Heart rhythm : the official journal of the Heart Rhythm Society, Jan 13, 2015
Since the release of the second generation cryoballoon (CB2; Arctic Front AdvanceTM) and the desi... more Since the release of the second generation cryoballoon (CB2; Arctic Front AdvanceTM) and the design modification with improved cooling characteristics, technique, dosing, and complication profile is significantly different compared to that of first generation cryoballoon. A comprehensive report of CB2 procedural recommendations has not been published. To review the current best practices from a group of experienced centers to create a user's consensus guide for CB2 ablation. High-volume operators with a combined experience of over three thousand CB2 cases were interviewed, and consensus for technical and procedural best practice was established. Comprehensive review of the CB2 ablation best practice guide will provide the detailed technique of achieving safer and more effective outcome for CB2 AF ablation.
Water science and technology : a journal of the International Association on Water Pollution Research, 2001
Two management scenarios, the base case and the full voluntary program implementation scenarios, ... more Two management scenarios, the base case and the full voluntary program implementation scenarios, are simulated with the three-dimensional Chesapeake Bay estuary model package to study the improvement of dissolved oxygen (DO) over the bay in response to the reduction of nutrient loads. The base case scenario is based on the 1985 nutrient management practices and the associated loads from the watershed and airshed to the bay. The full voluntary program implementation scenario is based on an expanded non-point source and point source program applying current technologies in nutrient and sediment management. The implementation of best management practices is assumed to be by voluntary participation, encouraged by a maximum 75% cost share by the states. The ten-year average (1985-1994) total nitrogen and total phosphorus loads to the bay are reduced 40% and 47%, respectively, from the base case to the full voluntary program implementation scenario. The average annual anoxia and hypoxia v...
Background and Purpose-Cerebral ischemia has been proposed as contributing mechanism to secondary... more Background and Purpose-Cerebral ischemia has been proposed as contributing mechanism to secondary neuronal injury after intracerebral hemorrhage (ICH). Possible tools for investigating this hypothesis are diffusion-weighted (DWI) and proton magnetic resonance spectroscopic imaging ( 1 H-MRSI). However, magnetic field inhomogeneity induced by paramagnetic blood products may prohibit the application of such techniques on perihematoma tissue. We report on the feasibility of DWI and 1 H-MRSI in the study of human ICH and present preliminary data on their contribution to understanding perihematoma tissue functional and metabolic profiles. Methods-Patients with acute supratentorial ICH were prospectively evaluated using DWI and 1 H-MRSI. Obscuration of perihematoma tissue with both sequences was assessed. Obtainable apparent diffusion coefficient (Dav) and lactate spectra in perihematoma brain tissue were recorded and analyzed. Results-Nine patients with mean age of 63.4 (36 to 87) years were enrolled. Mean time from symptom onset to initial MRI was 3.4 (1 to 9) days; mean hematoma volume was 35.4 (5 to 80) cm 3 . Perihematoma diffusion values were attainable in 9 of 9 patients, and 1 H-MRSI measures were obtainable in 5 of 9 cases. Dav in perihematoma regions was 172.5 (120.0 to 302.5)ϫ10 Ϫ5 mm 2 /s and 87.6 (76.5 to 102.1)ϫ10 Ϫ5 mm 2 /s in contralateral corresponding regions of interest (Pϭ0.002). One patient showed an additional area of reduced Dav with normal T 2 intensity, which suggests ischemia. 1 H-MRSI revealed lactate surrounding the hematoma in 2 patients. Conclusions-DWI and 1 H-MRSI can be used in the study of ICH patients. Our preliminary data are inconsistent with ischemia as the primary mechanism for perihematoma tissue injury. Further investigation with advanced MRI techniques will give a clearer understanding of the role that ischemia plays in tissue injury after ICH. (Stroke. 2000;31:726-732.)
