Gallium nitrate inhibits accelerated bone turnover in patients with bone metastases.

Bone metastases are a major source of morbidity in patients with cancer. Previously, we found that gallium nitrate was a highly effective treatment for cancer-related hypercalcemia. Laboratory studies have shown that this drug inhibits bone resorption in vitro and that short-term treatment in vivo increases the calcium content of bone. We evaluated the clinical effects of gallium nitrate on biochemical parameters of increased bone turnover in 22 patients with bone metastases. Treatment with gallium nitrate for five to seven days caused a median reduction in 24-hour urinary calcium excretion of 66% relative to baseline measurements (P less than .01). Hydroxyproline (OHP) excretion was also significantly reduced (P less than .01). The greatest reduction in hydroxyprolinuria occurred in patients with high baseline excretion. Ionized serum calcium and serum phosphorous declined significantly after treatment (P less than .01 for each). Serum immunoreactive parathyroid hormone (PTH) increased significantly (P less than .01), as did serum levels of 1,25 (OH)2-vitamin D3 (P less than .05). Urinary phosphorous excretion and serum levels of 25-OH-vitamin D3 were not significantly changed. No major toxic reactions occurred as a result of this treatment. These results indicate that gallium nitrate significantly reduces biochemical parameters associated with accelerated bone turnover and that this agent may be useful for preventing pathologic conditions associated with bone metastases.

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Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide

Cancers ◽

10.3390/cancers13143577 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3577

Author(s):

Julia Gerstmeier ◽

Anna-Lena Possmayer ◽

Süleyman Bozkurt ◽

Marina E. Hoffmann ◽

Ivan Dikic ◽

...

Keyword(s):

Vitamin D3 ◽

Ex Vivo ◽

Active Form ◽

Treatment Resistance ◽

Serum Levels ◽

Disease Recurrence ◽

Primary Brain Tumor ◽

High Rate ◽

Therapeutic Doses

Glioblastoma (GBM) is the most common and most aggressive primary brain tumor, with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evidence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infiltrative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the expression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show, using in vitro limiting dilution assays, quantitative real-time PCR, quantitative proteomics and ex vivo adult organotypic brain slice transplantation cultures, that therapeutic doses of calcitriol, the hormonally active form of vitamin D3, reduce stemness to varying extents in a panel of investigated GSC lines, and that it effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to completely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in follow-up studies.

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Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-1515 ◽

2016 ◽

Vol 101 (6) ◽

pp. 2371-2379 ◽

Cited By ~ 34

Author(s):

Mariko Miyashita ◽

Kaori Koga ◽

Gentaro Izumi ◽

Fusako Sue ◽

Tomoko Makabe ◽

...

Keyword(s):

Dna Synthesis ◽

Vitamin D3 ◽

Serum Levels ◽

Cell Counting ◽

Prostaglandin E ◽

Viable Cell Number ◽

Prostaglandin E Synthase ◽

1,25 Dihydroxy Vitamin D3 ◽

Microsomal Prostaglandin E Synthase

Abstract Context: Endometriosis is an estrogen-dependent, chronic inflammatory disease. Recent studies have shown that vitamin D (VD) is an effective modulator of the immune system and plays an important role in controlling many inflammatory diseases. Objective: The objective of the study was to clarify the in vitro effects of 1,25-dihydroxy vitamin D3 (1,25[OH]2D3) on human endometriotic stromal cells (ESCs) and to determine the serum levels of VD in endometriosis patients. Design, Patients, and Main Outcome Measures: ESCs were isolated from ovarian endometrioma and cultured with 1,25(OH)2D3. Gene expression of IL-8, cyclooxygenase-2, microsomal prostaglandin E synthase-1, microsomal prostaglandin E synthase-2, cytosolic prostaglandin E synthase, 15-hydroxyprostaglandin dehydrogenase, matrix metalloproteinase (MMP)-2, and MMP-9 was examined using quantitative RT-PCR. The production of IL-8 and prostaglandin E2 was measured using an ELISA and an enzyme immunoassay. Viable cell number was assessed using a cell-counting assay, and DNA synthesis was assessed using the bromodeoxyuridine incorporation assay. Apoptosis was assessed using flow cytometry. The expression of inhibitory-κBα protein was detected using Western blotting. The serum levels of 25-hydroxyvitamin D3 and 1,25(OH)2D3 were measured by a RIA. Results: In vitro studies showed that 1,25(OH)2D3 significantly reduced IL-1β- or TNF-α-induced inflammatory responses, such as IL-8 expression and prostaglandin activity. 1,25(OH)2D3 also reduced viable ESC numbers and DNA synthesis but did not affect apoptosis. MMP-2 and MMP-9 expressions were reduced by 1,25(OH)2D3. 1,25(OH)2D3 inhibited nuclear factor-κB activation. The serum 25-hydroxyvitamin D3 levels were significantly lower in women with severe endometriosis than in the controls and women with mild endometriosis. Serum 1,25(OH)2D3 levels were not different between groups. Conclusions: VD modulates inflammation and proliferation in endometriotic cells, and a lower VD status is associated with endometriosis. Taken together, VD supplementation could be a novel therapeutic strategy for managing endometriosis.

