Animals ; Antineoplastic Agents, Alkylating/pharmacology* ; Breast Neoplasms/drug therapy* ; Cell Line ; Cell Line, Tumor ; Cyclophosphamide/pharmacology* ; Ginkgo biloba/chemistry* ; Mammary Neoplasms, Animal/drug therapy* ; Mice ; Plant Extracts/administration & dosage*

Epithelial ovarian cancer (OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients will develop recurrent ovarian cancer (ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the cellular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies.
Antineoplastic Agents, Alkylating ; therapeutic use ; Clinical Trials as Topic ; DNA Damage ; Dioxoles ; administration & dosage ; pharmacology ; therapeutic use ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Neoplasm Recurrence, Local ; drug therapy ; Neoplasms, Glandular and Epithelial ; drug therapy ; Ovarian Neoplasms ; drug therapy ; Polyethylene Glycols ; administration & dosage ; Tetrahydroisoquinolines ; administration & dosage ; pharmacology ; therapeutic use ; Tumor Microenvironment

This study was performed to validate the effectiveness and safety of concurrent chemoradiotherapy and adjuvant therapy with temozolomide for newly diagnosed glioblastoma multiforme as a standard treatment protocol. Between 2004 and 2011, patients newly diagnosed with glioblastoma who were treated with temozolomide during concurrent chemoradiotherapy and adjuvant chemotherapy were included from a single institution and analyzed retrospectively. The primary endpoint was overall survival, and the secondary endpoints were progression-free survival, response, and safety. A total of 71 patients were enrolled in this study. The response rate was 41% (29/71), and the tumor control rate was 80% (57/71). In the 67 patients who completed the concurrent chemoradiotherapy with temozolomide, the median overall survival was 19 months and the 1- and 2-yr overall survival rates were 78.3% and 41.7%, respectively. The median progression free survival was 9 months, and the 1- and 2-yr progression free survival rates were 33.8% and 14.3%, respectively. The mean duration of survival after progression of disease in salvage treatment group was 11.9 (1.3-53.2) months. Concurrent chemoradiotherapy with temozolomide resulted in grade 3 or 4 hematologic toxic effects in 2.8% of the patients. The current protocol of temozolomide during and after radiation therapy is both effective and safe and is still appropriate as the standard protocol for treatment of glioblastoma. An active salvage treatment might be required for a better prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Alkylating/administration & dosage ; Brain Neoplasms/diagnosis/*mortality/*therapy ; Chemoradiotherapy, Adjuvant/methods/mortality ; Comorbidity ; Dacarbazine/administration & dosage/*analogs & derivatives ; Female ; Glioblastoma/diagnosis/*mortality/*therapy ; Hematologic Diseases/*mortality ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prevalence ; Radiotherapy, Conformal/mortality ; Republic of Korea/epidemiology ; Risk Factors ; Survival Rate ; Treatment Outcome ; 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

Antineoplastic Agents, Alkylating ; administration & dosage ; Child ; Humans ; Intravitreal Injections ; Male ; Melphalan ; administration & dosage ; Neoplasm Seeding ; Retinal Neoplasms ; drug therapy ; pathology ; Retinoblastoma ; drug therapy ; pathology ; Vitreous Body ; pathology

OBJECTIVETo investigate the safety of treatment with ophthalmic artery cannulation for intra-arterial chemotherapy (IAC) for children with intraocular retinoblastoma (RB).

METHODIn the RB Treatment Center of General Hospital of Armed Police Forces between January 2009 and September 2011, 42 patients who were diagnosed intraocular RB and treated with ophthalmic artery cannulation for IAC, 8 patients were treated 1 circle, 31 patients were treated 2 circles and 3 patients were treated 3 circles (total, 96 times). Each month had IAC once. The ophthalmic and the whole body evaluations were performed during IAC and after IAC for each circle, the blood cell count, alanine aminotransferase (ALT), serum creatinine (Scr), CK-MB content before and after IAC for 1 circle, 2 circles and 3 circles were determined.

