BACKGROUNDBoth survivin and lung resistance related protein (LRP) are related to the chemoresistances in hepatocellular carcinoma (HCC). But the relationship between survivin and LRP is indefinite. The aim of this study was to investigate the effects of down-regulation of survivin on LRP expressions and the reversal of chemoresistances in HCC both in vitro and in vivo.

METHODSThe expressions of survivin were detected by RT-PCR and Western blotting in HCC cell line SMMC-7721 and SMMC-7721/ADM. The sensitivities of these two cell lines to ADM were evaluated by MTT assays. SiRNA which targeted survivin was transfected into SMMC-7721/ADM cells, then the sensitivity of SMMC-7721/ADM cells to ADM and the expressions of survivin and LRP were detected respectively. SMMC-7721/ADM cells were transplanted subcutaneously into nude mice to establish xenograft tumors. Antitumor activities of RNA interference (RNAi) targeting survivin, various doses of ADM and combination therapies were observed respectively. Possible toxicities were evaluated. LRP expression changes were tested. Student's t test was used for evaluating statistical significance.

RESULTSThe expressions of survivin in SMMC-7721/ADM cell line showed significant elevation compared to those in SMMC-7721 cell line (P < 0.05). Positive siRNA down-regulated the expressions of survivin significantly (P < 0.05). SiRNA targeting survivin could sensitize SMMC-7721/ADM cells to ADM and down-regulate the expressions of LRP significantly (P < 0.05). Growths of the tumors were significantly inhibited in positive siRNA group as compared with those in the control group from the 8th day (P < 0.05). Combination therapies caused significant tumor inhibitions compared with tumors of nude mice in the other three groups respectively (P < 0.05). No toxicities were found in nude mice treated by siRNA and combination therapies. The expressions of LRP were markedly reduced in tumors treated with siRNA targeting survivin (P < 0.05).

CONCLUSIONSDown regulation of survivin gene by RNAi can increase chemosensitivity of HCC both in vitro and in vivo. The reversal of drug resistance may be reduced through the inhibitions of LRP.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Blotting, Western ; Carcinoma, Hepatocellular ; drug therapy ; genetics ; metabolism ; Cell Line, Tumor ; Doxorubicin ; therapeutic use ; Drug Resistance, Neoplasm ; Humans ; Inhibitor of Apoptosis Proteins ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microtubule-Associated Proteins ; genetics ; metabolism ; Mitolactol ; therapeutic use ; Mitomycins ; therapeutic use ; RNA Interference ; physiology ; RNA, Small Interfering ; genetics ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Vault Ribonucleoprotein Particles ; genetics ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo summarize the clinicopathological characteristics and prognostic factors of primary pulmonary mucinous adenocarcinoma (PPMA).

METHODSThe clinicopathological manifestations and radiological appearances of 57 PPMA patients surgically treated and pathologically proved between Jan. 2001 and Dec. 2006 were retrospectively analyzed. The cumulated survival rate was calculated by life table method.

RESULTSThere were no specific clinical manifestations in PPMA patients, while the tumors were radiologically pleomorphologic. Of these 57 patients, 5 were in stage Ia, 20 in stage Ib, 1 in stage IIb, 11 in stage IIIa, 6 in stage IIIb and 14 in stage IV. The cumulated 1-, 3- and 5-year survivals of those with complete resection were 88.0%, 55.0% and 55.0%, respectively.

CONCLUSIONThe final correct diagnosis of primary pulmonary mucinous adenocarcinoma should be made by pathology. Though the treatment is not different, the prognosis of the patients with primary pulmonary mucinous adenocarcinoma is better than that of those with adenocarcinoma.

Adenocarcinoma, Mucinous ; pathology ; therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cisplatin ; therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Lung Neoplasms ; pathology ; therapy ; Male ; Middle Aged ; Mitomycins ; therapeutic use ; Neoplasm Staging ; Pneumonectomy ; Prognosis ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Vinblastine ; therapeutic use

OBJECTIVETo determine the in vitro possible clastogenic and cytotoxic activities of Ulva rigida crude extracts (URE), and identify their antigenotoxic and protective effects on chemotherapeutic agent mitomycine-C (MMC).

