Metallothionein (MT) is a family of ubiquitous, low molecular weight ($6,000{\sim}7,000D$), cysteine-rich ($30{\sim}35%$) inducible protein with a high affinity to metal ions and has no aromatic amino acids and histidine. Some of the known functions of MT include detoxification of heavy metals and alkylating agents and neutralization of free radicals. Also, this protein has been reported to involve in tumor pathophysiology and therapy resistance. MT expression may affect a number of cellular processes including gene expression, apoptosis, proliferation and differentiation. Many reports on the physiological and biochemical properties of MT have been published, but ultrastructural reports on the localization of MT in human gastric cancer tissues are extremely rare. The present study was undertaken to examine the ultrastructural features and the localization of MT within the gastric adenocarcinoma. Ultrastructures of gastric cancer cells were characterized by the high nuclear cytoplasmic ratio, the interdigitation between cells, the irregular nucleus containing much heterochromatin and the wide distribution of free ribosomes in the cytoplasm. Immunohistochemical reaction for MT was prominent in the gastric adenocarcinoma. And the immunogold labellings were more prominent within the nucleus than the cytoplasm. Particularly, immunogold particles were numerously seen at nulcleolus or nucleolar associated heterochromatin. These results suggest that MT expression by gastric cancer cells is associated with cell proliferative activity and is possibly synthesized in the cytoplasm, and then the protein is transported into the nucleus to participate in any transcriptional steps.
A statistical approach is used to investigate the relative economic advantages of pressurized water reactor (PWR) and pressurized heavy water reactor (PHWR-CANDU) nuclear power plants for hypothetical 900Mwe systems with the throwaway fuel cycle to be built in the Republic of Korea. Power cost is decomposed into the cost components related to the plant capital, operation and maintenance, working capital requirements and fuel cycle operation. The calculation of construction cost is performed with the modified version of computer code ORCOST, and the modified POWERCO-50 is used to evaluate the cost components. Most of economic parameters are treated as statistical variables, each being given with a certain range. Through a random sampling procedures. the probability histograms on unit plant construction costs and power generating costs are obtained. The power cost probability histograms of the PWR and the PHWR plants overlap considerably, and the power costs of two systems appear to be almost same with the PHWR power cost being 0.4mil1/kwh lower compared with 39.4 mills/kwh for the PWR plant (July 1986 US-dollars). When a construction period of PHWR plant is longer by one year than that of PWR plant, there is no difference in the unit power cost of two plants. This comparison leads to no definite conclusion on the cost advantage of the PWR plant versus the PHWR plant. We conclude that the selection issue of nuclear power plants in Korea still remains an open question and that future effort to solve this question should be made toward economic quantification of those factors such as technology transfer and localization.
Objective: 68Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68Ga-NGUL in healthy volunteers and the lesion detection rate of 68Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68Ga-NGUL PET/CT or conventional imaging. Among them, 68Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion: 68Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68Ga-NGUL is a valuable option for prostate cancer imaging.
Kim, Seon-Gu;Kim, Chang-Guhn;Lee, Kang-Mo;Kim, Hye-Won;Min Byung-Cheol;Choi, See-Sung;Lee, Jong-Deuk;Yang, David J.;Kim, E. Edmund;Lee, Hyun-Chul;Won Jong-Jin
The Korean Journal of Nuclear Medicine
/
v.32
no.4
/
pp.374-381
/
1998
Purpose: I-131 labeled (2'-deoxy-2'-iodo-${\beta}$-D-arabinofuranosyl) adenine (IAD) may be involved in DNA synthesis during active proliferation of tumor cells. We conducted this study to find out the biodistribution of IAD and it's feasibility for scintigraphic tumor imaging. Materials and Methods: Tosyl acetyl-adenosine was dissolved in acetonitrile, and I-131-NaI was added and heated to synthesize IAD. Female Fisher 344 rats innoculated with breast tumor cells were injected with 0.27 MBq of IAD. Rats were sacrificed at 0.5, 1, 2, 4, 24h and the % of injected dose per gram of tissue (%ID/g) was determined. For scintigraphy, rats bearing breast cancer were administered with 1.11 MBq of IAD and imaging was performed after 2 and 24h. Then, rat body was fixed and microtomized slice was placed on radiographic film for autoradiography. Results: %ID/g of tumor was 0.74 (0.5h),0.73 (1h), 0.55 (2h), 0.38 (4h), and 0.05 (24h), respectively. At 1h after injection, %ID/g of tumor was higher than that of heart (0.34), liver (0.42), spleen (0.47), kidney (0.69), muscle (0.14), bone (0.33) and intestine (0.51). However, %ID/g of tumor was lower than blood (1.06), lung (0.77), and thyroid (177.71). At 4h, %ID/g of tumor in comparison with other tissue did not change. Tumor contrast expressed by tumor to blood ratio was 0.69 and tumor to muscle ratio was 5.11 at 1h. However, these ratios did not improve through 24h. On autoradiogram and scintigraphy at 2 and 24 hour, the tumor was well visualized. Conclusion: This results suggest that IAD may have a potential for tumor scintigraphy. However, further work is needed to improve localization in tumor tissue.
