OBJECTIVETo approach the sequential release of antitumor drugs and promote the effect of chemotherapy.

METHODSAdriamycin (ADM) and carboplatin (CBP) were respectively microcapsulated with ethylcellulose by organic phase separation. The morphology and sizes of the microcapsules were observed and measured with light microscope and scanning electromicroscope. The contents and the release rates of ADM and CBP in microcapsules were measured with fluorescence spectrophotometer and high-efficiency phantom chromatic (HPC) spectrum respectively. The antitumor sensitivity test in vitro was devised with MTT assay.

RESULTSThe microcapsules of ADM and CBP were spherical in shape with diameters of 196 +/- 64 micro m and 214 +/- 48 micro m respectively. The contents of one-layer and two-layer CBP and ADM microcapsules were 51.4%, 35.7% and 39.8% respectively, with the release rates in vitro of 62.4%/day, 54.8%/day and 48.2%/8 h. The results of drug sensitivity test in vitro demonstrated that the current preparation has never affected the stability and antitumor activity of CBP and ADM.

CONCLUSIONMicrocapsules with different drugs and different thickness of material have different release rate. Combined arterial chemoembolization with different microcapsules could approach the sequential release and promote the effect of chemotherapy.

Antineoplastic Agents ; administration & dosage ; chemistry ; Carboplatin ; administration & dosage ; Cellulose ; administration & dosage ; analogs & derivatives ; Chemoembolization, Therapeutic ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Humans ; Tumor Cells, Cultured

In this study, the buffering capacity of amphiphilic pH-sensitivity copolymer poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEOZ-CHMC) was evaluated. The ammonium sulfate gradient method was used to prepare doxorubicin hydrochloride (DOX x HCl)-loaded liposomes (DOX-L), and then the post-insertion method was used to prepare PEOZ-CHMC and polyethylene glycol-distearoyl phosphatidyl ethanolamine (PEG-DSPE) modified DOX x HCl-loaded liposomes (PEOZ-DOX-L and PEG-DOX-L). The physico-chemical properties, in vitro drugs release behavior, cellular toxicity and intracellular delivery of liposomes were evaluated, separately. The results showed that PEOZ-CHMC has a satisfactory buffering capacity. The sephadex G-50 column centrifugation method and dynamic light scattering were used to determine the encapsulation efficiency (EE) and particle size of liposomes. The EE and particle size of DOX-L were (97.3 ± 1.4) % and 120 nm, respectively, and the addition of PEOZ-CHMC or PEG-DSPE had no influence on EE and particle size. The zeta potentials of three kinds of liposomes were negative. The release behavior of various DOX liposomes in vitro was investigated by dialysis method. In phosphate buffer solution (PBS) at pH 7.4, DOX x HCl was released from PEOZ-DOX-L in a sustained manner. While in PBS at pH 5.0, the release rate of DOX x HCl from PEOZ-DOX-L increased significantly, which suggested DOX x HCl was released from PEOZ-DOX-L in a pH-dependent manner. The intracellular delivery of liposomes was investigated by confocal laser scanning microscopy (CLSM). The CLSM images indicated that PEOZ-DOX-L showed efficient intracellular trafficking including endosomal escape and release DOX x HCl into nucleus, as well as the DOX-L and PEG-DOX-L had no this effect. The cytotoxicity of liposomes against MCF-7 cells was detected by using MTT assay. The results showed that antiproliferative effects of PEOZ-DOX-L enhanced with pH value decreased, whereas DOX-L and PEG-DOX-L did not have any significant difference in inhibitions at different pH conditions. Therefore, the problems of the inhibition of cellular uptake of liposomes and the failed endosomal escape of pH-sensitive liposomes by PEG chain can be overcome by the pH-sensitive liposomes constructed by PEOZ-CHMC.
Cell Nucleus ; Doxorubicin ; analogs & derivatives ; chemistry ; Endosomes ; Formates ; chemistry ; Humans ; Liposomes ; chemistry ; MCF-7 Cells ; Microscopy, Confocal ; Particle Size ; Phosphatidylethanolamines ; Polyamines ; chemistry ; Polyethylene Glycols ; chemistry

OBJECTIVETo explore the clinical efficacy and adverse effects of GHA(G-CSF+homoharringtonin+cytarabine C) and new combined priming chemotherapeutic regimens(GHAA/GHTA) with high efficacy and low toxicity for treatment of relapsed and refractory acute myeloid leukemia(AML) and myelodysplastic syndrome(MDS), and to analyze the relation of above-mentioned regimens with the expression of co-stimuolating molecule B7.1.

METHODSStandard GHA regimen consisting of G-CSF: 100 µg/(m2·d) subcutaneous injection, d 0-14; homoharringtonine: 1.0 mg/(m2·d) intravenous drip, d 1-14; Ara-C: 7.5-10 mg/(m2·d) subcutaneous injection, q12h, d 1-14. Other regimens as GHAA/GHTA were combined respectively with aclarubicin 20 mg d 1-7, or pirarubicin 20 mg d 1-7. 74 patients with refractory AML and 46 patients with MDS received these priming chemotherapy. The clinical efficacy and toxicity of above-mentioned priming chemotherapy were compared with 56 patients received routine chemotherapy (MA/TAE) respectively. And the expression of costimulatory molecule B7.1 on leukemia cells in patients of different subtypes was also detected by immunofluoressence and its relationship with clinical efficiency was explored.

RESULTS(1) for AML patients treated with priming chemotherapy, the total remission was 67.56% (CR 54.05%, PR 13.51%), which was much higher than that of patients received routine chemotherapy (P<0.05). The CR rate of AML-M2 and AML-M5 group (65.51%, 61.90% respectively) was much higher than that of AML other subtypes (P<0.05), and the longest remission period lasted for 4 years; (2) for MDS patients treated with priming chemotherapy, the total remission was 60.87% (CR 45.65%, PR 15.22%), which was also significantly higher than that of patients received routine chemotherapy (P<0.05); (3) in comparison with patients received standard GHA priming regimen, the remission rate of combined priming chemotherapy GHAA/GHTA was significantly higher both in patients with AML (85.18%) and MDS (81.25%); (4) side effects after chemotheropy, including granulocyte deficiency, thrombocytopenia and anemia etc, lasted for 7-14 days; the severe infection rate was 1%, there were no severe bleeding, digest effect and damage of function in heart, liver and kidney. The therapy-related mortality was zero. Compared with routine chemotherapy, priming chemotherapy proved significantly safe and effective (P<0.05); (5) the expression rate of costimulatory molecule B7.1 showed large variance between AML and MDS, it was higher in AML-M2/AML-M5 and lower in AML of other subtypes (P<0.05). In the same case, B7.1 expression was positive correlated with efficiency of priming chemotherapy.

CONCLUSIONGHA priming chemotherapy, as well as other combination regimens GHAA/GHTA, are well-tolerated, effective regimens for refractory AML and advanced MDS, without severe side effects and therapy-related mortality. Especially the new regimens GHAA/GHTA has better efficacy, which are proved more efficient than conventional GHA. Efficiency of priming chemotherapy is positive correlated with B7.1 expression, its mechanism will be further explored.

Aclarubicin ; analogs & derivatives ; Antineoplastic Combined Chemotherapy Protocols ; B7-1 Antigen ; Cohort Studies ; Cytarabine ; Doxorubicin ; analogs & derivatives ; Granulocyte Colony-Stimulating Factor ; Granulocytes ; Harringtonines ; Humans ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes ; Recurrence ; Thrombocytopenia

Adenocarcinoma ; therapy ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Squamous Cell ; therapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Hysterectomy ; Lymph Node Excision ; methods ; Middle Aged ; Uterine Cervical Neoplasms ; therapy

