1.Combined anti-tumor therapeutic effect of targeted gene, hyperthermia, radionuclide brachytherapy in breast carcinoma
Dao-zhen, CHEN ; Qiu-sha, TANG ; Jing-ying, XIANG ; Fei, XU ; Li, ZHANG ; Jun-feng, WANG
Chinese Journal of Nuclear Medicine 2011;31(2):82-86
Objective To investigate the antitumor therapeutic effect of combined therapy of magnetic induction heating by nano-magnetic particles, herpes simplex virus thymidine kinase gene(HSV-tk suicide gene) and internal radiation in mice bearing MCF-7 breast carcinoma. Methods The transfection reagents, plasmids heat shock protein-HSV-tk (pHSP-HSV-tk), ferroso-ferric oxide nano-magnetic fluid flow and 188Re-ganciclovir-bovine serum albumin-nanopaticles (GCV-BSA-NP) were prepared. The heating experiments in vivo were carried out using ferroso-ferric oxide nano-magnetic fluid flow. Sixty mice tumor models bearing MCF-7 breast carcinoma were established and randomly divided into six groups. Group A was the control group, B was gene transfection therapy group, C was hyperthermia group, D was gene transfection therapy combined with radionuclide brachytherapy group, E was gene therapy combined with hyperthermia group, and F was gene therapy, hyperthermia combined with radionuclide brachytherapy group. The tumor growth, tumor mass and histopathological changes were evaluated. The expression of HSV-tk in the groups of B, D, E and F was detected by RT-PCR. Poisson distribution and one-way analysis of variance (ANOVA) were used for statistical analysis by SPSS 10.0 software. Results In the animal heating experiments, the temperature of tumor increased up to 39.6 ℃, 43.2 ℃, and 48.1 ℃ quickly with different injected doses (2, 4 and 6 mg respectively) of nano-magnetic particles and maintained for 40 min. The temperature of tumor tissue reduced to 36.8 ℃, 37.5 ℃ and 37.8 ℃ in 10 min when alternating magnetic field (AMF) stopped. The tumor mass in Groups C ((452.50 ±30.29) mg), D ((240.98 ±35.32)mg), E((231.87 ±27.41) mg) and F ((141.55 ±23.78) mg) were much lower than that in Group A ((719.12±22.65) mg) (F=800.07, P<0. 01), with the most significant treatment effect in Group F.The tumor mass in Group B((684.05 ±24.02) mg) was higher than that in Group D (t =32. 805, P <0. 05). Semi-quantitative RT-PCR analysis showed that the expression of HSV-tk in Groups B and D (0.33 ±0. 13 and 0. 46 ±0.12) was significantly different from that in Groups E and F (0.66 ±0.13 and 0.74 ±0. 11)(F = 21. 573, P < 0.05). Conclusion Combined use of hyperthermia, gene therapy and radionuclide brachytherapy could effectively depress the growth of MCF-7 breast carcinoma, thus possessing treatment potential for this tumor.
2.Protective effect of ATP on skeletal muscle satellite cells damaged by H2O 2.
Fei, FEI ; Dao-Li, ZHU ; Li-Jun, TAO ; Bao-Zhu, HUANG ; Hong-Hong, ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2015;35(1):76-81
This study investigated the protective effect of ATP on skeletal muscle satellite cells damaged by H2O2 in neonatal rats and the possible mechanism. The skeletal muscle satellite cells were randomly divided into four groups: normal group, model group (cells treated with 0.1 mmol/L H2O2 for 50 s), protection group (cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h, and then with 0.1 mmol/L H2O2 for 50 s), proliferation group (cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h). MTT assay, FITC+PI+DAPI fluorescent staining, Giemsa staining and immunofluorescence were performed to examine cell viability and apoptosis, and apoptosis-related proteins. The results showed that the survival rate of skeletal muscle satellite cells was decreased and the apoptosis rate was increased after H2O2 treatment (P<0.01). Different doses of ATP had different effects on skeletal muscle satellite cells damaged by H2O2: the survival rate of muscle satellite cells treated with ATP at 4, 2, or 1 mmol/L was increased. The protective effect was most profound on cells treated with 2 mmol/L ATP. Immunofluorescence showed that ATP could increase the number of Bcl-2-positive cells (P<0.01) and decrease the number of the Bax-positive cells (P<0.01). It was concluded that ATP could protect skeletal muscle satellite cells against H2O2 damage in neonatal rats, which may be attributed to the up-regulation of the expression of Bcl-2 and down-regulation of Bax, resulting in the suppression of apoptosis.