Engineered nanomaterials are at the leading edge of the rapidly developing nanosciences and are f... more Engineered nanomaterials are at the leading edge of the rapidly developing nanosciences and are founding an important class of new materials with specific physicochemical properties different from bulk materials with the same compositions. The potential for nanomaterials is rapidly expanding with novel applications constantly being explored in different areas. The unique size-dependent properties of nanomaterials make them very attractive for pharmaceutical applications. Investigations of physical, chemical and biological properties of engineered nanomaterials have yielded valuable information. Cytotoxic effects of certain engineered nanomaterials towards malignant cells form the basis for one aspect of nanomedicine. It is inferred that size, three dimensional shape, hydrophobicity and electronic configurations make them an appealing subject in medicinal chemistry. Their unique structure coupled with immense scope for derivatization forms a base for exciting developments in therapeutics. This review article addresses the fate of absorption, distribution, metabolism and excretion (ADME) of engineered nanoparticles in vitro and in vivo. It updates the distinctive methodology used for studying the biopharmaceutics of nanoparticles. This review addresses the future potential and safety concerns and genotoxicity of nanoparticle formulations in general. It particularly emphasizes the effects of nanoparticles on metabolic enzymes as well as the parenteral or inhalation administration routes of nanoparticle formulations. This paper illustrates the potential of nanomedicine by discussing biopharmaceutics of fullerene derivatives and their suitability for diagnostic and therapeutic purposes. Future direction is discussed as well.
Purpose To examine the efficacy, safety, and tolerability of STX209 in patients with ASD, age 5-2... more Purpose To examine the efficacy, safety, and tolerability of STX209 in patients with ASD, age 5-21 years. STX209 (arbaclofen) is a selective GABA-B agonist associated with behavioral improvements and disease-modifying effects in animal models of fragile X syndrome (FXS). It is hypothesized to modulate mGluR5 receptor signaling, and to augment inhibitory neurotransmission. In a previous 8-week, open-label study of 32 subjects with Autism Spectrum Disorder (ASD), STX209 was associated with significant improvement on the ABC-Lethargy/Social Withdrawal (ABC-LSW) subscale, the Social Responsiveness Scale, and the Vineland Adaptive Behavior Scales, Second Edition (VABS) Communication score. Methods A 12-week, double-blind, placebo-controlled trial was conducted in subjects who met DSM-IV criteria for Autistic Disorder, Asperger’s Disorder, or PDD-NOS, and who had a minimum score of 8 on the ABC-LSW subscale. Up to 2 concomitant psychoactive medications were permitted, excluding antipsycho...
Background: Fragile X syndrome (FXS) is the most common known cause of autism, and the most commo... more Background: Fragile X syndrome (FXS) is the most common known cause of autism, and the most common genetic cause of intellectual disability. Animal models of FXS show that it is characterized by an elevated ratio of excitatory:inhibitory neurotransmission, and by abnormal synaptic plasticity, which results from excessive signaling in the mGluR pathway. STX209 (arbaclofen) is a GABA-B agonist that augments inhibitory neurotransmission, and that rescues many abnormal phenotypes in FXS animal models. In a randomized, controlled study of 63 children and young adults with FXS, post-hoc analysis showed that STX209 was associated with significant improvement on the Aberrant Behavior Checklist (ABC) – Social Avoidance scale, which has been specifically validated in the FXS population (Sansone et al., 2011). Other post-hoc analyses showed improvements on the Socialization domain of the Vineland Adaptive Behavior Scales (VABS) among subjects with more severe social impairment at baseline. Ane...
Cardiac arrest due to chest wall blows (commotio cordis) has been reported with increasing freque... more Cardiac arrest due to chest wall blows (commotio cordis) has been reported with increasing frequency in children, and only about 15% of victims survive. Automated external defibrillators (AEDs) have been shown to be life saving in adults with cardiac arrest, but data on their use in children are limited. In a swine model of commotio cordis designed to be most relevant to young children, we assessed the efficacy of a commercially available AED for recognition and termination of ventricular fibrillation. Ventricular fibrillation was produced in anesthetized juvenile swine by precordial impact from a baseball under controlled conditions. Animals were randomized to defibrillation after 1, 2, 4, or 6 minutes of ventricular fibrillation. Twenty-six swine underwent 50 ventricular fibrillation inductions. Sensitivity of the AED for recognition of ventricular fibrillation was 98%, and specificity for nonshockable episodes was 100%. All episodes of ventricular fibrillation were successfully terminated by the AED. In this experimental model of commotio cordis, the AED proved to be highly sensitive and specific for recognition of ventricular fibrillation and effective in terminating the arrhythmia and restoring sinus rhythm. These findings suggest that early defibrillation with the AED could save young lives on the athletic field.
