-
Hung-Wei Yang,
Hao-Li Liu,
Meng-Lin Li,
I-Wen Hsi,
Chih-Tai Fan,
Chiung-Yin Huang,
Yu-Jen Lu,
Mu-Yi Hua,
Hsin-Yi Chou,
Jiunn-Woei Liaw,
Chen-Chi M Ma, Kuo-Chen Wei
[show abstract]
[hide abstract]
ABSTRACT: Nanomedicine can provide a multi-functional platform for image-guided diagnosis and treatment of cancer. Although gold nanorods (GNRs) have been developed for photoacoustic (PA) imaging and near infra-red (NIR) photothermal applications, their efficiency has remained limited by low thermal stability. Here we present the synthesis, characterization, and functional evaluation of non-cytotoxic magnetic polymer-modified gold nanorods (MPGNRs), designed to act as dual magnetic resonance imaging (MRI) and PA imaging contrast agents. In addition, their high magnetization allowed MPGNRs to be actively localized and concentrated by targeting with an external magnet. Finally, MPGNRs significantly enhanced the NIR-laser-induced photothermal effect due to their increased thermal stability. MPGNRs thus provide a promising new theranostic platform for cancer diagnosis and treatment by combining dual MR/PA imaging with highly effective targeted photothermal therapy.
Biomaterials 04/2013; · 7.40 Impact Factor
-
Shu-Mei Chen,
Hua-Chien Chen,
Shu-Jen Chen,
Chiung-Yin Huang,
Pin-Yuan Chen,
Tai-Wei Erich Wu,
Ly-Ying Feng,
Hong-Chieh Tsai,
Tai-Ngar Lui,
Chuen Hsueh, Kuo-Chen Wei
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive type of glioma and carries the poorest chances of survival. There is therefore an urgent need to understand the mechanisms of glioma tumorigenesis and develop or improve therapeutics. The aim of this study was to assess the possible prognostic value of cyclin-dependent kinase 6 (CDK6) and the effects of microRNA-495 (miR-495) manipulation on CDK6 expression and cell survival in glioma cells. METHODS: Analyses of clinical specimens from GBM patients were used. Expression of CDK6 was analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. Expression of CDK6 was also analyzed after over-expression of miR-495 in T98 cells; both cell proliferation and RB phosphorylation were examined. Cell proliferation, cell cycle distribution, and RB phosphorylation were also examined after knockdown of CDK6 in U87-MG and T98 cells. RESULTS: Analyses of clinical specimens from GBM patients identified that CDK6 is significantly expressed in gliomas. CDK6 antigen expression was higher in tumor cores and margins than in adjacent normal brain tissues, and higher levels of CDK6 expression in the tumor margin correlated with decreased survival. Over-expression of miR-495 in T98 cells downregulated the expression of CDK6 and inhibited retinoblastoma phosphorylation, and knockdown of CDK6 in U87-MG and T98 cells by siRNAs resulted in cell cycle arrest at the G1/S transition and inhibition of cell proliferation. CONCLUSIONS: This study revealed miR-495 is down-regulated in glioma tissues. Furthermore, miR-495 regulated CDK6 expression and involved in glioma cell growth inhibition, which indicated the possible role of miR-495 in tumor progression.
World Journal of Surgical Oncology 04/2013; 11(1):87. · 1.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recombinant adeno-associated viral (rAAV) vectors are potentially powerful tools for gene therapy of CNS diseases, but their penetration into brain parenchyma is severely limited by the blood-brain barrier (BBB) and current delivery relies on invasive stereotactic injection. Here we evaluate the local, targeted delivery of rAAV vectors into the brains of mice by noninvasive, reversible, microbubble-facilitated focused ultrasound (FUS), resulting in BBB opening that can be monitored and controlled by magnetic resonance imaging (MRI). Using this method, we found that IV-administered AAV2-GFP (green fluorescence protein) with a low viral vector titer (1×10 vg/g) can successfully penetrate the BBB-opened brain regions to express GFP. We show that MRI monitoring of BBB-opening could serve as an indicator of the scale and distribution of AAV transduction. Transduction peaked at 3 weeks and neurons and astrocytes were affected. This novel, noninvasive delivery approach could significantly broaden the application of AAV-viral-vector-based genes for treatment of CNS diseases.
