Therapeutic features of endostar, a modified endostatin, on ascites tumor in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of endostar in controlling ascites tumor formation in mice.</p><p><b>METHODS</b>Mouse models bearing ascites tumors were established via intraperitoneal injection of H22 and S180 cell lines. Eighty-eight ICR mice were randomly assigned into 4 groups, namely the control group (0.9% normal saline) and 3 endostar groups with 8 mg/kg endostar administration daily, every other day or every two days. The peritoneal membrane permeability of the mice was assessed using Evan blue staining. The body weight curve of mice was drawn, and the cumulative ascites volume and number of red cells and tumor cells in the malignant ascites were determined. The survival of the mice was evaluated to assess the therapeutic effect of endostar.</p><p><b>RESULTS</b>Compared with the control group, the mice receiving daily endostar injection showed obviously lower ascites accumulation and peritoneal capillary permeability (P<0.05) with reduced count of ascites tumor cells and red cells and tumor burden of the abdominal cavity. The mice with daily endostar injection also showed longer survival than the control group.</p><p><b>CONCLUSIONS</b>Continuous intraperitoneal injection can be the optimal means for endostar administration for treatment of malignant ascites.</p>

Adriamycin combined with hyperthermia inhibits transplanted B cell lymphoma in nude mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of adriamycin combined with hyperthermia on tumor formation and growth of human B lymphoma cell line (Raji) in nude mice.</p><p><b>METHODS</b>Twenty-four BALB/C nude mice were divided into control group (37 degrees celsius;), chemotherapy group (37 degrees celsius;+ADM), hyperthermia group (42 degrees celsius;) and thermochemotherapy group (42 degrees celsius;+ADM), and in each mouse, 5 x 10(6) Raji cells were injected subcutaneously. The time and rate of tumor formation were observed, the tumor diameter was measured every 3 days and the tumor volume calculated to obtain the growth curves of the tumors. Three weeks after tumor formation, all the mice were executed to observe the histopathological changes of the tumor with HE staining.</p><p><b>RESULTS</b>The time of tumor formation in the control, chemotherapy, hyperthermia and thermochemotherapy groups were 11.2-/+1.7, 20.2-/+2.3, 15.3-/+1.6 and 23.8-/+1.7 days, respectively. Three weeks after tumor formation, the average weight of the tumors were 3.33-/+0.57, 2.26-/+0.28, 2.76-/+0. 26 and 1.73-/+0. 33 g, respectively, and the tumor growth inhibition rate was 48.0% in the thermochemotherapy group.</p><p><b>CONCLUSION</b>Thermochemotherapy can be effective in inhibiting tumor growth and provides an alternative of adjuvant therapy for malignant B cell lymphoma.</p>

Therapeutic effects of cryoablation, radiofrequency ablation, and microwave coagulation against VX2 liver cancer: a comparative study in rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To Compare the therapeutic effects of cryocareTM cryoablation, radiofrequency ablation(RFA), and and microwave coagulation (MCT) in rabbits with VX(2) liver cancer.</p><p><b>METHODS</b>Forty-five rabbits with VX(2) liver cancer were randomly and equally allocated into 5 groups to receive treatment with cryocare cryoablation (group A), radiofrequency ablation (group B), microwave coagulation (group C), surgical resection (group D) and control group (group E), respectively. The residual tumor tissues and metastasis (intrahepatic, lung, abdominal lymphoid node, and abdominal implantation) were observed after the treatments, with also detection of soluble interleukin-2 receptor ( sIL-2R) and recording of the survival time of the rabbits.</p><p><b>RESULTS</b>Significant differences were found in the occurrence of tumor residue (chi(2)=20.700, P=0.0000), intrahepatic metastasis (chi(2)=15.652, P=0.0004), and abdominal implantation tumor (chi(2)=13.894, P=0.0008) between the 5 groups, but not in lung and abdominal lymph node metastasis. sIL-2R levels differed significantly only after but not before the treatments (F=31.58, P=0.000) between groups A to D and group E (t=10.119, P=0.000). The treatments in groups A to D all resulted in prolonged survival of the rabbits as compared with the control (F=73.084, P=0.000), and cryocareTM cryoablation and surgical resection showed similarly better effect than RFA and MCT.</p><p><b>CONCLUSION</b>Cryocare cryoablation can be more effective than RFA and MCT in reducing tumor residue and metastasis and prolonging the survival time of rabbits with VX(2) liver cancer, and RFA and MCT are comparable for their therapeutic effects.</p>

Effect of hyperthermia in combination with chemotherapy on K562/AO2 cells in vitro / 中国实验血液学杂志

