• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3715-3721
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• 2015

Leukemia is a clonal disorder with blocked normal differentiation and cell death of hematopoietic progenitor cells. Traditional modalities with most used radiation and chemotherapy are nonspecific and toxic which cause adverse effects on normal cells. Differentiation inducing therapy forcing malignant cells to undergo terminal differentiation has been proven to be a promising strategy. However, there is still scarce of potent differentiation inducing agents. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), has potential differentiation inducing activity in human chronic erythro-megakaryoblastic leukemia K562 cells. MTT assays and flow cytometric analysis demonstrated that ASP inhibited K562 cell proliferation and arrested the cell cycle at the G0/G1 phase. ASP also triggered K562 cells to undergo erythroid differentiaton as revealed by morphological changes, intensive benzidine staining and hemoglobin colorimetric reaction, as well as increased expression of glycophorin A (GPA) protein. ASP induced redistribution of STAT5 protein from the cytoplasm to the nucleus. Western blotting analysis further identified that ASP markedly sensitized K562 cells to exogenous erythropoietin (EPO) by activating EPO-induced JAK2/STAT5 tyrosine phosphorylation, thus augmenting the EPO-mediated JAK2/STAT5 signaling pathway. On the basis of these findings, we propose that ASP might be developed as a potential candidate for chronic myelogenous leukemia inducing differentiation treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6549-6556
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• 2013

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression and relapse, and thus represent a critical target for therapeutic intervention. Hence, it is extremely urgent to explore new therapeutic strategies directly targeting LSCs for acute myelogenous leukemia (AML) therapy. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), effectively inhibited human AML $CD34^+CD38^-$ cell proliferation in vitro culture in a dose-dependent manner while sparing normal hematopoietic stem and progenitor cells at physiologically achievable concentrations. Furthermore, ASP exerted cytotoxic effects on AML K562 cells, especially LSC-enriched $CD34^+CD38^-$ cells. Colony formation assays further showed that ASP significantly suppressed the formation of colonies derived from AML $CD34^+CD38^-$ cells but not those from normal $CD34^+CD38^-$ cells. Examination of the underlying mechanisms revealed that ASP induced $CD34^+CD38^-$ cell senescence, which was strongly associated with a series of characteristic events, including up-regulation of p53, p16, p21, and Rb genes and changes of related cell cycle regulation proteins P16, P21, cyclin E and CDK4, telomere end attrition as well as repression of telomerase activity. On the basis of these findings, we propose that ASP represents a potentially important agent for leukemia stem cell-targeted therapy.

• Investigative Magnetic Resonance Imaging
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• v.14 no.1
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• pp.74-77
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• 2010

Granulocytic sarcoma is a manifestation of myelogenous leukemia, which means a solid mass consisting of primitive precursors of the granulocytic series of white blood cells. We present CT and MR imaging findings of bilateral sino-orbital granulocytic sarcoma in a 22-month-old boy. The mass involved bilateral orbital fossa which resulted in bilateral proptosis. Moreover, the mass extended to the almost skull base including paranasal sinuses, maxilla, temporal bone, zygomatic bone, sphenoid bone, ethmoid, and palatine bone. The adjacent dura was continuously thickened and the lower half of cavernous sinus was also involved. The patient was diagnosed as AML (M5) with t(8,21) translocation through a chromosome study from the bone marrow.

• Natural Product Sciences
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• v.8 no.3
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• pp.100-102
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• 2002

Three lignans were isolated from a methanol extract of Lindera erytherocarpa Makino (Lauraceae) are evaluated in vitro cytotoxicity using three cancer cell line assay. The compounds were identified as methyllinderone (1), linderone (2), and kanakugiol (3) by spectroscopic methods. Amongst the compounds, methyllinderone (1) showed significant cytotoxicity against mouse melanoma (B16-FlO), human acetabulum fibrosarcoma (HT1080), and choronic myelogenous leukemia (K562) cancer cell lines with $ED_{50}$ values of 2.2, 2.5, 8.3 ${\mu}g/ml$, respectively.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.203-209
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• 2004

Molecular docking using Lamarckian genetic algorithm of AutoDock 3.0 (AD3) was employed to understand in retrospect the selectivity of phenylaminopyrimidine (PAP) derivatives against the kinase domain c-Abl, implicated in chronic myelogenous leukemia (CML). The energetics of protein-ligand complex was scored using AD3 to identify active drug conformations while Ligplot and ligand protein contact (LPC) programs were used to probe schematic molecular recognition of the bound inhibitor to the protein. Results signify correlation between model and crystal structures of STI-571 compound or Imatinib (IM), a PAP derivative and now clinically proven for its efficacy in CML. A prospect active form Abl inhibitor scaffold from matlystatin class of compounds will be published elsewhere.

• Journal of Ginseng Research
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• v.22 no.3
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• pp.188-192
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• 1998

We established the model of clonogenic assay with human tumor cell line such as Calu-3 (lung carcinoma), HEC- lB (endometrial adenocarcinoma) , HEp-2 (larnyx carcinoma), Hs-5787 (breast carcinoma), K-562 (chronic myelogenous leukemia), SF-188 (brain carcinoma), SNU-1 (stomach carcinoma) and WiDr (colon carcinoma) . We investigated growth inhibition of solvent (EtOH, MeOH) and water (100$^{\circ}C$, 121$^{\circ}C$) extracts from Korean red ginseng by clonogenic assay. The results of clonogenic assay showed that EtOH extract had growth inhibition against Calu-3, SF-188 and SNU-1, MeOH extract had growth inhibition against Calu-3, Hs-5787, K-562, and WiDr, but water extract at 100$^{\circ}C$ and water extract at 121$^{\circ}C$ had not growth inhibition against used cell lines.

