For many animals the centrosome consists of a pair of centrioles and surrounding pericentriolar materials (PCMs). PCMs have been known to play roles during cell division. It is known that centrioles are necessary to assemble centrosomal components. However, many types of oocytes undergo meiosis without centrioles. It is known that in nonmurine mammalian species, the sperm introduces an intact proximal centriole unlike sea urchin where two centrioles are introduced. In case of mouse sperm, the presence of centrosome is not clear In this study, a monoclonal antibody was developed to investigate centrosome during mouse germ cell and early embryo development. Results of immunostaining and Western blotting in CHO cells suggest that the monoclonal antibody recognizes a nuclear and centrosomal protein, thus called NCP. The NCP monoclonal antibody was used to screen a cDNA expression library prepared from 12.5 mouse brain to isolate NCP gene. Nucleotide size of NCP gene obtained from immunoscreening was about 5.5kb. It is determined that the NCP may be closely related with pericentriolar material -1 gene (Pcm-1) from the result of sequencing analysis. The molecular weight, 66kDa, calculated by known DNA sequence in database is consistent with that of detected from Western blotting using CHO cell lysates. Therefore, it is assumed that NCP may be alternative splicing form of Pcm-1 of which molecular weight is 228kDa. In mouse oocytes, NCP was distributed in nucleus as in CHO cells. It was shown that the NCP was localized around neck region, probably the centrosome in mouse neck region. Interestingly, dramatic change in distribution of NCP was also shown in male germ cell development. Finally, we observed the cellular distribution of NCP during early embryo development. NCP was detected in nucleus as well as centrosome foci. It is suggested that the centrioles reassembly we occurring in blastocysts and then affects the distribution of NCP.
Fifty seven patients with differentiated thyroid carcinoma were performed radioactive iodine-131 whole body scans after administration of diagnostic dose $(2\sim10\;mCi)$ and therapeutic dose $(30\sim150\;mCi)$ within three months. We evaluated the state of radioactive iodine-131 uptakes in whole body scan to detect correct metastasis of thyroid carcinoma. The results are as follows: 1) In 20 of the 57 patients (35%), the therapeutic scan showed the additional uptakes that were not seen in the diagnostic scan. 2) In 9 (64.2%) of the 14 patients who had been received the thyroid ablation theraphy with I-131 previously, new additional lesions were found in the therapeutic scan but only 11 (25%) of the 32 patients who had not been received the thyroid ablation theraphy disclosed new uptake lesions (p < 0.01). 3) The additional uptake lesions of therapeutic scan were significantly more common in the bony metastatic foci (55.7%) than other areas (p < 0.01). In 11 (55%) of 20 patients, additional uptake regions were anterior neck areas (thyroid bed or regional lymph node). We conclude that diagnostic scan with $2\sim5$ mCi I-131 is inadequate in evaluating residual iodine avid tissues of patients with thyroid carcinoma. Also post-theraphy I-131 whole body scan would be important to evaluate the correct staging and prognosis of thyroid carcinoma, and to follow-up patients.
The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor-&B (NF-κB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-κB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.
Proceedings of the Korean Society of Medical Physics Conference
/
2004.11a
/
pp.91-95
/
2004
Several MRI studies have reported reductions in temporal lobe volumes in Alzheimer's disease (AD). Measures have been usually obtained with regions-of-interest (ROI) drawn manually on selected medial and lateral portions of the temporal lobes, with variable choices of anatomical borders across different studies. We used the automated voxel-based morphometry (VBM) approach to investigate gray matter abnormalities over the entire extension of the temporal lobe in 10AD patients (MM5E 22)and 22 healthy controls. Foci of significantly reduced gray matter volume in AD patients were detected in both medial and lateral temporal regions, most significantly in the right and left posterior parahippocarmpal gyri. At a more flexible statistical threshold (P<0.01, uncorrected for multiple comparisons), circumscribed foci of significant gray matter reduction were also detected in the right amygdala/enthorinal cortex, the anterior and posterior borders of the superior temporal gyrus bilaterally, and the anterior portion of the left middle temporal gyrus. These VBM results confirm previous findings of temporal lobe atrophic changes in AD, and suggest that these abnormalities may be confined to specific sites within that lobe, rather than showing a widespread distribution.
