• Title/Summary/Keyword: tumor response

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Methyl 9-Oxo-(10E,12E)-octadecadienoate Isolated from Fomes fomentarius Attenuates Lipopolysaccharide-Induced Inflammatory Response by Blocking Phosphorylation of STAT3 in Murine Macrophages

  • Choe, Ji-Hyun;Yi, Young-Joo;Lee, Myeong-Seok;Seo, Dong-Won;Yun, Bong-Sik;Lee, Sang-Myeong
    • Mycobiology
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    • v.43 no.3
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    • pp.319-326
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    • 2015
  • Fomes fomentarius is a fungus of the Polyporaceae family and is used in traditional oriental therapies. Although the anti-inflammatory activities of this species have been previously reported, the identity of the bioactive compounds responsible for this activity remains unknown. Here, we investigated whether methyl 9-oxo-(10E,12E)-octadecadienoate (FF-8) purified from F. fomentarius exerts anti-inflammatory activity in murine macrophages stimulated with lipopolysaccharide (LPS). FF-8 suppressed secretion of nitric oxide (NO) and prostaglandin $E_2$ through downregulation of inducible NO synthase and cyclooxygenase-2 expression induced by LPS. In addition, pretreatment of cells with FF-8 led to a reduction in levels of secreted inflammatory cytokines such as tumor necrosis factor-${\alpha}$ and interleukin-6 in macrophages stimulated with LPS. Conversely, FF-8 did not affect nuclear factor ${\kappa}B$, p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase pathways. Instead, FF-8 specifically interfered with signal transducer and activator of transcription 3 (STAT3) phosphorylation induced by LPS. Collectively, this study demonstrated that FF-8 purified from F. fomentarius suppresses inflammatory responses in macrophages stimulated with LPS by inhibiting STAT3 activation. Further studies will be required to elucidate the anti-inflammatory effect of FF-8 in vivo.

Experimental Study of Yongdamsagantang on the Anti-viral Activity and Immune Response to Mice (龍膽瀉肝湯의 抗바이러스 活性 및 免疫反應에 對한 實驗的 考察)

  • Kim, Nam-Kwen;Kim, Jong-han;Lim, Gyu-sang;Hwang, Choong-yeon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.11 no.1
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    • pp.1-22
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    • 1998
  • During the last few years, nitric oxide(NO) as a potent macrophage-derived effector molecule against a variety of bacteria, parasites, and tumors has received increasing attention. More recent studies suggest that NO also has antiviral effects in both murine and human cells. The objective of the current study was to determine the effect of Yongdamsagantang(YST) on the production of NO. Stimulation of mouse peritoneal macrophages with YST after the treatment of recombinant $interferon-{\gammer}(rlFN-{\gammer})$ resulted in the increased NO synthesis. YST had no effect on NO synthesis by itself. When YST was used in combination with $rIFN-{\gammer}$, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of YST on NO synthesis was shown 6 hour after treatment with $rIFN-{\gammer}$. This increase in NO synthesis was reflected as increased amount of inducible NO synthase(iNOS) protein. NO production was inhibited by $N^G-monomethyl-L-arginine$. The increased production of NO from $rIFN-{\gammer}$ plus YST-stimulated cells was decreased by the treatment with staurosporin. In addition, synergy between $rIFN-{\gammer}$ and YST was mainly dependent on YST-induced tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ secretion. These results suggest that the capacity of YST to increase NO production from $rIFN-{\alpha}-primed$ mouse peritoneal macrophages is the result of YST-induced $TNF-{\alpha}$ secretion.

