Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest

Cho, Han Jin,Lim, Do Young,Kwon, Gyoo Taik,Kim, Ji Hee,Huang, Zunnan,Song, Hyerim,Oh, Yoon Sin,Kang, Young-Hee,Lee, Ki Won,Dong, Zigang,Park, Jung Han Yoon MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.2

<P>Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. <I>In vitro</I> cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.</P>

실리콘 겔에 활성화된 복강 대식세포의 interleukin-6 및 tumor necrosis factor-α에 의한 섬유모세포 중식 자극

김환묵,한상배,이백권,이종원,한기택,천지훈 大韓成形外科學會 1998 Archives of Plastic Surgery Vol.25 No.5

Silicone gel breast implants may induce local(fibrous capsular contracture) or systemic(rheumatoid arthritis, systemic sclerosis, etc) complications. The exact mechanism of fibrous capsular contracture has not been fully understood. In the present study, we tried to find out the effect of silicone gel on the fibroblast proliferation which has been known as a major contributing factor in fibrous capsular contracture formation. In vitro, activated macrophages are known to secrete monokines which affect fibroblast proliferation and collagen synthesis. And tumour necrosis factor-α(TNF-α) and interleukin-6(IL-6), which were released by macrophages, were reported as potent stimulator of fibroblast proliferation. The goal of this study is to investigate the role of macrophages and tumour necrosis factor-αor interleukin-6 in the interaction of fibroblasts and silicone gel. We designed four groups, two experimental and two control, using Institute for Cancer Research(ICR) mouse peritioneal macrophage and silicone gel. For the preparation of the conditioned medium of macrophages, peritoneal macrophages were prepared and cultured for 24 hours on the silicone gel-coated and naked (not coated) surface [silicone gel-macrophage conditioned medium(SCM; experimental group) and normal polystyrene-macrophage conditioned medium(NCM; control group) respectively]. To correct the effect of 10% fetal bovine serum which was included in Rapid Prototyping and Manufacturing Institute (RPMI) 1640 medium and draw the effect only by macrophages, the RPMI 1640 medium with 10% fetal bovine serum was cultured by the same method on the silicone gel-coated and naked surface (silicone gel-macrophage free conditioned medium; SFM and normal polystyrene-macrophage free conditioned medium; NFM respectively). Each conditioned medium was added onto NIH 3T3 fibroblasts culture at a final 25% concentration of total culture medium and followed by the cultivation for 24 hours. For antibody neutralizing experiments, each conditioned medium was preincubated with polyclonal rabbit anti-mouse TNF-α antibody or polyclonal rat anti-mouse IL-6 antibody for 1 hour and then, conditioned medium with antibody was added to the culture medium of NIH 3T3 fibroblasts by the same method. After 24 hours cultivation, total number of viable fibroblast(cell growth), DNA synthesis and collagen synthesis of fibroblasts with each medium were measured by sulforhodamine B(SRB) assay, 3H-thymidine and 3H-proline incorporation respectively. The results were as follows: 1. In the experiment about the effect of the conditioned medium on the fibroblast activity, the experimental group(SCM), compared with the control group(NCM), showed a significant increase of the cell growth (p<0.01), a significant decrease of DNA synthesis(p<0.001), but no significant difference in the collagen synthesis. 2. In the experiment about the effect of polyclonal rabbit anti-mouse TNF-α antibody on the fibroblast activity, after the addition of antibody the experimental group, compared with the control group, showed a significant decrease of the cell growth(p<0.001), a significant increase of DNA synthesis(p<0.01), but no significant difference in the collagen syn thesis. 3. In the experiment about the effect of polyclonal rat anti-mouse IL-6 antibody on the fibroblast activity, after the addition of antibody the experimental group, compared with the control group, showed a significant decrease of the cell growth(p<0.001), a significant increase of DNA synthesis(p<0.0001), but no significant difference in the collagen synthesis. In conclusion, culture supernatants (conditioned medium) of peritoneal macrophages, activated by silicone gel, stimulate the NIH 3T3 fibroblast proliferation. TNF-α and IL-6, products of macrophage, are involved in the stimulation of NIH 3T3 fibroblast proliferation in an in vitro condition.

프로스타글란딘 E₁ 투영와 외과적 지연 처치가 당뇨 흰쥐의 횡복직근피판의 생존에 미치는 영향

조성필,전영준,송윤상,한기택 大韓成形外科學會 2002 Archives of Plastic Surgery Vol.29 No.6

Extranodal Interdigitating Dendritic Cell Sarcoma Presenting in the Pleura: A Case Report

Han, Hye-Suk,Lee, Ok-Jun,Lim, Sung-nam,An, Jin Young,Lee, Ki Man,Choe, Kang Hyeon,Lee, Ki Hyeong,Kim, Seung Taik The Korean Academy of Medical Sciences 2011 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.26 No.2

<P>Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from the antigen-presenting cells of the immune system. This disease usually involves the lymph nodes, and rarely, extranodal sites may be affected. The authors report a case of extranodal IDCS presenting in the pleura. A 32-yr-old man presented with progressive chest pain. Imaging studies showed diffuse pleural thickening with pleural effusion. Morphological and immunohistochemical analysis of an incisional biopsy of the pleura were consistent with a diagnosis of IDCS; tumor cells were positive for S100 and CD45, but negative for CD1a, CD21, CD35, B cell and T cell markers. The patient was administered chemotherapy, but died of progressive disease. Although its incidence is extremely rare, this case suggests that extranodal IDCS should be considered in the differential diagnosis of undifferentiated neoplasms and that immunohistochemical staining be performed using appropriate markers.</P>

수혜부와의 접촉이 제한된 하복부 도서형 피판의 재혈관화

한기택,안상태,심형곤 大韓成形外科學會 1999 Archives of Plastic Surgery Vol.26 No.4

Island flaps have been widely used for the management of soft tissue defects in reconstructive surgery. The necrosis of the flap has been a catastrophe in clinical fields. It is well known that revascularization to the flap after ligation of its pedicle comes from the recipient bed and flap margins. The authors investigated the effects of the ischemic recipient bed on island flap survival after the ligation of its pedicle in the rats. One hundred and thirty inferior epigastric island flaps were divided into three groups(GroupⅠ, GroupⅡ, and GroupⅢ) according to the degree(0%,20%, and 60%) of interruption of contact of flap with the recipient bed, respectively. In Group Ⅰ,the vascular pedicles were ligated before and on the 0, 2nd, 3rd, 4th and 5th days after flap elevation, and in GroupⅡ&Ⅲ, the vascular pedicles were ligated on the 2nd, 3rd, 4th and 5th days after flap elevation. Flap survival was assessed on the 3rd day after pedicle ligation. Microangiographic studies were also performed on the 3rd day after pedicle ligation to study revascularization within the flap and the change of blood vessels around the flap margins. The results were as follows: 1. Flap survival was increased significantly in the flaps with pedicle ligation on the 4th and 5th postoperative days compared to those at the 2nd and 3rd postoperative days. 2. From the 3rd postoperative day, flap survival was not influenced significantly by the degree of limited bed contact and the date of pedicle ligation. 3. In spite of limited bed contact, the flap will likely survive with abundant revascularization from the flap margins. In conclusion, the flaps?? with limited bed contact were revascularized significantly from the flap margin by the 3rd postoperative day.

A Study on the Genetic Inheritance of Ankyloglossia Based on Pedigree Analysis

Han, Soo-Hyung,Kim, Min-Cheol,Choi, Yun-Seok,Lim, Jin-Soo,Han, Ki-Taik Korean Society of Plastic and Reconstructive Surge 2012 Archives of Plastic Surgery Vol.39 No.4

Background Ankyloglossia or tongue-tie is a congenital anomaly characterized by an abnormally short lingual frenum. Its prevalence in the newborn population is approximately 4%. Its mode of inheritance has been studied in some articles, but no conclusion has been established. Also, no relevant report has been published in Korea. This study was conducted to elucidate the genetic inheritance of ankyloglossia via pedigree analysis. Methods In this study, 149 patients with no other congenital anomaly who underwent frenuloplasty between March 2001 and March 2010 were studied. Pedigrees were made via pre- or post-operative history taking, and patients with uncertain histories were excluded. In the patient group that showed a hereditary nature, the male-to-female ratio, inheritance rate, and pattern of inheritance were investigated. Results One hundred (67.11%) of the patients were male and 49 (32.89%) were female (male-female ratio=2.04:1). Ninety-one (61.07%) patients reported no other relative with ankyloglossia, and 58 (38.93%) patients had a relative with this disease. The inheritance rate was 20.69% in the 58 cases with a hereditary nature. In the group with no family history of ankyloglossia, the male-female ratio was 3.79:1, which significantly differed from that of the group with a family history of ankyloglossia. X-chromosome mediated inheritance and variation in the gene expression was revealed in the pedigree drawn for the groups with hereditary ankyloglossia. Conclusions Ankyloglossia has a significant hereditary nature. Our data suggest X-linked inheritance. This study with 149 patients, the first in Korea, showed X-linked inheritance in patients with a sole anomaly.