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CA 15.3 with Urinary Calcium Excretion is Useful in the Diagnosis and Monitoring of Bone Metastases from Breast Cancer

The International Journal of Biological Markers ◽

10.1177/172460089300800402 ◽

1993 ◽

Vol 8 (4) ◽

pp. 208-214

Author(s):

G.C. Yadav ◽

A. Rao ◽

M.M. Motawy ◽

N. Safadi ◽

M. Jameel Ahmed

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Bone Metastases ◽

Serum Levels ◽

Urinary Calcium ◽

Response To Therapy ◽

Urinary Calcium Excretion ◽

Calcium Excretion ◽

Diagnostic Efficacy ◽

Ca 15.3

Serum levels of breast carcinoma antigen (CA 15.3) and urinary calcium excretion (UCa) were determined in 73 patients with breast cancer: 36 without bone metastases (stage I-IV) and 37 with bone metastases. The patients in the latter group were further investigated at 2,4 and 6 months from the start of treatment. Both markers showed significant elevations in the group with bone metastases (CA 15.3: P = 1.0×10–6, UCa: P = 8.6×10–9). The bone metastasis index (BMI), which represents the combination of the markers, had better diagnostic efficacy (90%) than CA 15.3 alone (84%) or UCa alone (82%). During treatment of bone metastasis, the longitudinal levels of the markers showed a highly significant association with the therapeutic response assessed by the UICC criteria. For identifying progression of disease, the diagnostic efficacy of CA 15.3, UCa and a combination of both, the so-called Biochemical Index of Response (BIR), was 65%, 70% and 79%, respectively, at two months and 89%, 84% and 92% at four months. Application of the tandem, CA 15.3 with UCa, was very useful for the detection of bone metastases and the prediction of response to therapy.

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In vivo and in vitro pharmacokinetics and metabolism studies of 26,26,26,27,27,27-6F-1,25(OH)2 vitamin D3 (Falecalcitriol) in rat: induction of vitamin D3-24-hydroxylase (CYP24) responsible for 23S-hydroxylation in target tissues and the drop in serum levels

Xenobiotica ◽

10.1080/004982599238425 ◽

1999 ◽

Vol 29 (6) ◽

pp. 603-613 ◽

Cited By ~ 13

Author(s):

S. KOMURO ◽

M. SATO ◽

H. KANAMARU ◽

H. KANEKO ◽

I. NAKATSUKA ◽

...

Keyword(s):

Vitamin D3 ◽

Serum Levels

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Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases their Susceptibility to Temozolomide

10.20944/preprints202106.0691.v1 ◽

2021 ◽

Author(s):

Julia Gerstmeier ◽

Anna-Lena Possmayer ◽

Süleyman Bozkurt ◽

Marina E. Hoffmann ◽

Ivan Dikic ◽

...

Keyword(s):

Vitamin D3 ◽

Ex Vivo ◽

Active Form ◽

Treatment Resistance ◽

Serum Levels ◽

Disease Recurrence ◽

Primary Brain Tumor ◽

High Rate ◽

Organotypic Brain Slice

: Glioblastoma (GBM) is the most common and most aggressive primary brain tumor with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evi-dence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infil-trative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the ex-pression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show using in vitro limiting dilution assays, quantita-tive real-time PCR and ex vivo adult organotypic brain slice transplantation cultures that thera-peutic doses of calcitriol, the hormonally active form of vitamin D3, reduces stemness to varying extent in a panel of investigated GSC lines and effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to com-pletely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in fol-low-up studies.

