• 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
    • 한국미생물생명공학회:학술대회논문집
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    • 한국미생물생명공학회 2003년도 2003 Annual Meeting, BioExhibition and International Symposium
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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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    • 제14권5호
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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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    • 제71권4호
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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.

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

  • 문지영;문경래;박상기;정윤영;김은영
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제14권2호
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    • pp.171-180
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    • 2011
  • 목 적: 고지방식이를 섭취한 흰쥐에서 식이 유발인자인 NPY와 장내 운동 조절인자인 Cajal 간질세포의 변화를 관찰하고자 하였다. 대상 및 방법: 동일 연령의 Sprague-Dawley계 수컷 흰쥐를 임의로 대조군(7마리)과 고지방식이군(7마리)으로 분리한 후, 대조군에는 일반 흰쥐 사료를 충분히 섭취시켰으며, 고지방식이군에게는 60% kcal 지방이 포함된 사료(중앙실험동물센터)를 6주 동안 물과 함께 충분히 섭취하도록 하였다. 6주 후 시상하부 조직 절편에 rabbit polyclonal NPY (1 : 1000, Abcam)항체를 반응시키고, 소장의 조직 절편에 rabbit polyclonal c-kit (1 : 400, Neuromics)항체를 반응시켜서 면역조직화학 검사를 시행하였다. 결 과: 고지방식이군의 시상하부에서 NPY의 면역 반응성이 강하게 나타났으며, 특히 PVN에서 NPY의 면역 반응 세포수의 증가를 관찰할 수 있었다. 고지방식이군에서 소장의 Auerbach's plexus 부위의 Cajal 간질 세포의 면역 반응성이 떨어졌으며, 환상근과 종주근 내 Cajal 간질 세포 수도 현저히 감소하였다. 결 론: 고지방식이를 섭취한 흰쥐에서 시상하부 NPY 면역반응 신경세포수와 발현의 증가는 NPY의 저항성과 관련되며, 소장에서 Cajal 간질 세포의 감소는 장운동의 이상을 초래할 수 있음을 나타낸다.

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

  • 홍수지;황인선;안미정;신태균;주홍구;박현정;지영흔
    • 대한수의학회지
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    • 제45권4호
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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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    • 제43권9호
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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.

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

  • 김동훈;강동욱;김경희;김주헌;박미자
    • 대한세포병리학회지
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    • 제13권2호
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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.

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) (Immunocytochemical study of the endocrine cels in the gastrointestinal tract of the Korean native cattle)

  • 조성환;키타무라 노부오
    • 대한수의학회지
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    • 제28권2호
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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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    • 제4권4호
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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

  • 김세진
    • 인터넷정보학회논문지
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    • 제22권5호
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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.