• Title/Summary/Keyword: Genetic therapy

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Different Association of Manganese Superoxide Dismutase Gene Polymorphisms with Risk of Prostate, Esophageal, and Lung Cancers: Evidence from a Meta-analysis of 20,025 Subjects

  • Sun, Guo-Gui;Wang, Ya-Di;Lu, Yi-Fang;Hu, Wan-Ning
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1937-1943
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    • 2013
  • Altered expression or function of manganese superoxide dismutase (MnSOD) has been shown to be associated with cancer risk but assessment of gene polymorphisms has resulted in inconclusive data. Here a search of published data was made and 22 studies were recruited, covering 20,025 case and control subjects, for meta-analyses of the association of MnSOD polymorphisms with the risk of prostate, esophageal, and lung cancers. The data on 12 studies of prostate cancer (including 4,182 cases and 6,885 controls) showed a statistically significant association with the risk of development in co-dominant models and dominant models, but not in the recessive model. Subgroup analysis showed there was no statistically significant association of MnSOD polymorphisms with aggressive or nonaggressive prostate cancer in different genetic models. In addition, the data on four studies of esophageal cancer containing 620 cases and 909 controls showed a statistically significant association between MnSOD polymorphisms and risk in all comparison models. In contrast, the data on six studies of lung cancer with 3,375 cases and 4,050 controls showed that MnSOD polymorphisms were significantly associated with the decreased risk of lung cancer in the homozygote and dominant models, but not the heterozygote model. A subgroup analysis of the combination of MnSOD polymorphisms with tobacco smokers did not show any significant association with lung cancer risk, histological type, or clinical stage of lung cancer. The data from the current study indicated that the Ala allele MnSOD polymorphism is associated with increased risk of prostate and esophageal cancers, but with decreased risk of lung cancer. The underlying molecular mechanisms warrant further investigation.

Isolation of Mouse Ig Heavy and Light Chain Genomic DNA Clones, and Construction of Gene Knockout Vector for the Generation of Humanized Xenomouse (인간 단클론 항체 생산용 Humanized Xenomouse 제작의 기초 소재인 생쥐 Ig 중사슬 및 경사슬 Genomic DNA 클론의 확보 및 유전자 적중 벡터의 제작)

  • Lee, Hee-kyung;Cha, Sang-hoon
    • IMMUNE NETWORK
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    • v.2 no.4
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    • pp.233-241
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    • 2002
  • Background: Monoclonal antibodies (mAb) of rodent origin are produced with ease by hybridoma fusion technique, and have been successfully used as therapeutic reagents for humans after humanization by genetic engineering. However, utilization of these antibodies for therapeutic purpose has been limited by the fact that they act as immunogens in human body causing undesired side effects. So far, there have been several attempts to produce human mAbs for effective in vivo diagnostic or therapeutic reagents including the use of humanized xenomouse that is generated by mating knockout mice which lost Ig heavy and light chain genes by homologous recombination and transgenic mice having both human Ig heavy and light gene loci in their genome. Methods: Genomic DNA fragments of mouse Ig heavy and light chain were obtained from a mouse brain ${\lambda}$ genomic library by PCR screening and cloned into a targeting vector with ultimate goal of generating Ig knockout mouse. Results: Through PCR screening of the genomic library, three heavy chain and three light chain Ig gene fragments were identified, and restriction map of one of the heavy chain gene fragments was determined. Then heavy chain Ig gene fragments were subcloned into a targeting vector. The resulting construct was introduced into embryonic stem cells. Antibiotic selection of transfected cells is under the progress. Conclusion: Generation of xenomouse is particularly important in medical biotechnology. However, this goal is not easily achieved due to the technical difficulties as well as huge financial expenses. Although we are in the early stage of a long-term project, our results, at least, partially contribute the successful generation of humanized xenomouse in Korea.

Plasmodium falciparum Genotype Diversity in Artemisinin Derivatives Treatment Failure Patients along the Thai-Myanmar Border

  • Congpuong, Kanungnit;Hoonchaiyapoom, Thirasak;Inorn, Kornnarin
    • Parasites, Hosts and Diseases
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    • v.52 no.6
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    • pp.631-637
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    • 2014
  • Genetic characteristics of Plasmodium falciparum may play a role in the treatment outcome of malaria infection. We have studied the association between diversity at the merozoite surface protein-1 (msp-1), msp-2, and glutamate-rich protein (glurp) loci and the treatment outcome of uncomplicated falciparum malaria patients along the Thai-Myanmar border who were treated with artemisinin derivatives combination therapy. P. falciparum isolates were collected prior to treatment from 3 groups of patients; 50 cases of treatment failures, 50 recrudescences, and 56 successful treatments. Genotyping of the 3 polymorphic markers was analyzed by nested PCR. The distribution of msp-1 alleles was significantly different among the 3 groups of patients but not the msp-2 and glurp alleles. The allelic frequencies of K1 and MAD20 alleles of msp1 gene were higher while RO33 allele was significantly lower in the successful treatment group. Treatment failure samples had a higher median number of alleles as compared to the successful treatment group. Specific genotypes of msp-1, msp-2, and glurp were significantly associated with the treatment outcomes. Three allelic size variants were significantly higher among the isolates from the treatment failure groups, i.e., $K1_{270-290}$, $3D7_{610-630}$, $G_{650-690}$, while 2 variants, $K1_{150-170}$, and $3D7_{670-690}$ were significantly lower. In conclusion, the present study reports the differences in multiplicity of infection and distribution of specific alleles of msp-1, msp-2, and glurp genes in P. falciparum isolates obtained from treatment failure and successful treatment patients following artemisinin derivatives combination therapy.

Expression Patterns of Cancer Stem Cell Markers During Specific Celecoxib Therapy in Multistep Rat Colon Carcinogenesis Bioassays

  • Salim, Elsayed I;Hegazi, Mona M;Kang, Jin Seok;Helmy, Hager M
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1023-1035
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    • 2016
  • The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemically-induced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.

Distribution of EGFR Mutations Commonly Observed in Primary Lung Adenocarcinomas in Pakistan as Predictors for Targeted Therapy

  • Ahmed, Zeeshan Ansar;Moatter, Tariq;Siddiqui, Areeba;Pervez, Shahid
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7125-7128
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    • 2014
  • Background: Acquired genetic alterations and presence of sensitizing mutations in the tyrosine kinase domain of EGFR and other signaling molecules have been found in different subsets of primary lung adenocarcinoma. The commonest EGFR mutations are small in frame deletions of exon 19 and a point mutation (L858R) in exon 21, having a combined occurrence of around 90%. The objective of this study was to determine the frequency and types of EGFR mutations in primary lung adenocarcinomas in Pakistan. Materials and Methods: EGFR mutations in tumor samples were screened by multiplex real time PCR. Briefly, DNA from formalin fixed paraffin-embedded tissue was amplified with primers and probes specific to 43 different EGFR mutations in a Cobas z 480 instrument. The assay detects mutations in four exons (18-21) of the EGFR gene. Results: Out of 94 patients, 65 were males and 29 females with a M:F ratio of 2.2: 1. The median age was 62 years (range, 28 - 85 years). In our biopsy samples 70 (74%) cases were of primary lung adenocarcinoma, whereas 24 (26%) were confirmed metastatic adenocarcinoma of primary lung origin. EGFR mutation was positive in 29% of the patients. The highest frequency of L858R was observed in 48% of these, followed by deletion in exon 19 (44%). In addition, other rare mutations such as compound G718X:S768I and insertions in exon 20 insertion were detected in approximately 4% of the patients. Conclusions: This study showed that Del 19 and L858R are the most frequent mutations in Pakistani lung adenocarcinoma patients and around 29% of the patients were found eligible for erlotinib therapy.

Risk Factors and Diet Therapy for Atherosclerosis -Emphasis on quality (P/S ratio) of fat- (동맥경화증과 관련된 대사장애와 예방 및 치료식이 -지방(脂防) (P/S 비율)을 중심(中心)으로-)

  • Lee, Ki-Yull;Ahn, Hong-Seok;Leekim, Yang-Cha
    • Journal of Nutrition and Health
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    • v.12 no.3
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    • pp.9-23
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    • 1979
  • The known risk factors for atherosclerosis include plasma low density lipoproteins (LDL)or Cholesterol, low PUFA in the diet, hypertension, and high Na intake, obesity, diabetes, lack of exercise, cigarette smoking, sugar, low fiber and nicotinic acid in the diet, sources of Protein foods, and Psychological factors. Among various dietary factors, fat is known as the most serious causative agent for atherosclerosis. The genetic factor is a18o known as an important one but is out of scope in this paper. Since atherosclerosis is a progressive disease which may develop for many years before showing any definitive symptoms, it is very important to develop preventive programs especially in the country like Korea that is not quite overdevelopted as some western countries. In this paper all the factors mentioned above were reviewed and the dietary suggestion were made on the basis of the content of polyunsaturated and saturated fat in the diet to prevent or/and to cure this disease. Most of the available data on diet therapy with emphasis. on P/S ratio were tabulated together. after tile patient's habitual dietary intake is analized the guidelines of personalized fat-controlled diet can be recommended. It is of utmost importance to develop Korean diets for beth prevention and cure of atherosclerosis emphasizing individual eating habit in the near future which can be more Practicaly used both at home and in the hospital.

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Methodological Research in Development of Intelligence (지력증진(智力增進)에 관(關)한 방법론적(方法論的) 연구(硏究))

  • Kim Jang-Hyun
    • The Journal of Pediatrics of Korean Medicine
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    • v.13 no.2
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    • pp.93-110
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    • 1999
  • The intelligence is the capacity to recognize the things and implies the meaning of abstract thought, learning and adaptability to the circumstance. Recently, as the promotion of learning ablility and memory attracts many people's attention, many studies of this have been accomplished but the pharmacological methods could not promote the intelligence and memory. In oriental medical theory, the human body is composed of four elements - essence, energy, sprit, blood and among these elements, sprit is considered as the concept of vital energy and mind. Especially, from the Jang-Fu physiological point of view, the memory is closly related with the heart and kidney In oriental medicine, some experiments on animal and literature studies on the subject of memory promotion have done. But because of difference in memory mechanism between man and animal, it is not in reason to apply the result of experiment on animal to human. Therefore I have methodological study of memory promotion to set up the concept of oriental medicine and experimental theory about this and can obtain such conclusion. 1. The oriental medical therapy for memory promotion is following. nourishing the heart and blood, regulating the function of spleen, relieving the mental stress, reinforcing the heart and kidney, invigorating and enriching the blood. 2. The insufficient intelligence in a child is considered to not be full and in an old man, it is considered to decline by degrees. 3. It is needed to molecular biological study of neurotransmitter after the using of oriental medical therapy. 4. It is possible to study using the genetic mutation or observing the collateral of brain nerve cell.

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Analysis on the Traditional Knowledge Appearing in "Yi, SeikKan Experience Prescriptions" Which is a Book on Medicine in Joseon Dynasty in the 16th Century : with a Focus on Medical Treating with Eating Foods Using Porridge and Rice (16세기 조선 의서 "이석간경험방"에 나타난 전통지식 분석 : 죽과 밥을 이용한 식치 처방을 중심으로)

  • Oh, Junho
    • Journal of Society of Preventive Korean Medicine
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    • v.17 no.1
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    • pp.125-135
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    • 2013
  • Objectives : Medical treating with eating foods is one of important therapies in East Asian traditional medical knowledge and is referred as a therapy to treat diseases through foods. Since the food cannot be separated from ordinary people living, the medical treating with eating foods is a therapy with strong locality and contains many autogenous parts. Methods : Recently, the world is showing much interest for genetic resources, and the concept of intellectual property is rapidly expanding as the field of 'new knowledge property right' as well. Thus, the knowledge of medical treating with eating foods recently draws much attention in the economic aspect beyond the scholarly interest for traditional medicine. Here, I would like to summarize and report the contents related to medical treating with eating foods on "Yi, SeikKan experience prescriptions" which was discovered before. Results & Conclusions : First, medical treating with eating porridge on "Yi, SeikKan experience prescriptions" is classified into one with nonglutinous rice as the main ingredient and the other with other grains as the main ingredient. It is differently utilized depending on the nature of the grain. Second, medical treating with eating rice on "Yi, SeikKan experience prescriptions" was born from our nation's unique way of living and is classified into one way to eat rice mixed with ground medicinal herbs, another one to cook and eat rice with mixed grains and the other way to use as the external application. Medical treating with eating rice is assumed to replace the meal. Third, "food section" was given separately and discussed in this book. There were some parts different from existing medical knowledge due to the accumulation of experience using medicinal herbs. Fourth, we should pay attention to experience a book on medicine where vibrant medical information has been recorded in order to discover and process our traditional knowledge resources as a useful form.

A Literatural study on the hemorrhoids and hemorrhoids complicated by anal fistula (痔瘡과 痔瘻에 對한 文獻的 考察)

  • No, Hyun-Chan;Rho, Sek-Seon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.10 no.1
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    • pp.284-305
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    • 1997
  • A Literatural study on the etiological factors, classification, prescription of hemorrhoids and hemorrhoids complicated by anal fistula following results were obtained. 1. The cause of hemorrhoids are long time sit, long time gate, overfatigue, overeating, imbalance of stool( constipation or diarrhea), pregnant fertility(overfatigue after childbirth, insufficiency of middle warmer energy), uncontrol sexual excess, pathgenic factors of wetness, heat, wind, dry, genetic cause, excess of anxiety, pile up of heat poison, weakness of entrails and viscera. The cause of hemorrhoid complicated by anal fistula are attack of external wind, heatness, dry, fire, wetness(pathgenic factors), inapporiate treatment and chronic disease, greasy diet, excess of anxiety, constipation, uncontrol sexual excess, obstacle of circulation of vital energy and blood on anal site. 2. Classification of hemorrhoids are female hemorrhoids, male hemorrhoids, pulse hemorrhoids, intestines hemorrhoids, vital energy hemorrhoids, wine hemorrhoids, blood hemonhoids, flowing hemorrhoids. Classification with other method are external hemorrhoids, internal hemorrhoids, mixed hemorrhoids, excrescence hemorrhoids, nipple homorrhoids. External hemorrhoids is classified of varicosis of hemorrhoidal vein, connective tissue form, thrombus form. Classification of hemorrhoid complicated by anal fistula are simple lower hemorrhoid, lower mixed hemorrhoid, deep hemorrhoid, outer of one hole hemorrhoid, a horseshoe hemorrhoids. Once more classificated of four are space of sphincter muscle form, penetration sphincter muscle form, upper of sphincter muscle form, outer of sphincter muscle form. 3. Therapy method of hermorrhoid and hemorrhoid complicated by anal fistula are internal method, fumigation method method, ointment, method of close with medicine, necrotizing method, hot medicated compress( gxternal method), injection, insertion, bind, (operation) and acupuncture therapy (the others method) 4. Herb medicine for many used of internal method are Scutellaria baikalensis George(黃芩), Coptis japonia Makino(黃連), Rehmania giutinosa Liboschitz ex Fischer & Meyer(生地黃), Poncirus trifoliata Refinesque(枳殼), Sanguisorba officinalis Linne(地楡), Sophora japonica L.(槐花), Cnidium officinale Makino (川芎), Astragalus membranaceus Bunge(황기), Angelica gigas Nakai (當歸). 5. Herb medicine for many used of fumigation are Schlechtendalia Chinesis J. Bell (五倍子), Artemisia Vulgaris L. var indica Maxim(艾葉), Poncirus trifoliata Refinesque (枳殼), Nepeta japonica Maximowicy(荊芥), And herb medicine for many used of ointment are Calomelas(輕粉), Alum(白礬), Boswellia carterii Birdwood(乳香), Os Draconis Fossilia Ossis Mastodi(龍骨).

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Oriental and Western Medical Study on the cause and treatment of Obesity (비만의 원인과 치료에 대한 동서의학적 고찰)

  • Lee, Sang-Bong;Keum, Dong-Ho;Lee, Myeong-Jong
    • The Journal of Dong Guk Oriental Medicine
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    • v.5
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    • pp.33-52
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    • 1996
  • The purpose of this study was to investigate efficient treatment in obesity. In order to help clinical application in obesity treatment, this study was performed to investigate the cause and treatment in obesity. The main finding of this study were as follows. 1. In the cause of oriental medicine in obesity, that were moisture(濕), phlegm(痰), gore(瘀), the productive heat(積熱), overeating, supemutrition, underaction, heredity and habitude, psychologic factor(stress) etc. 2. In the western medicine, the cause of obesity were genetic cause, endocrine disorder, hypothalamic extraodinary and secondary effect of drug. But simple obesity is the greater part. Also there were psychologicai and environmental causes. 3. Ear acupuncture of wide application were Naebunbi, Sinmun, Taejang, $ij{\check{o}}m$, $Pyej{\check{o}}m$, $Bij{\check{o}}m$ etc. 4. Body acupuncture of application were $Naej{\check{o}}ng$, $Sangg{\check{o}}h{\check{o}}$, Pungnyung, Kokchi, $Sam{\check{o}}mgyo$, $Umn{\check{o}}ngch{\check{o}}n$ etc. 5. In oriental medical treatment of obesity, Bangpungtongs ngsan(防風通聖散), Daesihotang(大柴胡湯), Seungkitang(承氣湯), Bangkihwangkitang(防己黃?湯), Richulsaryeungtang(二朮四笭湯), Taeksatang(澤瀉湯), Opieum(五皮飮), Gongyundan(控涎丹) etc were wide applicated. 6. The western medical treatment in obesity encourage the dietary cure, exercise cure and behavior adjustment than medical therapy or operation. In treatment of obesity, the dietary cure and herb-drug therapy, ear acupuncture and body acupuncture are effective. But weight maintenance after treating is more important. After all the continuous dietary cure, behavior adjusting cure and exercise cure are necessary.

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