TMZ-SLN were prepared by emulsification-low temperature solidification method with stearic acid. The formulation and the preparation conditions were optimized by orthogonal experiments using entrapment efficiency as the evaluation index. The morphology was detected by transmission electron microscope. The Zeta potentials and the particle size distribution were evaluated by Laser Doppler Anemometry. The entrapment efficiencies and the drug release characteristics in vitro were assessed. The result showed that TMZ-SLN were concinnous and spherical in shape. The mean diameter (d(av) ) was 65.0 +/- 6.2 nm and the Zeta potential was -37.2 mV. The average entrapment efficiency was 58.9% +/- 1.21 %. The drug release behavior in vitro conformed to Higuchi Equation. The formation of a new material phase was testified by analysis of differential scanning calorimetry.
Antineoplastic Agents, Alkylating ; administration & dosage ; chemistry ; Dacarbazine ; administration & dosage ; analogs & derivatives ; chemistry ; Drug Carriers ; chemistry ; Lipids ; chemistry ; Nanoparticles ; chemistry ; Particle Size ; Stearic Acids ; chemistry

OBJECTIVETo compare the therapeutic efficacy of two regimens of postoperative radiotherapy with concurrent chemotherapy using temozolomide (TMZ) and teniposide (VM-26) plus semustine (Me-CCNU) in adult patients with grade III-IV cerebral gliomas.

METHODSNinety-six adult postoperative patients with grade III-IV cerebral gliomas were randomized into two groups (n=48) to receive 60 Gy radiotherapy with concurrent TMZ treatment (TMZ-RT group) and radiotherapy with VM-26 plus Me-CCNU treatments (VM-RT group). The adverse effects of marrow depression, gastrointestinal toxicity and acute radiation-induced brain injury were observed. The immediate effect and survival outcome of the patients were compared between the two groups.

RESULTSNo adverse effects beyond grade III were observed in the two groups. TMZ-RT group showed a significantly lower incidence of grade I-II adverse effects than VM-RT group (P<0.05). The median survival time and 1-, 2-, and 3-year survival rates of the patients in TMZ-RT group were 28 months, 72.9%, 54.2% and 31.3%, respectively, showing significant differences from those in VM-RT group (16 months, 62.5%, 33.3% and 16.7%, respectively, P<0.05).

CONCLUSIONRadiotherapy with concurrent TMZ chemotherapy is an effective regimen with mild toxicities for treatment of adult malignant cerebral glioma.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Brain Neoplasms ; therapy ; Chemoradiotherapy ; methods ; Dacarbazine ; administration & dosage ; analogs & derivatives ; Female ; Glioma ; therapy ; Humans ; Male ; Middle Aged ; Postoperative Period ; Semustine ; administration & dosage ; Teniposide ; administration & dosage ; Young Adult

OBJECTIVETo study the therapeutic effect of intranasal administration of temozolomide (TMZ) for brain-targeting delivery in a rat model bearing orthotopic C6 glioma xenografts.

METHODSForty Wistar rat bearing brain C6 glioma xenograft were randomly divided into 4 groups and treated with physiological saline solution or with TMZ by intravenous injection, gavage or intranasal administration. The tumor size, rat survival time and pathological changes were observed in each group.

RESULTSMagnetic resonance imaging showed a significantly reduced volume of glioma in intranasal TMZ group compared with that in the control, intraveneous TMZ injection group and TMZ gavage groups (12.45∓2.49 mm(3) vs 60.16∓4.12, 33.17∓3.56, and 35.16∓4.36 mm(3), respectively, P<0.05). The median survival time of the C6 glioma-bearing rats was also significantly longer in intranasal TMZ group than in the other 3 groups (31.0 days vs 20, 19, and 21.5 days, respectively, P<0.05). In the glioma xenografts, PCNA expression was the lowest and tumor cell apoptosis rate the highest in intranasal TMZ group.

