Kim, Ju-Ock;Jung, Sung-Soo;Park, Hee-Sun;Kim, Myoung-Hoon;Kim, Sun-Young;Lee, Young-Ha
Tuberculosis and Respiratory Diseases
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제52권4호
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pp.317-329
/
2002
Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.
Adult respiratory distress syndrome (ARDS) is of particular interest because of its severity of the associated lung injury and its high mortality. However, the pathophysiologies of ARDS in infant and childhood groups are still not well clarified inspite of many previous investigations. To investigate the time course of pathophysiology of ARDS in infant and childhood groups, this study was designed with experimental endotoxin-induced ARDS model using young rabbits (8 week-old). Material and Method: Rabbits were divided into the control group (n=8) and the endotoxin-treated group (n=32). The endotoxin group was subdivided into 4 groups by the sampling times as 3, 6, 12 and 24 hr-groups (G- $E_{3,6,12,24,}$ each n=8). The experimental ARDS was made by a bolus injection of endotoxin (Escherichia coli serotype 055 : B5, 0.50 mg/kg) via rabbit ear vein. For evaluation of the hematologic and inflammatory markers, and superoxide dismutase (SOD) concentrations, the blood samples were taken from the heart. The bronchoalveolar lavage fluid (BALF) were obtained for analysis of the leukocytes and protein concentration. With biopsy of the lung, histopathologic changes of the lung were also evaluated. Result: In the endotoxin groups, significant leukopenia (owing to pancytopenia) occurred in 3 and 6-hr groups, which was followed by significant leukocytosis (owing to neutrophilia) in the 12 and 24-hr groups (p<0.05). Serum levels of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1 $\beta$ (IL-1 $\beta$) in the endotoxin groups were higher than those of control group (p<0.05). Serum levels of superoxide dismutase (SOD) of G- $E_{3}$ and G- $E_{6}$ were higher than those of control group, whereas those of G- $E_{12}$ were lower than those of control groups (p<0.05). Total leukocyte counts and protein con-centrations in BALF were significantly elevated in the endotoxin groups compared to the control group (p < 0.05). The hemorrhagic pattern of BALF showed occurred in the endotoxin groups. The endotoxin groups (in G- $E_{6}$) had severe infiltration of inflammatory cells (lymphocyte and monocyte) in the pulmonary interstitium and parenchyma, migrations of neutrophil and eosinophil into alveolar spaces and interstitial widening, which are the evidences of acute lung injury. In the endotoxin groups, there were significant positive correlations between the BALF findings and the immunologic markers (TNF-$\alpha$, IL-1$\beta$, SOD) (p<0.05). Conclusion: Severe acute lung injury occurred in all the endotoxin-treated rabbits. The pathophysiologic findings were so progressive until 6-hr by time dependant pattern, and then recovered slowly, Variable hematologic, immuno-logic, and pathologic factors were well correlated in the development and progression of endoxin-induced lung injury. The pathophysiologic responses were sensitive and rapid in young rabbit Young rabbit seemed to be a useful experimental animal model for infant and childhood groups.roups.
Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.
Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.
Journal of the Korean Society of Food Science and Nutrition
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제40권12호
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pp.1662-1667
/
2011
Anthocyanins belong to a group of flavonoid compounds and are well known for their various health beneficial effects, which include antioxidative activities. Among them, the major anthocyanins isolated from seed coat of black soybean (Glycine max L.) were previously characterized as glycosides containing glucopyranose. Asthma is an allergic disease that is strongly associated with various immune cells, including basophils and mast cells. Eosinophils, basophils, and mast cells play important roles in allergic asthma through the release of inflammatory mediators such as asthma-specific T-helper 2 (Th2) cytokines and subsequent amplification of asthma symptoms via degranulation. Rat basophilic leukemia RBL-2H3 cells are the most common in vitro models for evaluating allergic reactions. In this study, we examined the effects of anthocyanin from seed coat of black soybean on antigen-stimulated degranulation and Th2 cytokine production in RBL-2H3 cells. Cell degranulation was evaluated by measuring the release of ${\beta}$-hexosaminidase. ${\beta}$-Hexosaminidase release and Th2 cytokine production in RBL-2H3 cells was much higher upon stimulation with IgE-antigen complex than those in untreated control cells. Anthocyanins significantly suppressed IgE-antigen complex-induced degranulation of RBL-2H3 cells and inhibited IgE-antigen complex-mediated interleukin (IL)-4, IL-13, and tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) production in RBL-2H3 cells. These findings suggest that anthocyanins from seed coat of black soybean effectively inhibit allergic reactions and may have beneficial effects against allergic asthma.
Park, Ja Ram;Kim, Min Su;Kim, Jeong Mi;Chung, Hyeon Suk;Lee, Chung Hwan;Back, Geum Mun
The Journal of Korean Society for Radiation Therapy
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제29권2호
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pp.9-17
/
2017
Purpose: The tissue description and electron density indicated by the Computed Tomography(CT) number (also known as Hounsfield Unit) in radiotherapy are important in ensuring the accuracy of CT-based computerized radiotherapy planning. The internal metal implants, however, not only reduce the accuracy of CT number but also introduce uncertainty into tissue description, leading to development of many clinical algorithms for reducing metal artifacts. The purpose of this study was, therefore, to investigate the accuracy and the clinical applicability by analyzing date from SMART MAR (GE) used in our institution. Methode: and material: For assessment of images, the original images were obtained after forming ROIs with identical volumes by using CIRS ED phantom and inserting rods of six tissues and then non-SMART MAR and SMART MAR images were obtained and compared in terms of CT number and SD value. For determination of the difference in dose by the changes in CT number due to metal artifacts, the original images were obtained by forming PTV at two sites of CIRS ED phantom CT images with Computerized Treatment Planning (CTP system), the identical treatment plans were established for non-SMART MAR and SMART MAR images by obtaining unilateral and bilateral titanium insertion images, and mean doses, Homogeneity Index(HI), and Conformity Index(CI) for both PTVs were compared. The absorbed doses at both sites were measured by calculating the dose conversion constant (cCy/nC) from ylinder acrylic phantom, 0.125cc ionchamber, and electrometer and obtaining non-SMART MAR and SMART MAR images from images resulting from insertions of unilateral and bilateral titanium rods, and compared with point doses from CTP. Result: The results of image assessment showed that the CT number of SMART MAR images compared to those of non-SMART MAR images were more close to those of original images, and the SD decreased more in SMART compared to non-SMART ones. The results of dose determinations showed that the mean doses, HI and CI of non-SMART MAR images compared to those of SMART MAR images were more close to those of original images, however the differences did not reach statistical significance. The results of absorbed dose measurement showed that the difference between actual absorbed dose and point dose on CTP in absorbed dose were 2.69 and 3.63 % in non-SMRT MAR images, however decreased to 0.56 and 0.68 %, respectively in SMART MAR images. Conclusion: The application of SMART MAR in CT images from patients with metal implants improved quality of images, being demonstrated by improvement in accuracy of CT number and decrease in SD, therefore it is considered that this method is useful in dose calculation and forming contour between tumor and normal tissues.
Kwon, Da Hye;Choi, Eun Ok;Hwang, Hye-Jin;Kim, Kook Jin;Hong, Su Hyun;Lee, Dong Hee;Choi, Yung Hyun
Journal of Life Science
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제28권2호
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pp.207-215
/
2018
Inflammatory response and oxidative stress play critical roles in the development and progression of many human diseases. Therefore, a great deal of attention has been focused on finding functional materials that can control inflammation and oxidative stress simultaneously. The purpose of this study was to investigate the effects of Socheongja and Socheong 2, Korean black seed coat soybean varieties, on the inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Our data indicated that the extracts of Socheongja (SCJ) and Socheong 2 (SC2) significantly suppressed LPS-induced production of nitrite oxide (NO) and prostaglandin $E_2$, key pro-inflammatory mediators, by suppressing the expression of inducible NO synthase and cyclooxygenase-2. It was also found that SCJ and SC2 reduced the LPS-induced secretion of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$, which was concomitant with a decrease in the protein levels. In addition, SCJ and SC2 markedly diminished LPS-stimulated intracellular reactive oxygen species accumulation, and effectively enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression. Furthermore, LPS-induced activation of mitogen-activated protein kinases (MAPKs) was abrogated by SCJ and SC2. Taken together, these data suggest that SCJ and SC2 may offer protective roles against LPS-induced inflammatory and oxidative responses in RAW 264.7 macrophages through attenuating MAPKs pathway, and these effects are mediated, at least in part, through activating Nrf2/HO-1 pathway. Given these results, we propose that SCJ and SC2 have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by over-activation of macrophages.
Purpose: To suggest the optimal radiation fields after a surgical resection based on a nationwide survey on the principles of radiotherapy for rectal cancer in the Korean Patterns on Care Study. Materials and method: A consensus committee, composed of radiation oncologists from 18 hospitals in Seoul Metropolitan area, developed a survey format to analyze radiation oncologist's treatment principles for rectal cancer after a surgical resection. The survey format included 19 questions on the principles of defining field margins, and was sent to the radiation oncologists in charge of gastrointestinal malignancies in all korean hospitals (48 hospitals). Thirty three ($69\%$) oncologists replied. On the basis of the replies and literature review, the committee developed guidelines for the optimal radiation fields nor rectal cancer Results: The following guidelines were developed: superior border between the lower tip on the L5 vertebral body and upper sacroiliac joint; inferior border $2\~3$ cm distal to the anastomosis in patient whose sphincter was saved, and $2\~3$ cm distal to the perineal scar In patients whose anal sphincter was sacrificed; anterior margin at the posterior lip of the symphysis pubis or $2\~3$ cm anterior to the vertebral body, to include the internal iliac lymph node and posterior margin $1.5\~2$ cm posterior to the anterior surface of the surface, to include the presacral space with enough margin. Comparison with the guidelines, the replies on the superior margin coincided in 23 cases ($70\%$), the inferior margin after sphincter saving surgery in 13 ($39\%$), the inferior margin after adbominoperineal resection in 32 ($97\%$), the lateral margin in 32 ($97\%$), the posterior margins in 32 ($97\%$) and the anterior margin in 16 ($45\%$). Conclusion: These recommendations should be tailored to each patient according to the clinical characteristics such as tumor location, pathological and operative findings, for the optimal treatment. The adequacy of these guidelines should be proved be following the Korean Patterns of Care Study.
Journal of the korean academy of Pediatric Dentistry
/
제26권3호
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pp.499-506
/
1999
The odontoma is relatively a common benign odontogenic tumor and caused by overgrowth of odontogenic tissues. The recent classification by World Health Organization divides odontoma into 2 groups such as compound odontoma and complex odontoma. Compound odontoma comprises dental tissues, resembling the morphology of a tooth and has predilection for the anterior maxilla. In contrast, complex odontoma has unorganized mass, not resembling the normal tooth and has predilection for the posterior mandible. The etiology of odontoma is unknown and almost asymptomatic. So, it usually is found in routine radiographic examination, and most common presenting symptom is impacted or unerupted permanent teeth and retained primary teeth. It can occurs almost anywhere in jaws. It is desirable that odontoma should be removed by surgical enucleation including follicle and surrounding soft tissues. Considering the age and behavioral cooperation of patient, the development of permanent dentition, the location of odontoma in jaw, the need for the concomitant operative dentistry, operation is performed in outpatient department with/without sedation or under general anesthesia with endotracheal intubation. In this case report, 2 patients with compound odontoma were treated by surgical enucleation including follicle and surrounding soft tissues. One patient, about 5 years old, was treated under general anesthesia and concomitant operative dentistry was performed. The other patient, about 11 years old, was treated under local anesthesia in outpatient department. In 2 cases, after 4 months, surgical defects were filled with new bone and normalization of eruption path of impacted permanent teeth was observed.
The respiratory gating radiation therapy which Irradiates only in the stable respiratory period with analyzing the periodic motion of a reflective marker on the patient's abdomen has been applied to the precise radiation treatment in order to minimize the effect of organ motion induced by the respiration. This respiratory gating system establishes irradiation region using the amplitude-based or phase-based method. Although phase-based method Is preferred because of the stability in the real treatment conditions, it has some limits to explain the exact correlation between the marker motion and organ motion. Even when the variation of amplitude which can introduce target motion considered as an error is produced, the phase-based method has the possibility to irradiate including the error positions. In this study, the error analysis program was developed for the verification of the tumor position's variation correlated with the variation of marker's amplitude which can be occurred during a phase-based respiratory sating treatment. The analysis program was tested with a virtual treatment record file and with a record file using moving phantom which were modified considering the irregular amplitude's variation simulating the real clinical situations. In both cases, accurate discrimination of error points and error calculation were produced. When the treatment record files of a real patient were analyzed with the program, the accurate recognition and calculation of the error points were also verified. The analysis program developed in this study will be applied as a useful tool for the analysis of errors due to the irregular variation of patients' respiration during the phase-base respiratory gating radiation treatment.
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