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OBJECTIVES pStage IVB oral cavity squamous cell carcinoma (OCSCC) is defined as either pT4b or pN3 disease. We sought to devise an improved prognostic stratification of this patient group. METHODS Between December 2003 and January 2018,... more
OBJECTIVES pStage IVB oral cavity squamous cell carcinoma (OCSCC) is defined as either pT4b or pN3 disease. We sought to devise an improved prognostic stratification of this patient group. METHODS Between December 2003 and January 2018, we retrospectively reviewed the clinical records of 1331 consecutive patients with OCSCC who received tumor excision and neck dissection. The number of patients with pT4a/pT4b, pT1N3b/pT2N3b/pT3N3b/pT4N3b, and pStage IVA/IVB was 370/83, 3/49/42/142, and 332/295, respectively. RESULTS The 5-year rates of disease-free survival (DFS) and disease-specific survival (DSS) for patients with pT4a/pT4b disease were 64%/63% (p = 0.973) and 72%/69% (p = 0.672), respectively. The 5-year DFS and DSS rates for patients with pT1N3b/pT2N3b/pT3N3b/pT4N3b disease were 67%/65%/40%/42% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002) and 100%/68%/45%/49% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002), respectively. We devised a new definition for pStage IV by considering patients with pT4bN0-2 and pT1-2N3b diseases as pStage-IVA. The number of patients with pStage IVA/IVB (pT3-4N3b) was 443/184. The 5-year rates of AJCC pStage IVA/IVB and the newly proposed pStage IVA/IVB (pT3-4N3b) were as follows: DFS, 74%/52% and 72%/42%; DSS, 83%/58% and 81%/47%; respectively, all p value < 0.001. CONCLUSIONS The clinical outcomes of pT4b and pT4a OCSCC are similar. However, patients with pT3-4N3b disease have a less favorable 5-year prognosis compared with cases with pT1-2N3b. In light of the unfavorable outcomes, pT3-4N3b disease should continue to be classified as pStage IVB. Conversely, pT4bN0-2 and pT1-2N3b diseases portend a less adverse prognosis and should therefore be downstaged to pStage IVA.
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MethodsWe sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE),... more
MethodsWe sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC).ResultsBetween 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p &lt; 0.001), distant metastases (DM, 6%/18%/40%, p &lt; 0.001), disease‐free survival (DFS, 78%/63%/46%, p &lt; 0.001), disease‐specific survival (DSS, 85%/71%/49%, p &lt; 0.001), and overall survival (OS, 68%/55%/39%, p &lt; 0.001). Multivariable analysis identified the following variables as independent prognosticators for 5‐year outcomes: ENE (LC/NC/DM/DFS/DSS/OS), poorly differentiated tumors (NC/DM/DFS/DSS/OS), positive margins (LC/DFS), lymphatic invasion (DFS/DSS/OS), perineural invasion (DM), and age ≥65 years (OS).ConclusionsIn addition to ENE, poor tumor differentiation was identified as the second most relevant adverse RF for patients with pT3–4 OCSCC. We suggest that the NCCN guidelines should include poor tumor differentiation as an adverse RF to refine and tailor clinical management.
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MicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from poorly invasive parental cell... more
MicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from poorly invasive parental cell populations, we used microarray expression analysis to identify a relative and specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p correlated with poor overall survival of patients with OSCCs. miR-491-5p overexpression in invasive OSCC cells suppressed their migratory behavior in vitro and lung metastatic behavior in vivo. We defined the G-protein—coupled receptor kinase-interacting protein 1 (GIT1)—as a direct target gene for miR-491-5p control. GIT1 overexpression was sufficient to rescue miR-491-5p–mediated inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing phenocopied the ability of miR-491-5p to inhibit migration/invasion and metastasis of OSCC cells. Mechanistic investigations indicated that miR-491-5p overexpression or GIT1 attenuation reduced focal adhesions, with a concurrent decrease in steady-state levels of paxillin, phospho-paxillin, phospho-FAK, EGF/EGFR-mediated extracellular signal–regulated kinase (ERK1/2) activation, and MMP2/9 levels and activities. In clinical specimens of OSCCs, GIT1 levels were elevated relative to paired normal tissues and were correlated with lymph node metastasis, with expression levels of miR-491-5p and GIT1 correlated inversely in OSCCs, where they informed tumor grade. Together, our findings identify a functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers for prognosis in this cancer. Cancer Res; 74(3); 751–64. ©2013 AACR.