CONCLUSIONIntranasal TMZ administration can suppress the growth of C6 glioma in rats and may serve as an effective strategy for glioma treatment.

Administration, Intranasal ; Animals ; Antineoplastic Agents, Alkylating ; administration & dosage ; Apoptosis ; Brain Neoplasms ; drug therapy ; Cell Line, Tumor ; Dacarbazine ; administration & dosage ; analogs & derivatives ; Drug Delivery Systems ; Glioma ; drug therapy ; Magnetic Resonance Imaging ; Neoplasm Transplantation ; Rats ; Rats, Wistar

INTRODUCTIONThe use of adjuvant temozolomide (TMZ) in patients managed with surgery and adjuvant radiation therapy (RT) for glioblastoma multiforme (GBM) has been demonstrated to improve median and 2-year survival in a recent large international multicentre study. To confirm this result in routine clinical practice, an audit of the management and outcome of patients with GBM at The Cancer Institute Radiation Oncology was performed.

MATERIALS AND METHODSAll patients with GBM managed radically at The Cancer Institute Radiation Oncology from May 2002 to 2006 were entered into a prospective database. Patient, tumour and treatment factors were analysed for association with the outcome of median survival (MS). Survival was calculated using the Kaplan-Meier technique and correlation was assessed using Cox proportional hazards regression.

RESULTSForty-one patients with GBM were managed with radical intent over the 4- year period. The median age was 54 years and 66% were Eastern Cooperative Oncology Group (ECOG) 0-1 performance status. Macroscopic, subtotal and biopsy alone procedures were performed in 61%, 29% and 10% of patients, respectively. The median time from surgery to RT was 26 days. Adjuvant TMZ was used in 44% of patients (n = 18). The MS of the total group was 13.6 months, with a 24% 2-year overall survival. The use of TMZ was associated with improved MS (19.6 versus 12.8 months; P = 0.035) and improved 2-year survival (43% versus 0%). A requirement of dexamethasone dose greater than 4 mg at the end of RT (P = 0.012) was associated with worse survival, but there was no association of MS with age, ECOG, tumour size or extent of surgery.

CONCLUSIONThe median and 2-year survival outcomes are comparable to the results of the European Multicentre Study and justify the continued use of TMZ in routine clinical practice.

Antineoplastic Agents, Alkylating ; administration & dosage ; therapeutic use ; Brain Neoplasms ; drug therapy ; radiotherapy ; surgery ; Chemotherapy, Adjuvant ; Dacarbazine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Female ; Glioblastoma ; drug therapy ; radiotherapy ; surgery ; Humans ; Male ; Middle Aged ; Prospective Studies ; Singapore ; Survival Analysis

OBJECTIVETo evaluate the effects and the toxicity of the protocol of CDV combined with CiE as pre-operative chemotherapy in childhood stage IV neuroblastoma.

METHODSThe clinical data of 27 children aged from 1.2 to 8 years with neuroblastoma in stage IV was retrospectively studied. The primary sites of the diseases were abdomen (n = 21), posterior mediastinum (n = 4) and pelvic cavity (n = 2). Twenty three patients had bone marrow metastasis. Twelve patients had bone metastasis. All patients were treated with the CDV protocol (cyclophosphamide + doxorubicin + vincristine) for 3 cycles and the CiE protocol (cisplatin + etoposide) for 2 cycles. Neuroblastoma therapeutic response evaluation criterion and common terminology criteria for adverse events of National Cancer Institute were used to evaluate effects and chemotherapy related toxicity.

RESULTSAll patients received the pre-operative chemotherapy. The overall response rate was 82%. After chemotherapy, 24 patients received operations. Total resection of primary tumor was found in 14 patients (58%) and part resection in 10 patients (42%). The most common chemotherapy related toxicity was bone marrow suppression: grade IV suppression of neutrophils (n = 27), reduction in hemoglobin (III grade, n = 7; IV grade, n = 20) and reduction in platelet (III grade, n = 2; IV grade, n = 25). Infection was found in all patients and was controlled with antibiotics. I or II grade lesions of digestive, liver and kidney were found and could be recovered after therapy. Grade I neurotoxicity occurred in 2 patients (7%). The heart function damage was not found in any of patients.

