• Title/Summary/Keyword: Small cells

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Application of Toxicogenomic Analysis to the Monitoring of Environmental Toxicity Using Recombinant Bioluminescent Bacteria and Cultured Mammalian Cells

  • Choi, Sue Hyung;Gu, Man Bock;Yasuyuki, Sakai
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 2003.06a
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    • pp.129-131
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    • 2003
  • Recombinant bioluminescent bacteria and cultured human cells were applied for toxicogenomic analysis of environmentally hazardous chemicals. Recombinant bioluminescent biosensing cells were used to detect and classify the toxicity caused by various chemicals. Classification of toxicity was realized based upon the chemicals' mode of action using DNA-, oxidative-, protein, and membrane-damage sensitive strains. As well, a simple double-layered cell culture system using Caco-2 cells and Hep G2 cells, which mimic the metabolic processes occurring in humans, such as adsorption through the small intestine and biotransformationin both the small intestine and the liver, was developed to investigate the toxicity of hazardous materials to humans. For a more in-depth analysis, a DNA microarray was used to study the transcriptional responses of Caco-2 and Hep G2 cells to benzo〔a〕pyrene.

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Induction of cytoprotective autophagy by morusin via AMP-activated protein kinase activation in human non-small cell lung cancer cells

  • Park, Hyun-Ji;Park, Shin-Hyung
    • Nutrition Research and Practice
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    • v.14 no.5
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    • pp.478-489
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    • 2020
  • BACKGROUND/OBJECTIVES: Morusin, a marker component of Morus alba L., possesses anti-cancer activity. The objective of this study was to determine autophagy-inducing effect of morusin in non-small cell lung cancer (NSCLC) cells and investigate the underlying mechanism. SUBJECTS/METHODS: Autophagy induction and the expression of autophagy-related proteins were analyzed by LC3 immunofluorescence and western blot, respectively. The role of autophagy and AMP-activated protein kinase (AMPK) was determined by treating NSCLC cells with bafilomycin A1, an autophagy inhibitor, and compound C, an AMPK inhibitor. Cytotoxicity and apoptosis induction were determined by MTT assay, trypan blue exclusion assay, annexin V-propidium iodide (PI) double staining assay, and cell cycle analysis. RESULTS: Morusin increased the formation of LC3 puncta in the cytoplasm and upregulated the expression of autophagy-related 5 (Atg5), Atg12, beclin-1, and LC3II in NSCLC cells, demonstrating that morusin could induce autophagy. Treatment with bafilomycin A1 markedly reduced cell viability but increased proportions of sub-G1 phase cells and annexin V-positive cells in H460 cells. These results indicate that morusin can trigger autophagy in NSCLC cells as a defense mechanism against morusin-induced apoptosis. Furthermore, we found that AMPK and its downstream acetyl-CoA carboxylase (ACC) were phosphorylated, while mammalian target of rapamycin (mTOR) and its downstream p70S6 kinase (p70S6K) were dephosphorylated by morusin. Morusin-induced apoptosis was significantly increased by treatment with compound C in H460 cells. These results suggest that morusin-induced AMPK activation could protect NSCLC cells from apoptosis probably by inducing autophagy. CONCLUSIONS: Our findings suggest that combination treatment with morusin and autophagy inhibitor or AMPK inhibitor might enhance the clinical efficacy of morusin for NSCLC.

Enhanced Sensitivity to Gefitinib after Radiation in Non-Small Cell Lung Cancer Cells

  • Choi, Yun-Jung;Rho, Jin-Kyung;Back, Dae-Hyun;Kim, Hye-Ryoun;Lee, Jae-Cheol;Kim, Cheol-Hyeon
    • Tuberculosis and Respiratory Diseases
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    • v.71 no.4
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    • pp.259-265
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    • 2011
  • Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation. Methods: We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis. Results: PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings. Conclusion: The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.

Changes in Neuropeptide Y-Immunoreactive Cells in the Hypothalamus and Cajal Interstitial Cells in the Small Intestine of Rats with High-Fat Diet (고지방식이에 의한 흰쥐의 시상하부 Neuropeptide Y-면역반응 신경세포와 장내 Cajal 세포의 변화)