3.A new lactone derivative from plant endophytic fungus Periconia sp. F-31.
De-wu ZHANG ; Ji-mei LIU ; Ri-dao CHEN ; Min ZHANG ; Li-yan YU ; Jun WU ; Jun-gui DAI
China Journal of Chinese Materia Medica 2015;40(12):2349-2351
To investigate the secondary metabolites of endophytic fungi Pericinia sp. F-31. Column chromatography on silica gel, Sephadex LH-20 and semi-preparative HPLC were used to separate and purify the compounds. Two compounds were isolated from the fermentation broth of Periconia sp. Their structures were identified as 5-(1-hydroxyhexyl) -6-methyl-2H-pyran-2-one (1) and 2-(3-hydroxy-4-methylphenyl) -propanoic acid (2). Compound 1 was a new lactone compound, compound 2 was new natural product, and the NMR data of compound 2 was reported for the first time.
Annona
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microbiology
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Ascomycota
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chemistry
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genetics
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isolation & purification
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metabolism
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Drugs, Chinese Herbal
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chemistry
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isolation & purification
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metabolism
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Endophytes
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chemistry
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genetics
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isolation & purification
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metabolism
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Lactones
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chemistry
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isolation & purification
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metabolism
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Mass Spectrometry
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Molecular Structure
4.Preliminary experimental research on glucocorticoid for treatment of nitrogen dioxide induced acute pulmonary edema in rats.
Xun-miao ZHANG ; Dao-yuan SUN ; Liang TANG ; Yan-jun YUAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2010;28(11):822-826
OBJECTIVETo investigate the therapeutic effect of glucocorticoids on the acute pulmonary edema in rats induced by nitrogen dioxide (NO₂).
METHODSThirty SD female rats were randomly equally divided into 5 groups: normal control group, NO₂ exposed group, high-, middle- and low-dose of glucocorticoids treated group (6 rats per group). 6 rats in the normal control group were exposed to room air for 30 min, and the other rats to NO₂. 18 rats in the glucocorticoids group were treated with different doses of dexamethasone (6.0, 3.0, 1.0 mg/kg), while the rats in the NO₂ poisoning group were treated with normal saline (2.5 mg/kg). The lung wet/dry (W/D) weight ratio was calculated, and plasma atrial natriuretic peptide (ANP) levels, superoxide dismutase (SOD) activity from whole blood, plasma interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α) and Interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay (ELISA).
RESULTSThe lung W/D ratios were increased significantly in glucocorticoids treated group and NO₂-exposed group compared with normal control group (P < 0.05), while they were significantly reduced in glucocorticoids treated group as compared with NO₂-exposed group (P < 0.05). SOD activity in whole blood in glucocorticoids treated group and NO₂-exposed group was significantly lower than that of normal control group (P < 0.05), while it was no significant difference between that of glucocorticoids treated group and NO₂-exposed group (P > 0.05). Plasma ANP was significantly increased in NO₂-exposed group compared with normal control group (P < 0.05), while it was significantly decreased in glucocorticoids treated group compared with NO₂-exposed group (P > 0.05). Plasma TNF-α of high-, middle- and low-dose of glucocorticoids treated group [(27.04 ± 8.19), (40.10 ± 9.09), (39.76 ± 9.60) pg/ml] was decreased significantly as compared with NO₂-exposed group (68.55 ± 27.84 pg/ml) (P < 0.05). Plasma IL-6 in high- and middle-dose of glucocorticoids treated group [(15.97 ± 6.18), (19.69 ± 5.52) pg/ml] was significantly decreased as compared to NO₂-exposed group [(29.29 ± 9.31) pg/ml] (P < 0.05). Plasma IL-10 in high-, middle- and low-dose of glucocorticoids treated group [(23.24 ± 5.14), (27.78 ± 8.17), (33.29 ± 10.42) pg/ml] was significantly reduced compared with NO₂-exposed group [(44.38 ± 9.19) pg/ml] (P < 0.05). Plasma IFN-γ in high- and middle-dose of glucocorticoids treated group [(7.21 ± 4.55), (19.23 ± 4.35) pg/ml] was reduced compared with NO₂-exposed group [(30.83 ± 6.82) pg/ml] (P < 0.05).
