• Title/Summary/Keyword: Tumor initiation

검색결과 137건 처리시간 0.024초

Molecular imaging of polarized macrophages in tumors

  • Ran Ji Yoo;Yun-Sang Lee
    • 대한방사성의약품학회지
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    • 제7권1호
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    • pp.41-49
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    • 2021
  • Diversity and flexibility are two typical hallmarks of macrophages. Two types of macrophages, M1(classically activated macrophages) and M2(alternatively activated macrophages) exist at both ends of the commonly known macrophage polarization. M1 macrophages have inflammatory properties and are primarily responsible for defending against invading bacteria in our body. On the other hand, M2 macrophages are involved in anti-inflammatory responses and tissue remodeling. Polarized migration of macrophages is of increasing interest in regulating the initiation, generation, and resting phases of inflammatory diseases. In this review, it intend to discuss the properties and functions of tumor-associated macrophages based on polarized macrophages that affect inflammatory diseases. In addition, the purpose of this study is to investigate a molecular imaging approach that targets macrophages that affect tumor growth by controlling the polarization of macrophages that affect tumor diagnosis and treatment.

Control and Mechanism of Tumor Promotion in UV-Carcinogenesis

  • Ueda, Masato;Budiyanto, Arief;Ashida, Masashi;Bito, Toshinori;Ichihashi, Masamitsu
    • Journal of Photoscience
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    • 제9권2호
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    • pp.221-224
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    • 2002
  • Carcinogenesis can be theoretically divided to intiation step and promotion step. Intiation associates with genetic alterations including p53 tumor suppressor gene and ras oncogene. Promotion involves in clonal expansion of of an initiated cell by epigenetic mechanism, mainly through signal transduction and gene expression. Ultraviolet light (UV) acts as both initiator and promoter. Initiation is closely related with DNA damage induced by UV, including cyclobutane pyrimidine dimers, (6-4) photoproducts and 8-hydroxy-2'-deoxyguanosine. Cyclobutane pyrimidine dimers and (6-4) photoproducts are directly induced by UV, while 8-hydroxy-2'-deoxyguanosine is induced indirectly by the reactive oxygen species. Because initiation is an irreversal genetic event, while promotion is a reversal and epigenetic event, to know the molecular mechanisms of tumor promotion in UV-carcinogenesis is crucial to develop preventive medicine and suppress UV-carcinogenesis. Because ROS is also involved in signal transduction of the cell, anti-oxidant could be the good candidate of anti-promoting agent. Here, we describe the suppressive effect of UV-carcinogenesis by various anti-oxidant including olive oil. In addition, we discuss about the mechanism of UVB-induced expression of cyclooxygenase-2, which might be a representative molecule involved in promotion of UV-carcinogenesis.

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Interacting network of Hippo, Wnt/β-catenin and Notch signaling represses liver tumor formation

  • Kim, Wantae;Khan, Sanjoy Kumar;Yang, Yingzi
    • BMB Reports
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    • 제50권1호
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    • pp.1-2
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    • 2017
  • Acquiring a selective growth advantage by breaking the proliferation barrier established by gatekeeper genes is a centrally important event in tumor formation. Removal of the mammalian Hippo kinase Mst1 and Mst2 in hepatocytes leads to rapid hepatocellular carcinoma (HCC) formation, indicating that the Hippo signaling pathway is a critical gatekeeper that restrains abnormal growth in hepatocytes. By rigorous genetic approaches, we identified an interacting network of the Hippo, Wnt/${\beta}$-catenin and Notch signaling pathways that control organ size and HCC development. We found that in hepatocytes, the loss of Mst1/2 leads to the activation of Notch signaling, which forms a positive feedback loop with Yap/Taz (transcription factors controlled by Mst1/2). This positive feedback loop results in severe liver enlargement and rapid HCC formation. Blocking the Yap/Taz-Notch positive feedback loop by Notch inhibition in vivo significantly reduced the Yap/Taz activities, hepatocyte proliferation and tumor formation. Furthermore, we uncovered a surprising inhibitory role of Wnt/${\beta}$-catenin signaling to Yap/Taz activities, which are important in tumor initiation. Genetic removal of ${\beta}$-catenin in the liver of the Mst1/2 mutants significantly accelerates tumoriogenesis. Therefore, Wnt/${\beta}$-catenin signaling, known for its oncogenic property, exerts an unexpected function in restricting Yap/Taz and Notch activities in HCC initiation. The molecular interplay between the three signaling pathways identified in our study provides new insights in developing novel therapeutic strategies to treat liver tumors.