PLoS ONE 01/2013; 8(2):e57682. · 4.09 Impact Factor
-
Kuo-Chen Wei,
Po-Chun Chu,
Hay-Yan Jack Wang,
Chiung-Yin Huang,
Pin-Yuan Chen,
Hong-Chieh Tsai,
Yu-Jen Lu,
Pei-Yun Lee,
I-Chou Tseng,
Li-Ying Feng,
Peng-Wei Hsu,
Tzu-Chen Yen,
Hao-Li Liu
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment.
PLoS ONE 01/2013; 8(3):e58995. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Microbubble-enhanced focused ultrasound (FUS) can enhance the delivery of therapeutic agents into the brain for brain tumor treatment. The purpose of this study was to investigate the influence of brain tumor conditions on the distribution and dynamics of small molecule leakage into targeted regions of the brain after FUS-BBB opening. A total of 34 animals were used, and the process was monitored by 7T-MRI. Evans blue (EB) dye as well as Gd-DTPA served as small molecule substitutes for evaluation of drug behavior. EB was quantified spectrophotometrically. Spin-spin (R1) relaxometry and area under curve (AUC) were measured by MRI to quantify Gd-DTPA. We found that FUS-BBB opening provided a more significant increase in permeability with small tumors. In contrast, accumulation was much higher in large tumors, independent of FUS. The AUC values of Gd-DTPA were well correlated with EB delivery, suggesting that Gd-DTPA was a good indicator of total small-molecule accumulation in the target region. The peripheral regions of large tumors exhibited similar dynamics of small-molecule leakage after FUS-BBB opening as small tumors, suggesting that FUS-BBB opening may have the most significant permeability-enhancing effect on tumor peripheral. This study provides useful information toward designing an optimized FUS-BBB opening strategy to deliver small-molecule therapeutic agents into brain tumors.
BioMed research international. 01/2013; 2013:627496.
-
[show abstract]
[hide abstract]
ABSTRACT: Current chemotherapeutic agents do not only kill tumor cells but also induce systemic toxicity that significantly limits their dosage. Focused ultrasound (FUS) in the presence of microbubbles (MBs) is capable of transient and local opening of the blood-brain barrier (BBB) that enhances chemotherapeutic drug delivery into the brain parenchyma for glioma treatment. Our previous results demonstrated the success of combining the use of drug (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU)-loaded MBs with FUS-induced BBB opening to improve local drug delivery and reduce systemic toxicity. Here we introduce novel VEGF-targeting, drug-loaded MBs that significantly further enhance targeted drug release and reduce tumor progression in a rat model, using the FUS-BBB opening strategy. This study suggests a promising direction for future MB design aimed at targeted brain tumor therapy, and the possible future extension of MB application towards theragnostic use.
Biomaterials 12/2012; · 7.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In this study, we develop a novel photoacoustic imaging technique based on gold nanorods (AuNRs) for quantitatively monitoring focused-ultrasound (FUS) induced blood-brain barrier (BBB) opening in a rat model in vivo. This study takes advantage of the strong near-infrared absorption (peak at ≈ 800 nm) of AuNRs and the extravasation tendency from BBB opening foci due to their nano-scale size to passively label the BBB disruption area. Experimental results show that AuNR contrast-enhanced photoacoustic microscopy (PAM) successfully reveals the spatial distribution and temporal response of BBB disruption area in the rat brains. The quantitative measurement of contrast enhancement has potential to estimate the local concentration of AuNRs and even the dosage of therapeutic molecules when AuNRs are further used as nano-carrier for drug delivery or photothermal therapy. The photoacoustic results also provide complementary information to MRI, being helpful to discover more details about FUS induced BBB opening in small animal models.
