Improved detectability of sex steroids from frozen sections of breast cancer tissue using GC-triple quadrupole-MS

Moon, Ju Yeon; McNamara, Keely May; Lee, Jung‐Jin; Chung, Bong Chul; Sasano, Hironobu; Choi, Man Ho

doi:10.1016/j.jsbmb.2017.12.012

Cited by 18 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whilst this area has always been of interest, it was hampered by inadequate quantitative techniques. Thankfully this area of research has evolved very rapidly over the past number of years and in breast cancer the work of the Sasano group has proved to be hugely innovative ( 30 ). We now know that there is a high degree of intratumoral heterogeneity amongst patients and it will be of interest to understand if these correlate with not only patient outcome but also other factors known to impact steroid levels such as diet, adiposity, and exercise.…”

Section: Discussionmentioning

confidence: 99%

“…Another DHEA metabolite, androstenediol, has also been implicated as a driver of tumorigensis in breast cancers with low intra-tumorial estradiol levels ( 29 ), highlighting the relevance of individual tumor intracrinology. A recent study by Moon et al ( 30 ) has made great strides in accurately quantifying steroid levels within breast cancer tumors and, of note, whilst levels of prohormones were the most abundant they also reported huge amounts of variation among patients emphasizing this as a key area of future research. It is therefore of great interest to understand how circulating sex-steroid precursors exert their role on breast tumor survival, particularly in the setting of anti-estrogen therapy failure.…”

Section: Ar and Androgens In Normal Breast Tissue And Breast Cancermentioning

confidence: 99%

“…From the past number of decades it is apparent that altered response to hormonal stimulus is a hallmark of these tumors with a shift towards growth factor dependency often a common feature ( 37 – 41 ). Recently, there has been a resurgence of interest in elucidating the role of other nuclear receptors, and indeed other hormones, in driving breast tumorigensis ( 30 , 42 , 43 ). Many studies have centered upon the potential role of AR, however, due to its ubiquitous presence within breast cancers this is proving to be challenging ( 40 ).…”

Section: Ar and Androgens In Normal Breast Tissue And Breast Cancermentioning

confidence: 99%

See 2 more Smart Citations

The Divergent Function of Androgen Receptor in Breast Cancer; Analysis of Steroid Mediators and Tumor Intracrinology

Bleach

McIlroy

2018

Front. Endocrinol.

View full text Add to dashboard Cite

Androgen receptor (AR) is the most widely expressed steroid receptor protein in normal breast tissue and is detectable in approximately 90% of primary breast cancers and 75% of metastatic lesions. However, the role of AR in breast cancer development and progression is mired in controversy with evidence suggesting it can either inhibit or promote breast tumorigenesis. Studies have shown it to antagonize estrogen receptor alpha (ERα) DNA binding, thereby preventing pro-proliferative gene transcription; whilst others have demonstrated AR to take on the mantle of a pseudo ERα particularly in the setting of triple negative breast cancer. Evidence for a potentiating role of AR in the development of endocrine resistant breast cancer has also been mounting with reports associating high AR expression with poor response to endocrine treatment. The resurgence of interest into the function of AR in breast cancer has resulted in various emergent clinical trials evaluating anti-AR therapy and selective androgen receptor modulators in the treatment of advanced breast cancer. Trials have reported varied response rates dependent upon subtype with overall clinical benefit rates of ~19–29% for anti-androgen monotherapy, suggesting that with enhanced patient stratification AR could prove efficacious as a breast cancer therapy. Androgens and AR have been reported to facilitate tumor stemness in some cancers; a process which may be mediated through genomic or non-genomic actions of the AR, with the latter mechanism being relatively unexplored in breast cancer. Steroidogenic ligands of the AR are produced in females by the gonads and as sex-steroid precursors secreted from the adrenal glands. These androgens provide an abundant reservoir from which all estrogens are subsequently synthesized and their levels are undiminished in the event of standard hormonal therapeutic intervention in breast cancer. Steroid levels are known to be altered by lifestyle factors such as diet and exercise; understanding their potential role in dictating the function of AR in breast cancer development could therefore have wide-ranging effects in prevention and treatment of this disease. This review will outline the endogenous biochemical drivers of both genomic and non-genomic AR activation and how these may be modulated by current hormonal therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Ar and Androgens In Normal Breast Tissue And Breast Cancermentioning

confidence: 99%

Section: Ar and Androgens In Normal Breast Tissue And Breast Cancermentioning

confidence: 99%

See 1 more Smart Citation

The Divergent Function of Androgen Receptor in Breast Cancer; Analysis of Steroid Mediators and Tumor Intracrinology

Bleach

McIlroy

2018

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…This is the case in ethoxycarbonylation, which was used for estrogen determinations in hair [ 50 ]. More recently, it has been tested to quantify 15 estrogens, 6 androgens, and 2 progestins in breast tissue samples [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

GC/MS in Recent Years Has Defined the Normal and Clinically Disordered Steroidome: Will It Soon Be Surpassed by LC/Tandem MS in This Role?

