• 제목/요약/키워드: Ovarian metastasis

검색결과 69건 처리시간 0.027초

튜머로이드-혈관신생 상호작용의 가시화를 위한 개방형 구조 미세유체 칩 개발 (Development of open-top microfluidic chip for visualization of interactions between tumoroids and angiogenic sprouting)

  • 김승규;김지원;박준하;오상윤;신현정;전성윤
    • 한국가시화정보학회지
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    • 제18권3호
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    • pp.84-89
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    • 2020
  • Cancer cells secrete angiogenic factors, and nearby vasculatures make new blood vessels essential for cancer development and metastasis in response to these soluble factors. Many efforts have been made to elucidate cancer-endothelial cell interactions in vitro. However, not much is known due to the lack of a suitable co-culture platform. Here, we introduce a 3D printing-based microfluidic system that mimics the in vivo-like cancer-endothelial cell interactions. The tumoroids and endothelial cells are co-cultured, physically separated by porous fibrin gel, allowing communication between two cell types through soluble factors. Using this microfluidic system, we were able to visualize new vessel formation induced by tumoroids of different origins, including liver, breast, and ovary. We confirmed that the ovarian tumoroids most induced angiogenesis while the other two cancer types suppressed it. Utilization of the proposed co-culture platform will help the researchers unveil the underlying mechanisms of the dynamic interplay between tumor and angiogenesis.

암 치료 표적으로써 OTUB1 (Deubiquitinase Otubain 1 as a Cancer Therapeutic Target)

  • 김동은;우선민;권택규
    • 생명과학회지
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    • 제30권5호
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    • pp.483-490
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    • 2020
  • 유비퀴틴 시스템은 ubiquitin ligases와 deubiquitinases (DUBs)에 의해 타겟 기질의 ubiquitination 유무에 따라 안정화, 활성화, 국소화 및 상호작용을 변화시키고 암 발병의 관여하는 다양한 생물학적 과정을 조절한다. DUBs는 촉매 domain에 따라 6그룹으로 나뉘어지는데, 그 중에서 OTU 그룹 내 대부분의 DUB는 세포의 연속적 신호반응(cell signaling cascade)을 조절할 수 있다. 특이하게도 OTU 그룹에 속하는 otubain 1 (OTUB1)은 정규적(canonical) 활성과 비정규적(non-canonical) 활성을 모두 가지고 있다. 본 보고에서는 OTUB1의 canonical, non-canonical 활성 조절에 있어서 다양한 신호전달경로 및 OTUB1의 역할에 대해 기술하였다. OTUB1은 이 두 종류의 활성 경로를 통하여, OTUB1은 암 관련 신호 전달 체계에 중요한 FOXM1, ERα, KRAS 및 EMT를 조절하고 암세포 증식 및 전이 능력 향상 및 항암제에 대한 내성을 나타낸다. 또한 임상적으로 전이성 및 종양 분화도가 높은 암 조직에서 OTUB1의 발현이 높으며, 이에 따라 환자의 생존율이 감소하는 등 나쁜 예후를 나타낸다. 따라서, 임상적으로 적용할 수 있는 OTUB1 억제제의 개발이 이루어진다면 OTUB1은 종양 치료에 있어 중요한 진단마커이자 치료적인 타겟이 될 수 있다.

위암 환자에서 p53과 HSP27의 임상병리학적 의의 (Clinicopathological Significance of p53 and HSP27 in Gastric-cancer Patients)

