scholarly journals Novel protein markers of androgen activity in humans: proteomic study of plasma from young chemically castrated men

2021 ◽  
Author(s):  
Aleksander Giwercman ◽  
Barbara Sahlin ◽  
Indira Pla Parada ◽  
Krzysztof Pawlowski ◽  
Carl Fehninger ◽  
...  
Keyword(s):  
Gnrh Antagonist ◽  
Cag Repeat ◽  
Activity Levels ◽  
Protein Markers ◽  
Protein Biomarkers ◽  
Fructose Bisphosphate ◽  
Mineral Density ◽  
Testosterone Undecanoate ◽  
Proteomic Study ◽  
New Protein

Background: Reliable biomarkers of androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs. normal testosterone values and some androgen deficiency linked pathologies.<br />Methods: Blood samples from 30 healthy GnRH-antagonist treated males were collected at three time points: a) before GnRH antagonist administration; b) 3 weeks later, just before testosterone undecanoate injection, and c) after additional 2 weeks. Subsequently they were analysed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardio-metabolic parameters, bone mineral density as well as androgen receptor CAG repeat lengths, were explored.<br />Results: Using ROC analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6) and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (< 8 nmol/L) vs. normal (> 12 nmol/L) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD levels also showed association with AR CAG-repeat lengths.<br />Conclusions: We identified potential new protein biomarkers of testosterone action. Further investigations to eluciadate their clinical potential are warranted.<br />Funding: The work was supported by ReproUnion 2.0 (grant no 20201846), which is funded by the Interreg V EU program.

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

scholarly journals Plasma Protein Biomarkers Associated with Higher Ovarian Cancer Risk in BRCA1/2 Carriers

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2300
Author(s):  
Hee-Sung Ahn ◽  
Jung Yoon Ho ◽  
Jiyoung Yu ◽  
Jeonghun Yeom ◽  
Sanha Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Plasma Protein ◽  
Normal Subjects ◽  
Genetic Alterations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ovarian Cancer Risk ◽  
Protein Markers ◽  
Protein Biomarkers ◽  
Proteomics Approach ◽  
Risk Reducing

Ovarian cancer (OC) is the most lethal gynecologic malignancy and in-time diagnosis is limited because of the absence of effective biomarkers. Germline BRCA1/2 genetic alterations are risk factors for hereditary OC; risk-reducing salpingo-oophorectomy (RRSO) is pursued for disease prevention. However, not all healthy carriers develop the disease. Therefore, identifying predictive markers in the BRCA1/2 carrier population could help improve the identification of candidates for preventive RRSO. In this study, plasma samples from 20 OC patients (10 patients with BRCA1/2 wild type (wt) and 10 with the BRCA1/2 variant (var)) and 20 normal subjects (10 subjects with BRCA1/2wt and 10 with BRCA1/2var) were analyzed for potential biomarkers of hereditary OC. We applied a bottom-up proteomics approach, using nano-flow LC-MS to analyze depleted plasma proteome quantitatively, and potential plasma protein markers specific to the BRCA1/2 variant were identified from a comparative statistical analysis of the four groups. We obtained 1505 protein candidates from the 40 subjects, and SPARC and THBS1 were verified by enzyme-linked immunosorbent assay. Plasma SPARC and THBS1 concentrations in healthy BRCA1/2 carriers were found to be lower than in OC patients with BRCA1/2var. If plasma SPARC concentrations increase over 337.35 ng/ml or plasma THBS1 concentrations increase over 65.28 mg/ml in a healthy BRCA1/2 carrier, oophorectomy may be suggested.

Circulating Biomarkers Related to Osteocyte and Calcium Homeostasis between Postmenopausal Women with and without Osteoporosis

2021 ◽  
Vol 21 ◽  
Author(s):  
Chin Yi Chan ◽  
Shaanthana Subramaniam ◽  
Norazlina Mohamed ◽  
Norliza Muhammad ◽  
Fitri Fareez Ramli ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Postmenopausal Women ◽  
Calcium Homeostasis ◽  
Bone Cells ◽  
Control Group ◽  
Protein Markers ◽  
Mineral Density ◽  
Hydroxyvitamin D ◽  
Hip Bmd ◽  
Turnover Markers

Background: The currently available bone turnover markers are mostly derived from osteoblasts or osteoclasts. Protein markers derived from osteocytes, the most abundant bone cells that can regulate bone turnover activities by other cells, are less explored. Objective: This study aimed to compare the circulating markers of osteocytes and calcium homeostasis between Malaysian postmenopausal women with and without osteoporosis. Method: Postmenopausal women with (n=20) or without osteoporosis (n=20) as determined by dual-energy X-ray absorptiometry were randomly drawn from a bone health cohort. Their fasting blood was collected and assayed by a multiplex immunoassay panel. Results: The results showed that osteoprotegerin and sclerostin levels were significantly lower among postmenopausal women with osteoporosis than the normal control. No significant differences in other markers were observed between the two groups. Sclerostin level correlated positively with spine bone mineral density (BMD), while 25-hydroxyvitamin D correlated negatively with hip BMD in the control group. No significant correlation was observed between other markers with spine or hip BMD. Conclusion: These data provide an insight into the possible roles of osteocyte markers, especially osteoprotegerin and sclerostin in classifying subjects with osteoporosis. However, the lack of association between these markers and BMD indicates that osteoporosis is a complex and multifactorial condition.

scholarly journals SAT-044 Treatment of Hypogonadal Men with a New Oral Testosterone Undecanoate (TU) Formulation Improves Psychosexual, Well-Being and Body Composition and Bone Density Parameters

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ronald S Swerdloff ◽  
John K Amory ◽  
Adrian S Dobs ◽  
Christina Wang ◽  
Theodore M Danoff ◽  
...  
Keyword(s):  
Body Composition ◽  
Well Being ◽  
Clinic Visit ◽  
Dose Titration ◽  
Mineral Density ◽  
Open Label ◽  
Testosterone Undecanoate ◽  
Active Comparator ◽  
Sf 36 ◽  
The Impact

Abstract Introduction and Objective: A new, first-in-class oral testosterone (T) replacement therapy product [T-undecanoate (TU) capsules] was recently approved by FDA to treat hypogonadal men. Clinical trials were conducted to evaluate, in part, the impact of oral TU therapy on important secondary efficacy endpoints: Psychosexual and/or general well-being (Trial I and II); and body composition and bone mineral density (BMD) (Trial II). Subject and Methods: Hypogonadal men (AM serum T ≤ 300 ng/dL) age 18 to 65 (Trial I) or 75 years old (Trial II) were randomized into open-label, active-comparator (T-gel/solution) trials. Subjects received: Trial 1: Oral TU (n=166) or a topical T solution (n=55) for 4-6 mos.; or Trial II: Oral TU (n=162) or T-gel (n=163) for 12 mos. The starting oral TU dose (with food) was 237 mg, BID in Trial I and 316 mg, BID in Trial II; up to 2 dose-titration opportunities were available to achieve eugonadal T concentrations (assayed by LC-MS/MS). In Trial I, Psychosexual Daily Questionnaires (PDQ) were completed by study subjects for 7 days at baseline and prior to final clinic visit (Day 105-180). In Trial II, the SF-36 well-being questionnaire was completed on Days 0, 30, 90, 180, 270 and 365 and PDQs were completed for 7 days prior to clinic visits on these same days. In Trial II body composition and BMD was assessed by DEXA scan on Days 0, 180 and 365. Safety was monitored by physical exam and standard clinical lab tests. Results: Mean serum T in response to oral TU was 489 ± 155 ng/dL (mean ± SD) (Trial I) and 628 ± 342 ng/dL (Trial II); 84% of subjects in each trial achieved mean T concentrations in the eugonadal range. Statistically significant mean changes from baseline (p&lt;0.0001) for most SF-36 well-being parameters were observed in both oral TU and T-gel groups. Psychosexual questionnaire results also demonstrated statistically significant improvement over baseline (p&lt;0.0001) in most parameters at Day 30 and all timepoints thereafter in both trials. On Days 180 and 365 (v. baseline) oral TU was associated with a significant reduction in fat mass [-1.92 ± 2.79 (SD) and -2.4 ± 3.6 kg, respectively] (p&lt;0.0001) and an increase in lean body mass [+2.87 ± 2.73 and +3.15 ± 2.69 kg, respectively] (p&lt;0.0001). Oral TU increased mean BMD over baseline on Days 180 and 365 in spine [+0.013 ± 0.035 and +0.018 ± 0.042 g/cm2, respectively (p&lt;0.0001)] and hip [+0.006 ± 0.019 and +0.012 ± 0.023 g/cm2, respectively (p&lt;0.0001)]. Oral TU exhibited a safety profile consistent with commonly prescribed topical T-comparators. Modest increases in cuff sBP of 2.8 ± 11.84 (SD) mm Hg and 1.8 ± 10.76 mm Hg were observed in Trial I for both oral TU and the comparator T-solution. Conclusions: Treatment of hypogonadal men with oral TU yielded circulating mean T concentrations in the mid-eugonadal range and significantly improved psychosexual, general well-being, body composition and BMD parameters comparable to transdermal T administration.

scholarly journals Bone mineral density in young adults: the influence of vitamin D status, biochemical indicators, physical activity and body composition

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Anna Kopiczko ◽  
Monika Łopuszańska-Dawid ◽  
Karol Gryko
Keyword(s):  
Physical Activity ◽  
Bone Mineral Density ◽  
Vitamin D ◽  
Body Composition ◽  
Total Cholesterol ◽  
Bone Mineral ◽  
Activity Levels ◽  
Fat Percentage ◽  
Mineral Density ◽  
Physical Activity Levels