Detection of EGFR Mutation Status in Lung Adenocarcinoma Specimens with Different Proportions of Tumor Cells Using Two Methods of Differential Sensitivity

Han, Hye-Suk,Lim, Sung-nam,An, Jin Young,Lee, Ki Man,Choe, Kang Hyeon,Lee, Ki Hyeong,Kim, Seung Taik,Son, Seung-Myoung,Choi, Song-Yi,Lee, Ho-chang,Lee, Ok-Jun Elsevier 2012 JOURNAL OF THORACIC ONCOLOGY Vol.7 No.2

<P>To evaluate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma specimens with different proportions of tumor cells using two methods with different sensitivities.</P>

Chemoprevention of Helicobacter pylori-associated Gastric Carcinogenesis in a Mouse Model : Is It Possible?

Hahm, Ki Baik,Song, Young Joon,Oh, Tae Young,Lee, Jeong Sang,Surh, Young-Joon,Kim Young Bae,Yoo, Byung Moo,Kim, Jin Hong,Han, Sang Uk,Nahm, Ki Taik,Kim, Myung-Wook,Kim, Dae Yong,Cho, Sung Won 한국생화학분자생물학회 2003 BMB Reports Vol.36 No.1

Although debates still exist whether Helicobacter pylory infection is really class I carcinigen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer, Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increase COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, expecially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were eva,uated. C57BL/6 mice werre sacrificed 50 weeks after H. pylori infection. Colonization rates of H.pylory, degree of gastric inflammation and other pathological changes including atrophic gastitis and metaplasia, serum levels and mRNA transcripts of various mouse cytoknes and chemokines, and NF-κ]B binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H.pylori infected group administrated with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of Nf-κB binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-r, RANTES, TNF-α, TNFR p75, IL-1β in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H.pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinfalmmatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastirc cancer, that is, that gastric cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.

난소암 세포주에서 Mullerian Inhibiting Substance의 증식 억제 효과

류기성 ( Ki Sung Ryu ),서미영 ( Mi Young Seo ),조윤성 ( Yun Sung Jo ),김미란 ( Mee Ran Kim ),김진우 ( Jin Woo Kim ),한구택 ( Goo Taik Han ),이준모 ( Joon Mo Lee ),김장흡 ( Jang Heub Kim ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.11

목적: 임신 7주경 태아 고환의 미숙 Sertoli 세포에서 생산되어 Muller관을 퇴행시키는 Mullerian inhibiting substance (MIS)는 성 발달과 가임기 여성의 생식생리 기전을 조절하는 이외에 Muller관으로부터 발생하는 일부 종양과 세포주의 성장을 in vivo와 in vitro에서 억제한다는 사실이 밝혀졌다. 이에 본 연구자들은 난소상피암 세포주들에서 MIS type II 수용체 (MISR II)의 발현을 확인하고, MIS를 투여하여 MIS의 세포 증식 억제효과와 그 기전을 밝힘으로서 종양치료제로서 MIS의 임상적 사용에 대한 가능성을 알아보고자 하였다. 연구 방법: 난소암 세포주인 SKOV-3, OVCAR-3 및 OVCAR-8에서 면역조직화학염색법으로 MISR II의 발현여부를 확인하였다. 난소암 세포주의 생존도는 고순도 MIS를 투여하여 24시간과 48시간동안 배양한 후 MTT assay로 측정하였다. MIS에 의한 세포주기 변화는 DNA 염색 후 flow cytometer로 분석하였으며 세포자멸사는 annexin-V-FITC 염색방법을 이용하여 flow cytometer로 평가하였다. MIS에 의한 난소암 세포주의 성장억제 감수성 차이와 세포자멸사 기전을 알아보기 위해 western blot 분석법을 이용하였다. 결과: 모든 난소암 세포주에서 MISR II 발현이 관찰되었지만, 발현정도는 OVCAR-8에서 제일 강했다. 세포 생존도는 OVCAR-8만이 MIS의 처치 용량과 시간에 따라 감소하였고, OVCAR-3은 고농도 MIS로 48시간 투여한 경우에만 의의 있게 감소하였으나, SKOV-3은 반응하지 않았다. Flow cytometer로 조사한 세포주기 변화는 OVCAR-8에서 10 μg/mL MIS로 24시간 처치한 경우에 G1세포주기 정지 소견을 보였으며, 48시간 후에는 세포자멸사를 의미하는 sub G0G1분기 분획이 7.02%로 나타나, MIS는 세포주기의 변화를 먼저 일으킨 후 세포자멸사를 유발하였다. OVCAR-3에서는 48시간 후 sub G0G1분기가 3.32%였으나 SKOV-3에서는 변화가 없었다. Annexin-V-FITC 염색방법으로, OVCAR-8과 OVCAR-3에서 48시간 MIS 처치 후에 각각 8.05%와 3.67%의 세포자멸사가 관찰되었다. Western blot 분석으로, OVCAR-8에서 MIS에 의한 세포 증식 억제에 이은 세포자멸사는 p16단백 증가와 연관이 있다고 판단된다. 또한 MIS는 OVCAR-8에서 MISR II와 결합한 후 pRb 비의존적인 세포내 경로를 통해 간접적으로 E2F1 활성 증가로 세포자멸사를 유도할 가능성이 있다. 결론: 본 연구에서 MIS가 난소암 세포주에서 증식 억제와 세포자멸사를 일으키는 기전을 완전히 규명하지는 못하였지만, MIS가 MIS 수용체를 발현하는 난소암에 대하여 in vitro에서 효과적인 항종양능을 나타낸다는 사실을 확인할 수 있었다. 향후 더 많은 연구로 MIS가 MIS 수용체를 발현하는 종양의 생물학적 조절제 혹은 치료제로 개발될 것이라고 예상된다. Objective: In order to explore Mullerian inhibiting substance (MIS) effects on the ovarian neoplasia, the expression and localization of the MIS type II receptor (MISR II), the growth inhibitory effects of MIS, and the underlying molecular mechanisms were investigated in the ovarian cancer cell lines. Methods: Expression of MISR Ⅱ were studied in SKOV-3, OVCAR-3, and OVCAR-8 cell lines by immunohistochemical staining. The antiproliferative effects of MIS in these cell lines were investigated by methylthiazoletetrazolium (MTT) assay, fluorescence-activated cell sorting (FACS) analysis, annexin-V-FITC binding, and western blot analysis. Results: All cell lines showed strong specific staining for MISR II, although staining in OVCAR-8 cells was more intense than that in SKOV-3 and OVCAR-3. Treatment of OVCAR-8 cells with MIS led to a dose- and time-dependent inhibition of cell growth and survival was determined use by MTT assay. But OVCAR-3 cells exhibited growth inhibition at higher doses after 48 hours of treatment and SKOV-3 cells did not demonstrate response. Using FACS analysis, exposure of OVCAR-8 cells to MIS (71 nM) resulted in G1 arrest after 24 hours of treatment. This pattern was changed by time-dependent increase in the percentage of cells with a sub G0G1 DNA content, suggesting apoptosis, after 48 hours of treatment. These results suggested that cell death be preceded by cell cycle arrest. Time-related induction of apoptosis was also observed in this cell line as measured by annexin-V-FITC binding. In OVCAR-8 cells, the growth inhibitory effects of MIS were mediated through specific induction of CDKI p16 protein expression and via regulation of E2F1 in the absence of detectable levels of pRb. We estimated that OVCAR-3 cells were affected by MIS through p16-independent, alternative mechanistic pathways, since the growth inhibitory effects of MIS were minimal. SKOV-3 cells did not express p16 protein. Conclusion: We have demonstrated that ovarian cancer cells express the MISR II. Epithelial ovarian cancer cells respond to MIS by growth inhibition. Although the precise mechanisms of MIS mediated inhibition of ovarian cancer cell growth have not been fully defined, these data suggest that MIS has activity against ovarian cancers in vitro and may also be an effective targeted therapy for ovarian cancer.