METHODSAnti-clastogenic and anti-genotoxic activities of Ulva rigida crude extracts (URE) were studied using chromosome aberration (CA), sister chromatid exchange (SCE), and micronuclei (MN) tests in human lymphocytes cultured in vitro.

RESULTSThe chromosome aberration, sister chromatid exchange or micronuclei tests showed that URE at concentrations of 10, 20, and 40 microg/mL had no clastogenic activity in human lymphocyte cell culture. Three doses of URE significantly decreased the number of chromosomal aberrations and the frequencies of SCE and MN when compared with the culture treated with MMC (P < 0.0001).

CONCLUSIONAlthough URE itself is not a clastogenic or cytotoxic substance, it possesses strong antigenotoxic, anti-clastogenic, and protective effects on MMC in vitro.

Antibiotics, Antineoplastic ; pharmacology ; Antimutagenic Agents ; pharmacology ; Cells, Cultured ; Chlorophyta ; Chromosome Aberrations ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Lymphocytes ; drug effects ; metabolism ; Micronucleus Tests ; Mitomycins ; pharmacology ; Mutagens ; toxicity ; Plant Extracts ; chemistry ; pharmacology ; Sister Chromatid Exchange ; drug effects

OBJECTIVETo evaluate in vitro anti-tumor effect of chemotherapeutic drugs on human gastric cancer cells, and investigate the relationship with Bcl-2 expression.

METHODSSingle cell suspension was prepared from fresh gastric cancer tissue and exposed to taxol (Tax), 5-fluorouracil (5-FU), cisplatin (CDDP), adriamycin (ADM), mitomycin (MMC) respectively for 48 hours. Metabolic activity and inhibitory rate of cells were detected by MTT assay. Expression of Bcl-2 was examined with immunohistochemistry.

RESULTSThe inhibitory rates of cancer cells exposed to chemotherapeutic drugs were different and Tax, 5-FU, CDDP had remarkably higher rates than ADM and MMC. The lower differentiated gastric cancer cells were more sensitive than the higher ones. Positive expression rate of Bcl-2 was 80% and the positive cells showed resistance to 5-FU, ADM and MMC.

CONCLUSIONSChemosensitive testing by MTT assay can constitute the prediction for the application of chemotherapeutic drugs individually. Overexpression of Bcl-2 may contribute to multiple drug-resistance of tumors.

Adult ; Aged ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Cell Survival ; Cisplatin ; pharmacology ; therapeutic use ; Doxorubicin ; pharmacology ; therapeutic use ; Drug Screening Assays, Antitumor ; Female ; Fluorouracil ; pharmacology ; therapeutic use ; Humans ; Male ; Middle Aged ; Mitomycin ; pharmacology ; therapeutic use ; Mitomycins ; pharmacology ; therapeutic use ; Paclitaxel ; pharmacology ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; Tumor Cells, Cultured

OBJECTIVETo explore the expression of multidrug resistance gene 1 ( MDR1), glutathione-S-transferases-pi (GST-pi) in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlation with chemotherapy resistance.

METHODSMDR1 and GST-pi expressions were analyzed by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) and flow cytometry (FCM) at mRNA and protein levels, respectively. Chemotherapy sensitivity on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were detected by MTT assay.

RESULTSThe nonsensitive rates on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were 41.18%, 17.7%, 47.1%, 50.0%, 76.5%, 61.8% and 52.9%, respectively. The expression of P-glycoprotein (P-gp) and GST-pi in tumor tissues was 1.54 and 2.58 (relative fluorescence intensity). Chi2 analysis showed that there was a positive correlation between P-gp expression and drug resistance on ADM, GST-pi expression and resistance on ADM, DDP and MMC (P < 0.05). There was not seen obvious correlation between expression of MDR1, GST-pi and age, gender, pathological type, tumor size in osteosarcoma and soft tissue sarcoma patients (P > 0.05). The expression of GST-pi was increased in patients receiving preoperative chemotherapy. The rate of postoperative recurrence was higher in patients with higher GST-pi expression level than those with lower GST-pi expression level before operation (P < 0.05).

