Purpose: Anaplastic gliomas constitute a heterogeneous group of tumors with different therapeutic responses to adjuvant chemotherapy with alkylating agents. O 6 -Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, is one of the implicated factors in glioma chemoresistance.The prognostic value of MGMTremains controversial due in part to the fact that previous published studies included heterogeneous groups of patients with different tumor grades. The aim of this study was to evaluate the prognostic significance of MGMT in patients with anaplastic glioma. Experimental Design: Ninety-three patients with anaplastic glioma were analyzed for MGMT protein expression by immunohistochemistry. In addition, for those patients from whom a good yield of DNA was obtained (n = 40), MGMT promoter methylation profile was analyzed by methylation-specific PCR. MGMT prognostic significance was evaluated together with other well-known prognostic factors. Results: Fifty-one tumors (54.8%) showed nuclear staining of MGMT. There was a trend towards longer overall survival for those patients with negative MGMT immunostaining (hazard ratio,1.66; P = 0.066). In a secondary analysis including those patients who actually received chemotherapy (n = 72), the absence of MGMTexpression was independently associated with better survival (hazard ratio, 2.12; P = 0.027). MGMT promoter methylation was observed in 50% of the analyzed tumors. No statistical correlation between MGMT expression and MGMT promoter hypermethylation was observed. Conclusions: Unlike previous studies, we did not find a correlation between MGMT promoter methylation and survival. However, we observed a correlation between MGMT protein expression and survival in those patients who received chemotherapy thus suggesting that the absence of MGMTexpression is a positive predictive marker in patients with anaplastic glioma.Anaplastic gliomas (WHO grade 3) show a wide variability of clinical outcome. Despite optimal treatment, mainly consisting of gross total resection followed by radiotherapy and chemotherapy with alkylating agents (1), therapeutic response and survival times vary considerably. This fact suggests that a large number of factors, including patient, tumor, and treatment characteristics, may influence the outcome (2 -4).Alkylating agents cause cell death by forming cross-links between adjacent strands of DNA due to alkylation of the O 6 position of guanine. The cellular DNA repair protein O 6 -methylguanine-DNA methyltransferase (MGMT) inhibits the cross-linking of double-stranded DNA by removing alkylating lesions (5 -7). A direct relationship between MGMT activity and resistance to alkylating nitrosoureas and methylating agents (i.e., ionizing radiations) has been well documented in cell lines and xenografts derived from a variety of human tumors, including gliomas (8). Moreover, depletion of MGMT activity with the substrate analogue inhibitor O 6

In many chemical and allied manufacturing systems, product quality is controlled based on postprocess quality inspection on sampled final products. Statistical analysis of the identified quality problems is then utilized to improve process operation, and thus the quality of succeeding products. Although this type of reactive quality control (QC) is necessary, it is not only inefficient because it “waits for” the occurrence of product quality problems, but also ineffective due to usually a significant time lag from problem identification, through solution derivation, to action taking. Furthermore, the derived solutions for problem solving are mostly heuristic in nature. This paper introduces a proactive product QC approach, which is established based on the concept of integrated product and process (IPP) control. Aiming at simultaneous dynamic control of process operation and product manufacturing, this approach ensures all‐time systematic control of both process performance and product quality. From the view point of both process control and product control, it is shown that IPP control can be realized by resorting to a well known scheme, cascade control. The IPP control problem for Single‐Input‐Single‐Output systems can be formulated rigorously, and the control laws can be identified readily. A synthesized IPP control system can effectively reject disturbances on the process and the product, and have excellent set‐point tracking capability, regardless of the type of interaction between the process and the product. The efficacy and attractiveness of the IPP control system design methodology are demonstrated through two types of case studies. © 2007 American Institute of Chemical Engineers AIChE J, 2007

Meningiomas represent the second most common central nervous system neoplasms in adults and account for 26% of all primary brain tumors. Although most are benign, between 5% and 15% of meningiomas are atypical (grade II) whereas 1-2% are anaplastic meningiomas (grade III). Although histological grade is the most relevant prognostic factor, there are some unusual cases in which establishing a diagnosis of high-grade meningioma following 2000 World Health Organization (WHO) histological criteria is extremely difficult. Therefore, the aim of the present study was to evaluate the predictive value of Ki-67 labeling index and its contribution to current WHO classification in predicting tumor recurrence and overall survival in patients with high-grade meningiomas. A total of 28 patients (with 16 atypical meningiomas and 12 anaplastic meningiomas) were evaluated for demographic, clinical, radiological and therapeutic variables, and for Ki-67 immunohistochemistry. Median Ki-67 labeling index in the whole series was 7.0 (0.5-31.5) with no differences with respect to the histological grade (P = 0.87). In the univariate analysis, Ki-67 labeling index and postoperative Karnofsky performance status were identified as significant prognostic factors of tumor recurrence and overall survival. The multivariate analysis demonstrated that Ki-67 labeling index is the only independent predictor of both tumor recurrence and overall survival. More importantly, this predictive value was maintained in both patients with atypical and patients with anaplastic meningioma.

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