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International Journal of Molecular... Jan 2024The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no...
The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no overexpression of HER-2. However, TNBC can express the androgen receptor (AR) or estrogen receptor β (ERβ). Also, TNBC secretes steroid hormones and is influenced by hormonal fluctuations, so the steroid inhibition could exert a beneficial effect in TNBC treatment. The aim of this study was to evaluate the effect of dutasteride, anastrozole and ASP9521 in in vitro processes using human TNBC cell lines. For this, immunofluorescence, sensitivity, proliferation and wound healing assays were performed, and hormone concentrations were studied. Results revealed that all TNBC cell lines expressed AR and ERβ; the ones that expressed them most intensely were more sensitive to antihormonal treatments. All treatments reduced cell viability, highlighting MDA-MB-453 and SUM-159. Indeed, a decrease in androgen levels was observed in these cell lines, which could relate to a reduction in cell viability. In addition, MCF-7 and SUM-159 increased cell migration under treatments, increasing estrogen levels, which could favor cell migration. Thus, antihormonal treatments could be beneficial for TNBC therapies. This study clarifies the importance of steroid hormones in AR and ERβ-positive cell lines of TNBC.
Topics: Humans; Androgens; Receptors, Estrogen; Triple Negative Breast Neoplasms; Estrogen Receptor beta; Cell Line, Tumor; Estrogens; Receptors, Androgen; Steroids; Estrogen Receptor alpha; Cell Proliferation
PubMed: 38338747
DOI: 10.3390/ijms25031471 -
The Journal of Dermatology May 2024Dutasteride 0.5 mg is a dual inhibitor of 5α-reductase type I and II and was approved in Korea in 2009 for treating androgenetic alopecia (AGA) in men. We...
Dutasteride 0.5 mg is a dual inhibitor of 5α-reductase type I and II and was approved in Korea in 2009 for treating androgenetic alopecia (AGA) in men. We investigated the 5-year efficacy and safety of dutasteride 0.5 mg in Korean men with AGA using the basic and specific (BASP) classification. This retrospective analysis included 99 male AGA patients aged ≥18 years who were treated with dutasteride 0.5 mg for at least 5 years from October 2009 to December 2016 at Kyung Hee University Hospital in Gangdong. Patient photographs were scored using the BASP classification, and the Investigator Global Assessment (IGA) was performed using a seven-point scale. Patient improvement (IGA score ≥1) and prevention of disease progression (IGA score ≥0) were 89.9% (89/99) and 93.9% (93/99), respectively. According to the BASP classification, 52.5% (52/99) of the basic type, 75% (15/20) of the specific F type, and 82.2% (60/73) of the specific V type showed clinical improvement after 5 years of treatment. Dutasteride demonstrated long-term safety and efficacy in Korean male patients with AGA over a period of at least 5 years, with results comparable to those of other long-term efficacy studies of finasteride 1 mg in male patients with AGA.
Topics: Humans; Male; Alopecia; Dutasteride; Retrospective Studies; Adult; 5-alpha Reductase Inhibitors; Republic of Korea; Middle Aged; Treatment Outcome; Young Adult; Disease Progression; Time Factors; Aged
PubMed: 38321615
DOI: 10.1111/1346-8138.17138 -
Expert Opinion on Pharmacotherapy Feb 2024Treating alopecia can be challenging. The available treatments are topical minoxidil, low-dose oral minoxidil (LDOM), and 5-α reductase inhibitors like finasteride and... (Review)
Review
INTRODUCTION
Treating alopecia can be challenging. The available treatments are topical minoxidil, low-dose oral minoxidil (LDOM), and 5-α reductase inhibitors like finasteride and dutasteride. Only topical minoxidil and finasteride 1 mg daily are FDA-approved, while the rest are used off-label. Recent research has suggested that oral minoxidil may be a safe and effective treatment for both female androgenetic alopecia (female AGA) and male androgenetic alopecia (male AGA).
AREAS COVERED
In this review, we explore the pharmacokinetics, mechanism of action, safety, and efficacy of oral minoxidil. Additionally, we discuss its effectiveness compared to other treatments available for female AGA and male AGA.
EXPERT OPINION
LDOM has demonstrated a favorable efficacy and safety profile in several trials. Subsequently, its use for the treatment of male AGA and female AGA is increasing. However, its use remains off-label, and through increased usage, we will get a better idea of the best dosage and monitoring guidelines. LDOM has also been used with some effectiveness in other forms of hair loss.
Topics: Male; Female; Humans; Minoxidil; Finasteride; Alopecia; 5-alpha Reductase Inhibitors; Treatment Outcome
PubMed: 38315101
DOI: 10.1080/14656566.2024.2314087 -
Spectrochimica Acta. Part A, Molecular... Apr 2024Here, we present the new application of solid-state Vibrational Circular Dichroism (VCD) spectroscopy to differentiate several dutasteride (DS) solvatomorphs - the model...
Here, we present the new application of solid-state Vibrational Circular Dichroism (VCD) spectroscopy to differentiate several dutasteride (DS) solvatomorphs - the model active pharmaceutical ingredient (API). Several crystalline DS hydrochloride hydrates solvated with methanol, ethanol, acetonitrile, acetone, and acetic acid were prepared. In contrast to almost identical IR spectra, the VCD ones were very sensitive to changes in the sample composition. We marked significant differences in the shape of VCD spectra of studied DS solvatomorphs, DS hydrates, and DS polymorphic forms. Our findings, supported by DFT calculations, show that VCD spectroscopy has the pronounced ability to distinguish their crystal arrangements. We believe that this contribution will extend the use of VCD in the pharmaceutical industry for developing and designing new chiral drug products for the identification, description, and in-depth probing of several pharmaceutical solvatomorphs in the future.
Topics: Circular Dichroism; Bulk Drugs; Spectrophotometry, Infrared; Methanol; Stereoisomerism
PubMed: 38295593
DOI: 10.1016/j.saa.2024.123851 -
Cureus Dec 2023Benign prostatic hyperplasia (BPH) is a progressive disease that causes low urinary tract symptoms (LUTS). As prostatic volume grows, the prostatic urethra may become...
BACKGROUND
Benign prostatic hyperplasia (BPH) is a progressive disease that causes low urinary tract symptoms (LUTS). As prostatic volume grows, the prostatic urethra may become completely obstructed, resulting in full urine retention and acute hypogastric pain. Our research aimed to identify the optimal trial without catheter (TWOC) therapeutic approach and identify those factors that are associated with the recurrence of complete urinary retention (CUR).
METHODOLOGY
The study enrolled with complete urinary retention and BPH were included in the study, after the insertion of a Foley catheter. The patients received tamsulosin 0.4 mg/day as an alpha-blocker treatment. In our investigation, patients who encountered complete urinary retention were randomly categorized into four groups based on the duration of urinary catheterization as determined by the attending urologist.
RESULTS
Maintaining the urethrovesical catheter for three to seven days was related to the highest success of spontaneous urination, which was statistically significant compared to other study groups. (p=0.0007). Age over 70 years, no alpha-blocker before the urinary retention episode, and prostatic volume exceeding 50 ml were all associated with decreased TWOC efficacy. We found the highest rates of spontaneous urination were after three to seven days of urinary catheterization.
CONCLUSION
BPH and complete urine retention can be managed by TWOC in many cases. Several factors affect the test's efficacy. Prolonged urinary catheter maintenance over seven days, prostatic volume over 50 ml, and age over 70 years are poor prognostic indicators.
PubMed: 38259407
DOI: 10.7759/cureus.50980 -
Pharmaceutical Nanotechnology Jan 2024Dutasteride is approximately three times more potent than finasteride in treating alopecia. For reducing systemic exposure to dihydrotestosterone (DHT), researchers have...
BACKGROUND
Dutasteride is approximately three times more potent than finasteride in treating alopecia. For reducing systemic exposure to dihydrotestosterone (DHT), researchers have shown special interest in developing topical formulations for treating androgenic alopecia. Dutasteride emulsification may lead to good skin penetration and improved availability in different lipophilic skin environments.
OBJECTIVES
This study aimed to encapsulate the drug into the lipidic carrier system for better local availability in the scalp skin, develop and evaluate nanoemulgel of dutasteride to ensure efficient topical administration, and perform the in-vivo activity of the developed gel for improved efficacy against alopecia.
METHODS
Dutasteride-loaded nanoemulsion was prepared by a high-speed homogenizer, followed by thickening of the dispersion using Carbopol 934. Skin permeation and accumulation were investigated in the excised skin of male Swiss albino mice. The nanoemulgel was characterized based on pH, stress stability, viscosity, and hardness.
RESULTS
The optimized dutasteride-loaded nanoemulsion had a size of 252.33 ± 8.59 nm, PDI of 0.205 ± 0.60, and drug content of 98.65 ± 1.78%. Stress stability was performed was well observed in nanoemulsion formulation. Nanoemulgel evaluation results were as follows: pH 5-6 was desirable for topical application, hardness was 43 gm, and spreadability was 79 gm with in vitro release of nanoemulgel at 91.98% and permeation study at 13.67%.
CONCLUSION
The in vivo studies demonstrated the growth of newer hair follicles and increased hair diameter and length in dutasteride-loaded nanoemulgel-treated alopecia animals compared to the marketed sample and testosterone-treated group. Provided with the same and long-term storage stability, the developed formulation is supposed to offer a good option for the topical administration of dutasteride in treating androgenic alopecia.
PubMed: 38173065
DOI: 10.2174/0122117385269151231031161411 -
American Journal of Clinical and... 2023Herbal supplements are widely used to enhance prostate health. These supplements may contain several types of plant sterols, vitamins, and minerals. By weight, however,... (Review)
Review
Herbal supplements are widely used to enhance prostate health. These supplements may contain several types of plant sterols, vitamins, and minerals. By weight, however, plant sterols make up an abundant ingredient component, with saw palmetto extract or its primary component, beta-sitosterol, often comprising the most abundant sterol. Saw palmetto extract/beta-sitosterol has been shown to promote anti-tumorigenic processes in prostate cancer cells and rodent models of prostate cancer. It has also been shown to inhibit the 5α-reductase enzyme, thereby behaving similarly to finasteride and dutasteride, which are widely used to treat prostatic enlargement, or benign prostatic hyperplasia (BPH). The aim of this study is to critically examine , , and human clinical studies to assess the safety and clinical utility of herbal supplements containing saw palmetto extract/beta-sitosterol for prostate health. The results of this study suggest multiple mechanisms through which beta-sitosterol represses prostate cancer and , particularly through its pro-apoptotic effect on prostate epithelial cells. Multiple studies also show that beta-sitosterol significantly improves lower urinary tract symptoms (LUTS) associated with BPH, but to an extent that is generally less effective than that achieved by pharmaceutical grade alpha-adrenergic receptor antagonists or 5α-reductase inhibitors. This latter finding suggests that supplements containing beta-sitosterol might be most appropriate for younger men with minimal LUTS who don't wish to embark on a clinical drug regimen for BPH treatment.
PubMed: 38148931
DOI: No ID Found -
ChemistryOpen May 2024Phosphodiesterase type 5 (PDE5) is a multidomain protein that plays a crucial role in regulating cellular cyclic guanosine monophosphate (cGMP), a key signaling molecule...
Phosphodiesterase type 5 (PDE5) is a multidomain protein that plays a crucial role in regulating cellular cyclic guanosine monophosphate (cGMP), a key signaling molecule involved in various physiological processes. Dysregulation of PDE5 and cGMP signaling is associated with a range of vasodysfunctional disorders, necessitating the development of effective therapeutic interventions. This study adopts comprehensive approach, combining virtual screening and molecular dynamics (MD) simulations, to repurpose FDA-approved drugs as potential PDE5 inhibitors. The initial focus involves selecting compounds based on their binding affinity. Shortlisted compounds undergo a meticulous analysis for their drug profiling and biological significance, followed by the activity evaluation and interaction analysis. Notably, based on binding potential and drug profiling, two molecules, Dutasteride and Spironolactone, demonstrate strong potential as PDE5 inhibitors. Furthermore, all atom MD simulations were employed (500 ns) to explore dynamic behavior of Dutasteride and Spironolactone in complexes with PDE5. Principal components analysis (PCA) and free energy landscape (FEL) analyses are further leveraged to decipher that the binding of Dutasteride and Spironolactone stabilizes the structure of PDE5 with minimal conformational changes. In summary, Dutasteride and Spironolactone exhibit remarkable affinity for PDE5 and possess characteristics that suggest their potential as therapeutic agents for conditions associated with PDE5 dysfunction.
Topics: Drug Repositioning; Phosphodiesterase 5 Inhibitors; Humans; Molecular Dynamics Simulation; Cyclic Nucleotide Phosphodiesterases, Type 5; Spironolactone; Dutasteride; Principal Component Analysis; Molecular Docking Simulation; Protein Binding
PubMed: 38060834
DOI: 10.1002/open.202300196 -
Cureus Oct 2023The foramen ovale serves as an opening between the right and left atria at the site of the fossa ovalis in the fetus during uterine life. During fetal life, it makes...
The foramen ovale serves as an opening between the right and left atria at the site of the fossa ovalis in the fetus during uterine life. During fetal life, it makes it possible for venous blood from the maternal placenta with oxygen and nutrients to bypass the immature fetal lung and get transported to the left side of the heart and onto the systemic circulation. This hole from the right to the left atrium is usually occluded at the time of birth or shortly after birth, due to increased pressures in the left-sided cardiac cavities associated with normal breathing during delivery or shortly afterwards. If the foramen ovale remains open and fails to fuse beyond the first year of life, it is known as a patent foramen ovale (PFO). PFO occurs when, during fetal life, the septum primum and secundum, which develop and overlap normally, fail to fuse at birth. This results in the persistence of communication between the right and left atria. Paradoxical embolism from the right to the left side of the heart can occur through a PFO, causing a cryptogenic stroke or embolic stroke of an undetermined source in an otherwise healthy adult. There was a debate on the long-term benefits of closure. However, data from the randomized evaluation of the recurrent stroke comparing PFO closure to established current standard of care treatment (RESPECT) trial and two randomized trials (patent foramen ovale closure or anticoagulants versus antiplatelet therapy to prevent stroke recurrence (CLOSE) and reduction by dutasteride of prostate cancer events (REDUCE)) have clarified that there is a benefit to closure. In this case report, we describe a patient who presented with cryptogenic stroke, the investigations, imaging modalities for diagnosis of PFO, and procedure for closure. We also describe long-term outcomes and management following closure.
PubMed: 37954786
DOI: 10.7759/cureus.46895