• The Korean Journal of Nuclear Medicine
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• v.7 no.1
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• pp.39-43
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• 1973

The bone marrow scans with colloidal $^{198}Au$ were performed on 33 cases with hematologically normal patients and patients with various blood dyscrasia. Bone marrow aspirations were done at iliac crest in all cases but one. A correlation between the scan findings and an erythroid cellularity was evaluated. The following results were obtained. 1) Out of 33 cases, 23 (about 70%) showed a correlation between $^{198}Au$ marrow uptakes on the scans and the erythroid cellularity. 2) The diseases in which no correlation existed between $^{198}Au$ uptake and erythroid cellularity were aplastic anemia, acute leukemia and chronic myelogenous leukemia.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.478-484
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• 2004

The novel 1-(1-benzoylindoline-5-sulfonyl)-4-phenyl-4,5-dihydroimidazolones 2 shows highly potent and broad cytotoxicities. Their cytotoxicities against human lung carcinoma A549, human chronic myelogenous leukemia K562, and human ovarian adenocarcinoma SK-OV-3 are compatible with doxorubicin. Compound 2p (1-[(4-aminobenzoyl)indoline-5-sulfonyl])-4-phenyl-4,5-dihydroimidazolone) exhibits a cytotoxicity that is far more potent than doxorubicin and also exhibits highly effective antitumour activities against murine (3LL, Colon 26) and human xenograft (NCI-H23, SW620) tumor models.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.605-610
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• 2003

According to the Leukemia and Lymphoma Society, leukemia is a malignant disease (cancer) that originates in a cell in the marrow. It is characterized by the uncontrolled growth of developing marrow cells. There are two major classifications of leukemia: myelogenous or lymphocytic, which can each be acute or chronic. The terms myelogenous or lymphocytic denote the cell type involved. Thus, four major types of leukemia are: acute or chronic myelogenous leukemia and acute or chronic lymphocytic leukemia. Leukemia, lymphoma and myeloma are considered to be related cancers because they involve the uncontrolled growth of cells with similar functions and origins. The diseases result from an acquired (not inherited) genetic injury to the DNA of a single cell, which becomes abnormal (malignant) and multiplies continuously. In the United States, about 2,000 children and 27,000 adults are diagnosed each year with leukemia. Treatment for cancer may include one or more of the following: chemotherapy, radiation therapy, biological therapy, surgery and bone marrow transplantation. The most effective treatment for leukemia is chemotherapy, which may involve one or a combination of anticancer drugs that destroy cancer cells. Specific types of leukemia are sometimes treated with radiation therapy or biological therapy. Common side effects of most chemotherapy drugs include hair loss, nausea and vomiting, decreased blood counts and infections. Each type of leukemia is sensitive to different combinations of chemotherapy. Medications and length of treatment vary from person to person. Treatment time is usually from one to two years. During this time, your care is managed on an outpatient basis at M. D. Anderson Cancer Center or through your local doctor. Once your protocol is determined, you will receive more specific information about the drug(s) that Will be used to treat your leukemia. There are many factors that will determine the course of treatment, including age, general health, the specific type of leukemia, and also whether there has been previous treatment. there is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. the vast history of experience of traditional oriental medicine with medicinal plants may facilitate the identification of novel anti leukemic compounds. In the present investigation, we studied 31 kinds of anti leukemic medicinal plants, which its pharmacological action was already reported through many experimental articles and oriental medical book: 『pharmacological action and application of anticancer traditional chinese medicine』 In summary: Used leukemia cellline are HL60, HL-60, Jurkat, Molt-4 of human, and P388, L-1210, L615, L-210, EL-4 of mouse. 31 kinds of anti leukemic medicinal plants are Panax ginseng C.A Mey; Polygonum cuspidatum Sieb. et Zucc; Daphne genkwa Sieb. et Zucc; Aloe ferox Mill; Phorboc diester; Tripterygium wilfordii Hook .f.; Lycoris radiata (L Her)Herb; Atractylodes macrocephala Koidz; Lilium brownii F.E. Brown Var; Paeonia suffruticosa Andr.; Angelica sinensis (Oliv.) Diels; Asparagus cochinensis (Lour. )Merr; Isatis tinctoria L.; Leonurus heterophyllus Sweet; Phytolacca acinosa Roxb.; Trichosanthes kirilowii Maxim; Dioscorea opposita Thumb; Schisandra chinensis (Rurcz. )Baill.; Auium Sativum L; Isatis tinctoria, L; Ligustisum Chvanxiong Hort; Glycyrrhiza uralensis Fisch; Euphorbia Kansui Liou; Polygala tenuifolia Willd; Evodia rutaecarpa (Juss.) Benth; Chelidonium majus L; Rumax madaeo Mak; Sophora Subprostmousea Chunet T.ehen; Strychnos mux-vomical; Acanthopanax senticosus (Rupr.et Maxim.)Harms; Rubia cordifolia L. Anti leukemic compounds, which were isolated from medicinal plants are ginsenoside Ro, ginsenoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, Aspargus polysaccharide A.B.C.D, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, Ge 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A 13 oxyingenol Kansuiphorin B. These investigation suggest that it may be very useful for developing more effective anti leukemic new dregs from medicinal plants.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.209-217
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• 1994

Between July 1987 and December 1992, we treated 22 patients with chronic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation(TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6fractions/3days (6 patients) or 1320 cGy/8 fractions/4days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were $58.5\%$ and $41.2\%$, respectively, and the relapse rate was $36\%$ among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase ($76\%\;vs\;33\%$, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation ($50\%\;vs\;0\%$, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patients remains in the chronic phase.