• 제목/요약/키워드: Cancer stem cell

검색결과 411건 처리시간 0.026초

Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

  • Awan, Tashfeen;Iqbal, Zafar;Aleem, Aamer;Sabir, Noreen;Absar, Muhammad;Rasool, Mahmood;Tahir, Ammara H.;Basit, Sulman;Khalid, Ahmad Mukhtar;Sabar, Muhammad Farooq;Asad, Sultan;Ali, Agha Shabbir;Mahmood, Amer;Akram, Muhammad;Saeed, Tariq;Saleem, Arsalan;Mohsin, Danish;Shah, Ijaz Hussain;Khalid, Muhammad;Asif, Muhammad;Haq, Riazul;Iqbal, Mudassar;Akhtar, Tanveer
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권11호
    • /
    • pp.5469-5475
    • /
    • 2012
  • Background and Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival ($43.7{\pm}4.24$ weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). Conclusions: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.

연소형 골수단구성 백혈병에서의 동종 조혈 모세포 이식 (Allogeneic Hematopoietic Stem Cell Transplantation in Juvenile Myelomonocytic Leukemia)

  • 유건희;유동길;이수현;성기웅;조은주;구홍회
    • Clinical and Experimental Pediatrics
    • /
    • 제48권2호
    • /
    • pp.178-185
    • /
    • 2005
  • 목 적 : JMML은 소아에서 발생하는 매우 드문 종류의 백혈병으로서 통상적인 항암화학요법만으로는 완치가 어려워 동종 조혈 모세포 이식을 시행하여야 한다. 아직 국내에서는 본 질환의 조혈 모세포 이식 성적에 대한 보고가 없어 저자들은 단일기관에서 경험한 JMML 환자의 동종 조혈 모세포 이식 성적을 보고하고자 하였다. 방 법 : 8개월에서 39개월 된 11명의 JMML 환자를 대상으로 동종 조혈 모세포 이식을 시행하였다. 조혈 모세포의 공급원으로 비혈연 골수 혹은 제대혈 7례, HLA 일치 형제 공여자 3례, HLA 1 항원 불일치 가족 공여자 1례 등을 이용하였다. 모든 환자들은 이식 전 항암화학요법을 시행 받았고 일부 환자에게는 13-cis-retinoic acid(CRA)를 사용하였다. 결 과 : 총 11례 중 3례만이 이식 전 치료로 혈액학적 및 임상적 완전관해에 도달하였다. 이식 후 1개월째 첫 키메리즘 평가 결과 완전 공여자 키메리즘 5례, 혼합 키메리즘 5례, 자가회복 1례였다. 혼합 키메리즘 상태에서 비장종대가 해소되지 않았던 1례에서 면역억제제의 급속 감량과 함께 CRA를 지속적으로 투여한 결과 완전 공여자 키메리즘으로의 전환과 함께 완전관해가 유도되었다. 자가회복 되었던 1례는 이식 후 조기 재발하였으나 복합 항암화학요법과 CRA의 투여로 이차 완전관해가 유도되었다. 결과적으로 11례 중 6례가 이식 후 정중 추적기간 15.5개월간 무사건 생존 중이다. 사망한 3례는 모두 완전 공여자 키메리즘에 실패하였던 경우들로서 질병의 재발 혹은 진행이 사망의 원인이었다. 결 론 : 본 연구 결과 JMML의 근치에는 동종 조혈 모세포 이식 후 이식편대 백혈병 효과가 중요한 역할을 담당하며 CRA도 긍정적 역할을 가지는 것으로 사료된다. 이식 후에도 완전관해에 도달하지 못하고 혼합 키메리즘 양상을 보이는 경우, 면역 억제제를 조기 감량하는 정책과 함께 CRA를 도입함으로써 완치의 가능성을 높일 수 있을 것으로 기대된다.

