• Korean Journal of Clinical Laboratory Science
• /
• v.36 no.2
• /
• pp.178-184
• /
• 2004

This research focuses on the overall evaluation of tumor protein (p53) and cell growth marker (Ki-67) in their functions as carcinogenic factors in both a HPV-infected group and in a HPV-noninfected group with the precancerous dysplasia of uterine cervix. Histological grades were determined by the H&E staining and the expression level of p53 and Ki-67 were tested by the immunohistochemistry method. The results were as follows. Among the total of 66 cases, p53 (+) was observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values correlate with the increase of dysplasia intensity in HPV-noninfected group and showed significant correlation (p<0.05), but there were no significant difference from the HPV-infected group. Among a total of 66 cases, the mitotic index of Ki-67 (+) were observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values were significantly different against dysplasia intensity (p<0.05), but showed no significant difference from HPV infection. After cross comparing the statistical parameters of p53 and ki-67 in their significance, p53 was shown to be statistically significant with Ki-67 while there was no statistically significant difference with Ki-67 (p<0.05). Taken together, tumor protein (p53) and an index of Ki-67 observed in cervical dysplasia and in HPV related dysplasia of cervix uterine did not have any notable significance with HPV infection. The incidence rate of p53, however, had some significant correlation with dysplasia while Ki-67 had no particular statistical significance. As a result, p53 and Ki-67 can be considered as effective diagnostic markers in predicting the disease progression of dysplasia to cervical cancer.

• Journal of Life Science
• /
• v.21 no.3
• /
• pp.417-423
• /
• 2011

Thymosin ${\beta}4$ (TB-4) has been reported to play a key role in tumor growth, metastasis and angiogenesis. In addition, TB-4 induced the expression of vascular endothelial growth factor (VEGF) and stabilized the hypoxia-inducible factor (HIF)-$1{\alpha}$ in melanoma cells. Although the importance of thymosin ${\beta}4$ in angiogenesis and metastasis has been proven, there are few studies that show the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$. This study was conducted to analyze the relationship among these proteins in various tumors. Using tissue microarray analysis, we investigated the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$ in various tumors to identify the expression patterns and relationships of these proteins in certain tumors. TB-4 was highly expressed in osteosarcoma, colon adenocarcinoma, esophageal squamous cell carcinoma, kidney and urinary bladder transitional carcinoma, lung cancer, and liver cancer. HIF-$1{\alpha}$ was highly expressed in nasal cavity inverted papilloma, lung cancer, and esophageal squamous cell carcinoma. The expression patterns of TB-4 and HIF-$1{\alpha}$ were almost similar and co-localized. VEGF expression was high in the blood vessels in tumors, but usually not high in the tumors themselves. VEGF was moderately expressed in stomach cancer, liver angiosarcoma, gall bladder adenocarcinoma, and uterus endometrial adenocarcinoma. The expression patterns of VEGF shows similarities in certain tumors including stomach cancer, osteosarcoma, liposarcoma, lung cancer, liver cancer, gall bladder adenocarcinoma, esophageal squamous cell carcinoma, stomach cancer, colorectal carcinoma and renal cell carcinoma. These results suggest that the expression patterns of TB-4, HIF-$1{\alpha}$ and VEGF were co-localized and related to tumorigenesis and angiogenesis of certain tumors.

• YAKHAK HOEJI
• /
• v.44 no.4
• /
• pp.340-346
• /
• 2000

Cervical cancer is one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papilloma viruses (HPV types 16 and 18) and cervical cancer has been well known. An extract of natural products, named as Somatid, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. This Somatid inhibited the proliferation of human cervical cancer cell lines (C-33A, SiHa, CaSki) and HaCaT keratinocytes in a dose response manner, In vitro binding assay and ELISA showed that Somatid inhibited the in vitro biding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, Somatid inhibited the in vitro binding of E7 and Rb which is essential tumor suppressor for the control of cell cycle. The levels of mRNA for E6 and E7 were also decreased by Somatid. Our data suggested that Somatid inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus can be used as a putative anti-HPV agent for the treatment of cervical carcinomas caused by HPV.

