• Journal of Life Science
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• v.26 no.3
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• pp.376-386
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• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.236-242
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• 1996

Intracranial tuberculoma results from hematogenous spread of pulmonary, intestinal or urogenital tuberculosis. However, it might be caused by pulmonary tuberculosis, mainly. Clinically, symptoms of intracranial tuberculoma are headache and seizure, its symptoms are simillar to intracranial tumor. A 25-year-old-unmarried shopgirl was visited to this hospital because of headache, dizziness and visual disturbance for couple weeks in Sep. 1995. She had been treated with anti-tuberculosis agents of miliary tuberculosis during past nine months period. Brain MRI revealed intracranial tuberculoma and brain edema but not involved optic nerve. Ophthalmic examination revealed severe papilledema and splinter hemorrhage with bitemporal hemianopsis and central scotoma. This finding was strongly suggested of optic disc tuberculoma. Her symptoms became much better following repeated retrobulbar steroid injection with continuous anti-tuberculosis agents. We report a interesting case with intracranial tuberculoma and optic disc tuberculoma associated by miliary tuberculosis during anti-tuberculous treatment.

• Journal of Society of Preventive Korean Medicine
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• v.18 no.1
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• pp.125-138
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• 2014

Objective : Polycan, exopolymers purified from Aureobasidium pullulans SM-2001 and calcium gluconate have been showed favorable inhibitory effects on the periodontitis and related alveolar bone losses through antioxidant and anti-inflammatory activities, respectively. In the present study, we intended to observe the possible synergic effects of mixed formula consisted of Polycan and calcium gluconate on ligation-induced experimental periodontitis and related alveolar bone losses in rats, and to select the fittest compositions for further developing as effective agents to ameliorate periodontal diseases. Method : Experiments were conducted as two separated two tests - first is synergic effects of Polycan and calcium gluconate 1:1, 1:9 and 9:1 mixtures, and second is 1:99, 2:98, 4:96, 8:92 and 1:9 mixtures. Experimental periodontal diseases were induced by ligature placed around the cervix of upper left incisior teeth of rats. One day after ligation placements, 200mg/kg of each single or mixed formulas of Polycan or/and calcium gluconate were orally administered for 10 days. The changes on the alveolar bone loss index and maxillary bone mineral density (BMD) were observed for detecting alveolar bone losses, and for anti-inflammatory effects, myeloperoxidase (MPO) activities and proinflammatory cytokine (tumor necrosis factor; TNF-${\alpha}$) contents were also evaluated in gingival tissues around ligature placed incisior teeth. The results of mixtures were compared with those of singe Polycan and calcium gluconate treated rat. Results : Each single or mixed formulas of Polycan or/and calcium gluconate favorably and significantly inhibited the inflammatory changes. The inhibitory effects of mixed formula consisted of Polycan and calcium gluconate 1:9 showed against periodontitis and related alveolar bone losses as compared with those of each Polycan and calcium gluconate single formula (p<0.05). In second experiment, Polycan and calcium gluconate 2:98, 4:96, 8:92 and 1:9 mixed formulas also showed significant increased anti-inflammatory and inhibitory effects against alveolar bone losses as compared with those of each single formula. Among them, Polycan and calcium gluconate 2:98 showed the highest efficacy against to ligation-induced experimental periodontitis and related alveolar bone losses. Conclusion : The results obtained in this study suggest that appropriated mixtures of Polycan and calcium gluconate showed synergic inhibitory effects against ligation-induced experimental periodontitis and related alveolar bone losses in rats. Moreover, Polycan and calcium gluconate 2:98 showed the highest efficacies in this experiment, suggesting the fittest composition for further developing as effective agents to ameliorate periodontal diseases.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.126-133
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• 2021