  • 이하균;권성준;백승삼
    • Journal of Gastric Cancer
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    • 제4권3호
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    • pp.169-175
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    • 2004
  • Purpose: The tumor suppressor gene p53 has been shown to be a factor in the carcinogenesis or progression of gastric cancer. The mutant p53 has been reported to cause a higher risk of lymph-node metastasis. Futhermore, mutation of the p53 has been linked to a poor prognosis for gastric cancer. The heat shock protein-27 (HSP27), a stress protein, has also been reported to be a poor prognostic factor in ovarian and breast cancers. However, in gastric-cancer patients, controversies exist as to its influence on the prognosis. In the present study, we used an immunohistochemical stain to observe the effects of p53 and HSP27 on the clinicopathological factors and on the prognosis for gastric-cancer patients. Materials and Methods: To evaluate the significance of p53 and HSP27 in gastric cancer patients, we analyzed 212 cases of gastric cancer (stage I.IV). Tissue samples of 212 patients were stained immunohistochemically for the mutant p53 protein and for HSP27. The correlations between protein expression and the clinicopathological factors were investigated. Results: The overall expression rates for p53 and HSP27 were $36.9\%\;and\;27.8\%$, respectively. p53 and HSP27 were correlated to each other because the HSP27 expression rate was higher in the p53-positive group (P=0.046). Statistically, the p53 and the HSP27 expression rates were significantly increased in the case of tumor invasiveness, lymphatic metastasis and vessel involvement. Therefore, they play a role in cancer progression. The 5-year survival rates of the p53-positive and the p53-negative groups were $62.8\%\;and\;60.1\%$, respectively (P=0.793) while the 5-year survival rates for the HSP27-positive and HSP27-negative groups were $54.2\%\;and\;63.1\%$, respectively (P=0.090). Conclusion: p53 and HSP27 were correlated to each other in our immunohistochemical study of gastric carcinomas and they were not independent prognostic factors in gastric- cancer patients. However, further studies are needed to determine their prognostic values for gastric-cancer patients.

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Utility of Surgical Resection in the Management of Metachronous Krukenberg's Tumors of Gastric Origin

  • Kim, Gwon-Sik;Kim, Kap-Choong;Kim, Beom-Su;Kim, Tae-Hwan;Yook, Heong-Hwan;Oh, Sung-Tae;Kim, Byung-Sik
    • Journal of Gastric Cancer
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    • 제10권3호
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    • pp.111-117
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    • 2010
  • Purpose: The aim of this study was to determine the prognostic factors and the significance of metastatectomy for Krukenberg's tumors of gastric origin.Materials and Methods: Among the patient who underwent gastric surgery from 1992 through 2005, 90 female patients with Krukenberg's tumors of gastric origin were identified. We retrospectively reviewed the clinicopathologic characteristics, prognostic factors, and treatments for primary gastric cancer. We also investigated the prognostic risk factors for the onset of metachronous Krukenberg's tumors and the survival time of patients who underwent an operation for metachronous Krukenberg's tumors. Results: The presence of a synchronous Krukenberg's tumor (mean survival time=17.6 months, P<0.01), peritoneal seeding (14.5 months, P<0.01), and non-curative resection (15.1 months, P<0.01), were statistically significant prognostic factors for survival time in female patients with gastric cancer. The stage of primary gastric cancer (P=0.049) and lymph node metastasis (P=0.011) were statistically significant risk factors for recurrence time of a metachronous Krukenberg's tumor. In the metachronous Krukenberg's tumor group (n=53), the mean survival time of the metastatectomy group (n=46, 43.2 months, P=0.012) was longer than that in the chemotherapy or conservative treatment groups (n=7 and 24 months, respectively). Metastatectomy, presense or abscence of residual tumor and extent of residual tumor were significant prognostic factors for survival time in female patients with metachronous Krukenberg's tumor of gastric origin. Conclusions: A close observation and evaluation with ultrasound or computed tomography is necessary in female patients with advanced gastric cancer to detect a metachronous Krukenberg's tumor as soon as possible. The surgeon must operate more aggressively in patients with metachronous Krukenberg's tumors.

Ginsenoside Rg3의 항암효능 연구의 진보 (Recent Progress in Research on Anticancer Activities of Ginsenoside-Rg3)

  • 남기열;최재을;홍세철;표미경;박종대
    • 생약학회지
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    • 제45권1호
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    • pp.1-10
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    • 2014
  • Ginsenoside Rg3 (G-Rg3) is one of protopanaxadiol ginsenosides characteristic of red ginseng, steamed and dried ginseng (Panax ginseng), which has recently attracted much attention for its antitumor properties in vitro and in vivo animal models. Experimental studies have demonstrated that it could promote cancer cell apoptosis, inhibit cancer cell growth, the apoptosis of cancer cells, adhesion, invasion and metastasis, and also prevent an angiogenetic formation in prostate, breast, ovarian, colorectal, gastric, liver and lung cancer etc. It has shown the antitumor activities by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (vascular endothelial growth factor), tumor suppressors (p53 and p21), cell death mediators (caspases, Bcl-2, Bax), inflammatory response molecules ($NF-{\kappa}B$ and COX-2), protein kinases (JNK, Akt, and AMP-activated protein kinase) and Wnt/${\beta}$-catenin signaling. In addition, the combination of Rg3 and chemotherapeutic agents have synergistically enhanced therapeutic efficacy and reduced antagonistically side effects. Furthermore, it can reverse the multidrug resistance of cancer cells, prolong the survival duration and improve life quality of cancer patients. Taken together, accumulating evidences could provide the potential of G-Rg3 in the treatment of cancers and the feasibility of further randomized placebo controlled clinical trials.

개에서 난관 선암종, 질 섬유종 및 자궁축농증 병발 1예 (Concurrence of Uterine Tube Adenocarcinoma, Vaginal Fibroma, and Pyometra in a Dog)

  • 전은기;김일화;장동우;모인필;강현구
    • 한국임상수의학회지
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    • 제30권4호
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    • pp.310-314
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    • 2013
  • 12년령 암컷 혼혈견이 외음부에 돌출된 질 종양으로 내원하였다. 이 환자는 정상적으로 변과 오줌을 배출하였고 임신 경험은 없었다. 혈청생화학적인 소견상 질소혈증, 경미한 고나트륨 혈증과 alkaline phosphatase 값의 상승이 있었다. 혈액학적 검사 소견은 정상이었다. 초음파 검사에서 좌 우측 자궁각의 내강에 존재하는 액체로 인하여 무에코성에서 저에코성으로 나타났고 심하게 종대되어 있었다. 또한, 우측 난관의 종양 내에 국소적으로 저에코성 영역이 나타났다. 컴퓨터단층촬영에서는 우측 난소낭, 액체로 인해 확장된 자궁, 확장된 질과 질의 종양이 관찰되었다. 본 환자에 대해 난소자궁적출술과 회음부 절개술을 통한 종양절제술을 실시하여 난관과 질에 존재하는 종양을 제거하였다. 본 환자는 난관 선암종, 질 섬유종, 자궁축농증이 병발한 첫 번째 사례로 여겨진다.

Wnt에 의한 epithelial-to-mesenchymal transition에서 PFKFB2의 역할 (The Role of Phosphofructokinase-2/Fructose-2,6-bisphosphatase 2 (PFKFB2) in Wnt-induced Epithelial-mesenchymal Transition)

