Colon rectal cancer is one of the frequently diagnosed cancers worldwide. In recent times the drug discovery for colon cancer is challenging because of their speedy metastasis and morality of these patients. C-jun N-terminal kinase signaling pathway controls the cell cycle survival and apoptosis. Evidence has shown that JNK1 promotes the tumor progression in various types of cancers like colon cancer, breast cancer and lung cancer. Recent study has shown that inhibiting, JNK1 pathway is identified as one of the important cascades in drug discovery. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened ChEMBL dataset against JNK1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top compounds to be more specific with JNK1 comparing the affinity with JNK2 and JNK3.The drugs which exhibited higher binding were subjected to Conceptual - Density functional theory. The results showed mainly Entrectinib and Exatecan showed better binding to the target.
Kim, Jung-Min;Kim, Dong-Huan;Hayashi, Taro;Ishida, Yuji;Maeda, Mika;Sakura, Tatsuya
Journal of radiological science and technology
/
v.15
no.1
/
pp.65-78
/
1992
Routine chest radiography is generally imaged by high voltage technique but some radiological technologists use low voltage for imaging. High voltage is usually said between $120\;kV{\sim}140\;kV$. Some RTs like using heavy filtration but others seldom like using it. However which is better for use calcium tungustate film screen system or ortho system and high contrast film or wide latitude c-type film for the exculusive use of chest radiography. We could not make a decision which is ideal method for use. In my opinion any method is not always exellent for chest radiography. In my experiments that I had at Kaken hospital in Japan last year I expect to keep the balance between image quality and diagnostic range and to reduce radiation dose for patients. My experiments are as follows. 1. We have looked into system characteristics(speed and contrast) in accordance with kVp($80{\sim}140$) and added filter($no{\sim}1/16\;VL$) in three screen film systems(BX3+CRONEX4, SRO750+MGH, SRO750+MGL). 2. We have looked into skin dose and film dose with same D=1.8 lung field density in accordance with kVp($80{\sim}140$) and added filter($no{\sim}1/16\;VL$) in three screen film systems. 3. We have compared with the evaluation between correlation of physical image quality(MTF) and optical diagnostic capability. Result are follows. 1. Speed of BX3+CRONEX4 became higher in accodance with kVp and thickness of filter but speed of ortho system was not as like regular system. Thicker filter diminished the speed over 100 kV range in SRO750+MGL. In case of SRO750+MGH speed of 1/16VL filter was looked into lower than speed of 1/4VL filter. Sensitivity of ortho system depends on tube voltage and added filter. 2. Skin dose has been detected $225\;{\mu}Gy{\sim}66\;{\mu}Gy$ in BX3+CRONEX4 from 80 kV, no filter to 140 kV, 1/16VL filter. SRO750+MGH could reduce the patient dose $1/2{\sim}1/3$ level in comparison to that of BX3+CRONEX4. 3. The higher kV was the worse MTF became the thicker filter was the worse MTF became too. MTF of BX3+CRONEX4 was detected better than MTF of SRO750+MGH but SRO750+MGH's optical detectability of small lesion in lung field came out better than that of BX3+CRONEX4. Conclusion Recently routine chest radiography is generally imaged by high voltage but it seems to be there are some questions in using of film screen combination. In high voltage chest radiography the subject contrast will come down that means latitude become wider. In this case if we select the low contrast film screen system(C or L type) the film contrast will fall down extremly and detectability of small lesion will be deteriorated. Wide latitude C, L type film has a merit of high detectability on mediastinum. Furthermore high contrast film screen system has the advantage to keep the high contrast in low density region as like mediastinum and heart shadow. Therefore in low subject contrast high voltage chest radiography we would rather choose the high contrast film screen system(H type) I think. From a view point of patient dose detectability of mediastinum and lung field. The optimum technical facter was found out 120 kV, 1/16VL filter : BX3+CRONEX4, 140 kV, 1/4VL filter : SRO750+MGH, 100 kV, 1/4VL filter : SRO750+MGL.
