• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1891-1898
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• 2016

Imperata cylindrica, a tall tufted grass which has multiple pharmacological applications is one of the key ingredients in various traditional medicinal formula used in India. Previous reports have shown that I. cylindrica plant extract inhibited cell proliferation and induced apoptosis in various cancer cell lines. To our knowledge, no studies have been published on the effect of I. cylindrica leaf extract on human oral cancers. The present study was undertaken in order to evaluate the anticancer properties of the leaf extract of I. cylindrica using an oral squamous cell carcinoma cell line SCC-9 as an in vitro model system. A methanol extract from dried leaves of I. cylindrica (ICL) was prepared by standard procedures. Effects of the ICL extract on the morphology of SCC-9 cells was visualized by microscopy. Cytotoxicity was determined by MTT assay. Effects of the ICL extract on colony forming ability of SCC-9 cells was evaluated using clonogenic assay. Cell cycle analysis was performed by flow cytometry and induction of apoptosis was determined by DNA fragmentation assay. The ICL extract treatment caused cytotoxicity and induced cell death in vitro in SCC-9 cells in a dose-dependent manner. This treatment also significantly reduced the clonogenic potential and inhibited cell proliferation by arresting the cell cycle in the G2/M phase. Furthermore, DNA fragmentation assays showed that the observed cell death was caused by apoptosis. This is the first report showing the anticancer activity of the methanol extracts from the leaves of I. cylindrica in human oral cancer cell line. Our data indicates that ICL extract could be considered as one of the lead compounds for the formulation of anticancer therapeutic agents to treat/manage human oral cancers. The natural abundance of I. cylindrica and its wide geographic distribution could render it one of the primary resource materials for preparation of anticancer therapeutic agents.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.915-921
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• 2013

Background: Hepatocellular carcinoma is one of the leading causes of mortalities worldwide. The search for new therapeutic targets is of utmost importance for improved treatment. Altered expression of HDAC1 in hepatocellular carcinoma (HCC) and its requirement for liver formation in zebrafish, suggest that it may regulate key events in liver carcinogenesis and organogenesis. However, molecular mechanisms of HDAC1 action in liver carcinogenesis are largely unknown. The present study was conducted to identify HDAC1 interacting proteins in HepG2 cells using modified SH-double-affinity purification coupled with liquid mass spectrophotemetery. Materials and Methods: HepG2 cells were transfected with a construct containing HDAC1 with a C-terminal strepIII-HA tag as bait. Bait proteins were confirmed to be expressed in HepG2 cells by western blotting and purified by double affinity columns and protein complexes for analysis on a Thermo LTQ Orbitrap XL using a C18 nano flow ESI liquid chromatography system. Results: There were 27 proteins which showed novel interactions with HDAC1 identified only in this study, while 14 were among the established interactors. Various subunits of T complex proteins (TCP1) and prefoldin proteins (PFDN) were identified as interacting partners that showed high affinity with HDAC1 in HepG2 cells. Conclusions: The double affinity purification method adopted in this study was very successful in terms of specificity and reproducibility. The novel HDAC1 complex identified in this study could be better therapeutic target for treatment of hepatocellular carcinoma.

• Clinical and Experimental Pediatrics
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• 제59권9호
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• pp.374-380
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• 2016

Purpose: Patients with unresectable, relapsed, or refractory osteosarcoma need a novel therapeutic agent. Metformin is a biguanide derivative used in the treatment of type II diabetes, and is recently gaining attention in cancer research. Methods: We evaluated the effect of metformin against human osteosarcoma. Four osteosarcoma cell lines (KHOS/NP, HOS, MG-63, U-2 OS) were treated with metformin and cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were evaluated using flow cytometric analysis, and migration and wound healing assay were performed. Fourteen female Balb/c-nude mice received KHOS/NP cell grafts in their thigh, and were allowed access to metformin containing water (2 mg/mL) ad libitum. Tumor volume was measured every 3-4 days for a period of 4 weeks. Results: Metformin had a significant antiproliferative effect on human osteosarcoma cells. In particular, metformin inhibited the proliferation and migration of KHOS/NP cells by activation of AMP-activated protein kinase and consequent inhibition of the mammalian target of rapamycin pathway. It also inhibited the proliferation of cisplatin-resistant KHOS/NP clone cells. Analysis of KHOS/NP xenograft Balb/c-nude models indicated that metformin displayed potent in vivo antitumor effects. Conclusion: Further studies are necessary to explore metformin's therapeutic potential and the possibilities for its use as an adjuvant agent for osteosarcoma.