Faithful transmission of genetic information depends on accurate chromosome segregation as cells exit from mitosis, and errors in chromosomal segregation are catastrophic and may lead to aneuploidy which is the hallmark of cancer. In eukaryotes, an elaborate molecular control system ensures proper orchestration of events at mitotic exit. Phosphorylation of specific tyrosyl residues is a major control mechanism for cellular proliferation and the activities of protein tyrosine kinases and phosphatases must be integrated. Although mitotic kinases are well characterized, phosphatases involved in mitosis remain largely elusive. Here we identify a novel variant of mouse protein tyrosine phosphatase containing domain 1 (Ptpcd1), that we named Ptpcd2. Ptpcd1 is a Cdc14 related centrosomal phosphatase. Our newly identified Ptpcd2 shared a significant homology to yeast Cdc14p (34.1%) and other Cdc14 family of phosphatases. By subcellular fractionation Ptpcd2 was found to be enriched in the cytoplasm and nuclear pellets with catalytic phosphatase activity. By means of immunofluorescence, Ptpcd2 was spatiotemporally regulated in a cell cycle dependent manner with cytoplasmic abundance during mitosis, followed by nuclear localization during interphase. Overexpression of Ptpcd2 induced mitotic exit with decreased levels of some mitotic markers. Moreover, Ptpcd2 failed to colocalize with the centrosomal marker ${\gamma}$-tubulin, suggesting it as a non-centrosomal protein. Taken together, Ptpcd2 phosphatase appears a non-centrosomal variant of Ptpcd1 with probable mitotic functions. The identification of this new phosphatase suggests the existence of an interacting phosphatase network that controls mammalian mitosis and provides new drug targets for anticancer modalities.
Kim, Deog-Yoon;Kim, Sang-Eun;Lee, Dong-Su;Ahn, Cu-Rie;Chung, June-Key;Lee, Myung-Chul;Koh, Chang-Soon
The Korean Journal of Nuclear Medicine
/
v.25
no.2
/
pp.259-265
/
1991
The purpose of this study is to investigate the ability of I-131 labeled polyclonal human immunoglobulin to localize an infection. In our country, indium-111 labeled leukocyte or Tc-99m labeled IgG are not readily available because of compex, time-consuming procedure and cost. So we tried to localize infection with I-131 labeled IgG which could be easily prepared. Six rats, infected with staphylococcus aureus in a thigh muscle, received I-131 labeled IgG intravenously and I-131 labeled bovine serum albumin (BSA) were injected to other 5 infected rats. Scintigrams were made at 1, 4, 24, 48, 72 hour later. The radiopharmaceutical demonstrated significant accumulation at the site of infection. The accumulation of I-131 labeled IgG at the site of infection was significantly (P<0.05) higher than that of I-131 labeled BSA at 48, 72 hour. Similar finding could be found at 24 hour imaging, but it was not significant statistically. Therefore it was found that vascular permeability alone could not account for the mode of action of I-131 labeled IgG and it was considered that specific binding played a role. In conclusion, focal sites of inflammation can be detected with I-131 labeled nonspecific human polyclonal IgG and it seems that this method can also be applied to localization of human infection.
Kim, Wan-Seop;Lee, Won-Mi;Hong, Eun-Kyung;Park, Moon-Hyang;Lee, Jung-Dal
The Korean Journal of Cytopathology
/
v.9
no.2
/
pp.213-219
/
1998
Glycogen-rich clear ceil carcinoma of the breast is an unusual variant of carcinoma with a recorded incidence of $1.4{\sim}3%$ of breast carcinomas. The cytologic characteristics have not been well described. We report two cases of glycogen-rich clear cell carcinoma with corresponding fine needle aspiration(FNA) cytologic findings and compare them to infiltrating ductal carcinoma and other clear ceil malignancies with a review of literature. One was a 62-year-old woman exhibiting a palpable mass of the right breast. The smears showed atypical tight cell clusters and individually scattered single cells containing leanly or clear abundant cytoplasm with well defined cytoplasmic margins. Mild to moderate nuclear pleomorphism and a prominent nucleolus were present. The other was a 42-year-old woman who was admitted with a right breast mass. The smears showed moderately cellular, tightly cohesive tumor cells. The cytoplasmic outline was generally well demarcated. The tumor cells Contained foamy to clear abundant cytoplasm with large and small vacuoles. The nuclear pleomorphism was marked. Both tumors resected by modified radical mastectomy, were diagnosed as glycogen-rich clear cell carcinoma. Histologically, the clear cell nature of tumor cells were not characteristic enough to predict this type of the tumor. Some cytologic features can be distinguished other clear cell breast cancer from glycogen-rich carcinoma. Recognition of these unusual patterns in a breast FNAC should raise the suspicion of a clear cell carcinoma including glycogen-rich subtype. Cytological localization of glycogen using PAS and D-PAS staining may permit the correct Identification and differential diagnosis of this tumor.