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the aglycone derivatives of major ginsenosides, has been shown to have an anticancer activity toward a variety of cancers. This study was initiated with an attempt to evaluate its anti-cancer activity toward human endometrial cancer by cell and xenograft mouse models. Methods: Human endometrial cancer (HEC)-1A cells were incubated with different 20(S)-PPD concentrations. 20(S)-PPD cytotoxicity was evaluated using MTT assay. Apoptosis was detected using the annexin V binding assay and cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-9 were assessed using western blotting. HEC-1A cell tumor xenografts in athymic mice were generated by inoculating HEC-1A cells into the flank of BALB/c female mice and explored to validate 20(S)-PPD anti-endometrial cancer toxicity. Results: 20(S)-PPD inhibited HEC-1A cell proliferation in a dose-dependent manner with an IC50 value of 3.5 μM at 24 h. HEC-1A cells morphologically changed after 20(S)-PPD treatment, bearing resemblance to Taxol-treated cells. Annexin V-positive cell percentages were 0%, 10.8%, and 58.1% in HEC-1A cells when treated with 0, 2.5, and 5 μM of 20(S)-PPD, respectively, for 24 h. 20(S)-PPD subcutaneously injected into the HEC-1A cell xenograft-bearing mice three times a week for 17 days manifested tumor growth inhibition by as much as 18% at a dose of 80 mg/kg, which sharply contrasted to controls that showed an approximately 2.4-fold tumor volume increase. These events paralleled caspase-9 activation and PARP cleavage. Conclusion: 20(S)-PPD inhibits endometrial cancer cell proliferation by inducing cell death via a caspase-mediated apoptosis pathway. Therefore, the 20(S)-PPD-like ginsenosides are endowed with ample structural information that could be utilized to develop other ginsenoside-based anticancer agents.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.1
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• pp.95-108
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• 2014

Cosmetics are products used over long periods by the public, and their safety is very important. Contact dermatitis induced by cosmetics is the result of an inflammatory response of the skin to direct irritancy. The initial event that this inflammatory response is observed is the release of pro-inflammatory cytokines. In this study, the anti-inflammatory activities of extracts from Korean herb medicines were investigated using RAW264.7 macrophage. Among the fifty one extracts tested, the ethanol extracts from Biotae Orientalis Folium, Biotae Orientalis Folium (roasted), Cyperi Rhizoma, Nepetae Spica, Benincasae Semen, Dioscoreae Rhizoma, Dioscoreae Rhizoma (roasted), Mori Ramulus, Pini Ramulus and Alismatis Rhizoma reduced the cytotoxicity and inhibited the productions of Nitric oxide (NO) and cytokines such as interleukin (IL)-1${\beta}$, IL-6 and tumor necrosis factor (TNF)-${\alpha}$n lipopolysaccharide (LPS)-induced RAW264.7 macrophage. Additionally, they didn't induce the skin irritation when tested the human patch test. Overall, the result of this study suggests that the extracts of the ten Korean herb medicines are useful cosmetic agents for preventing the skin irritation.

• Journal of Pharmacopuncture
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• v.20 no.1
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• pp.52-56
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• 2017

Objectives: Neutrophils represent the front line of human defense against infections. Immediately after stimulation, neutrophilic enzymes are activated and produce toxic mediators such as pro-inflammatory cytokines, nitric oxide (NO) and myeloperoxidase (MPO). These mediators can be toxic not only to infectious agents but also to host tissues. Because flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of inflammation. In the present study, the effects of rutin on stimulus-induced NO and tumor necrosis factor $(TNF)-{\alpha}$ productions and MPO activity in human neutrophils were investigated. Methods: Human peripheral blood neutrophils were isolated using Ficoll-Hypaque density gradient centrifugation coupled with dextran T500 sedimentation. The cell preparations containing > 98% granulocytes were determined by morphological examination through Giemsa staining. Neutrophils were cultured in complete Roswell Park Memorial Institute (RPMI) medium, pre-incubated with or without rutin ($25{\mu}M$) for 45 minutes, and stimulated with phorbol 12-myristate 13-acetate (PMA). Then, the $TNF-{\alpha}$, NO and MPO productions were analyzed using enzyme-linked immunosorbent assay (ELISA), Griess Reagent, and MPO assay kits, respectively. Also, the viability of human neutrophils was assessed using tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and neutrophils were treated with various concentrations of rutin ($1-100{\mu}M$), after which MTT was appended and incubated at $37^{\circ}C$ for 4 hour. Results: Rutin at concentrations up to $100{\mu}M$ did not affect neutrophil viability during the 4-hour incubation period. Rutin significantly decreased the NO and $TNF-{\alpha}$ productions in human peripheral blood neutrophils compared to PMA-control cells (P < 0.001). Also, MPO activity was significantly reduced by rutin (P < 0.001). Conclusion: In this in vitro study, rutin had an anti-inflammatory effect due to its inhibiting NO and $TNF-{\alpha}$ productions, as well as MPO activity, in activated human neutrophils. Treatment with rutin may be considered as a therapeutic strategy for neutrophil-mediated inflammatory/autoimmune diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2179-2183
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• 2014

