The MGMT level in tumor tissue specimens may be a predictive marker of survival in patients with malignant astrocytoma that is independent of other previously described prognostic variables.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl adducts from DNA and may be important in tumor resistance to alkylation chemotherapy. MGMT was visualized in human cells and tumor tissues with monoclonal antibodies against MGMT and immunofluorescence microscopy, and fluorescent signals were quantified by digital image analysis. MGMT was found both in the cytoplasm and the nucleus, and in either locale the protein reacts with alkylated DNA bases and becomes inactivated and lost from the cell. Cell lines in culture and xenografts showed a broad normal distribution of nuclear MGMT levels, but human brain tumors often showed a skewed distribution, with a significant fraction of cells with high levels of MGMT. O(6)-Benzylguanine, a suicide substrate inactivator for MGMT activity, reduced MGMT in human cells and in a mouse xenograft to levels undetectable by antibody assay 1 h post-treatment. In melanoma specimens taken from a patient 3 h post-treatment with temozolomide, MGMT levels were reduced by 70%. This quantitative immunofluorescence assay can be used to monitor MGMT and it depletion in human tumors to improve the use of alkylating agents in cancer chemotherapy.

Regression testing is frequently performed in a time constrained environment. This paper explains how 0/1 knapsack solvers (e.g., greedy, dynamic programming, and the core algorithm) can identify a test suite reordering that rapidly covers the test requirements and always terminates within a specified testing time limit. We conducted experiments that reveal fundamental trade-offs in the (i) time and space costs that are associated with creating a reordered test suite and (ii) quality of the resulting prioritization. We find knapsack-based prioritizers that ignore the overlap in test case coverage incur a low time overhead and a moderate to high space overhead while creating prioritizations exhibiting a minor to modest decrease in effectiveness. We also find that the most sophisticated 0/1 knapsack solvers do not always identify the most effective prioritization, suggesting that overlap-aware prioritizers with a higher time overhead are useful in certain testing contexts.

PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy.