• Journal of Microbiology and Biotechnology
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• v.11 no.5
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• pp.749-755
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• 2001

High Electromagnetic Field (EMF) with an intensity of 1 mT (Tesla) inhibited the growth of both human normal lung and immune T cell down to $20-30\%$, compared to that of an unexposed case. The human T-cells, Jurkat, were more severely affected by EMF than the human lung cells, which showed a relatively slow cell growth and substantial releas of $Ca^+2$ (3.5 times higher than the human T-cells). However, the growth of hepatoma carcinoma, Hep3B, was enhanced by twice that of an unexposed case. The EMF intensity and exposure time did not affect the growth of the cancer cells very much, while it significantly affected the growth of normal cells. Accordingly, it is possible that EMFs may play a role in the initiation of cancer. The EMFs disturbed the signal transduction and membrane systems, such that a five times higher amount of PKC-${\alpha}$ was released from the cell membrane than in the control. Extended exposure to EMFs, for more than 48 hours, also led to 1 $90\%$ necrotic death pattern from apoptotic cell death. Finally, EMF at an intensity of 1mT with a 24-T exposure promoted the differentiation of HL-60 cells to monocytes/macrophages, possibly causing potential acute leukemia.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.2
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• pp.110-122
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• 2005

Adenoid cystic carcinoma (ACC) of salivary glands has a protracted clinical course with perineural invasion, delayed onset of hematogenous metastasis, and poor responses to classical cytotoxic chemotherapic agents. Most deaths from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the dissemination of metastatic cells is important for the design of more effective therapy of salivary cancer. I determined in vitro expression of epidermal growth factor receptor (EGFR) and its downstream effectors and vascular endothelial growth factor receptor (VEGFR)-2 on a human salivary ACC cell line (ACC2). I also evaluated the expression of EGF and VEGF signaling molecules and metastasis-related proteins on human salivary ACC cells orthotopically growing in nude mice. In Western blot and immunohistochemical analyses, EGFR and VEGFR-2 were presented and phosphorylated in ACC2 cells. In human parotid cancer xenografts in nude mice, EGF and VEGF signaling molecules, IL-8, and MMP-9 were expressed at markedly higher levels than in normal parotid tissues. Moreover, tumor-associated endothelial cells of this orthotopic parotid tumor expressed phosphorylated VEGFR-2 and phosphorylated Akt, which is a cell-survival protein. These data show that those biomarkers can be molecular targets for therapy of salivary ACC, which has a propensity for delayed lung metastasis.

• Korean Journal of Veterinary Research
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• v.27 no.2
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• pp.269-275
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• 1987

Radiation-induced life shortening, carcinogenesis and other pathological changes were investigated in NIH(GP) mice after $^{60}Co-{\gamma}$ ray irradiation(100~700rads). The results were summarized as follows: 1. There were little difference in body weights, hematological examination and other clinical findings between normal and irradiated groups. 2. Mean survival time of the mice after irradiation were decreased dose-dependently. 3. Main gross findings of the mice irradiated were appeared as enlargement of spleen, thymus and lymph nodes, tumorous nodules of lung and cyst of ovary. Especially, enlargement of thymus was promineort in high dose group. 4. Microscopically, there were various findings including myeloid leukemia, thymic lymphoma, lung adenoma, adenosquamous cell carcinoma of pancreas, pneumonia and other pathological changes. Especially thymic lymphoma was highly frequent in the 700 rads group.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4347-4351
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• 2015

Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens. Materials and Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). Results: There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05). Conclusions: Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.111-116
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• 2013

Background: Cigarette smoking is the major risk factor for development of lung cancer. Identification of effects of tobacco on airway gene expression may provide insight into the causes. This research aimed to compare gene expression of large airway epithelium cells in normal smokers (n=13) and non-smokers (n=9) in order to find genes which discriminate the two groups and assess cigarette smoking effects on large airway epithelium cells.Materials and Methods: Genes discriminating smokers from non-smokers were identified by applying a neural network clustering method, growing self-organizing maps (GSOM), to microarray data according to class discrimination scores. An index was computed based on differentiation between each mean of gene expression in the two groups. This clustering approach provided the possibility of comparing thousands of genes simultaneously. Results: The applied approach compared the mean of 7,129 genes in smokers and non-smokers simultaneously and classified the genes of large airway epithelium cells which had differently expressed in smokers comparing with non-smokers. Seven genes were identified which had the highest different expression in smokers compared with the non-smokers group: NQO1, H19, ALDH3A1, AKR1C1, ABHD2, GPX2 and ADH7. Most (NQO1, ALDH3A1, AKR1C1, H19 and GPX2) are known to be clinically notable in lung cancer studies. Furthermore, statistical discriminate analysis showed that these genes could classify samples in smokers and non-smokers correctly with 100% accuracy. With the performed GSOM map, other nodes with high average discriminate scores included genes with alterations strongly related to the lung cancer such as AKR1C3, CYP1B1, UCHL1 and AKR1B10. Conclusions: This clustering by comparing expression of thousands of genes at the same time revealed alteration in normal smokers. Most of the identified genes were strongly relevant to lung cancer in the existing literature. The genes may be utilized to identify smokers with increased risk for lung cancer. A large sample study is now recommended to determine relations between the genes ABHD2 and ADH7 and smoking.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.347-355
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• 1999

Background: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate($PIP_2$) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate($IP_3$) and diacylglycerol. PLC-${\gamma}1$, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-yl have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by $IP_3$, phosphatidic acid, etc. Very recently, another PLC-${\gamma}1$ activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-${\gamma}1$ activator, AHNAK, in lung cancer specimens and their paired normal. Methods: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract Immunohistochemical stain was performed with primary antibody against AHNAK protein. Results: Twenty-two among twenty-eight lung cancer tissues showed overexpression of AHNAK protein (eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomas). The resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot Conclusion: The overexpression of PLC-${\gamma}1$ activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-${\gamma}1$ act in concerted manner in carcinogenesis.

• Journal of Pharmacopuncture
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• v.5 no.1 s.8
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• pp.27-42
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• 2002

Objective: The purpose of this study was to investigate the acute and subacute toxicity and sarcoma- 180 anti-cancer effects of Herbal acupuncture with Triglii Semen in mice and rats. Method: Balble mice were injected intraperitoneally with Triglii semen Herbal acupuncture for $LD_{50}$ and acute toxicity test. Sprague Dawley rats were injected intraperitoneally with Triglii semen Herbal acupuncture for subacute toxicity test. The Triglii semen Herbal acupuncture was injected on Chung-wan(CV12) of mice with S-180 cancer cell line. Results: 1. In acute toxicity test, the $LD_{50}$ value was $7.49{\times}10^3$ml, 0.30ml/kg.2. The body weights of mice treated with Triglii semen Herbal acupuncture increased during the acute toxicity test. 3. In acute toxicity test of serum biochenrical values of mice, total protein was decreased in treatment groups I, 2 and 3, albunrin was decreased in treatment groups 2 and 3 compared to the control group. GOT was increased in treatment group I and Alk. Phosphatase was increased in treatment groups 1,2 and 3 compared to the normal group(p<0.05). 4.ln subacute toxicity test, severe tissue injury was found in lung and liver. 5. In subacute toxicity test, the body weight was decreased in treatment groups I and 2 compared to the normal group and the weight of liver. lung and kidney were increased in treatment groups 1, 2 and 3 compared to the normal group.(p<0.05) 6. In subacute toxicity test, RBC, HGB and HCT were decreased in treatment groups 1 and 2 compared to the normal group. MCV was increased in treatment group1 compared to the normal group, MCH was increased in treatment groups 1 and 2 compared to the control group in complete blood count test.(p<0.05) 7. In subacute toxicity test, total protein was decreased in treatment groups 1 and 2 compared to the nonnal group, BUN was increased in treatment groups 1 and 2 compared to the nonnal group, creatinine and uric acid were decreased in treatment groups 1 and 2 compared to the normal group, glucose was increased in treatment group 2 compared to the nonnal group, triglycelide was decreased in treatment groups I and 2 compared to the normal group, total cholesterol was increased in treatment groups 1 and 2 compared to the control group. GOT was decreased in treatment group 2 compared to the normal and control group, AIk. Phosphatase was increased in treatment group 1 compared to the normal and control group.(p<0.05) 8. Median survival time was 17days in treatment group 2 for S- 180 cancer cell treated with Triglii semen Herbal acupuncture. 9. Natural killer cell activity was insignificant for S-180 cell treated with Triglii semen Herbal acupuncture.(p<0.05) 10. lnterieukin-2 productivity was decreased for S-180 cell treated with Triglii semen Herbal acupuncture compared to the normal and control group.(p<0.05) Conclusion: According to the results, we can conclude Herbal-acupuncture with Triglii semen caused toxicity, and caused no effects in S-180 cancer cell.

• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.395-403
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• 1993

Background: The cell cycle is composed of a series of steps which can be negatively or positively regulated by various factors. Alteration or inactivation of p53 by mutations, or by its interactions with oncogene products of DNA tumor viruses, can lead to cancer. Mutations of the p53 gene occur frequently in human primary lung cancers and the wild-type p 53 allele is often concomitantly deleted. These suggest that deprivation of suppressive role of the wild-type p53 may ensure tumor cell growth presumable by the mutant p53 gene. Methods: In an attempt to investigate this hypothesis, a mutant p53 gene was immunohistochemically demonstrated in the formalin-fixed paraffin-embedded tissue sections of lung cancers by using a monoclonal antibody p53 (Ab-3 and clone DO7). Results: The expression of p53 (DO7) was found in all four normal lung tissues, four small cell carcinomas, and four non small cell carcinomas in histologic types of lung cancer. In the six normal lung tissues the expressions of p53 (Ab-3) were not found. Contrarily, the expression of p53 (Ab-3) was found in the nuclei of lung cancers among fifteen (46.9%) of thirty-two cases studied. The expression of p53 (Ab-3) was disclosed in three case (37.5%) of eight small cell carcinomas and twelve cases (50.0%) of twenty-four non small cell carcinomas in histologic types of lung cancer. Conclusion: These findings suggest that expression of the mutant p53 is related to the one of events in the pathogenesis of human lung cancer and the role of the other oncogenes might be also related to the development of lung cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.551-557
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• 2015

Background: Differentiating morphologic features based on hematoxylin-eosin (HE) staining is the most common method to classify pathological subtypes of non-small-cell lung cancer (NSCLC). However, its accuracy and inter-observer reproducibility in pathological diagnosis of poorly differentiated NSCLC remained to be improved. Materials and Methods: We attempted to explore the role of immunohistochemistry (IHC) staining in diagnosing pulmonary squamous cell carcinoma (SQCC) with poorly differentiated features by HE staining or with elevated serum adenocarcinoma-specific tumor markers (AD-TMs). We also compared the difference of epidermal growth factor receptor (EGFR) mutation rate between patients with confirmed SQCC and those with revised pathological subtype. Logistic regression analyses were used to test the association between different factors and diagnostic accuracy. Results: A total of 132 patients who met the eligible criteria and had adequate specimens for IHC confirmation were included. Pathological revised cases in poor differentiated subgroup, biopsy samples and high-level AD-TMs cases were more than those with high/moderate differentiation, surgical specimens and normal-level AD-TMs. Moreover, biopsy sample was a significant factor decreasing diagnostic accuracy of pathological subtype (OR, 4.037; 95% CI 1.446-11.267, p=0.008). Additionally, EGFR mutation rate was higher in patients with pathological diagnostic changes than those with confirmed SQCC (16.7% vs 4.4%, p=0.157). Conclusions: Diagnosis based on HE staining only might cause pathological misinterpretation in NSCLC patients with poor differentiation or high-level AD-TMs, especially those with biopsy samples. HE staining and IHC should be combined as pathological diagnostic standard. The occurrence of EGFR mutations in pulmonary SQCC might be overestimated.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10387-10391
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• 2015

Background: This study aimed to identify any association between the p73 gene G4C14-to-A4T14 polymorphism and risk of non-small cell lung cancer (NSCLC) in the south of China. Materials and Methods: We genotyped the p73 gene polymorphism of peripheral blood DNA from 168 patients with NSCLC and 195 normal controls using HRM (high resolution melting) and PCR-CTPP (polymerase chain reaction with confronting two-pair primers). Results: The results of genotyping by HRM and PCR-CTPP were consistent with direct sequencing, the p73 genotype distribution in 168 lung cancer patients being as follows: GC/GC 101 cases (60.1%), GC/AT 59 cases (35.1%), AT/AT 8 cases (4.8%). The carriers of AT/AT genotype had a significantly reduced risk of NSCLC (OR=0.370; 95%CI: 0.170-0.806; p=0.010) as compared with non-carriers. However, we found no relations between p73 genotypes and histological type (p=0.798, $x^2=0.452$), tumor stage (p=0.806, $x^2=0.806$), or lymph node metastasis (p=0.578, $x^2=1.098$). Conclusions: Our findings suggest that the p73 G4C14-to-A4T14 polymorphism may be a modifier of NSCLC susceptibility in the Chinese population.