Background: In vitro, in vivo and clinical studies have demonstrated anti-cancer effects of deuterium depleted water (DDW). The nature of this agents action, cytotoxic or cytostatic, remains to be elucidated. We here aimed to address the point by examining effects on different cell lines. Materials and Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) -based cytotoxicity analysis was conducted for human breast, stomach, colon, prostate cancer and glioblastoma multiforme cell lines as well as human dermal fibroblasts. The cell lines were treated with decreasing deuterium concentrations of DDW alone, paclitaxel alone and both. One way analysis of variance (ANOVA) was used for statistical analysis. Results: Treatment with different deuterium concentrations of DDW alone did not impose any significant inhibitory effects on growth of cell lines. Paclitaxel significantly decreased the survival fractions of all cell lines. DDW augmented paclitaxel inhibitory effects on breast, prostate, stomach cancer and glioblastoma cell lines, with influence being more pronounced in breast and prostate cases. Conclusions: DDW per se does not appear to have inhibitory effects on the assessed tumor cell lines as well as normal fibroblasts. As an adjuvant, however, DDW augmented inhibitory effects of paclitaxel and thus it could be considered as an adjuvant to conventional anticancer agents in future trials.

• Journal of Gastric Cancer
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• v.19 no.4
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• pp.375-392
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• 2019

Preoperative chemo- and radiotherapeutic strategies followed by surgery are currently a standard approach for treating locally advanced gastric and esophagogastric junction cancer in Western countries. However, in a large number of cases, the tumor is extremely resistant to these treatments and the patients are exposed to unnecessary toxicity and delayed surgical therapy. The current clinical trials evaluating the combination of preoperative systemic therapies with modern targeted and immunotherapeutic agents represent a unique opportunity for identifying predictive biomarkers of response to select patients that would benefit the most from these treatments. However, it is of utmost importance that these potential biomarkers are corroborated by extensive preclinical and translational research. The aim of this review article is to present the most promising biomarkers of response to classic chemotherapeutic, anti-HER2, antiangiogenic, and immunotherapeutic agents that can be potentially useful for personalized preoperative systemic therapies in gastric cancer patients.

• Journal of Life Science
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• v.27 no.6
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• pp.640-645
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• 2017

Clerodendrum trichotomum (CT) leaves and stems have been used in folk medicine for their anti-hypertension, arthritis, rheumatism, and anti-inflammatory properties. This study was performed to evaluate the potential of CT as an anti-oxidant and anti-inflammatory agent. CT leaves were extracted using 70% ethanol (EtOH). Then, using this extract, a hexane, chloroform ($CHCl_3$), ethyl acetate (EtOAc), and n-butanol (BuOH) fraction was prepared. The polyphenol contents were higher in the EtOAc fraction ($78.08{\mu}g/mg$) and BuOH fraction ($77.54{\mu}g/mg$) compared to the other fractions. Also, these two fractions exhibited strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging activities. Xanthine oxidase inhibitory activities were higher in the $CHCl_3$ fraction ($IC_{50}=4.43{\mu}g/ml$) and EtOAc fraction ($IC_{50}=5.69{\mu}g/ml$). Moreover, the EtOAc fraction effectively inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells ($IC_{50}=18.87{\mu}g/ml$). Thus, we investigated the effects of the EtOAc fraction on the expression of pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 cells. The treatment of the EtOAc fraction ($100{\mu}g/ml$) effectively decreased the levels of the tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$) and interleukin-6 (IL-6), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These results suggest the potential for CT extract and fractions as promising anti-oxidant and anti-inflammatory agents.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.103-110
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• 1999

A thromboembolic event in patients later given a diagnosis of cancer is the result rather than the cause of the cancer. The risk of hidden cancer is significantly higher for patients with recurrent idiopathic thromboembolism compared to those with secondary deep vein thrombosis. Microemboli from hepatic or adrenal metastases and large-sized emboli from the great veins invaded by the tumor are the sources of tumor embolization The intraarterial tumor emboli less likely invade the arterial wall. Thrombus formation and organization may be capable of destroying tumor cells within pulmorlary blood vessels. Therefore, all tumor emboli are not true metastases. The treatment of deep vein thrombosis and pulmonary embolism in patients with cancer consists of anticoagulation with heparin and warfarin, venacaval filters, appropriate anti-neoplastic agents, and surgical methods(embolectomy, thromboendarterectomy). However, considerable literatures suggest that oral anticoagulant such as warfarin is ineffective in the treatment of those. We report a case of primary unknown squamous cell carcinoma incidentally found in the thrombus after pulmonary embolectomy.