Journal of Biomedical Optics 06/2012; 17(6):061222. · 3.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Liver cirrhosis was identified as an independent predictor of poor outcomes in patients suffering trauma and in those undergoing major surgeries. The aim of this study was to report the authors' experiences treating patients with cirrhosis who undergo brain surgeries.
Between 2004 and 2009, 121 consecutive patients with cirrhosis underwent 144 brain procedures. Patients were categorized as Child-Turcotte-Pugh (referred to as "Child") Class A, B, or C. The patient profiles, including the severity of cirrhosis, reason for surgery, complications, and prognosis factors, were analyzed.
In this retrospective study, the overall surgical complication rate for patients with cirrhosis was 52.1% and the mortality rate was 24.3%. For patients with acute traumatic brain injury (TBI), the complication, rebleeding, and mortality rates reached 84.4%, 68.8%, and 37.5%, respectively. Surgery for TBI was a significant risk factor for postoperative complications (p = 0.0002) and postoperative hemorrhage (p < 0.0001). Otherwise, according to the Child classification, the complication rate increased in a stepwise fashion from 38.7% to 60% to 84.2%, the rebleeding rate from 29.3% to 48.0% to 63.2%, and the mortality rate from 5.3% to 38% to 63.2% for Child A, B, and C, respectively. The Child classification was associated with higher risk of complications-Child B vs A OR 2.84 (95% CI 1.28-6.29), Child C vs A OR 5.39 (95% CI 1.32-22.02). It was also associated with risk of death-Child C vs A OR 30.43 (95% CI 7.71-120.02), Child B vs A OR 10.88 (95% CI 3.42-34.63).
Liver cirrhosis is a poor comorbidity factor for brain surgery. The authors' results suggest that the Child classification used independently is a poor prognostic factor; in addition, grave outcomes were observed in patients with TBI.
Journal of Neurosurgery 05/2012; 117(2):348-53. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Uncertainty in arterial input function (AIF) estimation is one of the major errors in the quantification of dynamic contrast-enhanced MRI. A blind source separation algorithm was proposed to determine the AIF by selecting the voxel time course with maximum purity, which represents a minimal contamination from partial volume effects. Simulations were performed to assess the partial volume effect on the purity of AIF, the estimation accuracy of the AIF, and the influence of purity on the derived kinetic parameters. In vivo data were acquired from six patients with hypopharyngeal cancer and eight rats with brain tumor. Results showed that in simulation the AIF with the highest purity is closest to the true AIF. In patients, the manually selection had reduced purity, which could lead to underestimations of K(trans) and V(e) and an overestimation of V(p) when compared with those obtained by the proposed blind source separation algorithm. The derived kinetic parameters in the tumor were more susceptible to the changes in purity when compared with those in the muscle. The animal experiment demonstrated good reproducibility in blind source separation-AIF derived parameters. In conclusion, the blind source separation method is feasible and reproducible to identify the voxel with the tracer concentration time course closest to the true AIF. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 03/2012; 68(5):1439-49. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Glioblastoma multiforme (GBM) is a highly malignant brain tumor. The blood-brain barrier (BBB) provides a major obstacle to chemotherapy since therapeutic doses cannot be achieved by traditional drug delivery without severe systemic cytotoxic effects. Recently, microbubble (MB)-enhanced focused ultrasound (FUS) was shown to temporally and locally disrupt the BBB thereby enhancing drug delivery into brain tumors. Here we propose the concept of smart, multifunctional MBs capable of facilitating FUS-induced BBB disruption while serving as drug-carrying vehicles and protecting drugs from rapid degradation. The designed MBs had a high loading capacity (efficiency of 68.01 ± 4.35%) for 1,3-bis(2-chloroethyl)-1- nitrosourea (BCNU). When combined with FUS (1-MHz), these BCNU-MBs facilitated local BBB disruption and simultaneously released BCNU at the target site, thus increasing local BCNU deposition. Encapsulation of BCNU in MBs prolonged its circulatory half-life by 5-fold, and accumulation of BCNU in the liver was reduced 5-fold due to the slow reticuloendothelial system uptake of BCNU-MBs. In tumor-bearing animals, BCNU-MBs with FUS controlled tumor progression (915.3%-39.6%) and improved median survival (29 days-32.5 days). This study provides a new approach for designing multifunctional MBs to facilitate FUS-mediated chemotherapy for brain tumor treatment.
