• Title, Summary, Keyword: tumor initiation

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Merlin, a regulator of Hippo signaling, regulates Wnt/β-catenin signaling

  • Kim, Soyoung;Jho, Eek-hoon
    • BMB Reports
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    • v.49 no.7
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    • pp.357-358
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    • 2016
  • Merlin, encoded by the NF2 gene, is a tumor suppressor that exerts its function via inhibiting mitogenic receptors at the plasma membrane. Although multiple mutations in Merlin have been identified in Neurofibromatosis type II (NF2) disease, its molecular mechanism is not fully understood. Here, we show that Merlin interacts with LRP6 and inhibits LRP6 phosphorylation, a critical step for the initiation of Wnt signaling. We found that treatment of Wnt3a caused phosphorylation of Merlin by PAK1, leading to detachment of Merlin from LRP6 and allowing the initiation of Wnt/β-catenin signaling. A higher level of β-catenin was found in tissues from NF2 patients. Enhanced proliferation and migration caused by knockdown of Merlin in glioblastoma cells were inhibited by suppression of β-catenin. Conclusively, these results suggest that sustained Wnt/β-catenin signaling activity induced by abrogation of Merlin-mediated inhibition of LRP6 phosphorylation might be a cause of NF2 disease.

Reduced Telomere Length in Colorectal Carcinomas

  • Feng, Tong-Bao;Cai, Lei-Ming;Qian, Ke-Qing;Qi, Chun-Jian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.443-446
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    • 2012
  • Purpose: Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. The aim of this study was to determine whether telomere length is associated with the colorectal carcinoma. Patients and methods: A total of 148 colorectal cancer (CRC) samples and corresponding adjacent non-cancerous tissues were evaluated for telomere length, P53 mutation, and cyclooxygenase-2 (COX-2) mutation detected by fluorescent immunohistochemistry. Telomere length was estimated by real-time PCR. Samples with a T/S>1.0 have an average telomere length greater than that of the standard DNA; samples with a T/S<1.0 have an average telomere length shorter than that of the standard DNA. Results: Telomeres were shorter in CRCs than in adjacent tissues, regardless of tumor stage and grade, site, or genetic alterations (P=0.004). Telomere length in CRCs also had differences with COX-2 status (P=0.004), but did not differ with P53 status (P=0.101), tumor progression (P=0.244), gender (P=0.542), and metastasis (P=0.488). There was no clear trend between T/S optimal cut-off values (<1 or > 1) and colorectal tumor progression, metastasis, gender, P53 and COX-2 status. Conclusion: These findings suggesting that telomere shortening is associated with colorectal carcinogenesis but does not differ with tumor progression, gender, and metastasis.

The Effect of Hypnotics on Sleep Quality and Cognitive Function in Patients with Brain Tumors

  • Chang, Min Cheol;Chun, Min Ho
    • Journal of Korean Neurosurgical Society
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    • v.63 no.2
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    • pp.261-267
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    • 2020
  • Objective : We investigated the effect of hypnotics on sleep quality, cognitive function, and depressive mood in patients with insomnia following brain tumor resection. Methods : From patients who underwent brain tumor resection, we recruited 10 patients with insomnia who received hypnotics for more than 1 week during a 3-week follow-up period (insomnia group). We also recruited 12 control patients with brain tumors but without insomnia (control group). We evaluated sleep quality at baseline and 3 weeks later using the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), the Stanford Sleepiness Scale (SSS), and the Epworth Sleepiness Scale (ESS) and investigated cognitive function and depression using the Computerized Neuropsychological Test and the Beck Depression Inventory (BDI). Results : At baseline, SSS, ISI, PSQI, and BDI scores were significantly higher and visual continuous performance test (VCPT) and auditory continuous performance test (ACPT) scores were significantly lower in the insomnia than in the control group. Three weeks later, the patients who had received hypnotics had significantly higher ISI, PSQI, ESS, VCPT, ACPT, visual span forward and backward, and visual recognition test scores, and significantly lower BDI scores. Conclusion : Quality of sleep in patients with insomnia following brain tumor resection was initially poor but improved significantly after taking hypnotic medication. Further, the hypnotic medications appeared to contribute to the amelioration of cognitive impairments and depressive moods in patients who previously underwent brain tumor resection. We thus recommend the use of hypnotics for patients with brain tumors with insomnia.

The Effects of Blood-acting and Stasis-eliminating therapy on Anti-tumor and hematogenic metastasis (활혈화어법(活血化瘀法)의 항종양(抗腫瘍) 및 혈행(血行) 전이(轉移)에 대(對)한 고찰(考察))

  • Park, Mee-Ryong;Lee, Yeon-Weol;Cho, Jung-Hyo;Son, Chang-Kyu;Yoo, Hwa-Seung;Cho, Chong-Kwan
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.9 no.1
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    • pp.53-63
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    • 2003
  • This study was analyzed the effects of blood-activating and stasis-eliminating herbs on anti-tumor and hematogenic metastasis. The metastasis and recurrence of tumor was the basis of yudok(yudu) on remained tumor cell and stagnation of blood, thermotoxo, phlegm, asthenia of healthy enerngy, stagnation of vital energy. Malignant tumor is caused by carcinogen and go through the progress of initiation, promotion, progression, it is closely related with Eohyul$(y{\grave{u}}xi {\breve{e}})$. Symptoms of blood stasis disease are purplish tongue, mass, fixed stabbing pain, ecchymosis of nail, hypodermic petechia, dermal thesaurismosis, melena, ecchymoma, disturbance of circulation. Effects on the therapy of activating blood circulation and congestion are anti-tumor, anti-coagulation, anti-hemolysis, anti-solution, anti-inflammation, anti-infection, control of blood circulations, control of connective tissue metabolism and control of immunity. They can directly kill the cancer cells entering the blood circulation, inhibit the formation of tumor embody and reduce the blood hyperviscosity. It is suggested that these herbs can be used to prevent and treat blood metastasis of cancer under the guidance of syndrome differentiation.

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The Effect of Bromocriptine Treatment for Invasive Prolactinoma (침습성 프로락틴 분비 뇌하수체 선종에서 Bromocriptine의 치료효과)

  • Yang, Moon-Sool;Kim, Sun-Ho;Lim, Seung-Gil;Lee, Seung-Koo
    • Journal of Korean Neurosurgical Society
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    • v.37 no.4
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    • pp.275-281
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    • 2005
  • Objective: The prolactinoma is the most common pituitary tumor and sometimes shows severe invasiveness to the adjacent cavernous sinus, especially in the male patient. The dopamine agonist can be used as an alternative treatment modality to surgery. But, the transsphenoidal or transcranial approach for tumor removal has been more preferred treatment option of neurosurgeons in invasive prolactinoma. Especially rapid decompression of mass effect and resolution of the neurologic deficit is demanded. The prospective study is done in order to identify the therapeutic efficacy of bromocriptine as an initial treatment option for the invasive prolactionomas. Methods: Twenty patients with invasive prolactinoma were studied. Preoperative neurological and endocrinological evaluations were done, and size and invasiveness of the tumor was estimated on MRI. Bromocriptine was administrated by increasing dose planning reaching maximum dose at 1 month of treatment, with close neurological and endocrinological monitoring. At 3months after treatment, MRI was taken and decision was made whether to continue bromocriptine or to have surgical intervention. Results: Thirteen patients showed excellent result with only bromocriptine treatment. These patients showed not only marked reduction of tumor volume and prolactin level, but also, improving clinical symptoms and other hormonal deficits. 13patients who had visual field defect and decreased visual acuity had all improved visual symptoms. But, the remaining 4patients required surgical treatment due to insufficient reduction of tumor size inspite of normalized prolactin level within 3months. Remaining 2patients had $20{\sim}30%$ of tumor size reduction, but prolactin level was not normalized. One patient required radiation therapy. Conclusion: Bromociptine can be used as initial treatment for the invasive prolactinomas with careful monitoring of the neurological and endocrinological status. It should be carefully followed up for tumor size reduction within 3 months after initiation of treatment.

Inhibitory effect of dietary turmeric (Curcuma longa L.) ethanol extract on DMBA-induced mammary carcinogenesis in rats (울금 투여에 의한 DMBA 유발 랫드 유선암화과정 억제효과)

  • Kim, Min Sook;Jeong, Kyu Shik;You, Mi-Kyoung;Kim, Hyeon-A
    • Korean Journal of Food Preservation
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    • v.21 no.3
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    • pp.301-307
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    • 2014
  • The purpose of this study was to examine the potential of turmeric (Curcuma longa L.) to inhibit 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in rats. Female Sprague Dawley rats were fed a control diet (NC and DC) or an ethanol extract of turmeric (DT) diet until the end of the experiment. The rats in the DC and DT groups were administered a single dose of DMBA (50 mg/Kg) by oral gavages at 50 days of age. The turmeric ethanol extracts decreased the incidence and multiplicity of DMBA-induced mammary tumor. The turmeric ethanol extract significantly decreased the tumor cell proliferation. The turmeric also significantly decreased the tumor grade based on the degree of the tubule formation. The results suggest that the ethanol extract of turmeric has an inhibitory effect against mammary carcinogenesis, and that such chemopreventive effect may be related to the inhibition of the initiation and the proliferation of tumor cells.

