• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8533-8539
• /
• 2016

Background: B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine-based chemotherapy. Materials and Methods: In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL. Results: Observed apoptosis rates were: group 1, $42{\pm}1.04%$; group 2, $21{\pm}0.57%$; group 3, $19{\pm}2.6%$; and group 4, % $0.01{\pm}0.01$. The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of $63{\pm}1.6%$, which was again higher than in other groups. Conclusions: In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis.

• BMB Reports
• /
• v.49 no.7
• /
• pp.382-387
• /
• 2016

Reactive oxygen species generated under oxidative stress are involved in neuronal diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of the GST family and is known to play important roles in cell survival. We investigated the effect of GSTpi against oxidative stress-induced hippocampal HT-22 cell death, and its effects in an animal model of ischemic injury, using a cell-permeable PEP-1-GSTpi protein. PEP-1-GSTpi was transduced into HT-22 cells and significantly protected against H2O2-treated cell death by reducing the intracellular toxicity and regulating the signal pathways, including MAPK, Akt, Bax, and Bcl-2. PEP-1-GSTpi transduced into the hippocampus in animal brains, and markedly protected against neuronal cell death in an ischemic injury animal model. These results indicate that PEP-1-GSTpi acts as a regulator or an antioxidant to protect against oxidative stress-induced cell death. Our study suggests that PEP-1-GSTpi may have potential as a therapeutic agent for the treatment of ischemia and a variety of oxidative stress-related neuronal diseases.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.3
• /
• pp.1213-1217
• /
• 2015

Background: Gastric cancer is the second most common cause of cancer- related deaths worldwide and ranks $11^{th}$ or $14^{th}$ among all deaths. Patients with advanced disease require supportive care along with the medical and/or surgical treatment. Aim: To assess the need for palliative care for patients with advanced tumours along with standard clinical therapy. Materials and Methods: Eighty-four patients with metastatic (stage 4) gastric cancer, including both patients who had received surgical treatment or not, were followed up in Bagcilar Training and Research Hospital, Division of Medical Oncology between 2011 and 2014. They were categorised as supportive care (-) (Group 1, n=37) and (+) groups (Group 2, n=47) and evaluated retrospectively. Results: Demographic characteristics of the patients were as follows: mean age, Group 1, $65.2{\pm}10.5$ years, Group $2,63.7{\pm}11.3$ years; male/female ratio, Group 1, 21/16, Group 2, 28/19; distribution of Eastern Cooperative Oncology Group (ECOG) performance scores of 0 and 1, Group 1, ECOG 0 (n=9) and 1 (n=14), Group 2, ECOG 0 (34) and 1 (n=13) (p<0.0001); patients receiving second-line, Group 1 (n=7) and Group 2 (n=22) (p<0.008) or third - line chemotherapy,Group 2 (n=6) (p<0.02); mortality rates, Group 1, (n=28; 75.6%) and Group 2 (n=30; 63.8%); progression-free survival (PFS) rates, Group 1, $17.4{\pm}6$ weeks, Group 2, $28.3{\pm}16.2$ weeks; statistically significant overall survival rates, Group 1, $20.8{\pm}8.2$ weeks and Group 2, $28.3{\pm}162$ weeks (p<0.01). Conclusions: The supportive care team (medical oncologist, general surgeon, internal medicine specialist, algologist, psychiatrist and radiologist) can play a role in the treatment of metastatic gastric tumours, with improvements shown in terms of the performance status of cases, eligibility of patients to be on chemotherapy programmes for longer duration and overall survival rates in Turkey.

• Biomedical Science Letters
• /
• v.3 no.1
• /
• pp.11-20
• /
• 1997

A regulation of differentiation in human neuroblastoma cells remains poorly understood, although it is of great importance in the clinical therapy of neuroblastoma. This study was aimed to elucidate effects of DNA synthesis inhibitors on the differentiation of neuroblastoma cells on the basis of morphological, biochemical and molecular respects. Three DNA synthesis inhibitors, sodium butyrate, hydroxyurea, cytosine arabinoside were used to explore their effects on the cellular morphology, the expression of c-myc and the elevation of choline acetyltransferase activity. They led to the extension or neurite-like processes reflecting differentiation or IMR-32 cells. In addition, the treatment of three DNA synthesis inhibitors resulted in the remarkable increases in the expression of c-myc as well as the stimulation of choline acetyltransferase activity which is involved in the synthesis of acetylcholine in the differentiated cholinergic neurons. Taken together, these results indicate that DNA synthesis inhibitors play an important role in the induction of cellular differentiation in IMR-32 cells. Furthermore these DNA synthesis inhibitors seem to be future useful to give an important clue (for the treatment of neuroblastoma).

• Korean Journal of Clinical Laboratory Science
• /
• v.47 no.3
• /
• pp.117-124
• /
• 2015

Mesenchymal stem cells (MSCs) are an attractive tool in tissue engineering as they have the required potential to treat injured articular cartilage. UV-exposed DTOPV (S-triazine bridged p-phenylene vinylene) is a biocompatible and fluorescent polymer with a hydrophilic surface. Previous studies have demonstrated that the surface wettability and hydrophilicity play critical roles in regulating cell adhesion and proliferation. The objective of this study was to improve the potential of in vitro MSC differentiation into Chondrocytes using DTOPV. MSCs were cultured on two different substrates: (1) tissue culture polystyrene (TCPS) as a reference and (2) UV-exposed and patterned DTOPV films. Chondrogenesis of MSCs was induced for two weeks on TCPS and DTOPV in the presence of an induction medium containing transforming growth factor (TGF)-${\beta}3$. Interestingly, the MSCs on TCPS adhered and spread, while those on DTOPV tended to form aggregates within several days. The cells cultured on DTOPV for two weeks had a round morphology, with stronger Safranine O staining of the extracellular matrix than that of the cells cultured on TCPS. Also, Type II collagen gene was significantly expressed in cells induced on DTOPV. These results indicate that chondrogenic differentiation of MSCs proceeds more rapidly on DTOPV than on TCPS. Therefore, in cartilage tissue engineering, DTOPV could be used to induce effective chondrogenic differentiation of MSCs.

• Journal of Gastric Cancer
• /
• v.15 no.4
• /
• pp.246-255
• /
• 2015

Purpose: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. Materials and Methods: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sex-matched patients (nonmetachronous group) were enrolled. Background mucosal pathologies such as atrophy and intestinal metaplasia (IM) were evaluated endoscopically. The expression levels of CDX1, CDX2, Sonic hedgehog (SHH), and SOX2 were evaluated based on H. pylori eradication and the development of metachronous lesions. Results: The eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.036). Open-type atrophy (P=0.003) and moderate-to-severe IM (P=0.001) occurred more frequently in the metachronous group. In patients with an initial diagnosis of dysplasia, the eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.002). In addition, open-type atrophy was more frequent in the metachronous group (P=0.047). In patients with an initial diagnosis of carcinoma, moderate-to-severe IM occurred more frequently in the metachronous group (P=0.003); however, the eradication failure rate was not significantly different between the two groups. SHH and SOX2 expression was increased, and CDX2 expression was decreased in the nonmetachronous group after eradication (P<0.05). Conclusions: Open-type atrophy, moderate-to-severe IM, and H. pylori eradication failure were significantly associated with metachronous lesions. However, eradication failure was significantly associated with dysplasia, but not carcinoma, in the metachronous group. Thus, H. pylori eradication may play an important role in preventing metachronous lesions after ER for precancerous lesions before carcinomatous transformation.

• IMMUNE NETWORK
• /
• v.2 no.1
• /
• pp.53-59
• /
• 2002

Background: Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anemias, with the majority of patients responding to immunosuppressive therapy. Fas, a member of the tumor necrosis factor (TNF) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon gamma (IFN-${\gamma}$) and TNF-${\alpha}$ can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. Methods: In order to investigate the involvement of apoptosis in the pathogenesis of aplastic anemia (AA), we measured the expression of Fas antigen and caspase-3 on bone marrow (BM) mononuclear cells (MNCs) of AA in the presence or absence of IFN-${\gamma}$, TNF-${\alpha}$, or macrophage inflammatory protein 1-${\alpha}$ (MIP-$1{\alpha}$). Results: We confirmed that AA BM MNCs were more apoptotic and highly expressed Fas antigen than normal donors. Stimulation by IFN-${\gamma}$, TNF-${\alpha}$, or MIP-$1{\alpha}$ increased Fas antigen and caspase-3 expression in AA BM MNCs than BM MNCs of normal donors. Anti-Fas monoclonal antibody enhanced IFN-${\gamma}$, TNF-${\alpha}$, or MIP$1{\alpha}$ mediated caspase-3 expression in BM MNCs of normal donors. Among these three cytokines, IFN-${\gamma}$ enhanced apoptosis most strongly via Fas-caspase-3 pathway. Conclusion: These results suggest that Fas signal pathway may play a role in the pathophysiology of aplastic anemia and negative hematopoietic regulators like IFN-${\gamma}$ can induce apoptosis of bone marrow progenitors in part by Fas induction.

• Journal of Periodontal and Implant Science
• /
• v.23 no.3
• /
• pp.359-373
• /
• 1993

The ultimate objective of periodontal therapy is not only stopping the progression of periodontal disease, but also promoting the regeneration of lost periodontal tissue. Guided Tissue Regeneration, which is based on the principle that the goal of periodontal regeneration can be achieved by preventing apical migration of gingival epithelium and blocking cells originating from connective tissue, has been developed and used as a clinical procedure, and although it has shown excellent results in connective tissue healing, there have not been many studies showing its effect on the regeneration of alveolar bone loss due to periodontal disease. The objectives of this study are to investigate the result of 12 months-long treatment following guided tissue regeneration using expanded polytetrafluoroehylene membrane, and to observe the presence of regenerated alveolar bone. Forty-one teeth from 28 patients with clinical diagnosis of periodontitis has been selected. In fifteen of those interproximal intrabony defects, only flap operation had been carried out, and designated as the control group. Twenty-six intrabony defects received e-PTFE membrane following flap operation, and designated as the experimental group. Eleven teeth whose membrane had been exposed were excluded from the experiment. Various measurements including probing depth, loss of attachment, probing bone level and gingival recession have been recorded at 6th month and 12th month, and the significance of the changes has been analyzed. The results are as follows: 1. Probing depth at 6th and 12th month has shown a significant decrease in both groups (p<0.01), but significantly higher decrease was found in the experimental group compared to the control at the month(p<0.05). 2. Loss of attachment at 6th and 12th month has shown a significant decrease in both groups, but significantly higher decrease was found in the experimental group compared to the control (p<0.05). 3. Probing bone level at 6th and 12th month has shown a insignificant decrease in the control group and significant decrease in the experimental group (p<0.01). Significantly higher decrease in probing bone level was found in the experimental group (p<0.05). 4. Gingival recession at 6th and 12th month has shown a statistically significant increase (p<0.05), and the control group showed higher increase compared to the experimental group although no statistical significance was found. As these results have shown, the use of e-PTFE membrane in intrabony pockets results in marked decrease in the loss of attachment and probing bone level. This seems to indicate that e-PTFE membrane may play a role in alveolar bone regeneration in intrabony defects.

• Journal of Periodontal and Implant Science
• /
• v.35 no.2
• /
• pp.461-474
• /
• 2005

The ultimate goal of periodontal therapy is the regeneration of periodontal tissue and the repair of function. For more than a decade there have been many efforts to develop materials and methods of treatment to promote periodontal tissue regeneration. Recently many efforts are concentrated on the regeneration potential of material used in traditional medicine. Safflower(Carthamus tinctorius L.) seed extract(SSE) have long clinically used in Korea to promote bone formation and prevent osteoporosis. The purpose of this study was to examine the effects of SSE on bone formation in human osteoblastic cell line. Human fetal osteoblastic cell line(hFOB 1.19) was cultured with DMEM and SSE($1{\mu}g/ml$, $10{\mu}g/ml$, $100{\mu}g/ml$, $1mg/ml$) at $34^{\cdot}C$ with 5% $CO_2$ in 100% humidity. The proliferation, differentiation of the cell was evaluated by several experiments. Cell proliferation was significantly increased at $10{\mu}g/ml$, $100{\mu}g/ml$, 1mg/ml of SSE after 3 and 7 days incubation(p<0.05). Cell spreading assay was significantly increased at $100{\mu}g/ml$ of SSE after 3 days and $1{\mu}g/ml$, $10{\mu}g/ml$, $100{\mu}g/ml$, 1mg/ml of SSE after 7 days(p<0.05). Alkaline Phosphatase(ALP) level was significantly increased in $10{\mu}g/ml$, $100{\mu}g/ml$, 1mg/ml of SSE(p<0.05). Collagen synthesis was significantly increased at $10{\mu}g/ml$, $100{\mu}g/ml$, 1mg/ml of SSE(p<0.05). A quantified calcium accumulation was significantly increased at $10{\mu}g/ml$, $100{\mu}g/ml$ of SSE(p<0.05). ALP and osteocalcin mRNA was expressed in $100{\mu}g/ml$ of SSE by RT-PCR. These results indicate that SSE are capable of increasing osteoblasts mineralization and may play an important role in bone formation.

• Korean Journal of Plant Resources
• /
• v.25 no.5
• /
• pp.578-585
• /
• 2012

Cytokines released from innate immune cells play key roles in the regulation of the immune response. Red Ginseng (RG, steamed and dried root of Panax ginseng C.A. Meyer) is known to show different pharmacological effects by changed composition of saponins compared with Panax Ginseng. In this study, we examined the immunomodulatory effects of RG on the regulation of cytokine release in mice. RG was injected i.p at doses of 0.5, 5 and 50 mg/kg for 6 weeks. We assessed that the weight index of immune organs such as thymus, and spleen, and the mitogen blastogenesis of splenocytes. We also determined the levels of circulating cytokines in serum from RG-treated mice using ELISA assay. The weight index of thymus and spleen, and proliferation of mitogen response of splenocytes have increased in the RG-injected groups. In addition, the levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-6, IL-12 and IL-2 concentrations have significantly increased in the serum of RG-treated mice, but that of IL-10 has not. These results suggest that RG has immune stimulating effects and could be useful as a immunoregulator of circulating cytokine release in vivo.