First-principles studies on two-dimensional B3O3 adsorbent as a potential drug delivery platform for TEPA anticancer drug.

The remarkable properties of pristine B3O3 nanosheet as a nanocarrier for adsorption and desorption of TEPA anticancer drug for designing potential drug delivery platform were investigated using periodic DFT calculations. We studied the adsorption energy of all stable complexes formed between the drug molecule and B3O3 in gas and aqueous phases along with electronic structure analysis of complexes. Different adsorption configurations were studied for drug/B3O3 complexes, including the interaction of the C atom of the triangular ring, O atom in the TEPA drug with the B atom in B3O3, and indirect drug interaction the middle of the R1 ring cavity of the B3O3 nanosheet. The take-up of TEPA prompts a substantial change of 68.13% in the band gap (Eg) of the B3O3 nanosheet in the most stable complex. The present study results affirmed the application of B3O3 nanosheet as a potential vehicle for TEPA drugs in the treatment of cancerous tissues.

Combined-modality treatment of leptomeningeal gliomatosis.

OBJECTIVE: Leptomeningeal gliomatosis (LG) is a clinically uncommon metastatic complication of high-grade gliomas (HGGs), for which there is no consensus regarding treatment. The goal of this study was to determine the toxicity and response rate of combined-modality therapy for the treatment of patients with HGGs and LG. METHODS: Eighteen patients (10 men and 8 women), ranging in age from 28 to 70 years (median, 38 yr), with clinically, neuroradiologically, and cytologically documented LG received intraventricular chemotherapy. Tumor histological types included anaplastic astrocytoma (10 patients) and glioblastoma multiforme (8 patients). Concurrent radiotherapy (11 patients) or systemic chemotherapy (13 patients) was administered as clinically indicated. Methotrexate was administered initially, and treatment was continued for patients in stable or improved condition. For patients who experienced progression, cytosine arabinoside was administered as second-line therapy, followed by N,N',N"-triethylenethiophosphoramide as third-line therapy. Patients underwent bimonthly evaluations with cerebrospinal fluid cytological assessments and neurological examinations. RESULTS: Four to 13 cycles (median, 5 cycles) of intraventricular chemotherapy were administered. Toxicity included aseptic meningitis (12 patients), radiation-induced enteritis (2 patients), and myelosuppression of Grade II or less (4 patients). No patient required hospitalization or transfusions, and no treatment-related deaths occurred. Partial responses were observed for 6 patients, and 12 patients demonstrated progressive disease. The median duration of response was 3 months (range, 2-4 mo). Survival times after the initiation of intraventricular chemotherapy ranged from 2 to 8 months (median, 3.5 mo). The cause of death was progressive LG (14 patients), combined LG and HGG (3 patients), and HGG (1 patient). CONCLUSION: For this small cohort of patients, combined-modality therapy had modest toxicity but minimal palliative efficacy. For the majority of patients with LG, supportive care should be considered.

Pharmacokinetics of thio-TEPA and TEPA in the conventional dose-range and its correlation to myelosuppressive effects.

A total of 13 patients with ovarian cancer were studied during the initial two courses of i.v. thio-TEPA treatment they underwent after primary surgery. Following an increase in the dose from 60 to 80 mg for the second course, no sign of saturation of thio-TEPA elimination processes or of formation of the metabolite TEPA occurred, indicating dose-independent pharmacokinetics. Myelosuppression after courses was registered by serial measurements of platelets and leukocytes. The time to platelet nadir was quite uniformly 3 weeks and tended to be longer than that of leukocytes, which averaged 2 weeks but showed greater interindividual variation. Linear regression analyses of pharmacokinetic parameters versus myelosuppression revealed statistically significant correlations between thio-TEPA pharmacokinetics and the percentage of reductions in leukocytes and platelets at their mean nadirs. In contrast, no such correlation could be demonstrated for TEPA despite its greater exposure to the body in terms of AUC. We advocate further investigation of this pharmacokinetic-pharmacodynamic relationship so as to establish individualized dosing of thio-TEPA.

Evaluation of spin labeled TEPA and CCNU analogs against osteosarcoma and MNU-induced mammary carcinoma of the SD-rat.

The effectiveness to reduce tumor growth by 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6-tetramethylpiperidinyl)- 1-nitrosourea (SLCNU) and N,N,N,'N'- bis(1,2-ethanediyl)-N"-(1-oxyl-2,2,6,6-tetramethyl- 2-piperidinylaminocarbonyl)-phosphoric triamide (SLDU) was studied in osteosarcoma and MNU-induced mammary carcinoma in the SD-rat. Both compounds elicited neither an inhibitory effect on these tumors nor an increase in the mean/median life span as compared to the control group.

[Endolymphatic use of solutions of alkylating substances in a mixture with iodolipol in malignant neoplasms]. / Ob éndolimfaticheskom primenenii rastvorov alkiliruiushchikh veshchestv v smesi s iodolipolom pri zlokachestvennykh novoobrazovaniiakh.

The results of endolymphatic chemotherapy and lymphography in 57 cases of different malignant neoplasms in the lymphatic system are presented. Procedures for making alcohol-oil solution of benzo-TEP, ether-oil solution of tio-TEP and alcohol-oil emulsion of cyclophosphamide are discussed and the clinical evaluation of the results of their application is given. The therapeutic effect of endolymphatic infusions of the mixtures of alkylating agents and iodolipol was assessed on the basis of clinical, histological and radiological examination of malignant lesions of lymph nodes. It is shown that the efficacy of endolymphatic chemotherapy is determined by the susceptibility of neoplasms to antitumor drugs and the availability of the latter at lymph node metastases.

Fertility regulation in male rats and hamsters with alkylating agents.

A single intratesticular injection of TEPA or Thio-TEPA induced a period of infertility lasting 1-2 months. Restoration of fertility was characterized by a reduction of the litter size resulting from the first inpregnation post-treatment. There was no evidence of tissue pathogenesis 6-12 months after treatment.

[Dependence of the cytogenetic effect on TEPA concentration in human lymphocyte culture]. / Zavisimost' tsitogeneticheskogo deistviia ot kontsentratsii TEPA v kul'ture limfotsitov cheloveka.

The authors studied the cytogenetic action of TEPA (tris/2-methyl-1-azyridinyl) on the human lymphocyte culture. It was shown that the increase of the mutagen concentration from 0.125 to 16.0 microgram/ml the cytogenetic effect for the portion of the aberrant metaphases rose from 6.0 to 61.0%, and for the total number of ruptures - from 7.96 to 116.3. A method of finding the least effective concentration of the substance under study in comparison with control is suggested; for TEPA it constitutes 0.120 microgram/ml. The percentage of chromatide ruptures remained constant in using different TEPA concentration and constitutes 51.72%. Cell distribution of chromosome ruptures is satisfactorily described by geometrical distribution.