scholarly journals Polymorphism of VDR Gene and the Sensitivity of Human Leukemia and Lymphoma Cells to Active Forms of Vitamin D

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 387
Author(s):  
Justyna Joanna Gleba ◽  
Dagmara Kłopotowska ◽  
Joanna Banach ◽  
Eliza Turlej ◽  
Karolina Anna Mielko ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Lines ◽  
Vitamin D3 ◽  
Human Leukemia ◽  
Lymphoma Cells ◽  
Vdr Gene ◽  
Vdr Polymorphism ◽  
Anti Cancer ◽  
The Impact ◽  
Morphology Changes

The active forms of vitamin D3 (calcitriol and tacalcitol) coupled to the vitamin D receptor (VDR) are known to exhibit anti-cancer properties. However, not all cancer cells are sensitive to the active forms of vitamin D3 and its analogs. The study aimed to determine whether polymorphism of VDR is responsible for the sensitivity of human leukemia and lymphoma cells to calcitriol and tacalcitol. The impact of calcitriol and tacalcitol on the proliferation and morphology of nine different leukemia and lymphoma cell lines was determined. Only MV-4-11, Thp-1, and HL-60 cell lines sensitive to proliferation inhibition by calcitriol and tacalcitol showed morphology changes. Subsequently, the levels of the VDR and 1,25D3-MARRS proteins of calcitriol and tacalcitol binding receptors and the VDR receptor polymorphism in human leukemia and lymphoma cells were ascertained. Contrary to the current understanding, higher levels of VDR are not responsible for the greater sensitivity of cells to calcitriol and tacalcitol. Importantly, we first showed that sensitivity to calcitriol and tacalcitol in leukemias and lymphomas could be determined by the VDR polymorphism. The FokI polymorphism and the presence of the “bat” haplotype were observed only in the sensitive cells.

scholarly journals Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus

2002 ◽  
pp. 803-808 ◽  
Author(s):  
B Gyorffy ◽  
B Vasarhelyi ◽  
D Krikovszky ◽  
L Madacsy ◽  
A Tordai ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Vitamin D Receptor ◽  
Vdr Gene ◽  
Vdr Polymorphism ◽  
The Impact ◽  
Vdr Polymorphisms

OBJECTIVE: Recent data have indicated the significance of vitamin D receptor (VDR) polymorphisms in type 1 diabetes mellitus (T1DM). We have studied the association of five known restriction enzyme polymorphisms of the VDR gene in patients with T1DM. DESIGN AND METHODS: One hundred and seven children with T1DM (T1DM for 5 Years; age, 1-14 Years; boys/girls, 57/50; body mass index, 17.0+/-2.3 kg/m(2); haemoglobin A(Ic) (HbA(Ic)), 7.87+/-1.05) and 103 healthy subjects were enrolled. The VDR polymorphisms ApaI, BsmI, FokI, TaqI and Tru9I ("a", "b", "f", "t" and "u" alleles respectively) were investigated. RESULTS: The "t" and "T" alleles miss the Hardy-Weinberg equilibrium (P<0.01) in control and diabetic populations; we therefore excluded this polymorphism from further analysis. We did not find a difference in the allele prevalence in T1DM patients and controls of any of the five polymorphisms. However, when the "b", "a" and "u" alleles were simultaneously compared in girls, there was a significantly higher prevalence in patients with diabetes compared with controls ("b"+"a"+"u" present/absent: healthy, 0/53; diabetic, 13/37; P<0.005). In boys the prevalence of "b"+"a"+"u" genotype was similar in T1DM and controls. CONCLUSIONS: The impact of the "t" allele cannot be investigated in this study population. Not a single VDR polymorphism increases the susceptibility to T1DM. The common presence of the "b", "a" and "u" alleles greatly increases the probability of T1DM in girls.

scholarly journals Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Damir Raljević ◽  
Viktor Peršić ◽  
Elitza Markova-Car ◽  
Leon Cindrić ◽  
Rajko Miškulin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Vitamin D ◽  
Coronary Artery ◽  
Vitamin D Receptor ◽  
Gene Polymorphisms ◽  
Vdr Gene ◽  
Vdr Polymorphism ◽  
Vdr Gene Polymorphisms ◽  
Vdr Polymorphisms