CONCLUSIONIndividual differences exist in chemotherapy sensitivity and expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcomas patients. Chemotherapy can induce up-regulation of GST-pi protein expression. Primary high expression of GST-pi is the main mechanism of resistance of osteosarcoma and soft tissue sarcomas to chemotherapy and is related to poor prognosis.

ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; genetics ; Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; drug therapy ; genetics ; metabolism ; Child ; Cisplatin ; therapeutic use ; Doxorubicin ; therapeutic use ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Flow Cytometry ; Follow-Up Studies ; Glutathione S-Transferase pi ; biosynthesis ; genetics ; Humans ; Male ; Middle Aged ; Mitolactol ; therapeutic use ; Mitomycins ; therapeutic use ; Osteosarcoma ; drug therapy ; genetics ; metabolism ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Sarcoma ; drug therapy ; genetics ; metabolism

OBJECTIVETo observe the therapeutic effect of Guben Xiaoliu Capsule (GXC) in treating advanced stage non-small cell lung cancer (NSCLC).

METHODSOne hundred and ninety-eight NSCLC in-patients were divided into the integrative treated group [Group A, 54 patients treated with chemotherapy (CT) plus GXC], the TCM treated group (Group B, 96 patients treated with GXC alone) and the chemotherapeutic group (Group C, 48 patients treated with CT alone). Randomized controlled observation was applied to the Group A and C. The clinical effect, quality of life (QOL), adverse reaction and survival period in the three groups were observed.

RESULTSThe immediate effective rate (CR + PR) in the Group A, B and C was 16.7%, 3.1% and 8.3%, respectively, in the Group A, it was better than that in the other two groups (P < 0.05). The improvement of clinical symptoms and QOL in the Group A and B were superior to those in the Group C (P < 0.05). The median survival rate in the three groups was 12, 15 and 9 months, respectively, the 1-, 2- and 3-year survival rate in Group A being 57.4%, 11.1% and 3.7%, respectively, in Group B, 67.7%, 9.4% and 3.1%, and in (Group C, 39.6%, 4.2% and 0, respectively, comparison between the three groups showed that the survival rates in the former two were higher than those in Group C (P < 0.05). Moreover, the incidence rate and degree of CT toxicity were milder in Group A than those in Group C (P < 0.05).

CONCLUSIONGXC has definite effect in treating NSCLC, it could raise the QOL, prolong the survival period of patients, also reduce the toxicity and enhance the efficacy of CT.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Capsules ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; mortality ; Cisplatin ; administration & dosage ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; mortality ; Male ; Middle Aged ; Mitomycins ; administration & dosage ; Phytotherapy ; Quality of Life ; Survival Analysis ; Survival Rate ; Vinblastine ; administration & dosage

OBJECTIVETo observe the effect of Astragalus injection (AI) combined with chemotherapy on quality of life (QOF) in patients with advanced non-small cell lung caner (NSCLC).

METHODSSixty-NSCLC patients were randomly divided into the treated group (n = 30, treated with AI combined with chemotherapy) and the control group (n = 30, treated with chemotherapy alone). Chemotherapy of MVP protocol was applied to both groups. AI was supplemented to the treated group by intravenous dripping 60 ml per day. Treatment of 21-28 days as one treatment cycle, and 2-3 treatment cycles were applied.

RESULTSThe effective rate in the treated group was 40.0% and in the control group was 36.7%, the mean remission rate in the treated and control group was 5.4 months and 3.3 months, the median survival period 11 months and 7 months, and the 1-year survival rate 46.75% and 30.0%, respectively, the differences of these indexes between the two groups were all significant (P < 0.05). Moreover, the clinical improving rate and QOF elevation rate in the treated group was 80.4% and 43.3%, as compared with those in the control group (50.0% and 23.3% respectively), the difference was also significant (P < 0.01).