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Antibody Response to Crude Cell Lysate of Propionibacterium acnes and Induction of Pro-Inflammatory Cytokines in Patients with Acne and Normal Healthy Subjects

  • Basal, E.;Jain, A.;Kaushal, G.P.
    • Journal of Microbiology
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    • v.42 no.2
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    • pp.117-125
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    • 2004
  • Propionibacterium acnes (P. acnes) plays an important role in the disease pathogenesis of acne vulgaris, a disorder of pilosebaceous follicles, seen primarily in the adolescent age group. In the present study, the presence of antibodies against P. acnes (MTCC1951) were detected in acne patient (n=50) and disease free controls (n=25) using dot-ELISA and Western blot assay. The ability of P. acnes to induce pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMCs), obtained from acne patients and healthy subjects, were also analysed. The patients (n=26) who were culture positive for skin swab culture, were found to have a more advanced disease and higher antibody titres (1:4000 to >1:16000) compared to the P. acnes negative patients (n=24) and normal controls (n=25). An analysis of patients' sera by western blot assay recognized a number of antigenic components of P. acnes, rang-ing from 29 to 205 kDa. The major reactive component was an approximately 96 kDa polypeptide, which was recognised in 92% (24 of 26) of the patients sera. Further, the P. acnes culture supernatant, crude cell lysate and heat killed P. acnes whole cells, obtained from 72-h incubation culture, were observed to be able to induce significant amounts of IL-8 and tumor necrosis factor alpha (TNF-${\alpha}$) by the PBMCs in both the healthy subjects and patients, as analysed by cytokine-ELISA. The levels of cytokines were significantly higher in the patients than the healthy subjects. A major 96 kDa polypep-tide reactant was eluted from the gel and was found to cause dose dependent stimulation of the pro-ductions of IL-8 and TNF-${\alpha}$. Thus, the above results suggest that both humoral and pro-inflammatory responses play major roles in the pathogenesis of acne.

The Effect of Aprepitant Regimen on the Prevention of High-Dose Cisplatin-Induced Nausea and Vomiting (Aprepitant Regimen의 고용량 Cisplatin 유발 오심 및 구토 예방 효과)

  • Park, Su-Jin;Choi, Ji-Seon;Ahn, Jin-Seok;Shin, Ka-Young;Min, Kyoung-A;Chung, Seon-Young;In, Yong-Won;Sohn, Kie-Ho
    • Korean Journal of Clinical Pharmacy
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    • v.20 no.1
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    • pp.17-23
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    • 2010
  • Aprepitant is a substance P/neurokinin-1 (NK1)-receptor antagonist that was approved in 2003 for prevention of CINV. In addition, updated anti-emetic guidelines that include the aprepitant regimen have been published by NCCN and ASCO. However there is scarce clinical data in Korea. The prospective study was performed to evaluate the prevention of high dose cisplatin induced nausea and vomiting in all patients who started high-dose cisplatin-based chemotherapy at our hospital. We checked the nausea severity and vomiting episodes by calling patients within 4 to 5 days after chemotherapy. The retrospective study was performed to compare the prevention of CINV in solid tumor patients who switched their anti-emesis regimen from the standard regimen to the aprepitant regimen. In aprepitant regimen, aprepitant was added to the same anti-emetic regimen used during previous cycles. We checked the nausea, vomiting grades and adverse events in electronic medical records (EMR). In prospective study, 195 patients were included in the analysis. 88.2% of patients achieved a complete response (no emesis and no rescue therapy). In retrospective study, 54 patients were reviewed. With aprepitant regimen, nausea and vomiting grades were improved in 22 patients (40.7%) and in 9 patients (16.7%), respectively. Compared with standard regimen, addition of aprepitant provided superior prevention against CINV in Korean patients receiving highly emetogenic cisplatin-based chemotherapy. Moreover, aprepitant significantly prevented CINV in patients who received the standard regimen to prevent CINV in previous chemotherapy cycles.

Codium fragile Ethanol Extraction Inhibited Inflammatory Response through the Inhibition of JNK Phosphorylation

  • Han, Sin-Hee;Kim, Young-Guk;Lee, Su-Hwan;Park, Chung-Berm;Choi, Han-Gil;Jang, Hye-Jin;Lee, Young-Seob;Kwon, Dong-Yeul
    • Preventive Nutrition and Food Science
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    • v.15 no.3
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    • pp.206-212
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    • 2010
  • Codium fragile (CF) is an edible green alga consumed as a traditional food source in Korea. In this study, the ethanol extract of CF was evaluated to determine if it has anti-inflammatory activity. Lipopolysaccharide (LPS), a toxin from bacteria, is a potent inducer of inflammatory cytokines, such as tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-6. Therefore, we studied whether CF extracts have an anti-inflammatory effect in LPS-induced murine macrophage cell lines (RAW 264.7). In the present study, IL-6 production was measured using an enzyme-linked immunosorbent assay (ELISA), prostaglandin $E_2$($PGE_2$) production was measured using the EIA kit, and cyclooxygenase (COX)-2 and mitogen-activated protein kinase (MAPK) activation were determined by Western blot analysis. IL-6 mRNA, COX-2 mRNA and iNOS mRNA expression were measured using reverse transcription-polymerase chain reaction (RT-PCR). The results indicated that CF extracts inhibit LPS-induced IL-6, NO and PGE2 production in a dose-dependent manner, as well as expression of iNOS and COX-2. CF extracts significantly inhibited LPS-induced c-Jun N-terminal kinase (JNK) 1/2 phosphorylation. Taken together, these findings may help elucidate the mechanism by which CF modulates RAW 264.7 cell activation under inflammatory conditions.

Genetic and Expression Analysis of the SIRT1 Gene in Gastric Cancers

  • Zhang, Cao;Song, Jae-Hwi;Kang, Young-Whi;Yoon, Jung-Hwan;Nam, Suk-Woo;Lee, Jung-Young;Park, Won-Sang
    • Journal of Gastric Cancer
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    • v.10 no.3
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    • pp.91-98
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    • 2010
  • Purpose: Silent mating-type information regulation 2 homologue 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. SIRT1 plays an important role in the regulation of cell death/survival and stress response in mammals. The aim of this study was to investigate whether the SIRT1 gene is involved in the development or progression of gastric cancers. Materials and Methods: SIRT1 and p53 genes in 86 gastric cancers were examined for genetic alterations by PCR-single strand conformation polymorphism sequencing, as well as SIRT1 protein expression in 170 gastric cancers by immunohistochemistry. Results: In the genetic analysis, we found SIRT1 and p53 mutations in two and 12 cases, respectively. Two missense mutations, c.599 C>T (T200I) and c.1258 G>A (E420K), were detected in the SIRT1 gene coding region. The SIRT1 and p53 mutation were found in mutually exclusive gastric cancers. The immunohistochemistry revealed that SIRT1 overexpression was found in 95 (55.9%) of 170 gastric cancers. Altered SIRT1 expression was not statistically associated with clinicopathological parameters, including tumor differentiation, location, lymph node metastasis, or p53 expression. Two cases with an SIRT1 mutation showed increased SIRT1 expression. Conclusions: These results suggest that genetic alterations and overexpression of the SIRT1 gene may contribute to gastric cancer development.

Four active monomers from Moutan Cortex exert inhibitory effects against oxidative stress by activating Nrf2/Keap1 signaling pathway

  • Zhang, Baoshun;Yu, Deqing;Luo, Nanxuan;Yang, Changqing;Zhu, Yurong
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.5
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    • pp.373-384
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    • 2020
  • Paeonol, quercetin, β-sitosterol, and gallic acid extracted from Moutan Cortex had been reported to possess anti-oxidative, anti-inflammatory, and anti-tumor activities. This work aimed to illustrate the potential anti-oxidative mechanism of monomers in human liver hepatocellular carcinoma (HepG2) cells-induced by hydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect of monomers was independence or synergy in mice stimulated by carbon tetrachloride (CCl4). Monomers protected against oxidative stress in HepG2 cells in a dose-response manner by inhibiting the generation of reactive oxygen species, increasing total antioxidant capacity, catalase and superoxide dismutase (SOD) activities, and activating the antioxidative pathway of nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that the in vitro antioxidant capacities of paeonol and quercetin were better than those of β-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levels of alanine transaminase and aspartate aminotransferase, augmented the contents of glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1 proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, β-sitosterol, and gallic acid play a defensive role against H2O2-induced oxidative stress through activating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidative properties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotective effects, which is independent rather than synergy.

The Radiotherapy Result of Esophageal Cancer (식도암의 방사선 치료 성적)

  • Chung, Woong-Ki;Ahn, Sung-Ja;Nah, Byung-Sik
    • Radiation Oncology Journal
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    • v.9 no.2
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    • pp.241-248
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    • 1991
  • Ninety patients of esophageal cancer treated with radiation since November 1985 to June 1990 at the Department of Therapeutic Radiology, Chonnam University Hospital, were analysed retrospectively regarding survival. Seventy five patients ($94.9\%$) revealed squamous cell carcinoma in its histologic type, and most of patients were in advanced stage with 25 patients ($27.8\%$) of T2 and 64 patients ($71.1\%$) of T3. Minimum follow up period was 12 months and median was 5 months. Overall actuarial 2 year survival rate was $11.6\%$. Two year survival rates according to the parameters such as treatment aim, T stage, site, length, radiation dose and response were compared and resulted that survival by tumor length only had statistically significant impact on survival of esophageal carcinoma.

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Evaluation of the Anti-inflammatory and Immunomodulatory Effects of BSASM Using in vitro Experiments (시험관내에서 천연물제제 BSASM의 항염증 및 면역억제 효능 평가)

  • Lee, Jong-Sung;Park, Yu-Mi;Park, Byung-Hwa;Jung, Kwang-Seon;Kim, Kuk-Hyun;Lee, Won-Hee;Park, Deok-Hoon
    • Korean Journal of Pharmacognosy
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    • v.34 no.3 s.134
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    • pp.228-232
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    • 2003
  • For effective management of atopic dermatitis, it is important to introduce a therapeutic agent although having the fewest side effects, has the greatest anti- inflammatory effect. In the course of screening anti-inflammatory agents, we obtained BSASM composed of several plant extracts. This study was designed to investigate anti-inflammatory and immunomodulatory effects of BSASM. As a first step, $NF-{\kappa}B$ luciferase reporter assay was performed to know the involvement of BSASM in the production of proinflammatory cytokines because $NF-{\kappa}B$ element has been known to play a major role in expression of cytokine genes such as interleukin-8 (IL-8) or tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$. LPS (lipolysaccharide)-induced $NF-{\kappa}B$ activation was inhibited by BSASM. In addition, we found the fact that BSASM inhibits LPS-induced produced production of IL-8 and $TNF-{\alpha}$ proinflammatory cytokines, indicating BSASM has anti-inflammatory effect. In interleukin-2 (IL-2) luciferase reporter assay in Jurkat T cells, BSASM reduced PHA (Phytohemagglutinin)-induced IL-2 luciferase activity, suggesting the possibility that BSASM might also have an immunomodulatory function in T cell-mediated immune response. Based on these results, we suggest the possibility that BSASM can be introduced to improve symptom of immune-related skin diseases, namely, atopic dermatitis.

Malignant Fibrous Histiocytoma of the Maxilla - Report of A Case - (상악골의 악성 섬유성 조직구종 - 증례보고 -)

  • Oh, Yoon-Kyeong;Yeo, Hwan-Ho
    • Radiation Oncology Journal
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    • v.13 no.3
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    • pp.225-231
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    • 1995
  • Malignant fibrous histiocytoma(MFH) of the maxilla is a rare malignant bone tumor Seven percents of all MFH occur in the head and neck. Approximately $12{\%}$ of these tumors occur in the maxilla. Local recurrence or distant metastasis was reported in $55{\%}$ of cases of maxillary MFH. The mean survival time of 30 months was reported from a review of 14 MFHs in the maxilla, mandible and oral soft tissues. MFH of the maxilla is best treated surgically but radical neck dissection does not appear to be indicated unless there is clinical evidence of lymph node metastases Although the use of radiation therapy for head and neck MFH has not been studied for a series of cases, individual cases of regression or histological change have been reported. Other authors have reported numbers of cases who received radiation therapy without benefit. Response to combination chemotherapy has been reported in $33{\%}$ of 23 patients with recurrent or metastatic MFH. We report here a case of MFH occurring in the maxilla with a review of literature about the clinical behavior and treatment of these lesions.

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