• Biomolecules & Therapeutics
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• 제3권4호
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• pp.316-321
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• 1995

All the pharmacological studies of LB17522 described here were carried out with high doses (fifteen to sixty times of the therapeutic dose) to determine an indication of potential side effects in clinical use in terms of the acute clinical signs, cardiovascular and central nervous system. LB10522 does not produce any observable clinical signs except for the symptoms such as moist eye, skin rash, slight salivation, vomitting, and slightly reduced activity. The effects of LB10522 on the hemodynamics and cardiac function of anesthetized beagle dogs are as follows; heart rates and mean arterial blood pressure had a tendency to increase mildly, which is a normal finding in anesthetized dogs. All the animals except for one showed relatively stable respiratory rates throughout the observation period. Each animal treated with LB10522 showed slight increase in the left cardiac work and left ventricular stroke work which are mainly related to corresponding increases in cardiac output. Femoral blood flow were shown to be increased in some animals treated with LB10522. The epileptogenic activities of various cephalosporins were assessed by a direct intracerebral injection of appropriate concentration of test articles. The CD$_{50}$ values (nmol) obtained from the analysis of the dose-response data are as follows; 78.2, 175.3, 156.3, and 53.5 for cefazolin, cephaloridine, ceftazidime, and LB 10522, respectively. LB10522 seems to be equipotent with cefazolin or to be three times more potent than cephaloridine and ceftazidime in causing adverse CNS stimulation. Taken into consideration all the information obtained, LB10522 is not supposed to induce much changes in the functions examined in these studies in man at therapeutic doses.s.

• Annals of Surgical Treatment and Research
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• 제95권5호
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• pp.240-248
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• 2018

Purpose: This study aimed to validate the synergistic effect of ABT-737 on docetaxel using MDA-MB-231, a triple negative breast cancer (TNBC) cell line overexpressing B-cell lymphoma-2 (Bcl-2). Methods: Western blot analysis was performed to assess expression levels of Bcl-2 family proteins and caspase-related molecules. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution was determined by flow cytometry analysis. Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk) was used for pretreatment to assess the role of caspases. Results: Cell viability of MDA-MB-231 after combination treatment with ABT-737 and docetaxel was significantly lower than that after docetaxel or ABT-737 monotherapy based on MTT assay (both P < 0.001), with a combination index of 0.41. The proportion of sub-G1 population after combination treatment was significantly higher than that after docetaxel or ABT-737 monotherapy (P = 0.001, P = 0.003, respectively). Pretreatment with z-VAD-fmk completely restored cell viability of MDA-MB-231 from apoptotic cell death induced by combination therapy (P = 0.001). Although pro-caspase-8 or Bid did not show significant change in expression level, pro-casepase-9 showed significantly decreased expression after combination treatment. Cleaved caspase-3 showed increased expression while poly (ADP-ribose) polymerase cleavage was induced after combination treatment. However, hypoxia-inducible factor 1-alpha and aldehyde dehydrogenase 1 totally lost their expression after combination treatment. Conclusion: Combination of ABT-737 with docetaxel elicits synergistic therapeutic effect on MDA-MB-231, a TNBC cell line overexpressing Bcl-2, mainly by activating the intrinsic pathway of apoptosis. Therefore, adjunct of ABT-737 to docetaxel might be a new therapeutic option to overcome docetaxel resistance of TNBCs overexpressing Bcl-2.