• Korean Journal of Pharmacognosy
• /
• v.35 no.4 s.139
• /
• pp.368-374
• /
• 2004

Cervical cancer is one of the leading causes of female death. Viral oncoproteins E6 and E7 are selectively retained and expressed in carcinoma cells infected with HPV (Human papillomavirus) type 16. The HPV is cooperated in immotalization and transformation of primary keratinocyte. E6 and E7 oncoproteins interfere the functions of tumor suppressor proteins p53 and retinoblasoma protein (pRb), respectively. Among a lots of natural products, Artemisia scoparia Waldstein et Kitamura has inhibitory effects on the binding between E6 oncoprotein and tumor suppressor p53, or the binding between E6 and E6 associated protein (E6AP), an E3 ubiquitin-protein ligase. HPV oncoprotein inhibitors from Artemisia scoparia W. were isolated by solvent partition and column chromatography (Silica gel, RP-18) and the inhibitory compounds were finally purified by HPLC using an ELISA screening system based on the binding between E6 and E6AP. The aim of this study is to identify the structure of inhibitory compounds and to investigate whether these compounds have inhibitory effects on the functions of E6 oncoprotein. We investigated whether 3,5-di-O-caffeoylquinic acid (DCQA) extracted from Artemisia scoparia W. Could inhibit the function of E6 oncoprutein. DCQA inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53 and also inhibited the proliferation of human cervical cancer cell lines (SiHa and CaSKi) in a dose response manner. These results suggest that DCQA inhibited the function of E6 oncoprotein, suggesting that it can be used as a potential drug for the treatment of cervical cancers infected with HPV.

• Korean Journal of Ecology and Environment
• /
• v.36 no.1 s.102
• /
• pp.83-94
• /
• 2003

Concentrated releases of zinc into water usually results from discharges associated with industrial purpose. The released zinc into soil is corroded and released into water. In aquatic environment, exess zinc is toxic to the organisms and causes the growth inhibition and malformation of them as a heavy metal. In this study, excess zinc toxicity was tested by FETAX (frog embryo teratogenetic assay with Xenopus)as in vivo system. Xenopus embryos at st.9 were exposed to $100{\sim}900\;{\mu}M$ of zinc for 7 days and 81% of individuals were survived in 100 ${\mu}M$, and 25% were survived in 1000M of zinc solution. In external malformations, swelled belly and intestinal dysplasia were common, and all of tested individuals showed these malformations in 200 ${\mu}M$ or higher concentration of zinc. In 400 ${\mu}M$ or higher concentration, all of tested tadpoles showed faded heart. Also, hypo-pigmentation, lens hernia and loose digestive track were very frequently found in 100 ${\mu}M$ of zinc. The histological study with paraffin section of zinc treated tadpoles showed following abnormalities; regeneration of photoreceptor on retina, reduced vitreous chamber in eye, reduction of red blood cells in heart, abnormal liver, swelling of pronephric cell, muscle dysplasia and palatal papilloma. These abnormalities may be caused by the degeneration of mitochondria, inhibition of cell adhesion, and the formation of leghemoglobin by zinc due to the substitution of $Ca^{2+}$ by $Zn^{2+}$. The body length was reduced due to the excess zinc. From a statistical result, body lengths of 300 ${\mu}M$ or higher concentrative g개ups was significantly reduced comparing that of control group. Recently, many spontaneous malformations and reduction of amphibians are reported, From the results of present study, excess zinc mi호t be a factor of amphibian reduction, and the control of zinc discharges is very important.

• The Korean Journal of Nuclear Medicine
• /
• v.34 no.5
• /
• pp.371-380
• /
• 2000

Purpose: Thallim-201 ($^{201}Tl$) brain SPECT, which can represent cellular activity of brain lesions, may provide more useful information in differentiating between benign and malignant brain lesions more so than CT of MRI, that merely represents anatomic changes or breakdown of blood brain barrier. We used $^{201}Tl$ brain SPECT prospectively to evaluate the utility of $^{201}Tl$-indices as an indicator of benign or malig nant lesions. Materials and Methods: We studied 28 patients. There were 13 cases of benign lesions (3: nonspecific benign lesion, 3: meningioma, 2: low grade glioma, 1: tuberculoma, central neurocytoma, hemangioblastoma, radiation necrosis, and choroid plexus papilloma) and 15 cases of malignant lesions (6: glioblastoma multiforme, 5: anaplastic glioma, 2: medulloblastoma, 1: metastasis and lymphoma). In all patients, CT and/or MRI were obtained and then $^{201}Tl$ brain SPECT was obtained with measuring mean $^{201}Tl$ index and peak $^{201}Tl$ index. An unpaired t-test was performed to compare the $^{201}Tl$-indices and pathologic diagnoses to evaluate the utility of $^{201}Tl$-indices as all indicator of benign or malignant lesions. Results: There were no statistically significant difference in $^{201}Tl$-indices between benign and malignant brain lesion (p>0.05). Conclusion: These results demonstrated that we could not use $^{201}Tl$ indices on brain SPECT alone as an indicator of benign or malignant brain lesions.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.8 no.1
• /
• pp.31-40
• /
• 2005

Purpose: This study aimed to provide, as a basic material, the experiences of endoscopy in diagnosis and treatment of tumorous conditions in the upper gastrointestinal tract in children. Methods: The objects were 26 patients diagnosed as having tumorous conditions in the upper gastrointestinal tract among 1,283 patients who underwent upper gastrointestinal endoscopic examination at the Department of Pediatrics, Pusan National University Hospital, from January 1994 to July 2004 retrospectively. The characteristics of patients, the chief complaints for endoscopic examination, the sorts of tumors diagnosed, the endoscopic findings of tumors, and the treatment of tumors were analysed. Results: 1) Eleven male and fifteen female were included, whose mean age was $6.93{\pm}4.02years$. 2) The chief complaints for endoscopic examination were abdominal pain (80.7%), vomiting or nausea (30.8%), and gastrointestinal beeding (30.7%) in order. 3) Six cases of ectopic pancreas, five cases of sentinel polyp, three cases of papilloma and vallecular cyst, two cases of Brunner's gland hyperplasia and gastric submucosal tumor, one case of gastrointestinal stromal tumor, duodenal intramural hematoma, T cell lymphoma, lipoma, and Peutz-Jeghers syndrome were diagnosed by endoscopy with or without biopsy. 4) The location of tumors was in the pharynx (19.2%), esophagus (7.7%), gastro-esophageal junction (23.0%), stomach (30.7%) and duodeneum (26.9%). 5) The size of tumors was less than 10 mm in 53.8%, 10~20 mm in 26.9%, more than 20 mm 19.2%. 6) Treatments for tumors included resection by laser, surgical resection, endoscopic polypectomy with a forcep or snare, and observation 7) There was no significant complication. Conclusion: Various and not a few tumors were found in the upper gastrointestinal tract. The endoscopy was accurate, effective, and safe means for diagnosis and treatment of those lesions in children.

• Tuberculosis and Respiratory Diseases
• /
• v.53 no.3
• /
• pp.275-284
• /
• 2002

Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

• Proceedings of the KOR-BRONCHOESO Conference
• /
• 1977.06a
• /
• pp.6.2-7
• /
• 1977

Hoarseness, caused by any condition that interfers with normal phonatory function of larynx, is the most important symtom of the laryngeal disease. The air pollution is the serious social problom today due to irritation of the respiratory mucosa and secondary respiratory disease. It is significant to study whether, in resent years, the patients with complant of hoarseness has being increased or decreased, compare to past years. The authors report a statistical analysis on 400 cases with chief complain of horseness at the Department of Otolaryngology, Hanil Hospital during past 7 years from Jan. I, 1970 to Dec. 31, 1976. The results were as follows; 1) Among total out patients of 14, 731 who visited to the department of otolaryngology, the patients with hoarseness numbered to 400(2.7%). 2) Among total of 400 cases, male were 211 and female were 189. The incidence was slightly higher in male than female with ratio 1.1 to 1 in sex distribution. 3) The uderlying diseases causing hoarseness in order of frequency were Acute Laryngitis (158 cases, 39.5%), Chronic Laryngitis (103 cases, 27.3 %), Vccal Nodule (37 cases, 9.3%), Vocal cord paralysis (34 cases, 8.5%), Laryngeal Polyp (32 cases, 8%), Laryngeal Ca. (13 cases, 3.5%), and Laryngeal Tbc. (9 cases, 2.3%). Particulary, Laryngeal Ca., Laryngeal polyp and Laryngeal Papilloma were extremely high in male but the remainings were equally distributed in sex group distribution. 4) The highest incidence occurred in 3rd decade (113 cases, 28.5%), the next 4th and 2nd decade in the age group distribution. Acute and Chronic Laryngitis were widely distributed in age group distribution but the highest incidence was noted between 3rd and 4th decade (145 cases, 55.5%). The highest incidence was 3rd decade in Laryngeal polyp, 3rd and 4th decade in Vocal Nodule, 4th and 5th decade in Laryngeal Tbc. and Vocal cord paralysis and 5th decade in Laryngeal Ca. 5) The underlying disease causing hoarsness were evenly occurred in monthly distribution but relatively high incidence was observed between April and June (35.5%) compared to winter. 6) In durational distribution, the highest incidence was within 10 days (26%) from onset to consultation. 317 cases (80%) were visited to the clinic within 1 year.