The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis

  • Christopher J. Occhiuto;Jessica A. Moerland;Ana S. Leal;Kathleen A. Gallo;Karen T. Liby
    • Molecules and Cells
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    • 제46권3호
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    • pp.176-186
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    • 2023
  • The oxidative balance of a cell is maintained by the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. This cytoprotective pathway detoxifies reactive oxygen species and xenobiotics. The role of the KEAP1/NRF2 pathway as pro-tumorigenic or anti-tumorigenic throughout stages of carcinogenesis (including initiation, promotion, progression, and metastasis) is complex. This mini review focuses on key studies describing how the KEAP1/NRF2 pathway affects cancer at different phases. The data compiled suggest that the roles of KEAP1/NRF2 in cancer are highly dependent on context; specifically, the model used (carcinogen-induced vs genetic), the tumor type, and the stage of cancer. Moreover, emerging data suggests that KEAP1/NRF2 is also important for regulating the tumor microenvironment and how its effects are amplified either by epigenetics or in response to co-occurring mutations. Further elucidation of the complexity of this pathway is needed in order to develop novel pharmacological tools and drugs to improve patient outcomes.

랫드의 간압발생과정에서 홍삼의 항암효과와 자연살해세포의 (Involvement of the Enhancement of Natural Killer Cell Activity on the Anti-Cancer Effect of Red Gingseng during Rat Hepatocarcinogenesis)

  • 강경선;이영순
    • Toxicological Research
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    • 제13권1_2호
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    • pp.23-27
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    • 1997
  • This study was performed to examine the anti-cancer effect of Red Ginseng in the DENGalN-PH-induced hepatic tumor model system in rats. One hundred of male SPF Sprague-Dawley rats(6weeks old) were randomly divided into five groups. Rats in groups 1, 2, 3, and 4 were administered to diethylnitrosamine intraperitoneally 200 mg/kg body weight for the caner initiation. Rats in group 5 were given to saline as a control. On two weeks after cancer initiation, rats in groups 1 and 3 were fed on diet containing 0.01% of acethylaminofiuorene(AAF) which is strong cancer-promotor for 6 weeks, while rats in groups 2 and 4 were fed on water containing 0.05% of phenobarbital which is weak cancer.promotor for 6 weeks. Rats in groups 1 and 2 were treated with diet containing 3% of Red Ginseng for six weeks(from 9th week till 15th week after cancer initiation). Rats in all groups were necropsied time-sequencially at 8, 15, and 36 weeks. The hepatic lesions of rat treated with carcinogens expressed glutathione S-transferase placental form(GST-P) at 8 week. The GST-P positive foci of rats treated with AAF were larger than that of any other rats, while the GST-P positive foci of rats treated with AAF and red ginseng were significantly decreased. This anti-cancer effect of Red ginseng might be involved in the enhacement of natural killer cell activity. To know whether there is direct relationship between Red Ginseng and natural killer cell activity, the activity of natural killer cell was examined after treatment AAF, AAF+Red ginseng and Red ginseng only, respectively. Comparing with natural killer cell activity in AAF-treated group, natural killer cell activity was significantly activated in AAF+ Red ginseng-treated group. This indicated that Red ginseng might enhance natural killer activity after treatment carcinogen in rats. These results suggested that Red ginseng might have a cancer prevention ability by promoting natural killer cell activity during hepatocarclnogenesis.

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인삼의 Crown Gall Tumor형성에 관한 연구 (Formation of Crown Gall Tumor in Panax ginseng C.A. Meyer)

  • 최광태;양덕춘
    • Journal of Ginseng Research
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    • 제10권1호
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    • pp.45-54
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    • 1986
  • 인삼에 이용할 수 있는 vector system의 개발연구의 일환으로 우선 Agrobacterium spp.를 인삼의 잎, 줄기 및 뿌리에 접종하여 crown gall tumor의 형성 및 탈분화 그리고 Agrobacterium spp.의 opine화합물의 이용정도등을 조사하였던 바 그 결과를 요약하면 다음과 같다. 1. Agrobacterium tumefaciens C58은 인삼의 모든 부위에서 crown gall tumor를 형성하였으나 secondary tumor나 teratoma는 형성하지 못했다. 2. Wild type Agrobacterium tumefaciens Y101, Y104, Y109는 crown gall tumor를 형성하였으며, tumor의 형태, 크기 그리고 생장 정도는 strain별로 차이가 있었다. 3. Agrobacterium tumefaciens Y194는 특히 amorphic tumor를 형성하였다. 4. 줄기에서 형성된 tumor조직에서 callus를 유기하고자 phytohormone free배지 및 2,4-D 첨가 배지에 접종한 결과 전혀 callus가 형성되지 않았다. 5. 뿌리에서 형성된 callus가 형성되긴 하였으나 출현빈도가 극히 낮았으며, 정상 조직과는 달리 2,4-D의 효과가 미미하였다. 6. Agrobacterium spp.에 의한 opone화합물의 이용능력을 조사한 결과, Agrobacterium tumefacciens Y104, Y110 과 C58은 nopaline type이었고 Y109는 octopine type이었으며, Y101은 nopaline과 octopine 어느것도 이용하지 못하였다.