CONCLUSIONSThe protocol of CDV combined with CiE as pre-operative chemotherapy might be effective in children with stage IV neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Cisplatin ; administration & dosage ; adverse effects ; Cyclophosphamide ; administration & dosage ; adverse effects ; Dacarbazine ; administration & dosage ; adverse effects ; Etoposide ; administration & dosage ; adverse effects ; Female ; Humans ; Infant ; Male ; Neuroblastoma ; drug therapy ; Retrospective Studies ; Vincristine ; administration & dosage ; adverse effects

OBJECTIVETo evaluate whether involved-field (IF) radiotherapy is equally effective and less toxic in comparison with extended-field (EF) radiotherapy for patients with early-stage Hodgkin's disease (HD) who received combined modality therapy.

METHODSThe data of 88 early-stage HD patients treated with combined modality therapy were retrospectively reviewed. According to Ann Arbor classification, 12 patients (13.7%) had stage IA disease, 56 stage IIA (63.6%), and 20 IIB (22.7%). Forty-two (47.7%) patients underwent involved field radiotherapy (IF group), whereas the other 46 (52.3%) received extended field radiotherapy (EF group).

RESULTSOf 6 patients who developed recurrence, 3 (7.1%) were in IF group and the other 3 (6.5%) in EF group. Only one patient's recurrence developed inside the radiation field in EF group. Three patients (7.2%) in IF group and 9 (19.5%) in EF group had WHO grade 1 and 2 leukopenia (P = 0.089). Overall survival rate at 1-, 2- and 3-year was 100.0%, 97.1%, and 97.1% in IF group versus 100.0%, 100%, and 95.8% in EF group (P = 0.86), respectively. Freedom from progression survival rate at 1-, 2- and 3-year was 97.6%, 94.8%, and 91.7% in IF group versus 97.8%, 93.2%, and 93.2% in EF group (P = 0.65), respectively.

CONCLUSIONCompared with extended-field radiotherapy, involved-field radiotherapy is equally effective and less toxic for patient with early-stage Hodgkin's disease treated with combined modality therapy.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Bleomycin ; administration & dosage ; Combined Modality Therapy ; Dacarbazine ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Hodgkin Disease ; drug therapy ; pathology ; radiotherapy ; Humans ; Leukopenia ; etiology ; Lymphatic Irradiation ; adverse effects ; methods ; Lymphatic Metastasis ; Male ; Mechlorethamine ; administration & dosage ; Middle Aged ; Neoplasm Staging ; Prednisone ; administration & dosage ; Procarbazine ; administration & dosage ; Recurrence ; Retrospective Studies ; Survival Rate ; Vinblastine ; administration & dosage ; Vincristine ; administration & dosage

This retrospective analysis compared standard regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with the dose-dense ABVD regimen (ABVD-21) in terms of efficacy and toxicity. Patients who had early-stage unfavorable or advanced Hodgkin's lymphoma (HL) according to German Hodgkin Study Group criteria from March 1999 to February 2011 were analyzed for treatment response, long-term survival and hematological toxicity. There were 85 patients in the ABVD-21 group and 118 patients in the ABVD group respectively. The complete remission rates after completion of treatment were 92.9% and 90.7% for ABVD-21 and ABVD, respectively. During a median follow-up period of 62 months, no significant difference was found in projected 10-year progression-free survival (PFS) and overall survival (OS) rates (84.7% and 94.1% respectively for ABVD-21; 81.4% and 91.5% for ABVD). Subgroup analyses showed that ABVD-21 was significantly better than ABVD for patients with IPS≥3 in terms of PFS and OS rates. Grade 3 to 4 leukopenia (51.8% vs. 28.8%, P=0.001) and neutropenia (57.6% vs. 39.0%, P=0.009) were more common with ABVD-21. We were led to conclude that dose-dense ABVD did not result in better tumor control and overall survival than did ABVD for early-stage unfavorable HL. However, patients at high risk, for example, with IPS≥3, may benefit from dose-dense ABVD.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Bleomycin ; administration & dosage ; Combined Modality Therapy ; methods ; Dacarbazine ; administration & dosage ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Doxorubicin ; administration & dosage ; Female ; Hodgkin Disease ; drug therapy ; pathology ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prednisone ; Retrospective Studies ; Vinblastine ; administration & dosage

