Design and construction of a 110 W green laser for medical application

In this paper, the design and the construction of a high-power side-diode-pumped Nd:YAG solid-state laser at repetition rates of 6 and 10 kHz has been presented. Second harmonic of the Nd:YAG laser with green light at 532 nm, with an average power of 111.5 W at 10 kHz repetition rate, and with 90 ns pulse duration, has been obtained by the nonlinear crystal of KTP with 59% conversion efficiency and 12% diode-to-green optical–optical efficiency in the linear resonator. Beam spot size and divergence is 4 mm and 8 mrad, respectively. The laser stability is about 97%. As a medical application of this laser, investigation of degree of effectiveness and penetration depth of laser on adenomas of resected prostate after open prostatectomy has been done.     

Optimal Biopsy Protocols for Prostate Cancer

Prostate cancer is the second leading cause of cancer-related death among American men. Biopsy for prostate cancer is a procedure known as transrectal ultrasound-guided needle biopsy. Because of the low resolution of ultrasound, the urologist cannot usually distinguish between cancerous and healthy tissue. For this reason, most biopsies follow standard protocols based on long-term experience of physicians. Recent studies indicate that these protocols have a significant rate of false negative diagnoses. In this research we use real prostate specimens removed by prostatectomy to develop a 3-D distribution map of cancer in the prostate, and use this to develop optimized biopsy procedures. The new procedures have detection rates that are significantly higher than those of current procedures, and thus have the potential to increase the rate of early detection of prostate cancer.     

Structural Studies and Anticancer Activity of a Novel Class of β‐Peptides

Functionalized oligomeric organic compounds with well‐defined β‐proline scaffold have been synthesized by a cycloadditive oligomerization approach in racemic and enantiopure forms. The structure of the novel β‐peptides was investigated by NMR spectroscopic and X‐ray methods determining the conformational shapes of the β‐proline oligomers in solution and solid states. The main structural elements subject to conformational switches are β‐peptide bonds between 5‐arylpyrrolidine‐2‐carboxylic acid units existing in Z/E configurations. The whole library of short β‐peptides and intermediate acrylamides has been tested on antiproliferative activity towards the hormone‐refractory prostate cancer cell line PC‐3 revealing several oligomeric compounds with low micromolar and submicromolar activities. Bromine‐substituted dimeric and trimeric acrylamides induced caspase‐dependent apoptosis of PC‐3 cells through cell‐cycle arrest and mitochondrial damage.     

Comprehensive two‐dimensional PC‐3 prostate cancer cell membrane chromatography for screening anti‐tumor components from Radix Sophorae flavescentis

Radix Sophorae flavescentis is generally used for the treatment of different stages of prostate cancer in China. It has ideal effects when combined with surgical treatment and chemotherapy. However, its active components are still ambiguous. We devised a comprehensive two‐dimensional PC‐3 prostate cancer cell membrane chromatography system for screening anti‐prostate cancer components in Radix Sophorae flavescentis . Gefitinib and dexamethasone were chosen as positive and negative drugs respectively for validation and optimization the selectivity and suitability of the comprehensive two‐dimensional chromatographic system. Five compounds, sophocarpine, matrine, oxymatrine, oxysophocarpine, and xanthohumol were found to have significant retention behaviors on the PC‐3 cell membrane chromatography and were unambiguously identified by time‐of‐flight mass spectrometry. Cell proliferation and apoptosis assays confirmed that all five compounds had anti‐prostate cancer effects. Matrine and xanthohumol had good inhibitory effects, with half maximal inhibitory concentration values of 0.893 and 0.137 mg/mL, respectively. Our comprehensive two‐dimensional PC‐3 prostate cancer cell membrane chromatographic system promotes the efficient recognition and rapid analysis of drug candidates, and it will be practical for the discovery of prostate cancer drugs from complex traditional Chinese medicines.     

Multiplexed Electrochemical Cancer Diagnostics With Automated Microfluidics

Microfluidic platforms can lead to miniaturisation, increased throughput and reduced reagent consumption, particularly when the processes are automated. Here, a programmable microcontroller is used for automation of a microfluidic platform configured to electrochemically determine the levels of 8 proteins simultaneously in complex liquid samples. The platform system is composed of a programmable Arduino microcontroller that controls inexpensive valve actuators, pump, magnetic stirrer and electronic display. The programmable microcontroller results in repeatable timing for each step in a complex assay protocol, such as sandwich immunoassays. Application of the platform is demonstrated using a multiplexed electrochemical immunoassay based on capture at the electrode surface of magnetic particles labelled with horseradish peroxidase and detection antibody. The multiplexed assay protocol is completed in less than 30 mins and results in detection of eight proteins associated with prostate cancer. The approach presented can be used to automate and simplify high‐throughput screening campaigns, such as detection of multiple biomarkers in patient samples.     

Intracellular Delivery of Glucose Oxidase for Enhanced Cytotoxicity toward PSMA‐Expressing Prostate Cancer Cells

Reactive oxygen species (ROS) forming enzymes are of significant interest as anticancer agents due to their potent cytotoxicity. A key challenge in their clinical translation is attaining site‐specific delivery and minimizing biodistribution to healthy tissues. Here, complexes composed of the ROS enzyme glucose oxidase (GOX), poly‐l ‐lysine‐grafted‐polyethylene glycol (PLL‐g‐PEG), and anti‐prostate specific membrane antigen (anti‐PSMA) monoclonal antibody are synthesized for localized delivery and uptake in prostate cancer cells. Formation of anti‐PSMA‐PLL‐g‐PEG/GOX results in nanoscale complexes ≈30 nm in diameter with a ζ‐potential of 6 mV. The anti‐PSMA‐PLL‐g‐PEG/GOX complexes show significant cytotoxicity (≈60% reduction in cell viability) against PSMA‐expressing LNCaP cells compared to unmodified GOX. Importantly, cytotoxicity in LNCaP cells occurrs concurrently with anti‐PSMA‐PLL‐g‐PEG/GOX uptake and increases in intracellular generation of ROS. These results demonstrate that cytotoxicity of ROS inducing enzymes can be enhanced by intracellular delivery compared to equivalent concentrations of free enzyme, providing a novel means for cancer therapy.     