  • 이수연;주민경;전현민;김초희;박혜경;강호성
    • 생명과학회지
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    • 제27권11호
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    • pp.1245-1255
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    • 2017
  • 암세포는 정상세포와는 다른 metabolism 특히 glycolytic switch를 나타낸다. Glycolytic switch는 암세포가 정상세포와 달리 산소가 충분한 상태에서도 미토콘드리아에 의존하지 않고 glycolysis를 통해 대부분의 ATP 에너지를 생성하는 현상이다. 또한 암세포는 invasion 및 metastasis 능력을 획득하기 위해 epithelial-mesenchymal transition (EMT)를 나타낸다. EMT와 glycolytic switch는 암세포의 생존 및 증식에 관여하는 중요한 현상이지만, 이들 상호작용 및 그 기작에 대한 연구는 아직 밝혀져 있지 않다. Snail은 EMT를 유도하는 주요한 전사인자이다. 본 연구진은 이전 연구에서 Snail이 발생 및 암성장에 관여하는 전사인자인 Dlx-2에 의해 조절됨을 밝혔다. 또한 Wnt가 Dlx-2/Snail cascade을 통하여 EMT 및 glycolytic switch을 유도함을 밝혔다. 본 연구에서는 glycolytic switch가 Wnt에 의한 EMT에 미치는 영향을 규명하고자 하였다. Dlx-2/Snail의 glycolytic switch target 유전자로 phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2)를 발굴하였다. PFKFB2는 fructose-2,6-bisphosphate (F2,6BP)의 합성 및 분해에 관여하는 효소로서 glycolysis에서 중요하게 작용한다. Wnt에 의해 PFKFB2 발현이 Dlx-2/Snail 의존적으로 증가함을 관찰하였다. 또한 PFKFB2를 knockdown한 결과 Wnt에 의한 EMT가 억제되므로 glycolytic switch가 Wnt에 의한 EMT에 관여할 가능성이 높을 것으로 보인다. 뿐만 아니라 PFKFB2 shRNA가 xenograft mouse model에서 tumor 성장 및 metastasis를 억제하는 것으로 나타났다. 또한 Human 암조직에서 정상조직에 비해 PFKFB2의 발현이 높음을 관찰하였다. 따라서 PFKFB2가 Wnt-Dlx-2/Snail-induced EMT 및 metastasis에서 중요한 역할을 할 것으로 예상된다.

인돌 (Indol-3-Carbinol)이 인체대장암세포 HT-29 세포의 투과성 밀착결합조절과 세포 침윤성 억제에 미치는 영향 (Indol-3-Carbinol Regulated Tight Junction Permeability and Associated-Protein Level and Suppressed Cell Invasion in Human Colon Cancer Cell Line, HT-29)

  • 김성옥;최영현;최원경
    • Journal of Nutrition and Health
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    • 제41권1호
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    • pp.13-21
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    • 2008
  • 본 실험은 인돌의 인체 대장암세포의 경과 및 전이억제와 TJ 활성 조절에 미치는 영향을 알아보기 위해 실험하였다. 인돌은 십자화 야채류인 양배추, 컬리플라워, 브로클리 등에 존재하는 glucosinolate, glucobrassicin의 대사산물 이다. 본 연구의 결과는 인돌이 대장암 세포 HT-29에서 농도 의존적으로 세포증식 저해를 나타내었다. 상처회복 실험을 통한 세포이동성과 세포 침윤성 실험결과 인돌이 암세포의 이동과 침윤성을 억제하였고 투과성상피세포의 전기적 저항성 측정치는 인돌 처리 세포에서 증가하였다. HT-29 세포에서 과발현을 나타내는 밀착결합 단백질인 claudin-1, claudin-5 발현은 인돌 처리로 유전자의 전사수준과 단백질 수준에서 유의적인 감소를 나타내었다. 이상의 결과에서 인돌이 HT-29 세포의 밀착결합과 그 구성 단백질 중 claudin 발현 현상을 회복시키므로 암 경과와 전이 억제를 나타내었다. 결론적으로, 천연 항암화합물인 인돌은 대장암 세포 HT-29에서 밀착결합 단백질인 claudin-1, -5을 억제하여 밀착결합을 활성화하므로 암 진행과 전이를 억제할 수 있는 인돌에 의한 새로운 기전을 보고합니다.

이종 이식된 구강편평세포 암종에서 Paclitaxel ($Taxol^{(R)}$)의 항암 효과 (THE ANTICANCER EFFECT OF PACLITAXEL($Taxol^{(R)}$) IN ORAL SQUAMOUS CELL CARCINOMA XENOGRAFT)

  • 김기환;김철환;한세진;이재훈
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제28권2호
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    • pp.95-110
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    • 2006
  • The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.