• 대한세포병리학회지
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• 제10권2호
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• pp.157-162
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• 1999

Primary non-Hodgkin's lymphoma of the lung is rare among extranodal lymphomas. The most common form is low grade B-cell type originated from the mucosa-associated lymphoid tissue (MALT) of the lung and primary peripheral T cell lymphoma of the lung is extremely rare. We recently experienced a case of fine needle aspiration cytology of primary peripheral T cell lymphoma of the lung in a 39-year-old male patient. The cytologic smears revealed some sheets of reactive epithelial cells, epithelioid histiocytes, and numerous polymorphous population of lymphoid cells composed of small and intermediate sized lymphoid cells and mature lymphocytes. Lymphoid cells were slightly larger than normal mature lymphocytes and showed significant irregularity of nuclear membrane. The internal nuclear structure was marked by chromatin clumping, clear parachromatin areas, and inconspicuous nucleoli. Histopathologically, atypical small lymphocytes infiltrated in the interstitium and alveolar sac. By the immunohistochemical study and molecular biologic study of gene rearrangement, the T cell clonality of atypical lymphoid cells was confirmed.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.1067-1072
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• 2013

Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of $SSC^{lo}\;Alde^{br}$ cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell $SSC^{lo}\;Alde^{br}$ cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers.

• Journal of Chest Surgery
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• 제53권1호
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• pp.22-27
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• 2020

Background: Previous studies have shown that lung cancer stem cells express CD133 and that certain cancer stem cells express cancer germline antigens (CGAs). The transcriptional regulation of CD133 is complicated and poorly understood. We investigated CD133 and CGA expression in a non-small cell lung cancer cell line. Methods: The expression levels of CD133 and CGAs (MAGE-6, GAGE, SSX, and TRAG-3) were measured in an NCI-H292 lung cancer cell line. The methylation status of the CD133 gene promoter region was analyzed. The expression levels and promoter methylation statuses of CD133 and CGAs were confirmed by treatment with the demethylating agent 5-aza-2'-deoxycytidine (ADC). Results: After treatment with ADC, CD133 expression was no longer detected. MAGE-6 and TRAG-3 were detected before ADC treatment, while GAGE and SSX were not detected. ADC treatment upregulated MAGE-6 and TRAG-3 expression, while GAGE expression was still undetected after treatment, and only weak SSX expression was observed. GAGE expression was not correlated with expression of CD133, while the levels of expression of MAGE-6, TRAG-3, and SSX were inversely correlated with CD133 expression. Conclusion: These results showed that CD133 expression can be regulated by methylation. Thus, the demethylation of the CD133 promoter may compromise the treatment of lung cancer by inactivating cancer stem cells and/or activating CGAs.

• Tuberculosis and Respiratory Diseases
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• 제80권1호
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• pp.1-10
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• 2017

Chronic obstructive pulmonary disease (COPD) is a critical condition with high morbidity and mortality. Although several medications are available, there are no definite treatments. However, recent advances in the understanding of stem and progenitor cells in the lung, and molecular changes during re-alveolization after pneumonectomy, have made it possible to envisage the regeneration of damaged lungs. With this background, numerous studies of stem cells and various stimulatory molecules have been undertaken, to try and regenerate destroyed lungs in animal models of COPD. Both the cell and drug therapies show promising results. However, in contrast to the successes in laboratories, no clinical trials have exhibited satisfactory efficacy, although they were generally safe and tolerable. In this article, we review the previous experimental and clinical trials, and summarize the recent advances in lung regeneration therapy for COPD. Furthermore, we discuss the current limitations and future perspectives of this emerging field.

• BMB Reports
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• 제50권2호
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• pp.79-84
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• 2017

Emphysema, a pathologic component of the chronic obstructive pulmonary disease, causes irreversible destruction of lung. Many researchers have reported that mesenchymal stem cells can regenerate lung tissue after emphysema. We evaluated if spheroid human adipose-derived mesenchymal stem cells (ASCs) showed greater regenerative effects than dissociated ASCs in mice with elastase-induced emphysema. ASCs were administered via an intrapleural route. Mice injected with spheroid ASCs showed improved regeneration of lung tissues, increased expression of growth factors such as fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF), and a reduction in proteases with an induction of protease inhibitors when compared with mice injected with dissociated ASCs. Our findings indicate that spheroid ASCs show better regeneration of lung tissues than dissociated ACSs in mice with elastase-induced emphysema.

• Tuberculosis and Respiratory Diseases
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• 제48권3호
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• pp.324-330
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• 2000

연구배경 : IGFs는 다양한 종양세포에서 세포분열 및 성장에 관여하는 것으로 알려진 펩티드로써 폐암 조직에서 IGF-1에 대한 항체를 이용하여 면역조직화학염색을 실시하여 폐암세포에서 이의 발현 및 조직학적 형태에 따라 발현의 정도를 비교해 보고자 하였다. 방 법 : 15명의 소세포성 폐암 환자와 42명의 비소세포성 폐암 환자를 대상으로 IGF-1에 대한 면역조직화학적 염색을 실시하였다. 결 과 : 모든 폐암 조직애서 IGF-1의 발현을 보였고 비소세포성 폐암조직은 소세포성 폐암조직보다 IGF-1에 대한 발현의 정도가 유의하게 증가되어 있었다. 결 론 : 폐암세포는 IGF-1의 발현을 보이며 이에 대한 면역조직화학염색은 폐암세포의 조직학적 형태를 감별하는데 도움을 줄 수 있다.

• Nutritional Sciences
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• 제7권3호
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• pp.144-150
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• 2004

We have investigated the effect of calcium spirulan(Ca-SP) isolated from a blue-green alga Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose and fructose, on invasion of both B16- BL6 melanoma cells, Colon 26 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters in a concentration-dependent manner. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no inhibitory effect on tumor cell migration to fibronectin-coated filters. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel- and laminin-substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin in a concentration-dependent fashion, while the pretreatment of laminin-substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contraset, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP in a dose-dependent manner. Seven intermittent ⅰ.ⅴ. injection of 100$\mu\textrm{g}$ of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung colonization of B16-BL6 melanoma cells in experimental metastasis model, by inhibiting the tumor invasion of basement membrane Matrigel, probably through the prevention of the adhesion and migration of tumor cells to laminin-substrate and of the heparanase activity.

• Archives of Pharmacal Research
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• 제26권10호
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• pp.861-867
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• 2003

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 $\mu$ g/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity. i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

• IMMUNE NETWORK
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• 제5권1호
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• pp.36-44
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• 2005

Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

• 한국임상수의학회지
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• 제32권6호
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• pp.530-535
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• 2015

11년령의 암컷 미니어처 푸들이 4개월의 혈흉으로 본 병원에 의뢰되었다. 신체검사에서, 비록 청진상에서 오른쪽 흉곽의 심음이 희미했으나 환축은 기민한 상태였다. 방사선 상에서 흉강은 흉수로 가득 차 있었다. 초음파 상에서는 양쪽 난소는 낭포성 변화가 관찰되었고 간에서 여러 개를 결절을 확인했다. 컴퓨터 단층 촬영에서 오른쪽 중간엽으로 들어가는 기관지의 허탈을 확인한 후에 거칠게 보였던 오른쪽 폐의 음영은 오른 중간엽 폐염전으로 진단되었다. 진단 5일후에 오른쪽 5번째 갈비뼈 사이로 접근하여 중간엽을 절제하였고 동시에 난소자궁적출술도 실시되었다. 병리조직학적 검사에서 양쪽 난소에서는 유두상 선암종이 나타났고, 중간엽에서는 난소에서 전이된 것으로 의심되는 선암종이 진단되었다. 환축은 2달동안 순조롭게 회복되었다. 그러나 4달 후에 환축은 호흡곤란으로 내원하였다. 방사선 상에서 흉수와 오른쪽 앞엽과 왼쪽 뒤엽이 허탈 되어 있었다. 그리고 흉수에서 전이로 의심되는 악성 상피종 세포가 관찰되었다. 보호자에게 항암 치료를 권해드렸으나 보류하셨고 환축은 퇴원하였다. 본 보고의 목적은 종양으로 인한 출혈성 흉수로 폐염전이 발생할 수 있는 드문 증례를 보고 하기 위함이다.