OBJECTIVETo report a case of interdigitating dendritic cell sarcoma (IDCS).

PATIENT MATERIALThe patient was a 41-year-old man with a lymph node bulging in the left neck. Laboratory examination of peripheral blood and bone marrow was abnormal. The diagnosis of IDCS was made by immunohistochemistry and electron microscopy. Treatment of this patient with ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine) resulted in obvious improvement, but did not control the tumor infiltration.

CONCLUSIONIDCS has no distinctive clinical or pathohistological characteristics. Immunohistochemistry and electron microscopy are crucial in distinguishing it from other histiocytic/dendritic cell neoplasms. IDCS displays an aggressive behaviour, and the responses to chemotherapy are variable.

Adult ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; administration & dosage ; Dacarbazine ; administration & dosage ; Dendritic Cell Sarcoma, Interdigitating ; diagnosis ; drug therapy ; metabolism ; Doxorubicin ; administration & dosage ; Humans ; Immunohistochemistry ; Male ; S100 Proteins ; analysis ; Treatment Outcome ; Vinblastine ; administration & dosage

OBJECTIVETo investigate the new mechanism of temozolomide (TMZ) induced anti-tumor effects on glioblastoma cells in vitro.

METHODSGrade IV glioma cell lines SHG44 and U251 cells were treated with TMZ. MTT test was used to determine the proliferation of glioma cells. Hoechst 33342 assay was used to detect apoptosis in the tumor cells. The cell cycle progression was assessed by flow cytometry. The level of intracellular reactive oxygen species (ROS) was detected using DCFH-DA probe. real-time PCR assay and Western blotting were used to analyze the expression of SIRT1.

RESULTSTreatment with TMZ for 72 hours inhibited cell proliferation (P < 0.05) and induced apoptosis in the two cell lines in a concentration-dependent manner. TMZ at 100 µmol/L significantly resulted in G(2)/M cell cycle arrest (66.16%, 69.65%), and triggered a robust increase in cell apoptosis [(33.4 ± 1.8)% and (26.8 ± 3.2)%]. TMZ remarkably increased reactive oxygen species (ROS) production (P < 0.05), indicating an overexpression of signal for SIRT1 activation.

CONCLUSIONSOur findings suggest that temozolomide mediates anti-tumor effects on glioma cells in vitro via ROS-dependent SIRT1 signaling pathway, therefore, provide a theoretical evidence for a new approach to improve the treatment of glioma in future.

Antineoplastic Agents, Alkylating ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dacarbazine ; administration & dosage ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; Glioblastoma ; pathology ; Humans ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; drug effects ; Sirtuin 1 ; metabolism

Aged ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; therapeutic use ; Dacarbazine ; therapeutic use ; Doxorubicin ; therapeutic use ; Hodgkin Disease ; drug therapy ; pathology ; Humans ; Leukemia, Hairy Cell ; drug therapy ; pathology ; surgery ; Male ; Mitoxantrone ; administration & dosage ; Neoplasms, Multiple Primary ; drug therapy ; pathology ; surgery ; Rituximab ; Splenectomy ; Vidarabine ; administration & dosage ; analogs & derivatives ; Vinblastine ; therapeutic use