A sub-pathway based method to identify candidate drugs for glioblastomas.

Glioblastomas (GBM) are the most common primary malignant brain tumors with a high invasiveness and resistance to radiation and other treatments. The need for the development of new therapeutic agents for GBM is urgent. Here, we aimed to explore the metabolic mechanism of GBM and identified potential novel drugs for GBM by a sub-pathway-based method. By using the GBM microarray data from "The Cancer Genome Atlas" database, we first identified the 274 differentially expressed genes between GBM and normal samples. Then, we identified 18 significant enriched metabolic sub-pathways that may involve in the development of GBM. Finally, by an integrated analysis of GBM-involved sub-pathways and drug-affected sub-pathways, we identified 66 novel small-molecular drugs capable to target the GBM-involved sub-pathways. Our method could not only identify existing drug (paclitaxel) for GBM, but also predict potentially novel agents (pergolide) that might have therapeutic effects. We also experimentally verified that pergolide could induce GBM cell death. These candidate small-molecular drugs identified by our approach may provide insights into a novel therapy approach for GBM.

WITHDRAWN: Discrimination of Parkinson-associated LRRK2 alleles by introduction of a single nucleotide mismatch into siRNA.

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[Comparison of MGMT and ERCC2 expression in temozolomide for the treatment of malignant glioma drug resistance and their genetic relationship].

OBJECTIVE: To study the impact of two human glioma tissue resistance genes MGMT and ERCC(2) on the temozolomide-based treatment of malignant gliomas and detect the relationship of their expressions. METHODS: A total of 58 malignant glioma patients aged 19 - 68 years old receiving a chemotherapy of temozolomide were followed up and classified as non-sensitive group (n = 30) and sensitive group (n = 28). Immunohistochemistry was employed to detect the expression rates of MGMT and ERCC(2). And the correlation between the expressions of two genes was analyzed by immunohistochemistry and RT-PCR (reverse transcription-polymerase chain reaction). RESULTS: The expression rates of MGMT and ERCC(2) were 10.71% and 3.57% in the sensitive group and 63.33% and 56.67% in the non-sensitive group. It had an obvious correlation with the expressions of MEGT and ERCC(2) through an analysis of immunohistochemistry and RT-PCR (both P < 0.01). CONCLUSION: The expressions of MGMT and ERCC(2) in the sensitive group are markedly lower than those in the non-sensitive group. The expression of two genes may be related to tumor prognosis. Maybe these two genes have an intrinsic link between their expressions. Both participate in the repair of cellular DNA damage and the formation of tumor drug resistance. And the prognosis has obvious relevance.

Gamma Knife irradiation-induced histopathological changes in the trigeminal nerves of rhesus monkeys.

OBJECT: The authors' goal was to observe histopathological changes in the trigeminal nerve after Gamma Knife surgery (GKS) in rhesus monkeys, and to investigate the radiobiological mechanism of GKS for primary trigeminal neuralgia. The nerve length-dosage effect of irradiation is also discussed. METHODS: One of 5 rhesus monkeys randomly served as a control, and the other 4 monkeys were randomly administered a target radiation dose of 60, 70, 80, or 100 Gy (a different dose in each animal). The size of the collimator was 4 mm, and the target point was the trigeminal nerve root. In each experimental monkey, one side was exposed to single-target-point irradiation, and the contralateral side was exposed to double-target-point irradiation. After 6 months, the trigeminal nerve root was examined using light microscopy, transmission electron microscopy, and immunohistochemistry. RESULTS: At each radiation dose, the damage to the nerve tissue by single-target-point irradiation was identical to that caused by double-target-point irradiation. In the trigeminal nerve tissues of the monkeys irradiated with 60 and 70 Gy, there was limited nerve demyelination and degeneration, fragmentation, or loss of axons. In the trigeminal nerve tissue of the monkey irradiated with 80 Gy, the nerve tissue showed a disordered structure. In the trigeminal nerve tissue of the monkey irradiated with 100 Gy, there was severe derangement in the structure of the nerve tissue, and extensive demyelination, fragmentation, and loss of axons. CONCLUSIONS: The target doses of 60 and 70 Gy have very little impact on the structure of the trigeminal nerve. Irradiation at 80 Gy can cause partial degeneration and loss of axons and demyelination. A 100-Gy dose can cause some necrosis of neurons. Comparing the single-target-point with the double-target-point irradiation, the extent of damage to the nerve tissue is identical, and no difference in the nerve length-dosage effect was found.

Effects of photodynamic therapy on the ultrastructure of glioma cells.

OBJECTIVE: To study the change in ultrastructure of C6 glioma cells after photodynamic therapy (PDT), to compare morphological differences in necrosis and apoptosis before and after PDT treatment, and to evaluate the effect of photodynamic therapy on the blood brain tumor barrier (BTB) of C6 glioma. METHODS: The model was produced by transplanting C6 glioma cells cultured in vitro using Peterson method into the caudate nuclei of Wister rats. The experiment group received PDT for two weeks after the operation. The sub-cellular structure, blood-brain-barrier (BBB) and BTB in both groups were observed under electron microscope. RESULTS: Apoptosis in different phases and necrosis could be observed in some C6 glioma cells. Swelling occurred on the ultrastructure of cellular organs such as mitochondria and endoplasmic reticulum in most of the cells. Damage to the BTB, reduction of the number of cellular organs in endothelial cells of the capillary blood vessels, stretch of the tight junction, and enlargement of the gaps between endothelial cells were also seen in the experiment group. Meanwhile, limited impact on the normal sub-cellular structures and BBB was observed. CONCLUSION: PDT could induce apoptosis and necrosis of C6 glioma cells due to the damage to the ultrastructure of mitochondria and endoplasmic reticulum. The weakened function of C6 glioma BTB initiated by PDT makes it possible to perform a combined therapy of PDT and chemotherapy for glioma.

Superior orbital rim approach for anterior communicating artery aneurysms: a surgical series of 27 patients.

There are debatable claims in the optimal approach for clipping of the anterior communicating artery (AcomA) aneurysm. The authors invented the superior orbital rim approach (SORA) as an alternative and minimally invasive approach for the treatment of AcomA aneurysm. The authors reviewed retrospectively all the medical records of 27 patients of subarachnoid hemorrhage due to ruptured AcomA aneurysm. who were admitted to Kosin University Gospel Hospital for last 2 yr. Fourteen women (51.9%) and 13 men (48.1%) were from 29 to 79 yr in age. The mean aneurysm size was 6.2 mm ranging from 4 to 12 mm. A favorable Glasgow outcome scale (GOS) of 4 or 5 was achieved in 92.6%, a GOS score of 3 in 3.7%, and 1 death (GOS 1) occurred in 3.7% of the patients. During the follow-up between 4 and 28 months (mean, 17.5 months) after the surgery, the prognosis of the patients and the cosmetic results were favorable compared with conventional approach. We became to believe that it was an alternative, effective and minimally invasive approach to the surgical treatment of AcomA aneurysm.