Papaya: A gifted nutraceutical plant - a critical review of recent human health research

  • Karunamoorthi, Kaliyaperumal;Kim, Hyung-Min;Jegajeevanram, Kaliyaperumal;Xavier, Jerome;Vijayalakshmi, Jayaraman
    • 셀메드
    • /
    • 제4권1호
    • /
    • pp.2.1-2.17
    • /
    • 2014
  • The plant kingdom is considered to be a repository of modern medicine, attributable to their rich source of bio-active molecules and secondary metabolites. It is indeed the Nutraceuticals that enhance immunity and ensure a healthier life because of their prophylactic and therapeutic values. Over centuries, papaya [Caricaceae; (Carica papaya Linn.)] is a renowned nutritious and medicinal plant. Each part of the papaya like root, stem, leaf, flower, fruit, seed, rinds, and latex has its own nutraceutical properties. It serves as food, cooking aid, and Ethnomedicine to prevent and treat wide-range of diseases and disorders. It has also been traditionally used as appetite enhancer, meat tenderizer, purgative, medicinal acne, abortifacient and vermifuge. Over decades, a series of scientific attempts were made to authenticate the nutraceutical properties of papaya. These studies validated that the papaya has antiplasmodial, antitrichochramal, antitrichomonal, antidengue, and anti-cancer activities. They have also exhibited that papaya possesses antiseptic, antiparasitic, anti-inflammatory, antidiabetic, and contraceptive features, and it helps in the management of sickle-cell anaemia, HIV, heart diseases and digestional disorders too. Nevertheless, the responsible bio-active molecules and their mode of actions remain indistinct and imprecise, and this calls for further pharmacological and clinical research on them. Conclusively, papaya is one of the naturally gifted plants; though its nutraceutical properties as a food or as a quasi-drug are poorly understood or undervalued by people. Accordingly, this scrutiny, demand for instigation of public health awareness campaigns to promote papaya consumption, so that the society shall acquire optimal benefits of papaya and in turn prevent and alleviate various diseases and illness.

등심초로부터 분리된 화합물의 항산화 활성 및 암세포 성장 억제 효과 (Antioxidant and Cytotoxic Activity of Compounds from the Stem of Juncus effusus)

  • 김예진;박찬익;박재성;안은미
    • Journal of Applied Biological Chemistry
    • /
    • 제57권1호
    • /
    • pp.47-51
    • /
    • 2014
  • 등심초(Juncus effusus)를 70% ethanol로 추출하고 이 추출물을 ethyl acetate분획, n-butanol 및 $H_2O$ 분획으로 나누었다. Ethyl acetate 분획에 대하여 silica gel, Sephadex LH-20 column chromatography를 반복 실시하여 2종의 화합물을 분리하였다. 화합물 1 (dehydroeffusol)과 2 (effusol)에 대하여 free radical 소거활성을 측정한 결과, dehydroeffusol (DPPH; $130{\pm}3.21{\mu}M$, ABTS; $39{\pm}3.51{\mu}M$)과 effusol (DPPH; $79{\pm}1.53{\mu}M$, ABTS; $24{\pm}2.73{\mu}M$)은 강한 항산화 활성을 나타내었다. 또한 이들 화합물들의 인체유래 위암세포(AGS), 폐암세포(A549)에 대한 성장억제 효과를 측정한 결과 모두 항암약물(CPA)과 유사하거나 더 높은 성장 저해 효과를 보였다.

The potential theragnostic (diagnostic+therapeutic) application of exosomes in diverse biomedical fields

  • Kim, Yong-Seok;Ahn, Jae-Sung;Kim, Semi;Kim, Hyun-Jin;Kim, Shin-Hee;Kang, Ju-Seop
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제22권2호
    • /
    • pp.113-125
    • /
    • 2018
  • Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.