Inhibitory activity of plant extracts on Cell-ECM adhesion (암세포에 대한 식물 추출물의 세포외 기질 접착저해 활성)

  • Lee, Sang-Myung;Lee, Ho-Jae;Lee, Choong-Hwan;An, Ren Bo;Na, Min-Kyun;Bae, Ki-Hwan;Kho, Yung-Hee
    • Korean Journal of Pharmacognosy
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    • v.31 no.4
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    • pp.394-400
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    • 2000
  • Tumor cell interaction with the extracellular matrix (ECM) is defined as the critical event of tumor invasion that signals the initiation of a metastatic cascade. To search for anti-metastatic agent from plants, several plant extracts were screened by cell- ECM anti-adhesion test. As result, Boehmeria pannosa, Dryopteris crassirhizoma, Scilla scilloides, and Agrimonia pilosa were shown a significant anti-adhesion activity.

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Sesquicillin, an Extracellular Matrix Adhesion Inhibitor, Inhibits the Invasion of B16 Melanoma Cells In vitro

  • Lee, Ho-Jae;Chun, Hyo-Kon;Chung, Myung-Chul;Lee, Choong-Hwan;Kho, Yung-Hee
    • Journal of Microbiology and Biotechnology
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    • v.9 no.1
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    • pp.119-121
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    • 1999
  • Tumor cell interaction with the extracellular matrix is defined as the critical event of tumor invasion that signals the initiation of a metastatic cascade. Sesquicillin has been identified as an inhibitor of melanoma cell adhesion to the components of the extracellular matrix (ECM) in cultured broth of fungal strain F60063. Sesquicillin strongly inhibited the adhesion of B16 melanoma cells to laminin, fibronectin, and typeIV collagen. It also inhibited B16 melanoma cell invasion of reconstituted basement membrane Matrigel in vitro in a dose-dependent manner. These results suggest that sesquicillin is a new class of nonpeptidic ECM adhesion inhibitor having anti-invasive activity.

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Role of MicroRNAs in the Warburg Effect and Mitochondrial Metabolism in Cancer

  • Jin, Li-Hui;Wei, Chen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7015-7019
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    • 2014
  • Metabolism lies at the heart of cell biology. The metabolism of cancer cells is significantly different from that of their normal counterparts during tumorigenesis and progression. Elevated glucose metabolism is one of the hallmarks of cancer cells, even under aerobic conditions. The Warburg effect not only allows cancer cells to meet their high energy demands and supply biological materials for anabolic processes including nucleotide and lipid synthesis, but it also minimizes reactive oxygen species production in mitochondria, thereby providing a growth advantage for tumors. Indeed, the mitochondria also play a more essential role in tumor development. As information about the numorous microRNAs has emerged, the importance of metabolic phenotypes mediated by microRNAs in cancer is being increasingly emphasized. However, the consequences of dysregulation of Warburg effect and mitochondrial metabolism modulated by microRNAs in tumor initiation and progression are still largely unclear.

DNA Methylation Biomarkers for Nasopharyngeal Carcinoma: Diagnostic and Prognostic Tools

  • Jiang, Wei;Cai, Rui;Chen, Qiu-Qiu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8059-8065
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    • 2016
  • Nasopharyngeal carcinoma (NPC) is a common tumor in southern China and south-eastern Asia. Effective strategies for the prevention or screening of NPC are limited. Exploring effective biomarkers for the early diagnosis and prognosis of NPC continues to be a rigorous challenge. Evidence is accumulating that DNA methylation alterations are involved in the initiation and progression of NPC. Over the past few decades, aberrant DNA methylation in single or multiple tumor suppressor genes (TSGs) in various biologic samples have been described in NPC, which potentially represents useful biomarkers. Recently, large-scale DNA methylation analysis by genome-wide methylation platform provides a new way to identify candidate DNA methylated markers of NPC. This review summarizes the published research on the diagnostic and prognostic potential biomarkers of DNA methylation for NPC and discusses the current knowledge on DNA methylation as a biomarker for the early detection and monitoring of progression of NPC.