Genome-Wide Transcriptome Analysis of Rice Seedlings after Seed Dressing with Paenibacillus yonginensis DCY84T and Silicon

Yoo, Yo-Han,Kim, Minjae,Chandran, Anil Kumar Nalini,Hong, Woo-Jong,Ahn, Hye Ryun,Lee, Gang Taik,Kang, Sungju,Suh, Dabin,Kim, Jin-O,Kim, Yeon-Ju,Jung, Ki-Hong MDPI AG 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.23

<P>Plant-growth-promoting bacteria (PGPB) are beneficial microorganisms that can also protect against disease and environmental stress. Silicon (Si) is the second most abundant element in soil, and is known to increase plant growth, grain yield, resistance to biotic stress, and tolerance to abiotic stress. Combined treatment of PGPB and Si has been shown to further enhance plant growth and crop yield. To determine the global effects of the PGPB and Si on rice growth, we compared rice plants treated with Paenibacillus yonginensis DCY84T (DCY84T) and Si with untreated rice. To identify the genes that respond to DCY84T+Si treatment in rice, we performed an RNA-Seq transcriptome analysis by sampling treated and untreated roots on a weekly basis for three weeks. Overall, 576 genes were upregulated, and 394 genes were downregulated in treated roots, using threshold fold-changes of at least 2 (log2) and p-values < 0.05. Gene ontology analysis showed that phenylpropanoids and the L-phenylalanine metabolic process were prominent in the upregulated genes. In a metabolic overview analysis using the MapMan toolkit, pathways involving phenylpropanoids and ethylene were strongly associated with upregulated genes. The functions of seven upregulated genes were identified as being associated with drought stress through a literature search, and a stress experiment confirmed that plants treated with DCY84T+Si exhibited greater drought tolerance than the untreated control plants. Furthermore, the predicted protein-protein interaction network analysis associated with DCY84T+ Si suggests mechanisms underlying growth promotion and stress tolerance.</P>