• Title, Summary, Keyword: tumor initiation

Search Result 117, Processing Time 0.037 seconds

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

  • Kim, Wantae;Khan, Sanjoy Kumar;Yang, Yingzi
    • BMB Reports
    • /
    • v.50 no.1
    • /
    • pp.1-2
    • /
    • 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.

Detection of progressive and regressive phase and LINE-1 retrotransposon in transfected dogs with transmissible venereal tumor during chemotherapy

  • Vural, Sevil Atalay;Haziroglu, Rifki;Vural, Mehmet R.;Polat, Ibrahim M.;Tunc, Arda S.
    • Journal of Veterinary Science
    • /
    • v.19 no.5
    • /
    • pp.620-626
    • /
    • 2018
  • Canine transmissible venereal tumor (CTVT) is a tumor that commonly occurs in genital and extragenital sites of both genders. Long interspersed nuclear elements (LINE-1) retrotransposon has a pivotal role in allogenic transfection among uncontrolled dog populations. This study aimed to perform pathomorphological, immunohistochemical, and in situ polymerase chain reaction (PCR) evaluation of CTVT (n = 18) in transfected dogs during chemotherapy. Immunohistochemically, tumor phases were investigated by using specific markers (CD3, CD4, CD8, CD79, and transforming growth factor beta [$TGF-{\beta}$]), and investigated an amplified specific sequence of TVT LINE-1 retrotransposon by in situ PCR. Polyhedral-shaped neoplastic cells that had large, round, hypo/hyperchromatic nuclei and eosinophilic cytoplasm were detected. All marker results were positive, especially in the early weeks of recovery. CD4 and $TGF-{\beta}$ markers were conspicuously positive at the initial stage. In situ PCR LINE-1 sequence was initially positive in only four cases. It is believed that the CD and $TGF-{\beta}$ markers provide phase identification at tumor initiation and during chemotherapy. It is thought that presence of T and B lymphocytes, which have roles in cellular and humoral immunity, is needed so that regression of the tumor is possible.

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

  • 강경선;이영순
    • Toxicological Research
    • /
    • v.13 no.1_2
    • /
    • pp.23-27
    • /
    • 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.

  • PDF

Post-traumatic Intramuscular Hemangioma of the Chest Wall

  • Ryu, Kyoung-Min;Lee, Won-Ae
    • The Korean Journal of Thoracic and Cardiovascular Surgery
    • /
    • v.44 no.6
    • /
    • pp.458-460
    • /
    • 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
    • /
    • v.43 no.2
    • /
    • pp.176-181
    • /
    • 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.

Korean Sa-Ahm Acupuncture for Treating Canine Oral Fibrosarcoma

  • Choi, Keum Hwa;Flynn, Kristi
    • Journal of Acupuncture & Meridian Studies
    • /
    • v.10 no.3
    • /
    • pp.211-215
    • /
    • 2017
  • A nine-year-old male neutered Golden Retriever presented with oral fibrosarcoma. Sa-Ahm Traditional Korean acupuncture was provided along with medicinal herb treatment. Based on Sa-Ahm's theory, the constitution of this case was hypoactive Large-Intestine (LI) meridian qi. The acupuncture treatment was focused on reinforcing LI meridian qi along with reinforcing Small-Intestine and Liver meridian qi. The necrosis of the tumor started from 8 months after treatments and was completely necrotized around 1 month after initiation of tumor necrosis. Karnofsky Performance Status score was 80 to 100 % throughout the treatment except during the active stage of tumor necrosis having KPS of 50%. In this study, oral fibrosarcoma was managed well by both Sa-Ahm acupuncture and medicinal herb treatment. The result suggested that Sa-Ahm acupuncture along with herbal treatment could be a potential medical option for canine oral FSA therapy.