Pacing and clinical electrophysiology : PACE, 2002
... Address for reprints: David L. Hayes, MD, MAYO Clinic, Sec-tion of Scientific Pub., 200 First... more ... Address for reprints: David L. Hayes, MD, MAYO Clinic, Sec-tion of Scientific Pub., 200 First St. ... When the atrial rate in-creases so that the atrial cycle length is less than the TARP (PVARP 1 AV delay), the next P wave would fall within the PVARP. ...
The controlled local delivery of antineoplastic agents by biodegradable polymers is a technique t... more The controlled local delivery of antineoplastic agents by biodegradable polymers is a technique that allows for exposure of tumor cells to therapeutic doses of an active agent for prolonged periods of time while avoiding high systemic doses associated with debilitating toxicities. The use of polymers for chemotherapy delivery expands the spectrum of available treatment of neoplasms in the central nervous system, and facilitates new approaches for the treatment of malignant gliomas. In this article, we discuss the rationale and history of the development and use of these polymers, and review the various agents that have used this technology to treat malignant brain tumors.
Minocycline, a tetracycline derivative, has been shown to inhibit tumor angiogenesis through inhi... more Minocycline, a tetracycline derivative, has been shown to inhibit tumor angiogenesis through inhibitory effects on matrix metalloproteinases. Previous studies have shown this agent to be effective against a rodent brain tumor model when delivered intracranially and to potentiate the efficacy of standard chemotherapeutic agents. In the present study, the in vivo efficacy of intracranial minocycline delivered by a biodegradable controlled-release polymer against rat intracranial 9L gliosarcoma was investigated to determine whether it potentiates the effects of systemic 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). Minocycline was incorporated into the biodegradable polymer polyanhydride poly[bis(p-carboxyphenoxy)propane-sebacic acid] (pCPP:SA) at a ratio of 50:50 by weight. The release kinetics of minocycline from the polymer were assessed. For the efficacy studies, female Fischer 344 rats were implanted with 9L glioma. Treatment with minocycline delivered by the pCPP:SA polymer at th...
Hyperthermia is used in combination with radiotherapy and/or chemotherapy in the treatment of var... more Hyperthermia is used in combination with radiotherapy and/or chemotherapy in the treatment of various types of cancer. Currently, the tumor cell response to hyperthermia is determined largely based on the size reduction of tumor mass, which is insensitive. We tested the feasibility of bioluminescent imaging (BLI) in evaluation of the tumor cell response to hyperthermia by exposing luciferase-expressing MDA-MB-231-luc human breast cancer cells to high temperature (43 °C) for 10 minutes to 2 hours. The tumor cells were the imaged and the light signal generated by the tumor cells was quantified with BLI. To validate its usefulness, the light signal intensity was comparatively analyzed with the tumor cell clonogenicity and cell viability, which were measured with classic clonogenic and MTT assays. The light signal intensity determined by BLI was closely correlated with the absolute number of viable cells as well as the cell viability measured with the traditional MTT assay under normal ...
It is important to understand the forces that shape the size and evolutionary histories of gene f... more It is important to understand the forces that shape the size and evolutionary histories of gene families. Here, we investigated the evolution of non-protein-coding RNA genes in the genomes of Caenorhabditis nematodes. We specifically focused on nested arrangements, that is, cases in which an RNA gene is entirely contained in an intron of another gene. Comparing these arrangements between species simplifies the inference of orthology and, therefore, of evolutionary fates of nested genes. Two distinct patterns are evident in the data. Genes encoding small nuclear RNAs (snRNAs) and transfer RNAs form large families, which have persisted since before the common ancestor of Metazoa. Yet, individual genes die relatively rapidly, with few orthologs having survived since the divergence of Caenorhabditis elegans and Caenorhabditis briggsae. In contrast, genes encoding small nucleolar RNAs (snoRNAs) are either single-copy or form small families. Individual snoRNAs turn over at a relatively sl...
