Agranulocytosis ; chemically induced ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Drug Resistance, Neoplasm ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Leucovorin ; adverse effects ; therapeutic use ; Neoplasm Staging ; Survival Analysis

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Humans ; Lymphoma, B-Cell ; classification ; drug therapy ; therapy ; Prednisone ; administration & dosage ; Stem Cell Transplantation ; Vincristine ; administration & dosage

OBJECTIVETo investigate the effect of Astragalus injection (AI) on left ventricular remodeling and the expression of apoptotic gene caspase-3 in rats after myocardial infarction (MI).

METHODSThe MI model was established. The experimental animals were divided into 4 groups, Group I (the sham-operated group), Group II (the sham-operated plus AI group), Group III (the model group), Group IV (the model plus AI group). Animals in the II and IV group were intraperitoneally injected with 2 ml AI once a day after operation, while animals in the I and III group were treated with normal saline of equal volume. After treated for 4 weeks successively, the structural change of left ventricle and the level of oxyproline in myocardium were observed, and expression of caspase-3 was determined by immunohistochemical method.

RESULTSAs compared with Group Ill, the ultrastructure of myocardium and indexes of left ventricular remodeling were improved, the myocardial content of oxyproline decreased (P < 0.05), the caspase-3 positive cells reduced and caspase-3 mRNA expression significantly down-regulated (P < 0.05).

CONCLUSIONAI can improve left ventricular remodeling, inhibit apoptosis by down-regulate the expression of apoptotic gene caspase-3 in rats after MI.

Animals ; Astragalus membranaceus ; Caspase 3 ; Caspases ; biosynthesis ; genetics ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; Injections ; Male ; Myocardial Infarction ; metabolism ; pathology ; physiopathology ; Myocardium ; ultrastructure ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Ventricular Remodeling ; drug effects

Objective To detect the genomic copy number variations(CNVs) of mice embryonic neural tissue with neural tube defects (NTDs) induced by methotrexate (MTX),and investigate the molecular genetic mechanisms between folic acid metabolism disorders and NTDs pathogenesis.Methods C57BL/6J NTD mice model was induced by MTX on gestational day 7.5,and the maternal serum and NTD embryonic neural tissues were collected;the array-comparative genomic hybridization(array-CGH) assay was utilized to analyze the whole genomic CNVs in NTD embryonic neural tissues;reverse transcription polymerase chain reaction(RT-PCR) was used to confirm the positive results;the maternal serum concentrations of folic acid and related metabolites and dihydrofolate reductase (DHFR) activity were detected by liquid chromatography-tandem mass spectrometry and enzymatic methods,respectively.Results ArrayCGH and RT-PCR results showed the 3 high confidence CNVs on XqE3,XqA1.1-qA2 and XqA1.1 in the NTD embryonic neural tissues.The NTD maternal serum concentrations of 5-methyltetrahydrofolate,5-formyltetrahydrofolic acid,S-adenosyl methionine and DHFR activity were reduced significantly compared with the control group,and there were statistical differences(all P ＜0.05).Conclusions There are obvious CNVs in embryonic neural tissue of NTD mice induced by MTX and folic acid dysmetabolism might cause mice embryonic neural tube developmental disorders through CNVs.

Objective: This study was designed to investigate the prognostic value of serum β2-micorglobulin(β2-MG) level in non-Hodgkin s lymphoma(NHL) patients and its correlation with Ann Arber staging system and the pathological type. Method: Serum β2-MG levels in 75 de novo NHL patients were measured by radioimmunoassay. Results: The β2-MG level in 75 NHL patients was higher than that in nomal control level in 52％ of the patients and correlated with the Ann Arber stage. There was significant difference between two groups (P<0.01). The international prognostic index (IPI) and the response rate to chemotherapy were also correlated with the β2-MG level in serum. The response rate, the complete response, and partial response were 87.2%, 61.5%, and 25.6% in normal serum β2-MG group, while in the high β2-MG group they were only 75.0%, 50.0%, and 25.0%, respectively, which were significantly different between the two groups (P<0.05). The difference of 5-year survival between the two groups was significant (64.1% vs 27.8%, P<0.05) and favorable in normal β2-MG group. Conclusion: β2-MG level in serum is an independen prognostic factor in de novo NHL, and the patients with abnormal β2-MG level in serum have a unfavorable prognosis.

OBJECTIVETo investigate the clinical characteristics and prognosis of patients with different subtypes of breast cancer: basaloid, HER-2 and luminal types, and try to find the evidence of individualized treatment for the patients.

METHODS1280 histologically and immunohistochemically proven patients with resectable breast cancer were treated, and the clinical data including characteristics, relapse and survival of the patients with different subtypes of breast cancer were analyzed retrospectively.