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PDF file - 856K, Selection of highly invasive oral cancer cells (S1); Overexpressing miR-491-5p inhibited lung metastasis in SCID mice (S2); The GIT1 mRNA level is upregulated in highly invasive OSCC lines (S3); GIT1 was overexpressed in... more
PDF file - 856K, Selection of highly invasive oral cancer cells (S1); Overexpressing miR-491-5p inhibited lung metastasis in SCID mice (S2); The GIT1 mRNA level is upregulated in highly invasive OSCC lines (S3); GIT1 was overexpressed in the highly invasive oral cancer lines (S4); Knockdown of GIT1 by siRNA-3 had no affect paxillin mRNA expression (S5); DN-FAK suppresses GIT1-induced cell migration and invasion in OSCC cells (S6); Effect of ERK1/2 on MMP2/9 mRNA expression in OSCC cells (S7); Overexpression of miR-491-5p did not decrease proliferation in OSCC cells before 72h time point (S8); Effect of the DN-MEK or PD98059 on GIT1 induced MMP2/9 mRNA expression in OSCC cells (S9); Depletion of FAK and GIT1 decreased the paxillin and FAK phosphorylation (S10); CGHNC9 cells were transfected with FAM-labeled miR-491-5p (S11).
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PDF file - 38K, Clinicopathologic features of patients (S1); Primers used in this study (S2); Venn diagram showing miR-491-5p targets through the TargetScan and DIANA-microT (S3).
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OBJECTIVES The postoperative outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) vary greatly. To improve risk stratification, we sought to identify genetic biosignatures by whole-exome sequencing (WES). MATERIALS AND... more
OBJECTIVES The postoperative outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) vary greatly. To improve risk stratification, we sought to identify genetic biosignatures by whole-exome sequencing (WES). MATERIALS AND METHODS We retrieved patients with OCSCC patients with paired freshly frozen malignant and non-malignant tissue specimens and performed WES by Illumina HiSeq4000 platform. We further applied a tree-based method to analyze copy number variations and obtain signature classification and driver-gene identification. We further confirmed the prognostic impact of the WES biosignature in an external independent validation set. RESULTS We examined 168 paired samples from patients with surgically treated OCSCC. Similar to the literature, the most commonly mutated genes were TP53 (66%), FAT1 (32%), and NOTCH1 (24%). The signatures 13 (APOBEC Cytidine deaminase [C > G]), 1 (spontaneous deamination of 5-methylcytosine), and 7 (UV exposure) showed the highest concordance rates. Using the MutSigCV, MuSiC, 20/20+, OncodriveFML, e-Driver, OncodriveCLUST, and tree-based methods, we identified a nine-gene OCSCC panel (RYR1, HLA-B, TSHZ2, PCDH17, DNAH17, GRID1, SBNO2, KSR2, and GCN1L1) predicting survival outcomes in our sample. We used the TCGA database to validate the prognostic value of the panel independently. Furthermore, gene-gene covariance analysis confirmed the coexistence of several gene alterations. CONCLUSION We identified and independently validated a WES biosignature that predicts outcomes in surgically treated OCSCC in Taiwan, a betel-quid-chewing-prevent area. We proposed that the panel might help clinical trial designation for adjuvant therapy based on the risk stratification from the novel gene panel and identify targets for liquid biopsy monitoring during surveillance.
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According to the AJCC third to seventh edition staging manuals (1988–2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018)... more
According to the AJCC third to seventh edition staging manuals (1988–2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018) introduced a depth of invasion (DOI) > 20 mm as a criterion for pT4a. Subsequently, a revision maintained that tumors > 4 cm with a DOI > 10 mm should be classified as pT4a. We sought to analyze the prognostic impact of the three distinct criteria identifying pT4a disease. We examined 667 consecutive patients with pT3-4 buccal/gum/hard palate/retromolar SCC who underwent surgery between 1996 and 2016. pT1/pT2 (n = 108/359) disease were included for comparison purposes. The 5-year outcomes of patients with pT1/pT2/without (n = 406)/with tumor > 4 cm/DOI > 10 mm (n = 261), pT1/pT2/DOI ≤ 20 mm (n = 510)/> 20 mm (n = 157), and pT1/pT2/without (n = 305)/with through cortex/skin invasion (n = 362) were as follows: disease-specific survival (DSS), 98%/89%/79%/65%, p < 0.001, 98%/89%/78%/59%, p < 0.001, and 98%/89%79%/69%, p < 0.001; overall survival (OS), 90%/79%/63%/51%, p < 0.001, 90%/79%/63%/42%, p < 0.001, and 90%/79%/65%/52%, p < 0.001. In pT3-4 disease, a tumor > 4 cm/DOI > 10 mm was an independent adverse prognosticator for 5-year DSS rate, DOI > 20 mm was an independent adverse prognosticator for 5-year DSS and OS rates, whereas through cortex/skin invasion independently predicted 5-year OS rates. All of the three criteria (tumor > 4 cm/DOI > 10 mm, DOI > 20 mm, and through cortex/skin invasion) identify high-risk patients, which should be reflected in further revisions of pT4a classification in OCSCC.
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Although patients with buccal squamous cell carcinoma (SCC) usually show acceptable outcomes, local control and survival rates are generally lower than those observed for tongue SCC. This study was designed to compare the clinical... more
Although patients with buccal squamous cell carcinoma (SCC) usually show acceptable outcomes, local control and survival rates are generally lower than those observed for tongue SCC. This study was designed to compare the clinical outcomes of Taiwanese patients with these two common oral cavity malignancies. Patients with first primary buccal or tongue SCC who were included in the Taiwanese Cancer Registry Database between 2004 and 2012 were eligible. The study sample consisted of 16,379 patients (7870 buccal SCC and 8509 tongue SCC) who received surgery with or without adjuvant therapy. The 5-year disease-specific survival (DSS) and overall survival (OS) rates served as the outcome measures. Compared with tongue SCC, patients with buccal SCC had a higher prevalence of males (95.7% vs. 86.4%, p<0.0001), pT4 disease (21.4% vs. 12.7%, p<0.0001), and p-Stage IV (30.4% vs. 24.8%, p<0.0001) but a lower frequency of pN2 disease (15.2% vs. 18.5%, p<0.0001). The 5-year DSS and O...
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We sought to investigate whether there is evidence of field cancerization in patients with oral cavity squamous cell carcinoma (OSCC) enrolled in a betel quid chewing area. We also assessed whether betel quid chewing is an independent... more
We sought to investigate whether there is evidence of field cancerization in patients with oral cavity squamous cell carcinoma (OSCC) enrolled in a betel quid chewing area. We also assessed whether betel quid chewing is an independent risk factor for field cancerization in OSCC patients. We retrospectively examined the records of 1570 OSCC patients who underwent radical tumor resection between 1996 and 2011. A total of 1243 study participants (79%) had a positive history of betel quid chewing before surgery. Of the 767 patients treated with surgery alone, 599 (78%) were preoperative chewers, whereas a history of preoperative betel quid chewing was identified in 644 (80%) of the 803 patients who received adjuvant therapy. The 5-year control, survival, and second primary tumors (SPTs) rates served as the main outcome measures. Regardless of the treatment modality, more than 70% of the SPTs were located in the oral cavity or soft palate. Despite a similar risk profile in terms of tumor...
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Research Interests: Dentistry, Medicine, Humans, Internal Medicine, Female, and 15 moreMale, Oral Oncology, Mandible, Aged, Middle Aged, Neoplasm Invasiveness, Mouth Neoplasms, Adult, Public health systems and services research, Chemoradiotherapy, Lymph nodes, neoadjuvant therapy, masseter muscle, Disease Free Survival, and Neoplasm staging
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Radiolabeled annexin V (ANV) has been widely used for imaging cell apoptosis. Recently, a novel ANV-Kunitz-type protease inhibitor fusion protein, ANV-6L15, was found to be a promising probe for improved apoptosis detection based on its... more
Radiolabeled annexin V (ANV) has been widely used for imaging cell apoptosis. Recently, a novel ANV-Kunitz-type protease inhibitor fusion protein, ANV-6L15, was found to be a promising probe for improved apoptosis detection based on its higher affinity to phosphatidylserine (PS) compared to native ANV. The present paper investigates the feasibility of apoptosis detection using radioiodinated ANV-6L15. Native ANV and ANV-6L15 were labeled with iodine-123 and iodine-125 using Iodogen method. The binding between the radioiodinated proteins and erythrocyte ghosts or chemical-induced apoptotic cells was examined. ANV-6L15 can be radioiodinated with high yield (40%−60%) and excellent radiochemical purity (>95%).123I-ANV-6L15 exhibited a higher binding ratio to erythrocyte ghosts and apoptotic cells compared to123I-ANV. The biodistribution of123I-ANV-6L15 in mice was also characterized.123I-ANV-6L15 was rapidly cleared from the blood. High uptake in the liver and the kidneys may limit t...
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MicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from poorly invasive parental cell... more
MicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from poorly invasive parental cell populations, we used microarray expression analysis to identify a relative and specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p correlated with poor overall survival of patients with OSCCs. miR-491-5p overexpression in invasive OSCC cells suppressed their migratory behavior in vitro and lung metastatic behavior in vivo. We defined the G-protein—coupled receptor kinase-interacting protein 1 (GIT1)—as a direct target gene for miR-491-5p control. GIT1 overexpression was sufficient to rescue miR-491-5p–mediated inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing phenocopied the ability of miR-491-5p to inhibit migration/invasion and metastasis of OSCC cells. Mechanistic investigations indicated that ...
Research Interests: Oncology, MicroRNA, Cancer, Biology, Metastasis, and 15 moreCancer Research, Medicine, Humans, Mice, Animals, microRNAs, Neoplasm Invasiveness, Mouth Neoplasms, Cell Cycle Proteins, Focal Adhesions, Invadopodia, Focal Adhesion Kinase, Matrix Metalloproteinase, Neoplasm metastasis, and lung neoplasms
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The purpose of this study was to investigate if a novel parameter, the stress-to-rest ratio of the signal-to-noise ratio (RSNR) obtained with a cadmium zinc telluride (CZT) SPECT scanner, could be used to distinguish triple-vessel disease... more
The purpose of this study was to investigate if a novel parameter, the stress-to-rest ratio of the signal-to-noise ratio (RSNR) obtained with a cadmium zinc telluride (CZT) SPECT scanner, could be used to distinguish triple-vessel disease (TVD) patients. . One hundred and two patients with suspected coronary artery disease were retrospectively involved. Each subject underwent a Tl-201 SPECT scan and subsequent coronary angiography. Subjects were separated into TVD ( = 41) and control ( = 61) groups based on coronary angiography results using 50% as the stenosis cutoff. The RSNR was calculated by dividing the stress signal-to-noise ratio (SNR) by the rest SNR. Summed scores were calculated using quantitative perfusion SPECT (QPS) for all subjects. . The RSNR in the TVD group was found to be significantly lower than that in the control group (0.83 ± 0.15 and 1.06 ± 0.17, resp.; < 0.01). Receiver-operating characteristic (ROC) analysis showed that RSNR can detect TVD more accurately...
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An increased level of brain amyloid deposition and a decreased level of cerebral spinal fluid (CSF) Aβ42 are currently considered reliable biomarkers of Alzheimer's disease (AD); however, the usefulness of plasma Aβ levels are not... more
An increased level of brain amyloid deposition and a decreased level of cerebral spinal fluid (CSF) Aβ42 are currently considered reliable biomarkers of Alzheimer's disease (AD); however, the usefulness of plasma Aβ levels are not well-established. This study investigated the relationships between plasma Aβ levels and cerebral amyloidosis in 36 non-demented patients with major depressive disorder (MDD). All participants underwent F-florbetapir PET imaging and provided a blood sample at the same time for immunomagnetic reduction assay to measure the plasma levels of Aβ40 and Aβ42. We found inverse associations of the plasma Aβ42 level and the Aβ42/Aβ40 ratio, and a positive association of the plasma Aβ40 level, with cerebral amyloid deposition in the precuneus, parietal and posterior cingulate cortex. Subgroup analyses in subjects with higher F-florbetapir uptake values or MDD with amnestic mild cognitive impairment revealed more pervasive relationships of plasma Aβ measures with...
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The purpose of this study was to investigate whether multidisciplinary team care (MDTC) is associated with outcomes in oral cavity squamous cell carcinoma (SCC). We retrospectively examined 1616 patients with oral cavity SCC who underwent... more
The purpose of this study was to investigate whether multidisciplinary team care (MDTC) is associated with outcomes in oral cavity squamous cell carcinoma (SCC). We retrospectively examined 1616 patients with oral cavity SCC who underwent radical surgery between 1996 and 2011. The study participants were classified into 2 subgroups according to the use of MDTC. Five-year outcomes were significantly better in the MDTC group than in the no-MDTC group (neck control, 88% vs 84%, p = .0397; disease-specific survival [DSS], 83% vs 78%, p = .0114; and overall survival [OS], 70% vs 64%, p = .0002, respectively). Among patients who were scheduled to undergo adjuvant therapy, the number who completed their adjuvant treatment was significantly higher in the MDTC group than in the no-MDTC group (90% vs 60% to 70%, p < .001). The association of MDTC with improved outcomes may be potentially explained by a better therapeutic alliance between the patient and the tumor board, and/or a greater th...
Research Interests: Nursing, Dentistry, Treatment Outcome, Medicine, Humans, and 15 moreInternal Medicine, Female, Male, Clinical Sciences, Aged, Middle Aged, Oral Squamous Cell Carcinoma (OSCC), Mouth Neoplasms, Adult, Patient Care Team, Survival Rate, Retrospective Studies, Oral Cavity, Adjuvant, and Neoplasm staging
Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [Tc99m]-TRODAT with SPECT imaging.Procedures. A normal [Tc99m]-TRODAT template was first formed based on 28 healthy controls.... more
Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [Tc99m]-TRODAT with SPECT imaging.Procedures. A normal [Tc99m]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n=365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis.Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic func...
Research Interests: Nuclear medicine, Medicine, Humans, Female, Male, and 13 moreYoung Adult, Biomed, Aged, Middle Aged, Single Photon Emission Computed Tomography, Adult, Retrospective Studies, Radiopharmaceuticals, Sensitivity and Specificity, Receiver Operating Characteristic, Parkinson Disease, Case Control Studies, and Corpus striatum
The blood-brain barrier (BBB) can be transiently and locally opened by focused ultrasound (FUS) in the presence of microbubbles (MBs). Various imaging modalities and contrast agents have been used to monitor this process. Unfortunately,... more
The blood-brain barrier (BBB) can be transiently and locally opened by focused ultrasound (FUS) in the presence of microbubbles (MBs). Various imaging modalities and contrast agents have been used to monitor this process. Unfortunately, direct ultrasound imaging of BBB opening with MBs as contrast agent is not feasible, due to the inability of MBs to penetrate brain parenchyma. However, FUS-induced BBB opening is accompanied by changes in blood flow and perfusion, suggesting the possibility of perfusion-based ultrasound imaging. Here we evaluated the use of MB destruction-replenishment, which was originally developed for analysis of ultrasound perfusion kinetics, for verifying and quantifying FUS-induced BBB opening. MBs were intravenously injected and the BBB was disrupted by 2 MHz FUS with burst-tone exposure at 0.5-0.7 MPa. A perfusion kinetic map was estimated by MB destruction-replenishment time-intensity curve analysis. Our results showed that the scale and distribution of FUS...
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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... more
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(9) 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 significant...
