Metabolism of selective 20-epi-vitamin D3 analogs in rat osteosarcoma UMR-106 cells: Isolation and identification of four novel C-1 fatty acid esters of 1α,25-dihydroxy-16-ene-20-epi-vitamin D3

Flarakos, Caroline Ceailles; Weiskopf, Andrew; Robinson, Matthew; Wang, Guoshun; Vouros, Paul; Sasso, Gino J.; Uskoković, Milan R.; Reddy, G. Satyanarayana

doi:10.1016/j.steroids.2016.12.013

Cited by 4 publications

(6 citation statements)

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“…Ions at m/z 540 and 450 are produced by successive losses of TMS-OH and m/z 131 (i) is the α-cleavage product from the 25-TMSO group. The only other ion of note is m/z 217 (z) whose proposed mechanism of formation is shown in Scheme 133 (Flarakos et al, 2017;Gathungu et al, 2013;Sekimoto et al, 1999).…”

Section: Mass Spectrometry Of Tms Derivatives ▪mentioning

confidence: 99%

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Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Harvey

Vouros

2019

Mass Spectrometry Reviews

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This review describes the mass spectral fragmentation of trimethylsilyl (TMS) and related alkylsilyl derivatives used for preparing samples for analysis, mainly by combined gas chromatography and mass spectrometry (GC/MS). The review is divided into three sections. The first section is concerned with the TMS derivatives themselves and describes fragmentation of derivatized alcohols, thiols, amines, ketones, carboxylic acids and bifunctional compounds such as hydroxy‐ and amino‐acids, halo acids and hydroxy ethers. More complex compounds such as glycerides, sphingolipids, carbohydrates, organic phosphates, phosphonates, steroids, vitamin D, cannabinoids, and prostaglandins are discussed next. The second section describes intermolecular reactions of siliconium ions such as the TMS cation and the third section discusses other alkylsilyl derivatives. Among these latter compounds are di‐ and trialkyl‐silyl derivatives, various substituted‐alkyldimethylsilyl derivatives such as the tert‐butyldimethylsilyl ethers, cyclic silyl derivatives, alkoxysilyl derivatives, and 3‐pyridylmethyldimethylsilyl esters used for double bond location in fatty acid spectra. © 2019 Wiley Periodicals, Inc. Mass Spec Rev 0000:1–107, 2019

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Section: Mass Spectrometry Of Tms Derivatives ▪mentioning

confidence: 99%

“…SCHEME 133. Proposed mechanism (Flarakos, et al, 2017) for the formation of the diagnostic fragment ion at m/z 217 (z) from the TMS derivative of 1,25-dihydroxy-2-16-diene-20-epi-vitamin D 3 . (1981c)).…”

Section: Iic12a Tetrahydrocannabinolsmentioning

confidence: 99%

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Harvey

Vouros

2019

Mass Spectrometry Reviews

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“…Optimizing vitamin D compounds for in vivo anticancer efficacy is aimed at ensuring a favorable balance between calcium mobilizing actions, which result in hypercalcemia, and enhancing the anticancer actions of targeting the VDR. Several medicinal chemistry groups undertook this goal, led in many ways by the group of Milan Uskokovic at Hoffman la Roche, 64,[188][189][190][191][192][193][194][195][196][197][198][199][200] alongside Lisa Binderup at Leo Pharmaceuticals, [201][202][203][204] as well as other groups in academic settings, including Gary Posner. [205][206][207][208] Together, these and other investigators have synthesized a blizzard of vitamin D analogues that have many promising properties, being resistant to metabolism and yet have tolerable impact on serum calcium levels.…”

Section: Human Epidemiologic Findings and Clinical Trialsmentioning

confidence: 99%

Vitamin D Receptor Signaling and Cancer

Campbell

Trump

2017

Endocrinology and Metabolism Clinics of North America

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The primary biological action of the secosteroid hormone vitamin D (1,25(OH) 2 D 3 ) is to bind to the vitamin D receptor (NR1I1/VDR) and to regulate serum calcium levels. As a downstream consequence, the actions of the receptor control bone formation and maintenance. The first clinical manifestation of insufficient VDR endocrine signaling, rickets, was discovered by Daniel Whistler in the Netherlands in the 17th century; 300 years later, the VDR gene was cloned by Bert O'Malley and coworkers. 1 Between these dates, research into vitamin D was at the forefront of areas of public health, chemistry and biochemistry including the light catalyzed synthesis of vitamin D 3 by Adolf Windaus. For this work, he received the Nobel Prize in Chemistry (1928). Work in the 1960s and 1970s led to analyses of vitamin D endocrine metabolism and led to remarkable strides describing biochemical synthesis of 1,25(OH) 2 D 3 and the diverse biology in which VDR participates.The precursor of 1,25(OH) 2 D 3 , cholecalciferol or vitamin D 3 , is produced in the skin and converted in the liver to 25-hydroxyvitamin D 3 , (25(OH)D 3 ); circulating levels of 25(OH)D 3 serve as a useful index of vitamin D total body stores. A further hydroxylation occurs in the principally in the kidney at the carbon 1 position by 25-hydroxyvitamin D-1α-hydroxylase (encoded by CYP27B1) to produce the biologically active hormone, 1,25(OH) 2 D 3 . A second mitochondrial cytochrome P450 enzyme, the 24-hydroxylase (encoded by CYP24A1), can use both 25(OH)D and 1,25(OH) 2 D 3 as substrates, and is the first step in the inactivation pathway for these metabolites. Because of the direct role 1,25(OH) 2 D 3 plays in control of serum calcium levels, elevated levels of 1,25(OH) 2 D 3 block its synthesis and induce inactivation and accelerate catabolism 2 via induction of CYP24A1, in a classical negative feedback loop.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). The first report that VDR actions could control cancer cell growth were discovered partly through serendipity, and partly through logical extension of other studies. Reports in the 1970s identified purified cell fractions that bound 1,25(OH) 2 D 3 with high affinity, 14 and encouraged investigators to begin to consider what were the molecular actions of the VDR in the classic tissues involved in calcium homeostasis, for example, skin, bone, intestine, and kidney. 15 In 1981, Kay Colston and coworkers 16 were first to demonstrate that 1α,25(OH) 2 D 3 at nanomolar concentrations inhibited human melanoma cell proliferation in vitro. That the workers used a cancer cell model was serendipitous; cancer cell models are more readily available to study in cell culture experiments than nonmalignant counterparts, and in this case 16 the cells chosen were available in an adjacent laboratory. Campbell and Trump In parallel, it was also known that retinoids, which are also small lipophilic molecules that target NRs, could drive cell differentiation, for exa...

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“…The neoadjuvant chemotherapy, which is integrated with the standard treatment plan nowadays, may reduce the tumor size and eliminate the micrometastases, thus prolonging event-free survival (EFS) and overall survival (OS) of the patients [ 16 ]. The neoadjuvant chemotherapy protocol consisting of doxorubicin, cisplatin, ifosfamide, and a high dose of methotrexate has been widely used and associated with an increased OS rate [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Correlation between Prognostic Factors and the Histopathological Response to Neoadjuvant Chemotherapy in Osteosarcoma: A Retrospective Study

Prabowo

Setiawan

Kamal

et al. 2021

International Journal of Surgical Oncology

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Background.Multimodality treatment, incorporating neoadjuvant chemotherapy and adjuvant chemotherapy, is the standard management plan for osteosarcoma that increases the overall survival (OS) rate. However, data regarding prognostic factors affecting the histopathological response following neoadjuvant chemotherapy is limited. Patients and Methods. We retrospectively reviewed patients diagnosed with osteosarcoma in our center between 2008 and 2018. We classified patient characteristics according to gender, age, tumor size, site and stage at diagnosis, site of metastasis, type of surgery, necrosis rate based on the Huvos grading system, and the number of neoadjuvant chemotherapy cycles. We divided response to neoadjuvant chemotherapy into poor responder for patients with Huvos grades 1 and 2 and good responder for patients with Huvos grades 3 and 4. We also documented patients’ survival and follow-up information. Results. We reviewed 64 patients within 5–65 years of age, dominated by men (62.5%). The distal femur (53.1%) was the most common site of osteosarcoma. Fifteen (23.4%) patients had a good response while 49 (76.6%) patients were poor responders to neoadjuvant chemotherapy based on the Huvos grading system. Based on multivariate analysis, gender ( p = 0.012), age ( p = 0.029), symptom duration ( p = 0.004), and tumor enlargement after neoadjuvant chemotherapy ( p < 0.001) were significantly associated with histopathological response. A scoring system was proposed integrating these significant variables (age > 20 years = 1 point, female gender = 1 point, symptom duration > 12 weeks = 1 point, and increased tumor size after neoadjuvant chemotherapy = 2 points). This scoring system divides patients into two groups with a total score of more than two predicting a poor responder to neoadjuvant chemotherapy. Conclusions. Age, gender, symptoms duration, and tumor size after neoadjuvant chemotherapy are the prognostic features that affect the histopathological response to neoadjuvant chemotherapy in patients with osteosarcoma.

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Metabolism of selective 20-epi-vitamin D3 analogs in rat osteosarcoma UMR-106 cells: Isolation and identification of four novel C-1 fatty acid esters of 1α,25-dihydroxy-16-ene-20-epi-vitamin D3

Cited by 4 publications

References 44 publications

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Vitamin D Receptor Signaling and Cancer

Correlation between Prognostic Factors and the Histopathological Response to Neoadjuvant Chemotherapy in Osteosarcoma: A Retrospective Study

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