• 대한본초학회지
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• 제24권1호
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• pp.79-88
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• 2009

Objectives : It has been recently shown that Piperis Longi Fructus (PLF) is involved in the reduction of eosinophil recruitment and production of Th2 cytokines in vivo. However, the main therapeutic mechanisms of PLF remains a matter of considerable debate. To investigate the therapeutic mechanisms of PLF, we examined the influence of PLF on regulatory T cells number, IgE, histamine production in vivo and Th1/Th2 cytokine balance in vitro. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by i.p. injections of 0.2 $m\ell$ alum-precipitated Ag containing 100 ${\mu}g$ of OVA bound to 4 mg of aluminum hydroxide in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 min/day on 3 days/week for 12 weeks(at a flow rate of 250 L/min, 2.5％ ovalbumin in normal saline) and PLF (150 mg/kg) were orally administered 3 times a week for 8 weeks. Splenocytes from C57BL/6 mice at 8 weeks of age were stimulated with anti-CD3 (1 mg/ml) plus anti-CD28 (1 mg/ml) antibody for 48hrs. IL-4 and IFN-$\gamma$ in the culture supernatants were measured by ELISA Results : The suppressive effects of PLF on asthma model were demonstrated by the increase the number of regulatory T cells and by reducing IgE, histamine production in vivo and modulation of Th1/Th2 cytokine balance. Conclusions : These results indicate that PLF has a deep inhibitory effects on asthma model mice by increase the number of regulatory T cells, and by reducing IgE, histamine production.

• 대한한의학회지
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• 제44권1호
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• pp.38-55
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• 2023

Objectives: The purpose of this study was to provide direction for future research in the field of Korean medicine by analyzing microbiome based technologies emerging as a new diagnostic and treatment paradigm. Methods: To achieve the purpose of the study intellectual property data was used. After establishing citation network from registered microbiome-related US patents, citation network was analyzed by knowledge persistence-based main path approach to understanding technological trajectories. Furthermore, community detection algorithms were used to quantitatively identifying specific technological domain in a particular time period. Results: Results shows that early technologies in livestock industry contribute most to the recent patents. Knowledge in the patents flow through the path of food and beverage technological domain, and finally are inherited to the recent development of diagnosis, treatment and prevention technic. Conclusions: This study indicate that developing diagnostic tools which can link the composition of microbiome to specific diseases should be given high priority. Researches should lead to novel therapeutic strategies. Specifically, improving reliability of pattern identification and finding effective therapeutic compositions based on principles of Korean medicine is necessary.

• Journal of Ginseng Research
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• 제48권2호
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• pp.190-201
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• 2024

Background: Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive. Methods: Female MRL/lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples. Podocyte function and ultrastructure were detected. Publicly available single-cell RNA sequencing data and flow cytometry analysis were employed to investigate B cell subpopulations. Metabolomics analysis was adopted. SIRT1 and AMPK expression were analyzed by immunoblotting and immunofluorescence assays. Results: CK reduced proteinuria and protected podocyte ultrastructure in MRL/lpr mice by suppressing circulating anti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK with Rhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated the resolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstating podocyte morphology and mobility by normalizing the expression of nephrin and SYNPO. Conclusions: Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restoration of renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocyte function. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity of renal B cell subsets during LN.

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1982년도 제16차 학술대회연제순서 및 초록
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• pp.11.2-12
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• 1982

최근 우리나라에 있어서도 후두미세수술의 발달로 음성외과 분야에 대한 관심이 높아졌으며 음성장애 환자의 진단 및 치료면에서도 괄목할 만한 발전을 가져왔다. 우리는 작금의 음성외래에서 진단되는 음성장애 환자중에서 특히 성대의 유리연(遊離緣)을 따라서 평행하는 선상(線狀)의 성대구 (聲帶溝)를 보게되는데 이와같이 성문의 폐쇄부전을 동반하는 성대구증 (Sulcus Vocalis)은 1901 년 Salvi에 의해서 처음으로 명명보고된 이래로 유럽과 일본등에서 다수 보고된 바있으나. 우리나라에서는 비교적 관심이 적었던 질환으로 그 뚜렷한 원인과 치료에 대해서는 아직도 정설이 없는 상태이다. 이에 본 교실에서는 1981년 5월부터 1982년 3월까지 본원 음성언어연구실로 내원한 성대구증환자 35예에 대하여 일련의 음성검사를 시행하여 약간의 치험을 고찰한 바 있기에 그 결과를 보고하는 바이다. 1 ) 발생 빈도는 음성 장애를 주소로 내원한 290 예의 환자 중 35예로써 약 12 %였다. 2) 발병연령은 10세 이하에서 19예 (54%)로 가장 많았으며 다음은 10대, 20대의 순이였다. 3 ) 발병연령은 대부분의 예에서 불명이었으나 4예에서는 홍역 후에, 3예에서는 심한 감기 후에 병발했으며, 2 예는 선천적인 것으로 사려되었다. 4) 예중 25예 (71 %)에서 양측성이었고, 좌,우 편측성인 경우가 각각 8예 (23 %), 및 2예 (6 %)였다. 5 ) 임상증상은 거의가 애성을 주소로 하고 있었으며 7 예에서는 만성후두염을 동반하고 있었다. 6 ) 공기역학적검사에서는 20 예(57 %)에 서 최대발성지속시간 (Maximal Phonation time)이 감소되어 있었고, 발성율(發聲率, Phonation Quotient)은 22예(63 %)에서 증가되었으며, 발성시평균호기유율(Mean Air Flow Rate)은 23예 (66 %)에서 증가되었다. 7 ) 스트로보스코피(Stroboscopy) 를 시행할 수 있었던 33예 중 31예 (93%)에서 성문폐쇄부전 (glottic chink)이 있었으며 양측성대의 진동성은 거의 전례에서 규칙적 (regular)이었고, 4예(12 %)에서 비대칭(asymmetric)이었으며, 진폭 (amplitude) 은 5 예 (21 %)에서 감소되었으며, 점막파동(mucosal wave) 은 24 예 (73 %)에서 감소되었다. 8) 치료로서 상기 환자중 5예에서 성대내 테프론(Teflon) 주입을 실시하였고 1예에서 성대구절제술(Sulcusectomy)를 실시하였는데 테프론을 주입한 1예에서 증상의 호전이 있었을 뿐 다른 예에서는 효과가 뚜렷치 않아서 앞으로의 원격성적이 요망되었다.

• Radiation Oncology Journal
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• 제20권2호
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• pp.147-154
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• 2002

목적 : 현재까지 방사선에 대한 저산소세포의 감수성을 높이기 위한 많은 실험적 및 임상적 연구가 진행되어 왔으나, 아직 적절한 방법이 개발되지 못한 상태이다. 본 연구에서는 혈관수축 이완 및 혈액점도 저하를 통하여 말초혈류 증가작용을 갖고 있는 Ginkgo biloba extract (GBE)가 종양내 대사상태에 어떠한 변화를 가져오는지를 $^{31}P$ 핵자기 공명 분광법을 통하여 알아보고자 하였다. 방법 : $100\;mm^3$에서 $130\;mm^3$의 섬유육종을 갖는 18마리의 C3H 마우스를 각각 9 마리씩 두 군으로 분리하였다. 한 군은 GBE로 전처치를 하지 않았으며 나머지 다른 한 군은 $^{31}P$ 자기공명분광법을 시행하기 24시간 전에 100 mg/kg의 GBE를 복강내로 투여하여 전처치를 하였다. 우선 각 군에서 $^{31}P$ 자기공명분광법을 실시하여 대조 spectrum을 얻었으며 그 후 100 mg/kg의 GBE를 재투여 하고 약 1시간 후에 $^{31}P$ 자기공명분광법을 다시 실시하였다. 결과 : 전처치를 하지 않은 군에서는 GBE 투여 전의 평균 pH, PCr/Pi, PME/ATP, Pi/ATP, PCr/(Pi+PME) 수치를 GBE 투여 후 1시간에 측정한 값과 비교하였을 때 통계학적인 차이가 없었다. 그러나 전처치를 한 군에서는 GBE 투여 전의 평균 PCr/Pi, Pi/ATP, PCr/(Pi+PME)수치가 0.49, 0.77, 0.17에서 GBE 투여 후에는 0.74, 0.57, 0.28로 변화하였으며 이는 paired-t test상 통계학적으로 의미있는 차이였다. 결론 : 전처치를 한 군에서 GBE의 재투여로 대사상태가 현저히 호전되었으며 이는 간접적으로 GBE 에 의한 방사선감수성의 증가가 혈류 증가 및 이에 따른 대사상태 호전에 기인함을 나타낸다.