The Journal of the Korean Society for Microbiology
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v.19
no.1
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pp.85-108
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1984
In order to study the relationship between resistance of tumor cells to anticancer drugs and immunologic cytotoxicity and their chromosome number, a line of cancer cells (NS-1) was exposed to BCNU and CCNU in vitro. Characteristics of the distribution of chromosome number of the survived cells were then comparatively analyzed. Effect of immune mediated cytotoxicity, i.e. complement and cell-mediated cytotoxicity, on the ploidy characteristics was observed in the same way. NS-1 cells were found to be a population of neoplastic cells of heterogeneity having 5 to 115 chromosomes per cell in metaphase. The majority of the cells were belong to the class of chromosome number 56 to 60 which were considered as the stem cell line. Dramatic changes in the distribution of chromosome number following drug treatment were not observed. However the range of chromosome distribution was slightly changed. Characteristics of chromosomal distribution of drug treated cells were not significantly varied by different doses of drug treated. Changed chromosomal distribution patterns of drug treated cells were reversible, especially the cells having 56 to 60 chromosomes recovered rapidly. Cells having 41-60 and 61-80 chromosomes among cells treated with BCNU and cells with 41-60 chromosomes after CCNU treatment were the major population which regenerated continuously. Following BCNU treatment cells having 61-80 chromosomes were not varied much whereas CCNU treatment affects the population in the same class. Chromosomal aberrations were significantly enhanced by BCNU and CCNU treatment. The frequency of chromosomal aberrations was greater in cells having more than 40 chromosomes compared with that in cells having less than 40 chromosomes. Changes in ploidy characteristics of the cells following complement mediated and cell mediated cytotoxicity were not significant. Therefore it was tentatively concluded that association of numerical distribution pattern of NS-1 cells with the response to the treatment used in this experiment was not recognized.
This study was performed to investigate the modifying effect of the general (GPA) and the fermented pilose antler (FPA) on experimental hepatocarcinogenesis and Natural Killer cell activity in rats. Specific pathogen free, 5-week male Sprague-Dawley rats were divided into four groups. To induce hepatocarcinogenesis, diethylnitrosamine (DEN, 200 mg/kg, i.p.) was used as a tumor initiator and was given in a single dose at experimental onset. All rats were given a partial hepatectomy (PH) at 3 weeks after experimental onset. Sodium phenobarbital (PB, 0.05% in diet), GPA (0.075% in diet) and FPA (0. 075% in diet) were given from 2 to 8 weeks. Group I of the initiation control group was only given DEN. As initiation-promotion group, Group II was given DEN and then PB. Group III and IV were given DEN-PB-GPA and DEN-PB-FPA, respectively. In hematological analysis, as compared with Group I. the number of white blood cells were significantly increased in the GPA (p<0.01) and the FPA treated group (p<0.05), respectively. Natural killer (NK) cell activity by flow cytometer (FCM) analysis was higher in group of treated with the GPA (35%) than that of the FPA (27.5%), but not significant. Result of the immunohistochemical staining of the glutathione S-transferase placental form (GST-p) indicated that the number of and area of the pre-neoplastic lesions was not significantly changed in Group III and IV compared Group II, respectively. In conclusion, the GPA and the FPA treatment significantly increased the number od WBC in peripheral blood, but the enhancing NK activity and the modifying effect on the experimental hepatocarcinogenesis were not observed.
To evaluate the anti-oxidant and anti-tumor potential of the green pepper (Capsicum annuum L. cv. DangZo), total polyphenol content, radical scavenging activities and anti-tumor properties were measured. The total polyphenol content of the 70% ethanol extracts from green pepper (Capsicum annuum L. cv. DangZo) was 30.29 mg gallic acid equivalent/g extract. The DPPH radical and hydroxyl radical scavenging activities of 70% ethanol extracts of green pepper (Capsicum annuum L. cv. DangZo) were documented at 2.87 and 10.55, respectively. For ${\alpha}$-glucosidase and ${\alpha}$-amylase inhibitory activity, 70% ethanol extracts of green pepper (Capsicum annuum L. cv. DangZo) were documented at 35.67% and 58.41% respectively. The green pepper (Capsicum annuum L. cv. DangZo) demonstrated greater capability in terms of anti-neoplastic activity vis-a-vis colon cancer cell lines when compared to other cancer cell lines.s. er (Capsicum annuum L. cv. DangZo) higher activities of anticancer activities on colon cancer cell lines compared to other cancer cell lines.
