Mechanistic, Energetic and Structural Aspects of the Adsorption of Carmustine on the Functionalized Carbon Nanotubes

Using density functional theory, noncovalent interactions and two mechanisms of covalent functionalization of drug carmustine with functionalized carbon nanotube（CNT） have been investigated. Quantum molecular descriptors of noncovalent configurations were studied. It was specified that binding of drug carmustine with functionalized CNT is thermodynamically suitable. NTCOOH and NTCOCl can bond to the NH group of carmustine through OH（COOH mechanism） and Cl（COCl mechanism） groups, respectively. The activation energies, activation enthalpies and activation Gibbs free energies of two pathways were calculated and compared with each other. The activation parameters related to COOH mechanism are higher than those related to COCl mechanism, and therefore COCl mechanism is suitable for covalent functionalization. COOH functionalized CNT（NTCOOH） has more binding energy than COCl functionalized CNT（NTCOCl） and can act as a favorable system for carmustine drug delivery within biological and chemical systems（noncovalent）. These results could be generalized to other similar drugs.

Apoptosis of Glioblastoma U251 Cells Induced by Carmustine Combined All-trans Retinoic Acid via Regulating Cyclin E and p27kip 1

The effect and mechanism of carmustine（BCNU） combined with all-trans retinoic acid（ATRA） on the apoptosis of human glioblastoma U251 cells were investigated by means of 3-（4,5-dimethylthiazol-2-yl）-2,5-diphe- nyltetrazolium bromide（MTT） assay, flow cytometry, reverse transcription-polymerase chain reaction（RT-PCR） and Western blot analysis. The results show that BCNU or ATRA shows time- and dose-dependent inhibition effects on human glioblastoma U251 cells and the combination of BCNU with ATRA shows an synergistic inhibition effect on human glioblastoma U251 cells, and the combined BCNU and ATRA can significantly inhibit the proliferation of human glioblastoma U251 cells, and induce the apoptosis of them, making the cells arrest in the stage of G1 phase, the stage of S and G2 phases decline, the rate of the apoptosis of human glioblastoma U251 cells increase, the corresponding mRNA expression of cyclin E and cyclin-dependent kinase 2（CDK2） downregulated and the correspon- ding mRNA expression of p27kip 1 unregulated. In addition, the combined BCNU and ATRA reduced the protein expression of nuclear factor kappa B（NF-κB）. Taken together, these results suggest that the treatment of human glioblastoma U251 cells with a combination application of ATRA and BCNU can exert synergistic effect, the course of this kind of combination chemotherapy may likely be associated with multiple molecular mechanisms for apoptosis, furthermore, the cyclin E and p27kip 1 should be considered as novel targets for controlling the growth of glioblastoma cells.

Malignant Cerebral Edema Secondary to Gliadel Wafers in the Early Postsurgical Period

High grade gliomas are the commonest intrinsic brain tumours and account for more average years of life lost than all the common cancers. It has become the commonest cause of cancer death in men under the age of 45 and women under the age of 35. Although surgical resection can greatly reduce tumour bulk, complete excision is virtually impossible due to the infiltrative nature of these tumours. In an attempt to treat the infiltrating tumour cells, there has been much interest in using local therapies inserted at the time of surgery. The authors report a case of fatal cerebral edema unresponsive to aggressive medical and surgical assessment that finally evolved to premature death in the early postsurgical period, after the craniotomy and implantation of Gliadel wafers. They note that high doses of dexamethasone were insufficient to prevent cerebral edema and death. A search for corticosteroid use and dosing for patients treated with Gliadel wafers in the published literature revealed no recommendations on the doses of steroids to be administered. In our opinion this is a very important issue and maybe the key point for the treatment of this disease, and may need to be addressed with treatment guidelines in the near future in order to ensure better results on patient’s survival. Prior to this case review there had been two similar report but a later presentation. So we think that this is the first case report of acute fulminant cerebral edema secondary to gliadel wafers in the early period.