Application of an LC–ESI–QTOF–MS method for evaluating clindamycin concentrations in plasma and prostate microdialysate of rats

Clindamycin is used for infections caused by Gram-positive and Gram-negative anaerobic pathogens and Gram-positive aerobes. Propionibacterium acnes is an important opportunistic microorganism of the human skin and is related to prostatitis. An LC–electrospray ionization–quadrupole time-of-flight–MS method was validated for determining clindamycin concentrations in plasma and prostate microdialysate. Clindamycin separation was carried out on a C₁₈ column at 0.5 mL/min. The mobile phase employed gradient elution of formic acid and methanol. A mass spectrometer was operated in positive electrospray ionization mode to monitor ion 425.1784 and 253.1152 for clindamycin and cimetidine (internal standard), respectively. Linearity was obtained at 0.5–10.0 μg/mL (plasma) and 0.05–1.0 μg/mL (microdialysate) with coefficients of determination ≥0.999. The intra- and inter-day precision (coefficient of variation - CV%) values were ≤13.83% and 12.51% for plasma, respectively, and ≤10.90% and 9.35% for microdialysate, respectively. The accuracy was between 90.82% and 108.25% for plasma, and 96.97% and 106.98% for microdialysate. The present method was fully validated and applied to investigate clindamycin concentrations in both plasma and prostate by microdialysis in Wistar rats (80 mg/kg, intravenous). Because the penetration of antibiotics into the prostate may be restricted, this method allows us to investigate the prostate concentrations of clindamycin for the first time.     

Three‐phase solvent bar liquid‐phase microextraction combined with high‐performance liquid chromatography to determine sarcosine in human urine

Sarcosine is a potential prostate cancer marker. In this study, we developed a method of three‐phase solvent bar liquid‐phase microextraction combined with high‐performance liquid chromatography to determine sarcosine after derivatization with 4‐dimethylarminoazobenzene‐4‐sulfonyl chloride from human urine. The effects of different extraction conditions on extraction efficiency were investigated and optimized. Under optimum experimental conditions, a calibration graph exhibited linearity over the range of 0.05–25 μmol/L with a correlation coefficient (r²) of 0.9990. The enrichment factor was 168, and the detection limit was 0.02 μmol/L. The method was successfully used to analyze sarcosine in human urine and non‐invasive detection, and good spiked recoveries ranging from 90.5 to 93.6% were obtained. The proposed method exhibited high sensitivity, high enrichment factor, good precision, and a simple setup. It may contribute to the early accurate diagnosis and the progression monitoring of prostatic carcinoma.     

Synthesis and Evaluation of Novel 1,2,6-Thiadiazinone Kinase Inhibitors as Potent Inhibitors of Solid Tumors

A focused series of substituted 4H-1,2,6-thiadiazin-4-ones was designed and synthesized to probe the anti-cancer properties of this scaffold. Insights from previous kinase inhibitor programs were used to carefully select several different substitution patterns. Compounds were tested on bladder, prostate, pancreatic, breast, chordoma, and lung cancer cell lines with an additional skin fibroblast cell line as a toxicity control. This resulted in the identification of several low single digit micro molar compounds with promising therapeutic windows, particularly for bladder and prostate cancer. A number of key structural features of the 4H-1,2,6-thiadiazin-4-one scaffold are discussed that show promising scope for future improvement.     

New Polyesterified Ursane Derivatives from Leaves of Maesa membranacea and Their Cytotoxic Activity

Maesa membranacea A. DC. (Primulaceae) is a plant species that has been frequently used by practitioners of the traditional ethnobotany knowledge from northern and central Vietnam. However, the chemical constituents of the plant remained unknown until recently. Chromatographic separation of a chloroform-soluble fraction of extract from leaves of M. membranacea led to the isolation of two new polyesterified ursane triterpenes (1–2) and two known apocarotenoids: (+)-dehydrovomifoliol (3) and (+)-vomifoliol (4). The chemical structures of the undescribed triterpenoids were elucidated using 1D and 2D MNR and HRESIMS spectral data as 2α,6β,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20β-diol (1) and 2α,6β,22α-triacetoxy-urs-12-ene-3α,11α,20β-triol (2). The newly isolated triterpenoids were tested for their cytotoxic activity in vitro against two melanoma cell lines (HTB140 and A375), normal skin keratinocytes (HaCaT), two colon cancer cell lines (HT29 and Caco-2), two prostate cancer cell lines (DU145 and PC3) and normal prostate epithelial cells (PNT-2). Doxorubicin was used as a reference cytostatic drug. The 2α,6β,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20β-diol demonstrated cytotoxic activity against prostate cancer cell lines (Du145—IC₅₀ = 35.8 µg/mL, PC3—IC₅₀ = 41.6 µg/mL), and at a concentration of 100 µg/mL reduced viability of normal prostate epithelium (PNT-2) cells by 41%.