Abstract Background Vitamin D deficiency is associated with cardiovascular diseases, including coronary artery diseases (CAD). As vitamin D manifests its biological function through its vitamin D receptor (VDR), VDR gene polymorphisms potentially affect VDR functionality and vitamin D activity. Therefore, the objective of this study was to analyze three well-studied VDR gene polymorphisms—Fok1 (rs2228570), BsmI (rs1544410) and Taq1 (rs731236)—in a cohort of CAD patients after acute myocardial infarction. Methods In the presented cross-sectional study, 155 participants with CAD after acute myocardial infarction and 104 participants in a control group without CAD were enrolled. The participants in both groups were Caucasians of European origin. The genotyping of VDR polymorphisms rs2228570, rs1544410 and rs731236 was assessed by RT-PCR. Results The results show an association between the T/T genotype of the BsmI (rs1544410) and the G/G genotype of the Taq1 (rs731236) VDR polymorphism and CAD patients after acute myocardial infarction. There was no association between the Fok1 (rs2228570) VDR polymorphism and CAD patients after acute myocardial infarction. Conclusion The presented results suggest a potential association of the BsmI (rs1544410) and Taq1 (rs731236) VDR polymorphisms with CAD patients after myocardial infarction.

Vitamin D as Radiosensitizer: A Review in Cell Line -

2020 ◽  
Vol 10 (6) ◽  
pp. 315-324
Author(s):  
Fahmi Radityamurti ◽  
Fauzan Herdian ◽  
Tiara Bunga Mayang Permata ◽  
Handoko Handoko ◽  
Henry Kodrat ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Differentiation ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agent ◽  
Medical Literature ◽  
In Vitro Studies ◽  
Anti Cancer

Introduction: Vitamin D has been shown to have anti-cancer properties such as antioxidants, anti-proliferative, and cell differentiation. The property of vitamin D as an anticancer agent triggers researchers to find out whether vitamin D is useful as a radiosensitizer. Multiple studies have been carried out on cell lines in various types of cancer, but the benefits of vitamin D as a radiosensitizer still controversial. This paperwork aims to investigate the utilization of Vitamin D3 (Calcitriol) as radiosensitizer in various cell line through literature review.Methods: A systematic search of available medical literature databases was performed on in-vitro studies with Vitamin D as a radiosensitizer in all types of cell lines. A total of 11 in-vitro studies were evaluated.Results: Nine studies in this review showed a significant effect of Vitamin D as a radiosensitizer agent by promoting cytotoxic autophagy, increasing apoptosis, inhibiting of cell survival and proliferation, promoting gene in ReIB inhibition, inducing senescene and necrosis. The two remaining studies showed no significant effect in the radiosensitizing mechanism of Vitamin D due to lack of evidence in-vitro settings.Conclusion: Vitamin D have anticancer property and can be used as a radiosensitizer by imploring various mechanism pathways in various cell lines. Further research especially in-vivo settings need to be evaluated.

scholarly journals P1.20 CDX2 VDR Polymorphism Impinges on the Response of Cultured Breast Cancer Cell Lines to Vitamin D

2012 ◽  
Vol 23 ◽  
pp. v17-v18
Author(s):  
C. Pulito ◽  
I. Terrenato ◽  
A. Sacconi ◽  
F. Biagioni ◽  
M. Mottolese ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Vdr Polymorphism

scholarly journals THE IMPACT OF DIFFERENT REGIMENS OF VITAMIN D3 ON GLUCOSE HOMEOSTASIS IN TYPE 2 DIABETIC PATIENTS

2019 ◽  
pp. 21-26
Author(s):  
SAMIA MOHAMED ALI ◽  
YEHIA MOSTAFA GHANEM ◽  
OLA ATEF SHARAKI ◽  
WAFAA AHMED HEWEDY ◽  
ESRAA SAEED HABIBA
Keyword(s):  
Vitamin D ◽  
Glucose Homeostasis ◽  
Vitamin D3 ◽  
Antidiabetic Drugs ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Parenteral Dose ◽  
Vitamin D Levels ◽  
The Impact

Objective: Vitamin D has a role in the regulation of pancreatic β-cell function and insulin sensitivity. Accordingly, Vitamin D deficiency is considered to be a risk factor for the development of type 2 diabetes mellitus (T2DM) and its complications. Therefore, the aim of the study was to assess and compare the effect of different regimens of Vitamin D3 on glucose homeostasis in patients with T2DM. Methods: The study included 80 patients with T2DM taking oral antidiabetic drugs. The patients were randomized to receive antidiabetic drugs alone or with different regimens of Vitamin D3 for 3 months. Vitamin D3-treated patients were supplemented by either daily oral 4000 IU Vitamin D3, weekly oral 50,000 IU Vitamin D3, or a single parenteral dose of 300,000 IU Vitamin D3. In addition to the assessment of patient characteristics, laboratory measurements of serum creatinine, blood urea, total and ionized calcium, serum phosphorus, fasting blood glucose, fasting serum insulin, homeostasis model assessment of insulin resistance, hemoglobin A1c, and 25(OH) Vitamin D levels were measured at the beginning and after 3 months. Results: After 3 months, the increased Vitamin D levels resulting from the daily and weekly oral doses of Vitamin D3 caused a significant decrease in metabolic parameters, whereas the parenteral dose demonstrated a non-significant decrease. Conclusion: Oral daily and weekly doses of Vitamin D3 could improve glucose homeostasis equally in patients with T2DM and better than a single parenteral dose of Vitamin D3.

