• Title/Summary/Keyword: tumour

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AntagomiR-27a Targets FOXO3a in Glioblastoma and Suppresses U87 Cell Growth in Vitro and in Vivo

  • Ge, Yun-Fei;Sun, Jun;Jin, Chun-Jie;Cao, Bo-Qiang;Jiang, Zhi-Feng;Shao, Jun-Fei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.963-968
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    • 2013
  • Objective: To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. Methods: The miR-27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. Results: qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. Conclusion: MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells.

The Oncological Safety of Nipple-Sparing Mastectomy: A Systematic Review of the Literature with a Pooled Analysis of 12,358 Procedures

  • Headon, Hannah Louise;Kasem, Abdul;Mokbel, Kefah
    • Archives of Plastic Surgery
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    • v.43 no.4
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    • pp.328-338
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    • 2016
  • Nipple-sparing mastectomy (NSM) is increasingly popular as a procedure for the treatment of breast cancer and as a prophylactic procedure for those at high risk of developing the disease. However, it remains a controversial option due to questions regarding its oncological safety and concerns regarding locoregional recurrence. This systematic review with a pooled analysis examines the current literature regarding NSM, including locoregional recurrence and complication rates. Systematic electronic searches were conducted using the PubMed database and the Ovid database for studies reporting the indications for NSM and the subsequent outcomes. Studies between January 1970 and January 2015 (inclusive) were analysed if they met the inclusion criteria. Pooled descriptive statistics were performed. Seventy-three studies that met the inclusion criteria were included in the analysis, yielding 12,358 procedures. After a mean follow up of 38 months (range, 7.4-156 months), the overall pooled locoregional recurrence rate was 2.38%, the overall complication rate was 22.3%, and the overall incidence of nipple necrosis, either partial or total, was 5.9%. Significant heterogeneity was found among the published studies and patient selection was affected by tumour characteristics. We concluded that NSM appears to be an oncologically safe option for appropriately selected patients, with low rates of locoregional recurrence. For NSM to be performed, tumours should be peripherally located, smaller than 5 cm in diameter, located more than 2 cm away from the nipple margin, and human epidermal growth factor 2-negative. A separate histopathological examination of the subareolar tissue and exclusion of malignancy at this site is essential for safe oncological practice. Long-term follow-up studies and prospective cohort studies are required in order to determine the best reconstructive methods.

Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs

  • Noh, Keumhan;Kang, Wonku
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.648-658
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    • 2017
  • 7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

Two Cases of Tyrosinemia; One with Hepatocellular Carcinoma and the other with Acute Liver Failure (타이로신 혈증 2례; 간암이 유발된 1례와 급성 간부전으로부터 회복된 1례의 비교)

  • Kim, Sook Za;Song, Woong Ju;Jeon, Young Mi;Levy, Harvey L.
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.13 no.1
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    • pp.48-53
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    • 2013
  • Tyrosinemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma in childhood or early adolescence. We studied a 37-year-old woman with tyrosinemia I whose severe liver disease in infancy and rickets during childhood were resolved with dietary therapy. From 14 years of age, she resumed unrestricted diet with the continued presence of the biochemical features of tyrosinemia, yet maintained normal liver function. In adult years, she accumulated only a small amount of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6-1G>T, and a novel missense mutation, p.Q279R. Studies of resected liver revealed the absence of hydrolytic activity and immunological expression of fumarylacetoacetate hydrolase in tumour. In the non-tumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase were found. This case demonstrates the high risk of liver cancer in tyrosinemia I even in a seemingly favorable biological environment. In this study of tyrosinemia I, Case 2 with negative succinylacetone accumulation and the recovery of acute liver failure was compared with Case 1. Diet restriction and NTBC treatment are crucial to prevent hepatocellular carcinoma until liver transplant can take place and cure the condition. Further studies are needed to examine cases where liver cancer did not result despite clinical symptoms/signs of tyrosinemia type I.

