• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8759-8763
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• 2014

Background: Non-hodgkin lymphoma (NHL) is a diverse group of disease encompassing divergent tumor types with contrasting clinical behaviors. We aimed to evaluate the usefulness of Ki67 index in segregating indolent from aggressive NHL and its association with clinical parameters. Materials and Methods: During a study period of 4.5 years, a total of 215 cases of lymphomas were diagnosed among of which 172 cases were NHL. Ki67 immunohistochemical staining was performed by the DAKO envision method. Average proportion of tumor cells stained was calculated to determine the proliferative index. Results: The mean age at diagnosis was 46.2 years +19.8 (3-81) with a male to female ratio of 1.5:1. Mean Ki67 index for indolent NHL included 23% for small cell, 25% for mantle cell, 28.5% for marginal zone and 34.6% for follicular lymphoma. On the other hand, mean Ki67 index for aggressive lymphomas were 66.4%, 66.9%, 80.3%, 83.3% and 94.4% for diffuse large B cell, T cell (NOS), anaplastic large cell, lymphoblastic and burkitts lymphoma respectively. No significant correlation was found between Ki67 index and other clinical parameters like age and extra nodal involvement. Conclusions: Ki67 index is a valuable IHC marker to distinguish indolent from aggressive lymphomas especially in small needle biopsies where exact typing may not be possible.

• Journal of Korean Neurosurgical Society
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• v.30 no.7
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• pp.861-869
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• 2001

Objective : In this study, we investigated the relationship between the histologic grading of meningiomas and proliferative potentials determined by the Ki-67, proliferating cell nuclear antigen(PCNA) and flow cytometry (FCM) with the aim of determining whether these potentials can be used as a parameter to the proliferative activity, in particular of atypical and malignant meningiomas. Methods : This study consisted of 47 meningiomas(6 malignant, 14 atypical, and random sampled 27 benign meningiomas). By immunohistochemical staining of Ki-67 and PCNA on formalin-fixed, paraffin-embedded sections, the anti-human rabbit polyclonal antibody against Ki-67 antigen and anti-PCNA monoclonal antibody(PC10) scores were counted. FCM was also performed on paraffin-embedded tissue using a selective staining technique for DNA. DNA ploidy, S-phase fraction, and proliferative index(PI)) were determined. Results : The results are summarized as follows ; 1) Proliferation rates as assessed by Ki-67 and PCNA closely correlated with the degree of anaplastic histologic features. 2) Proliferative potentials determined by FCM(S-phase fraction and PI) were not able to distinguish between benign and atypical/malignant meningiomas. 3) DNA ploidy was not a useful indicator of histologic grade in these tumors. 4) Proliferative potentials such as Ki-67 staining index(SI) and PCNA SI did not correlate with the ploidy pattern. 5) There was a linear correlation between Ki-67 SI and PCNA SI, but we could not find a correlation between Ki-67 SI and S-phase fraction or PI. Our results also did not show a statistically signficant correlation between PCNA SI and S-phse fraction or PI. Conclusions : We conclude that evaluation of the proliferative potentials with Ki-67 and PCNA is important as an additional factor for the prediction of malignancy in meningiomas. A dual study of Ki-67 and PCNA SIs on the same tissue might improve the accuracy with which the proliferative potential of a tumor can be predicted. We demonstrated that FCM in meningiomas is not valuable in predicting the behavior of these neoplasms, but we did observe a trend toward more malignancy with higher percent S-phase fraction and higher PI. Analysis of the S-phase fraction and PI might therefore be a useful tool to discriminate among histologic grades of meningiomas.

• IMMUNE NETWORK
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• v.2 no.2
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• pp.96-101
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• 2002