RESULTSOf the 1280 breast cancer patients, basaloid, HER-2 and luminal types accounted for 20.9%, 23.2% and 55.9%, respectively. Basaloid type was more likely to be found in younger patients frequently with a family history of breast cancer. HER-2 type usually had a tumor of larger size with more advanced stage disease and more metastatic lymph nodes. Luminal type was likely to occur in aged patients with an earlier stage disease. The recurrence rates in basaloid, HER-2 and luminal types were 25.0%, 27.9% and 11.7%, respectively. Patients with basaloid or HER-2 type were found to have a significantly higher recurrence rate than the patients with luminal type breast cancer (P < 0.001), but no significant difference was observed between the basaloid and HER-2 types. However, patients with basaloid type breast cancer were more likely to develop lung metastasis than HER-2 type (13.4% vs. 7.1%, P = 0.017). Up to December 2006, the 5-year disease-free survival (DFS) rates for patients with basaloid, HER-2 and luminal types were 72.2%, 68.2% and 86.2% (P < 0.001), respectively. The overall 5-yr survival (OS) rates of the three groups were 88.6%, 83.8% and 95.8% (P < 0.001) , respectively. Of the patients with luminal type breast cancer, HER2-negative patients had a higher DFS (86.2% vs 57.0%, P < 0.001) and OS (95.8% vs 87.7%, P = 0.0001) compared with those with HER2-positive. The results of Multivariate Cox Regression showed that tumor size and lymph node state were the most important factors influencing the prognosis.

CONCLUSIONEach subtype of breast cancer has somewhat its own specific clinical features in terms of recurrence pattern and prognosis, therefore, individualized treatment regimen may be required.

Adult ; Aged ; Breast Neoplasms ; classification ; metabolism ; pathology ; therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Rate ; Young Adult

Objective: This study was designed to improve complete remission(CR) rate in the patients with advanced lymphoblastic lymphoma by using early extensive induction chemotherapy. Method:A total of 11 cases of untreated lymphoblastic lymphoma in Stage Ⅲ /Ⅳ were received CVDLP regimen, including cytoxan(CTX) 1000 mg/m2 d1， vincristine(VCR) 1.5 mg/m2 d1,d8,d15,d21， Adriamycin(ADR) 40 mg/m2 d1， d2， d21， L-asparaginase(L-ASP) 10000 U/m2 d15～24， Prednison 60 mg/m2 d1～28， gradually decreased dosage at d15. methotrexate＋ Ara-C IT qw× 4. Efficacy were evaluated at d28～35. Simultaneously,retrospective analysis for 9 cases of untreated lymphoblastic lymphoma in Stage Ⅲ /Ⅳ treated with 2 cycles of CHOP were made. Efficacy were evaluated at d35. Results: CVDLP group: 10/11 cases of patients achieved CR, and 1/11 case had PR, rate of complete remission was 90.9％ ;10/11 cases had Grade Ⅳ hematological toxicity,1/11 cases had Grade Ⅲ hematological toxicity(WHO). CHOP group:3/9 got CR;5/9 got PR;1/9 had MR,rate of complete remission was 33％ . 3/9 had Grade Ⅲ hematology toxicity;6/9 had GradeⅡ hematological toxicity. Conclusion:CVDLP regimen can induce higher CR rate than CHOP regimen in untreated lymphoblastic lymphoma with Stage Ⅲ /Ⅳ , but hematology toxicity was also higher than CHOP regimen. However this induction regimen is safe and viable with strengthening supportive care.

OBJECTIVETo confirm the therapeutic effect of dendritic cell (DC) vaccine on treatment for mice with lymphoma and the protective effect of DC vaccine loaded with different antigens on the tumor-bearing BAL B/c mice.

METHODSFirstly, a mouse tumor model was set up by s. c. inoculation of 1 x 10(6)/mouse A20 tumor cells. Then different DC vaccines were injected, respectively, and the tumor size and survival time were observed. Secondly, the immunized mice with DC vaccines were challenged with A20 tumor cells, and observed whether a new tumor occurred in the mice and the time of survival.

RESULTSThe tumor of mice immunized with Id-DC vaccines grew slower than the controls (mean time of survival was 40.4 days vs. 33.4 days), but statistically not significantly different. The tumor of mice injected with CPP-Id-DC vaccines grew slower than that injected with Id-DC vaccines and controls, and one of 5 mice got CR and the tumor in another one mouse became stable. The median survival time was 70.8 days during a 90-days observation period. The difference was significant (P<0.01). The mice injected with Id-DC vaccines were challenged with A20 tumor cells showed new tumor occurred at 7 - 12 days, and 1 of the 5 mice survived for 60 days. The mice injected with CPP-Id-DC vaccines had no tumor.

