Surface-enhanced Raman scattering (SERS) tags that serve as exogenous contrast agents for SERS-ba... more Surface-enhanced Raman scattering (SERS) tags that serve as exogenous contrast agents for SERS-based bioimaging are comprised of size- and shape-controlled plasmonic nanostructures. For maximum SERS activity and image contrast, the localized surface plasmon resonance (LSPR) wavelength of SERS tags based on individual nanostructures must match with the excitation wavelength (typically in the near-infrared (NIR) therapeutic window, i.e., 650–900 nm). However, under the resonant excitation, these SERS tags typically exhibit very high photothermal conversion efficiency, resulting in excessive heat that can perturb or even damage the biological species being imaged. Here, we demonstrate bioenabled synthesis of a novel class of ultrabright SERS probes with built-in and accessible electromagnetic hotspots formed by densely packed satellite nanoparticles grown on a plasmonic core. Through the rational choice of the shape of the core, the LSPR wavelength of Au superstructures can be tuned to be either off- or on-r...
INTRODUCTION AND OBJECTIVES: Renal cell carcinoma (RCC) has a higher lethal potential than any ot... more INTRODUCTION AND OBJECTIVES: Renal cell carcinoma (RCC) has a higher lethal potential than any other urological malignancy. Currently, no screening marker exists for RCC. Previous studies have found elevated urine concentrations of aquaporin-1 (AQP1) and perilipin-2 (PLIN2) in patients with RCC compared to healthy controls. We compare pre-operative urine concentrations of AQP1 and PLIN2 in RCC patients with pre-operative urine concentrations in prostate cancer (ACP) and bladder cancer (TCC) patients. Our goal is to demonstrate specificity of these markers to detect RCC among the most common genitourinary malignancies. METHODS: Patients were enrolled into the study from February 28, 2012, to October 16, 2012. Pre-operative urine samples were obtained from 35 patients with clear and papillary RCC who underwent either a partial or radical nephrectomy, 27 patients with ACP who underwent a radical prostatectomy, and 28 patients with TCC who underwent either a transurethral resection of bladder tumor or radical cystectomy. Urine AQP1 and PLIN2 concentrations were determined by Western blot procedures normalized to the urinary creatinine excretion. Wilcoxon Rank Sum Test compared urine concentrations of AQP1 and PLIN2 between RCC, TCC, and ACP patients. RESULTS: The median urine AQP1 and PLIN2 for RCC patients were 33 and 37 relative absorbance/mg urinary creatinine. Patients with TCC had median AQP1 and PLIN2 concentrations of 2 and 6, while ACP patients had median AQP1 and PLIN2 of 3 and 5. Using the Wilcoxon Rank Sum test, there was a statistical difference in urinary AQP1 and PLIN2 concentrations between RCC patients and both patients with TCC and ACP (p-value 0.0001 for both). CONCLUSIONS: There is a statistically significant elevation in the pre-operative urine concentrations of AQP1 and PLIN2 in RCC patients compared to patients with TCC and ACP. Knowing that the urinary concentrations of AQP1 and PLIN2 are elevated in patients with RCC compared to healthy controls, we believe that AQP1 and PLIN2 have high potential to be used as screening biomarkers for RCC. Source of Funding: Funding is from two grants: R01CA141521 and the Barnes Jewish Hospital Foundation.
The present studies investigate the effects of glucocorticoids on the function of the parathyroid... more The present studies investigate the effects of glucocorticoids on the function of the parathyroid glands using primary cultures of bovine parathyroid cells. Treatment of parathyroid cell cultures with dexamethasone for 48 h caused a dose-dependent stimulation of PTH secretion. The minimal concentration of dexamethasone required for a significant stimulation of PTH secretion was 0.1 nM. The stimulatory effect of dexamethasone on the secretion of PTH was found within 12 h of treatment with 100 nM dexamethasone. The steroids deoxycorticosterone and cortexolone, which do not have glucocorticoid activity were without effect of PTH secretion. Since glucocorticoids may modulate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in other tissues, additional studies were performed to evaluate the interactions of glucocorticoids and 1,25-(OH)2D3. Addition of 1,25-(OH)2D3 to parathyroid cell cultures for 48 h significantly suppressed PTH secretion. In the presence of dexamethasone, however, 1,25-(OH)2D3 also significantly decreased PTH secretion, although it did not reduce PTH secretion to control levels. The treatment of parathyroid cell cultures with 100 nM dexamethasone did not affect the parathyroid cell content of 1,25-(OH)2D3 receptors. In summary, these studies indicate that glucocorticoids significantly increase the secretion of PTH in vitro. This stimulatory effect can be inhibited by 1,25-(OH)2D3. The parathyroid gland is an additional site of physiological antagonism of glucocorticoids and 1,25-(OH)2D3.
In the present studies, we used fluoride and pertussis toxin, potent modulators of guanine nucleo... more In the present studies, we used fluoride and pertussis toxin, potent modulators of guanine nucleotide binding proteins (G proteins), to examine the role of G proteins, cytosolic calcium ([Ca]i) and cAMP in the regulation of PTH secretion from dispersed bovine parathyroid cells. NaF suppressed PTH secretion and cAMP content and increased [Ca]i levels in a dose-dependent manner. Prior removal of extracellular calcium with EGTA completely blocked the NaF-induced increase in [Ca]i, but did not prevent the NaF-induced inhibition of PTH secretion and cAMP content. Pretreatment with 10(-5) M verapamil or 10(-4) M diltiazem blocked neither the NaF-induced suppression of PTH secretion and cAMP content nor the increase in [Ca]i. Manganese chloride (10(-4) M) significantly inhibited the NaF-induced increase in [Ca]i, but did not block the NaF-induced suppression of PTH secretion and cAMP content. Pertussis toxin blocked neither the NaF-induced increase in [Ca]i nor suppression of PTH secretion and cAMP content. Our data suggest that (1) NaF might stimulate a calcium channel resulting in the increase in [Ca]i by acting on a G protein in a manner resistant to the inhibition by pertussis toxin; (2) the NaF-induced increase in [Ca]i is not directly linked to the suppression of PTH secretion, and (3) the NaF-induced suppression of PTH secretion might be explained at least in part by the decrease in cell cAMP content.
The spectrum of activities promoted by calcitriol has been found to extend far beyond a role in c... more The spectrum of activities promoted by calcitriol has been found to extend far beyond a role in calcium homeostasis. Calcitriol has been shown to have important immunomodulating properties. The major limitation of calcitriol therapy is its accompanying calcemic activity. The recent development of analogs of vitamin D, that retain the properties of calcitriol with less calcemic activity, may offer a potential therapeutic tool in the treatment of uremic bone disease and other clinical conditions such as psoriasis and leukemia. Among these analogs 22-oxacalcitriol (OCT), 1,25-(OH)2-24-homo-D3, 1,25-(OH)2-22-ene-24-homo-D3, formerly MC 903 (now Calcipotriol), and 1,25-(OH)2-16-ene-23-yne-D3 have been shown to have important biological effects.
Surface-enhanced Raman scattering (SERS) tags that serve as exogenous contrast agents for SERS-ba... more Surface-enhanced Raman scattering (SERS) tags that serve as exogenous contrast agents for SERS-based bioimaging are comprised of size- and shape-controlled plasmonic nanostructures. For maximum SERS activity and image contrast, the localized surface plasmon resonance (LSPR) wavelength of SERS tags based on individual nanostructures must match with the excitation wavelength (typically in the near-infrared (NIR) therapeutic window, i.e., 650–900 nm). However, under the resonant excitation, these SERS tags typically exhibit very high photothermal conversion efficiency, resulting in excessive heat that can perturb or even damage the biological species being imaged. Here, we demonstrate bioenabled synthesis of a novel class of ultrabright SERS probes with built-in and accessible electromagnetic hotspots formed by densely packed satellite nanoparticles grown on a plasmonic core. Through the rational choice of the shape of the core, the LSPR wavelength of Au superstructures can be tuned to be either off- or on-r...
INTRODUCTION AND OBJECTIVES: Renal cell carcinoma (RCC) has a higher lethal potential than any ot... more INTRODUCTION AND OBJECTIVES: Renal cell carcinoma (RCC) has a higher lethal potential than any other urological malignancy. Currently, no screening marker exists for RCC. Previous studies have found elevated urine concentrations of aquaporin-1 (AQP1) and perilipin-2 (PLIN2) in patients with RCC compared to healthy controls. We compare pre-operative urine concentrations of AQP1 and PLIN2 in RCC patients with pre-operative urine concentrations in prostate cancer (ACP) and bladder cancer (TCC) patients. Our goal is to demonstrate specificity of these markers to detect RCC among the most common genitourinary malignancies. METHODS: Patients were enrolled into the study from February 28, 2012, to October 16, 2012. Pre-operative urine samples were obtained from 35 patients with clear and papillary RCC who underwent either a partial or radical nephrectomy, 27 patients with ACP who underwent a radical prostatectomy, and 28 patients with TCC who underwent either a transurethral resection of bladder tumor or radical cystectomy. Urine AQP1 and PLIN2 concentrations were determined by Western blot procedures normalized to the urinary creatinine excretion. Wilcoxon Rank Sum Test compared urine concentrations of AQP1 and PLIN2 between RCC, TCC, and ACP patients. RESULTS: The median urine AQP1 and PLIN2 for RCC patients were 33 and 37 relative absorbance/mg urinary creatinine. Patients with TCC had median AQP1 and PLIN2 concentrations of 2 and 6, while ACP patients had median AQP1 and PLIN2 of 3 and 5. Using the Wilcoxon Rank Sum test, there was a statistical difference in urinary AQP1 and PLIN2 concentrations between RCC patients and both patients with TCC and ACP (p-value 0.0001 for both). CONCLUSIONS: There is a statistically significant elevation in the pre-operative urine concentrations of AQP1 and PLIN2 in RCC patients compared to patients with TCC and ACP. Knowing that the urinary concentrations of AQP1 and PLIN2 are elevated in patients with RCC compared to healthy controls, we believe that AQP1 and PLIN2 have high potential to be used as screening biomarkers for RCC. Source of Funding: Funding is from two grants: R01CA141521 and the Barnes Jewish Hospital Foundation.