Combination of Farnesyl Transferase Inhibitor (Tipifarnib) with Perifosine Induces Apoptosis through phos-PDK1 in Human Lymphoma and Leukemia Cell Lines.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1488-1488 ◽  
Author(s):  
Ebenezer David ◽  
Rajni Sinha ◽  
Claire Torre ◽  
Jonathan L. Kaufman ◽  
Sagar Lonial
Keyword(s):  
Cell Death ◽  
Western Blot ◽  
Cell Lines ◽  
Blot Analysis ◽  
Leukemia Cell ◽  
Human Leukemia ◽  
Targeted Agents ◽  
Leukemia Cell Lines ◽  
Targeted Agent ◽  
The Impact

Abstract Introduction: Novel agents as anti-cancer therapy are used in the setting of specific molecular abnormalities that provide a survival advantage for malignant cells. One such agent, tipifarnib, is theoretically targeted at Ras mutations which are present in a number of different human cancers. Our previous experience with the FTIs (David et al, in press Blood) has demonstrated that they are ideal agents to combine with other targeted agents. We have investigated the combination of the AKT inhibitor perifosine with tipifarnib in human leukemia and lymphoma cell lines with the hypothesis that the combination of 2 targeted agents will disrupt separate survival pathways and ultimately result in synergistic tumor cell death. Methods: In this study we used the human leukemia cell lines HL-60, Jurkat, and the lymphoma cell line HT. Western blot analysis was used to assess for the effect of either single agent perifosine, tipifarnib, or the combination on AKT, p-AKT, PDK-1, and caspase cleavage. Flow cytometry was utilized to assess for Annexin V staining following combination therapy. Results:Dose escalation studies demonstrated that doses of tipifarnib up to 5μm demonstrated a significant cell death in HL-60 and HT cells. Perifosine doses of 1–5uM also induced cell death in both HL-60 and HT cells. When apoptosis was assessed using western blot analysis of caspase 3 activity and cleavage, the combination of perifosine and tipifarnib demonstrated significant apoptosis using low doses of both agents. The apoptosis was associated with downregulation of phos-PDK1, with a resultant downregulation in p-AKT. The level of phos-PDK1 was completely inhibited in less than 24 hrs in both the HL-60 and HT cell lines in combination than when either agent was given alone. Conclusion: The combination of perifosine, and AKT targeted agent, with tipifarnib, a Ras targeted agent, appear to induce significant cell death in lymphoma and leukemia cell lines with rapid downregulation of p-AKT via the PDK-1 pathway. This apoptosis occurs in vitro using concentrations well below those that have been achieved in current clinical trials using these agents. Additional studies are being carried out to further delineate the mechanism of synergy as well as to further explore the impact of sequence of administration using this combination. Further studies are also planned to xplore the impact of the combination on primary human leukemia and lymphoma cells from the blood and bone marrow.

scholarly journals Vitamin D receptor as a target for breast cancer therapy

2017 ◽  
Vol 24 (4) ◽  
pp. 181-195 ◽  
Author(s):  
Alyson Murray ◽  
Stephen F Madden ◽  
Naoise C Synnott ◽  
Rut Klinger ◽  
Darran O'Connor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Active Form ◽  
Cancer Cell Line ◽  
Breast Cancer Cell Lines ◽  
Negative Cell ◽  
Anti Cancer

Considerable epidemiological evidence suggests that high levels of circulating vitamin D (VD) are associated with a decreased incidence and increased survival from cancer, i.e., VD may possess anti-cancer properties. The aim of this investigation was therefore to investigate the anti-cancer potential of a low calcaemic vitamin D analogue, i.e., inecalcitol and compare it with the active form of vitamin D, i.e., calcitriol, in a panel of breast cancer cell lines (n = 15). Using the MTT assay, IC50concentrations for response to calcitriol varied from 0.12 µM to >20 µM, whereas those for inecalcitol were significantly lower, ranging from 2.5 nM to 63 nM (P = 0.001). Sensitivity to calcitriol and inecalcitol was higher in VD receptor (VDR)-positive compared to VDR-negative cell lines (P = 0.0007 and 0.0080, respectively) and in ER-positive compared to ER-negative cell lines (P = 0.043 and 0.005, respectively). Using RNA-seq analysis, substantial but not complete overlap was found between genes differentially regulated by calcitriol and inecalcitol. In particular, significantly enriched gene ontology terms such as cell surface signalling and cell communication were found after treatment with inecalcitol but not with calcitriol. In contrast, ossification and bone morphogenesis were found significantly enriched after treatment with calcitriol but not with inecalcitol. Our preclinical results suggest that calcitriol and inecalcitol can inhibit breast cancer cell line growth, especially in cells expressing ER and VDR. As inecalcitol is significantly more potent than calcitriol and has low calcaemic potential, it should be further investigated for the treatment of breast cancer.

scholarly journals The role of vitamin D3 in signaling pathways – potential anticancer properties of calcitriol and its analogues

2019 ◽  
Vol 73 ◽  
pp. 920-936
Author(s):  
Olga Wiecheć
Keyword(s):  
Vitamin D ◽  
Cancer Cells ◽  
Vitamin D3 ◽  
Active Form ◽  
Signalling Pathways ◽  
Active Metabolites ◽  
Anticancer Properties ◽  
Anti Cancer ◽  
Worse Prognosis

Vitamin D, for many years after the discovery, primarily was associated with bone metabolic processes. Currently, many studies indicate its beneficial effect in the prevention and treatment of many diseases, including cancer. However, deficiency of vitamin D is associated with greater tendency to get sick and worse prognosis in treatment, especially cancer. Calcitriol, an active form of vitamin D (1.25(OH)2D3) and its analogues have a pleiotropic activity, including anti-cancer properties. Many studies indicate, that the active forms of vitamin D3 may show anti-proliferative effects in cancer cells by inhibiting the cell cycle, inducing differentiation or leading to apoptosis and enhancing autophagy. Also, extremely important are the possibilities of reducing the invasiveness of tumours through the influence on angiogenesis or adhesion and others. Especially, the anti-cancer role of vitamin D3 is suggested in the case of tumors whose cells express VDR receptors. Interestingly, many cancer cells not only express the VDR receptors, but also due to the expression of CYP27B1 and CYP24A hydroxylases, they can regulate metabolism of calcitriol. Many of the studies using vitamin D3 show that calcitriol and its analogues, due to the influence on cancer cells, can play promising roles in anticancer therapies. Consider the broad pleiotropism of the action of active metabolites of vitamin D3 and the development of research in this field, the current work presents the effect of active forms of vitamin D on some signalling pathways and the regulation of selected proteins in various cancers.

scholarly journals Vitamin D sebagai Terapi Potensial Anak Gizi Buruk

2019 ◽  
Vol 1 (1) ◽  
pp. 61-70
Author(s):  
Lisa Dwi Aryani ◽  
Muhammad Aldy Riyandry
Keyword(s):  
Vitamin D ◽  
Literature Review ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Child Nutrition ◽  
Infant Health ◽  
Well Being ◽  
High Dose ◽  
Z Score ◽  
The Impact

Masalah malnutrisi (gizi buruk) masih menjadi isu kesehatan global. Gizi buruk merupakan penyebab kematian tertinggi anak di negara berkembang. Malnutrisi adalah keadaan kekurangan energi dan protein berat akibat ketidakseimbangan antara ambilan makanan dengan kebutuhan gizi. Keadaan malnutrisi energi-protein sering dikaitkan dengan temuan kasus defisiensi vitamin D. Berdasarkan studi epidemiologi >50% anak malnutrisi berat juga mengalami defisiensi vitamin D. Pengoreksian melalui diet terapeutik sebagai standar pengobatan hanya mengandung vitamin D dalam jumlah sedang sehingga tidak cukup adekuat untuk mencukupi kebutuhan anak. Pemberian tambahan vitamin D3 dosis tinggi sebanyak 200.000 IU (5 mg) diduga mampu mengoreksi keadaan gizi buruk dengan meningkatkan berat badan dan nilai z-score anak. Literature review ini bertujuan untuk menjelaskan pengaruh pemberian vitamin D dalam memperbaiki tampilan klinis anak gizi buruk. Metode yang digunakan dalam artikel ini adalah penelusuran artikel melalui database NCBI dan Google Scholar. Tahun penerbitan sumber pustaka adalah dari tahun 2004 hingga 2019 dengan 29 sumber pustaka. Tema dalam artikel yang dikumpulkan yaitu terkait gambaran pengaruh pemberian vitamin D dalam meningkatkan berat badananak gizi buruk. Hasil dari sintesa 24 artikel yang telah ditemukan terdapat pengaruh pemberian vitamin D (cholecalciferol) terhadap kenaikan berat badan sebagai hasil kumulatif lemak di jaringan adiposa sehingga cukup potensial sebagai terapi gizi buruk.   Kata kunci: Vitamin D, gizi buruk, berat badan, cholecalciferol   VITAMIN D AS POTENTIAL THERAPY FOR MALNUTRITION CHILD   ABSTRACT Malnutrition (malnutrition) is still a global health problem. Malnutrition is the highest cause of deaths children in developing countries. Malnutrition is the impact of lack of energy and protein due to an imbalance between food intake and nutritional needs. The symptoms are marasmus, kwashiorkor or marasmik-kwashiorkor. Energy-protein malnutrition is often related to the case finding of vitamin D deficiency, which is caused by epidemiological studies>50% of severely malnourished children also have vitamin D deficiency. Correcting malnutrition with a therapeutic diet as a standard is sufficient to meet the child's needs. An additional 200,000 IU (5 mg) of high-dose vitamin D3 supplements can replace malnutrition by increasing the child's weight and z-score. This review summarizes the role of vitamin D as a potential therapy in improving infant health and well-being and malnutrition. The method taken by the article was made using the literature review method, involving 29 books, national or international journals. The results of a review of 24  articles that show the difference between vitamin D (cholecalciferol) and weight gain as a result of cumulative fat in adipose tissue through increased intracellular calcium, is quite potentially used as a supplementary therapy for child nutrition.   Keywords: vitamin D, malnutrition, weight, cholecalciferol

scholarly journals Vitamin D Deficiency Enhances Non-typeable Haemophilus Influenzae Clearance During Repeated Infections but Worsens Lung Function, Irrespective of Cigarette Smoke Exposure

2021 ◽  
Author(s):  
Jef Serré ◽  
Ajime Tom Tanjeko ◽  
Carolien Mathyssen ◽  
Tobias Heigl ◽  
Dana Paulina Cook ◽  
...  
Keyword(s):  
Vitamin D ◽  
Lung Function ◽  
Vitamin D Deficiency ◽  
Cigarette Smoke ◽  
Vitamin D3 ◽  
Inflammatory Cells ◽  
Cigarette Smoke Exposure ◽  
Copd Patients ◽  
Repeated Infections ◽  
The Impact

Abstract Background: In chronic obstructive pulmonary disease (COPD), exacerbations cause acute inflammatory flare-ups and increase the risk for hospitalization and mortality. Exacerbations are common in all disease stages and are often caused by bacterial infections e.g., non-typeable Heamophilus influenzae (NTHi). Accumulating evidence also associates vitamin D deficiency with the severity of COPD and exacerbation frequency. However, it is still unclear whether vitamin D deficiency when combined with cigarette smoking would worsen and prolong exacerbations caused by repeated infections with the same bacterial strain. Methods: vitamin D sufficient (VDS) and deficient (VDD) mice were exposed to nose-only cigarette smoke (CS) for 14 weeks and oropharyngeally instilled with NTHi at week 6, 10 and 14. Three days after the last instillation, mice were assessed for lung function, remodeling, inflammation and immunity. The impact of VDD and CS on inflammatory cells and immunoglobulin (Ig) production was also assessed in non-infected animals while serum Ig production against NTHi and dsDNA was measured in COPD patients before and 1 year after supplementation with Vitamin D3. Results: VDD enhanced NTHi eradication, independently of CS and complete eradiation was reflected by decreased anti-NTHi Ig’s within the lung. In addition, VDD led to an increase in total lung capacity (TLC), lung compliance (Cchord), MMP12/TIMP1 ratio with a rise in serum Ig titers and anti-dsDNA Ig’s. Interestingly, in non-infected animals, VDD exacerbated the CS-induced anti-NTHi Ig’s, anti-dsDNA Ig’s and inflammatory cells within the lung. In COPD patients, serum Ig production was not affected by vitamin D status but anti-NTHi IgG increased after vitamin D3 supplementation in Vitamin D insufficient patients before treatment. Conclusion: During repeated infections, VDD facilitated NTHi eradication and resolution of local lung inflammation through production of anti-NTHi Ig, independently of CS but it also produced autoantibodies. In COPD patients, vitamin D supplementation might be protective against NTHi infections in vitamin D insufficient patient. Future research is needed to decipher the protective or self-destructive effects of VDD on adaptive immunity.Trail registration: ClinicalTrails, NCT00666367. Registered 23 April 2008, https://www.clinicaltrials.gov/ct2/show/study/NCT00666367

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