  • Moon, Ji-Young;Moon, Kyung-Rae;Park, Sang-Kee;Chung, Yoon-Young;Kim, Eun-Young
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.14 no.2
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    • pp.171-180
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    • 2011
  • Purpose: The aim of this study was to assess changes in neuropeptide Y (NPY) immunoreactivity in the hypothalamus and interstitial cells of Cajal (ICC) in the small intestine of rats fed high-fat diets (HFD). Methods: Male Sprague-Dawley rats (200~250 g body weight) were randomly divided into two groups, which were the control group (normal chow diet for 6 weeks), and the HFD group (rodent diet with 60% kcal fat for 6 weeks). The immunoreactivity of NPY in the hypothalamus and ICC in the small intestine was evaluated after every feed for 6 weeks. Results: NPY immunoreactivity was observed strongly in the hypothalamic nuclei in the HFD group compared to the control group. The numbers of NPY-immunoreactive (IR) cells were significantly higher in the paraventricular hypothalamic nucleus in the HFD group than in the control group. In the region of Auerbach's plexus (AP) of small intestine, the staining intensity of the ICC-IR cells was reduced in the HFD group compared to the control group. The numbers of ICC in the small intestine with HFD, including ICC in the inner circular and outer longitudinal muscle were significantly lower than in the control group. Conclusion: This study suggested that increasing NPY-IR cells in the hypothalamus may reflect resistance of NPY action after a HFD, and decreasing ICC-IR cells in the small intestine after a HFD is functionally significant in gastrointestinal motility.

Coexpression of PCNA and p21 for DNA repair in small intestinal crypt cells of mouse with 60Co γ-rays irradiation (방사선을 조사한 마우스의 소장 음와세포에서 DNA 수복을 위한 PCNA와 p21의 발현 양상)

  • Hong, Suji;Hwang, Insun;Ahn, Meejung;Shin, Taekyun;Joo, Hong-gu;Park, HyunJeong;Jee, Youngheun
    • Korean Journal of Veterinary Research
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    • v.45 no.4
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    • pp.457-464
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    • 2005
  • The irradiation of radioactive ${\gamma}-ray$ induces apoptosis of radiosensitive organs for homeostasis. In this study, we investigated the repair mechanisms for homeostasis in the small intestine after cell damage by $^{60}Co\;{\gamma}-ray$ irradiation. The apoptosis was most frequently observed in the crypt cells of the small intestine after four and six hours by radioactive ${\gamma}-ray$ irradiation, and the frequency of apoptosis was proportional to the amount of irradiation. Also, the number of apoptotic cells was coincident with expression pattern of p53. Interestingly, PCNA (proliferating cell nuclear antigen) which is engaged in DNA replication and repair was expressed in apoptotic cells of small intestinal crypts. Also, it was observed that cell-cycle regulator p21 which is known to induce cell-cycle arrest is co-expressed in the same apoptotic cells of irradiated small intestinal crypt cells. These findings suggest that the co-expression of PCNA and p21 proteins, which may lead to resistance to DNA damage through cell-cycle arrest is closely associated with repair of damaged gastrointestinal cells after ${\gamma}-ray$ irradiation.

Identification of piRNAs in Hela cells by massive parallel sequencing

  • Lu, Yilu;Li, Chao;Zhang, Kun;Sun, Huaqin;Tao, Dachang;Liu, Yunqiang;Zhang, Sizong;Ma, Yongxin
    • BMB Reports
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    • v.43 no.9
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    • pp.635-641
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    • 2010
  • Piwi proteins and Piwi-interacting RNAs (piRNAs) have been implicated in transposon control in germline from Drosophila to mammals. To examine the profile of small RNA expression in human cancer cells and explore difference in small RNA transcriptome, small RNA libraries prepared from wildtype, HILI overexpressed and HILI knockdowned Hela cells were sequenced using Solexa technology. piRNAs and other repeat-associated small RNAs were observed in Hela cells. By using in situ hybridization, piR-49322 was localized in the nucleolus and around the periphery of nuclear membrane in Hela cells. Following the overexpression of HILI, the retrotransposon elements LINE1 was significantly repressed, while LINE1-associated small RNAs decreased in abundance. The present study demonstrated that HILI along with piRNAs plays a role in LINE1 suppression in Hela cancer cell line.

Urinary Cytologic Findings of Small Cell Neuroendocrine Carcinoma -A Case Report- (방광의 소세포 신경내분비 암종의 요 세포학적 소견 - 1 예 보고 -)

  • Kim, Dong-Hoon;Kang, Dong-Wook;Kim, yuug-Hee;Kim, Ju-Heon;Park, Mee-Ja
    • The Korean Journal of Cytopathology
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    • v.13 no.2
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    • pp.78-83
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    • 2002
  • We report the cytologic features of a case of primary small cell carcinoma of the urinary bladder with high grade transitional cell and signet ring cell carcinomatous components. A 64-year-old male presented with gross hematuria for one week. Computed tomography revealed an ill-defined mass in the left lateral wall of the urinary bladder. Urinary cytology showed hypercellularity with predominantly isolated single cells and clustered cells. They have scanty cytoplasm and naked hyperchromatic nuclei with finely granular nuclear chromatin and rare nucleoli. The tumor cells occurred predominantly singe cells, but a few in clusters. Nuclear molding was prominent. No glandular formation or nesting was noted. The second tumor cells had high nuclear/cytoplasmic ratio, irregular nuclear membrane, and coarse granular chromatin. The background was inflamed and necrotic. The histoiogic findings of transurethral resection were mainly composed of small cell carcinoma, and partly transitional cell and signet ring cell carcinomatous components. Small cell neuroendocrine carcinoma have distinctive cytologic features to make a proper diagnosis.

Immunocytochemical study of the endocrine cels in the gastrointestinal tract of the Korean native cattle (한우(韓牛)의 위장관(胃腸管)에 존재(存在)하는 내분비세포(內分泌細胞)의 면역세포화학적(免疫細胞化學的) 연구(硏究))

  • Cho, Sung-whan;Kitamura, Nobuo
    • Korean Journal of Veterinary Research
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    • v.28 no.2
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    • pp.251-259
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    • 1988
  • Regional distribution and relative frequency of endocrine cells in ten portions of the gastrointestinal tract of the Korean native cattle were observed by immunocytochemical methods using specific antisera against chromogranin, serotonin, somatostatin, glucagon, bovine pancreatic polypeptide(BPP), motilin, gastric inhibitory polypeptide(GIP), neurotensin, secretin, gastrin and substance P. The results observed are summarized as follows: In the abomasum, chromogranin-, serotonin-, somatostatin-, motilin-, glucagon-, gastrin-, and substance P-immunoreactive cells were found. Chromogranin-and serotonin-immunoreactive cells were more numerous in the fundic region than pyloric region. Somatostatin- and gastrinimmunoreactive cells were numerous in the pyloric region than in the fundic region. In the small intestine, chromogranin-, serotonin-, somatostatin-, glucagon-, BPP-, motilin-, gastrin-, GIP-, neurotensin-, secretin-, and substance P-immunoreactive cells were detected. Chromogranin-, somatostatin-, GIP- and secretin-immunoreactive cells were most numerous in the duodenum, while BPP-, motilin-, glucagon-, neurotensin- and substance P-immunoreactive cells were rarely seen in the small intestine. In the large intestine, chromogranin-, serotonin- and BPP-immunoreactive cells were widely distributed and most numerous in the rectum. Somatostatin-, glucagon- and substance P-immunoreactive cells were rarely seen in the large intestine.

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Immunohistochemistry of Gastrointestinal Endocrine Cells in the Meckel′s Diverticulum of the Bean Goose, Anser fabalis Latham

  • Ku, Sae-Kwang;Lee, Hyeung-Sik;Park, Ki-Dae;Lee, Jae-Hyun
    • Animal cells and systems
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    • v.4 no.4
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    • pp.375-379
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    • 2000
  • The appearance of some gastrointestinal endocrine cells in the Meckel's diverticulum (MD) of the bean goose, Anser fabalis Latham was observed using specific antisera against serotonin, gastrin, cholecystokinin (CCK)-8, glucagon, secretin, somatostatin and human pancreatic polypeptide (HPP) with the peroxidase antiperoxidase (PAP) method. Among these specific antisera, serotonin-, gastrin-, CCK-8-, somatostatin- and HPP-immunoreactive cells were demonstrated in this study. Serotonin-, gastrin- and somatostatin-immunoreactive cells were detected at moderate frequency and CCK-8- and HPP-immunoreactive cells was rare and low frequencies, respectively. These immunoreactive cells were located in the superficial epithelium, intestinal crvpt and intestinal glands with spherical or spindle shaped cells having long cytoplasmic processes (open typed-cell). Mucosal layer of MD was composed of simple columnar epithelium and numerous intestinal glands. In addition, numerous lymphatic tissues were also demonstrated. In conclusion, histological profiles of MD were similar to any parts of the large intestine, especially the cecum, but the appearance, distribution and relative frequency of gastrointestinal endocrine cells were similar to those of upper parts of the small intestine. Although the exact digestive functions were unknown, the finding that the appearance, distribution and relative frequency of gastrointestinal endocrine cells in MD is similar to small intestine may be considered as distinct evidence that this organ may have some digestive functions.

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End-to-End Delay Analysis of a Dynamic Mobile Data Traffic Offload Scheme using Small-cells in HetNets

  • Kim, Se-Jin
    • Journal of Internet Computing and Services
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    • v.22 no.5
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    • pp.9-16
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    • 2021
  • Recently, the traffic volume of mobile communications increases rapidly and the small-cell is one of the solutions using two offload schemes, i.e., local IP access (LIPA) and selected IP traffic offload (SIPTO), to reduce the end-to-end delay and amount of mobile data traffic in the core network (CN). However, 3GPP describes the concept of LIPA and SIPTO and there is no decision algorithm to decide the path from source nodes (SNs) to destination nodes (DNs). Therefore, this paper proposes a dynamic mobile data traffic offload scheme using small-cells to decide the path based on the SN and DN, i.e., macro user equipment, small-cell user equipment (SUE), and multimedia server, and type of the mobile data traffic for the real-time and non-real-time. Through analytical models, it is shown that the proposed offload scheme outperforms the conventional small-cell network in terms of the delay of end-to-end mobile data communications and probability of the mobile data traffic in the CN for the heterogeneous networks.