RESULT(1) In 52 eyes of 42 patients, 44 eyes (84.6%) were in remission. (2) Successful IAC was achieved in all cases, no severe side effects occurred during IAC. (3) The main ophthalmic complications were eyelid edema and blepharoptosis after IAC, the incidence for 1 circle was 18% (2/11) and 9% (1/11); for 2 circles was 29% (11/38) and 21% (8/38); for 3 circles was all 100% (3/3). The rare complications were vitreous hemorrhage and heterotropia, the incidence was all 2% (1/42). The incidence of eyelid edema and blepharoptosis had no significant differences for 1 circle IAC compared with 2 circles (P > 0.05); the incidence of eyelid edema and blepharoptosis had significant differences for 3 circles IAC compared with 2 circles and 1 circle (P < 0.01). (4) No fever, septicemia and other systemic toxic effects occurred. (5) ALT of 19% patients (8/42) elevated temporarily and CK-MB of 24% patients (10/42) increased. The blood cell counts, ALT, Scr, and CK-MB content before IAC had no significant differences compared with that at 24 h after IAC for 1 circle, 2 circles and 3 circles (P > 0.05).

CONCLUSIONOphthalmic artery cannulation for IAC is a safe and effective method in treating intraocular stage retinoblastoma.

Antineoplastic Agents, Alkylating ; administration & dosage ; therapeutic use ; Catheterization ; methods ; Child, Preschool ; Female ; Humans ; Infant ; Infusions, Intra-Arterial ; Liver Function Tests ; Male ; Melphalan ; administration & dosage ; therapeutic use ; Neoplasm Staging ; Ophthalmic Artery ; Postoperative Complications ; epidemiology ; Retinal Neoplasms ; drug therapy ; pathology ; Retinoblastoma ; drug therapy ; pathology ; Retrospective Studies ; Treatment Outcome

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

No abstract available.
Angiogenesis Inhibitors/administration & dosage/*therapeutic use ; Antineoplastic Agents, Alkylating/administration & dosage/*therapeutic use ; Humans ; Melphalan/administration & dosage/*therapeutic use ; Multiple Myeloma/*drug therapy ; Prednisone/therapeutic use ; Thalidomide/administration & dosage/*therapeutic use ; Treatment Outcome

Adult ; Aged ; Agranulocytosis ; chemically induced ; Antineoplastic Agents, Alkylating ; administration & dosage ; adverse effects ; therapeutic use ; Brain Neoplasms ; secondary ; therapy ; Carcinoma, Non-Small-Cell Lung ; pathology ; Chemoradiotherapy ; Dacarbazine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Female ; Humans ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Remission Induction ; Survival Rate ; Vomiting ; chemically induced

OBJECTIVENimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas.

METHODSThe patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred. Individualized chemotherapy was administered based on O(6)-methylguanine-DNA methyltransferase (MGMT) expression and previous chemotherapy responses in combined with nimotuzumab.

RESULTSFourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 (median 7.5 times). Combined chemotherapy regimens included: continuous 21-day temozolomide (10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin (1 case), and teniposide plus nimustine (1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively. Disease control rate (PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI: 0.7 - 7.3) and PFS at 6 months was 30.6%. The most common toxicities include grade I-II neutropenia (2 cases), thrombocytopenia (2 cases), lymphopenia (1 case), nausea and vomitting (3 case) and asymptomatic transaminase increase (1 case). One patient developed grade IV neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash.

CONCLUSIONSNimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.

Adolescent ; Adult ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Agents, Alkylating ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Astrocytoma ; drug therapy ; Child ; Cisplatin ; administration & dosage ; adverse effects ; Dacarbazine ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Glioblastoma ; drug therapy ; Glioma ; drug therapy ; Humans ; Infusions, Intravenous ; Male ; Nausea ; chemically induced ; Neutropenia ; chemically induced ; Nimustine ; administration & dosage ; adverse effects ; Teniposide ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced ; Young Adult