CONCLUSIONHigh-, middle-, low-dose glucocorticoids all can improve the permeability of alveolar wall and capillary, and have nonspecific anti-inflammatory effects. The therapeutic effects on pulmonary edema are significant. High and middle dose of glucocorticoids treated group are more useful for decreased inflammatory factors.
Animals ; Disease Models, Animal ; Female ; Glucocorticoids ; therapeutic use ; Nitrogen Dioxide ; toxicity ; Pulmonary Edema ; chemically induced ; drug therapy ; Rats ; Rats, Sprague-Dawley
5.Portal size of prophylactic postoperative radiotherapy for esophageal carcinoma
Xue-Ying QIAO ; Dao-An ZHOU ; Qiang LIN ; Xian-Shu GAO ; Zhi-Guo ZHOU ; Wei WANG ; Jun ZHANG ;
Chinese Journal of Radiation Oncology 2005;0(05):-
Objective To compare and analyze the effect of prophylactic postoperative radiotherapy for esophageal carcinoma.Methods 102 such patients were treated with prophylactic radiotherapy after radical resection,to a total dose of 50-60 Gy.The extensive portal included supraclavicular region on both sides,entire mediastinum,the site of anastomosis and left gastric lymph node region in 43 patients.The re- gional portal range was different according to the different location of primary lesion in 59 patients.Results The 1-,3- and 5-year survival rate was 76%,51% and 43% respectively,with a median survival of 30 months.The 1-,3- and 5-year survival rate was 77%,52% and 41% in the extensive portal and 76%, 49% and 45% in the regional portal,respectively(P=0.884).According to multivariate analysis,N stage, number of metastatic lymph nodes and tumor length were independent prognostic factors.Conclusions Regional portal does not lower the survival rate when prophylactic postoperative radiotherapy is used in e- sophageal carcinoma.
7.Suprapubis-assisted umbilical laparoendoscopic mini-dual-site surgery for varicocele: a report of 80 cases.
Dao-Sheng LUO ; Jun-Hua MO ; Mu LI ; Zeng-Qiang ZHANG ; Jian-Jun LU ; Zhen-Feng LIANG ; Qi-Wu MI ; Xiang-Zhou SUN ; Chun-Hua DENG
National Journal of Andrology 2014;20(5):430-434
OBJECTIVETo study the safety, effectiveness and feasibility of suprapubis-assisted umbilical laparoendoscopic mini-dual-site surgery (SAU-LEMDS) in the treatment of varicocele.
METHODSThis study included 80 varicocele patients aged 24 - 44 (mean 28.5 +/- 2.6) years, 25 cases of grade I, 45 cases of grade II and 10 cases of grade III, 58 cases in the left side, 6 in the right and 16 in both sides, and all with asthenospermia. The patients were treated by SAU-LEMDS under subarachnoid anesthesia combined with general anesthesia in a supine position with a head-down-feet-up slope of 15 degrees. Two 5 mm trocars were inserted bilaterally at the umbilical edge, one with a 5 mm 30 degrees laparoscope placed in it, and another into the abdominal cavity below the pubic hairline with a 5 mm laparoendoscopic clipper placed in it. The operation procedure was similar to that of standard laparoscopic ligation of spermatic veins, with reservation of the spermatic artery and double-ligation of spermatic veins. And the procedure was repeated for the contralateral lesion in the bilateral cases. Postoperative follow-up was conducted for the incidences of orchiatrophy and testicular hydrocele and changes of seminal parameters.
RESULTSAll the operations were successful, with the mean operation time of (10 +/- 5.0) min (range 8 to 25 min) for the unilateral cases and (18 +/- 6.5) min (range 15 to 30 min) for the bilateral cases, the mean blood loss of (1.5 +/- 0.5) ml (range 1 to 2 ml), and the mean postoperative hospital stay of (2 +/- 0.5) d (range 1.5 to 3 d). The patients were followed up for 6 -24 (12 +/- 2.5) months, which showed significant improvement in sperm motility as compared with the baseline ([28.53 +/- 5.21] vs [19.62 +/- 3.56]%, P < 0.05), with 28 cases (35.0%) restored to normal. Recurrence was found in 4 cases (5.0%). Testicular hydrocele occurred in 7 cases (8.75%), but orchiatrophy in none. The scars in the umbilicus and suprapubis were invisible because of the wrinkles and pubic hair.