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Post-traumatic Intramuscular Hemangioma of the Chest Wall

  • Ryu, Kyoung-Min;Lee, Won-Ae
    • Journal of Chest Surgery
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    • 제44권6호
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    • pp.458-460
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    • 2011
  • Intramuscular hemangioma originated in chest wall is a rare benign tumor, with no relevant reports in Korea. In most cases, the tumor is discovered before the age of 30 years and it is reported that trauma operates as the initiation factor. It is essential to concern the clinical suspicion and conduct a CT scan for diagnosis. The principle of treatment is surgical excision with clear resection margin. The authors of this study report a case of surgical excision for post-traumatic intramuscular hemangioma of the chest wall with review of literature.

Oncogenic RUNX3: A Link between p53 Deficiency and MYC Dysregulation

  • Date, Yuki;Ito, Kosei
    • Molecules and Cells
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    • 제43권2호
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    • pp.176-181
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    • 2020
  • The RUNX transcription factors serve as master regulators of development and are frequently dysregulated in human cancers. Among the three family members, RUNX3 is the least studied, and has long been considered to be a tumor-suppressor gene in human cancers. This idea is mainly based on the observation that RUNX3 is inactivated by genetic/epigenetic alterations or protein mislocalization during the initiation of tumorigenesis. Recently, this paradigm has been challenged, as several lines of evidence have shown that RUNX3 is upregulated over the course of tumor development. Resolving this paradox and understanding how a single gene can exhibit both oncogenic and tumor-suppressive properties is essential for successful drug targeting of RUNX. We propose a simple explanation for the duality of RUNX3: p53 status. In this model, p53 deficiency causes RUNX3 to become an oncogene, resulting in aberrant upregulation of MYC.

고지방식이에서 일반식이로의 전환이 유방암의 성장 및 전이에 미치는 영향 (Effect of dietary changes from high-fat diet to normal diet on breast cancer growth and metastasis)

  • 박성화;정인경;김정현
    • Journal of Nutrition and Health
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    • 제53권4호
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    • pp.369-380
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    • 2020
  • 본 연구에서는 일반식이로의 식이 제한이 고지방식이로 촉진된 유방암의 성장과 전이에 미치는 영향과 그 기전을 알아보았다. 8주간 고지방식이를 섭취시킨 후 유방암을 유방 조직에 이식하거나 꼬리 정맥으로 통해 전이시켰으며, 암 생성 및 전이 후 HFC군은 고지방식이를, DR군은 일반식이로 전환시켜 사육하였다. 본 연구 결과, 원발성 유방암의 경우, HFC군과 DR군의 체중에는 차이가 없었으나 간과 비장, 신장 주변의 지방세포의 무게에서 유의한 차이를 보였다. DR군이 HFC군에 비해 유방암의 개시를 지연시켰으며, 유방암의 성장과 무게를 유의하게 감소시켰다. 일반식이로의 전환에 의한 유방암 성장 억제는 세포 분열 억제와 세포사멸을 조절하는 인자의 발현 감소에 의한 caspase-3의 활성 촉진에 의한 것으로 나타났다. 또한, 식이 제한은 폐로 전이된 유방암의 수를 유의미하게 감소시켰다. 본 실험 결과, 일반식이로의 제한은 고지방식이로 촉진된 유방암의 성장과 전이를 억제하는 효과를 나타내며, 이는 유방암 세포의 성장 억제와 사멸 유도에 의한 것으로 나타났다. 따라서, 유방암의 성장이나전이를 억제하기 위해서는 총 섭취 열량을 조절하고, 지방의 섭취량을 줄이는 균형 잡힌 식이를 섭취하도록 해야 할 것으로 사료된다.

Tumor lysis syndrome following sorafenib treatment in hepatocellular carcinoma

  • Kim, Shin Young;Kim, Hee Yeon;Kim, Yu Seung;Lee, Sang Min;Kim, Chang Wook
    • Journal of Yeungnam Medical Science
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    • 제32권1호
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    • pp.47-49
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    • 2015
  • Sorafenib is indicated for the treatment of advanced hepatocellular carcinoma (HCC), but although rare, tumor lysis syndrome (TLS) can be fatal in HCC patients with a large tumor burden. The authors describe the case of a 55-year-old hepatitis B carrier who visited our clinic with progressive dyspnea for 3 weeks. Chest and abdominal computed tomography revealed a huge HCC in the left lobe of the liver with invasion of the inferior vena cava, right atrium, and pulmonary arteries. After 8 days of sorafenib administration, TLS was diagnosed based on the characteristic findings of hyperuricemia, hyperkalemia, and acute kidney injury with massive tumor necrosis by follow-up imaging. Despite discontinuation of sorafenib and supportive care, the patient's clinical course rapidly deteriorated. The authors describe a rare but fatal complication that occurred soon after sorafenib initiation for HCC. Careful follow-up is required after commencing sorafenib therapy for the early diagnosis and management of TLS.