The present studies investigate the effects of glucocorticoids on the function of the parathyroid... more The present studies investigate the effects of glucocorticoids on the function of the parathyroid glands using primary cultures of bovine parathyroid cells. Treatment of parathyroid cell cultures with dexamethasone for 48 h caused a dose-dependent stimulation of PTH secretion. The minimal concentration of dexamethasone required for a significant stimulation of PTH secretion was 0.1 nM. The stimulatory effect of dexamethasone on the secretion of PTH was found within 12 h of treatment with 100 nM dexamethasone. The steroids deoxycorticosterone and cortexolone, which do not have glucocorticoid activity were without effect of PTH secretion. Since glucocorticoids may modulate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in other tissues, additional studies were performed to evaluate the interactions of glucocorticoids and 1,25-(OH)2D3. Addition of 1,25-(OH)2D3 to parathyroid cell cultures for 48 h significantly suppressed PTH secretion. In the presence of dexamethasone, however, 1,25-(OH)2D3 also significantly decreased PTH secretion, although it did not reduce PTH secretion to control levels. The treatment of parathyroid cell cultures with 100 nM dexamethasone did not affect the parathyroid cell content of 1,25-(OH)2D3 receptors. In summary, these studies indicate that glucocorticoids significantly increase the secretion of PTH in vitro. This stimulatory effect can be inhibited by 1,25-(OH)2D3. The parathyroid gland is an additional site of physiological antagonism of glucocorticoids and 1,25-(OH)2D3.
In the present studies, we used fluoride and pertussis toxin, potent modulators of guanine nucleo... more In the present studies, we used fluoride and pertussis toxin, potent modulators of guanine nucleotide binding proteins (G proteins), to examine the role of G proteins, cytosolic calcium ([Ca]i) and cAMP in the regulation of PTH secretion from dispersed bovine parathyroid cells. NaF suppressed PTH secretion and cAMP content and increased [Ca]i levels in a dose-dependent manner. Prior removal of extracellular calcium with EGTA completely blocked the NaF-induced increase in [Ca]i, but did not prevent the NaF-induced inhibition of PTH secretion and cAMP content. Pretreatment with 10(-5) M verapamil or 10(-4) M diltiazem blocked neither the NaF-induced suppression of PTH secretion and cAMP content nor the increase in [Ca]i. Manganese chloride (10(-4) M) significantly inhibited the NaF-induced increase in [Ca]i, but did not block the NaF-induced suppression of PTH secretion and cAMP content. Pertussis toxin blocked neither the NaF-induced increase in [Ca]i nor suppression of PTH secretion and cAMP content. Our data suggest that (1) NaF might stimulate a calcium channel resulting in the increase in [Ca]i by acting on a G protein in a manner resistant to the inhibition by pertussis toxin; (2) the NaF-induced increase in [Ca]i is not directly linked to the suppression of PTH secretion, and (3) the NaF-induced suppression of PTH secretion might be explained at least in part by the decrease in cell cAMP content.
The spectrum of activities promoted by calcitriol has been found to extend far beyond a role in c... more The spectrum of activities promoted by calcitriol has been found to extend far beyond a role in calcium homeostasis. Calcitriol has been shown to have important immunomodulating properties. The major limitation of calcitriol therapy is its accompanying calcemic activity. The recent development of analogs of vitamin D, that retain the properties of calcitriol with less calcemic activity, may offer a potential therapeutic tool in the treatment of uremic bone disease and other clinical conditions such as psoriasis and leukemia. Among these analogs 22-oxacalcitriol (OCT), 1,25-(OH)2-24-homo-D3, 1,25-(OH)2-22-ene-24-homo-D3, formerly MC 903 (now Calcipotriol), and 1,25-(OH)2-16-ene-23-yne-D3 have been shown to have important biological effects.
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