The prevalence of primary liver carcinoma (PLC) is relatively high in Clonorchis sinensis (CS) endemic areas in Korea. PLC is a malignant tumor which can be subclassified into hepatocellular carcinoma and cholangiocarcinoma(CC). CC has been associated with clonorchiasis, but it is unclear whether clonorchiasis is associated with hepatocarcinogenesis. This experiment was designed to investigate relationships between clonorchiasis and early changes of hepatocarcinogenesis. Sixteen Sprague-Dawley rats weighing 150g were divided into two groups of 8 rats in each. All rats were fed choline-devoid(CD) diet for 4 weeks. Group 1 was given 0.015-0.020% diethylnitrosamine(DEN) as drinking water for 1 week. After one week, the rats were treated orally with 1% N-acetylaminofluorene(AAF) (5 times per week for 2 weeks). Group 2 was treated equally to group 1 except for CS infection during AAF treatment. Two rats in each group were sacrificed at 4th, 5th, 6th and 7th week of the experiment. Livers were stained with OV -6, proliferating cell nuclear antigen(PCNA) and GST-p. Results were as follows: Group 2 livers showed more oval cell proliferation in parenchyma and portal areas at the 4th, 5th, 6th and 7th weeks than did livers of group 1 (p<0.01). PCNA was mostly localized in oval cell populations, rather than hepatocytes and biliary cells. The ratio of oval cells to hepatocytes was much higher in group 2 than in group l(p<0.01 The ratio of hepatocytes to biliary cells is higher in group 2 than in group 1 (p<0.05), More group 2 acidophilic foci reacted to GST-p monoclonal antibody than in the noninfected group. It appeared that CS infection promoted potentially precancerous acidophilic foci and oval cell proliferation.
The purpose of this study was to evaluate the usefulness of whole body F-18 FDG PET scan for detecting postoperative recurrence of cancer. One hundred four cancer patients after operation were enrolled(14 brain tumor, 15 head and neck cancer, 23 gynecologic cancer, 16 gastrointestinal cancer, 16 thyroid cancer, and 20 other cancers). Besides conventional images(CI) including CT and MRI, F-18 FDG PET scan was obtained on ECAT EXACT 47 scanner(Siemens-CTI), beginning 60 minutes after injection of 370MBq(10mCi) of F-18 FDG. Regional scan was also obtained with emission image. Transmission images using Ge-68 were carried out for attenuation correction in both whole body and regional images. Findings of PET, and CI were confirmed by pathology or clinical follow up. The sensitivity and specificity of PET for detecting recurrence were 94% and 92%, respectively. Contrarily, the sensitivity and specificity of CI were 78% and 68%. CI results were negative and PET results were positive in 11 cases. The biopsy or clinical follow-up of those cases confirmed recurrence of tumor. False negative cases of CI were frequent in patients with gynecologic cancers. Also we measured the serum concentration of tumor markers in patients with gynecologic cancer(CA125), thyroid cancer(thyroglobulin), and colorectal cancer(CEA). The sensitivity and specificity of tumor markers were 71% and 84%, respectively, We conclude that F-18 FDG PET can be used valuably in detecting recurrent foci of a wide variety of malignancy compared to conventional diagnostic methods.
Selenium is an essential micronutrient for normal body function and functions as an essential constituent of selenoproteins. This study was carried out to investigate effect of selenium on the formation of colonic aberrant crypt foci (ACF) and tumor formation in a mouse model. Five-week old ICR mice were acclimated for one week and fed different selenium diet (0.02, 0.1, and 0.5 ppm) for 12 weeks. Animals received three intraperitoneal injections of azoxymethane (10 mg/kg B.W. in saline for 3 weeks), followed by 2% dextran sodium sulfate in the drinking water for a week. There were four experimental groups, including a normal control group and three different selenium levels groups. After sacrifice, the total numbers of aberrant crypt (AC) and ACF were measured in the colonic mucosa after methylene blue staining. The number of tumors was noted for tumor incidence. Liver selenium concentration was measured using ICP-AES method. Gutathione peroxidase (GPx) activity was determined using a GPx assay kit in the liver and colon. TUNEL assay and proliferating cell nuclear antigen (PCNA) staining were performed to examine the cell apoptosis and cell proliferation, respectively. Immunohistochemistry of $\beta$-catenin was also performed on the mucous membrane tissue of colon. The activity of GPx in the liver and colon was decreased in the selenium-deficient diet group while it was increased in the selenium-overloaded diet group. Apoptotic positive cells were increased in the selenium-overloaded diet group but decreased in the selenium-deficient diet group. PCNA staining area was decreased in the selenium-overloaded diet group. In addition, the $\beta$-catenin protein level in the selenium-deficient diet group was increased but decreased in the selenium-overloaded diet group. These results indicate that dietary selenium might exert a modulating effect on colon cancer by inhibiting the development of ACF and colon tumor formation in this mouse model.
Purpose: It was reported that CT-based measured attenuation correction (CT-MAC) produced radioactivity concentration values significantly higher than $^{68}Ge$-based segmented attenuation correction (Ge-SAC) in PET images. However, it was unknown whether the radioactivity concentration difference resulted from different sources (CT vs. Ge) or types (MAC vs. SAC) of attenuation correction (AC). We evaluated the influences of the source and type of AC on the radioactivity concentration differences between reconstructed PET images in normal subjects and patients. Material and Methods: Five normal subjects and 35 patients with a known or suspected cancer underwent $^{18}F-FDG$ PET/CT. In each subject, attenuation corrected PET images using OSEM algorithm (28 subsets, 2 iterations) were reconstructed by 4 methods: CT-MAC, CT-SAC, Ge-MAC, and Ge-SAC. The physiological uptake in normal subjects and pathological uptake in patients were quantitatively compared between the PET images according to the source and type of AC. Results: The SUVs of physiological uptake measured in CT-MAC PET images were significantly higher than other 3 differently corrected PET images. Maximum SUVs of the 145 foci with abnormal FDG uptake in CT-MAC images were significantly highest among 4 differently corrected PET images with a difference of 2.4% to 5.1% (p<0.001). The SUVs of pathological uptake in Ge-MAC images were significantly higher than those in CT-SAC and Ge-MAC PET images (p<0.001). Conclusion: Quantitative radioactivity values were highest in CT-MAC PET images. The adoption of MAC may make a more contribution than the adoption of CT attenuation map to such differences.
Purpose: To evaluate diagnostic sensitivity of nuclear imaging in the detection of residual thyroid tissue and metastatic lesion, we have compared neck scintigrams with Tc-99m pertechnetate (Tc-99m scan) and high dose I-131 iodide (I-131 scan) in patients with differentiated thyroid cancer. Subjects and Methods: One hundred thirty-five thyroidectomized patients for differentiated thyroid cancer were enrolled in this study. Twenty-three had a previous history of radioiodine therapy. Planar and pin-hole images of anterior neck with Tc-99m were acquired at 20 minutes after injection, followed by I-131 scan three days after high-dose radioiodine therapy within 7 days interval. Patients were asked to discontinue thyroid hormone replacement more than 4 weeks. Results: All subjects were in hypothyroid state. Seventy out of 135 patients (51.9%) showed concordant findings between Tc-99m and I-131 scans. I-131 scan showed higher number of uptake foci in all of 65 patients showing discordant finding. Tc-99m scan showed no thyroid bed uptake in 34 patients, whereas 23 of them (67.6%) showed bed uptake in I-131 scan. Tc-99m scan did not show any uptake in thyroid bed in 11 of 112 patients without previous history of radioiodine therapy, but 9 of them showed bed uptake in I-131 scan. Tc-99m scan showed no bed uptake in all of the 23 patients with previous history of radioiodine therapy, in contrast 14 of them (60.9%) showed bed uptake in I-131 scan. Conclusion: These results suggest that Tc-99m scan has poor detectability for residual thyroid tissue or metastatic lesion in thyroidectomized differentiated thyroid cancer patients, compared to high dose I-131 therapy scan. Tc-99m scan could not detect any remnant tissue or metastatic lesion in patients with previous history of radioiodine treatment, especially.
Salim, Elsayed I;Hegazi, Mona M;Kang, Jin Seok;Helmy, Hager M
Asian Pacific Journal of Cancer Prevention
/
v.17
no.3
/
pp.1023-1035
/
2016
The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemically-induced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.
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