CONCLUSIONThe DC loaded with CPP-Id was better than that loaded with Id alone in treating B cell lymphoma, and It can enhance their antitumor responses and prolong the survival time of the A20 tumor animal models. The vaccine of DC loaded with CPP-Id can protect mice from A20 tumor cell challenge.

Animals ; Cancer Vaccines ; immunology ; therapeutic use ; Cell Line, Tumor ; Cells, Cultured ; Dendritic Cells ; immunology ; Female ; Immunoglobulin Idiotypes ; immunology ; Lymphoma ; immunology ; pathology ; therapy ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Peptide Fragments ; therapeutic use ; Peptides ; therapeutic use ; Random Allocation

OBJECTIVETo investigate the therapeutic effect, long term survival and side effect on NSCLC patients treated with nadaplatin combined with paclitaxol and cisplatin combined with paclitaxol.

METHODSNSCLC patients with stage IIIB or IV were randomized into two groups in this prospective clinical study. TN group: nadaplatin 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks. TP group: DDP 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks.

RESULTSSixty patients were enrolled and 57 were evaluable with 30 in TN group and 27 in TP group. The overall response rate were 43.3% vs. 48.1% (P = 0.716), and the disease control rate were 86.7% vs. 88.8% in TN and TP group (P = 0.799), respectively. The median survival time was 14.3 vs. 13.0 months, and the 1- and 2-year survival rate was 62.5% vs. 59.1%, 0% vs. 5.8% in TN and TP group (P = 0.839), respectively. The rates of neutropenia and thrombocytopenia were similar in TN and TP groups whereas more patients in TP group than in TN group suffered from anemia (38.5% vs. 17.5%, P = 0.001), nausea and vomiting (82.6% vs. 35.6%, P = 0.000), fatigue (35.9% vs. 14.1%, P = 0.000) and peripheral neurotoxicity (50.0% vs. 21.9%, calculated by case, P = 0.023).

CONCLUSIONNadaplatin combined with paclitaxol is an effective treatment regimen for NSCLC patients. When compared with similar regimen with cisplatin, the response rate and survival were similar; however, nadaplatin regimen shows some superiority as regards some treatment side effect.

Adult ; Aged ; Anemia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; adverse effects ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Paclitaxel ; administration & dosage ; adverse effects ; Prospective Studies ; Remission Induction ; Survival Analysis ; Thrombocytopenia ; chemically induced ; Treatment Outcome

OBJECTIVETo investigate the expressions of mRNA and protein of p38, Osx, PI3K, Akt1 in the rats bone with chronic fluorosis.

METHODSDental fluorosis were observed and the fluoride contents in the urine and bone were detected by fluorin-ion selective electrode. The morphologic changes and ultrastructure of rats' bone were observed by light and electronic microscopy. The expressions of protein and mRNA of p38, Osx, PI3K and Akt1 were detected by immunohistochemistry and real-time PCR, respectively. The contents of BALP and BGP in serum were detected by ELISA.

RESULTSThe rates of dental fluorosis in the fluorosis rats were increased, and the fluoride contents in bone and urine of the fluorosis rats were increased compared to the control group, the difference was statistically significant (P < 0.05). The bone trabeculae thickness and density and the thickness of bone cortex in fluorosis rats were remarkably increased, the space of bone trabeculae was reduced, and in accordance with the matching morphometrical indices, the difference was statistically significant (P < 0.05) as compared with the control rats. The contents of BALP [(54.61 ± 2.27) U/L] and BGP [(2.38 ± 0.16) µg/L]in the fluoride groups were higher than those in the control group, the difference was statistically significant (P < 0.05). Ultrastructurally, the broadening of the osseouslacuna was observed. The reduced protuberances of the osteocytes, the unclear organelle structure, pyknosis, karyotheca increasation and edged chromatin were also observed. Compared to the control group, the expressions of protein and its mRNA of p38, Osx, PI3K and Akt1 were higher in the fluorosis rats than those in the control rats, and the difference was statistically significant (P < 0.05). There is no any expression of p38, Osx, PI3K and Akt1 in the osteocytes in fluorosis rats.

CONCLUSIONSThe over-expression of p38, Osx, PI3K and Akt1 in bone tissue of fluorosis rats may relate to the accumulation of fluorine in the body. The bone injury mainly occur in the stage of the differentiation and proliferation. The upregulation of P38MARK signal path and PI3K/Akt1 signal path may be involved in the pathogenesis of bone injury caused by fluoride.

Alkaline Phosphatase ; blood ; Animals ; Bone and Bones ; metabolism ; pathology ; ultrastructure ; Fluoride Poisoning ; metabolism ; pathology ; Fluorides ; metabolism ; urine ; Fluorosis, Dental ; metabolism ; pathology ; Immunohistochemistry ; Microscopy, Electron, Transmission ; Osteocalcin ; blood ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Sodium Fluoride ; toxicity ; Transcription Factors ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism