroid Diseases; Receptors, Drug; Skin Diseases; Thyroid Neoplasms; Vitamin D Deficiency

Vitamin D3 might benefit prostate cancer (PCa) patients because prostate cells can locally synthesize the active hormone calcitriol.. Our objective was to determine the effects of oral vitamin D3 on vitamin D metabolites and PCa proliferative activity in prostate tissue.. We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada.. PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol.. Vitamin D3 (400, 10 000, or 40 000 IU/d) was orally administered before radical prostatectomy.. We evaluated vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety measures, PTH, and prostate-specific antigen (PSA) were also assessed.. Prostate tissue and serum levels of vitamin D metabolites, including calcitriol, increased dose dependently (P < .03) and were significantly higher in the 40 000-IU/d group than in every other dose group (P < .03). Prostate vitamin D metabolites correlated positively with serum levels (P < .0001). Ki67 measures did not differ significantly among vitamin D dose groups. However, cross-sectional analysis indicated that the calcitriol level attained in prostate was inversely associated with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign tissue (P < .05). Safety measures did not change adversely with dosing. Compared with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose groups at the end of the study (P < .02).. Oral vitamin D3 raised prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and PTH. Although Ki67 expression did not differ among dose groups, its levels correlated inversely with prostate calcitriol. These suggestions of clinical benefit justify continued clinical research.

Topics: Aged; Carcinoma; Cholecalciferol; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Ki-67 Antigen; Male; Middle Aged; Prostatic Neoplasms; Staining and Labeling; Tissue Array Analysis; Validation Studies as Topic; Vitamin D

We wanted to investigate vitamin D in low-risk prostate cancer.. The objective of the study was to determine whether vitamin D(3) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen (PSA) or in the rate of progression.. In this open-label clinical trial (Investigational New Drug 77,839), subjects were followed up until repeat biopsy.. All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, both in Charleston, SC.. All subjects had a diagnosis of low-risk prostate cancer. Fifty-two subjects were enrolled in the study, 48 completed 1 yr of supplementation, and 44 could be analyzed for both safety and efficacy objectives.. The intervention included vitamin D(3) soft gels (4000 IU).. Adverse events were monitored throughout the study. PSA serum levels were measured at entry and every 2 months for 1 yr. Biopsy procedures were performed before enrollment (for eligibility) and after 1 yr of supplementation.. No adverse events associated with vitamin D(3) supplementation were observed. No significant changes in PSA levels were observed. However, 24 of 44 subjects (55%) showed a decrease in the number of positive cores or decrease in Gleason score; five subjects (11%) showed no change; 15 subjects (34%) showed an increase in the number of positive cores or Gleason score.. Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3) supplementation at 4000 IU/d.

Topics: Aged; Biopsy, Fine-Needle; Carcinoma; Cholecalciferol; Dietary Supplements; Dose-Response Relationship, Drug; Down-Regulation; Humans; International System of Units; Male; Middle Aged; Population Surveillance; Prostate; Prostatic Neoplasms; Risk Factors; Time Factors; Treatment Outcome; Watchful Waiting

Vitamin D3 might benefit prostate cancer (PCa) patients because prostate cells can locally synthesize the active hormone calcitriol.. Our objective was to determine the effects of oral vitamin D3 on vitamin D metabolites and PCa proliferative activity in prostate tissue.. We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada.. PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol.. Vitamin D3 (400, 10000, or 40000 IU/d) was orally administered before radical prostatectomy.. We evaluated vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety measures, PTH, and prostate-specific antigen (PSA) were also assessed.. Prostate tissue and serum levels of vitamin D metabolites, including calcitriol, increased dose dependently (P<.03) and were significantly higher in the 40000-IU/d group than in every other dose group (P<.03). Prostate vitamin D metabolites correlated positively with serum levels (P<.0001). Ki67 measures did not differ significantly among vitamin D dose groups. However, cross-sectional analysis indicated that the calcitriol level attained in prostate was inversely associated with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign tissue (P<.05). Safety measures did not change adversely with dosing. Compared with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose groups at the end of the study (P< .02).. Oral vitamin D3 raised prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and PTH. Although Ki67 expression did not differ among dose groups, its levels correlated inversely with prostate calcitriol. These suggestions of clinical benefit justify continued clinical research.