Telomeres are the ends of the linear chromosomes of eukaryotes and consist of tandem GT-rich repeats in telomere sequence i.e. 500-3000 repeats of 5'-TTAGGG-3' in human somatic cells, which are shortened gradually with age. The G-rich overhang of telomere sequence can adopt different intramolecular fold-backs and tetra-stranded DNA structures, in vitro, which inhibit telomerase activity. In this report, DNA binding agents to telomere sequence were studied novel therapeutic possibility to destabilize telomeric DNA sequences. Oligonucleotides containing the guanine repeats in human telomere sequence were synthesized and used for screening potential antitumor drugs. Telomeric DNA sequence was characterized using spectral measurements and CD spectroscopy. CD spectrum indicated that the double-stranded telomeric DNA is in a right-handed conformation. Polyacrylamide gel electrophoresis was performed for binding behaviors of antitumor compounds with telomeric DNA sequence. Drugs interacted with DNA sequence caused changes in the electrophoretic mobility and band intensity of the gels. Depending on the binding mode of the anticancer drugs, telomeric DNA sequence was differently recognized and the efficiency of cleavage of DNA varies in the bleomycin-treated samples under different conditions. DNA cleavage occurred at about 1% by the increments of 1 mM bleomycin-Fe(III). These results imply that the stability of human telomere sequence is important in conjunction with the cancer treatment and aging process.
Antineoplastic Agents/*metabolism ; Bleomycin/metabolism/pharmacology ; Circular Dichroism ; Comparative Study ; DNA/chemistry/drug effects/*metabolism ; DNA Damage ; Dactinomycin/metabolism ; Doxorubicin/*analogs & derivatives/metabolism ; Human ; Nogalamycin/metabolism ; Nucleic Acid Conformation ; *Repetitive Sequences, Nucleic Acid ; Telomere/drug effects/*genetics

OBJECTIVETo investigate the clinical value of neoadjuvant chemotherapy in the treatment of operable breast cancer.

METHODSA total of 120 patients with pathologically proven operable breast cancer were randomized into two groups to receive 2-4 cycles of neoadjuvant chemotherapy with docetaxel combined with pirarubicin (TThp) or docetaxel combined with epirubicin (TE). Operations were performed two weeks after the neoadjuvant chemotherapy. The short-term therapeutic effect, toxic reaction and the impact of neoadjuvant chemotherapy on the choice of surgical approaches were evaluated.

RESULTSThe total effective rate for the primary sites was 87.2% in these patients, and the rate of breast conservation significantly increased from 12.7% to 41.8% (P<0.05), with a tumor resection rate of 97.2%. The major adverse effects of the therapy included leukopenia, nausea, vomiting and alopecia.

CONCLUSIONNeoadjuvant chemotherapy can enhance the breast conservation rate, lower the clinical staging of the tumors and minimize the surgery area to improve the postoperative quality of life of the patients.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; surgery ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Epirubicin ; administration & dosage ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; methods ; Taxoids ; administration & dosage

BACKGROUNDThe aim of this research was to investigate the impact of post-transplantation adjuvant chemotherapy in the prevention of tumor recurrence and metastasis for hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation.

METHODSA total of 117 patients with HCC exceeding the Milan criteria who had undergone orthotopic liver transplantation (OLT) from August 2002 to February 2009 were enrolled and retrospectively analyzed. The patients were divided into four groups according to chemotherapy regimens and the impact of different chemotherapy regimens on survival, disease-free survival, and adverse effects were compared.

RESULTSOne year survival rates for the gemicitabine, conventional chemotherapy, oxaliplatin plus capecitabine and the best supportive care (BSC) group were 87.5%, 84.2%, 81.6%, and 67.5%. The 3-year survival rates were 48.1%, 25.9%, 31.6%, and 33.7%, respectively for the four groups. One year disease free survival rates for the four groups were 69.8%, 47.4%, 53.8%, and 45.7% respectively. And 3-year disease free survival rates were 43.2%, 23.7%, 23.6%, and 25.1% for the four groups. Stratification analysis showed that the gemcitabine regimen and conventional chemotherapy could significantly improve the survival rate and disease free survival rate for HCC patients who had major vascular invasion and/or microvascular invasion after liver transplantation compared with BSC group.

CONCLUSIONSFor HCC patients beyond Milan criteria, especially who had vascular invasion and/or micorvascular invasion, post-transplantation adjuvant chemotherapy can significantly improve survival. Gemcitabine is a proper regimen for postoperative adjuvant chemotherapy. Conventional chemotherapy can also benefit patients, but the adverse effects are not satisfactory.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; surgery ; Chemotherapy, Adjuvant ; methods ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Doxorubicin ; adverse effects ; therapeutic use ; Female ; Humans ; Liver Neoplasms ; drug therapy ; surgery ; Liver Transplantation ; Male

OBJECTIVETo investigate the impact of the drug resistance on the radioresistance in human pancreatic cancer cell lines.

