• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2837-2840
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• 2012

We investigated whether IFN-${\beta}$ inhibits the growth of human malignant glioma and induces glioma cell apoptosis using the human IFN-${\beta}$ gene transfected into glioma cells. A eukaryonic expression vector ($pSV2IFN{\beta}$) for IFN-${\beta}$ was transfected into the glioma cell line SHG44 using liposome transfection. Stable transfection and IFN-${\beta}$ expression were confirmed using an enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was also assessed by Hoechst staining and electron microscopy. In vivo experiments were used to establish a SHG44 glioma model in nude mice. Liposomes containing the human IFN-${\beta}$ gene were injected into the SHG44 glioma of nude mice to observe glioma growth and calculate tumor size. Fas expression was evaluated using immunohistochemistry. The IFN-${\beta}$ gene was successfully transfected and expressed in the SHG44 glioma cells in vitro. A significant difference in the number of apoptotic cells was observed between transfected and non-transfected cells. Glioma growth in nude mice was inhibited in vivo, with significant induction of apoptosis. Fas expression was also elevated. The IFN-${\beta}$ gene induces apoptosis in glioma cells, possibly through upregulation of Fas. The IFN-${\beta}$ gene modulation in the Fas pathway and apoptosis in glioma cells may be important for the treatment of gliomas.

• Journal of Oral Medicine and Pain
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• 제37권4호
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• pp.189-193
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• 2012

구강내의 다발성 색소침착은 애디슨증후군, 포이츠-예거 증후군과 같은 선천성질환에 의하여 유발되거나, 악성 흑색종, 흑색극세포종, 신경섬유종증과 같은 국소적인 질환, 흡연, 만성 외상, 약물 복용 등에 의해서 유발될 수 있다. 이러한 질환 중 악성흑색종과 같은 질환은 생명을 위협할 수 있는 질환이므로 구강 내 색소 침착이 발견될 경우 정확한 진단이 필수적이다. 이러한 병소의 정확한 감별 진단을 위해서는 구강 내 색소 침착을 유발할 수 있는 원인에 대해서 숙지하고 있어야 하며, 상세한 병력 청취가 중요하다. 또한, 필요 시 혈액검사를 비롯한 이화학검사를 시행하거나 생검을 통하여 조직병리학적인 소견을 확인하고, 주기적으로 환자의 임상 소견에 대한 평가를 시행하여 변화를 확인하여야 한다. 그 동안 일반적으로 색소 침착을 유발하는 것으로 알려졌던 약물 외에, 만성 C형 간염 환자에서 페그인터페론 알파와 리바비린의 병용 요법 중 발생한 구강 내 다발성 색소 침착 증례가 있어 문헌 상에 보고되었던 만성 C형 간염 환자의 약물치료와 연관된 구강 내 색소 침착의 증례들과 함께 고찰해 보고자 한다.

• IMMUNE NETWORK
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• 제3권3호
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• pp.182-187
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• 2003

Background: The mushroom Phellinus linteus (PL) has been shown to have the anti-tumor and immunostimulatory effects. We hypothesized that the hot water extract of PL (WEPL) exerts its significant immunostimulatory effect by inducing production of the Th1-derived cytokine interferon-${\gamma}$ (IFN-${\gamma}$) by T lymphocytes. Methods: T lymphocytes were isolated from the mice fed with 200 mg/kg of WEPL once a day for 4 weeks, and then stimulated with the mitogen concanavaline A (Con A). IFN-${\gamma}$ gene and intracellular protein expressions were analyzed by RT-PCR and flow cytometry, respectively. The production of IFN-${\gamma}$ was measured by enzyme-linked immunosorbent assay. Results: WEPL significantly enhanced the transcription of IFN-${\gamma}$ mRNA. The effect of WEPL on IFN-${\gamma}$ expression was further supported by a concomitant increase in the number of cells with intracellular IFN-${\gamma}$ protein as well as the secretion of IFN-${\gamma}$. However, WEPL did not modulate either gene expression or protein secretion of interleukin-4, a Th2-associated cytokine, by Con A-stimulated T lymphocytes. Conclusion: Our results demonstrate that one of the potentially beneficial anti-tumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-${\gamma}$ secretion by T lymphocytes.