Topics: Carcinoma; Cholecalciferol; Humans; Ki-67 Antigen; Male; Prostatic Neoplasms; Vitamin D

Both insulin resistance (IR) and vitamin D deficiency (VDD) are found to be associated with many cancer types. In this study, we evaluated the presence of IR and VDD in thyroid cancer patients based on controls. Total 344 papillary thyroid cancer and 116 controls were part of the study. Glucose, insulin, homeostasis model analysis-insulin resistance (HOMA-IR) (control group 2.12 ± 0.9 and patient group 3.6 ± 1.1; p < 0.0001), LDL were significantly high; HOMA-S and vitamin D3 levels (control group 19.11 ± 8 and patient group 17 ± 16; p = 0.004) were significantly low in the patient group. Vitamin D deficiency (64/108 in controls vs 166/235; p = 0.026) and insulin resistance (24/108; 115/235; p < 0.0001) were more frequent in papillary thyroid cancer patients. After regression analysis, tumor diameter showed significant association with log-HOMA-IR (B = 0.315; p = 0.017) and log-vitamin D3 (B = 0.207; p = 0.04). Vitamin D deficiency and insulin resistance frequencies show no difference between micro- and macropapillary thyroid cancers. Receiver operating characteristic curve shows the best cutoff point for tumor diameter showing that the presence of lymph node metastasis was 0.65 cm with 81.2 % sensitivity and 52 % specificity. Best cutoff point for the capsular invasion tumor diameter was 0.75 cm with 83.3 % sensitivity and 60.4 % specificity. No difference between follicular and classical type papillary thyroid carcinomas has been yet discovered. As a result, thyroid cancer patients are more insulin resistant and vitamin D3 deficient. Vitamin D3 levels and HOMA-IR index may affect tumor diameter. Tumor size that is lower than 1 cm (0.65-0.75 cm) may be related with capsular invasion and lymph node involvement.

Topics: Adult; Carcinoma; Carcinoma, Papillary; Case-Control Studies; Cholecalciferol; Female; Folic Acid; Homeostasis; Humans; Insulin Resistance; Male; Middle Aged; ROC Curve; Thyroglobulin; Thyroid Cancer, Papillary; Thyroid Neoplasms; Vitamin B 12

The classic role of vitamin D is its effect on calcium and phosphate homeostasis. The subject of interest in recent years has been its non-calcemic impact on neoplastic processes and the immune system. The aim of the study was to assess 25(OH)D3 concentrations in patients treated for papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT).. The study included 80 patients aged 19-83 years (average age 52.96 years) treated between 2000-2011 in Swietokrzyskie Centrum Onkologii. The analysis was conducted in two groups of patients: a PTC group of 40 women aged 19 to 83 years (average age 50.40 years) and a HT group of 40 women aged 30 to 75 years (average age 55.73 years). The group of PTC patients was further divided into two subgroups: 19 patients with micro. carcinoma (T1a) and 21 patients with a higher grade of cancer (>T1a). A group of patients with HT comprised women treated with subsitutive doses of L-thyroxine for hypothyroidism. The serum concentration of 25(OH)D3 was compared in both groups: PTC vs. HT. Among patients with PTC serum 25(OH)D3 was analysed depending on the concentration of TSH: TSH< or = 0.1 microlU/ml vs. TSH> 0.1 microlU/ml, and depending on the stage of cancer: Tla vs.> T1a.. There were no differences in the prevalence of hypovitaminosis and vitamin D deficiency in both groups (65% of patients with PTC vs. 62.5% with HT). In the PTC group no statistically significant differences in serum 25(OH)3, depending on the con. centration of TSH and cancer clinical stage, were found.. This study showed no difference in concentrations of 25(OH)D3 in patients with papillary thyroid cancer and Hashimoto's thy. roiditis. Patients with PTC showed no relationship between serum 25(OH)D3 and clinical stage of the disease or TSH.level.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Cholecalciferol; Female; Hashimoto Disease; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyrotropin; Young Adult