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Focal Adnexal Dysplasia in a Dog (개에서 Focal Adnexal Dysplasia 증례)

  • Park, Ho-Il;Hur, Won-Suk;Cho, Eun-Sang;Song, Sin-Hwa;Jeong, Seong-Mok;Cho, Sung-Whan;Son, Hwa-Young
    • Journal of Veterinary Clinics
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    • v.26 no.3
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    • pp.259-262
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    • 2009
  • Focal adnexal dysplasia(FAD) is a rare non-neoplastic lesion of adnexal appendages that occurs in dogs and has good prognosis. We report a case in which FAD diagnosis was favored by its histopathological features. A 8-year-old, castrated male American cocker spaniel dog presented with papillomatous masses on the distal phalanx of left forelimb. Histopathologically, the stroma was sharply demarcated from the adjacent dermis and subcutis. The adnexa was surrounded and interspersed with abundant, hyalinized collagen and the numerous sebaceous lobules distributed haphazardly around hair follicles, which is thickened, dilated and tortuous with abundant keratin. Epidermis was acanthotic. Proliferative lesions of the skin region are very common with similar gross features, thus the basic histopathological examination supported by additional diagnostic methods allow to establish the definitive diagnosis in most cases of cutaneous tumor or tumor-like lesions. And it is important that physicians and pathologists are aware of this unusual tumour-like nonneoplastic lesion.

Induction of Cytokines and Nitric Oxide in Murine Macrophages Stimulated with Enzymatically Digested Lactobacillus Strains

  • Kim, Dong-Woon;Cho, Sung-Back;Yun, Cheol-Heui;Jeong, Ha-Yeon;Chung, Wan-Tae;Choi, Chang-Weon;Lee, Hyun-Jeong;Nam, In-Sik;Suh, Guk-Hyun;Lee, Sang-Suk;Lee, Byong-Seak
    • Journal of Microbiology
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    • v.45 no.5
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    • pp.373-378
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    • 2007
  • Based on observations that lactic acid bacteria have the ability to activate macrophages, we assessed the potential effects of eight different Lactobacillus strains treated with gastrointestinal enzymes on the production of nitric oxide and various cytokines in macrophages. RAW 264.7 murine macrophage cells were cultured with either precipitates or supernatants of Lactobacillus strains digested with pepsin followed by pancreatin. The increased production of nitric oxide and interleukin $(IL)-1{\beta}$, IL-6, IL-12 and tumour necrosis factor $(TNF)-{\alpha}$ were observed when cultured with precipitates, and this effect was largely strain-dependent. In contrast, the exposure of RAW 264.7 cells to supernatants produced weaker or nearly undetectable effects in comparison to the effects of exposure to precipitates. The induction of nitric oxide appeared to be unaffected. These results demonstrate that nitric oxide and cytokines were effectively induced when the bacterial precipitate was treated with macrophages. The results of the present study also indicate that Lactobacillus strains treated with digestive enzymes are capable of stimulating the production of nitric oxide and cytokines in macrophages, which may modulate the gastrointestinal immune function of the host when it is given as a feed additive.

Mobi-Kids Study: Exposure Assessment of Electromagnetic Radiation from Mobile Phones I. Analysis on Exposure Types (Mobi-Kids Study: 휴대전화의 전자파 노출량 평가 I. 노출 유형 분석)

  • Lee, Ae-Kyoung;Wi, Hyunho;Yoon, Yonghyun;Kim, Dae-Keon;So, Jae-Sang;Lee, Byungje;Choi, Hyung-Do
    • The Journal of Korean Institute of Electromagnetic Engineering and Science
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    • v.24 no.10
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    • pp.1017-1026
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    • 2013
  • Four countries are participating in exposure assessment for Mobi-Kids Study. Each country evaluates RF and ELF exposure from mobile phones considering telecommunication system and environment in the corresponding area. The results will be used to determine accumulation exposure level of each subject in case and control groups to assess the potential carcinogenic effects of childhood and adolescent exposure to radio frequency(RF) and extremely low frequency( ELF) from mobile phones on the central nervous system. This paper analyzes exposure types of mobile phones which have been used in Korea for about 10 years, based on Mobi-Kids protocol. It includes investigation of mobile phone models released in the domestic market, design of numerical phone models to represent each exposure type, and measurement of ELF radiation from mobile phones.

DISTRACTION OSTEOGENESIS FOLLOWED BY IMPLANT INSTALLATION ON THE RECONSTRUCTED MANDIBLE WITH A FREE ILIAC BONE GRAFT IN A ODONTOGENIC MANDIBULAR MYXOMA PATIENT : CASE REPORT (하악 치성점액종 환자에서 유리장골이식으로 재건된 하악골의 골신장술 후 임플란트식립 : 증례보고)

  • Lim, Hun-Jun;Kim, Moon-Seob;Lee, Dae-Jung;Lee, Jong-Bok;Min, Seung-Ki;Paeng, Jun-Young
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.31 no.5
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    • pp.419-424
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    • 2009
  • Odontogenic myxoma, a rare tumour that occurs in the jaws, locally invasive, destructive tumors that do not metastasize to lymph nodes. Large odontogenic myxoma on mandible is treated by mandibulectomy, defected mandible is reconstructed by bone graft. Reconstructed mandible is difficult to reconstruct dentition using implant because of deficiency of bone amount. So it is necessary to additional bone graft. But a poor aspect of soft tissue lead to unsatisfactory result. Because of distraction osteogenesis is possible to reconstruction of an amount of bone and soft tissue, that is advantage to reconstruction of alveolar bone on reconstructed mandible. We report with review of literatures the 25 years old male patient who had odontogenic myxoma in left mandible, was undergone mandibulectomy and successfully implant installation and prosthetic restoration after distraction osteogenesis(Track $Plus^{(R)}$, KLS Martin, Germany) on the reconstructed mandible with a free iliac bone graft, and we have conservative and successful result.

DESIGN AND ANALYSIS OF RANDOMIZED CLINICAL TRIALS REQUIRING PROLONGED OBSERVATION OF EACH PATIENT I. INTRODUCTION AND DESIGN

  • Peto R.;Pike M.C.;Armitage P.;Breslow N.E.;Cox D.R.;Howard S.V.;Mantel N.;Mcpherson K.;Peto J.;Smith P.G.
    • 대한예방의학회:학술대회논문집
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    • 1994.02b
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    • pp.206-233
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    • 1994
  • The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part!, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and would be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials, however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.

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RNA-Seq De Novo Assembly and Differential Transcriptome Analysis of Korean Medicinal Herb Cirsium japonicum var. spinossimum

  • Roy, Neha Samir;Kim, Jung-A;Choi, Ah-Young;Ban, Yong-Wook;Park, Nam-Il;Park, Kyong-Cheul;Yang, Hee-sun;Choi, Ik-Young;Kim, Soonok
    • Genomics & Informatics
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    • v.16 no.4
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    • pp.34.1-34.9
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    • 2018
  • Cirsium japonicum belongs to the Asteraceae or Compositae family and is a medicinal plant in Asia that has a variety of effects, including tumour inhibition, improved immunity with flavones, and antidiabetic and hepatoprotective effects. Silymarin is synthesized by 4-coumaroyl-CoA via both the flavonoid and phenylpropanoid pathways to produce the immediate precursors taxifolin and coniferyl alcohol. Then, the oxidative radicalization of taxifolin and coniferyl alcohol produces silymarin. We identified the expression of genes related to the synthesis of silymarin in C. japonicum in three different tissues, namely, flowers, leaves, and roots, through RNA sequencing. We obtained 51,133 unigenes from transcriptome sequencing by de novo assembly using Trinity v2.1.1, TransDecoder v2.0.1, and CD-HIT v4.6 software. The differentially expressed gene analysis revealed that the expression of genes related to the flavonoid pathway was higher in the flowers, whereas the phenylpropanoid pathway was more highly expressed in the roots. In this study, we established a global transcriptome dataset for C. japonicum. The data shall not only be useful to focus more deeply on the genes related to product medicinal metabolite including flavolignan but also to study the functional genomics for genetic engineering of C. japonicum.