• IMMUNE NETWORK
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• 제2권4호
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• pp.202-207
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• 2002

Background: Kawasaki disease is an acute febrile illness with systemic vasculitis which primarily affects children, We examined the production of leptin in plasma and gene expressions of CXC chemokines in peripheral blood mononuclear cells from patients with Kawasaki disease. Methods: Consecutive 39 samples from 13 patients according to the different clinical stages (acute, subacute, convalescent) of Kawasaki disease were collected. The plasma leptin levels according to clinical stages of Kawasaki disease were examined by ELISA and the expression of IP-10, Mig and IL-8 mRNAs in 39 samples (13 samples of each stage) from 13 cases were examined by RT-PCR. Results: There were not significant changes of plasma leptin levels according to the clinical stages of Kawasaki disease. The mean values of plasma leptin concentrations during each of the stages (n=13, p>0.05, pg/ml) were $335.8{\pm}549.0$ in acute, $358{\pm}347.6$ in subacute, and $443.6{\pm}645.9$ in convalescent stage. The mRNAs of IP-10, Mig, and IL-8 were expressed in 13/13 (100%), 2/13 (15%), 9/13 (69%) during acute stage, 13/13 (100%), 6/13 (46%), 13/13 (100%) during subacute stage, and 13/13 (100%), 4/13 (31%), 10/13 (77%) during the convalescent stage, respectively. In three patients, the production of leptin and expression of IP-10 mRNA were dramatically decreased according to the process of the clinical stages. In five patients with prominent cervical lymphadenopathy, the expression of IL-8 mRNA during the subacute stage was more elevated than the acute and convalescent stages. Conclusion: This data suggests that the production of leptin and the gene expressions of IP-10, Mig and IL-8 seem to have no significant correlation to the clinical stages of Kawasaki disease. However, expression patterns of IP-10, Mig and IL-8 mRNA may be related to the specific clinical manifestations, and the expression of IP-10 may also be correlated to leptin levels with pericardial involvement.

• IMMUNE NETWORK
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• 제10권5호
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• pp.164-172
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• 2010

Background: We tested the hypothesis that dengue haemorrhagic fever (DHF) is associated with a $T_H1$-skewed immune response as opposed to dengue fever (DF). Methods: We estimated intracellular (in T-cells) and serum levels of designate $T_H1/T_H2$ cytokines [interferon-${\gamma}$ (IFN-${\gamma}$), interleukin-4 (IL-4), and tumor necrosis factor-${\alpha}$] and macrophage inflammatory protein-$1{\alpha}$ (MIP-$1{\alpha}$) at admission, 48h, and day 5 in 20 adults with dengue (DF=10, DHF=10) and 10 dengue-naive healthy controls. Results: At admission, intracellular IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells and proportion of MIP-$1{\alpha}$-positive CD8+ T-cells were significantly higher in patients with DHF [7.21 (5.36~10.81) vs. 3.04 (1.75~4.02); p=0.011 and 6.2% (3.2~8.2%) vs. 2.4% (2.0~3.6%); p=0.023]. The latter showed a significant positive correlation with IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells (Spearman's rho=0.64; p=0.003), percentage-change in haematocrit (rho=0.47; p=0.048), and serum alanine amino-transferase level (rho=0.61; p=0.009). Conclusion: We conclude that DHF is associated with a $T_H1$-skewed immune response. Further, MIP-$1{\alpha}$ in CD8+ T-cells is an important immunologic correlate of disease severity in dengue.

• IMMUNE NETWORK
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• 제14권5호
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• pp.255-259
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• 2014

Physical activity could be considered one of the factors that affect the immune system status and function. To find the relation between exercise and cytokines, we examined the possible effects of an 8-week endurance training program on the serum levels of cytokines, including tumour necrosis factor-alpha (TNF-${\alpha}$) and interferon-gamma (IFN-${\gamma}$) in sedentary men. A total of 30 healthy young male volunteers were randomly divided into an endurance training group and a control group. The training group followed a specific exercise protocol (running on a treadmill for 15~30 min at 50~70% maximal heart rate) for 8 weeks and the control group did not participate in any exercise program. Venous blood samples were collected from both the groups 24 h before and 24 h and 48 h after the exercise. Repeated ANOVA was used for statistical purposes. The serum levels of TNF-${\alpha}$ and IFN-${\gamma}$ were determined by ELISA. Significant (p<0.05) and non-significant (p>0.05) decreases were observed in the serum levels of IFN-${\gamma}$ and TNF-${\alpha}$, respectively, after the 8-week endurance training program. Our findings indicated that an 8-week endurance exercise may affect the serum levels of some inflammatory cytokines, suggesting the beneficial role of this training protocol in elderly population and people with certain conditions (inflammation of the vertebrae or other inflammatory diseases).