This study was purposed to investigate the inhibitory effect, apoptosis, Bcl-2 and P-gp expression of K562/AO2 cells by hyperthermia combined with adriamycin. The working concentration of adriamycin against K562/AO2 was determined by MTT assay. The hyperthermia and chemotherapy were used alone or in combination, then the cell survival rate was detected at 48 hours. The inhibitory effect was evaluated by MTT assay. The apoptosis rate, Bcl-2 and P-gp expression of K562/AO2 were determined by flow cytometry. The concentration of adriamycin in the experiment was defined as its IC(50) at 48 hours action. The results indicated that the hyperthermia at 40, 41 and 42 degrees C for 60 minutes showed obvious inhibitory effect on K562/AO2 cells (p < 0.01). Adriamycin chemotherapy combined with hyperthermia showed more obvious inhibitory effect on K562/AO2. According to flow cytometric analysis, the hyperthermia and adriamycin used alone or in combination could obviously increase the apoptosis rate and down-regulate Bcl-2 and P-gp expression of K562/AO2 cells (p < 0.01). It is concluded that the adriamycin chemotherapy combined with hyperthermia for 60 minutes shows obvious inhibitory effect on K562/AO2 cells, which increases the apoptosis rate and down-regulates expression of Bcl-2 and P-gp.

Thermotherapy enhances the sensitivity of lymphoma cell line Raji to chemotherapy in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of thermotherapy on the intracellular adriamycin concentration and apoptosis of Raji cells in vitro.</p><p><b>METHODS</b>The working concentration of adriamycin against Raji cells was determined with MTT assay. Raji cells were subjected to thermotherapy (at 40 degrees Celsius;, 41 degrees Celsius; or 42 degrees Celsius;) and chemotherapy with adriamycin alone or in conjunction, and the cell survival rates were determined 48 h after the treatment. The cell growth inhibition effect of the treatment was evaluated with MTT assay, and the apoptotic rates of Raji cells and alteration of intracellular adriamycin concentration were determined by flow cytometry.</p><p><b>RESULTS</b>The IC(50) of adriamycin was defined as the working concentration in the experiment. Thermotherapy at 40, 41 and 42 degrees Celsius; for 60 min in conjuction with chemotherapy significantly inhibited the growth of Raji cells (P<0.01). The results of flow cytometry showed that thermotherapy and adriamycin chemotherapy, used either alone or in combination, significantly increased the apoptotic rates of Raji cells (P<0.01), and thermotherapy remarkably increased the intracellular concentration of adriamycin.</p><p><b>CONCLUSION</b>Adriamycin chemotherapy combined thermotherapy for 60 min can increase the intracellular concentration of adriamycin and the apoptosis rates of Raji cells.</p>

Expression of NKG2D ligands in multidrug-resistant nasopharyngeal carcinoma cell line CNE2/DDP and their effects on cytotoxicity of natural killer cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the expression of NKG2D ligands on human nasopharyngeal carcinoma cell line CNE2 and the multidrug-resistant lin CNE2/DDP and investigate its impact on cytotoxicity of natural killer (NK) cells.</p><p><b>METHODS</b>Expression of NKG2D ligands on the surface of CNE2 and CNE2/DDP cells was analyzed by flow cytometry, and their HLA genotypes, along with inhibitory killer cell immunoglobulin-like receptors (KIRs) expressed on NK cells from 5 healthy donors, were determined by PCR with sequence specific primers. Cytotoxicity of NK cells against CNE2 and CNE2/DDP cells was evaluated by LDH-releasing assay at different effector-to-target ratios (E:T). In blocking experiments, different monoclonal antibodies (mAb) were added to the target cells at the E:T of 20:1 ratio.</p><p><b>RESULTS</b>The HLA genotypes of CNE2 and CNE2/DDP cells were A2, 24, B18, 35, Cw4, 7, and the inhibitory KIR genotypes of the 5 healthy donors were KIR2DL1, KIR2DL3, KIR3DL1, and KIR3DL2, mismatched with the HLA -class I molecules expressed by the CNE2 and CNE2/DDP cells. The expression of MHC class I chain-related proteins A and B (MICA and MICB) on CNE2 cells was higher than that on CNE2/DDP cells (P<0.01), and ULBP1 and ULBP3 were not detectable. NK cells displayed highly in vitro cytotoxicity against CNE2 and CNE2/DDP cells with a mean cell lysis rate of (10.50-/+2.17)%, (4.98-/+0.95)%; (27.68-/+1.47) %, (15.48-/+2.10) %; (36.99-/+3.13) %, (28.46-/+4.30) %; (55.00-/+2.20) %, (40.95-/+2.21) %, respectively, corresponding to the E:T ratios of 5:1, 10:1, 20:1, and 30:1 (P<0.01). Blocking experiments confirmed that killing of CNE2 and CNE2/DDP cells by NK cells was efficiently inhibited by anti-MICA, anti-MICB, and anti-ULBP2 mAbs, whereas anti-ULBP1 and anti-ULBP3 mAbs had no effects on the cytotoxicity of the NK cells.</p><p><b>CONCLUSION</b>Expression of NKG2D ligands on CNE2 and CNE2/DDP cells is correlated with NK cell-mediated lysis, and NK cells display higher cytotoxicity against parental CNE2 cells than the multidrug-resistant CNE2/DDP cells.</p>

Expression of HLA class I molecules and MHC class I chain-related molecules A/B in K562 and K562/AO2 cell lines and their effects on cytotoxicity of NK cells / 中国实验血液学杂志

The study was aimed to investigate the expression of HLA class I molecules and MHC class I chain-related molecules A/B (MICA/MICB) in K562 and adriamycin (ADM)-resistant K562 cell lines (K562/AO2) and their effect on cytotoxicity of NK cells. Expression of HLA class I molecules and MICA/MICB on the surface of K562 and K562/AO2 cell lines were analyzed by flow cytometry. Cytotoxicity of NK cells (isolated from 3 healthy persons) against K562 and K562/AO2 cells were detected by LDH releasing assay at different effect-to-target cell ratios (E:T). In blocking experiments, anti-MHC class I monoclonal antibody (McAb) (W6/32, a pan anti-HLA class I antibody) and anti-MHC class I chain-related molecules McAb (BAMO-1, specifically against MICA and MICB) were added to the target cells at E:T of 10:1. The results showed that the expression of MHC class I chain-related molecules on K562 was higher than that on K562/AO2 (P=0.000), and HLA class I molecules were not detectable on both cells. Cytotoxicities of NK cells against K562 and K562/AO2 cells were (29.32 +/- 0.12)%, (45.33 +/- 0.78)%, (58.37 +/- 0.87)%, (72.37 +/- 0.96)% and (12.47 +/- 0.91)%, (24.36 +/- 1.11)%, (33.29 +/- 1.03)%, (53.87 +/- 1.27)% at E:T ratios of 5:1, 10:1, 20:1 and 30:1 respectively (P=0.000), the cytotoxicity of NK cells on K562 cells was significantly higher than that on K562/A02 cells at different E:T ratios. Blocking experiments confirmed that at E:T of 10:1 killing of NK cells against K562 and K562/AO2 cells was efficiently inhibited by BAMO-1, whereas W6/32 had no effect on K562 and K562/AO2 cells. It is concluded that the expression of MHC class I chain-related molecules on K562 and K562/AO2 cells is correlated with NK cell-mediated lysis. NK cells display higher cytotoxicity against parental K562 cells than multi-drug resistant K562/AO2 cells. Down-regulation of MICA/B in multi-drug resistant tumor cell lines leads to reduction of susceptibility to NK lysis.

Apoptosis and Bcl-2 expression of cell line K562/AO2 treated with adriamycin in combination with hyperthermia / 中华物理医学与康复杂志

Objective To investigate the inhibitory effect of adriamycin in combination with hyperthermia on apoptosis and bcl-2 expression in the chronic leukemic cell line K562/AO2 in vitro.Methods The working con- centration of adriamycin against K562/AO2 determined by using methyl thiazolyl tetrazolium(MTT) assay was used to treat the chronic leukemic cell line K562/AO2 in vitro alone or in combination with hyperthermia induced using a hot water bath at 40,41 or 42℃.The inhibitory effect was evaluated by MTT assay.The apoptosis rates and bcl-2 ex- pression of K562/AO2 were determined by flow cytometry.Results The working concentration of adriamycin in the study was defined as its 50% inhibition concentration (IC50).A 60 min session of hyperthermia at 40℃,41℃or 42℃was associated with significant growth inhibition of the cell line K562/AO2.Adriamycin chemotherapy alone and with hyperthermia significantly inhibited the growth of K562/AO2.All treatments significantly increased apoptosis rates and down-regulated bcl-2 expression of the K562/AO2 cell line.Conclusion Adriamycin chemotherapy com- bined with 60 min sessions of hyperthermia showed significant suppression effect on K562/AO2 cell proliferation.The treatment can increase apoptosis rates and down-regulate bcl-2 expression.