DNA methylation: an epigenetic mark of cellular memory

  • Kim, Mirang;Costello, Joseph
    • Experimental and Molecular Medicine
    • /
    • v.49 no.4
    • /
    • pp.11.1-11.8
    • /
    • 2017
  • DNA methylation is a stable epigenetic mark that can be inherited through multiple cell divisions. During development and cell differentiation, DNA methylation is dynamic, but some DNA methylation patterns may be retained as a form of epigenetic memory. DNA methylation profiles can be useful for the lineage classification and quality control of stem cells such as embryonic stem cells, induced pluripotent cells and mesenchymal stem cells. During cancer initiation and progression, genome-wide and gene-specific DNA methylation changes occur as a consequence of mutated or deregulated chromatin regulators. Early aberrant DNA methylation states occurring during transformation appear to be retained during tumor evolution. Similarly, DNA methylation differences among different regions of a tumor reflect the history of cancer cells and their response to the tumor microenvironment. Therefore, DNA methylation can be a useful molecular marker for cancer diagnosis and drug treatment.

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

  • Park, Seung hwa;Jung, InKyung;Kim, Jung-Hyun
    • Journal of Nutrition and Health
    • /
    • v.53 no.4
    • /
    • pp.369-380
    • /
    • 2020
  • Purpose: It has been previously reported that breast tumor incidence, growth, and metastasis are stimulated by high-fat diet but reduced by caloric restriction. However, few studies have elucidated the effects of dietary change from a high-fat diet after breast cancer initiation. Therefore, in this study, we attempted to provide practical assistance to breast cancer prevention and management by investigating the effects of dietary change from a high-fat diet to normal diet on breast cancer growth and metastasis. Methods: The experimental animals were divided into 2 groups (high-fat diet control [HFC] group and diet restriction [DR] group) and consumed a high-fat diet for 8 weeks. 4T1 cells were transplanted into subcutaneous fat or tail vein to measure the growth and metastasis of breast cancer. The HFC and DR groups continuously ingested either high-fat diet or AIG-93G diet for 5 weeks or 3 weeks, respectively. Cell proliferation and apoptosis markers from tumor tissues were analyzed by Western blot analysis. The data were analyzed using the SPSS 25.0 package program. Results: The results show that the DR group significantly reduced breast tumor initiation, growth, and tumor tissue weight compared to the HFC group. The DR group suppressed tumor growth by decreasing proliferation and inducing apoptosis through down-regulation of Bcl-xL and up-regulation of caspase-3 activity. Furthermore, the DR group significantly reduced numbers of metastasized tumors in lung tissues. Conclusion: These results suggest that dietary change from a high-fat diet to normal diet decreased breast growth by reducing cell proliferation and inducing apoptosis and metastasis. Taken together, these results indicate that dietary change to a low-fat and balanced diet might suppress breast tumor growth and metastasis even after tumor diagnosis.

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

  • 최광태;양덕춘
    • Journal of Ginseng Research
    • /
    • v.10 no.1
    • /
    • pp.45-54
    • /
    • 1986
  • These studies were carried out to obtain the basic information about transformation of ginseng plant by potential vector system, utilization of opine compound by Agrobacterium sap. , and initiation of crown gall tumor callus. Crown gall tumors were induced from stem of Panax ginseng C.A. Meyer by infection of Agrobacterium tumefaciens. Therefore, it was clarified that transformation of ginseng by Ti plasmid was possible. The crown gall tumors induced by Agrobacterium tumefaciens isolated. from the soil were different in a shape, size, and growth rate. Especially, infection of ginseng by Agrobacterium tumefaciens Y104 led to the amorphic tumor, Tumor tissue derived from stem crown gall could not be continuously cultured on the medium which did not contain phytohormone, and did not form the callus even on the medium supplemented with 2,4-D. On the other hand, the root crown gall tumors formed the calli but the formation rate of callus was quite low. As for the utilization of octopine and nopaline, it was found that 3 strains of Agrobacterium app., Y104, Y110 and C58, utilized nopaline only, Y109 utilized octopine, and Y101 failed to utilize either compound.

  • PDF

Tumor lysis syndrome following sorafenib treatment in hepatocellular carcinoma

  • Kim, Shin Young;Kim, Hee Yeon;Kim, Yu Seung;Lee, Sang Min;Kim, Chang Wook
    • Yeungnam University Journal of Medicine
    • /
    • v.32 no.1
    • /
    • pp.47-49
    • /
    • 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.