CONCLUSIONAI combined with chemotherapy can significantly improve the QOF in NSCLC patients of advanced stage.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Astragalus membranaceus ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Carcinoma, Squamous Cell ; drug therapy ; Cisplatin ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Mitomycins ; therapeutic use ; Phytotherapy ; Quality of Life ; Vinblastine ; therapeutic use

OBJECTIVETo establish human multidrug-resistant lung carcinoma cell line (D6/MVP) with its characteristics studied.

METHODSIntermittent administration of high-dose MMC, VDS and DDP (MVP) was used to induce human lung carcinoma cell line (D6) to a multidrug-resistant variety (D6/MVP). MTT assay was used to study the multidrug resistance of D6/MVP to multianticarcinogen. Flow cytometry was used to study the cell cycle distribution and the expression of P-gp, multidrug resistance-associated protein (MRP) and GSH/GST.

RESULTS1. D6/MVP was resistant to many anti-tumor agents, with the IC(50) 13.3 times higher and the drug resistance 2 - 6 times higher than D6, 2. The multiplication time of D6/MVP was prolonged and the cell number of S-phase decreased while that of G1- and G(2)-phase increased and 3. The expression of P-gp and MRP was enhanced significantly (96.2% vs 51.7%), but the expression of GSH/GST kept stable.

CONCLUSIOND6/MVP is a multidrug-resistant cell line possessing the basic characteristics of drug-resistance.

ATP-Binding Cassette, Sub-Family B, Member 1 ; analysis ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Cell Line, Tumor ; Cisplatin ; administration & dosage ; Drug Resistance, Multiple ; Flow Cytometry ; Glutathione ; analysis ; Glutathione Transferase ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Mitomycins ; administration & dosage ; Vinblastine ; administration & dosage

Purpose: To prevent the occurrence of secondary cataract after ECCE with PC-IOL implantation and evaluate the safety and effectiveness of Mitomycin C and 5-FU when used intraocular as an irrigating solution for its prevention in rabbits Materials and Methods: 15 rabbits were divided into 3 groups: Group A was given 5-50 mg/ml FU in 500 cc of BSS plus solution; Group B received MMC 0.2 percent mg/ml in 500 cc BSS; and Group C served as control with pure BSS. The study was done in accordance with the guidelines published by ARVO. The investigated drug solution was used as irrigating solution in cataract extraction performed in rabbits. Postoperatively, the rabbits examined under slit lamp from the 1st post op day and every 3 days thereafter. Their globes were enucleated 2 wks post op and 4 weeks post op, and sent to Pathology Laboratory for processing Results: Group A and Group B showed clear posterior capsule with no evidence of epithelial cell migration. Group C showed evidence of minimal to moderate epithelial cell migration and proliferation with fibrosis Conclusion: Mitomycin C (MMC) and 5-FU minimized and even prevented secondary cataract formation, with no effect on ocular structures when used as an irrigating solution.
Animal ; MITOMYCIN ; MITOMYCIN C ; MITOMYCINS

The luminous intensity of dark variant (S1) separated from photobacterium phosphoreum (A2) was 1/10,000 less than that of wild-type. Ethidium bromide (EB) (0.6 mg/L), Mytomycin C (MC, 0.05 mg/L), 2-amino fluorene (2-AF, 1.0 mg/L) all could strongly induce reversion mutation for S1 within 24 h and increase reversion ratio significantly. The results of experiments indicated that these revertants had stable genetic characteristic and the mutation may take place at gene levels. The mutagenesis to S1 caused by EB, MC and 2-AF was detected and it may be used as a new rapid, simple and sensitive method for gene toxicant monitoring.
Ethidium ; pharmacology ; toxicity ; Genetic Variation ; Luciferases ; biosynthesis ; Luminescent Measurements ; Mitomycins ; pharmacology ; toxicity ; Mutagens ; Mutation ; drug effects ; Photobacterium ; genetics ; Toxicology ; methods ; Transcription, Genetic ; drug effects