Research Interests: Genetics, Cancer, Magnetic Resonance Imaging, Biology, Cell Biology, and 15 moreMedicine, Brain, Genetic Enhancement, Mice, Blood brain barrier, Animals, Gene transfer techniques, Male, Focused Ultrasound, Astrocytes, Green Fluorescent Protein, Gene Delivery, Fluorescent Antibody Technique, Contrast Media, and Focused
Functional brain SPECT is playing an increasingly important role in evaluating CNS conditions in patients with systemic lupus erythematosus (SLE). However, SPECT findings varied in different studies because of their small population.... more
Functional brain SPECT is playing an increasingly important role in evaluating CNS conditions in patients with systemic lupus erythematosus (SLE). However, SPECT findings varied in different studies because of their small population. Furthermore, earlier researchers, being restricted by the resolution of the camera, might not have been able to evaluate deep-seated nuclei such as the basal ganglia and thalamus. In this study, we describe the different patterns of SPECT findings in SLE patients with CNS involvement. Seventy-two SLE patients (aged 14-67 yr; mean 33.2 yr) were divided into three groups: Group 1 with definite neuro-psychiatric disorder (including stroke, seizures and psychosis); Group 2 with minor neuropsychiatric disorders (headache, dizziness and recent memory impairment); and Group 3 without any neuropsychiatric symptoms or signs. Ninety minutes after injection of 1110 MBq 99mTc-HMPAO, brain SPECT was performed using a dual-head camera and fan-beam collimator. In addi...
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Dopamine transporter (DAT) binding is decreased in Machado-Joseph disease (MJD) patients. To further investigate the DAT activity in asymptomatic MJD (aMJD) gene carriers, we performed this prospective study using (99m)Tc-TRODAT-1... more
Dopamine transporter (DAT) binding is decreased in Machado-Joseph disease (MJD) patients. To further investigate the DAT activity in asymptomatic MJD (aMJD) gene carriers, we performed this prospective study using (99m)Tc-TRODAT-1 ([(99m)Tc][2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]-methyl](2-mercaptoethyl)amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo-[1R-(exo-exo)])) brain SPECT on 5 aMJD gene carriers, 10 age-matched MJD patients, and 10 age-matched healthy control subjects. Brain SPECT images were acquired 4 h after intravenous injection of 925 MBq (25 mCi) (99m)Tc-T RODAT-1, which is known to bind specifically to the DAT on the nigrostriatal terminals. By fusing these SPECT images with a striatal atlas, obtained from MRI, binding of this tracer in the entire striatum was measured and the uptake values in bilateral striatal areas were compared between these 3 groups. The uptake values of the aMJD gene carriers (P < 0.001) and MJD patients (P...
Research Interests: Magnetic Resonance Imaging, Nuclear medicine, Medicine, Dopamine, Prospective studies, and 15 moreHumans, Internal Medicine, Caudate Nucleus, Female, Pubmed, Male, Pedigree, Membrane transport proteins, Clinical Sciences, Adult, Dopamine Transporter, Asymptomatic, Putamen, Corpus striatum, and Brain SPECT
Using (99m)Tc-TRODAT-1 ((99m)Tc-[2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]-oct-2-yl]-methyl](2-mercaptoethyl) amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo-[1R-(exo-exo)])) brain SPECT imaging, we measured... more
Using (99m)Tc-TRODAT-1 ((99m)Tc-[2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]-oct-2-yl]-methyl](2-mercaptoethyl) amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo-[1R-(exo-exo)])) brain SPECT imaging, we measured striatal dopamine transporters (DATs) activity in multiple system atrophy (MSA) to investigate the possibility of differentiating it from Parkinson's disease (PD) and to correlate the findings with the parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes of MSA. Forty-nine patients with probable MSA (30 MSA-P, 19 MSA-C), a disease control group of 36 age- and disease duration-matched patients with probable PD, and a healthy control group of 33 age-matched healthy volunteers participated in a SPECT study. The ratios of specific striatal binding-to-nonspecific occipital binding, including the striatum-to-occipital ratio (S/O), putamen-to-occipital ratio (P/O), caudate nucleus-to-occipital ratio (C/O), and putamen-to-caudate nucleus ratio (P/C), were ca...