CONCLUSIONSAU-LEMDS is safe, effective and feasible for the treatment of varicocele. It is superior to umbilical laparoendoscopic single-site surgery (U-LESS) for its less invasiveness, simpler operation, and better cosmetic appearance.
Adult ; Asthenozoospermia ; Humans ; Laparoscopy ; adverse effects ; methods ; Length of Stay ; Ligation ; methods ; Male ; Operative Time ; Postoperative Period ; Recurrence ; Spermatic Cord ; blood supply ; Testicular Hydrocele ; etiology ; Treatment Outcome ; Umbilicus ; Varicocele ; surgery ; Veins
8.Flavonoids from whole plants of Lagopsis supina.
Jing ZHANG ; Dao-ran PANG ; Zheng HUANG ; Hui-xia HUO ; Yue-ting LI ; Jiao ZHENG ; Qian ZHANG ; Yun-fang ZHAO ; Peng-fei TU ; Jun LI
China Journal of Chinese Materia Medica 2015;40(16):3224-3228
The flavonoids were investigated from the whole plants of Lagopsis supina. The compounds were isolated and purified by various column chromatography, and their structures were identified by physiochemical properties and spectroscopic data. Two flavones were isolated from the CH2Cl2 layer of Lagopsis supina extract and identified as genkwanin (1) and 5-hydroxy-7,4'-dimethoxyflavone (2), respectively. Ten flavonoid glycosides were isolated from the water layer of Lagopsis supina and elucidated as kaempferol-3-O-6" (3-hydroxy-3-methylglutaryl) -β-D-glucoside (3), quercetin-3-O-6"-(3-hydroxy-3-methylglutaryl) -β-D-glucoside (4), quercetin-3-O-β-D-glucoside(5), kaempferol-3-Of3-D-glucoside ( 6), isorhamnetin-3-O-/-D-glycopyranoside (7), apigenin-7-O-6-D-glucoside (8), luteolin-7-O-β-D-glucoside (9), chrysoeriol-7-O-β-D-glucoside (10), rutin (11 ), and kaempferol-3-β-(6"-p-coumaroyl) -β-D-glucoside (tiliroside, 12). Compounds 3 and 4 were firstly isolated from Lamiaceae family, and compounds 1-12 were isolated from the plants of Lagopsis genus for the first time.
Drugs, Chinese Herbal
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chemistry
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isolation & purification
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Flavonoids
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chemistry
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isolation & purification
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Lamiaceae
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chemistry
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Molecular Structure
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Spectrometry, Mass, Electrospray Ionization
9.Biological mechanisms of human-derived leukemia stem cells senescence regulated by Angelica sinensis polysaccharide.
Dao-Yong JIA ; Jun LIU ; Cheng-Peng LI ; Jing LI ; Meng-Si ZHANG ; Yan-Yan ZHANG ; Jing PENG-WEI ; Chun-Yan XU ; Ya-Ping WANG
China Journal of Chinese Materia Medica 2015;40(1):112-117
OBJECTIVETo explore the biological mechanisms underlying Angelica sindsis polysaccharide (ASP) -induced aging of human-derived leukemia stem cells (LSCs) in vitro.
METHODAcute myelogenous leukemia stem cells were isolated by magnetic activated cell sorting (MACS). The ability of LSC proliferation treated by various concentration of ASP(20-80 mg · L(-1)) in vitro for 48 hours were tested using cell counting Kit-8 ( CCK8) , colony forming were evaluated by methylcellulose CFU assay. The ultra structure changes of AML CD34+ CD38- cells were analyzed by transmission electron microscopy. The aging cells were detected with senescence-β-galactosidase Kit staining. Expression of aging-related p53, p21, p16, Rb mRNA and P16, Rb, CDK4 and Cyclin E protein were detected by quantitative reverse transcription polymerase chain reaction( qRT-PCR) and Western blotting, respectively.