• BMB Reports
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• 제45권5호
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• pp.281-286
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• 2012

Osteoclasts are multinucleated cells that are formed by the fusion of pre-fusion osteoclasts (pOCs). The fusion of pOCs is known to be important for osteoclastic bone resorption. Here, we examined the effect of IFN-${\gamma}$ on the fusion of pOCs. IFN-${\gamma}$ greatly increased the fusion of pOCs in a dose-dependent manner. Furthermore, IFN-${\gamma}$ induced pOC fusion even in hydroxyapatite-coated plates used as a substitute for bone. The resorption area of pOCs stimulated with IFN-${\gamma}$ was significantly higher than that of the control cells. IFN-${\gamma}$ induced the expression of dendritic cell-specific transmembrane protein (DC-STAMP), which is responsible for the fusion of pOCs. IFN-${\gamma}$ enhanced DC-STAMP expression in a dose-dependent manner. The mRNA expression of c-Fos and nuclear factor of activated T cells (NFAT) c1 was enhanced in the pOCs treated with IFN-${\gamma}$. Taken together, these results provide a new insight into the novel role of IFN-${\gamma}$ on the fusion of pOCs.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7555-7559
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• 2015

Background: CML includes 30% of all leukemias, and occurs from childhood to old age. The present study was a retrospective analysis of chronic phase CML patients registered to a Hematology Clinic in Kermanshah, Iran, with checking of treatment options. Materials and Methods: Between 2002 and 2014, 85 CML patients referred to our hematology clinic were enrolled in our study. We surveyed age, sex, B-symptoms, splenomegaly, Sokal score, Hasford score, treatment and survival in all patients. Philadelphia chromosome analysis was conducted for each patient by conventional cytogenetics. We compared treatment in the patients with three drugs, imatinib, hydroxyurea (HU) and interferon alpha (IFN-${\alpha}$). Results: The mean age of the patients at diagnosis was $47.5{\pm}14.5years$ (range, 23-82 years), with 43 (50.6%) being male. Some 13 (15.3%) were referred to our clinic for the first time with B-symptoms and 44 patients (51.8%) had splenomegaly. The Sokal score for 77 (90.6%) was low, 4 (4.7%) was intermediate and 4(4.7%) was high, but Hasford (Euro) scores for all patients were low. The 5-year survival rate for treated patients with imatinib, imatinib plus HU and imatinib plus HU plus IFN-${\alpha}$ was 90.5%, 81.1% and 55.6%, respectively Conclusions: The results show that imatinib therapy alone provides better survival in CML patients compared to HU or IFN-${\alpha}$. Combinations of IFN-${\alpha}$ and/or HU with imatinib probably reduce survival.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5025-5030
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• 2015

Immunoregulatory cytokines have an influence on hepatitis C virus (HCV) infection outcome. This study aimed to determine whether single nucleotide polymorphisms (SNP) in IFN- ${\gamma}$ and IL-10 genes are associated with susceptibility and/or are markers of prognosis regarding chronic hepatitis C outcomes. IFN ${\gamma}$ (+874T/A) and IL-10 (-1082G/A) genotypes were determined in 75 HCV genotype 4 patients with different disease severities (chronic hepatitis, n=25, liver cirrhosis and hepatocellular carcinoma (HCC) on top of liver cirrhosis, n=50) and 25 healthy participants using allele-specific polymerase chain reaction. No statistical differences in allele or genotype distributions of IFN ${\gamma}$ and IL-10 genes were detected between patients and controls or between patientgroups. No significant difference in the frequency of IL-10 SNP at position -1082 or IFN-${\gamma}$ at position +874T/A was found between chronic HCV genotype 4 and with progression of disease severity in liver cirrhosis or HCC. In conclusion; interferon-${\gamma}$ and interleukin-10 gene polymorphisms are not predictors of disease progression in patients with chronic hepatitis C (Genotype-4).

• Journal of Korean Neurosurgical Society
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• 제63권4호
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• pp.444-454
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• 2020

Objective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-α/IFN-β receptor/STAT and IFN-γ/IFN-γ receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-α and IFN-γ while no change on the hypoxia-inducible factor-1α and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/STAT signaling triggered by IFN-α and IFN-γ.