• Molecules and Cells
• /
• 제38권3호
• /
• pp.273-278
• /
• 2015

The induction of angiogenesis is a crucial step in tumor progression, and therefore, efficient inhibition of angiogenesis is considered a powerful strategy for the treatment of cancer. In the present study, we report that the lipophilic antimicrobial peptides from EML-CAP3, a new endophytic bacterial strain isolated from red pepper leaf (Capsicum annuum L.), exhibit potent antiangiogenic activity both in vitro and in vivo. The newly obtained antimicrobial peptides effectively inhibited the proliferation of human umbilical vein endothelial cells at subtoxic doses. Furthermore, the peptides suppressed the in vitro characteristics of angiogenesis such as endothelial cell invasion and tube formation stimulated by vascular endothelial growth factor, as well as neovascularization of the chorioallantoic membrane of growing chick embryos in vivo without showing cytotoxicity. Notably, the angiostatic peptides blocked tumor cell-induced angiogenesis by suppressing the expression levels of hypoxia-inducible $factor-1{\alpha}$ and its target gene, vascular endothelial growth factor (VEGF). To our knowledge, our findings demonstrate for the first time that the antimicrobial peptides from EML-CAP3 possess antiangiogenic potential and may thus be used for the treatment of hypervascularized tumors.

• 대한두경부종양학회지
• /
• 제14권1호
• /
• pp.70-75
• /
• 1998

Tumor growth and metastasis depends on angiogenesis. Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells in vitro and promotes neoangiogenesis in vivo. Objective: Follicular thyroid cancers(FTC) are a vascular tumor and traditionally metastasize via blood vessels. Likely other cancers, angiogenesis may playa important role in FTC. We, therefore, investigated the expression of VEGF and microvascular density by immunohistochemistry in FTC and follicular adenoma(FA). Materials and Methods: Findings of immunohistochemical stainings for VEGF and CD31 were measured by grading scale from +1 to 4+(strongest) and by counting the stained microvessels in 14 FTCs and 14 FAs. Results: 1) Expression of VEGF. a) FTCs have stronger expression than FAs in areas of tumor adjacent to capsule($mean{\pm}SD\:\;3.2{\pm}0.9\;vs\;2.0{\pm}0.9$, p<0.01) and in central area($2.3{\pm}0.7\;vs\;1.3{\pm}0.6$, p<0.01). b) The VEGF expression of capsular area in FTCs are higher than that of central area(p<0.05). 2) Microvascular density by CD31. a) FTCs have more microvessels than FAs in areas of adjacent to capsule($78.9{\pm}27.3\;vs\;38.7{\pm}15.6$, p<0.01) and in central area($75.5{\pm}23.3\;vs\;27.8{\pm}10.7$, p<0.01). b) In FTCs, the number of microvessels of capsular area are more than that of central tumor area, but not significant statistically(p>0.05). Conclusion: The higher expression of VEGF and microvascular density in FTC suggests angiogenesis plays an important role in progression of FTC.

• 동의생리병리학회지
• /
• 제17권5호
• /
• pp.1309-1314
• /
• 2003

We examined the effects of Oak Smoke Flavoring (OSF, Holyessing) on the cell proliferation of DU145 and PC3 human prostate carcinoma cell line. OSF treatment resulted in a concentration-dependent inhibition of the cell viability in both DU145 and PC3 cell lines. The anti-proliferative effects by OSF treatment in DU145 and PC3 cells were associated with morphological changes such as membrane shrinking and cell rounding up. DNA flow cytometric histograms showed that population of S phase of the cell cycle was increased by OSF treatment in a dose-dependent manner. Western blot analysis revealed that cyclin B1 and cdc2 proteins were reduced by OSF treatment in DU145 cells, whereas cyclin A was markedly inhibited in PC3 cells. Furthermore, we observed an increase of Cdk inhibitor p16 and p27 protein, and an inhibition of phosphorylation of pRB by OSF treatment in a dose-dependent manner. The present results indicated that OSF-induced inhibition of human prostate carcinoma cell proliferation is associated with the blockage of S phase progression.

• Radiation Oncology Journal
• /
• 제29권4호
• /
• pp.219-227
• /
• 2011

Purpose: This study evaluated the treatment effectiveness and proper radiation dose of helical tomotherapy (HT) in spine oligometastases from gastrointestinal cancers. Materials and Methods: From 2006 to 2010, 20 gastrointestinal cancer patients were treated with HT for spine oligometastases (31 spine lesions). The gross tumor volume (GTV) was the tumor evident from magnetic resonance imaging images fused with simulation computed tomography images. Clinical target volume (CTV) encompassed involved vertebral bodies or dorsal elements. We assumed that the planning target volume was equal to the CTV. We assessed local control rate after HT for 31 spine metastases. Pain response was scored by using a numeric pain intensity scale (NPIS, from 0 to 10). Results: Spine metastatic lesions were treated with median dose of 40 Gy (range, 24 to 51 Gy) and median 5 Gy per fraction (range, 2.5 to 8 Gy) to GTV with median 8 fractions (range, 3 to 20 fraction). Median biologically equivalent dose (BED, ${\alpha}/{\beta}$ = 10 Gy) was 52 $Gy_{10}$ (range, 37.5 to 76.8 $Gy_{10}$) to GTV. Six month local control rate for spine metastasis was 90.3%. Overall infield failure rate was 15% and outfield failure rate was 75%. Most patients showed pain relief after HT (93.8%). Median local recurrence free survival was 3 months. BED over 57 $Gy_{10}$ and oligometastases were identified as prognostic factors associated with improved local progression free survival (p = 0.012, P = 0.041). Conclusion: HT was capable of delivering higher BED to metastatic lesions in close proximity of the spinal cord. Spine metastases from gastrointestinal tumors were sensitive to high dose radiation, and BED (${\alpha}/{\beta}$ = 10 Gy) higher than 57 $Gy_{10}$ could improve local control.

• Journal of Korean Neurosurgical Society
• /
• 제45권5호
• /
• pp.275-283
• /
• 2009

Objective : We retrospectively analyzed survival, local control rate, and incidence of radiation toxicities after radiosurgery for recurrent metastatic brain lesions whose initial metastases were treated with whole-brain radiotherapy. Various radiotherapeutical indices were examined to suggest predictors of radiation-related neurological dysfunction. Methods : In 46 patients, total 100 of recurrent metastases (mean 2.2, ranged 1-10) were treated by CyberKnife radiosurgery at average dose of 23.1 Gy in 1 to 3 fractions. The median prior radiation dose was 32.7 Gy, the median time since radiation was 5.0 months, and the mean tumor volume was $12.4cm^3$. Side effects were expressed in terms of radiation therapy oncology group (RTOG) neurotoxicity criteria. Results : Mass reduction was observed in 30 patients (65%) on MRI. After the salvage treatment, one-year progression-free survival rate was 57% and median survival was 10 months. Age(<60 years) and tumor volume affected survival rate(p=0.03, each). Acute (${\leq}$1 month) toxicity was observed in 22% of patients, subacute and chronic (>6 months) toxicity occurred in 21 %, respectively. Less acute toxicity was observed with small tumors (<$10cm^3$. p=0.03), and less chronic toxicity occurred at lower cumulative doses (<100 Gy, p=0.004). "Radiation toxicity factor" (cumulative dose times tumor volume of <1,000 Gy${\times}cm^3$) was a significant predictor of both acute and chronic CNS toxicities. Conclusion: Salvage CyberKnife radiosurgery is effective for recurrent brain metastases in previously irradiated patients, but careful evaluation is advised in patients with large tumors and high cumulative radiation doses to avoid toxicity.

• Radiation Oncology Journal
• /
• 제31권3호
• /
• pp.131-137
• /
• 2013

Purpose: We evaluated treatment outcomes of thymic carcinomas to determine prognostic factors for survival. Materials and Methods: Between May 1988 and May 2009, 41 patients had pathologic diagnosis of thymic carcinoma in Seoul National University Hospital, Seoul, Korea. Of these, 40 patients were followed up to 188 months after treatment. The mean age of all patients was 58.3 years and male to female ratio was 23 to 17. Results: Among 30 patients who underwent surgical resection, 26 achieved R0 resection and postoperative radiotherapy (PORT) was performed in 22 patients (73%). Various chemotherapeutic regimens were given with local treatment modalities, surgery and/or radiotherapy, in 12 patients. The 5-year locoregional control (LRC), distant metastasis-free survival, progression-free survival (PFS), and overall survival were 79.4%, 53.0%, 42.6%, and 63.6%, respectively. Patients with Masaoka stage I or II showed excellent prognosis of 5-year PFS around 90%. In advanced stages, invasion of the great vessels or atrium by thymic carcinomas was negative prognostic factor for PFS in univariate analysis. Lymph node involvement was statistically significant factor for LRC and PFS. Local or regional recurrence was infrequent after surgical resection followed by PORT, while distant metastasis was the major component of treatment failure. Conclusion: Complete resection followed by PORT provided remarkable local control without severe acute toxicities in patients with stage II and favorable stage III thymic carcinoma. Invasion of the great vessels or atrium was statistically significant prognostic factor for PFS.

