• Bioinformatics and Biosystems
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• v.1 no.1
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• pp.67-72
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• 2006

The aim of this paper is to discuss the effect of missing values in detecting differentially expressed genes in a cDNA microarray experiment in the context of a one sample problem. We conducted a cDNA micro array experiment to detect differentially expressed genes for the metastasis of colorectal cancer based on twenty patients who underwent liver resection due to liver metastasis from colorectal cancer. Total RNAs from metastatic liver tumor and adjacent normal liver tissue from a single patient were labeled with cy5 and cy3, respectively, and competitively hybridized to a cDNA microarray with 7775 human genes. We used $M=log_2(R/G)$ for the signal evaluation, where Rand G denoted the fluorescent intensities of Cy5 and Cy3 dyes, respectively. The statistical problem comprises a one sample test of testing E(M)=0 for each gene and involves multiple tests. The twenty cDNA microarray data would comprise a matrix of dimension 7775 by 20, if there were no missing values. However, missing values occur for various reasons. For each gene, the no missing proportion (NMP) was defined to be the proportion of non-missing values out of twenty. In detecting differentially expressed (DE) genes, we used the genes whose NMP is greater than or equal to 0.4 and then sequentially increased NMP by 0.1 for investigating its effect on the detection of DE genes. For each fixed NMP, we imputed the missing values with K-nearest neighbor method (K=10) and applied the nonparametric t-test of Dudoit et al. (2002), SAM by Tusher et al. (2001) and empirical Bayes procedure by $L\ddot{o}nnstedt$ and Speed (2002) to find out the effect of missing values in the final outcome. These three procedures yielded substantially agreeable result in detecting DE genes. Of these three procedures we used SAM for exploring the acceptable NMP level. The result showed that the optimum no missing proportion (NMP) found in this data set turned out to be 80%. It is more desirable to find the optimum level of NMP for each data set by applying the method described in this note, when the plot of (NMP, Number of overlapping genes) shows a turning point.

• Natural Product Sciences
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• v.3 no.1
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• pp.29-37
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• 1997

Protein Kinase C (PKC) is generally believed to play a central role in signal transduction, cellular growth control, gene expression, and tumor promotion. And it has been suggested that inhibitors of PKC might play important roles for the prevention and treatment of cancer. In order to investigate the possible inhibitors of PKC from natural products, PKC receptor binding assay was performed using bovine brain particulate as a source of PKC and the amount of $[^3H]Phorbol$ 12,13-dibutyrate (PDBu) bound to PKC was measured in the presence of test materials. Total methanol extracts from 100 kinds of natural products were partitioned into 3 fractions (n-hexane, ethyl acetate and aqueous layer) and their binding ability to the regulatory domain of PKC was evaluated. The ethyl acetate fractions of Morus alba $(roots,\;IC_{50}:\;156.6\;{\mu}g/ml)$, Rehmannia glutinosa $(roots,\;IC_{50}:\;134.3\;{\mu}g/ml)$, Lysimachia foenum-graecum $(roots,\;IC_{50}:\;167.8\;{\mu}g/ml)$, Polygonum cuspidata $(roots,\;IC_{50}:\;157.3\;{\mu}g/ml)$, Cnidium officinale $(aerial\;parts,\;IC_{50}:\;145.2\;{\mu}g/ml)$, and the hexane $(IC_{50}:\;179.3\;{\mu}g/ml)$ and the EtOAc fraction of Symplocarpus nipponicus $(roots,\;IC_{50}:\;155.9\;{\mu}g/ml)$ showed inhibitory activity of $[^3H]PDBu$ binding to PKC.

• Clinical and Experimental Pediatrics
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• v.57 no.9
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• pp.410-415
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• 2014

Purpose: Neurofibromatosis 1 (NF1) is an autosomal dominant condition caused by an NF1 gene mutation. NF1 is also a multisystem disorder that primarily affects the skin and nervous system. The goal of this study was to delineate the phenotypic characterization and assess the NF1 mutational spectrum in patients with NF1. Methods: A total of 42 patients, 14 females and 28 males, were enrolled in this study. Clinical manifestations and results of the genetic study were retrospectively reviewed. Results: Age of the patients at the time of NF1 diagnosis was $15.8{\pm}14.6$ years (range, 1-62 years). Twelve patients (28.6%) had a family history of NF1. Among the 42 patients, $Caf\acute{e}$-au-lait spots were shown in 42 (100%), neurofibroma in 31 (73.8%), freckling in 22 (52.4%), and Lisch nodules in seven (16.7%). The most common abnormal finding in the brain was hamartoma (20%). Mental retardation was observed in five patients (11.9%), seizures in one patient (2.4%), and plexiform neurofibromas (PNFs) in four patients (9.5%). One patient with PNFs died due to a malignant peripheral nerve sheath tumor in the chest cavity. Genetic analysis of seven patients identified six single base substitutions (three missense and three nonsense) and one small deletion. Among these mutations, five (71.4%) were novel (two missense mutations: p.Leu1773Pro, p.His1170Leu; two nonsense mutations: $p.Arg2517^*$, $p.Cys2371^*$; one small deletion: $p.Leu1944Phefs^*6$). Conclusion: The clinical characteristics of 42 Korean patients with NF1 were extremely variable and the mutations of the NF1 gene were genetically heterogeneous with a high mutation-detection rate.

• Nuclear Engineering and Technology
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• v.56 no.10
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• pp.4423-4436
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• 2024

The development and assessment of pharmaceutical dosage forms make considerable use of gamma-scintigraphy. Gamma scintigraphy is an imaging technique that is integrated with CT to assess and evaluate the targeting of drugs to various delivery sites, the impact of treatment, and the severity of the disease. A small number of radioisotopes were tagged with the delivery system and emitted radiation can be visualized by the gamma camera which forms a 2-D image displaying the tissue-specific distribution of radioactivity. The isotopes that are used widely include Technetium-99 m (99Tc), Iodine (131I), Fluorodeoxyglucose (18F-FDG), Fluoromisonidazole (18F-FMISO) and Gallium (Ga67), Indium (111In). This review mainly covers different applications of gamma scintigraphy for the assessment of drug targeting via different routes to different organs and their visualization by gamma scintigraphy. The review mainly focuses assessment of drug targeting in the tumor tissue, thyroid gland, brain, pulmonary pathway, skin deposition, detection of renal impairment as well as cardiac diseases, drug release from formulations, drug deposition in arthritis, drug retention in the scalp, and behavior of formulation when administered via intra-vaginal route. Various pre-clinical and clinical studies were included in the review that demonstrates the importance and future of gamma scintigraphy in sensing drug delivery.

• Journal of Oral Medicine and Pain
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• v.32 no.4
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• pp.449-453
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• 2007

Trigeminal neuralgia is defined as "a sudden, usually unilateral, brief stabbing recurrent pain in the distribution of one or more branches of the fifth cranial nerve" by the International Association for the Study of Pain(IASP). Trigeminal neuralgia is classified as an idiopathic trigeminal neuralgia with no apparent cause and a symptomatic trigeminal neuralgia which is caused by a structural lesion such as brain tumor. Over 80% of the tumors are meningioma, acoustic neuroma, and epidermoid tumors. Symptomatic trigeminal neuralgia can not be excluded even if old-aged patient does not have abnormal neurologic sign and symptom, and good response to pharmacotherapy. Therefore, initial examinations such as MRI or CT are essential to exclude symptomatic trigeminal neuralgia. When compared with CT, MRI, especially gadolinium enhanced MRI, has an increased sensitivity in the detection of intracranial lesions. The most effective medical treatment of trigeminal neuralgia is carbamazepine. The most common side effects of carbamazepine include drowsiness, dizziness, unsteadiness, nausea, anorexia. Hepatotoxicity, bone marrow depression are the most feared side effect of carbamazepine therapy but occurs rarely. It require periodic complete blood cell counts as well as hepatic and renal function tests. It has been recommended that complete blood cell counts is done every 2 weeks for the first 2months and then quaterly thereafter. Oxcarbazepine can be used if neutropenia occurs.

• Journal of Korean Neurosurgical Society
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• v.65 no.6
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• pp.790-800
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• 2022

Objective : EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. Methods : A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. Results : EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. Conclusion : Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.