Biomaterials 01/2012; 33(2):704-12. · 7.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.
Neurosurgical FOCUS 01/2012; 32(1):E4. · 2.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: By combining the advantage of multi-walled carbon nanotubes (MWCNTs) and iron oxide magnetic nanoparticles (MNs), we develop a magnetic dual-targeted nanocarrier for drug delivery. MWCNTs were functionalized with poly(acrylic acid) through free radical polymerization, decorated with MNs, conjugated with a targeting ligand folic acid (FA), for loading of an anti-cancer drug doxorubicin (DOX). The proposed methodology provides dual targeted delivery of the anti-cancer drug to cancer cells under the guidance of a magnetic field and through ligand-receptor interactions. The chemico-physical properties of the nanocarrier were characterized, in addition to its drug loading efficiency and drug releasing characteristics. Doxorubicin could be loaded to MWCNTs with high efficiency via π-π stacking and hydrogen bonding and showed enhanced cytotoxicity toward U87 human glioblastoma cells compared with free DOX. From transmission electron microscopy and confocal laser scanning microscopy, we confirmed that DOX-FA-MN-MWCNT could be efficiently taken up by U87 cells with subsequent intracellular release of DOX, followed by transport of DOX into the nucleus with the nanocarrier left in the cytoplasm. These properties make the magnetic nanocarrier a potential candidate for targeted delivery of DOX for cancer treatment.
Colloids and surfaces. B, Biointerfaces 01/2012; 89:1-9. · 2.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a commercial chemotherapeutic drug for treating malignant brain tumors, has poor thermal stability and a short half-life. Immobilization of BCNU on a nanocarrier might increase the thermal stability of BCNU and extend its half-life.
Nanosized graphene oxide (GO) could be modified by polyacrylic acid (PAA) to improve the aqueous solubility and increase the cell penetration efficacy of the nanocarrier. PAA-GO intended as a drug carrier for BCNU was prepared and characterized in this study. The size and thickness of PAA-GO was investigated by transmission electron microscopy and atomic force microscopy, and the presence of PAA functional groups was confirmed by electron spectroscopy for chemical analysis and thermogravimetric analysis. BCNU was conjugated to PAA-GO by covalent binding for specific killing of cancer cells, which could also enhance the thermal stability of the drug.
Single layer PAA-GO (about 1.9 nm) with a lateral width as small as 36 nm was successfully prepared. The optimum drug immobilization condition was by reacting 0.5 mg PAA-GO with 0.4 mg BCNU, and the drug-loading capacity and residual drug activity were 198 μg BCNU/mg PAA-GO and 70%, respectively. This nanocarrier significantly prolonged the half-life of bound BCNU from 19 to 43 hours compared with free drug and showed efficient intracellular uptake by GL261 cancer cells. The in vitro anticancer efficacy of PAA-GO-BCNU was demonstrated by a 30% increase in DNA interstrand cross-linking and a 77% decrease in the IC(50) value toward GL261 compared with the same dosage of free drug.
Nanosized PAA-GO serves as an efficient BCNU nanocarrier by covalent binding. This nanocarrier will be a promising new vehicle for an advanced drug delivery system in cancer therapy.