RESULTThe purity of the CD34 + CD38 - cells is (91.15 ± 2.41)% after sorted and showed good morphology. The proliferation of LSC was exhibited significantly concentration-dependent inhibited after exposure to various concentration of ASP. Treated by 40 mg · L(-1) ASP for 48 hours, the percentage of positive cells stained by SA-β-Gal was dramatically increased (P < 0.01) and the colony-formed ability has been weakened (P < 0.01). The observation of ultrastructure showed that cell heterochromatin condensation and fragmentation, mitochondrial swelling, lysosomes increased in number. Aging-related p53, p21, p16, Rb and P16, Rb were up-regulated, protein regulatory cell-cycle CDK4 and Cyclin E were down-regulated. ASP may induce the senescence of LSCs effectively in vitro, P16-Rb cell signaling pathway play a significant role in this process.
CONCLUSIONASP can induce human leukemia stem cell senescence in vitro, the mechanism involved may be related to ASP regulation P16-Rb signaling pathways.
Angelica sinensis ; chemistry ; Cell Cycle ; drug effects ; Cell Cycle Proteins ; genetics ; metabolism ; Cells, Cultured ; Cellular Senescence ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Leukemic ; drug effects ; Humans ; Leukemia ; drug therapy ; genetics ; metabolism ; physiopathology ; Neoplastic Stem Cells ; cytology ; drug effects ; Polysaccharides ; pharmacology ; Signal Transduction ; drug effects
10.Effect of combined administration of Angelica polysaccharide and cytarabine on liver of human leukemia NOD/SCID mouse model.
Jia-Hong ZHU ; Chun-Yan XU ; Xin-Yi MU ; Jun LIU ; Meng-Si ZHANG ; Dao-Yong JIA ; Yan-Yan ZHANG ; Guo-Ning HUANG ; Ya-Ping WANG
China Journal of Chinese Materia Medica 2014;39(1):121-125
Leukemia is a type of malignant tumors of hematopoietic system with the abnormal increased immature leukemia cells showing metastasis and invasion ability. Liver is one of the main targets of the leukemia cells spread to, where they may continue to proliferate and differentiate and cause liver function damage, even liver failure. Our previous studies showed that Angelica polysscharides (APS), the main effective components in Angelica sinensis of Chinese traditional medicine, was able to inhibit the proliferation and induced differentiation of the leukemia cells, however, its effect on the liver during the treatment remains elucidated. In the present study, the human leukemia NOD/SCID mouse model were established by implantation human leukemia K562 cells line, then the leukemia mouse were treated with APS, Ara-c or APS + Ara-c respectively by peritoneal injection for 14 days, to explore the effect and mechanism of the chemicals on the mouse liver. Compared to the human leukemia NOD/SCID mouse model group with the treatments of APS, Ara-c and APS + Ara-c, We found that severe liver damage and pathological changes of the liver were able to alleviate: First, the number of white blood cells in the peripheral blood was significantly lower and with less transplanted K562 leukemia cells; Second, liver function damage was alleviated as liver function tests showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBiL) were significantly reduced, while the albumin (Alb) was notably increased; Third, liver antioxidant ability was improved as the activities of the antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were significantly increased, and the contents of GSH and malonaldehyde (MDA) were decreased significantly in the liver; Fourth, the inflammation of the liver was relieved as the level of IL-1beta and IL-6, the inflammatory cytokines, were decreased significantly in the liver. Fifth, liver index was increased as the pathological observation showed that leukemia cells with diffused infiltration into the liver lobules were significantly reduced and with a remarkable increase of apoptotic positive cell rate by TUNEL test. Furthermore, the APS + Ara-c combined administration showed an even more significant positive effect. In conclusion, the APS, Ara-c therapy reduced the accumulation of leukemia cells within the liver, reduced the liver function damage and levels of inflammatory factors, improved antioxidant capacity of the liver tissue and thus alleviate the pathological changes of the liver. Moreover, the APS + Ara-c combination therapy may have an additive effect.
Angelica
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chemistry
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Animals
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Antineoplastic Combined Chemotherapy Protocols
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pharmacology
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Cell Line, Tumor
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Cytarabine
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administration & dosage
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Humans
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K562 Cells
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Leukemia
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drug therapy
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Liver
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drug effects
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Male
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Mice
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Mice, SCID
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Polysaccharides
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administration & dosage