• Title/Summary/Keyword: myelogenous

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Identification of STAT5a Inhibitors for Breast Cancer Treatment Through In silico Approach

  • Bavya Chandrasekhar;Dona Samuel Karen;Veena Jaganivasan
    • Journal of Integrative Natural Science
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    • v.17 no.1
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    • pp.13-20
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    • 2024
  • Female breast cancer is the fifth highest cause of mortality. Breast cancer is the most prevalent type of cancer in women globally, while it can also affect men. STAT5A plays a role in its development and progression. Given that activation of STAT5a is frequently linked to the growth and progression of tumors, STAT5a has been identified as a possible target for the therapy of several cancers. STAT5A, in particular, has proven to be overexpressed in various breast cancer cell lines and tumors, and it has been associated to the promotion of tumour cell proliferation and survival. STAT5A inhibition has been shown in vitro and in vivo to reduce the development of breast cancer cells. As a result, we have screened compounds from the FDA database that might serve as potential inhibitors of STAT5a through virtual screening, docking, DFT and MD simulation approaches. The drug Nilotinib has shown promising results inhibiting STAT5a. Further, in-vitro analysis will be carried forward to understand the anti-cancer activity.

Multidrug-resistance reversing activity of the local Citrus fruits in Jeju Island, Korea

  • Lee, Sook-Young;Kim, Sun-Min;Hwang, Eun-Ju
    • Proceedings of the Plant Resources Society of Korea Conference
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    • v.18 no.1
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    • pp.41-51
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    • 2005
  • We examined whether extracts from 14 local citrus spp. on Jeju Island (Korea) contained chemosensitizing activity that would increase the cytotoxic effect of vincristine(VCR) in drug-resistant cancer cells. We report that methanol extracts from fruits and flowers of some species had a chemosensitizing effect that reversed P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). Using drug-sensitive AML-2/WT and drug-resistant AML-2/D100 in the absence of VCR in human acute myelogenous leukemia cells we found that fruit or flower extracts alone generally had low cytotoxicity $(IC_{50}>200\;{\mu}g/ml)$. In studies examining the effect of extracts on 120 ng/ml VCR cytotoxicity in drug-resistant AML-2/D100 cells, we found that immature fruit extracts had greater chemosensitizing activity than either extracts from mature fruit or flower. Of the 14 species examined, the immature fruit extract from Inchangkyool (Citrus ichangiensis) showed the hishest chemosensitizing index(CI) valus. Immature fruit extracts of Hongkyool(C. tachibana), Byungkyool(C. platymamma), Cheongkyool(C. nippokoreana) and Jinkyool (C. sunki) also strongly potentiated VCR cytotoxicity in AML-2/D100 cells. The chemosensitizing effect of peel extracts was 2-10-fold that of whole fruit extracts from Hongkyool (C. tachibana), Byungkyool (C. platymamma) and Inchangkyool (C. inchangiensis). The CI values for flower extracts were higher than those for mature fruit extracts, but lower than those for immature fruit extracts. These results indicate that immature citrus fruits contain compounds that do not exert their activity solely through cytotoxicity. In particular, Incahngkyool (C. inchangiensis), Byungkyool(C.platymamma), Cheongkyool(C. nippokoreana) and Hongkyool (C. tahibana) may be useful sources of chemosensitizing compounds.

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Inhibition of Aminopeptidase N by Two Synthetic Tripeptides

  • Chung, Myung Chul;Hyo Kon Chun;Ho Jae Lee;Choong Hwan Lee;Su Il Kim;Yung Hee Kho
    • Journal of Microbiology and Biotechnology
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    • v.6 no.1
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    • pp.7-11
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    • 1996
  • MR-387Al (ARPA-Val-Pro) and A2 (AHPA-Val-Hyp) were prepared as aminopeptidase N inhibitors through the synthesis of peptide MR-387A and B analogues which contained 3-amino-2-hydroxy-4-phenyl butanoic acid (ARPA) as a zinc-chelating moiety. They are competitive inhibitors of aminopeptidase N with inhibition constants(Ki) of 4.1 $\times 10^{-7}\;and 1.1 \times 10^{-6}$ M, respectively. MR-387Al also strongly inhibited aminopeptidase B of human myelogenous leukemia K-562 cell with $IC_50$ of 0.35 $\mu$ M. Inhibitions of aminopeptidase N activity by ARPA-bearing inhibitors of various peptide chain lengths also have been studied. $IC_ 50$ values of AHPA-Val (bestatin), ARPA-Val-Pro (MR-387Al) and ARPA-Val-Pro-Leu (MR-387C) compared against porcine kidney aminopeptidase N were 20.1, 0.60 and 0.08 $\mu$ M, respectively. These results support that a multiple interaction between the $S_1\to S'_3$ sites of aminopeptidase N and the $P_1\to P'_3$ of the inhibitor plays a crucial role in stabilizing strongly the enzyme-inhibitor complex.