International Journal of Nanomedicine 01/2012; 7:1737-47. · 3.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor. It is a rapidly progressive, highly recurrent, fatal intracranial neoplasm, and the demand for novel treatment is urgent. Valproic acid (VPA) is a potential anticancer agent that belongs to a class of histone deacetylase (HDAC) inhibitors, targeting the epigenetic control of gene functions in cancer cells. This drug has been administered for the prevention or treatment of seizure disorder in GBM patients; therefore, a retrospective analysis may further our understanding of the effect of VPA on GBM patients.
A retrospective analysis of 102 patients with GBM was conducted to study the effects of VPA on disease outcome. Tumor samples from seven patients receiving VPA treatment between the first and second operations were obtained in order to verify the HDAC inhibitory activity of VPA in these patients.
In univariate analysis, administration of VPA within 2 weeks of initial diagnosis seemed to confer a survival benefit. However, stratified analysis according to chemotherapy showed that VPA did not have significant impact on the GBM patients' overall survival. Analysis of tissue samples from these patients revealed that a small subset of patients had increased histone acetylation after VPA treatment.
VPA treatment, when administered according to a protocol targeting seizure control, may result in HDAC inhibition in a small subset of patients, but does not significantly affect overall patient survival. Early administration of VPA as an adjunct to temozolomide chemotherapy may have its merits, but the optimal dosing schedule and target serum level require further investigation.
British Journal of Neurosurgery 12/2011; 26(3):347-54. · 0.88 Impact Factor
-
Hao-Li Liu,
Pin-Yuan Chen,
Hung-Wei Yang,
Jia-Shin Wu,
I-Chou Tseng,
Yan-Jung Ma,
Chih-Ying Huang,
Hong-Chieh Tsai,
Shu-Mei Chen,
Yu-Jen Lu,
Chiung-Yin Huang,
Mu-Yi Hua,
Yunn-Hwa Ma,
Tzu-Chen Yen, Kuo-Chen Wei
[show abstract]
[hide abstract]
ABSTRACT: To verify that low-frequency planar ultrasound can be used to disrupt the BBB in large animals, and the usefulness of MRI to quantitatively monitor the delivery of superparamagnetic iron oxide (SPIO) nanoparticles into the disrupted regions.
Two groups of swine subjected to craniotomy were sonicated with burst lengths of 30 or 100 ms, and one group of experiment was also performed to confirm the ability of 28-kHz sonication to open the BBB transcranially. SPIO nanoparticles were administered to the animals after BBB disruption. Procedures were monitored by MRI; SPIO concentrations were estimated by relaxivity mapping.
Sonication for 30 ms created shallow disruptions near the probe tip; 100-ms sonications after craniotomy can create larger and more penetrating openings, increasing SPIO leakage ∼3.6-fold than 30-ms sonications. However, this was accompanied by off-target effects possibly caused by ultrasonic wave reflection. SPIO concentrations estimated from transverse relaxation rate maps correlated well with direct measurements of SPIO concentration by optical emission spectrometry. We have also shown that transcranial low-frequency 28-kHz sonication can induce secure BBB opening from longitudinal MR image follow up to 7 days.
This study provides valuable information regarding the use low-frequency ultrasound for BBB disruption and suggest that SPIO nanoparticles has the potential to serve as a thernostic agent in MRI-guided ultrasound-enhanced brain drug delivery.
Journal of Magnetic Resonance Imaging 09/2011; 34(6):1313-24. · 2.70 Impact Factor
-
Hung-Wei Yang,
Mu-Yi Hua,
Hao-Li Liu,
Chiung-Yin Huang,
Rung-Ywan Tsai,
Yu-Jen Lu,
Ju-Yu Chen,
Hsiang-Jun Tang,
Han-Yi Hsien,
Yu-Sun Chang,
Tzu-Chen Yen,
Pin-Yuan Chen, Kuo-Chen Wei
[show abstract]
[hide abstract]
ABSTRACT: The successful delivery of anti-cancer drugs relies on the simultaneous capability to actively target a specific location, a sufficient lifetime in the active form in the circulation, and traceability and quantification of drug distribution via in vivo medical imaging. Herein, a highly magnetic nanocarrier (HMNC) composed of an Fe(3)O(4) core and an aqueous-stable, self-doped poly[N-(1-one-butyric acid)]aniline (SPAnH) shell was chemically synthesized. This nanocarrier exhibited a high capacity for 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) drug loading. BCNU and o-(2-aminoethyl)polyethylene glycol (EPEG) were covalently immobilized on the surface of the HMNC to form a self-protecting magnetic nanomedicine (i.e., SPMNM) that could simultaneously provide low reticuloendothelial system uptake, high active-targeting, and in vivo magnetic resonance imaging (MRI) traceability. Meanwhile, the SPMNM was found to reduce the phagocytosis by macrophages and reduce the hydrolysis rate of BCNU. The high magnetization (approximately 1.2-fold higher than Resovist) of the HMNC allowed efficient magnetic targeting to the tumor. The synergetic drug delivery approach provided approximately a 3.4-fold improvement of the drug's half-life (from 18 h to 62 h) and significantly prolonged the median survival rate in animals that received a low dose of BCNU, compared with those that received a high dose of free BCNU (63 days for those that received 4.5 mg BCNU/kg carried by the nanocarrier versus 50 days for those that received 13.5 mg of free-BCNU). This improvement could enhance the potential of magnetic targeting therapy in clinical applications of cancer treatments.
Biomaterials 06/2011; 32(27):6523-32. · 7.40 Impact Factor
-
Yin-Cheng Huang, Kuo-Chen Wei,
Chin-Hong Chang,
Jen-Tsung Yang,
Jih-Tsun Ho,
Chiung-Chyi Shen,
Chain-Fa Su,
Der-Yang Cho,
Hsin-I Ma,
Jia-Wei Lin,
E-Jian Lee,
Jionn-Jong Wu,
Ming-Dar Tsai,
Cheng-Kuei Chang,
Shen-Long Howng,
Chen-Nen Chang
[show abstract]
[hide abstract]
ABSTRACT: In 1995 a government-supported Universal National Health care system was implemented in Taiwan, which in 2008 was available to 98% of the population. This system offers affordable, rapid medical attention. A multi-center retrospective study was conducted to assess the prognosis of malignant glioma patients under this system. In 2005 and 2006, patients at 14 independent neuro-oncology centers with newly diagnosed malignant glioma were enrolled. The patient profile, pathology, treatment modalities, and prognosis were collected by questionnaire at each center. The Taiwan Neuro-Oncology Society was responsible for the data analysis. The overall median survival period, 1-year survival rate, and 2-year survival rate for patients with World Health Organization grade III glioma were 33.8 months, 81.4%, and 58.2%, respectively, and 15 months, 57.3%, and 33.9% in patients with grade IV glioma. The median survival period, 1-year survival rate, and 2-year-survival rate in patients receiving temozolomide adjuvant therapy was 36 months, 84.2%, and 61.8%, respectively, for patients with grade III glioma and 19.8 months, 73.1%, and 43.7%, for patients with grade IV glioma. The universal health care system in Taiwan offers a comparable prognosis with an affordable premium relative to other large series in developed countries.
Journal of Clinical Neuroscience 06/2011; 18(6):784-8. · 1.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Intracranial metastases are rarely clinically diagnosed in patients with hypopharyngeal squamous cell carcinoma (SCC). In almost all cases, metastatic locations were found at the cavernous sinus and have been considered to develop as perineural invasions.
We present a case of hypopharyngeal SCC with distant intracranial metastases through hematogenous spreading. Two cerebral parenchymal metastases from the hypopharyngeal SCC were histologically analyzed in a 49-year-old male patient. The right temporal lesion was diagnosed by craniotomy and treated with radiotherapy. The right occipital lesion was treated with stereotactic radiosurgery (SRS).
