Inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2) are nitration and oxidation related enzymes, and their correlations with tumors have been drawing more and more attention.There are 2 different viewpoints on the correlation between the 2 enzymes and hematological malignances,and their functioning mechanisms are still unclear.The selective inhibitors of NOS,COX,or the both may provide a new approach for the treatment of hematological malignancies.

0. 05). Conclusion: The HCAPl can be expressed in both normal peripheral white blood cells and the leukemic cells, and there is no difference in the protein levels between them.

Primary liver cancer,particularly hepatocellular carcinoma(HCC),is a common type of digestive tumor in China.The majority of HCC patients is diagnosed with advanced stage and thus cannot be treated with surgery and local treatment.Systemic therapy is considered to be the main treatment of advanced HCC.The effect of traditional cytotoxic drug chemotherapy on advanced HCC is not evident.Although sorafenib,a molecular-targeted drug,has survival benefits,this drug is expensive and has low objective effective rate of only 2%-3%. Metronomic chemotherapy has received increasing attention because it targets tumor angiogenesis for the treatment of advanced metastatic cancer.This article aimed to review the progress of metronomic chemotherapy in advanced HCC treatment.

Objective To evaluate the efficacy and side effects of standard-dose of dexamethasone and low-dose dexamethasone combined with thalidomide in treatment of multiple myeloma. Methods Thirtynine patients with multiple myeloma were randomly divided into 2 groups, who were treated with chemotherapy of thalidomide (200 mg/d) plus dexamethasone (40 mg d1-46728 days in standard-dose group and 20 mg dl-4d/28 days in low-dose group), for a total of 4 courses. The efficacy, survival time and adverse events were compared between the two groups. Results Complete remission rate, partial remission rate and overall response rate of the standard-dose group were 26.3 %, 35 % and 75 %, respectively; and those of the low-dose group were 15.8% , 36.8 % and 68.4 %, respectively. No statistical difference between the two groups (P >0.05 ) was observed. Lung infections, blood pressure elevation, blood glucose elevation, shingles and other adverse reactions in the standard-dose group were statistically higher than those in the low-dose group (P <0.05). Conclusion Efficacy on multiple myeloma of standard-dose and low-dose dexamethasone are similar, but adverse reactions are significantly increased.

Objective To study the effect of thalidomide and arsenic trioxide on the proliferation and apoptosis effect in human myelodysplastic syndrome cell line MUTZ-1 and explore its possible mechanism.Methods MUTZ-1 cells were cultured with different concentration of thalidomide alone, arsenic trioxide alone, and thalidomide plus arsenic trioxide for 48 h. The cell proliferation was analyzed by CCK-8 test, and cell apoptosis was analyzed by flow cytometry. The expression of Bmi-1 was analyzed by semi-quantitative RT-PCR. Results Thalidomide alone had no significant inhibition on growth of MUTZ-1 cells (P >0.05).Arsenic trioxide alone had obviously inhibited the cell proliferation (P <0.05). While thalidomide plus arsenic trioxide group had the great inhibition effect(CDI <0.7), and reveal was that two drugs had synergism effect on inhibiting the MUTZ-1 cells. Arsenic trioxide group of apoptosis rate was increased with higher concentrations of drug, a dose-dependent (r = 0.627, P <0.05), thalidomide in the rate of apoptosis with no increase in drug concentration significantly (r= 0.313, P> 0.05), and the combined group with the drug also increased the concentration of expression (P <0.05). In arsenic trioxide group the expression of Bmi-1 / β-actin declined with the increased concentration, a dose-dependent (r =-0.912, P<0.05), thalidomide group Bmi-1 / β-actin with the increased concentration of no significant decline (r =-0.594, P >0.05), the combined group Bmi-1 inhibition was significantly higher than arsenic trioxide, thalidomide in a separate drug group (CDI <0.7).Conclusion Thalidomide group had no significant growth inhibition. Arsenic trioxide on MUTZ-1 cells significantly inhibited the growth and increased in the combined group significantly.

Objective To evaluate the efficacy andtolerability of continuous low-dose cyclophosphamide and prednisone treatment of relapsed and refractory multiple myeloma. Methods84 relapsed and refractory multiple myeloma patients were enrolled, including 46 males and 38 females, the assess patients of 81 cases with average age of 69.7 (45-91)years. They were treated continuous with oral cyclophosphamide (50 mg/d) and prednisone (15 mg/d) and monthly follow-up.ResultsAverage follow-up time were 23.5(1-71)months.The assessed patients were 81 cases,with 52 cases (64.2 ％) responded.There were 2 cases(2.5 ％)CR,21 cases(25.9 ％) of PR,29 cases(35.8 ％)MR,19 cases(23.5 ％)NC and 10 cases (12.3 ％)PD.The median time to response was 2 months.In the patients who responded to the treatment,the median progression-free survival(PFS)and overall survival (OS) were 18(95 ％CI 12.8-23.2),29(95 ％CI 24.1-33.9)months.In the non-responding patients,the PFS and OS were 4(95 ％ CI 2.2-5.8) and 6(95 ％ CI 4.9-7.1)months.Two groups were statistically significant(P＜0.05).The most common toxicities included fatigue,nausea, neutropenia, hyperglycemia and lung infection. No patient withdrew from the study because of toxicity. Conclusions Continuous low-dose cyclophosphamide combined prednisone is a treatment options for relapsed and refractory MM patients.