Research Interests: Chemistry, Multiple System Atrophy, Nuclear medicine, Medicine, Humans, and 15 moreInternal Medicine, Caudate Nucleus, Female, Pubmed, Male, Differential Diagnosis, Membrane transport proteins, Clinical Sciences, Middle Aged, Atrophy, Radiopharmaceuticals, Putamen, Parkinson Disease, Corpus striatum, and ah
Research Interests: Materials Science, Neuroimaging, Fluorescence Microscopy, Nanomedicine, Nanoparticles, and 15 moreNanotechnology, Medicine, Cell line, Brain, Mice, Endocytosis, Female, Animals, Liposomes, Liposome, Biodistribution, Particle Size, Drug Carriers, Apomorphine, and Pharmacology and pharmaceutical sciences
Imaging of serotonin transporter (SERT) in the central nervous system may provide an important tool to evaluate some psychiatric disorders. Recently, a novel (123)I-labeled radiotracer,... more
Imaging of serotonin transporter (SERT) in the central nervous system may provide an important tool to evaluate some psychiatric disorders. Recently, a novel (123)I-labeled radiotracer, 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ((123)I-ADAM), has been developed that exhibited a high selectivity for SERT. The aim of this study was to characterize the biodistribution and specificity of (123)I-ADAM to SERT using quantitative autoradiography in both control and neurotoxin-treated animals. (123)I-ADAM (74 MBq) was injected intravenously into the mice to access its biodistribution in the brain via quantitative autoradiography. Further, rats with serotonin depleted by intraperitoneal injection of p-chloroamphetamine (PCA) were used to evaluate the specificity of (123)I-ADAM to SERT. The levels of biogenic amines were then measured and correlated with quantitative (123)I-ADAM labeling in control and PCA-treated rat brains. The autoradiographic results showed that (123)I-AD...
Research Interests: Chemistry, Nuclear medicine, Medicine, Serotonin, Brain, and 15 moreMice, Pubmed, Animals, Serotonin Transporter, Male, Membrane transport proteins, Clinical Sciences, Rats, Globus Pallidus, Autoradiography, Radiopharmaceuticals, Biogenic amines, Protein Binding, binding sites, and Dorsal raphe nucleus
Research Interests: Psychology, Adolescent, Medicine, Dopamine, Humans, and 15 moreCaudate Nucleus, Female, Male, Human Brain, Membrane transport proteins, Middle Aged, Adult, Dopamine Transporter, Clinical Assessment, Occipital Lobe, dopaminergic, Corpus striatum, Psychology and Cognitive Sciences, Medical and Health Sciences, and Positive and Negative Syndrome Scale
Research Interests: Bioengineering, Biomedical Engineering, Biotechnology, Drug delivery, Biological Sciences, and 15 moreAnatomy, Brain, Clinical Medicine, Blood brain barrier, Animals, Cavitation, Drug Delivery Systems, Disruption, Animal models, CNS, Diagnostic Radiology, Drug Distribution, Contrast Media, Extravasation, and Focused
Research Interests: Depression, Biology, Medicine, Intestinal Mucosa, Mice, and 15 moreAnimals, Peripheral Nervous System, Male, Central Nervous System, Membrane transport proteins, Clinical Sciences, Biodistribution, Autoradiography, Reproducibility of Results, Biological markers, Adrenal Gland, Radiopharmaceuticals, Sensitivity and Specificity, Binding Site, and Brain stem
We report on 2 brothers, Patients 1 and 2, who presented with a similar clinical syndrome consisting of resting tumor, bradykinesia, rigidity, and dysarthria at the ages of 40 and 43 years, respectively. An excellent response to levodopa... more
We report on 2 brothers, Patients 1 and 2, who presented with a similar clinical syndrome consisting of resting tumor, bradykinesia, rigidity, and dysarthria at the ages of 40 and 43 years, respectively. An excellent response to levodopa therapy was observed throughout the disease course. No gait or limb ataxia, slow saccades, or decreased tendon reflexes were detected, but unsteadiness of gait with propulsion developed recently in Patient 1 approximately 25 years after disease onset. Magnetic resonance imaging demonstrated mild atrophy of the pons and cerebellum in Patient 1 and cerebellar atrophy in Patient 2. Expanded CAG repeats, numbering 36, in one allele of the ataxin‐2 gene were identified in Patient 1 only; his brother was not available for this investigation. With [99mTc]TRODAT‐1 single photon emission computed tomography of the brain, a significant bilateral and asymmetrical reduction of striatal dopamine transporters was found in Patient 1 compared to healthy controls. T...