Kim, Bong-Ki;Lee, Yun-Jung;Cui, Xiang-Shun;Kim, Nam-Hyung
Proceedings of the KSAR Conference
/
2001.03a
/
pp.41-41
/
2001
Chromatin configuration and microtubule assembly were determined in porcine maturing and activated oocytes following intracytoplasmic sperm injection. Microtubule localization was confirmed using a mouse monoclonal antibody to $\alpha$-tubulin and detected using a fluorescent labeled goat anti-mouse secondary antibody. DNA was stained with propidium iodide. The image of microtubules and chromatin was captured using laser scanning confocal microscope. In germinal vesicle stage oocyte, sperm chromatin remained condensation and sperm derived microtubules were not observed at 8 to 12 h after sperm injection. At 24 h after injection, the sperm nucleus developed to the metaphase chromatin along the metaphase structure of female nucleus. In some metaphase I stage oocytes, sperm chromatin decondensed at 8 h to 12 h after injection, sperm aster was seen soon after sperm injection. At 24 h after sperm injection into metaphase I stage oocyte, male chromatin developed to the metaphase chromatin while female chromatin extruded first polar body and formed the metaphase chromatin. At 12 to 15 h after sperm injection into preactivated oocytes, condensed sperm nucleus was located in close proximity of female pronucleus. However, the condensed nucleus did not fuse with female pronucleus. In preactivated ocytes, injected sperm remained condensation, a few sperm organized small microtubular aster. Instead, maternal derived microtubules were organized near the female chromatin, which seem to move condensed male chromatin near to the female pronucleus. These results suggest that sperm nuclear decondensing activity and nucleation activity of centrosome during fertilization are cell cycle dependent. In absence of male functional centrosome, female origin centrosome takes over the role of microtubule nucleation for nuclear movement.
The R3V6 peptide includes a hydrophilic arginine stretch and a hydrophobic valine stretch. In previous studies, the R3V6 peptide was evaluated as a gene carrier and was found to have low cytotoxicity. However, the transfection efficiency of R3V6 was lower than that of poly-L-lysine (PLL) in N2A neuroblastoma cells. In this study, the transfection efficiency of R3V6 was improved in combination with high mobility group box 1A domain (HMGA). HMGA is originated from the nuclear protein and has many positively-charged amino acids. Therefore, HMGA binds to DNA via charge interaction. In addition, HMGA has a nuclear localization signal peptide and may increase the delivery efficiency of DNA into the nucleus. The ternary complex with HMGA, R3V6, and DNA was prepared and evaluated as a gene carrier. First, the HMGA/DNA complex was prepared with a negative surface charge. Then, R3V6 was added to the complex to coat the negative charges of the HMGA/DNA complex, forming the ternary complex of HMGA, R3V6, and DNA. A physical characterization study showed that the ternary complex was more stable than the PLL/DNA complex. The HMGA/R3V6/DNA complex had a higher transfection efficiency than the PLL/DNA, HMGA/DNA, or R3V6/DNA complexes in N2A cells. Furthermore, the HMGA/R3V6/DNA complex was not toxic to cells. Therefore, the HMGA/R3V6/DNA complex may be a useful gene delivery carrier.
Madjd, Zahra;Akbari, Mohammad Esmaeil;Zarnani, Amir Hassan;Khayamzadeh, Maryam;Kalantari, Elham;Mojtabavi, Nazanin
Asian Pacific Journal of Cancer Prevention
/
v.15
no.4
/
pp.1783-1789
/
2014
Background: The EMSY gene encodes a BRCA2-binding partner protein that represses the DNA repair function of BRCA2 in non-hereditary breast cancer. Although amplification of EMSY gene has been proposed to have prognostic value in breast cancer, no data have been available concerning EMSY tissue expression patterns and its associations with clinicopathological features. Materials and Methods: In the current study, we examined the expression and localization pattern of EMSY protein by immunohistochemistry and assessed its prognostic value in a well-characterized series of 116 unselected breast carcinomas with a mean follow up of 47 months using tissue microarray technique. Results: Immunohistochemical expression of EMSY protein was detected in 76% of primary breast tumors, localized in nuclear (18%), cytoplasmic (35%) or both cytoplasmic and nuclear sites (23%). Univariate analysis revealed a significant positive association between EMSY expression and lymph node metastasis (p value=0.045) and larger tumor size (p value=0.027), as well as a non-significant relation with increased risk of recurrence (p value=0.088), whereas no association with patients' survival (log rank test, p value=0.482), tumor grade or type was observed. Conclusions: Herein, we demonstrated for the first time the immunostaining pattern of EMSY protein in breast tumors. Our data imply that EMSY protein may have impact on clinicipathological parameters and could be considered as a potential target for breast cancer treatment.
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