AIM:To investigate a profile of gene differential expression in deficiency of spleen-QI syndrome(DSQ)patients.METHODS:4 DSQ patients and 4 healthy volunteers were selected.The gastric mucosa was taken to extract total RNA.The matched samples were hybridized on the gene chip.The fluorescent signals were scanned,the ratio of fluorescent value,the analysis of bioinformatics and t-test were also applied.Related genes were detected by real-time quantitated PCR.RESULTS:Between two groups,54 genes differentially expressed and 72.2% of them were down regulated.45 were genes about metabolism of nutrient substance and immunological regulation,and 71.1% were down regulated.4 had significant difference.Of 5 applied by real-time PCR,4 accorded with the results of the gene chip.CONCLUSION:The differentially expressed genes of DSQ patients are significantly down regulated,especially the genes involved in metabolism of nutrient substance and immunological regulation.

Objective To study the effects of CTLA4-Ig on mu rine allergic contact dermatitis.Methods Mice were exposed to DNFB to induce allergic contact dermatitis and were i njected with CTLA4-Ig.Ear swelling was measured 24h after antigen challenge.Splenocytes from treated mice were assayed for their ability to prolif erate in response to DNFB or FITC stimulation in vitro.Results Profound inhibition of contact hypersensitivity response(CHS )was shown by 69.7%in mice treated with CTLA4-Ig compared with mice treate d with PBS control.CT-LA4-Ig-treated mice displayed DNFB-specific tolerance,but exhibited a vigorous immune response to FITC when re-sensitizing 14days after the fir st challenge.Adoptive transfer of l ymphocytes from CTLA4-Ig-treated mice could induce inhibition of CHS in recipien t mice.Conclusions CTLA4-Ig can inhibit CHS by blocking B7/CD28co-stimulatory pathway,which provides a new way to suppress typeⅣallergic reaction.[

OBJECTIVETo study the effects of 4-1BBL on antitumor immunity induced in vivo by murine 4-1BBL gene transfected Hepa1-6.

METHODSRetrovirus vector was used to transfer the 4-1BBL gene into syngeneic murine heptocellular carcinoma cell line Hepa1-6. The products were termed as Hepa1-6/4-1BBL, and then the TCV4-1BBL was obtained by treating them with mitomycin (MMC). Three models (immunological model, early model, and later model) were established to study the antitumor effects of TCV4-1BBL.

RESULTS(1)In immunological models, the syngeneic mice were completely protected by inoculation with TCV4-1BBL, survived free from tumor for a long period (over 100 days). (2)In early models (7 days after inoculation), Hepa1-6 tumor cells showed strong immunogenicity effects and (3) In later models (14 days after inoculation), they had obvious antitumor effects and most of the tumors were disappeared.

CONCLUSIONSThe antitumor effect against syngeneic murine hepatocellular carcinoma in vivo is obviously enhanced by treating them with TCV4-1BBL

4-1BB Ligand ; Animals ; Cell Division ; immunology ; Female ; Liver Neoplasms, Experimental ; immunology ; pathology ; prevention & control ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Plasmids ; genetics ; immunology ; Transfection ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha ; genetics ; immunology

OBJECTIVETo observe treatment response, survival, safety and the improvement of ECOG in patients with refractory multiple myeloma (MM) with serious heart failure after the administration of continuous low-dose of cyclophosphamide combined with prednisone (CP).

METHODSFrom January 2005 to September 2013, a total of 75 patients were treated by metronomic chemotherapy with continuous low-dose cyclophosphamide (50 mg/d) and prednisone (15 mg/d).

RESULTSAmong the 75 patients, 2 were lost for follow-up. In the 73 available patients, the overall response was 64.4%, including 2 patients (2.7%) with complete remission (CR), 4 cases (5.5%) very good partial remission (VGPR), and 24 patients (32.9%) partial remission (PR). The median survival was 12 months (1-70 months) with a median onset time of 90 days (16-120) and a median progressive freedom survival of 12 months (1-60). The level of B-type natriuretic peptide in responders declined significantly, as compared to no responders [(336.6 ± 30.3) ng/L vs (906.4 ± 104.8) ng/L, P<0.01]. Common adverse events were as follows: 32 (43.8%) cases of bone marrow suppression, 26 (35.6%) cases of infection, 8 cases of dizzy as well as sleepiness (11.0%), 7(9.6%) cases of Cushing syndrome, 4 (5.5%) cases of secondary diabetes mellitus, and 3 (4.1%) cases of edema respectively.

CONCLUSIONThe metronomic chemotherapy of cyclophosphamide combined with prednisone had satisfactory impact on the treatment outcome, including the improvement of cardiac functions and physical capacities, better survival and safety in refractory MM with serious heart failure. It provides a novel regimen for such patients.

Antineoplastic Combined Chemotherapy Protocols ; Clinical Protocols ; Cyclophosphamide ; Heart Failure ; Humans ; Multiple Myeloma ; Prednisone ; Remission Induction ; Treatment Outcome