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Selective miRNA Expression Profile in Chronic Myeloid Leukemia K562 Cell-derived Exosomes

  • Feng, Dan-Qin;Huang, Bo;Li, Jing;Liu, Jing;Chen, Xi-Min;Xu, Yan-Mei;Chen, Xin;Zhang, Hai-Bin;Hu, Long-Hua;Wang, Xiao-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7501-7508
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    • 2013
  • Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1 kinase is a treatment of choice for control of CML. Objective: Recent studies have demonstrated that miRNAs within exosomes from cancer cells play crucial roles in initiation and progression. This study was performed to assess miRNAs within exosomes of K562 cells. Methods: miRNA microarray analysis of K562 cells and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also carried out. GO terms and signaling pathways were categorized into 66 classes (including homophilic cell adhesion, negative regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such as Wnt). Results: In exosomes, 49 miRNAs were up regulated as compared to K562 cells, and two of them were further confirmed by quantitative real-time PCR. There are differentially expressed miRNAs between K562 cell derived-exosomes and K562 cells. Conclusion: Selectively expressed miRNAs in exosomes may promote the development of CML via effects on interactions (e.g. adhesion) of CML cells with their microenvironment.

Physiological and Pharmacological Activites of Nutraceutical Tea by Leaves and Flowers of Domestic Camellia(Camellia japonica)

  • Lee, Sook-Young;Cha, Young-Ju;Lee, Jang-Won;Hwang, Eun-Ju;Kwon, Su-Jung;Cho, Su-In
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2003.10b
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    • pp.48-49
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    • 2003
  • This project was conducted to development several camellia tea mixed herb teas having any physiological effects. Leaves of tea tree contain many compounds, such as polysaccharides, volatile oils, vitamins, minerals, purines, alkaloids(eg. caffeine) and polyphenols(catechins and flavonoids). Although all three tea types(green, oolonr and black) have antibacterial and free radical capturing(antioxidizing) activities, the efficacy decreases substantially the darker the variety of tea is. This is due to lower contents of anti-oxidizing polyphenols remaining in the leaves. Unlike tea tree(Camellia sinensis), the biochemical features and effects of camellia(Camellia japonica) are not well known. Fresh mature leaf of sasanqua camellia(C. sasanqua), roasted young leaf tea(C. japonica) and fresh mature leaf and bark of camellia had high antibacterial activity against P. vulgaris and B. subtilis. In antifungal activity bioassay, young leaf roasted teas of camellia and sasanqua camellia had high activity against C. albicans and T. beigelil. Plant extracts from Camelia japonica had higher inhibitory activity against fungi than against bacteria. In cytotoxic effect against human acute myelogenous leukaemia cell extracts including fresh leaf(200$\mu\textrm{g}$/m1), bark(230$\mu\textrm{g}$/ml) and flower tea (320$\mu\textrm{g}$/m1)inhibited growth of AML cells.(중략)

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OSTEOMYELITIS OCCURRING LEUKEMIA PATIENT: A CASE REPORT (백혈병 환자에서 발생한 골수염 : 증례보고)

  • Kim, Bong-Gyun;Kim, Su-Gwan;Yeo, Hwan-Ho;Kim, Sang-Ryol
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.3
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    • pp.310-312
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    • 2000
  • Leukemia is a malignancy caused by precursor cells of white blood cell. It is a malignant tumor of hematopoietic organs, characterized by the disorder of hematopoietic function due to the proliferation of immature bone marrow cells or lymphatic cells and by abnormal tissue infiltration of leukemic cells. The major signs of leukemia are caused by the failure of bone marrow function. As the number of red blood cells decreases, anemia is to appear. The number of white blood cells in leukemia is usually increased but immature white blood cells circulating the body has little defense ability, thus become susceptible to infection. 27 year-old female patient who was treated chemotherapy and bone marrow transplantation after diagnosed as chronic myelogenous leukemia(CML) was diagnosed as osteomyelitis in mandible after clinical and dental radiographic film examination. Because of the result of examination, the involved tooth of the patient was extracted accompanied by sequestrectomy and saucerization under general anesthesia. After the patient had long term medication of antibiotics, the lesion was healed. Therefore. author, et al. report this case with literature review.

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The Effect of Mesenchymal Stem Cells on the Activation of Dendritic Cells in the Cell Culture Insert System (세포배양삽입체계(Cell Culture Insert System)에서 중간엽 줄기세포(Mesenchymal Stem Cell)가 수지상세포(Dendritic Cell)의 활성화에 미치는 영향)

  • Kim, Kee Won;Park, Suk Young;Lee, Kyung Bock;Kim, Hyun-su
    • IMMUNE NETWORK
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    • v.4 no.2
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    • pp.88-93
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    • 2004
  • Background: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigenpresenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. Methods: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. Results: MSC inhibit the CD83 and HLA-class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-$\gamma$ production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. Conclusion: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.

Successful Rechallenge with Imatinib in a Patient with Chronic Myeloid Leukemia Who Previously Experienced Imatinib Mesylate Induced Pneumonitis

  • Go, Seong Woo;Kim, Boo Kyeong;Lee, Sung Hak;Kim, Tae-Jung;Huh, Joo Yeon;Lee, Jong Min;Hah, Jick Hwan;Kim, Dong Whi;Cho, Min Jung;Kim, Tae Wan;Kang, Ji Young
    • Tuberculosis and Respiratory Diseases
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    • v.75 no.6
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    • pp.256-259
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    • 2013
  • Imatinib mesylate is a targeted therapy that acts by inhibiting tyrosine kinase of the bcr-abl fusion oncoprotein, which is specific to chronic myeloid leukemia (CML), and the c-transmembrane receptor, which is specific to gastrointestinal stromal tumors. Interstitial pneumonitis is a rare adverse event of imatinib therapy. It is clinically difficult to distinguish from infectious pneumonia, which can frequently occur due to the underlying disease. The standard treatment for imatinib-induced pneumonitis is to discontinue the medication and optionally administer corticosteroids. However, there are a few cases of successful retrial with imatinib. We describe a case of successful rechallenge of imatinib in a patient with imatinib-induced interstitial pneumonitis and CML without a recurrence of the underlying disease after 3 months of follow-up.

Oxidative Stress-Induced Apoptosis in Chronic Myelogenous Leukemia K562 Cells by an Active Compound from the Dithio-Carbamate Family

  • Khoshtabiat, Laya;Mahdavi, Majid;Dehghan, Gholamreza;Rashidi, Mohammad Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4267-4273
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    • 2016
  • Previous studies suggested that dithio-carbamates are potent apoptosis and anti-apoptosis inducing agents in various cancer cells. Here, the anti-proliferative and apoptosis inducing effects of a new derivative (2-NDC) from the dithio-carbamate family was examined in human leukemia K562 cells. We use thiazolyl blue tetrazolium bromide (MTT) to measure viability and cell growth inhibition. The 2-NDC showed effects on viability in a dose and time-dependent manner, inhibiting proliferation at concentrations of $10-30{\mu}M$ after 24-48 hours of treatment and increasing values after 72 hours at $40-120{\mu}M$. The cytotoxic effect of the compound was calculated with an $IC_{50}$ of $30{\mu}M$ after 24-hour. Apoptosis induction was confirmed by acridine orange-ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, flow cytometric assessment and also caspase-3 activation assay. Furthermore, enzymes level such as superoxide dismutase (SOD) and catalase (CAT) involved in oxidative stress were evaluated. The results of this study demonstrated insignificant increase of intracellular ROS levels for 24 hours and reduction after 48-72 hours. In addition to reduction of intracellular thiol, caspase-3 like activity was also decreased in a time-dependent manner in cells treated with 2-NDC. Thus 2-NDC can be considered as a good candidate for further pharmaceutical evaluations.

A Study on the Effect of Oral Cryotherapy on Nausea Vomiting and Oral Intake by Anti Cancer Chemotherapy in Pediatric Cancer Patient (구강냉요법이 암환아의 오심구토와 구강섭취량에 미치는 효과)

  • Jeon Hye Jeong;Kim Young Hae
    • Child Health Nursing Research
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    • v.7 no.1
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    • pp.108-117
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    • 2001
  • This research objected to the diagnosed patients as acute lymphoblastic leukemia, acute myelogenous leukemia, neuroblastoma, non-Hodgkins lymphoma, Hodgkin's disease, kidney tumor, myelodysplastic syndrom and juvenile chronic leukemia after admission in the 'P' hospital in Pusan from Aug. 1. 1999 to Jan. 31. 2000. The results of this study are summarized as follows. 1. On the specific character between the experimental(exp.) group and the control (con.) group : there were 7 of 4-7 years old patients(the most) in the experimental group(53.8%), 5 of 12 years old or older patients in the control group (38.5%). Patients who experienced operation were 7 in the exp. group(53.8%) and 6 in con. group(46.2%). The largest number of the patients' diagnosis was acute lymphoblastic leukemia by 5 in the exp. group(38.5%) and 4 in the con. group (30.8%). The hardest nausea came on the second day by 5 in the exp. group(38.5%), 9 in the con. group(69.2%). 2. P-score of the nausea vomiting on the number of daily anticancer drug administration : first day, the exp. group got 9.6 and the con. group 17.6(P = 0.03). 2nd day, 10.9 and 19.4(P = 0.00), 3rd day, 10.6 and 18.3(P = 0.00), 4th day 10.0 and 18.0, 5th day 10.9 and 16.8(P = 0.05). The score showed statistically significant difference(P < .05). 3. Oral intake didn't show statistically significant difference between two groups. However the average of Oral intake of the exp. group was continually higher than the con. group except to the first day after administration. In conclusion, nursing intervention and nutrition care are much more needed on the 2-3th day after administration to reduce nausea vomiting, and for remission of nausea and enlarging oral intake it is utilizable to apply the easy, economic Oral Cryotherapy to the young patients who undergo chemotherapy.

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