METHODSThree drug resistant pancreatic cancer cell sublines induced by fluorouracil (5-FU), adriamycin (ADM) and gemcitabine respectively, SW1990/FU, SW1990/ADM and SW1990/Gz, were tested for the cell cycle and radio-sensitivity with flow cytometry and clonogenic assay.

RESULTSCompared with SW1990, the cell cycle assay indicated higher G(0)/G(1) period percentage in SW1990/FU and SW1990/Gz, but the G(2)/M period percentage decreased; SW1990/FU had the same while SW1990/Gz had lower S period percentage. SW1990/ADM almost had a similar cell cycle with SW1990. Clonogenic assay showed both SW1990/FU and SW1990/Gz had greater survival fraction (SF(2)) than SW1990, but SW1990/ADM had seemingly similar SF(2) as SW1990.

CONCLUSIONDrug resistant pancreatic cancer cell lines have reduced G(2)/M period percentage and increased radioresistance.

Antineoplastic Agents ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Fluorouracil ; pharmacology ; Humans ; Pancreatic Neoplasms ; pathology ; Radiation Tolerance ; drug effects

This study was aimed to compare the efficacy and adverse effects of PD (bortezomib + dexamethasone) and VAD (vincristine + adriamycin + dexamethasone) as regimens for treatment of multiple myeloma patients. 21 and 31 multiple myeloma patients were enrolled in the PD and VAD groups respectively which received 2 to 5 courses of treatments, and both clinical effects and adverse reactions were observed. In the all 52 patients, 48 were newly diagnosed and the other 4 patients had accepted 1 to 2 courses of M2 or MP treatment, but didn't get PR. In 52 patients, 4, 4, 8 and 5 patients accepted 2, 3, 4 and 5 courses of PD regimen respectively, while 6, 11, 12 and 2 patients accepted 2, 3, 4 and 5 courses of VAD regimen respectively. The results indicated that the rate of good efficacy (both CR and VGPR) in PD group was 57.1%, while the rate of good efficacy in VAD group was 16.1%, there was significant difference (p = 0.0052). The percentage of patients who got CR, VGPR and PR in PD and VAD groups were 95.2% and 74.2% respectively, there was no significant difference (p = 0.1108). The incidences of adverse effects in 2 groups were similar, which included hematological toxicity, liver and kidney functional lesion, peripheral neuropathy, infection, interstitial pneumonia. It is concluded that compared with conventional VAD chemotherapy, PD may improve CR and VGPR rate in newly diagnosed patients with multiple myeloma, meanwhile it does not bring about more and worse toxicity.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; analogs & derivatives ; therapeutic use ; Dexamethasone ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Treatment Outcome ; Vincristine ; therapeutic use

OBJECTIVETo investigate the value of in vivo proton magnetic resonance spectroscopy (MRS) in the assessment of hepatocellular carcinoma (HCC) and monitor its metabolic change shortly after transcatheter arterial chemoembolization (TACE).

METHODSIn this prospective study, 28 consecutive patients with large HCC (> or = 3 cm in diameter) confirmed by fine needle aspiration biopsy were recruited. The 1H MRS of all hepatic lesions and some uninvolved liver parenchyma were performed with 1. 5T whole body MR scanner. Among them, 15 cases were evaluated again about one week after TACE. The main metabolites such as choline and lipid before and after interventional therapy were measured to assess the early response of the tumor.

RESULTSThe technical success rate of 1H MRS in liver was high (33/41, 80%), closely related to breath motion, location of lesion, and size of voxel. In spectra, the choline compound peak of HCC elevated compared with uninvolved liver parenchyma. After TACE, both the amplitude and the area of choline resonance peak significantly descended (choline-to-lipid ratios from 0.352 +/- 0.080 to 0.167 +/- 0.030, P = 0.026; from 0.205 +/- 0.060 to 0.070 +/-0.020, P = 0.042, respectively); yet lipid resonance peak ascended.

CONCLUSIONSIn vivo 1H MRS is technically feasible for the evaluation of large focal hepatic lesions, however, the reproducibility and stability are not as good as routine MR scan. 1H MRS can monitor the early stage metabolic changes of HCC after TACE but limitation like quantification still exists.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Carcinoma, Hepatocellular ; diagnosis ; therapy ; Chemoembolization, Therapeutic ; Cisplatin ; administration & dosage ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Liver ; pathology ; Liver Neoplasms ; diagnosis ; therapy ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged