• 제목/요약/키워드: First-in-human dose

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A review of Gymnophalloides seoi (Digenea: Gymnophallidae) and human infections in the Republic of Korea

  • Lee, Soon-Hyung;Chai, Jong-Yil
    • Parasites, Hosts and Diseases
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    • 제39권2호
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    • pp.85-118
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    • 2001
  • Studies on Gymnophalloides seoi (Digenea: Gymnophallidae) and human infections are briefly reviewed. This minute intestinal fluke was first discovered from a Korean woman suffering from acute pancreatitis and gastrointestinal troubles. It was described as a new species by Lee, Chai and Hong in 1993. The southwestern coastal village where the patient resided was found to be a highly endemic area, and additional endemic areas have been identified. The parasite is very small, 0.33-0.50 mm long and 0.23-0.33 mm wide. and characterized by the presence of a ventral pit. The first intermediate host remains unknown, but the second intermediate host has been found to be the oyster Crassostrea gigas. Man and the Palearctic oystercatcher Haematopus ostralegus have been shown to be natural definitive hosts , and wading birds including the Dentish plover Charadrius alexandrinus are highly susceptible to experimental infection. Gerbils, hamsters, cats, and several strains of mice were also susceptible laboratory hosts. In experimentally infected mice, the parasites inhabit the small intestine, pinching and sucking the root of villi with their large oral suckers, but they did not invade beyond the mucosa in immunocompetent mice. However, they were found to invade the submucosa in immunosuppressed mice. Human G. seoi infections have been found in at least 25 localities; 23 islands on the Yellow Sea or the South Sea, and 2 western coastal villages. The highest Prevalence was found in a village on Aphaedo. Shinan-fun (49% e99 Positive rate) : other areas showed 0.8-25.3% prevalence. Infected people complained of variable degrees of gastrointestinal troubles and indigestion. The infection can be diagnosed by recovery of eggs in the feces; however, an expert is needed to identify the eggs. Praziquantel, 10mg/kg in single dose, is effective for treatment of human infections. Eating raw oysters in endemic areas should be avoided.

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β-Elemene Induces Apoptosis in Human Renal-cell Carcinoma 786-0 Cells through Inhibition of MAPK/ERK and PI3K/Akt/mTOR Signalling Pathways

  • Zhan, Yun-Hong;Liu, Jing;Qu, Xiu-Juan;Hou, Ke-Zuo;Wang, Ke-Feng;Liu, Yun-Peng;Wu, Bin
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권6호
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    • pp.2739-2744
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    • 2012
  • Background: Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. ${\beta}$-Elemene, a promising anticancer drug extracted from a traditional Chinese medicine, has been shown to be effective against various tumors. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated. Methods: Human RCC 786-0 cells were treated with different concentrations of ${\beta}$-elemene, and cell viability and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by western blotting. Autophagy was evaluated by transmission electron microscopy. Results: ${\beta}$-Elemene inhibited the viability of 786-0 cells in a dose- and time-dependent manner. The anti-tumor effect was associated with induction of apoptosis. Further study showed that ${\beta}$-elemene inhibited the MAPK/ERK as well as PI3K/Akt/mTOR signalling pathways. Moreover, robust autophagy was observed in cells treated with ${\beta}$-elemene. Combined treatment of ${\beta}$-elemene with autophagy inhibitors 3-methyladenine or chlorochine significantly enhanced the anti-tumor effects. Conclusions: Our data provide first evidence that ${\beta}$-elemene can inhibit the proliferation of RCC 786-0 cells by inducing apoptosis as well as protective autophagy. The anti-tumor effect was associated with the inhibition of MAPK/ERK and PI3K/Akt/mTOR signalling pathway. Inhibition of autophagy might be a useful way to enhance the anti-tumor effect of ${\beta}$-elemene on 786-0 cells.