Shackleton

Pozo

Marcos

2018

Journal of the Endocrine Society

View full text Add to dashboard Cite

Gas chromatography/mass spectrometry (GC/MS) has been used for steroid analysis since the 1960s. The advent of protective derivatization, capillary columns, and inexpensive electron ionization bench-top single quadrupole soon made it the method of choice for studying disorders of steroid synthesis and metabolism. However, the lengthy sample workup prevented GC/MS from becoming routine for steroid hormone measurement, which was dominated by radioimmunoassay. It was the emergence of liquid chromatography/tandem MS (LC/MS/MS) that sparked a renewed interest in GC/MS for the multicomponent analysis of steroids. GC/MS is excellent at providing an integrated picture of a person's steroid metabolome, or steroidome, as we term it. We review the recent work on newly described disorders and discuss the technical advances such as GC coupling to triple quadrupole and ion trap analyzers, two-dimensional GC/MS, and alternative ionization and detection systems such as atmospheric pressure chemical ionization (APCI) and time of flight. We believe that no novel GC/MS-based technique has the power of GC(electron ionization)/MS/MS as a “discovery tool,” although APCI might provide ultimate sensitivity, which might be required in tissue steroidomics. Finally, we discuss the role of LC/MS/MS in steroidomics. This remains a challenge but offers shorter analysis times and advantages in the detection and discovery of steroids with a known structure. We describe recent advances in LC/MS steroidomics of hydrolyzed and intact steroid conjugates and suggest the technique is catching up with GC/MS in this area. However, in the end, both techniques will likely remain complementary and both should be available in advanced analytical laboratories.

show abstract

“…The main methods reported for conventional analysis of steroid hormones include radio immunoassay (RIA), 8 enzyme immunoassay (EIA), 9 and gas chromatography-mass spectrometry (GC-MS). 10,11 However, these methods experienced poor sensitivity, were labor intensive and lacked specicity. Chromatographic separation and identication using MS, enabled rapid qualitative analysis and accurate quantication of metabolites.…”

Section: Introductionmentioning

confidence: 99%

A sensitive approach for simultaneous quantification of carbonyl and hydroxyl steroids using 96-well SPE plates based on stable isotope coded-derivatization-UPLC-MRM: method development and application

et al. 2018

View full text Add to dashboard Cite

Steroid hormones are crucial substances that mediate a wide range of vital physiological functions. Because of the important biological significance of steroids, this paper presents a new targeted metabolic method based on adding stable isotope tags to hydroxyl containing and carbonyl containing steroid hormones with two pairs of synthesized derivatization reagents: deuterium 4-(dimethylamino)-benzoic acid (D 4 -DMBA), and D 5 -Girard P (D 5 -GP) using of ultra performance liquid chromatography-multiple reaction monitoring (UPLC-MRM). Firstly, an Oasis PRiME hydrophilic-lipophilic balance (HLB) 96-well solid phase extraction plate was used to pretreat a number of biological samples simultaneously. Secondly, hydroxyl and carbonyl steroids were labeled using two pairs of synthetic reagents, namely DMBA and D 4 -DMBA, and GP and D 5 -GP, respectively. Thirdly, the mixed products were detected using UPLC-MRM and the mass spectroscopy conditions were optimized. Methodology development showed that the sensitivity was enhanced 1 to >500-fold. Finally, the new method was applied to analysis of urine samples of healthy males, females and rats. The results revealed that the method can be sensitive and reliable for simultaneous quantification of steroid hormones containing hydroxyl and carbonyl groups in 12 min in a single run. This method provided a powerful tool for studying the metabolic mechanism of steroids and contributed to the development of targeted metabolomics.

show abstract

Improved detectability of sex steroids from frozen sections of breast cancer tissue using GC-triple quadrupole-MS

Cited by 18 publications

References 32 publications

The Divergent Function of Androgen Receptor in Breast Cancer; Analysis of Steroid Mediators and Tumor Intracrinology

The Divergent Function of Androgen Receptor in Breast Cancer; Analysis of Steroid Mediators and Tumor Intracrinology

GC/MS in Recent Years Has Defined the Normal and Clinically Disordered Steroidome: Will It Soon Be Surpassed by LC/Tandem MS in This Role?

A sensitive approach for simultaneous quantification of carbonyl and hydroxyl steroids using 96-well SPE plates based on stable isotope coded-derivatization-UPLC-MRM: method development and application

Contact Info

Product

Resources

About