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31.
Michael L. Mohler Arunima Sikdar Suriyan Ponnusamy Dong-Jin Hwang Yali He Duane D. Miller Ramesh Narayanan 《International journal of molecular sciences》2021,22(4)
Traditional endocrine therapy for prostate cancer (PCa) has been directed at suppression of the androgen receptor (AR) signaling axis since Huggins et al. discovered that diethylstilbestrol (DES; an estrogen) produced chemical castration and PCa tumor regression. Androgen deprivation therapy (ADT) still remains the first-line PCa therapy. Insufficiency of ADT over time leads to castration-resistant PCa (CRPC) in which the AR axis is still active, despite castrate levels of circulating androgens. Despite the approval and use of multiple generations of competitive AR antagonists (antiandrogens), antiandrogen resistance emerges rapidly in CRPC due to several mechanisms, mostly converging in the AR axis. Recent evidence from multiple groups have defined noncompetitive or noncanonical direct binding sites on AR that can be targeted to inhibit the AR axis. This review discusses new developments in the PCa treatment paradigm that includes the next-generation molecules to noncanonical sites, proteolysis targeting chimera (PROTAC), or noncanonical N-terminal domain (NTD)-binding of selective AR degraders (SARDs). A few lead compounds targeting each of these novel noncanonical sites or with SARD activity are discussed. Many of these ligands are still in preclinical development, and a few early clinical leads have emerged, but successful late-stage clinical data are still lacking. The breadth and diversity of targets provide hope that optimized noncanonical inhibitors and/or SARDs will be able to overcome antiandrogen-resistant CRPC. 相似文献
32.
Silicon - Nowadays, the starring attentions of the polylactic acid based composites are improved due to environmental awareness and diminution of petroleum oil. The bio-plastics were restricted to... 相似文献
33.
34.
Farrukh Aqil Jeyaprakash Jeyabalan Radha Munagala Iqbal Ahmad David J. Schultz Ramesh C. Gupta 《International journal of molecular sciences》2021,22(12)
Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by Cuminum cyminum (cumin) administered via the diet as cumin powder, as well as dried ethanolic extract. Groups of female ACI rats were given either an AIN-93M diet or a diet supplemented with cumin powder (5% and 7.5%, w/w) or dried ethanolic cumin extract (1%, w/w), and then challenged with subcutaneous E2 silastic implants (1.2 cm; 9 mg). The first appearance of a palpable mammary tumor was significantly delayed by both the cumin powder and extract. At the end of the study, the tumor incidence was 96% in the control group, whereas only 55% and 45% animals had palpable tumors in the cumin powder and extract groups, respectively. Significant reductions in tumor volume (660 ± 122 vs. 138 ± 49 and 75 ± 46 mm3) and tumor multiplicity (4.21 ± 0.43 vs. 1.16 ± 0.26 and 0.9 ± 0.29 tumors/animal) were also observed by the cumin powder and cumin extract groups, respectively. The cumin powder diet intervention dose- and time-dependently offset E2-related pituitary growth, and reduced the levels of circulating prolactin and the levels of PCNA in the mammary tissues. Mechanistically, the cumin powder diet resulted in a significant reversal of E2-associated modulation in ERα, CYP1A1 and CYP1B1. Further, the cumin powder diet reversed the expression levels of miRNAs (miR-182, miR-375, miR-127 and miR-206) that were highly modulated by E2 treatment. We analyzed the composition of the extract by GC/MS and established cymene and cuminaldehyde as major components, and further detected no signs of gross or systemic toxicity. Thus, cumin bioactives can significantly delay and prevent E2-mediated mammary tumorigenesis in a safe and effective manner, and warrant continued efforts to develop these clinically translatable spice bioactives as chemopreventives and therapeutics against BC. 相似文献
35.
N. S. Ramesh Don H. Rasmussen Gregory A. Campbell 《Polymer Engineering and Science》1994,34(22):1685-1697
The existing models based on classical nucleation theory are not able to explain satisfactorily the nucleation phenomenon of microcellular foams in thermoplastics. Here, we extend the analysis of Kweeder (24), who developed a new model that considers the presence of microvoids, resulting from the thermal processing history of the polymer, as potential nucleation sites. The nucleation model “concentrates” on the stresses and thus void formations in the rubber particles. Since these are pre-existing microvoids, bubble nucleation depends on the survival of these voids to grow rather than the formation of a new phase as modeled by classical nucleation theory. The population of viable microvoids with a sufficiently large radius to survive and overcome surface and elastic forces has been modeled to yield the cell density. A log-normal distribution, which relates to the rubber particle size, has been used to model the distribution of microvoids in the polymer composite material. The model depends on various process parameters such as saturation pressure, foaming temperature, concentration of nucleating agents, solubility of the blowing agent in the polymer, and the modulus. High impact polystyrene (HIPS) was added to polystyrene to obtain polymers with different concentrations of rubber gel particles, the nucleating agent, and used here for this study. 相似文献
36.
Epoxy resin is chosen for our present study owing to its exceptional combination of properties such as easy processing, high safety, excellent solvent and chemical resistance, toughness, low shrinkage on cure, good electrical, mechanical and corrosion resistance with excellent adhesion to many substrates. This versatility in formulation made epoxy resins widely applied for surface coatings, adhesives, laminates, composites, potting, painting materials, encapsulant for semiconductor and insulating material for electric devices. There are numerous paint/coating systems based on epoxy resin available for corrosion and fouling prevention. They however are not completely satisfactory in field applications, where high corrosion, fouling and flame resistance are required. The demand for epoxy resin as corrosion/fouling resistant coatings is restricted mainly due to its inferior characteristics like poor impact strength, high rigidity, and moisture absorbing nature besides inadequate flame retardant properties. It is for this reason that silicones and phosphorus-based compounds are used as modifier in this work by intercrosslinking network mechanism (ICN) to obtain epoxy resin with desired properties ideally suitable for field applications for preventing corrosion and fouling with flame retardantancy. The present work involves the development of solvent free silicone/phosphorus modified epoxy coating systems, since solvent free coating systems are widely used for numerous applications due to their lower cost per unit film thickness, freedom from fire and pollution hazard and ability to provide better performance. For the development of coating systems, epoxy resin (X) serves as base material, hydroxyl terminated polydimethylsiloxane (HTPDMS) as modifier, γ-aminopropyltriethoxysilane (γ-APS) as crosslinking agent and dibutyltindilaurate (DBTDL) as catalyst. Polyamidoamine (A), aromatic amine adducts (B) and phosphorus-containing diamine (C) were used as curing agents. The study also describes the evaluation of corrosion resistant behaviour of unmodified epoxy and siliconized epoxy coatings by potentiodynamic polarization method, electrochemical impedance spectroscopy (EIS), salt-spray and antifouling tests. The results are discussed. 相似文献
37.
Mechanical and Morphological properties of polyamide-6/ABS blend systems, compatibilized by styrene-maleic anhydride (SMA) copolymer, have been studied. The strength, modulus, and impact properties improved upon the addition of SMA. Morphological studies, using small angle light scattering, polarizing microscopy, and scanning electron microscopy, showed that SMA acts as a compatibilizer for the above system. © 1993 John Wiley & Sons, Inc. 相似文献
38.
Acrylonitrile butadiene rubber (NBR) was used as a polymeric plasticizer in poly(vinyl chloride) (PVC) for the partial replacement of di(2‐ethyl hexyl)phthalate (DEHP). The effect of this partial replacement on DEHP leaching from the PVC was evaluated at 10, 25, and 40°C. The study shows that the incorporation of NBR reduces the rate of DEHP leaching, the reduction being prominent at lower temperatures. Gas permeability of the NBR‐modified samples was also evaluated at the above temperatures using oxygen and carbon dioxide. A reduction in gas permeability is observed in NBR‐modified samples compared to the PVC plasticized with DEHP alone particularly in the case of carbon dioxide. Water vapor transmission rates of the NBR‐modified samples are higher than that of the control sample. The NBR‐modified PVC sample was found to be noncytotoxic in the in vitro cytotoxic evaluation both by direct contact and test on extract methods. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:4720–4727, 2006 相似文献
39.
A family of hydroxyapatite (HAP)‐filled chitosan (CHI)–poly(acrylic acid) (PAA) polyelectrolyte complexes was prepared for the development of a degradable biocompatible organic matrix with nascent HAP that will degrade in vivo over a period of time. The effects of complexation on the degradation profile of the composites as well as the interaction between the CHI–PAA matrix and HAP in the composite system were evaluated by studying the swelling behavior of these composites in phosphate‐buffered saline (PBS) by varying their CHI–PAA ratio and HAP content. All composite systems showed a general trend of three stages of swelling with the variation in the degree of equilibrium swelling. The percentage weight gain initially decreased in a linear way with increases in the HAP weight percentages, leading to a first equilibrium swelling, represented by the plateau; further increased to a greater extent; and finally stabilized. The CHI/PAA/HAP composites were stable in PBS up to a period of more than 45 days whereas the 50/50 CHI/PAA control sample showed a single equilibrium attained after a period of 288 h. Further exposure of the specimen to the medium led to its disintegration. It was also observed that, even though CHI and PAA were capable of binding HAP, because of the lack of efficient binding, the integrity of the CHI–HAP and PAA–HAP composites were lost within 48 h. The 50/50/80 CHI/PAA/HAP composition showed the minimum amount of swelling in the series. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4716–4722, 2006 相似文献
40.
R. S. Veerapur K. B. Gudasi M. B. Patil V. Ramesh Babu S. D. Bhat M. Sairam T. M. Aminabhavi 《应用聚合物科学杂志》2006,101(5):3324-3329
Interpenetrating polymeric network (IPN) membranes of sodium alginate (NaAlg) and various amounts of poly(hydroxyethylmethacrylate) (PHEMA) have been prepared and tested for the pervaporation dehydration of ethanol and tetrahydrofuran (THF). The presence of hydrophilic PHEMA in the IPN matrix was found to be responsible for increase in membrane selectivity to water. NaAlg–PHEMA IPN membrane containing 20 wt % of PHEMA exhibited a selectivity of 571 to water for the water–ethanol mixture and 857 for water–THF mixture. These data are much better than those observed for the pristine NaAlg membrane. However, flux of the IPN membranes was smaller than that of pristine NaAlg membrane. Comparatively higher flux values were observed for water–THF mixture than for water–ethanol mixture. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3324–3329, 2006 相似文献