Kim, Nayoung;Lee, Dong-Hee;Choi, Woo Seon;Yi, Eunbi;Kim, HyoJeong;Kim, Jung Min;Jin, Hyung-Seung;Kim, Hun Sik
BMB Reports
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v.54
no.1
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pp.44-58
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2021
Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.
Protein kinase C (PKC) is known to play a pivotal role in neoplastic transformation cells and its high expression is often found in a variety of types of tumors including oral cancer. While PKC is associated with the altered signal transduction pathway of the tumor cells, it is still unclear which isoform is involved in the carcinogenesis process. Since the cellular distributions and the roles of PKC are isoform-specific, it is very important to identify the specific target molecules to improve our understanding of the carcinogenesis processes. Thus, the present study attempted to perform chemical carcinogen-induced neoplastic transformation of human epithelial cells and analyze the specific isoform of PKCs involved in the cellular transformation. The study analyzed overall PKC responses upon MNNG(N-Methyl-N'-nitro-N-nitroso guanidine) exposure with [$^3H$] PDBu binding assay. PKC translocation was observed at high doses of MNNG treatment in the presence of extracellular calcium. Such effects were not observed in the absence of extracellular calcium. Translocational effects with exposure of MNNG was further enhanced in the presence of hydrocortisone. The result suggests that the type of PKC involved may be $Ca^{2+}$-dependent classical isoform and steroid hormone enhances PKC activation. Among cPKC isoforms examined, only $PKC-{\alpha}$ and r showed significant translocation of protein levels from cytosolic fraction to membrane fraction, as analyzed by immunoblot. $PKC-{\varepsilon}$ in nPKC class showed an inch·eased translocation, but other forms in this class did not show the effect. None of isoforms in aPKC class was affected by MNNG treatment. The study demonstrated that there was a certain specificity in the patterns of isoform induction follwong chemical carcinogen exposure and helped identify all the types of PKC isoforms expressed in human epithelial cells. It was revealed that PKC isoforms were activated in an early resonse to chemical carcinogen, suggesting that PKC be associated with carcinogenesis process from an early stage in this particular cell system. The study will contribute to improving our understanding of chemical-induced carcinogenesis in human cells and may provide a scientific basis to introduce the specific PKC inhibitors as an anticancer drug of epithelial cell-origin cancers including oral cancer.
Park, Eun Hye;Lee, Hyo Jung;Lee, Soo Yeon;Kim, Sun Young;Yi, Ho Keun;Lee, Dae Yeol;Hwang, Pyoung Han
Clinical and Experimental Pediatrics
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v.52
no.2
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pp.213-219
/
2009
Purpose:Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods:To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results:Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion:These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.