New journal of chemistry = Nouveau journal de chimie, 2014
Fluorescent metal nanoclusters (NCs) have given rise to a new class of fluorescent nanomaterials ... more Fluorescent metal nanoclusters (NCs) have given rise to a new class of fluorescent nanomaterials for the detection of heavy metals. Here, we design a simple, rapid and highly sensitive sensing nanosystem for the detection of Hg(2+) and Cu(2+) based on fluorescence quenching of ultrasmall DNA-Ag NCs. The fluorescence intensity of DNA-Ag NCs was selectively quenched by Hg(2+) and Cu(2+), and the limit of detection (LOD) was found to be 5 nM and 10 nM, respectively. The technique was renewable employment by EDTA addition and successfully applied to detection of Hg(2+) and Cu(2+) in domestic water samples. The quantum yield (QY) of DNA-Ag NCs was significantly higher to ~30% compared to traditional water-soluble fluorescent metal NCs. The DNA-Ag NC detection system make it potentially suitable for detecting Hg(2+) and Cu(2+) and monitoring water quality in a wide range of samples regulated under the Environmental Protection Agency.
Personalized diagnosis and treatment with allogenic or autologous cells have been intensively inv... more Personalized diagnosis and treatment with allogenic or autologous cells have been intensively investigated over the past decade. Despite the promising findings in preclinical studies, the clinical results to date have been largely disappointing. Some critical issues remain to be solved, such as how to monitor the migration, homing, survival, and function of the transplanted cells in vivo. In the past years, imaging techniques have been introduced to solve these issues based on a concept that cells can be transformed to a cellular imaging agent following labeling of the cells with an imaging agent. For this purpose, magnetic resonance imaging (MRI) is so far the first choice imaging modality and iron oxide-based nanoparticles are the most frequently applied labeling agents. However, most MRI cell tracking studies are currently still limited in in vivo visualization of the labeled cells, some critical elements for cell tracking studies are often incompletely characterized, which makes...
Immunotoxins are a group of protein-based therapeutics, basically comprising two functional moiet... more Immunotoxins are a group of protein-based therapeutics, basically comprising two functional moieties: one is the antibody or antibody Fv fragment that allows the immunotoxin to bind specifically to target cells; another is the plant or bacterial toxin that kills the cells upon internalization. Immunotoxins have several unique features which are superior to conventional chemotherapeutics, including high specificity, extraordinary potency, and no known drug resistance. Development of immunotoxins evolves with time and technology, but significant progress has been achieved in the past 20 years after introduction of recombinant DNA technique and generation of the first single-chain variable fragment of monoclonal antibodies. Since then, more than 1,000 recombinant immunotoxins have been generated against cancer. However, most success in immunotoxin therapy has been achieved against hematological malignancies, several issues persist to be significant barriers for effective therapy of hum...
Transferrin receptor (TfR) is overexpressed in human head and neck squamous cell carcinomas (HNSC... more Transferrin receptor (TfR) is overexpressed in human head and neck squamous cell carcinomas (HNSCCs). This study was carried out to investigate the feasibility of imaging HNSCC by targeting TfR using near-infrared fluorescent transferrin conjugate (TfNIR). Western blot analysis of four HNSCC cell lines revealed overexpression of TfR in all four lines compared with that in normal keratinocytes (OKFL). Immunocytochemistry further confirmed the expression of TfR and endocytosis of TfNIR in JHU-013 culture cells. Following intravenous administration of TfNIR (200 microL, 0.625 microg/microL), fluorescent signal was preferentially accumulated in JHU-013 tumor xenografts grown in the lower back (n=14) and oral base tissues (n=4) of nude mice. The signal in tumors was clearly detectable as early as 10 minutes and reached the maximum at 90 to 120 minutes postinjection. The background showed an increase, followed by a decrease at a much faster pace than tumor signal. A high fluorescent ratio...