To the best of our knowledge, there are no reports of hypopharyngeal SCC with cerebral metastases that developed via the hematogenous route. Radiotherapy along with surgery provides better outcomes, and SRS may improve the effect of treatments. Any subclinical neurological deficits should not be neglected, because awareness of this syndrome can lead to earlier diagnosis and alteration in treatment.
Neurosurgery 12/2010; 67(6):E1857-62. · 2.79 Impact Factor
-
Pin-Yuan Chen,
Hao-Li Liu,
Mu-Yi Hua,
Hung-Wei Yang,
Chiung-Yin Huang,
Po-Chun Chu,
Lee-Ang Lyu,
I-Chou Tseng,
Li-Ying Feng,
Hong-Chieh Tsai, [......],
Yu-Jen Lu,
Jiun-Jie Wang,
Tzu-Chen Yen,
Yunn-Hwa Ma,
Tony Wu,
Jyh-Ping Chen,
Jih-Ing Chuang,
Jyh-Wei Shin,
Chuen Hsueh, Kuo-Chen Wei
[show abstract]
[hide abstract]
ABSTRACT: Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and an extremely high mortality rate within 2 years of diagnosis, even when surgical, radiological, and chemotherapeutic interventions are applied. Intravenously administered drugs have limited use because of their adverse systemic effects and poor blood-brain barrier penetration. Here, we combine 2 methods to increase drug delivery to brain tumors. Focused ultrasound transiently permeabilizes the blood-brain barrier, increasing passive diffusion. Subsequent application of an external magnetic field then actively enhances localization of a chemotherapeutic agent immobilized on a novel magnetic nanoparticle. Combining these techniques significantly improved the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea to rodent gliomas. Furthermore, the physicochemical properties of the nanoparticles allowed their delivery to be monitored by magnetic resonance imaging (MRI). The resulting suppression of tumor progression without damaging the normal regions of the brain was verified by MRI and histological examination. This noninvasive, reversible technique promises to provide a more effective and tolerable means of tumor treatment, with lower therapeutic doses and concurrent clinical monitoring.
Neuro-Oncology 10/2010; 12(10):1050-60. · 5.72 Impact Factor
-
Mu-Yi Hua,
Hao-Li Liu,
Hung-Wei Yang,
Pin-Yuan Chen,
Rung-Ywan Tsai,
Chiung-Yin Huang,
I-Chou Tseng,
Lee-Ang Lyu,
Chih-Chun Ma,
Hsiang-Jun Tang,
Tzu-Chen Yen, Kuo-Chen Wei
[show abstract]
[hide abstract]
ABSTRACT: This study describes the creation and characterization of drug carriers prepared using the polymer poly[aniline-co-N-(1-one-butyric acid) aniline] (SPAnH) coated on Fe(3)O(4) cores to form three types of magnetic nanoparticles (MNPs); these particles were used to enhance the therapeutic capacity and improve the thermal stability of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a compound used to treat brain tumors. The average hydrodynamic diameter of the MNPs was 89.2 ± 8.5 nm and all the MNPs displayed superparamagnetic properties. A maximum effective dose of 379.34 μg BCNU could be immobilized on 1 mg of MNP-3 (bound-BCNU-3). Bound-BCNU-3 was more stable than free-BCNU when stored at 4 °C, 25 °C or 37 °C. Bound-BCNU-3 could be concentrated at targeted sites in vitro and in vivo using an externally applied magnet. When applied to brain tumors, magnetic targeting increased the concentration and retention of bound-BCNU-3. This drug delivery system promises to provide more effective tumor treatment using lower therapeutic doses and potentially reducing the side effects of chemotherapy.
Biomaterials 10/2010; 32(2):516-27. · 7.40 Impact Factor