Clinical and cytomorphological studies were carried out in 32 leukotic cattle from Tokachi and Kushiro districts in Hokkaido during the 12 year period from 1969 to 1980. The leukotic cattle were examined :and divided into four types(15 cases of the adult, 11 cases of the thymic, 4 casas of the calf and 2 cases of the skin types). The results obtained were as follows : 1. As for the frequency of the main clinical signs in each type, In the adult type, the main clinical signs (of decreasing order) are as follows: swelling of the superficial lymph nodes>depression and loss of weight>tachycardia>anorekia, anemia of the visible mucous membrane and tachypnea. Those of the thymic type were swelling of the thymus>swelling of the medial iliac lymph nodes> swelling of the superficial lymph nodes>tachypnea. Those of the calf type were swelling of the auperficial lymph nodes>depression and emaciation>tachypnea>anorexia, tachycardia, anemia of the visible mucous membrane and recumbency. Those of the skin type were generalized urticaria-like lesions in skin and swelling of superficial lymph nodes>and depression and loss of weight in the decreasing order of frequency. In addition, large tumor mass in the pelvic cavity and swelling of the medial iliac lymph nodes were detected through rectal palpation in 33.3% and 100% in the adult type cases, respectively. 2. As for the hematological findings, The frequency of occurrence of decreased erythrocyte counts in the decreasing order were as follows : adult>calf>thymic>and skin types. The increase in the total leukocyte count in the order of decreasing frequency were as follows: calf>thymic>adult>and skin types. The increase in the absolute lymphocyte counts was found to be at a low rate, 62.5% of all the cases examined. By contrast, the increase of 5% or more of abnormal lymphocyte rates was observed at a high rate, 96.9% of the total cases. 3. Abnormal lymphocytes were found in all cases examined for lymph nodes biopsied. 4. From the cytomorphological point of view, leukotic cells were divided into 3 types: reticulum cell, lymphoid cell and monocytic cell types. The adult type leukotic cattle were divided with reticulum cell type (66.7%), the lymphoid cell type(22.6%) and monocytic cell type(6.7%). The thymic type was lymphoip cell type(72.7%) and reticulum cell type(27.3%). In the calf type, all were lymphoid cell type while all of the skin type were reticulum cell type only. 5. The leukotic cattle had higher NP frequency in the blood and lymphoid tissue than non-1 eukotic cattle. Especially the adult type had the highest NP frequency. However, it was not recognized that NP were characteristic of leukotic cattle alone. 6. The above findings lead to the conclusion that the most effective diagnostic methods for bovine leukosis are the confirmation of swelling of the superficial and internal lymph nodes and thymus in addition to appearance of abnormal neoplastic cell in the peripheral blood and lymph nodes biopsied.
BRCA1 is a tumor suppresser gene in familial cases of breast cancer. It has been controversial whether the subcellular localization of BRCA1 is located in nuclei or cytoplasm in normal human breast cells. We found that a p220 protein was expressed in Type II Normal human breast epithelial cells (NHBEC) but not in Type I NHBEC in Western blot analysis using the 17F8 (3A2) antibody. Immunostaining using the same antibody revealed positive staining in nuclei, cytoplasm and perinuclei of Type II cells and negative staining in Type I NHBEC. The p220 protein, however, was expressed in SV40 immortalized Type I NHBEC and tumorigenic cells derived from them after x-ray and neu oncogene treatment. The subcelluar localization was mostly cytoplasmic and punctate in the nuclei. The breast carcinoma cell lines, MCF-7 and T47D, also expressed the p220 protein. Using RT-PCR, we observed the expression of BRCA1 mRNA in both Type I and Type II NHBEC. This result indicated that there might be mechanisms involved in post-translational or translational regulation of BRCA1 gene. It is speculated that the absence of BRCA1 protein expression in Type I NHBEC might playa role in their susceptibility to neoplastic transformation.
Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein ($AFP{\geq}600$ IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.
Park, Won-Young;Shin, Dong-Hoon;Kim, Jae-Ho;Lee, Min-Ki;Lee, Ho-Seok;Lee, Chang-Hun
Tuberculosis and Respiratory Diseases
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v.72
no.2
/
pp.132-139
/
2012
Background: Periostin is preferentially expressed in periosteum, indicating a potential role in bone formation. Recently, there have been emerging controversies about its role in invasion and metastasis of human malignancies. We attempted to determine the clinicopathological significance of periostin expression in non-small cell lung carcinoma (NSCLC). Methods: Immunohistochemical staining of periostin protein from 91 cases of NSCLCs was performed using tissue microarray blocks. The results were correlated with clinicopathological parameters. Results: Positive reaction to periostin was predominantly noted in the tumor stroma. The strongest reaction presented as a band-like pattern just around the tumor nests. Non-neoplastic lung tissue and most in-situ carcinomas did not show a positive reaction in their stroma. With respect to tumor differentiation, moderate to poor differentiated tumors (47/77) revealed even higher periostin expression than the well-differentiated ones (4/14) (p=0.024). High periostin expression was positively correlated with E-cadherin and p53 expression, but was not related with patient age, sex, tumor type, PCNA index, b-catenin, cyclin D1, pTNM-T, pTNM-N, stage, and patient survival (p>0.05). Conclusion: These results suggest that periostin might play a role during the biological progression of NSCLC, but may not be related to the clinical prognostic parameters.
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