Heart rhythm : the official journal of the Heart Rhythm Society, Jan 13, 2015
Since the release of the second generation cryoballoon (CB2; Arctic Front AdvanceTM) and the desi... more Since the release of the second generation cryoballoon (CB2; Arctic Front AdvanceTM) and the design modification with improved cooling characteristics, technique, dosing, and complication profile is significantly different compared to that of first generation cryoballoon. A comprehensive report of CB2 procedural recommendations has not been published. To review the current best practices from a group of experienced centers to create a user's consensus guide for CB2 ablation. High-volume operators with a combined experience of over three thousand CB2 cases were interviewed, and consensus for technical and procedural best practice was established. Comprehensive review of the CB2 ablation best practice guide will provide the detailed technique of achieving safer and more effective outcome for CB2 AF ablation.
Water science and technology : a journal of the International Association on Water Pollution Research, 2001
Two management scenarios, the base case and the full voluntary program implementation scenarios, ... more Two management scenarios, the base case and the full voluntary program implementation scenarios, are simulated with the three-dimensional Chesapeake Bay estuary model package to study the improvement of dissolved oxygen (DO) over the bay in response to the reduction of nutrient loads. The base case scenario is based on the 1985 nutrient management practices and the associated loads from the watershed and airshed to the bay. The full voluntary program implementation scenario is based on an expanded non-point source and point source program applying current technologies in nutrient and sediment management. The implementation of best management practices is assumed to be by voluntary participation, encouraged by a maximum 75% cost share by the states. The ten-year average (1985-1994) total nitrogen and total phosphorus loads to the bay are reduced 40% and 47%, respectively, from the base case to the full voluntary program implementation scenario. The average annual anoxia and hypoxia v...
Background and Purpose-Cerebral ischemia has been proposed as contributing mechanism to secondary... more Background and Purpose-Cerebral ischemia has been proposed as contributing mechanism to secondary neuronal injury after intracerebral hemorrhage (ICH). Possible tools for investigating this hypothesis are diffusion-weighted (DWI) and proton magnetic resonance spectroscopic imaging ( 1 H-MRSI). However, magnetic field inhomogeneity induced by paramagnetic blood products may prohibit the application of such techniques on perihematoma tissue. We report on the feasibility of DWI and 1 H-MRSI in the study of human ICH and present preliminary data on their contribution to understanding perihematoma tissue functional and metabolic profiles. Methods-Patients with acute supratentorial ICH were prospectively evaluated using DWI and 1 H-MRSI. Obscuration of perihematoma tissue with both sequences was assessed. Obtainable apparent diffusion coefficient (Dav) and lactate spectra in perihematoma brain tissue were recorded and analyzed. Results-Nine patients with mean age of 63.4 (36 to 87) years were enrolled. Mean time from symptom onset to initial MRI was 3.4 (1 to 9) days; mean hematoma volume was 35.4 (5 to 80) cm 3 . Perihematoma diffusion values were attainable in 9 of 9 patients, and 1 H-MRSI measures were obtainable in 5 of 9 cases. Dav in perihematoma regions was 172.5 (120.0 to 302.5)ϫ10 Ϫ5 mm 2 /s and 87.6 (76.5 to 102.1)ϫ10 Ϫ5 mm 2 /s in contralateral corresponding regions of interest (Pϭ0.002). One patient showed an additional area of reduced Dav with normal T 2 intensity, which suggests ischemia. 1 H-MRSI revealed lactate surrounding the hematoma in 2 patients. Conclusions-DWI and 1 H-MRSI can be used in the study of ICH patients. Our preliminary data are inconsistent with ischemia as the primary mechanism for perihematoma tissue injury. Further investigation with advanced MRI techniques will give a clearer understanding of the role that ischemia plays in tissue injury after ICH. (Stroke. 2000;31:726-732.)
Engineered nanomaterials are at the leading edge of the rapidly developing nanosciences and are f... more Engineered nanomaterials are at the leading edge of the rapidly developing nanosciences and are founding an important class of new materials with specific physicochemical properties different from bulk materials with the same compositions. The potential for nanomaterials is rapidly expanding with novel applications constantly being explored in different areas. The unique size-dependent properties of nanomaterials make them very attractive for pharmaceutical applications. Investigations of physical, chemical and biological properties of engineered nanomaterials have yielded valuable information. Cytotoxic effects of certain engineered nanomaterials towards malignant cells form the basis for one aspect of nanomedicine. It is inferred that size, three dimensional shape, hydrophobicity and electronic configurations make them an appealing subject in medicinal chemistry. Their unique structure coupled with immense scope for derivatization forms a base for exciting developments in therapeutics. This review article addresses the fate of absorption, distribution, metabolism and excretion (ADME) of engineered nanoparticles in vitro and in vivo. It updates the distinctive methodology used for studying the biopharmaceutics of nanoparticles. This review addresses the future potential and safety concerns and genotoxicity of nanoparticle formulations in general. It particularly emphasizes the effects of nanoparticles on metabolic enzymes as well as the parenteral or inhalation administration routes of nanoparticle formulations. This paper illustrates the potential of nanomedicine by discussing biopharmaceutics of fullerene derivatives and their suitability for diagnostic and therapeutic purposes. Future direction is discussed as well.
Purpose To examine the efficacy, safety, and tolerability of STX209 in patients with ASD, age 5-2... more Purpose To examine the efficacy, safety, and tolerability of STX209 in patients with ASD, age 5-21 years. STX209 (arbaclofen) is a selective GABA-B agonist associated with behavioral improvements and disease-modifying effects in animal models of fragile X syndrome (FXS). It is hypothesized to modulate mGluR5 receptor signaling, and to augment inhibitory neurotransmission. In a previous 8-week, open-label study of 32 subjects with Autism Spectrum Disorder (ASD), STX209 was associated with significant improvement on the ABC-Lethargy/Social Withdrawal (ABC-LSW) subscale, the Social Responsiveness Scale, and the Vineland Adaptive Behavior Scales, Second Edition (VABS) Communication score. Methods A 12-week, double-blind, placebo-controlled trial was conducted in subjects who met DSM-IV criteria for Autistic Disorder, Asperger’s Disorder, or PDD-NOS, and who had a minimum score of 8 on the ABC-LSW subscale. Up to 2 concomitant psychoactive medications were permitted, excluding antipsycho...
Background: Fragile X syndrome (FXS) is the most common known cause of autism, and the most commo... more Background: Fragile X syndrome (FXS) is the most common known cause of autism, and the most common genetic cause of intellectual disability. Animal models of FXS show that it is characterized by an elevated ratio of excitatory:inhibitory neurotransmission, and by abnormal synaptic plasticity, which results from excessive signaling in the mGluR pathway. STX209 (arbaclofen) is a GABA-B agonist that augments inhibitory neurotransmission, and that rescues many abnormal phenotypes in FXS animal models. In a randomized, controlled study of 63 children and young adults with FXS, post-hoc analysis showed that STX209 was associated with significant improvement on the Aberrant Behavior Checklist (ABC) – Social Avoidance scale, which has been specifically validated in the FXS population (Sansone et al., 2011). Other post-hoc analyses showed improvements on the Socialization domain of the Vineland Adaptive Behavior Scales (VABS) among subjects with more severe social impairment at baseline. Ane...
Cardiac arrest due to chest wall blows (commotio cordis) has been reported with increasing freque... more Cardiac arrest due to chest wall blows (commotio cordis) has been reported with increasing frequency in children, and only about 15% of victims survive. Automated external defibrillators (AEDs) have been shown to be life saving in adults with cardiac arrest, but data on their use in children are limited. In a swine model of commotio cordis designed to be most relevant to young children, we assessed the efficacy of a commercially available AED for recognition and termination of ventricular fibrillation. Ventricular fibrillation was produced in anesthetized juvenile swine by precordial impact from a baseball under controlled conditions. Animals were randomized to defibrillation after 1, 2, 4, or 6 minutes of ventricular fibrillation. Twenty-six swine underwent 50 ventricular fibrillation inductions. Sensitivity of the AED for recognition of ventricular fibrillation was 98%, and specificity for nonshockable episodes was 100%. All episodes of ventricular fibrillation were successfully terminated by the AED. In this experimental model of commotio cordis, the AED proved to be highly sensitive and specific for recognition of ventricular fibrillation and effective in terminating the arrhythmia and restoring sinus rhythm. These findings suggest that early defibrillation with the AED could save young lives on the athletic field.
Pacing and clinical electrophysiology : PACE, 2002
... Address for reprints: David L. Hayes, MD, MAYO Clinic, Sec-tion of Scientific Pub., 200 First... more ... Address for reprints: David L. Hayes, MD, MAYO Clinic, Sec-tion of Scientific Pub., 200 First St. ... When the atrial rate in-creases so that the atrial cycle length is less than the TARP (PVARP 1 AV delay), the next P wave would fall within the PVARP. ...
The controlled local delivery of antineoplastic agents by biodegradable polymers is a technique t... more The controlled local delivery of antineoplastic agents by biodegradable polymers is a technique that allows for exposure of tumor cells to therapeutic doses of an active agent for prolonged periods of time while avoiding high systemic doses associated with debilitating toxicities. The use of polymers for chemotherapy delivery expands the spectrum of available treatment of neoplasms in the central nervous system, and facilitates new approaches for the treatment of malignant gliomas. In this article, we discuss the rationale and history of the development and use of these polymers, and review the various agents that have used this technology to treat malignant brain tumors.
Minocycline, a tetracycline derivative, has been shown to inhibit tumor angiogenesis through inhi... more Minocycline, a tetracycline derivative, has been shown to inhibit tumor angiogenesis through inhibitory effects on matrix metalloproteinases. Previous studies have shown this agent to be effective against a rodent brain tumor model when delivered intracranially and to potentiate the efficacy of standard chemotherapeutic agents. In the present study, the in vivo efficacy of intracranial minocycline delivered by a biodegradable controlled-release polymer against rat intracranial 9L gliosarcoma was investigated to determine whether it potentiates the effects of systemic 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). Minocycline was incorporated into the biodegradable polymer polyanhydride poly[bis(p-carboxyphenoxy)propane-sebacic acid] (pCPP:SA) at a ratio of 50:50 by weight. The release kinetics of minocycline from the polymer were assessed. For the efficacy studies, female Fischer 344 rats were implanted with 9L glioma. Treatment with minocycline delivered by the pCPP:SA polymer at th...
Hyperthermia is used in combination with radiotherapy and/or chemotherapy in the treatment of var... more Hyperthermia is used in combination with radiotherapy and/or chemotherapy in the treatment of various types of cancer. Currently, the tumor cell response to hyperthermia is determined largely based on the size reduction of tumor mass, which is insensitive. We tested the feasibility of bioluminescent imaging (BLI) in evaluation of the tumor cell response to hyperthermia by exposing luciferase-expressing MDA-MB-231-luc human breast cancer cells to high temperature (43 °C) for 10 minutes to 2 hours. The tumor cells were the imaged and the light signal generated by the tumor cells was quantified with BLI. To validate its usefulness, the light signal intensity was comparatively analyzed with the tumor cell clonogenicity and cell viability, which were measured with classic clonogenic and MTT assays. The light signal intensity determined by BLI was closely correlated with the absolute number of viable cells as well as the cell viability measured with the traditional MTT assay under normal ...
It is important to understand the forces that shape the size and evolutionary histories of gene f... more It is important to understand the forces that shape the size and evolutionary histories of gene families. Here, we investigated the evolution of non-protein-coding RNA genes in the genomes of Caenorhabditis nematodes. We specifically focused on nested arrangements, that is, cases in which an RNA gene is entirely contained in an intron of another gene. Comparing these arrangements between species simplifies the inference of orthology and, therefore, of evolutionary fates of nested genes. Two distinct patterns are evident in the data. Genes encoding small nuclear RNAs (snRNAs) and transfer RNAs form large families, which have persisted since before the common ancestor of Metazoa. Yet, individual genes die relatively rapidly, with few orthologs having survived since the divergence of Caenorhabditis elegans and Caenorhabditis briggsae. In contrast, genes encoding small nucleolar RNAs (snoRNAs) are either single-copy or form small families. Individual snoRNAs turn over at a relatively sl...