Effects of Drynariae Rhizoma on the Proliferation of Human Bone Cells

  • Lee, Bu-Tae;Jeong, Ji-Cheon
    • 대한한의학회지
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    • 제24권4호
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    • pp.43-53
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    • 2003
  • Drynariae Rhizorna (DR), an herbal medicine known for its effect to purify blood quality and improve circulation, frequently appears as the main ingredient in prescriptions for bone injuries. Currently, how pharmacologically it contributes to the reformation of bone is unclear. In the present study, the effect of the aqueous extract of DR on bone cells was investigated in vitro for the first time. The human osteoprecursor cells (OPC-I) were incubated in the medium with different concentrations of the aqueous extract of DR and the cell proliferation was studied. When the concentration of DR aqueous extract was $<120{\;}\mu\textrm{g}/ml$, the proliferation of OPC-I was enhanced. However, the proliferation of OPC-I was inhibited by DR extract with the concentrations $>250{\;}\mu\textrm{g}/ml$. Under most treatments, the cells presented very pale expression for cyclooxygenase-2 (Cox 2) protein; a slightly intensified band showed at the highest DR concentration, 1.0 mg/ml during the course of culture. From the results, it was concluded that the aqueous extract of DR was found to directly stimulate the proliferation, alkaline phosphatase (ALP) activity, protein secretion and particularly type I collagen synthesis of OPC-I at dose-dependent manner.

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Resveratrol Exerts Dosage-Dependent Effects on the Self-Renewal and Neural Differentiation of hUC-MSCs

  • Wang, Xinxin;Ma, Shanshan;Meng, Nan;Yao, Ning;Zhang, Kun;Li, Qinghua;Zhang, Yanting;Xing, Qu;Han, Kang;Song, Jishi;Yang, Bo;Guan, Fangxia
    • Molecules and Cells
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    • 제39권5호
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    • pp.418-425
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    • 2016
  • Resveratrol (RES) plays a critical role in the fate of cells and longevity of animals via activation of the sirtuins1 (SIRT1) gene. In the present study, we intend to investigate whether RES could promote the self-renewal and neural-lineage differentiation in human umbilical cord derived MSCs (hUC-MSCs) in vitro at concentrations ranging from 0.1 to $10{\mu}M$, and whether it exerts the effects by modulating the SIRT1 signaling. Herein, we demonstrated that RES at the concentrations of 0.1, 1 and $2.5{\mu}M$ could promote cell viability and proliferation, mitigate senescence and induce expression of SIRT1 and Proliferating Cell Nuclear Antigen (PCNA) while inhibit the expression of p53 and p16. However, the effects were reversed by 5 and $10{\mu}M$ of RES. Furthermore, RES could promote neural differentiation in a dose-dependent manner as evidenced by morphological changes and expression of neural markers (Nestin, ${\beta}III-tubulin$ and NSE), as well as pro-neural transcription factors Neurogenin (Ngn)1, Ngn2 and Mash1. Taken together, RES exerts a dosage-dependent effect on the self-renewal and neural differentiation of hUC-MSCs via SIRT1 signaling. The current study provides a new strategy to regulate the fate of hUC-MSCs and suggests a more favorable in vitro cell culture conditions for hUCMSCs-based therapies for some intractable neurological disorders.

Anti-cancer Effect of Apigenin on Human Breast Carcinoma MDA-MB-231 through Cell Cycle Arrest and Apoptosis

  • Lee, Hwan Hee;Cho, Hyosun
    • 한국미생물·생명공학회지
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    • 제47권1호
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    • pp.34-42
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    • 2019
  • Apigenin, a common natural product that is found in many plants and vegetables, has been reported to have many biological activities, including antioxidative, anti-inflammatory, and anticancer effects. The triple-negative breast carcinoma cell line MDA-MB-231 is known to be highly invasive and resistant to chemotherapy. In this study, we investigated the anticancer effect of apigenin on human MDA-MB-231 cells. First, the cytotoxicity of apigenin toward MDA-MB-231 cells was analyzed by MTT assay. Then, the cell cycle and apoptotic effects of apigenin were examined, and the molecular mechanism underlying its anticancer activity was explored. Apigenin inhibited the growth of the cells in a dose-dependent manner, correlating with the cell cycle arrest at the G2-M phase as well as an increase of early apoptosis. The cell-cycle inhibitory effect was highly associated with the increased expression of p21 and decreased expression of CDK6, cyclin D1, and cyclin B1. The induction of apoptosis by apigenin was associated with the upregulated expression of cleaved PARP and cleaved caspase-3, -7, and -9.