Abstract Summary The aim of the study was to assess the associations of bone mineral density and bone mass with physical activity levels, vitamin D, phosphorus, magnesium, total cholesterol and triglyceride concentration and body composition in young women and men. Physical activity has the most significant effect on bone status especially in men. Purpose The aim of the study was to assess the associations of bone mineral density and bone mass with physical activity levels, vitamin D, phosphorus, magnesium, total cholesterol and triglyceride concentration and body composition in young women and men. Methods One hundred subjects aged 19–24 years were included. Bone mineral density (BMD) in distal and proximal parts was evaluated by forearm densitometry. Body composition was analysed with the use of JAWON-Medical-x-scan. The following biochemical indicators were analysed: 25(OH) D and 1,25(OH)2D, magnesium, phosphorus, total cholesterol and triglycerides. Physical activity levels were assessed by interview. Results Significant correlations between BMD and physical activity, skeletal muscle mass and body fat percentage were revealed in men. Among women, considerably weaker correlations of BMD with body composition and physical activity were noted than in men. BMD in the distal part correlated only with lean body mass, soft lean mass and body fat percentage. The strongest relationship between physical activity and bone mineral status parameters was noted for BMD in men. In women, physical activity did not affect BMD. Conclusions Physical activity has the most significant effect on bone status especially in men.

scholarly journals Effects of Five-Year Treatment with Testosterone Undecanoate on Metabolic and Hormonal Parameters in Ageing Men with Metabolic Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Davide Francomano ◽  
Andrea Lenzi ◽  
Antonio Aversa
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Vitamin D ◽  
Lipid Profile ◽  
Glycosylated Hemoglobin ◽  
Serum Vitamin ◽  
Mineral Density ◽  
Testosterone Undecanoate ◽  
Cholesterol Ratio ◽  
Serum Vitamin D

Metabolic and hormonal modifications after long-term testosterone (T) treatment have never been investigated. 20 hypogonadal men (mean T = 241 ng/dL–8.3 nmol/L) with metabolic syndrome (MS, mean age 58) were treated with T-undecanoate injections every 12 weeks for 60 months. 20 matched subjects in whom T was unaccepted or contraindicated served as controls. Primary endpoints were variations from baseline of metabolic and hormonal parameters. In T-group, significant reductions in waist circumference (−9.6±3.8 cm,P<0.0001), body weight (−15±2.8 Kg,P<0.0001), and glycosylated hemoglobin (−1.6 ± 0.5%,P<0.0001) occurred, along with improvements in insulin sensitivity (HOMA-I;−2.8 ± 0.6,P<0.0001), lipid profile (total/HDL-cholesterol ratio−2.9±1.5,P<0.0001), systolic and diastolic blood pressure (−23±10and−16±8mm Hg,P<0.0001, resp.), and neck and lumbar T-scores (+0.5±0.15 gr/cm2,P<0.0001;+0.7±0.8,P<0.0001, resp.). Also, serum vitamin D (+14.0±1.3 ng/mL,P<0.01), TSH (− 0.9±0.3 mUI/mL,P<0.01), GH (0.74±0.2 ng/mL,P<0.0001), and IGF1 (105±11 ng/mL,P<0.01) levels changed in T-group but not in controls. Normalization of T levels in men with MS improved obesity, glycemic control, blood pressure, lipid profile, and bone mineral density compared with controls. Amelioration in hormonal parameters, that is, vitamin D, growth hormone, and thyrotropin plasma levels, were reported.

Effect of past gymnastics participation on adult bone mass

1996 ◽  
Vol 80 (1) ◽  
pp. 226-232 ◽  
Author(s):  
E. M. Kirchner ◽  
R. D. Lewis ◽  
P. J. O'Connor
Keyword(s):  
Physical Activity ◽  
Residual Effect ◽  
Analysis Of Covariance ◽  
Whole Body ◽  
Activity Levels ◽  
Menstrual Irregularity ◽  
Mineral Density ◽  
The Past ◽  
Menstrual History ◽  
Adult Bone

The purposes of this study were to determine bone mineral density (BMD) of former female college gymnasts (FG; n = 18) and controls (FC; n = 15) by using dual-energy X-ray absorptiometry (Hologic QDR 1000W) and to examine the relationships between current and former activity levels, diet, menstrual history and BMD. Current physical activity, dietary intake, and menstrual irregularity were assessed with the use of standardized questionnaires. A study-designed questionnaire was used to assess past physical activity. The BMDs of the FG were significantly higher (P < 0.001) than the BMDs of FC for the lumbar spine, femoral neck, Ward's triangle, and whole body, even when the influences of current and past physical activity levels were statistically controlled via analysis of covariance. FG and FC did not differ in nutrient intakes, and there were no BMD differences between FG who always had regular menstrual cycles vs. those who had an interruption (= or = 3 mo) of their menstrual cycle in the past. The higher BMD in FG compared with FC suggests that past participation in college gymnastics may provide a residual effect on adult BMD.

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