A Japanese Black bull aged 20 years died following progressive loss of the body weight. Pathological examination disclosed multiple endocrine tumors including thyroid C cell carcinoma with metastases to the cervical lymph nodes and lung, adrenal pheochromocytoma and pituitary chromophobe adenoma in the pars distalis. The serum calcium content was as mildly low as 8.0 mg/dl at the terminal stage. The bull had daily ingested the ration containing 1.9 times the recommended calcium amount for 8 years and 120,000 units of vitamin D(3) for 5 years prior to death. The long-term dietary intake of moderately excessive calcium with vitamin D(3) might be related to the pathogenesis of the thyroid C cell carcinoma.

Topics: Adenoma; Adrenal Gland Neoplasms; Animals; Calcitonin; Calcium, Dietary; Carcinoma; Cattle; Cattle Diseases; Cholecalciferol; Male; Multiple Endocrine Neoplasia; Pheochromocytoma; Pituitary Neoplasms; Thyroid Neoplasms

Data from epidemiological studies has suggested that vitamin D deficiency may promote prostate cancer, although the mechanism is not understood. We have previously demonstrated the presence of vitamin D receptors (VDR) in three human prostate carcinoma cell lines (LNCaP, PC-3, and DU-145) as well as in primary cultures of stromal and epithelial cells derived from normal and malignant prostate tissues. We have also shown that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can elicit an antiproliferative action in these cells. In the present study we compared the biological actions of 1,25-(OH)2D3 to those of a series of natural vitamin D3 metabolites and several synthetic analogs of vitamin D3 known to exhibit less hypercalcemic activity in vivo. In ligand binding competition experiments, we demonstrated the following order of potency in displacing [3H]1,25-(OH)2D3 from VDR: EB-1089 > 1,25-(OH)2D3 > MC-903 > 1,24,25-(OH)3D3 > 22-oxacalcitriol (OCT) > 1 alpha,25-dihydroxy-16-enecholecalciferol (Ro24-2637) > 25-hydroxyvitamin D3, with EB-1089 being approximately 2-fold more potent than the native hormone. No competitive activity was found for 25-hydroxy-16,23-diene-cholecalciferol. When compared for ability to inhibit proliferation of LNCaP cells, MC-903, EB-1089, OCT, and Ro24-2637 exhibited 4-, 3-, and 2-fold greater inhibitory activity than 1,25-(OH)2D3. Interestingly, although OCT and Ro24-2637 exhibit, respectively, 10 and 14 times lower affinity for VDR than 1,25-(OH)2D3, both compounds inhibited the proliferation of LNCaP cells with a potency greater than that of the native hormone. The relative potency of vitamin D3 metabolites and analogs to inhibit cell proliferation correlated well with the ability of these compounds to stimulate prostate-specific antigen secretion by LNCaP cells as well as with their potency to induce the 25-hydroxyvitamin D3-24-hydroxylase messenger RNA transcript in PC-3 cells. In conclusion, these results demonstrate that synthetic analogs of vitamin D3, known to exhibit reduced calcemic activity, can elicit antiproliferative effects and other biological actions in LNCaP and PC-3 cell lines. It is noteworthy that although binding to VDR is critical for 1,25-(OH)2D3 action, the analog data indicate that additional factors significantly contribute to the magnitude of the biological response. Finally, the strong antiproliferative effects of several synthetic analogs known to exhibit less calcemic activity than 1,25-(OH)2D3 suggest that

Topics: Binding Sites; Calcitriol; Carcinoma; Cell Division; Cholecalciferol; Cytochrome P-450 Enzyme System; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Calcitriol; RNA, Messenger; Steroid Hydroxylases; Tumor Cells, Cultured; Vitamin D3 24-Hydroxylase

Topics: Animals; Calcium; Carcinoma; Cholecalciferol; Diet; Female; Iodine Radioisotopes; Male; Radiation Dosage; Rats; Rats, Inbred Strains; Thyroid Neoplasms