• Genomics & Informatics
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• v.19 no.4
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• pp.47.1-47.12
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• 2021

Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the few human oncogenic viruses, which causes a variety of malignancies, including Kaposi's sarcoma, multicentric Castleman disease, and primary effusion lymphoma, particularly in human immunodeficiency virus patients. The currently available treatment options cannot always prevent the invasion and dissemination of this virus. In recent times, siRNA-based therapeutics are gaining prominence over conventional medications as siRNA can be designed to target almost any gene of interest. The ORF57 is a crucial regulatory protein for lytic gene expression of KSHV. Disruption of this gene translation will inevitably inhibit the replication of the virus in the host cell. Therefore, the ORF57 of KSHV could be a potential target for designing siRNA-based therapeutics. Considering both sequence preferences and target site accessibility, several online tools (i-SCORE Designer, Sfold web server) had been utilized to predict the siRNA guide strand against the ORF57. Subsequently, off-target filtration (BLAST), conservancy test (fuzznuc), and thermodynamics analysis (RNAcofold, RNAalifold, and RNA Structure web server) were also performed to select the most suitable siRNA sequences. Finally, two siRNAs were identified that passed all of the filtration phases and fulfilled the thermodynamic criteria. We hope that the siRNAs predicted in this study would be helpful for the development of new effective therapeutics against KSHV.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8149-8153
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• 2016

An oncopathological state assessment was conducted among adults, children and teenagers in Aktobe region for 2004-2013. Overall the burden of mortality was in the range of 94.8-100.2 per 100,000 population, without any obvious trend over time. Ranking by pathology, the highest incidences among women were registered for breast cancer (5.8-8.4), cervix uteri (2.9-4.6), ovary (2.4-3.6) and corpus uteri, stomach, esophagus, without any marked change over time except for a slight rise in cervical cancer rates. In males, the first place in rank was trachea, bronchus and lung, followed by stomach and esophagus, which are followed by bladder, lymphoid and hematopoietic tissues pathology. Agian no clear trends were apparent over time. In children, main localizations in cancer incidence blood (acute lymphocytic leukemia, lymphosarcoma, acute myeloid leukemia, Hodgkin's disease), brain and central nervous system, bones and articular cartilages, kidneys, and eye and it's appendages, in both sexes. Similarly, in young adults, the major percentage was in blood and lymphatic tissues (acute myeloid leukemia, acute lymphocytic leukemia, Hodgkin's disease) a significant percentage accruing to lymphosarcoma, lymphoma, other myeloid leukemia and hematological malignancies as well as tumors of brain and central nervous system, bones and articular cartilages. This initial survey provides the basis for more detailed investigation of cancer epidemiology in Aktobe, Kazakhstan.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.99-105
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• 2005

Perchloroethylene (tetrachloroethylene, PCE), a dry cleaning and degreasing solvent, can enter ground-water through accidental leak or spills. PCE can be degraded to trichloroethylene (TCE), 1, 1-dichloroethylene (DCE) and vinyl chloride (VC) as potential bio-product. These compounds have been reported that they can cause clinical diseases and cytotoxicity. However, only a little genotoxic information of these compounds has been known. In this study, we investigated DNA single strand breaks of PCE, TCE, DCE and VC by single cell gel electrophoresis assay, (comet assay) which is a sensitive, reliable and rapid method for DNA single strand breaks with mouse lymphoma L5178Y cells. From these results, $37.5\;{\mu}g/ml$ of PCE, $189\;{\mu}g/ml$ of TCE and $56.4\;{\mu}g/ml$ of DCE were revealed significant DNA damages in the absence of S-9 metabolic activation system meaning direct-acting mutagen. And in the presence of S-9 metabolic activation system, $41.5\;{\mu}g/ml$ of PCE, $328.7\;{\mu}g/ml$ of TCE and $949\;{\mu}g/ml$ of DCE were induced significant DNA damage. In the case of VC, it was revealed a significant DNA damage in the presence of S-9 metabolic activation system. Therefore, we suggest that chloroethylene compounds (PCE, TCE, DCE and VC) may be induced the DNA damage in a mammalian cell.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.98-103
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• 1993

The present study was purposed to evaluate the incidence and the characteristics of metastatic "cold" lesions in $^{99m}Tc$-MDP bone scans of adult patients with solid malignancies. There were 29 cold lesions in 24 patients. The incidence of cold lesions was about 1% of total cases of bone scans for the patients with malignancy, or 2.5% of cases with bone metastases. Th primary sites of malignancies were lung (four cases), uterine cervix (three cases), kidney, nasopharynx, thyroid, urinary bladder, prostate, lymphoma (two cases each other), liver, breast and others (one case each other). But the relative incidence of cold lesion in lung cancer and breast cancer was low. The most frequent site of cold lesion was spine, and pelvis, skull and rib were followed. The incidence of cold lesion was related to the regional incidence of bone metastases. The size of the cold lesions was greater than that of the hot. There were six cases of single cold lesion without any other abnormalities and two cases of cold lesion which were initially hot. So it should be considered that bone metastases might be presented as cold lesions in bone scan.

• Journal of Pharmacopuncture
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• v.18 no.3
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• pp.32-41
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• 2015

Objectives: Condurango (Gonolobus condurango) extract is used by complementary and alternative medicine (CAM) practitioners as a traditional medicine, including homeopathy, mainly for the treatment of syphilis. Condurango bark extract is also known to reduce tumor volume, but the underlying molecular mechanisms still remain unclear. Methods: Using a cervical cancer cell line (HeLa) as our model, the molecular events behind condurango extract's (CE's) anticancer effect were investigated by using flow cytometry, immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Other included cell types were prostate cancer cells (PC3), transformed liver cells (WRL-68), and peripheral blood mononuclear cells (PBMCs). Results: Condurango extract (CE) was found to be cytotoxic against target cells, and this was significantly deactivated in the presence of N-acetyl cysteine (NAC), a scavenger of reactive oxygen species (ROS), suggesting that its action could be mediated through ROS generation. CE caused an increase in the HeLa cell population containing deoxyribonucleic acid (DNA) damage at the G zero/Growth 1 (G0/G1) stage. Further, CE increased the tumor necrosis factor alpha ($TNF-{\alpha}$) and the fas receptor (FasR) levels both at the ribonucleic acid (RNA) and the protein levels, indicating that CE might have a cytotoxic mechanism of action. CE also triggered a sharp decrease in the expression of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) both at the RNA and the protein levels, a possible route to attenuation of B-cell lymphoma 2 (Bcl-2), and caused an opening of the mitochondrial membrane's permeability transition (MPT) pores, thus enhancing caspase activities. Conclusion: Overall, our results suggest possible pathways for CE mediated cytotoxicity in model cancer cells.

• Toxicological Research
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• v.30 no.3
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• pp.211-220
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• 2014

Resveratrol has received considerable attention as a polyphenol with various biological effects such as anti-inflammatory, anti-oxidant, anti-mutagenic, anti-carcinogenic, and cardioprotective properties. As part of the overall safety assessment of HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, we assessed genotoxicity in three in vitro assays: a bacterial mutation assay, a comet assay, and a chromosomal aberration assay. In the bacterial reverse mutation assay, HS-1793 did not increase revertant colony numbers in S. typhimurium strains (TA98, TA100, TA1535 and TA1537) or an E. coli strain (WP2 uvrA) regardless of metabolic activation. HS-1793 showed no evidence of genotoxic activity such as DNA damage on L5178Y $Tk^{+/-}$ mouse lymphoma cells with or without the S9 mix in the in vitro comet assay. No statistically significant differences in the incidence of chromosomal aberrations following HS-1793 treatment was observed on Chinese hamster lung cells exposed with or without the S9 mix. These results provide additional evidence that HS-1793 is non-genotoxic at the dose tested in three standard tests and further supports the generally recognized as safe determination of HS-1793 during early drug development.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.71-77
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• 2019

Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer's disease (AD) induced by $A{\beta}_{1-42}$ and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin ($100{\mu}g/kg/day$), the cognitive impairment of mice induced by $A{\beta}_{1-42}$ was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and $A{\beta}_{1-42}$ accumulation in hippocampus. $A{\beta}_{1-42}$ induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression,suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.

• Journal of the Korean Society of Radiology
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• v.84 no.5
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• pp.1146-1151
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• 2023

Medullary thyroid carcinoma (MTC) is a rare malignancy that originates from the parafollicular cells of the thyroid gland. Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease and is the most common cause of hypothyroidism. Previous studies have frequently discussed the association among HT, papillary thyroid carcinoma, and thyroid lymphoma. However, there have been few reports on the ultrasonographic findings of concomitant HT and MTC. In the present case, a heterogeneous hypoechoic background parenchymal echogenicity, with intraglandular echogenic strands, and increased vascularity were observed. A concurrent, ill-defined, parallel-oriented, heterogeneous hypoechoic mass with central microcalcifications was located at the left thyroid gland, consistent with reported US findings of medullary thyroid carcinoma except for an ill-defined margin in our case.

• Investigative Magnetic Resonance Imaging
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• v.1 no.1
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• pp.119-124
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• 1997

Purpose: To assess the utility of magnetic resonance(MR) cerebral blood volume (CBV) map in the evaluation of brain tumors. Materials and Methods: We performed perfusion MR imaing preoperatively in the consecutive IS patients with intracranial masses(3 meningiomas, 2 glioblastoma multiformes, 3 low grade gliomas, 1 lymphoma, 1 germinoma, 1 neurocytoma, 1 metastasis, 2 abscesses, 1 radionecrosis). The average age of the patients was 42 years (22yr -68yr), composed of 10 males and S females. All MR images were obtained at l.ST imager(Signa, CE Medical Systems, Milwaukee, Wisconsin). The regional CBV map was obtained on the theoretical basis of susceptibility difference induced by first pass circulation of contrast media. (contrast media: IScc of gadopentate dimeglumine, about 2ml/sec by hand, starting at 10 second after first baseline scan). For each patient, a total of 480 images (6 slices, 80 images/slice in 160 sec) were obtained by using gradient echo(CE) single shot echo-planar image(EPI) sequence (TR 2000ms, TE SOms, flip angle $90^{\circ}$, FOV $240{\times}240mm,{\;}matrix{\;}128{\times}128$, slice-thick/gap S/2.S). After data collection, the raw data were transferred to CE workstation and rCBV maps were generated from the numerical integration of ${\Delta}R2^{*} on a voxel by voxel basis, with home made software (${\Delta}R2^{*}=-ln (S/SO)/TE). For easy visual interpretation, relative RCB color coding with reference to the normal white matter was applied and color rCBV maps were obtained. The findings of perfusion MR image were retrospectively correlated with Cd-enhanced images with focus on the degree and extent of perfusion and contrast enhancement. Results: Two cases of glioblastoma multiforme with rim enhancement on Cd-enhanced Tl weighted image showed increased perfusion in the peripheral rim and decreased perfusion in the central necrosis portion. The low grade gliomas appeared as a low perfusion area with poorly defined margin. In 2 cases of brain abscess, the degree of perfusion was similar to that of the normal white matter in the peripheral enhancing rim and was low in the central portion. All meningiomas showed diffuse homogeneous increased perfusion of moderate or high degree. One each of lymphoma and germinoma showed homogenously decreased perfusion with well defined margin. The central neurocytoma showed multifocal increased perfusion areas of moderate or high degree. A few nodules of the multiple metastasis showed increased perfusion of moderate degree. One radionecrosis revealed multiple foci of increased perfusion within the area of decreased perfusion. Conclusion: The rCBV map appears to correlate well with the perfusion state of brain tumor, and may be helpful in discrimination between low grade and high grade gliomas. The further study is needed to clarify the role of perfusion MR image in the evaluation of brain tumor.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.7-14
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• 1992

Between August 1988 and December 1991, 24 patients with intracranial tumors were treated with stereotactic radiosurgery(RS) using a 10 MV linear accelerator at Severance Hospital, Yonsei University College of Medicine. There were 5 meningiomas, 3 craniopharyngiomas, 9 glial tumors, 2 solitary metastases, 2 acoustic neurinomas, 2 pineal tumors, and 1 non-Hodgkin's lymphoma. Ten patients were treated as primary treatment after diagnosis with stereotactic biopsy or neuroimaging study. Nine patients underwent RS for post-op. residual tumors and three patients as a salvage treatment for recurrence after external irradiation. Two patients received RS as a boost followed by fractionated conventional radiotherapy. Among sixteen patients who were followed more than 6 months with neuroimage, seven patients (2 meningiomas, 4 benign glial tumors, one non-Hodgkin's lymphoma) showed complete response on neuroimage after RS and nine patients showed decreased tumor size. There was no acute treatment related side reaction. Late complications include three patients with symptomatic peritumoral brain edema and one craniopharyngioma with optic chiasmal injury. Through this early experience, we conclude that stereotactically directed single high doses of irradiation to the small intracranial tumors is effective for tumor control. However, in order to define the role of radiosurgery in the management of intracraniai tumors, we should get the long-term results available to demonstrate the benefits versus potential complications of this therapeutic modality.