Anti-inflammatory effects of proanthocyanidin-rich red rice extract via suppression of MAPK, AP-1 and NF-κB pathways in Raw 264.7 macrophages

  • Limtrakul, Pornngarm;Yodkeeree, Supachai;Pitchakarn, Pornsiri;Punfa, Wanisa
    • Nutrition Research and Practice
    • /
    • 제10권3호
    • /
    • pp.251-258
    • /
    • 2016
  • BACKGROUND/OBJECTIVES: Several pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages. MATERIALS/METHODS: Pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B ($NF-{\kappa}B$), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined. RESULTS: Our results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-${\alpha}$, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and $NF-{\kappa}B$ transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced $NF-{\kappa}B$ and AP-1 activation in LPS-activated Raw 264.7 cells. CONCLUSION: These observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, $NF-{\kappa}B$, and MAPKs pathways.

발효옻 추출물의 헬리코박터파이로리 생장억제 및 항염증 활성 (Anti-inflammatory activities of fermented Rhus verniciflua stem bark extract and its growth inhibitory effect on Helicobacter pylori)

  • 최은영;석기태;최한석;김명곤;권용수;김명조
    • 한국식품과학회지
    • /
    • 제48권5호
    • /
    • pp.502-507
    • /
    • 2016
  • 본 연구는 장수버섯(Fomitella fraxinea)을 이용하여 발효처리 한무독화 옻나무 추출물의 위장기능 개선능을 확인하고자 발효옻추출물을 이용하여 H. pylori 생장억제활성, 위암세포 생장억제활성과 항염증 활성을 평가하였다. H. pylori를 접종한 배지에 발효옻 추출물을 농도별로 첨가하였을 때 2.0 mg의 농도에서 4.0 mm의 생장억제환을 확인하였으며, 발효옻 추출물을 배지에 1.0-5.0 mg 농도로 혼합한 후 H. pylori을 접종한 경우에도 생장억제능이 확인되었다. 이를 바탕으로 세포 수준에서 H. pylori에 의해 유발된다고 알려진 위암과 위염 개선능을 평가하고자 세포독성을 나타내지 않은 0.1-1.0 mg/mL의 농도범위로 AGS 위암세포 생장억제활성 및 NO 생성 저해율을 확인하였다. 실험결과 0.25 mg/mL 이상의 농도에서 20% 이상의 위암세포 생장억제활성을 확인하였으며, LPS로 염증을 유도한 RAW 264.7 세포에서 추출물 0.25 mg/mL처리시 90%의 높은 NO 생성 저해율을 확인하였다. 염증유발인자인 iNOS와 COX-2의 발현 억제율은 0.50 mg/mL 농도에서 각각 50, 10%의 억제율을 보여 NO 생성저해율은 iNOS에 의한 영향인 것으로 사료된다. 상기 결과로 발효옻 추출물은 H. pylori 생장억제능 및 높은 NO 생성저해 활성이 확인됨으로서 간접적인 위암발생 억제제 및 항염증제로서의 이용가능성을 확인하였다. 따라서 발효옻 추출물을 이용한 위장개선 식의약 소재로서의 개발 가능성이 매우 높은 것으로 생각되며 이를 위해 추가적인 연구가 진행되어야 할 것으로 사료된다.

댕댕이나무 열매 추출물이 지방전구세포와 마우스 지방유래줄기세포의 분화 및 지방 생성 억제에 미치는 영향 (Effects of Lonicera caerulea extract on adipocyte differentiation and adipogenesis in 3T3-L1 cells and mouse adipose-derived stem cells (MADSCs))

  • 박미의;이창호;이해정
    • Journal of Nutrition and Health
    • /
    • 제52권1호
    • /
    • pp.17-25
    • /
    • 2019
  • 본 연구에서는 댕댕이나무 열매 추출물이 3T3-L1과 마우스 지방유래줄기세포의 지방 분화유도 및 지방생성에 미치는 영향을 살펴보았다. 3T3-L1에 댕댕이나무 열매 추출물을 처리하였을 때, 농도의존적으로 지방구의 생성을 줄였고 지방세포 분화에 있어서 중요한 전사인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1의 발현을 억제시켜 지방 합성이 감소됨을 확인하였다. 또한, 마우스 지방에서 분리한 줄기세포의 지방 분화과정에서도 댕댕이나무 열매 추출물이 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1의 단백질 발현을 감소시켜 지방 축적을 농도 의존적으로 억제하였다. 이상의 결과로 댕댕이나무 열매 추출물은 세포독성이 없는 농도에서 지방 세포의 분화를 억제 하는 것으로 확인되어 항비만 기능성 소재로서의 활용 가능성이 있을 것으로 사료된다.

MMP2 Gene-735 C/T and MMP9 gene -1562 C/T Polymorphisms in JAK2V617F Positive Myeloproliferative Disorders

  • Sag, Sebnem Ozemri;Gorukmez, Ozlem;Ture, Mehmet;Gorukmez, Orhan;Topak, Ali;Sahinturk, Serdar;Ocakoglu, Gokhan;Gulten, Tuna;Ali, Ridvan;Yakut, Tahsin
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권2호
    • /
    • pp.443-449
    • /
    • 2015
  • Background: Myeloproliferative disorders (MPDs) are clonal hematologic malignancies originating at the level of the pluripotent hematopoietic stem cell. Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of malignancy progression. Genetic variants in the MMP genes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. To our knowledge, this is the first investigation of associations between the -735 C/T and -1562 C/T polymorphisms in the MMP2 and MMP9 genes, respectively, and the risk of essential thrombocytosis (ET), and polycythemia vera (PV). Materials and Methods: The case-control study included JAK2V617F mutation positive 102 ET and PV patients and 111 controls. Polymorphisms were determined by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and electrophoresis. Results: No statistically significant differences were detected between patient (ET+PV) and control groups regarding genotype distribution for MMP2 gene-735 C/T and MMP9 gene -1562 C/T polymorphisms and C/T allele frequency (p>0.050). Statistically borderline significance was observed between PV and control groups regarding genotype distribution for the MMP9 gene -1562 C/T polymorphism (p=0.050, OR=2.26, 95%Cl=0.99-5.16). Conclusions: Consequently this study supported that CC genotype of MMP9 gene -1562 C/T polymorphism may be related with PV even if with borderline significance.

Clinical Manifestations and Risk Factors for Complications of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

  • Duangnapasatit, Boonlerd;Rattarittamrong, Ekarat;Rattanathammethee, Thanawat;Hantrakool, Sasinee;Chai-Adisaksopha, Chatree;Tantiworawit, Adisak;Norasetthada, Lalita
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권12호
    • /
    • pp.5013-5018
    • /
    • 2015
  • Background: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid lineages. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients. The major complications of Ph-negative MPNs are thrombosis, hemorrhage, and leukemic transformation. Objective: To study clinical manifestations including symptoms, signs, laboratory findings, and JAK2V617F mutations of Ph-negative MPN (PV, ET and PMF) as well as their complications. Materials and Methods: All Ph-negative MPN (PV, ET and PMF) patients who attended the Hematology Clinic at Maharaj Nakorn Chiang Mai Hospital from January, 1 2003 through December, 31 2013 were retrospectively reviewed for demographic data, clinical characteristics, complete blood count, JAK2V617F mutation analysis, treatment, and complications. Results: One hundred and fifty seven patients were included in the study. They were classified as PV, ET and PMF for 68, 83 and 6 with median ages of 60, 61, and 68 years, respectively. JAK2V617F mutations were detected in 88%, 69%, and 100% of PV, ET and PMF patients. PV had the highest incidence of thrombosis (PV 29%, ET 14%, and PMF 0%) that occurred in both arterial and venous sites whereas PMF had the highest incidence of bleeding (PMF 17%, ET 11%, and PV 7%). During follow up, there was one ET patient that transformed to acute leukemia and five cases that developed thrombosis (three ET and two PV patients). No secondary myelofibrosis and death cases were encountered. Conclusions: Ph-negative MPNs have various clinical manifestations. JAK2V617F mutations are present in the majority of PV, ET, and PMF patients. This study confirmed that thrombosis and bleeding are the most significant complications in patients with Ph-negative MPN.