AIMTo elucidate the metabolic pathway of glufosfamide in rats.

METHODSIn this study, a liquid chromatography-tandem mass spectrometric method was developed and applied to characterize the metabolites of glufosfamide in rat urine, after an i.v. administration of 50 mg x kg(-1). The analysis was performed under two ionization modes in two different chromatographic systems, separately. To make sure that the compounds detected in rat urine were metabolites or degradation products, the stability of glufosfamide, isophosphoramide mustard (M1), and the degradation products of M1 in urine were investigated.

RESULTSIn positive ionization mode, besides glufosfamide, two metabolites, isophosphoramide mustard and monoaziridinyl derivative of isophosphoramide mustard, were detected. In negative ionization mode, only glufosfamide itself was detected, while derivatives of isophosphoramide mustard have no response in such condition.

CONCLUSIONGlufosfamide was mainly unchanged excreted in urine, and two metabolites were detected as isophosphoramide mustard and monoaziridinyl derivative of isophosphoramide mustard.

Animals ; Antineoplastic Agents, Alkylating ; metabolism ; urine ; Gas Chromatography-Mass Spectrometry ; Glucose ; analogs & derivatives ; Ifosfamide ; analogs & derivatives ; Injections, Intravenous ; Male ; Phosphoramide Mustards ; metabolism ; urine ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effect of lentivirus-mediated Bcl-2 gene transfection in protecting human primary ovarian granulosa cells against phosphoramide mustard (PM)-induced apoptosis.

METHODSGranulosa cells were isolated from the follicle fluid of women undergoing in vitro fertilization and embryo transfer. The lentiviral vectors carrying Bcl-2 gene (pGC-FU-Bcl-2) and enhanced green fluorescence protein (pGC-FU-EGFP) were constructed and packaged into high-titer lentiviruses. The resulting recombinant lentivirus carrying Bcl-2 and EGFP genes or the empty vector were used to infect the primary human ovarian granulosa cells, followed by addition of PM in the cell culture, with untreated granulosa cells as the control. The cell apoptosis was detected by Annexin V and Hochst 33258 staining, and the expression of Bcl-2 protein was assessed using Western blotting.

RESULTSThe control granulosa cells showed an apoptotic rate of (1.93±0.28)%. The cells infected with pGC-FU-Bcl-2 prior to PM exposure had a apoptotic rate of (6.99±10.55)%, significantly higher than that of the control cells, but significantly lower than that of the cells with PM exposure only and those infected with the empty vector before PM exposure (P<0.05). The expression of Bcl-2 was the highest in the cells infected with pGC-FU-Bcl-2 prior to PM exposure (P<0.05).

CONCLUSIONLentivirus-mediated Bcl-2 gene transfection can protect human ovarian granulosa cells against PM-induced apoptosis by upregulating Bcl-2 protein expression.

Adult ; Apoptosis ; drug effects ; Female ; Genes, bcl-2 ; Genetic Vectors ; Granulosa Cells ; drug effects ; Humans ; Lentivirus ; genetics ; Phosphoramide Mustards ; Transfection

Hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain chemotherapeutic drugs. Hypoxic regions in tumors, therefore, represent attractive targets for cancer therapy. To date, five distinct classes of bioreactive prodrugs have been developed to target hypoxic cells in solid tumors. These hypoxia-activated prodrugs, including nitro compounds, N-oxides, quinones, and metal complexes, generally share a common mechanism of activation whereby they are reduced by intracellular oxidoreductases in an oxygen-sensitive manner to form cytotoxins. Several examples including PR-104, TH-302, and EO9 are currently undergoing phase II and phase III clinical evaluation. In this review, we discuss the nature of tumor hypoxia as a therapeutic target, focusing on the development of bioreductive prodrugs. We also describe the current knowledge of how each prodrug class is activated and detail the clinical progress of leading examples.
Anthraquinones ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Aziridines ; chemistry ; pharmacology ; Cell Hypoxia ; drug effects ; Humans ; Indolequinones ; chemistry ; pharmacology ; Molecular Structure ; NAD(P)H Dehydrogenase (Quinone) ; chemistry ; pharmacology ; Neoplasms ; drug therapy ; pathology ; Nitrogen Mustard Compounds ; chemistry ; pharmacology ; Nitroimidazoles ; chemistry ; pharmacology ; Phosphoramide Mustards ; chemistry ; pharmacology ; Prodrugs ; chemistry ; pharmacology ; Triazines ; chemistry ; pharmacology

No abstract available.
Ifosfamide*

No abstract available.
Ifosfamide*

Extraskeletal Ewing's sarcoma has been recognized as being histologically indistinguishable from Ewing's sarcoma of bone. Histopathologically, Ewing's sarcoma consists of solid sheets of small round cells with vesicular nuclei and scant cytoplasm, and the cells are arranged in irregular masses separated by strands of fibrous tissue. Extraskeletal Ewing's sarcoma may arise virtually anywhere, but it is most common in the deep soft tissues of the extremities. We report here on a 27-year-old woman with cutaneous extraskeletal Ewing's sarcoma. She presented with a subcutaneous tumor of the right upper arm, and this was without osseous involvement. The patient underwent wide local excision and she received chemotherapy with vincristine, cyclophosphamide, etoposide and ifosfamide. There has been no evidence of recurrence or metastasis during 16 months of follow up.
Adult ; Arm ; Cyclophosphamide ; Cytoplasm ; Etoposide ; Extremities ; Female ; Follow-Up Studies ; Humans ; Ifosfamide ; Neoplasm Metastasis ; Recurrence ; Sarcoma, Ewing ; Skin ; Vincristine

Neuroblastoma is the most common intraabdominal malignant tumor of childhood, with 40% arising from the adrenal gland. Bilateral adrenal involvement from synchronous development or metastatic spread of tumor is rarely seen in children with neuroblastoma. The patient was born with a spontaneous vaginal delivery. Birth weight was 3,200 g. Fetal ultrasonography showed a left adrenal cystic mass. At two weeks of age, she was admitted due to a massive abdominal distension and tachypnea. Percutaneous ultrasonography guided biopsy of the left adrenal mass was performed. The result of the biopsy was neuroblastoma. Vincristine and cyclophosphamide were administerd intravenously and 450 cGy of irradiation was added. Left adrenalectomy was accomplished and postoperative course was uneventful. The patient received cancer chemotherapy with a combination of carboplatin, ifosfamide and VP-16 and is now being followed up for three months. We have experienced a case of congenital bilateral neuroblastoma and report the case with brief review of related literatures.
Adrenal Glands ; Adrenalectomy ; Biopsy ; Birth Weight ; Carboplatin ; Child ; Cyclophosphamide ; Drug Therapy ; Etoposide ; Humans ; Ifosfamide ; Neuroblastoma* ; Tachypnea ; Ultrasonography ; Ultrasonography, Prenatal ; Vincristine

PURPOSE: To establish the feasibility of high dose ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by autologous stem cell transplantation (ASCT) in patients with high-risk or metastatic breast cancer. MATERIALS AND METHODS: High-risk breast cancer is defined as 10 or more involved axillary lymph nodes (n=3) or stage III (n=2). Patients with metastatic cancer have relapsed diseases after curative resection (n=10) or initially metastatic lesion (n=1). Colony stimulating factor with either cyclophosphamide or combination chemotherapy was administered to mobilize the stem cells. High dose chemotherapy consisted of ifosfamide 16 g/m2, carboplatin 1.8 g/m2, and etoposide 0.75 g/m2 (dose I) and later modified to ifosfamide 12 g/m2, carboplatin 1.35 g/m2, and etoposide 1.2 g/m2 (dose II). RESULTS: The median duration of grunulocyte nadir (<500/ microliter) was 11 (10~17) days and platelet transfusion dependency (<20,000/ microliter) was 11 (7~53) days in 14 patients who achieved engraftment. One out of 5 patients with high-risk breast cancer relapsed after high dose therapy. Two patients remain disease-free at 18th and 40th months. Two among the 4 patients treated with dose I died due to treatment-related complications. The responses of metastatic diseases to ICE chemotherapy were 1 continuing CR, 1 CR, 1 PR, 4 SD and 3 PD in 10 evaluable patients. CONCLUSION: High dose ICE chemotherapy, especially dose II and ASCT were feasible in high-risk or metastatic breast cancer.
Breast Neoplasms* ; Breast* ; Carboplatin* ; Colony-Stimulating Factors ; Cyclophosphamide ; Drug Therapy* ; Drug Therapy, Combination ; Etoposide* ; Humans ; Ice ; Ifosfamide* ; Lymph Nodes ; Platelet Transfusion ; Stem Cell Transplantation* ; Stem Cells*

Congenital cystic adenomatoid malformation(CCAM) is one of the most common congenital lung lesions. Clinical manifestations that show are neonatal respiratory distress, recurrent respiratory infection, pneumothorax, and hemothorax. But, there are patients who are asymptomatic until mid-childhood. The treatment of asymptomatic CCAM is controversial. There is a possibility to resolve it spontaneously, but late complications such as recurrent pulmonary infection, pneumothorax, hemothorax, and cancer, which includes bronchoalveolar carcinoma and rhabdomyocarcinoma, pleuropulmonary blastoma still remain. Some investigators advocate routine surgery for all cases of CCAM that are apparent at birth. A previously healthy 16-months-old girl who had suffered from a cough for 2 weeks was transferred to Asan Medical Center with CCAM. Due to a chest CT and fever, we first thought that she had CCAM with infection. After we treated her with antibiotics for one week, we performed surgery to confirm the diagnosis and to prevent further complication. But by surgical wedge resection, a pleuropulmonary blastoma was found. There were no evidence of metastasis and adjacent involvement. She started her chemotherapy with vincristine, actinomycin D and cyclophosphamide, and is now continuing maintenance chemotherapy with etoposide, vincristine, and Ifosfamide. We report pleuropulmonary blastoma that presented as CCAM. So we recommend surgical resection in asymptomatic CCAM to confirm the diagnosis and to prevent its malignant transformation, even not accompanied by symptoms.
Anti-Bacterial Agents ; Child ; Chungcheongnam-do ; Cough ; Cyclophosphamide ; Cystic Adenomatoid Malformation of Lung, Congenital* ; Dactinomycin ; Diagnosis ; Drug Therapy ; Etoposide ; Female ; Fever ; Hemothorax ; Humans ; Ifosfamide ; Lung ; Maintenance Chemotherapy ; Neoplasm Metastasis ; Parturition ; Pneumothorax ; Research Personnel ; Tomography, X-Ray Computed ; Vincristine

Desmoplastic small round cell tumor is a very rare malignancy. We report the case of a 26-year-old woman who suffered from dyspepsia and abdominal pain for 2 months. We performed an endoscopic biopsy of the duodenal mass and diagnosed her disease as desmoplastic small round cell tumor using immunohistochemical staining, fluorescence in situ hybridization, and reverse transcriptase polymerase chain reaction. Because the mass invaded the pancreas and superior mesenteric vein as well as duodenum and the disease was disseminated to liver and peritoneum, she received palliative chemotherapy using vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. The maximal response to chemotherapy was stable disease. The patient expired 9 months after diagnosis.
Abdominal Pain ; Adult ; Biopsy ; Cyclophosphamide ; Desmoplastic Small Round Cell Tumor ; Doxorubicin ; Duodenum ; Dyspepsia ; Etoposide ; Female ; Fluorescence ; Glycogen Storage Disease Type VI ; Humans ; Ifosfamide ; In Situ Hybridization ; Liver ; Mesenteric Veins ; Pancreas ; Peritoneum ; Reverse Transcriptase Polymerase Chain Reaction ; Vincristine