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Clinical effects of cinacalcet on biochemical parameters and bone mineral density in Japanese patients with primary hyperparathyroidism

Gazzetta Medica Italiana Archivio per le Scienze Mediche ◽

10.23736/s0393-3660.19.04069-5 ◽

2020 ◽

Vol 179 (3) ◽

Author(s):

Yomi Nakashima ◽

Aya Nozaki ◽

Ayako Ito ◽

Ichiro Horie ◽

Takao Ando ◽

...

Keyword(s):

Bone Mineral Density ◽

Primary Hyperparathyroidism ◽

Bone Mineral ◽

Biochemical Parameters ◽

Japanese Patients ◽

Clinical Effects ◽

Mineral Density

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Association between Vitamins and Minerals with Antioxidant Effects and Coronary Artery Calcification in Adults and Older Adults: A Systematic Review

Current Pharmaceutical Design ◽

10.2174/1381612825666190722101954 ◽

2019 ◽

Vol 25 (22) ◽

pp. 2474-2479 ◽

Cited By ~ 1

Author(s):

Alisson Diego Machado ◽

Gustavo Rosa Gentil Andrade ◽

Jéssica Levy ◽

Sara Silva Ferreira ◽

Dirce Maria Marchioni

Keyword(s):

Systematic Review ◽

Older Adults ◽

Coronary Artery ◽

Coronary Artery Calcification ◽

Serum Levels ◽

Antioxidant Compounds ◽

Increased Risk ◽

Coronary Events ◽

Antioxidant Effects

Background: Coronary Artery Calcification (CAC) is considered an important cardiovascular risk factor. There is evidence that CAC is associated with an increased risk of atherosclerosis, coronary events and cardiovascular mortality. Inflammation is one of the factors associated with CAC and despite the interest in antioxidant compounds that can prevent CAC, its association with antioxidants remains unclear. Objective: This study aimed to systematically review the association between vitamins and minerals with antioxidant effects and CAC in adults and older adults. Methods: We conducted a systematic review using PubMed for articles published until October 2018. We included studies conducted in subjects aged 18 years and older with no previous cardiovascular disease. Studies involving animal or in vitro experiments and the ones that did not use reference methods to assess the CAC, dietary intake or serum levels of vitamin or mineral were excluded. Results: The search yielded 390 articles. After removal of duplicates, articles not related to the review, review articles, editorials, hypothesis articles and application of the inclusion and exclusion criteria, 9 articles remained. The results of the studies included in this systematic review suggest that magnesium is inversely associated with CAC and results on the association between CAC and vitamin E have been conflicting. Conclusion: Additional prospective studies are needed to elucidate the role of these micronutrients on CAC.

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Investigation of Oral Subacute Toxicity and In-Vitro Antioxidant Activity of Standardized Methanolic Extract of Quercus serrata Leaves

Current Bioactive Compounds ◽

10.2174/1573407216999201224150602 ◽

2020 ◽

Vol 16 ◽

Author(s):

Maibam Beebina Chanu ◽

Biseshwori Thongam ◽

Khumukcham Nongalleima ◽

Hans Raj Bhat ◽

Surajit Kumar Ghosh ◽

...

Keyword(s):

Nitric Oxide ◽

Antioxidant Activity ◽

Biochemical Parameters ◽

Methanolic Extract ◽

Reducing Power ◽

Quercus Serrata ◽

Control Group ◽

Blood Cell Count ◽

Toxicological Profile

Background: Quercus serrata Murray leaves have been used traditionally in the treatment of diabetes, dysmenorrhoea, inflammation and urinary tract infection. So, far no study had been reported on the toxicological profile and antioxidant properties of the plant. Objective: The present study was aimed to investigate the in-vivo toxicological profile and in-vitro antioxidant activities of the methanolic extract of standardized Quercus serrata leaves. Methods: Per-oral sub-acute toxicity study was performed in rats using three dose levels (200, 400 and 800 mg/kg b.w.) of the extract for 28-days. Control group received gum acacia suspended in water. Bodyweight was measured weekly. Biochemical parameters were analysed using the serum, the blood-cell count was done using whole blood. Pathological changes were also checked in highly perfused tissues. Further, in-vitro reducing power assay, nitric oxide scavenging assay, DPPH free-radical scavenging assay were performed to check the antioxidant activity of the extract. Results: There were no significant alterations in the blood-cell count and biochemical parameters analysed in the treatment group when compared with the normal control. Histopathology study of liver, kidney, pancreas, heart and brain revealed normal cellular architecture in the treatment groups alike the control group animals. Quercus serrata also showed a significant reduction of DPPH with IC50 4.48±0.254 µg/mL, in-vitro reducing power activity with IC50121.65±0.320 µg/mL and nitric oxide scavenging activity IC50 106.43±0.338 µg/mL. Conclusion: The above study showed that standardized methanolic extract of Quercus serrata leaves was safe after subacute oral administration in rats and has good antioxidant potential.

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Salinity Effects on Gene Expression, Morphological, and Physio-Biochemical Responses of Stevia rebaudiana Bertoni In Vitro

Plants ◽

10.3390/plants10040820 ◽

2021 ◽

Vol 10 (4) ◽

pp. 820

Author(s):

Clara Azzam ◽

Sudad Al-Taweel ◽

Ranya Abdel-Aziz ◽

Karim Rabea ◽

Alaa Abou-Sreea ◽

...

Keyword(s):

Salt Tolerance ◽

Biochemical Parameters ◽

Large Scale ◽

Stevia Rebaudiana ◽

Multiple Shoots ◽

High Salt ◽

Stress Factors ◽

Stevia Rebaudiana Bertoni ◽

Nacl Concentration

Stevia rebaudiana Bertoni is a little bush, which is cultivated on a large scale in many countries for medicinal purposes and used as a natural sweetener in food products. The present work aims to conduct a protocol for stevia propagation in vitro to produce and introduce Stevia rebaudiana plants as a new sweetener crop to Egyptian agriculture. To efficiently maximize its propagation, it is important to study the influence of stress factors on the growth and development of Stevia rebaudiana grown in vitro. Two stevia varieties were investigated (Sugar High A3 and Spanti) against salt stress. Leaves were used as the source of explants for callus initiation, regeneration, multiplication and rooting. Some stress-related traits, i.e., photosynthetic pigments, proline contents, and enzyme activity for peroxidase (POD), polyphenol oxidase (PPO), and malate dehydrogenase (MDH) were studied. Murashig and Skoog (MS) medium was supplemented with four NaCl concentrations: 500, 1000, 2000, and 3000 mgL−1, while a salt-free medium was used as the control. The data revealed that salinity negatively affected all studied characters: the number of surviving calli, regeneration%, shoot length, the number of multiple shoots, number of leaf plantlets−1, number of root plantlets−1, and root length. The data also revealed that Sugar High A3 is more tolerant than Spanti. The total chlorophyll content decreased gradually with increasing NaCl concentration. However, the opposite was true for proline content. Isozyme’s fractionation exhibited high levels of variability among the two varieties. Various biochemical parameters associated with salt tolerance were detected in POD. Namely, POD4, POD6, POD 9 at an Rf of 0.34, 0.57, and 0.91 in the Sugar High A3 variety under high salt concentration conditions, as well as POD 10 at an Rf of 0.98 in both varieties under high salt concentrations. In addition, the overexpression of POD 5 and POD 10 at Rf 0.52 and 0.83 was found in both varieties at high NaCl concentrations. Biochemical parameters associated with salt tolerance were detected in PPO (PPO1, PPO2 and PPO4 at an Rf of 0.38, 0.42 and 0.62 in the Sugar High A3 variety under high salt concentrations) and MDH (MDH 3 at an Rf of 0.40 in both varieties at high salt concentrations). Therefore, these could be considered as important biochemical markers associated with salt tolerance and could be applied in stevia breeding programs (marker-assisted selection). This investigation recommends stevia variety Sugar High A3 to be cultivated under salt conditions.

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