• Toxicological Research
• /
• 제23권3호
• /
• pp.231-238
• /
• 2007

Evaluation of potentials of chemicals to alter expression of genes that are involved in carcinogenesis may serve useful tools in toxicological research. In this investigation, we developed reporter cell lines that expressed luciferase in response to transactivation of hypoxia inducible factor-1, P53 tumor suppressor and Nur77 of which roles have been well established in cancer development and progression. Whereas these reporter cell lines displayed low constitutive backgrounds, the reporter activities were significantly enhanced in response to $desferriosamine/CoCl_2$, adriamycin or 6-mercaptopurine, which are hypoxia mimicking chemicals, P53 activator or Nur77 inducer, respectively. The activation of the reporter was time- and dose-dependent. Known tumor initiators and promoters, such as phorbol 12-myristate 13-acetate and phorbol 12, 13-dicaprinate induced the reporter activity at as low as 10nM in these stable cell lines. Further, known anti-tumor promoters, such as ascorbic acid and ${\beta}-carotene$ repressed the reporter activities. These results indicate that our stable reporter cell lines could serve as a useful system for rapid assessment of carcinogenicity of toxic chemicals.

• Radiation Oncology Journal
• /
• 제11권2호
• /
• pp.303-309
• /
• 1993

Between November 1983 and December 1992, 121 patients with non-small cell lung cancer were treated with radiotherapy alone or combined with chemotherapy in Inje University, Seoul Paik Hospital. Of these,97 patients were evaluable and analyzed retrospectively. Group 1 (n=62)was treated with radiotherapy alone and group 2 (n=35) combined with chemotherapy. There were 7 patients, 1 patient with stage I and II ,20 patients, 11 patients with stage IIIA,28 patients, 20 patients with stage IIIB, and 6 patients, 3 patients with stage IV, respectively. Ninety percent of patients received more than 5000 cGy of radiaton. Median survival of patients in group 1 was 9 months, group 2 was 15 months. Overall 2 year survival rates of group 1 and 2 were $37\%\;and\;27\%$, respectively. Relapse free survival rates at 2 year were $27\%\;and\;15\%$, respectively. Overall survival rates at 5 year for group 1 and 2 were $15\%\;and\;11\%$, and relapse free survival rates were $16\%\;and\;6\%,$ respectively. Median survival of complete and partial responders was 47 months in group 1,18 months in group 2, and those of stable or progression was 6 months,11 months, respectively. The proportion of locoregional relapse and distant metastasis was not significantly different between group 1 and 2. The majority of relapse developed within 2 years. Although 2 cases of severe esophagitis and myelosuppression were noted in group 2, the treatment related toxicity was relatively acceptable. Our analysis showed no statistically significant differences between the two treatment groups in terms of response rate, survival, and sites of relapse.

• Molecules and Cells
• /
• 제43권6호
• /
• pp.539-550
• /
• 2020

Glioblastoma multiforme (GBM) is a fatal malignant tumor that is characterized by diffusive growth of tumor cells into the surrounding brain parenchyma. However, the diffusive nature of GBM and its relationship with the tumor microenvironment (TME) is still unknown. Here, we investigated the interactions of GBM with the surrounding microenvironment in orthotopic xenograft animal models using two human glioma cell lines, U87 and LN229. The GBM cells in our model showed different features on the aspects of cell growth rate during their development, dispersive nature of glioma tumor cells along blood vessels, and invasion into the brain parenchyma. Our results indicated that these differences in the two models are in part due to differences in the expression of CXCR4 and STAT3, both of which play an important role in tumor progression. In addition, the GBM shows considerable accumulation of resident microglia and peripheral macrophages, but polarizes differently into tumor-supporting cells. These results suggest that the intrinsic factors of GBM and their interaction with the TME determine the diffusive nature and probably the responsiveness to non-cancer cells in the TME.

• 한국자원식물학회:학술대회논문집
• /
• 한국자원식물학회 2018년도 춘계학술발표회
• /
• pp.8-8
• /
• 2018

Muscle atrophy, known as a sarcopenia, is defined as a loss of muscle mass resulting from a reduction in muscle fiber area or density due to a decrease in muscle protein synthesis and an increase in protein breakdown. Many conditions are associated with muscle atrophy, such as aging, denervation, disuse, starvation, severe injury and inflammation, prolonged bed rest, glucocorticoid treatment, sepsis, cancer, and other cachectic diseases. On the other hand, osteoarthritis (OA) is the most common form of joint disease and is wide spread in the elderly population and is characterized by erosion of articular cartilage, osteophyte formation, and subchondral bone sclerosis. The cytokine network plays an important role in the development and progression of OA with the inflammatory cytokine. Schisandrae Fructus (SF) derived from the ripe fruit of Schisandra chinensis (Turcz.) Baill. (Magnoliaceae) has been extensively used in traditional herbal medicines in Asia. It was originally used as a tonic and has been traditionally used for the treatment of many uncomfortable symptoms, such as cough, dyspnea, dysentery, insomnia, and amnesia for a long time. Previous reports have shown that SF and its related compounds possess various biological activities such as antioxidant, anti-inflammatory, anticancer, anti-microbial, antiseptic, anti-aging, hepatoprotective and immunostimulating effects. However, the therapeutic effects of SF on muscle atrophy and OA has not yet been evaluated. In the present study, we aimed to determine whether extracts of SF, the dried fruit of S. chinensis, mitigates the development of muscle atrophy and OA.