New journal of chemistry = Nouveau journal de chimie, 2014
Fluorescent metal nanoclusters (NCs) have given rise to a new class of fluorescent nanomaterials ... more Fluorescent metal nanoclusters (NCs) have given rise to a new class of fluorescent nanomaterials for the detection of heavy metals. Here, we design a simple, rapid and highly sensitive sensing nanosystem for the detection of Hg(2+) and Cu(2+) based on fluorescence quenching of ultrasmall DNA-Ag NCs. The fluorescence intensity of DNA-Ag NCs was selectively quenched by Hg(2+) and Cu(2+), and the limit of detection (LOD) was found to be 5 nM and 10 nM, respectively. The technique was renewable employment by EDTA addition and successfully applied to detection of Hg(2+) and Cu(2+) in domestic water samples. The quantum yield (QY) of DNA-Ag NCs was significantly higher to ~30% compared to traditional water-soluble fluorescent metal NCs. The DNA-Ag NC detection system make it potentially suitable for detecting Hg(2+) and Cu(2+) and monitoring water quality in a wide range of samples regulated under the Environmental Protection Agency.
Personalized diagnosis and treatment with allogenic or autologous cells have been intensively inv... more Personalized diagnosis and treatment with allogenic or autologous cells have been intensively investigated over the past decade. Despite the promising findings in preclinical studies, the clinical results to date have been largely disappointing. Some critical issues remain to be solved, such as how to monitor the migration, homing, survival, and function of the transplanted cells in vivo. In the past years, imaging techniques have been introduced to solve these issues based on a concept that cells can be transformed to a cellular imaging agent following labeling of the cells with an imaging agent. For this purpose, magnetic resonance imaging (MRI) is so far the first choice imaging modality and iron oxide-based nanoparticles are the most frequently applied labeling agents. However, most MRI cell tracking studies are currently still limited in in vivo visualization of the labeled cells, some critical elements for cell tracking studies are often incompletely characterized, which makes...
Immunotoxins are a group of protein-based therapeutics, basically comprising two functional moiet... more Immunotoxins are a group of protein-based therapeutics, basically comprising two functional moieties: one is the antibody or antibody Fv fragment that allows the immunotoxin to bind specifically to target cells; another is the plant or bacterial toxin that kills the cells upon internalization. Immunotoxins have several unique features which are superior to conventional chemotherapeutics, including high specificity, extraordinary potency, and no known drug resistance. Development of immunotoxins evolves with time and technology, but significant progress has been achieved in the past 20 years after introduction of recombinant DNA technique and generation of the first single-chain variable fragment of monoclonal antibodies. Since then, more than 1,000 recombinant immunotoxins have been generated against cancer. However, most success in immunotoxin therapy has been achieved against hematological malignancies, several issues persist to be significant barriers for effective therapy of hum...
Transferrin receptor (TfR) is overexpressed in human head and neck squamous cell carcinomas (HNSC... more Transferrin receptor (TfR) is overexpressed in human head and neck squamous cell carcinomas (HNSCCs). This study was carried out to investigate the feasibility of imaging HNSCC by targeting TfR using near-infrared fluorescent transferrin conjugate (TfNIR). Western blot analysis of four HNSCC cell lines revealed overexpression of TfR in all four lines compared with that in normal keratinocytes (OKFL). Immunocytochemistry further confirmed the expression of TfR and endocytosis of TfNIR in JHU-013 culture cells. Following intravenous administration of TfNIR (200 microL, 0.625 microg/microL), fluorescent signal was preferentially accumulated in JHU-013 tumor xenografts grown in the lower back (n=14) and oral base tissues (n=4) of nude mice. The signal in tumors was clearly detectable as early as 10 minutes and reached the maximum at 90 to 120 minutes postinjection. The background showed an increase, followed by a decrease at a much faster pace than tumor signal. A high fluorescent ratio...
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Papers by paul wang