Kim, Sang Hyun;Lee, Chang Hun;Sol, Mee Young;Song, Jin Mi;Lee, Jong Hyub;Lee, Min Ki;Kim, Jong Min
Tuberculosis and Respiratory Diseases
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v.58
no.5
/
pp.480-489
/
2005
Background : Dysregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. X-linked inhibitor of apoptosis (XIAP) is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. This study was designed to assess the pattern of expression and the prognostic value of XIAP in radically resected non-small cell lung carcinoma (NSCLC) patients. Method : The expression of XIAP and its relationship with clinicopathologic parameters (patient age, TNM stage, TNM-pT, TNM-pN, histologic type, VEGF expression, microvessel density, PCNA index) and overall survival were analysed with formalin-fixed, paraffin-embedded blocks from eighty cases of NSCLC. In addition, the apoptotic index (AI) was also assessed. Results : In a regard to histologic type, squamous cell carcinoma (SCC) showed XIAP expression in 91.3%(42/46) and adenocarcinoma (AC) in 61.8%(21/34). The difference was significant(p=0.001). There was no correlation between XIAP expression and other parameters. In the group of AC, XIAP expression showed the signifcant correlation with older age group ${\geq}58years$ and VEGF expression(p=0.028, p=0.014, respectively). The AI in the group with or without XIAP expression were $2.5{\pm}4.9%$ and $18.5{\pm}28.9%$, respectively(p=0.001). Both groups just aforementioned showed no significant difference in median survival time (42.5 months, 29.8 months, respectively). Conclusion : This study suggests that the XIAP expression in NSCLCs could have relation to inhibition of apoptosis, and show differential expression according to histologic type. However, its prognostic role during the progression of NSCLC needs to be further defined.
Radium is rock or soil of crust or uranium of building materials after radioactivity collapse process are created colorless and odorless inert gas that accrue well in sealed space like basement. It inflow to lung circulate respiratory organ and caused lung cancer because of deposition of lung or bronchial tubes. In this study, the air in the elementary school classroom nongdoeul tonkatsu place of measured values were compared using the calculated annual internal radiation exposure. La tonkatsu exposure measured in primary school classroom at least five schools when you close the windows in the average floor 0.56mSv 2 floors ground floor windows when opened 0.384mSv 048mSv 3 floors, 2 floor levels of the same three layers 0.31mSv 0.296mSv the human exposure to radon and radiation on the first floor of 3 floors above ground in a lot of exposure was moderate. When you close the window from the first floor up 0.384mSv 056mSv 3 floors with a minimum annual radiation exposure due to natural radiation in the 16 to 23.3 percent minimum 2.4mSv accounted for. When I opened the window to the maximum annual radiation exposure 2.4mSv 0.296mSv 0.31mSv least a minimum of 12.3 to 12.91% accounted for Results suggest that more than five chodeunghakgyoeun La tonkatsu domestic radon measurements conducted below regulatory requirements and internal exposure has also fall within the normal range. People The less the radiation exposure to the human body because it reduces the impact in the classroom in elementary school vent windows often reduced to the maximum radon concentration in the air, if called tonkatsu be able to reduce radiation exposure for the immune system is weak and elementary will be helpful to experiment more in the future for the school authorities called tonkatsu investigation is done to him if the action to establish a more secure school building facilities is thought would be helpful.
Park, So-Hyun;Jung, Won-Gyun;Rah, Jeong-Eun;Park, Sung-Yong;Suh, Tae-Suk
Progress in Medical Physics
/
v.21
no.4
/
pp.311-322
/
2010
In proton therapy, the analysis of secondary particles is important due to delivered dose outside the target volume and thus increased potential risk for the development of secondary cancer. The purpose of this study is to analyze the influence of secondary particles from proton beams on fluence and energy deposition in the presence of inhomogeneous material by using Geant4 simulation toolkit. The inhomogeneity was modeled with the condition that the adipose tissue, bone and lung equivalent slab with thickness of 2 cm were inserted at 30% (Plateau region) and 80% (Bragg peak region) dose points of maximum dose in Bragg curve. The energy of proton was varied with 100, 130, 160 and 190 MeV for energy dependency. The results for secondary particles were presented for the fluence and deposited energy of secondary particles at inhomogeneous condition. Our study demonstrates that the fluence of secondary particles is neither influenced insertion of inhomogeneties nor the energy of initial proton, while there is a little effect by material density. The deposited energy of secondary particles has a difference in the position placed inhomogeneous materials. In the Plateau region, deposited energy of secondary particles mostly depends on the density of inserted materials. Deposited energy in the Bragg region, in otherwise, is influenced by both density of inserted material and initial energy of proton beams. Our results suggest a possibility of prediction about the distribution of secondary particles within complex heterogeneity.
Inflammatory diseases, allergic and asthmatic disorders are caused by the mediator release from the activation of the phospholipase C (PLC), phospholipase D (PLD), methyltransferase or adenylate cyclase etc. during IgG or IgE cross-linking of high affinity receptors on mast cells or basophil surface. One important enzyme activated after IgG or IgE receptor cross-linking is PLD, the enzyme which converts phosphatidylcholine (PC) to phosphatidic acid (PA). Under the hypothesis that these may be some differences in mediator release according to the difference in PLD activity, we attempted to confirm the ginseng saponin effects on the PLD activity. We examined the PLD activity during the passively sensitized mast cell activation in the presence of single component of ginsenosides $(Rc,\;Rg_1,\;Rg_2,\;Rg_3)$. We also measured the amount of mediators (histamine and leukotrienes) released by stimulating with ovalbumin (OA) or calcium ionophore (CaI), Guinea Pig lung mast cells were purified using enzyme digestion, count current elutriation, and discontinuous Percoll density gradient. In purified mast cells prelabeled with $[^3H]$ arachidonic acid or $[^3H]$ palmitic acid, PLD activity was assessed more directly by the production of labeled PEt by PLD-mediated transphosphatidylation in the presence of ethanol. Histanine release was determined by Spectrophotofluorometry, and leukotrienes by radioimmunoassay. The PLD activity during the passively sensitized mast cell activation is increased up to $3{\sim}5times$. The PLD activity during the passively sensitized mast cell activation in the presence of all ginsenosides is decreased up to $4{\sim}11$ times. $Rg_l\;and\;Rg_2$ ginsenoside pretreatment decreased histamine and leukotrienes by 50% in the OA-induced or by 40% in the Cal-induced mast cell after passively sensitization. Rc pretreatment poorly decreased histamine but leukotrienes decreased by 70% in the OA-induced or by 35% in the Cal-induced mast cell. $Rg_3$ ginsenoside pretreatment increased histamine release without challenging OA or Cal but leukotrienes decreased. These observations indicate that single unit of ginsenosldes may be an important contributor to inhibit the release of histamine and leukotrienes in the guinea pig lung mast cells, that inhibits the PLD-mediated formation of DAG evoked by mast cell activation.
Kim, Young-Eun;Kim, Il-Wha;Moon, A-Ji;Kim, Nam-Kwen;Lee, Seung-Geun;Lee, Key-Sang
The Journal of Korean Medicine
/
v.31
no.5
/
pp.136-145
/
2010
Objectives: Electroacupuncture according to Voll (EAV) has been used to quantify the skin's electrical resistance and conductance over acupuncture points that, based on traditional Chinese medicine, represent the state of health or disease of the organ or tissue. However, it doesn't have enough objective data yet, so the purpose of this study was to aid in the use of EAV in analysis of cerebrovascular disease risk factors. Methods: This study researched the clinical statistics of 216 cases: cerebrovascular attack (CVA) group 43, control group 173. We measured control meridian points (CMP) on hands and feet and the cardio ankle vascular index (CAVI) which represents atherosclerosis severity, and sex, age, hypertension, diabetes, dyslipidemia, and obesity. The data were then analyzed by t-test, chi-square test and logistic regression. Results: Between the CVA and control groups, there were not statistically significant differences in CMP. However, logistic regression analysis of the presence of CVA, mean of CMP heart and lung, sex, age, DBP (diastolic blood pressure), and HDL (high density lipoprotein) cholesterol showed that the risk of CVA was 1.1 times increased with CMP heart (p=0.002), in men was 4.12 times higher than in women (p=0.001), 1.09 times higher with age (p=0.000), 1.04 times higher with DBP (p=0.045), while was lower by 0.924 times with CMP lung (p=0.005) and 0.957 times with HDL cholesterol (p=0.006). Conclusion: Although there were not clear evidence or mechanisms about EAV, this study showed that if we study EAV further, we may be able to apply EAV as an objective instrument of oriental medicine in cerebrovascular disease.
We previously reported that some components of ginsenosides decreased mediator releases evoked by the activation of mast cells with specific antigen-antibody reactions. This study aimed to assess the effects of ginsenosides ($Rb_2$, Re) on the mechanism of histamine release in the mast cell activation. We partially purified guinea pig lung mast cells by using enzyme digestion, the rough and the discontinuous percoll density gradient method. Mast cells were sensitized with $IgG_1$ and challenged with ovalbumin (OA). Histamine was assayed by fluorometric analyzer, leukotrienes by radioimmunoassay. Phospholipase D (PLD) activity was assessed more directly by the production of $[^3H]phosphatidylbutanol$ (PBut) which was produced by PLD-mediated transphosphatidylation in the presence of butanol. The amount of 1,2- diacylglycerol (DAG) were measured by the $[^3H]DAG$ labeled with $[^3H]palmitic$ acid or $[^3H]myristic$ acid. Pretreatment of $Rb_2$ ($300\;{\mu}g$) significantly decreased histamine release by 60%, but Re ($300\;{\mu}g$) increased histamine release by 34%. Leukotrienes release in $Rb_2$ was decreased by 40%, Re was not affected in the leukotrienes release during mast cell activations. An increasing PLD activity during mast cell activation was decreased by the dose-dependent manner in the pretreatment of $Rb_2$, but Re pretreatment facilitated the increased PLD activity during mast cell activation. The amount of DAG produced by phospholipase C (PLC) activity was decreased by $Rb_2$ pretreatment, but Re pretreatment was not affected. The amount of mass DAG was decreased by $Rb_2$ and Re pretreatment during mast cell activation. The data suggest that $Rb_2$ purified from Korean Red Ginseng Radix inhibits the DAG which is produced by the activation of mast cells with antigen-antibody reactions via both phosphatidylinositide-PLC and phosphatidylcholine-PLD systems, and then followed by the inhibition of histamine release. However, Re increases histamine release by stimulation of DAG production, which is mediated by phosphatidylcholine-PLD system rather than by phosphatidylinositide-PLC system, but inhibits the mass DAG production. Thus, it could be inferred that other mechanisms play a role in the increase of histamine release during mast cell activation.
Chickens from 10 to 32 weeks of age were inoculated with P. multocida via seven routs(intravenous, intramuscular, intraperitoneal, subcutaneous, into ear, intranasal, per oral). The development or distribution of disseminated intravascular coagulation (DIC) in multiple organs and the role of P. multocida endotoxins in disease process of fowl cholera were studied. The histological diagnosis of DIC was made by demonstration of fibrinous in arterioles, capillaries, venules and medium-sized blood vessels. The presence of fibrinous thrombi in blood vessels of multiple organs was observed in chickens which died within approximately 3 days post inoculation. Fibrinous thrombi were observed most frequently in the lung(90% of all cases with DIC) followed by liver (70%), kidney (60%), heart(20%), spleen, brain, pancreas, thymus and thyroid gland. The density of fibrinous thrombi (i.e. the number of thrombi per section) was greatest in the lung, followed by spleen, kidney, liver and heart. It is thought that the widespread hemorrhage of acute fowl cholera is also caused by P. multocida endotoxin which initiates DIC in variety of organs. The cause of death for the chickens after infection with acute fowl cholera is probably due to an endotoxin (septic) shock accompanied with DIC in multiple organs.
Background: CD44 is a glycoprotein on the cell surface which is involved in the cell-to-cell and cell-to-matrix interaction. The standard form, CD44s and multiple isoforms are determined by alternative splicing of 10 exons. Recent studies have suggested that CD44 may help invasion and metastasis of various epithelial tumors as well as activation of Iymphocytes and monocytes. The expression pattern of CD44 can be different according to tumor types. The author studied the expression pattern of CD44s and one of its variants, CD44v6 in non-small cell lung carcinomas (NSCLC) to find their implications on clinicopathologic aspects, including the survival of the patients. Material and Method: A total of 89 primary NSCLSs (48 squamous cell carcinomas, 33 adenocarcinomas, and 8 undifferentiated large cell carcinomas) were retrieved during the years between 1985 to 1994. The immunohisto chemistry was done by using monoclonal antibodies and the CD44 expression for angiogenesis was evaluated by counting the number of tumor microvessels. Result: Seventy-one (79.8$\%$) and 64 (71 .9$\%$) among 89 NSCLSs revealed the expression of CD44s and CD44v6, respectively. The expression of CD44s was well correlated with that of CD44v6 (r=0.710, p < 0.0001). The expression of CD44s and CD44v6 was associated with the histopathologic type of the NSCLCs, and squamous cell carcinoma was the type that showed the highest expression of CD44s and CD44v6 (p < 0.0001). Microvessel count was the highest in adenocarcinomas (113.6$\pm$69.7 on 200-fold magnification and 54.8$\pm$41.1 on 400-fold magnification) and correlated with the tumor size of TNM system (r=0.217, p=0.043) and CD44s expression (r=0.218, p=0.040). In adenocarcinoma, the patients with higher CD44s expression survived shorter than those with lower CD44s expression (p=0.0194) but there was no statistical significance on multivariate analysis(p=0.3298). Conclusion: The expression of both CD44s and CD44v6 may be associated with the squamous differentiation in non-small cell lung carcinomas. The relationship of CD44s expression with micro-vessel density of the tumor suggests an involvement of CD44s in tumor angiogenesis, which in turn would help tumor growth.
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