Anti-cancer and -Metastatic Effects of Lactobacillus Rhamnosus GG Extract on Human Malignant Melanoma Cells, A375P and A375SM

  • Lee, Jaehoon;Park, Sangkyu;Seo, Jeongmin;Roh, Sangho
    • International Journal of Oral Biology
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    • 제42권3호
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    • pp.107-115
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    • 2017
  • Human malignant melanoma is an aggressive skin cancer which has been rising at a greater rate than any other cancers. Although various new therapeutic methods have been developed in previous studies, this disease has properties of high proliferation and metastasis rate which remain obstacles that have lead to a poor prognosis in patients. It has been reported that a specific Lactobacillus extract has anti-cancer and -metastasis effect in vitro and in vivo. However, previous research has not specified precisely what effect the Lactobacillus rhamnosus GG (LGG) extract has had on human malignant melanomas. In this study, we showed that the LGG extract has anti-cancer and -metastasis effects on the human malignant melanoma cell lines, A375P and A375SM. At first, it was found that, while the LGG extract affects human neonatal dermal fibroblasts slightly, it induced the dose-dependent anti-cancer effect on A375P and A375SM by a WST-1 proliferation assay. As a result of a real-time PCR analysis, the expression patterns of several genes related to cell cycle, proliferation, and apoptosis were modulating in a manner that inhibited the growth of both malignant melanoma cell lines after the treatment of the LGG extract. Furthermore, genes related to the epithelial-mesenchymal transition were down-regulated, and migration rates were also decreased significantly by the LGG extract. Our study showed that the LGG extract could be used as a potential therapeutic source.

당귀로부터 정제한 Decursin의 인간 급성 단핵구성 백혈병 세포(THP-1 cells)의 세포 독성 및 Apoptosis에 미치는 영향 (Decursin from Angelica gigas Nakai Promotes Cytotoxicity and Induces Apoptosis in THP-1 cells, a Human Acute Monocytic Leukemia)

  • 김남석;정승일;김종석;오미진;오찬호
    • 생약학회지
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    • 제47권3호
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    • pp.197-203
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    • 2016
  • Decursin is a major component of the root of Angelica gigas(Umbelliferae), which has been traditionally used in Korea as a tonic and to treat anemia, hemiplegia, and women's diseases. The objective of this study is to identify the anti-cancer mechanism induced by decursin on apoptosis of human leukemia and lymphoma cells. Cytotoxicity of decursin on U937, HL-60, MOLT-4, THP-1 cells showed the significant effects. First of all, $IC_{50}$ of decursin on four cell lines was 27.1, 32.4, 17.4, $15.1{\mu}M$, respectively. So $IC_{50}$ in THP-1 cells was the smallest among 4 cell lines treated with decursin($15.1{\mu}M$). In order to understand the apoptosis-mechanism by decursin, we examined the gene expression of bcl-2(anti-apoptotic), bax(pro-apoptotic) and p53(tumor suppressor)after treating the THP-1 cells with decursin(10, 50 and $100{\mu}M$). It was found bcl-2 gene was decreased dose dependently, the expression level of bax gene of THP-1 cells treated with $100{\mu}M$ of decursin was about 3 times higher than those of control, and p53 gene was increased In the same concentration($100{\mu}M$), p53 gene was increased dose dependent manner. In protein express, bcl-2 and p53 protein showed a tendency to decrease. bax was increased about 4 fold. Therefore decursin is a useful chemotherapeutic agent against leukemia.

Recombinant Human Erythropoietin Therapy for a Jehovah's Witness Child With Severe Anemia due to Hemolytic-Uremic Syndrome

  • Woo, Da Eun;Lee, Jae Min;Kim, Yu Kyung;Park, Yong Hoon
    • Clinical and Experimental Pediatrics
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    • 제59권2호
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    • pp.100-103
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    • 2016
  • Patients with hemolytic-uremic syndrome (HUS) can rapidly develop profound anemia as the disease progresses, as a consequence of red blood cell (RBC) hemolysis and inadequate erythropoietin synthesis. Therefore, RBC transfusion should be considered in HUS patients with severe anemia to avoid cardiac or pulmonary complications. Most patients who are Jehovah's Witnesses refuse blood transfusion, even in the face of life-threatening medical conditions due to their religious convictions. These patients require management alternatives to blood transfusions. Erythropoietin is a glycopeptide that enhances endogenous erythropoiesis in the bone marrow. With the availability of recombinant human erythropoietin (rHuEPO), several authors have reported its successful use in patients refusing blood transfusion. However, the optimal dose and duration of treatment with rHuEPO are not established. We report a case of a 2-year-old boy with diarrhea-associated HUS whose family members are Jehovah's Witnesses. He had severe anemia with acute kidney injury. His lowest hemoglobin level was 3.6 g/dL, but his parents refused treatment with packed RBC transfusion due to their religious beliefs. Therefore, we treated him with high-dose rHuEPO (300 IU/kg/day) as well as folic acid, vitamin B12, and intravenous iron. The hemoglobin level increased steadily to 7.4 g/dL after 10 days of treatment and his renal function improved without any complications. To our knowledge, this is the first case of successful rHuEPO treatment in a Jehovah's Witness child with severe anemia due to HUS.

Performance Analysis of Low-level Radiation Shielding Sheet with Diamagnetic Nanoparticles

  • Cho, Jae-Hwan;Kim, Myung-Sam
    • Journal of Magnetics
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    • 제20권2호
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    • pp.103-109
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    • 2015
  • In this study, the authors attempted to produce a medical radiation shielding fiber that can be produced at a nanosize scale and that is, unlike lead, harmless to the human body. The performance of the proposed medical radiation shielding fiber was then evaluated. First, diamagnetic bismuth oxide, an element which, among elements that have a high atomic number and density, is harmless to the human body, was selected as the shielding material. Next, 10-100 nm sized nanoparticles in powder form were prepared by ball milling the bismuth oxide ($Bi_2O_3$), the average particle size of which is $1-500{\mu}m$, for approximately 10 minutes. The manufactured bismuth oxide was formed into a colloidal solution, and the radiation shielding fabric was fabricated by curing after coating the solution on one side or both sides of the fabric. The thicknesses of the shielding sheets prepared with bismuth oxide were 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, and 1.0 mm. An experimental method was used to measure the absorbed dose and irradiation dose by using the lead equivalent test method of X-ray protection goods presented by Korean Industrial Standards; the resultant shielding rate was then calculated. From the results of this study, the X-ray shielding effect of the shielding sheet with 0.1 mm thickness was about 55.37% against 50 keV X-ray, and the X-ray shielding effect in the case of 1.0 mm thickness showed shielding characteristics of about 99.36% against 50 keV X-ray. In conclusion, it is considered that nanosized-bismuth radiation shielding fiber developed in this research will contribute to reducing the effects of primary X-ray and secondary X-ray such as when using a scattering beam at a low level exposure.

Anti-Cancer Effects of Imperata cylindrica Leaf Extract on Human Oral Squamous Carcinoma cell line SCC-9 in Vitro

  • Keshava, Rohini;Muniyappa, Nagesh;Gope, Rajalakshmi;Ramaswamaiah, Ananthanarayana Saligrama
    • 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.