Search

Background: This retrospective observational study explored the therapeutic potential of combined androgen blockade (CAB) with bicalutamide (Bic-CAB) as an initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC) in Japan. Methods: The electronic health records of 159 patients with mHSPC from three Japanese institutions who received initial treatment with Bic-CAB between 2007 and 2017 were analyzed. The time to prostate-specific antigen (PSA) progression, duration of Bic-CAB treatment, and overall survival (OS), with various definitions for PSA progression, were assessed. A multivariate Cox proportional hazards model was constructed using clinical parameters to predict time to the end of Bic-CAB treatment and OS. Results: The median observation period was 46.4 months, and the median age of patients at diagnosis was 71 years. A total of 46.5% patients experienced PSA progression with a median survival duration of 29 months (according to Prostate Cancer Clinical Trials Working Group 3 criteria), and 49.1% patients achieved a PSA nadir < 0.2 ng/mL in a median time of 4.7 months. When stratified by PSA nadir and PSA change, patients at low risk for disease progression with a small PSA change due to low initial PSA had a 5-year OS of 100% and a 10-year OS of 75%. The OS during the observation period was 72.9 months. Conclusion: These findings highlight the potential effect of Bic-CAB in patients with mHSPC who were at low risk for disease progression. Initial treatment with Bic-CAB and adjusting treatment early based on PSA dynamics may be a reasonable treatment plan for these patients. [ABSTRACT FROM AUTHOR]

Levels of anticancer agents in cancer patients' body fluids are typically measured to adjust drug dosages or improve treatment results. The goal of this research is to present a new method for extracting bicalutamide (BCT) from biological samples using a responsive polymeric nanoadsorbent that reacts to temperature and near‐infrared radiation (NIR). To achieve this, the surface layers of tungsten disulfide nanosheets are modified using poly (N‐vinylcaprolactam) and three generations of polymeric dendrimers. The adsorbent product is then characterized using thermogravimetric analysis, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, and X‐ray diffraction techniques. The drug loading operation on the proposed adsorbent is studied through central composite design and response surface strategy, with optimization for temperature (25–45°C), pH (5–9), and contact time (2–18 min). Nonlinear kinetic and adsorption isotherm analysis results show the best fit with Langmuir and pseudo‐second‐order models. The drug release process from the BCT‐loaded adsorbent is investigated via an HPLC‐UV system under both NIR‐irradiated and non‐irradiated conditions. The suggested method demonstrates remarkable recovery rates for BCT spikes from urine (95.23%) and plasma (93.33%), respectively. Overall, the recommended strategy can be regarded as a potent analytical tool for evaluating BCT in complex biosamples. [ABSTRACT FROM AUTHOR]

The binding mechanism of molecular interaction between bicalutamide and human serum albumin (HSA) in a pH 7.4 phosphate buffer was studied using various spectroscopic techniques in combination with molecular modeling. Fluorescence data revealed that the fluorescence quenching of HSA by bicalutamide was a static quenching procedure. The binding constants and number of binding sites were evaluated at different temperatures. The thermodynamic parameters, ΔH and ΔS, were calculated to be 4.30 × 104 J·mol−1 and 245 J·mol−1·K−1, respectively, suggesting that the binding of bicalutamide to HSA was driven mainly by hydrophobic interactions and hydrogen bonds. The displacement studies indicated neither Sudlow's site I nor II but subdomain IB as the main binding site for bicalutamide on HSA. The binding distance between bicalutamide and HSA was determined to be 3.54 nm based on the Förster theory. Analysis of circular dichroism, synchronous, and 3D fluorescence spectra demonstrated that HSA conformation was slightly altered in the presence of bicalutamide. [ABSTRACT FROM AUTHOR]

The study presents a thorough and detailed analysis of bicalutamide's structural and conformational properties. Quantum chemical calculations were employed to explore the conformational properties of the molecule, identifying significant energy differences between conformers. Analysis revealed that hydrogen bonds stabilise the conformers, with notable variations in torsion angles. Conformers were classified into 'closed' and 'open' types based on the relative orientation of the cyclic fragments. NOE spectroscopy in different solvents (CDCl3 and DMSO-d6) was used to study the conformational preferences of the molecule. NOESY experiments provided the predominance of 'closed' conformers in non-polar solvents and a significant presence of 'open' conformers in polar solvents. The proportions of open conformers were 22.7 ± 3.7% in CDCl3 and 59.8 ± 6.2% in DMSO-d6, while closed conformers accounted for 77.3 ± 3.7% and 40.2 ± 6.2%, respectively. This comprehensive study underscores the solvent environment's impact on its structural behaviour. The findings significantly contribute to a deeper understanding of conformational dynamics, stimulating further exploration in drug development. [ABSTRACT FROM AUTHOR]

Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are highly aggressive neoplastic diseases that share numerous characteristics. In IBC and IMC, chemotherapy produces a limited pathological response and anti-androgen therapies have been of interest for breast cancer treatment. Therefore, the aim was to evaluate the effect of a therapy based on bicalutamide, a non-steroidal anti-androgen, with doxorubicin and docetaxel chemotherapy on cell proliferation, migration, tumor growth, and steroid-hormone secretion. An IMC-TN cell line, IPC-366, and an IBC-TN cell line, SUM149, were used. In vitro assays revealed that SUM149 exhibited greater sensitivity, reducing cell viability and migration with all tested drugs. In contrast, IPC-366 exhibited only significant in vitro reductions with docetaxel as a single agent or in different combinations. Decreased estrogen levels reduced in vitro tumor growth in both IMC and IBC. Curiously, doxorubicin resulted in low efficacy, especially in IMC. In addition, all drugs reduced the tumor volume in IBC and IMC by increasing intratumoral testosterone (T) levels, which have been related with reduced tumor progression. In conclusion, the addition of bicalutamide to doxorubicin and docetaxel combinations may represent a potential treatment for IMC and IBC. [ABSTRACT FROM AUTHOR]

A carbon paste sensor was modified with sepiolite clay particles (SC/CPE) to quantify the bicalutamide (BICA). BICA's probable oxidation mechanism and the interaction between calf thymus DNA (dsDNA) were investigated (in aqueous medium, pH 4.8) for the first time. Cyclic voltammetry (CV), Electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM) were used for the investigation of surface morphology and electrochemical characteristics. The effect of the amount of SC, supporting electrolyte, and pH was optimized. Under optimum conditions, the developed sensor exhibited a linear response between 0.223 and 20.0 μM. The detection of the limit was found to be 0.069 μM. The sensor was successfully applied to quantify BICA in biological and pharmaceutical samples. Finally, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) provided new insight into the interaction between BICA and ds‐DNA. The kinetic parameters for the free DNA, diffusion coefficient (D), heterogeneous rate constant (ks), and electrode surface concentration (Γ) were calculated to be 4.22×10−5 cm2 s−1, 0.57 s−1 and 7.67×10−9 mol cm−2, respectively. The (ds‐DNA)‐BICA complex parameters were 4.56×10−6 cm2 s−1, 0.70 s−1, and 1.61×10−9 mol cm−2. In addition, binding constant (K) and Gibbs free energy change (ΔG°) were 6.02×105 M−1 and −32.97 kJ mol−1, respectively. [ABSTRACT FROM AUTHOR]

A straightforward and efficient dispersive micro solid-phase extraction was developed for extracting bicalutamide and flutamide as anti-cancers in real water and biological samples. A proper sorbent composite, including a metal-organic framework (CIM-80 (Al)), magnetic Nickel oxide nanoparticles, and Chitosan, was prepared. The ratio of the sorbent components was optimised using an optimal mixture design to increase the efficiency of the synthesised sorbent in the extraction of analytes. The optimum value of CIM-80 (Al), magnetic Nickel oxide nanoparticles, and Chitosan in the sorbent composition was 0.36, 0.22, and 0.42. The sorbent was characterised using XRD, FTIR, SEM, TEM, VSM, and BET analysis. Factors affecting the microextraction process were evaluated and optimised using a fractional factorial design and a central composite design. Under optimum conditions, the procedure was linear in the concentration range of 1.2–356.4 ng mL−1 and 0.89–348.7 ng mL−1 with a coefficient of determination of 0.9951 and 0.9947 for the determination of bicalutamide and flutamide, respectively. The detection limits and inter-day RSDs % for the bicalutamide and flutamide determination were lower than 0.35 ng mL−1 and 6.21%, respectively. Analysis of real water, drug-free urine, drug-free plasma, and post-drug urine samples indicated that the method has a high ability to analyse water and biological samples for the bicalutamide and flutamide determination. The method's effects on the environment for the bicalutamide and flutamide determination were evaluated using the Green Analytical Procedure Index and Analytical Eco-Scale. [ABSTRACT FROM AUTHOR]

Background: Androgen blockers are an essential part of gender affirming care in post-pubertal transfeminine patients. Bicalutamide is a highly potent androgen receptor blocker that is used primarily in adults. We aimed to review our experience with the use of bicalutamide in transgender adolescents who were assigned male at birth. Methods: A retrospective review of medical records of transfeminine patients treated with bicalutamide during an 8-year period was conducted. Results: Forty patients, aged 15.5 ± 1.55 years were identified, of whom 21 (53%) were started on bicalutamide alone and 19 were started concurrently on estrogen. In patients on bicalutamide alone, 90.4% reported breast development at their first follow up visit, which occurred at a median of 7.1 months. Patients were treated for 29.4 ± 18.2 months. No episodes of liver toxicity related to bicalutamide were seen. Conclusions: Although these results are preliminary, bicalutamide appears to be a safe option for androgen blockade in transgender girls. [ABSTRACT FROM AUTHOR]