Background: Aerobic training can be defined as any physical exercise that increases the heart rate and enhances the body's intake of oxygen long enough to benefit the condition of body. Running, cycling, and swimming are examples of aerobic activities. This type of exercise optimises immune functions. Recently several experimental findings suggested that the regular swimming training increase immune response, but there have been very few reports which compare warm water exercise with cold water exercise in spleen lymphocytes. Methods: This study was designed to examine the effects of regular swimming training on Index, the number of lymphocytes, proliferative activity and production of reactive oxygen species (ROS) by splenocytes in BALB/c mice. Thirty six mice (6 week old) were performed 10 weeks of regular swimming training and they were divided into 6 groups according to the regular swimming training (CRG: control resting group, CEG: control exercise group, WRG: warm water trained resting group, WEG: warm water trained exercise group, CORG: cold water trained resting group, COEG: cold water exercise group). Analytical items were weight change, spleen index, the number of lymphocytes, proliferative activity and production of ROS. All data were expressed as mean and standard deviation by using SPSS package program (ver. 10.0). Results: The swimming training significantly decreased body weight, and increased spleen index, the number of lymphocytes and proliferative activity in the presence or absence of Con A and LPS added conditions. For the WRG and CORG, the quantity of ROS from splenocytes was higher than CRG, whereas, ROS by spleen lymphocytes was lower following 90 min acute exercise stress. Conclusion: These results suggested that the swimming training not only increases the number of lymphocytes but also increases proliferative activity by splenocytes in vitro.

• Journal of Korean Neurosurgical Society
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• v.40 no.6
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• pp.428-433
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• 2006

Objective : We investigated the pattern of glucose uptake in meningiomas using $^{18}F$-fluoro-2-deoxy-D-glucose[FDG] PET/CT. It was hypothesized that the degree of glucose uptake in each tumor could predict the histologic grade. Methods : In 19 patients with meningiomas, the Ki-67 proliferative index, standardized uptake values[SUV] of FDG uptake, tumor to contralateral gray matter ratio[TGR] of SUV, tumor size, edema grade, vascular endothelial growth factor[VEGF] expression, histopathologic grade and the blood supply pattern were assessed. Results : Of the 19 meningiomas, 8 were meningothelial, 1 fibrous, 2 transitional, 1 psammomatous, 2 angiomatous, and 5 atypical. The tumor proliferative index of Ki-67, tumor size, and peritumoral edema were larger in the histopathologic grade-2 meninigiomas than in the grade-1 meningioma group. There were no significant differences in SUV and TGR between two groups. Tumor size and peritumoral edema were significantly larger in VEGF-positive tumors than in negative tumors. Conventional angiography was performed in 12 patients. Dural supply was noted predominantly in 2 patients. Four patients had mainly pial cortical supply patterns. In tumors with more pial supply, VEGF was more frequently positive. There was a significant relation between SUV and Ki-67 and between SUV and peritumoral edema. Conclusion : We found FOG uptake in meningiomas is associated with proliferative potential, however, no clear limits of SUV and TGR can be set to distinguish between grade-1 and grade-2 meningiomas, which makes the assessment of malignancy grade using PET scan metabolic imaging difficult in individual cases.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.73-80
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• 2002

Purpose : Tumor growth in a given neoplasm is the net result of cell proliferation and cell loss, and apoptosis is the most significant component of continuous cell loss in most tumors. In this study, we examined non-Hodgkin's lymphoma (NHL, n=67) immunohistochemically for the presence of Bcl-2 oncoprotein and P53 protein and compared apoptotic indices (Als) and Ki-67 proliferative indices (percentages of Ki-67 positive cells). Materials and Methods : 67 patients with NHL were evaluated : 3 low-grade and 64 intermediate-grade. The phenotype was determined in 65 cases : 47 $(70\%)$ were B cell type and 18 $(27\%)$ were T ceil type. Als and Ki-67 proliferative indices were determined immunohistochemically and the overexpression of P53 and Bcl-2 protein were also evalutated. Results : The overexpressions of Bcl-2 protein and P53 protein were found in $40\%$ (26/65) and $31\%$ (20/65). The Al ranged from $0\%\;to\;15\%$ (mean 2.16, median 1.2). Cellular Bcl-2, which counteracts apoptosis, was significantly (p=0.005) associated with Als. Ki-67 proliferative indices ranged from $1\%\;to\;91\%$ (mean 55.4), and P53 was significantly (p=0.000) associated with Ki-67 proliferative indices. A positive correlation between Als and Ki-67 proliferative indices was revealed (p=0.012) in Bcl-2 positive patients. Conclusion : In NHL, we observed a correlation between Als and Bcl-2 expression, between Ki-67 proliferative indices and P53 expression, and between Als and Ki-67 proliferative indices in Bcl-2 positive patients. Our results suggest that cell apoptosis may be inseparable from cell proliferation during tumor growth.

• Korean Journal of Head & Neck Oncology
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• v.10 no.2
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• pp.200-205
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• 1994

Proliferating cell nuclear antgen(PCNA) plays an important role in DNA synthesis in nucleoli and is highly conserved non-histone nuclear protein composed of 261 amino acid. and is considered to correlated with the cells proliferative state, because it is synthesized particulary during the proliferative period of late Gland S-phase. Therefore, PCNA index meaningfully increases in the active or proliferative kinetic cells. By the use of recently developed monoclonal antibodies against PCNA, the immunohistochemical staining methods can make possible. These staining methods are the useful and productive one for ascertaining the cell's proliferating abillity. Moreover, immunohistochemical staining method with a antiPCNA antibody has particulrar advantages as follows. By means of these methods, we can stain the tissue that was already fixed in formalin or paraffin wax. We can see with naked eye that which cell is, where is differentiated through a microscope. Lastly, it maintains the whole tissue architecture and makes a search for the correlation. As we have seen above, the immunohistochemical staining methods for PCNA have been studied as an impotant factor that can find the cell proliferative kinetics in malignancy and biologic behavior of tumors. To investigate of the proliferative activity in thyroid nodule, Authors evaluated cell proliferative activity by immunostaing for PNCA in 45 pathologically confirmed solitary thyroid nodule. The results were as follows. 1) The benign nodules were 25 cases(Adenomatous Goiter: 20 cases, Follicular adenoma: 5 cases) and malignant nodules were 20 cases(Papillary Ca : 14 cases, Follicular Ca : 4 cases, Anaplastic Ca : 2 cases). 2) The Most prevalent age groups were 4th decade(11 cases), and the next group was 5th decade. 3) The average PCNA labelling indices were as follows. Adenomatous goiter(I6.9%), Follicular adenoma(37.6%), papillary Ca(26.3%), Follicular Ca(8.8%) and Anaplastic Ca(86.7%). There were no significant differences in benign(20.4) and malignant nodules (28.8%) except anaplastic Ca(p=0.3226). 4) When the average tumor size 2cm in papillary Ca, the PCNA indices were 26.0% (below 2cm) : 26.6% (above 2cm) (p=0.9642). The PCNA incidies were 23.9% (with lymphatic spread) : 28.7% (without lymphatic spread) (p=0.7056). There were no signlficant differences in the above cases. In conclusion, there were no significant differences in cell proliferative activity by staining for PCNA between benign and malignat nodules except anaplastic Ca.

• Tuberculosis and Respiratory Diseases
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• v.39 no.2
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• pp.150-158
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• 1992

Background: Although many authors have reported that the median survival time of surgically resected non-small cell lung cancer (NSCLC) was shorter in aneuploid than in diploid determined by flow cytometry, there are few reports about DNA ploidy using bronchial brushing material in all types of lung cancer. Method: The DNA ploidy test results of 109 consecutive patients with lung cancer were analyzed to find the relationship of DNA ploidy and anatomic or physiologic stage. And the differences of the response to various therapeutic modalities according to DNA ploidy were evaluated at least 8 weeks after the begining of the therapy. Results: Numbers of patients with DNA aneuploid pattern or high proliferative activity (S+G2M>22%) were not different among the various cell types of lung cancer. The relationship of DNA ploidy and anatomic or physiologic stage was not significant. However, NSCLC patients with high proliferative activity showed more advanced anatomic stage than those without that (p<0.05). The short-term response rate to therapy depended on the anatomic (p<0.005) or physiologic stages (p<0.05) in patients with NSCLC, and not on DNA ploidy or proliferative activity. Conclusion: DNA ploidy test using bronchial brushing material revealed that high proliferative activity means advanced anatomic stage, but it was not useful to predict the therapeutic response.

• Journal of Korean Neurosurgical Society
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• v.65 no.4
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• pp.558-571
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• 2022

Objective : The primary objective of this study was to identify predicting factors for local control (LC) of atypical meningioma, and we validated them with comparing the predicting factors for recurrence-free survival (RFS). We also examined the rate of LC after surgical resection with or without adjuvant treatment and RFS. Methods : Clinical and radiological records of patients with atypical meningiomas diagnosed at two institutes from January 2000 to December 2018 were reviewed retrospectively. Histopathological features were also reviewed using formalin-fixed paraffin embedded samples from pathological archives. Results : Of the 99 atypical meningiomas eligible for analysis, 36 (36.4%) recurred during the follow-up period (mean, 83.3 months; range, 12-232 months). The rate of 3-year LC and 5-year LC was 80.8% and 74.7%, respectively. The mean time-to-recurrence was 49.4 months (range, 12-150). The mean RFS was 149.3 months (95% confidence interval, 128.8-169.8 months) during the mean follow-up duration of 83.3 months (range, 12-232 months). Multivariate analysis using Cox proportional-hazard regression model showed that the extent of resection (hazard ratio [HR], 4.761; p=0.013), Ki67 index (HR, 8.541; p=0.004), mitotic index (HR, 3.275; p=0.044), and tumor size (HR, 3.228; p=0.041) were independently associated with LC. These factors were also statistically associated with RFS. In terms of radiotherapy after surgical resection, the recurrence was not prevented by immediate radiotherapy because of the strong effect of proliferative index on recurrence. Conclusion : The present study suggests that the extent of resection, proliferative index (according to Ki67 expression) and mitotic index, and tumor size are associated with recurrence of atypical meningiomas. However, our results should be further validated through prospective and randomized clinical trials to overcome the inborn bias of retrospective nature of the study design.

• Archives of Craniofacial Surgery
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• v.20 no.2
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• pp.139-143
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• 2019

Here we report a case of a focal atypical proliferative nodule (PN) arising from a congenital melanocytic nevus (CMN). Diagnosis was challenging because it had both benign and malignant clinical features. Unusual histopathology, immunohistochemistry, and intraoperative findings of this atypical PN are discussed. A 5-year-old girl was admitted for a congenital $5{\times}5cm$ sized scalp mass. This hemangioma-like soft mass showed biphasic characteristics such as a slow, gradual, and benign increase in size but worrisome dural invasion with cranial bone defect. We removed the scalp mass with clear resection margins. Interoperatively, we found that the cranial bone defect had already filled. Histopathologic examination showed CMN with focal atypical PN. The nodule showed sharp demarcation and cellular pleomorphism. However, in immunohistochemical study, Ki-67 proliferation index and expression levels of protein S-100 and Melan-A were very low. These were unusual findings of atypical PNs. Despite her worrisome preoperative radiologic features, she showed an indolent clinical course compatible with previously reported biologic behavior. The patient underwent follow-up inspection with magnetic resonance imaging every 6 months for up to 3 years. The nodule appeared to be stationary at the last visit.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.6
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• pp.777-785
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• 2010

The effect of two doses of different sources of zinc, inorganic (zinc oxide) or chelated (zinc glutamate chelate), on morphology and turn-over of the small intestine was assessed in early-weaned pigs orally challenged with enterotoxigenic E. coli K88 (ETEC). Sixty pigs weaned at 21 days were assigned to one of the following 5 diets: control (C); C+Zinc oxide (ZnO), either a 200 or a 2,500 mg Zn/kg dose; or C+zinc chelate with glutamic acid (Glu-Zn), either a 200 or a 2,500 mg Zn/kg dose. On d 2, the pigs were orally inoculated with 1.5 ml of a $10^{10}$ CFU/ml E. coli K88ac O148 suspension. Zinc supplements did not improve the performance of the pigs, but on d 5 faecal excretion of ETEC was reduced, and this was mainly due to high zinc doses (p<0.05). The villous height in the duodenum was improved by the zinc supplements (p<0.01) whatever the source and the level, whereas no effect was seen in the other two tracts of small intestine. The diet did not affect apoptosis and mitosis counts, while ETEC-susceptible pigs had more mitotic cells in the villi than non-susceptible pigs, particularly in the jejunum (p<0.01). The duodenum had fewer mitotic cells in the villi (p<0.05) and in the crypts (p<0.01) and more apoptotic cells in the villi. High dietary doses of ZnO or Zn-Glutamate improve villous height of the duodenum, but not of the jejunum and the ileum, and do not affect the epithelial proliferative activity and apoptotic index of intestinal mucosa of early-weaned pigs orally challenged with ETEC.