Clinical verification of Lou type warfarin pharmacokinetic dosing algorithms equation.

Mol Med Rep. 2018 Apr;17(4):6144-6149

Authors: Jiang J, Ji N, Lan J, Ge X, Du X

Abstract
Warfarin is the most commonly used oral anti-coagulant in clinic practice. However, it is difficult to recommend the correct dosage due to its narrow therapeutic window. The aim of the present study was to verify the clinical value of the Lou type equation, using pharmacogenetics‑based warfarin dosing algorithms to appropriately predict the actual maintenance dose. A total of 87 Chinese Han patients who required treatment with warfarin were enrolled and randomly divided into the experimental and control groups. In the experimental group, the first 3 doses of warfarin were calculated according to the Lou type equation. While in the control group, these 3 treatments were performed following the doctors' recommendations. Then the dose of warfarin was gradually adjusted to the stable dose according to the changes in the international standardized ratio. At the end of the 50 day experimental period, there were a greater number of patients in the experimental group who exhibited a stable blood concentration of warfarin than those in the control group (83.35 and 64.4%, respectively). In addition, the mean and median times for patients to obtain a stable dose in the experimental group were significantly shorter than those in the control group (mean, 18.2±1.7 and 27.3±2.0 days; and median, 11.7±1.1 and 20.5±1.8 days, respectively). The adverse reaction rate of the experimental group (9.5%) was markedly lower than that of the control group (26.7%). The occurrence of adverse reactions in the experimental group was also significantly later when compared with the control group (43.9±1.6 and 38.6±1.5 days, respectively). Furthermore, there was no significant difference between the average predicted dose (3.4±1.1 mg/day) and the average actual dose (3.5±1.4 mg/day; P=0.313). In conclusion, using the Lou type warfarin pharmacokinetic dosing algorithm equation to administer warfarin markedly shortened the adjustment time of warfarin to reach a stable dose and reduced the adverse reactions rate, thus supporting clinical feasibility.

PMID: 29436624 [PubMed - indexed for MEDLINE]

The N-recognin UBR4 of the N-end rule pathway is required for neurogenesis and homeostasis of cell surface proteins.

PLoS One. 2018;13(8):e0202260

Authors: Kim ST, Lee YJ, Tasaki T, Hwang J, Kang MJ, Yi EC, Kim BY, Kwon YT

Abstract
The N-end rule pathway is a proteolytic system in which single N-terminal amino acids of proteins act as a class of degrons (N-degrons) that determine the half-lives of proteins. We have previously identified a family of mammals N-recognins (termed UBR1, UBR2, UBR4/p600, and UBR5/EDD) whose conserved UBR boxes bind N-degrons to facilitate substrate ubiquitination and proteasomal degradation via the ubiquitin-proteasome system (UPS). Amongst these N-recognins, UBR1 and UBR2 mediate ubiquitination and proteolysis of short-lived regulators and misfolded proteins. Here, we characterized the null phenotypes of UBR4-deficient mice in which the UBR box of UBR4 was deleted. We show that the mutant mice die around embryonic days 9.5-10.5 (E9.5-E10.5) associated with abnormalities in various developmental processes such as neurogenesis and cardiovascular development. These developmental defects are significantly attributed to the inability to maintain cell integrity and adhesion, which significantly correlates to the severity of null phenotypes. UBR4-loss induces the depletion of many, but not all, proteins from the plasma membrane, suggesting that UBR4 is involved in proteome-wide turnover of cell surface proteins. Indeed, UBR4 is associated with and required to generate the multivesicular body (MVB) which transiently store endocytosed cell surface proteins before their targeting to autophagosomes and subsequently lysosomes. Our results suggest that the N-recognin UBR4 plays a role in the homeostasis of cell surface proteins and, thus, cell adhesion and integrity.

PMID: 30157281 [PubMed - in process]

Validation of A Nomogram for Achieving Target Trough Concentration of Vancomycin: Accuracy in Patients with Augmented Renal Function.

Ther Drug Monit. 2018 Aug 27;:

Authors: Ishii H, Hirai K, Sugiyama K, Nakatani E, Kimura M, Itoh K

Abstract
BACKGROUND: Adjustment of initial vancomycin (VCM) dosage has been recommended on the basis of the renal function nomogram in therapeutic drug monitoring guidelines in Japan. However, this nomogram has not been clinically validated, and few studies have focused on its usefulness in patients with risk of augmented renal function. Therefore, this study aimed to evaluate the validity of the VCM nomogram and the association between patient conditions related to augmented renal function and its accuracy.
METHODS: In this retrospective study, we screened data of 398 patients who received VCM and had estimated glomerular filtration rates (eGFRs) ≥ 30 mL·min·1.73 m. Patients who met nomogram dosing criteria were categorized into a nomogram group, and the associations of age, renal function, and individual conditions such as febrile neutropenia (FN), solid tumor, blood cancer, and brain injury with subtherapeutic concentrations (< 10.0 μg/mL) of VCM were evaluated.
RESULTS: In total, 177 patients were categorized into the nomogram group, and 83 (47%), 81 (46%), and 13 patients (7%) had VCM trough concentrations of 10-20, < 10, and > 20 μg/mL, respectively. Age < 50 years was only significantly associated with subtherapeutic trough concentrations. Specific conditions of patients such as FN, solid tumor, and blood cancer were associated with elevated VCM clearance; however, there was no decline in trough VCM concentrations regardless of the presence of the specific conditions.
CONCLUSIONS: The Japanese VCM dosing nomogram was effective in minimizing the number of instances of supra-therapeutic VCM serum concentrations; however, it lacked accuracy in achieving target trough concentrations. The accuracy of the nomogram could be enhanced by categorizing patients according to age. Nevertheless, this study provides novel evidence of the usefulness of this nomogram in avoiding subtherapeutic concentrations of VCM in patients with risk factors for augmented renal clearance.

PMID: 30157096 [PubMed - as supplied by publisher]

Individualized Tacrolimus Therapy for Pediatric Nephrotic Syndrome: Considerations for Ontogeny and Pharmacogenetics of CYP3A.

Curr Pharm Des. 2018 Aug 28;:

Authors: Sun JY, Xu ZJ, Sun F, Guo HL, Ding XS, Chen F, Xu J

Abstract
Tacrolimus is used initially as an immunosuppressant drug in solid organ transplant population. This calcineurin inhibitor has also been recommended by KDIGO Clinical Practice Guideline for Glomerulonephritis for the treatment of nephrotic syndrome in children and adults. Tacrolimus is characterized by a narrow therapeutic index and large pharmacokinetic (PK) variations. Therefore, routine therapeutic drug monitoring (TDM) is critical to keep tacrolimus blood levels within therapeutic range. Tacrolimus is mainly metabolized by cytochrome P450 (CYP) enzymes 3A5 and 3A4. Actually, for pediatric patients, they are totally different to adults. Profound changes in CYP3A expression and activity occur throughout fetal life and in the neonatal and childhood periods thereby influencing their catalytic function. CYP3A7, CYP3A5, and CYP3A4 display an age-dependent maturation pattern. Notably, the CYP3A7-CYP3A4 switch taking place during the very early life will affect tacrolimus metabolism. Meanwhile, CYP3A isoforms are polymorphic enzymes, especially for CYP3A5. Guideline has recommended that the tacrolimus dosage should be adjusted according to the CYP3A5 genotype. Additionally, genetic CYP3A4 variation (e.g., CYP3A4*22) is also associated with interindividual variability of exposure level to tacrolimus. However, age (ontogeny) sometimes trumps genetics (genotype) in determining the enzymatic functions (phenotype) in pediatric patients. It's important to discriminate at what age the ontogeny plays key roles and at what age genetic variation become a major determinant. Thus, we need to better understand the mechanisms driving the CYP3A maturation and integrate ontogeny and genetics into the tacrolimus disposition, thereby tailoring the dosage individually for pediatric NS patients at different developmental stages.

PMID: 30156148 [PubMed - as supplied by publisher]

Advances in Regenerative Medicine and Tissue Engineering: Innovation and Transformation of Medicine.

Stem Cells Int. 2018;2018:2495848

Authors: Dzobo K, Thomford NE, Senthebane DA, Shipanga H, Rowe A, Dandara C, Pillay M, Motaung KSCM

Abstract
Humans and animals lose tissues and organs due to congenital defects, trauma, and diseases. The human body has a low regenerative potential as opposed to the urodele amphibians commonly referred to as salamanders. Globally, millions of people would benefit immensely if tissues and organs can be replaced on demand. Traditionally, transplantation of intact tissues and organs has been the bedrock to replace damaged and diseased parts of the body. The sole reliance on transplantation has created a waiting list of people requiring donated tissues and organs, and generally, supply cannot meet the demand. The total cost to society in terms of caring for patients with failing organs and debilitating diseases is enormous. Scientists and clinicians, motivated by the need to develop safe and reliable sources of tissues and organs, have been improving therapies and technologies that can regenerate tissues and in some cases create new tissues altogether. Tissue engineering and/or regenerative medicine are fields of life science employing both engineering and biological principles to create new tissues and organs and to promote the regeneration of damaged or diseased tissues and organs. Major advances and innovations are being made in the fields of tissue engineering and regenerative medicine and have a huge impact on three-dimensional bioprinting (3D bioprinting) of tissues and organs. 3D bioprinting holds great promise for artificial tissue and organ bioprinting, thereby revolutionizing the field of regenerative medicine. This review discusses how recent advances in the field of regenerative medicine and tissue engineering can improve 3D bioprinting and vice versa. Several challenges must be overcome in the application of 3D bioprinting before this disruptive technology is widely used to create organotypic constructs for regenerative medicine.

PMID: 30154861 [PubMed]

A Nanomicellar Prodrug Carrier Based on Ibuprofen-Conjugated Polymer for Co-delivery of Doxorubicin.

Front Pharmacol. 2018;9:781

Authors: Li Z, Sun J, Huang Y, Liu Y, Xu J, Chen Y, Liang L, Li J, Liao Q, Li S, Zhou K

Abstract
Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug (NSAID), which is widely used to reduce fever and treat inflammation and acute pain. Recently, its application in cancer treatment is also being explored. In this work, we synthesized a well-defined IBU-based amphiphilic diblock copolymer via reversible addition fragmentation transfer (RAFT) polymerization of IBU-based vinyl monomer. The amphiphilic copolymer POEG-b-PVBIBU (denoted as POVI) was composed of a hydrophilic poly(oligo(ethylene glycol)) block and a hydrophobic IBU-bearing prodrug block, which was able to self-assemble into prodrug nanomicelles. In addition, it could serve as a carrier to co-load other drugs including doxorubicin (DOX), paclitaxel (PTX), and docetaxel (DTX). By using DOX as a model anti-cancer drug, the delivery function of POVI carrier, including the drug release, in vitro cytotoxicity, cellular uptake, and in vivo antitumor activity, was evaluated. DOX-loaded POVI micelles exhibited sustained release of DOX. Besides, DOX/POVI micelles were effectively taken up by tumor cells with an efficiency comparable to that of free DOX. Moreover, in vivo studies showed that POVI carrier itself had modest antitumor activity. After loading DOX, the antitumor activity was significantly increased, which was significantly higher than that of free DOX. Our results suggest that POVI polymer represents a simple and effective dual-functional carrier for co-delivery of IBU and DOX to improve the anticancer activity.

PMID: 30154714 [PubMed]

Dyslipidaemia: The PCSK9 adventure - humanizing extreme LDL lowering.

Nat Rev Cardiol. 2017 06;14(6):319-320

Authors: Shapiro MD, Fazio S

PMID: 28470176 [PubMed - indexed for MEDLINE]

Cariprazine In Bipolar Depression And Mania: State Of The Art.

CNS Neurol Disord Drug Targets. 2018 Aug 28;:

Authors: Mazza M, Marano G, Traversi G, Carocci V, Romano B, Janiri L

Abstract
BACKGROUND: Cariprazine is a piprazine derivative approved by the FDA in 2015 for the treatment of schizophrenia and bipolar manic or mixed episodes in adults. High affinity for D3 dopamine receptors and observed actions on 5HT1A, 5HT2A and alpha 1B receptors differentiate it pharmacologically from other antipsychotics.
METHOD: This review is a comprehensive and thorough summary of the most important findings on cariprazine use in bipolar mania and depression. Pharmacokinetics, pharmacogenetics, tolerability and safety adverse effects are discussed in this paper. Moreover, the results from pivotal clinical trials are presented.
RESULTS: Cariprazine represents an additional option for clinicians to treat patients with bipolar disorder. It shows a unique pharmacological profile and has demonstrated in randomized clinical trials efficacy and general tolerability compared to placebo in bipolar mania and seem to be a promising therapeutic option for bipolar depression.

PMID: 30152291 [PubMed - as supplied by publisher]

The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease.

Oxid Med Cell Longev. 2018;2018:4010395

Authors: Wen YD, Wang H, Zhu YZ

Abstract
The recognition of hydrogen sulfide (H2S) has been evolved from a toxic gas to a physiological mediator, exhibiting properties similar to NO and CO. On the one hand, H2S is produced from L-cysteine by enzymes of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST) in combination with aspartate aminotransferase (AAT) (also called as cysteine aminotransferase, CAT); on the other hand, H2S is produced from D-cysteine by enzymes of D-amino acid oxidase (DAO). Besides sulfide salt, several sulfide-releasing compounds have been synthesized, including organosulfur compounds, Lawesson's reagent and analogs, and plant-derived natural products. Based on garlic extractions, we synthesized S-propargyl-L-cysteine (SPRC) and its analogs to contribute our endeavors on drug development of sulfide-containing compounds. A multitude of evidences has presented H2S is widely involved in the roles of physiological and pathological process, including hypertension, atherosclerosis, angiogenesis, and myocardial infarcts. This review summarizes current sulfide compounds, available H2S measurements, and potential molecular mechanisms involved in cardioprotections to help researchers develop further applications and therapeutically drugs.

PMID: 30151069 [PubMed - in process]

Sex-dependent association of circulating sex steroids and pituitary hormones with treatment-free survival in chronic lymphocytic leukemia patients.

Ann Hematol. 2018 Sep;97(9):1649-1661

Authors: Allain EP, Venzl K, Caron P, Turcotte V, Simonyan D, Gruber M, Le T, Lévesque E, Guillemette C, Vanura K

Abstract
Chronic lymphocytic leukemia (CLL) is not considered a hormone-regulated cancer although sex is a recognized risk factor with men more frequently diagnosed and developing progressive disease. We hypothesized that variable hormonal exposure may have a sexually dimorphic influence on treatment-free survival (TFS). In 156 CLL cases, we quantitatively profiled 29 circulating steroids (progesterone, adrenal precursors, androgens, estrogens, and catechol estrogens) as well as luteinizing hormone (LH) and follicle-stimulating hormone. Median TFS was shorter for men than that for women (80.7 vs. 135.0 months, P = 0.033). Circulating hormone profiles in CLL patients were significantly different from those of healthy donors. In male CLL cases, higher LH levels were associated with shorter TFS (adjusted hazard ratio (HRadj) 2.11; P = 0.004). In female CLL cases, high levels of the potent androgens testosterone and dihydrotestosterone and the sum of methoxy estrogens were associated with an improved TFS with HRadj values of 0.24 (P = 0.007), 0.54 (P = 0.023), and 0.31 (P = 0.034), respectively. Reduced TFS was observed for women with CLL exhibiting high expression of the steroid-inactivating UGT2B17 enzyme. This study is the first to establish a link between the outcome of CLL patients, sex steroids, and pituitary hormones, revealing a sex-specific hormonal imbalance associated with disease progression.

PMID: 29781039 [PubMed - indexed for MEDLINE]

Pharmacokinetics of CYP2C9, CYP2C19, and CYP2D6 substrates in healthy Chinese and European subjects.

Eur J Clin Pharmacol. 2018 Mar;74(3):285-296

Authors: Lu S, Nand RA, Yang JS, Chen G, Gross AS

Abstract
PURPOSE: The aim of this analysis is to compare the pharmacokinetics of drug substrates in healthy Chinese and European subjects of aligned CYP2C9, CYP2C19, or CYP2D6 enzyme activity, providing further insight into drivers of interethnic differences in pharmacokinetics.
METHODS: Following identification of appropriate drug substrates, a comprehensive and structured literature search was conducted to identify single-dose pharmacokinetic data in healthy Chinese or European subjects with reported CYP2C9, CYP2C19, or CYP2D6 activity (genotype or phenotype). The ratio of drug AUC in the Chinese and European subjects classified with aligned enzyme activity was calculated (ethnicity ratio (ER)).
RESULTS: For 22/25 drugs identified, the ERs calculated indicated no or only limited interethnic differences in exposure (<twofold) in Chinese and European subjects with aligned polymorphic enzyme activity. The interethnic differences observed can reflect differences across populations in additional determinants of pharmacokinetics, although the notable between study variation and change over time in methods used to assign enzyme activity may also be contributing factors. There was no association between drug substrate fraction metabolized (fm) for CYP2C9, CYP2C19, or CYP2D6 and the ERs calculated.
CONCLUSION: The spectrum of pharmacokinetic determinants for each drug substrate and their differences across ethnic groups must be considered on a case-by-case basis in addition to metabolism by CYP2C9, CYP2C19, or CYP2D6. This analysis has also highlighted the challenges which arise when comparing published datasets if consistent methods to assign polymorphic enzyme activity have not been used.

PMID: 29181698 [PubMed - indexed for MEDLINE]

Role of intestinal microbiome in American ginseng-mediated colon cancer prevention in high fat diet-fed AOM/DSS mice [corrected].

Clin Transl Oncol. 2018 03;20(3):302-312

Authors: Wang CZ, Huang WH, Zhang CF, Wan JY, Wang Y, Yu C, Williams S, He TC, Du W, Musch MW, Chang EB, Yuan CS

Abstract
OBJECTIVE: Chronic intestinal inflammation is a risk factor for colorectal cancer (CRC) initiation and development. Diets that are rich in Western style fats have been shown to promote CRC. This study was conducted to investigate the role of intestinal microbiome in American ginseng-mediated CRC chemoprevention in a mouse model. The population and diversity of enteric microbiome were evaluated after the ginseng treatment.
METHODS: Using an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced gut inflammation and tumorigenesis mouse model, the effects of oral American ginseng on high fat diet-associated enteric pathology were determined. After establishment of a 16S rRNA illumina library from fecal samples, MiSeq sequencing was carried out to reveal the microbial population. The alpha and beta diversities of microbiome were analyzed.
RESULTS: American ginseng significantly attenuated AOM/DSS-induced colon inflammation and tumorigenesis by reducing the colitis score and colon tumor multiplicity. The MiSeq results showed that the majority of sequences fell into three phyla: Firmicutes, Bacteroidetes and Verrucomicrobia. Further, two significant abundance shifts at the family level, Bacteroidaceae and Porphyromonadaceae, were identified to support ginseng's anti-colitis and anti-tumor effects. In addition, alpha and beta diversity data demonstrated that ginseng led to a profound recovery from the AOM/DSS-induced dysbiosis in the microbial community.
CONCLUSION: Our results suggest that the CRC chemopreventive effects of American ginseng are mediated through enteric microbiome population-shift recovery and dysbiosis restoration. Ginseng's regulation of the microbiome balance contributes to the maintenance of enteric homeostasis.

PMID: 28808878 [PubMed - indexed for MEDLINE]

Recent advances in the understanding of severe cutaneous adverse reactions.

Br J Dermatol. 2017 Nov;177(5):1234-1247

Authors: Adler NR, Aung AK, Ergen EN, Trubiano J, Goh MSY, Phillips EJ

Abstract
Severe cutaneous adverse reactions (SCARs) encompass a heterogeneous group of delayed hypersensitivity reactions, which are most frequently caused by drugs. Our understanding of several aspects of SCAR syndromes has evolved considerably over the last decade. This review explores evolving knowledge of the immunopathogenic mechanisms, pharmacogenomic associations, in vivo and ex vivo diagnostics for causality assessment, and medication cross-reactivity data related to SCAR syndromes. Given the rarity and severity of these diseases, multidisciplinary collaboration through large international, national and/or multicentre networks to collect prospective data on patients with SCAR syndromes should be prioritized. This will further enhance a systematized framework for translating epidemiological, clinical and immunopathogenetic advances into preventive efforts and improved outcomes for patients.

PMID: 28256714 [PubMed - indexed for MEDLINE]

Long-term clinical response to treatment and maintenance of localized aggressive periodontitis: a cohort study.

J Clin Periodontol. 2017 Feb;44(2):158-168

Authors: Miller KA, Branco-de-Almeida LS, Wolf S, Hovencamp N, Treloar T, Harrison P, Aukhil I, Gong Y, Shaddox LM

Abstract
AIM: To evaluate long-term clinical response to periodontal therapy and maintenance in localized aggressive periodontitis (LAP).
MATERIALS AND METHODS: One hundred forty-one African Americans diagnosed with LAP, aged 5-25 years, were enrolled. Patients underwent periodontal mechanical debridement plus 1 week of amoxicillin/metronidazole. Mechanical therapy was repeated as needed and clinical parameters were recorded at baseline, 3, 6, 12, 18 and 24 months, and two additional annual follow-up visits after treatment. Radiographs from primary dentition of patients with LAP in permanent dentition, and additional healthy siblings (HS) were analysed retrospectively.
RESULTS: Periodontal therapy significantly improved probing depth and clinical attachment level up to 4 years (mean reductions: 2.18 ± 1.03 and 2.80 ± 1.43 mm, respectively). Percentage of affected sites was reduced at all time points and maintained up to 4 years. Non-compliance with antibiotics/appointments negatively affected the treatment response. Ninety per cent of LAP patients in permanent dentition and 32% of HS presented radiographic bone loss in primary dentition.
CONCLUSIONS: Mechanical debridement with 1 week of systemic antibiotics along with proper periodontal maintenance was effective in the treatment and successful maintenance of LAP for up to 4 years. LAP in permanent dentition may be preceded in the primary dentition. Clinicaltrials.gov #NCT01330719.

PMID: 27767222 [PubMed - indexed for MEDLINE]

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2018/08/28

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13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2018/08/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

GSK-3b 50 T/C polymorphism in bipolar disorder and its relationship with clinical phenotypes and treatment response.

J Affect Disord. 2018 Aug 17;241:433-435

Authors: Sathur Raghuraman B, Paul P, Nadella RK, Kapur V, Purushottam M, Jain S, Kannan R, Del Zompo M, Viswanath B

PMID: 30145514 [PubMed - as supplied by publisher]

Prevention of Prematurity: Advances and Opportunities.

Clin Perinatol. 2018 Sep;45(3):579-595

Authors: Govindaswami B, Jegatheesan P, Nudelman M, Narasimhan SR

Abstract
Preterm birth (PTB) rate varies widely and has significant racial and ethnic disparities. Although causal mechanisms are ill understood, socioenvironment, phenotype, and genotype provide insight into pathways for preventing PTB. Data suggest varied response to current medical interventions is explicable Approved by underlying pharmacogenomics. Currently, prevention focuses on minimizing iatrogenic PTB and risk reduction especially in those with prior PTB using proven medical and public health strategies. In the future, preventive approaches will be based on better understanding of sociodemography, nutrition, lifestyles, and underlying individual genetic and epigenetic variation. Statistical approaches and "big-data" models are critical in future study.

PMID: 30144857 [PubMed - in process]

Standardization of CTC AR-V7 PCR assay and evaluation of its role in castration resistant prostate cancer progression.

Prostate. 2018 Aug 23;:

Authors: Tommasi S, Pilato B, Carella C, Lasorella A, Danza K, Vallini I, De Summa S, Naglieri E

Abstract
BACKGROUND: Castration resistant prostate cancer (CRPC) represents the most aggressive status of this neoplastic disease, also characterized by the absence of biomarkers predictive of clinical outcome. New drugs as abiraterone or enzalutamide, affecting androgen receptor pathway at different levels, inhibit the proliferative advantage of prostate cancer cells with important long term benefits. Despite the advantages of this second-generation androgen deprivation therapy (ADT), resistance mechanisms, primitive or acquired, often develop. The existence of androgen receptor (AR) splice variants (AR-Vs), in particular AR-V7 expression detected in circulating tumor cells (CTCs), represents an example of acquired resistance, as evidenced in preclinical and clinical studies. Recent studies also have suggested the role of AR-V7 as a prognostic biomarker in mCRPC. In this field, hot topics are the methodology used to isolate CTC and the assay for AR-V7 measurement. Our study aims to develop a standardized operating procedure (SOP) to evaluate AR-V7 in CRPC.
METHOD: The application of a realized cell based Reference Sample as Standardized Quality Control tool for CTC-AR-V7 assay has been shown. Then the development, the performance evaluation and contextualization in a clinical setting of this standardized operating procedure (SOP) have been reported to evaluate the prognostic biomarker AR-V7 in metastatic prostate cancer.
RESULTS AND CONCLUSIONS: The standardized procedure has high sensitivity and specificity and enables the detection and quantification of the spliced variant with respect to the full length AR (AR-FL) mRNA in CTC DNA purified from the blood of patients with CRPC. This procedure has been further validated in a consecutive series of patients with mCRPC, confirming its role as prognostic biomarker.

PMID: 30141201 [PubMed - as supplied by publisher]

Alpha-Tocopherol Serum Levels Are Increased in Caucasian Women with Uterine Fibroids: A Pilot Study.

Biomed Res Int. 2018;2018:6793726

Authors: Ciebiera M, Szymańska-Majchrzak J, Sentkowska A, Kilian K, Rogulski Z, Nowicka G, Jakiel G, Tomaszewski P, Włodarczyk M

Abstract
Uterine fibroids (UFs) are benign tumors of the reproductive tract, arising from smooth muscle cells of the uterus. Steroid hormones, estrogen, and progesterone are considered to be the most important links in the pathophysiology of UFs. Alpha-tocopherol (AT) is the most active form of vitamin E. What is important as far as UFs are concerned is that ATs contain structural determinants, which makes them possible ligands for estrogen receptors (ERs). We present a retrospective cohort study performed in a university teaching hospital. We included a total of 162 patients divided into 2 groups: with UFs and controls. The effects of age, body mass index (BMI), positive medical history, parity, and AT serum concentrations on the risk for the development of UFs were investigated. Mean AT serum concentrations were 11.66 ± 4.97 μg/ml and 7.83 ± 3.13 μg/ml (medians 10.56 μg/ml and 7.42 μg/ml) in patients with UFs confirmed on ultrasound and controls, respectively. The presented difference was statistically significant. Higher BMI, positive family history, and low parity were found to be major risk factors for UFs. In our study, we confirmed that elevated serum AT concentration might be an important risk factor for UFs in Caucasian women. Further research in this area is necessary.

PMID: 30140700 [PubMed - in process]