Objective Delayed cerebral vasospasm has long been recognized as an important cause of poor outcome after an otherwise successful treatment of a ruptured intracranial aneurysm, but it remains a pathophysiological enigma despite intensive research for more than half a century. Method Summarized in this review are highlights of research from North America, Europe and Asia reflecting recent advances in the understanding of delayed ischemic deficit. Result It will focus on current accepted mechanisms and on new frontiers in vasospasm research. Conclusion A key issue is the recognition of events other than arterial narrowing such as early brain injury and cortical spreading depression and of their contribution to overall mortality and morbidity.
Cancer cells show constitutive upregulation of glycolysis, and the concentration of lactate thus produced correlates with prognosis. Here, we examined whether lactate concentration and lactate transporter expression are related to migration and invasion activity. We found that the expression of the monocarboxylate transporters MCT1 and MCT4, but not MCT5, in human lung cancer cell lines was significantly correlated with invasiveness. To clarify the effects of MCT1 and MCT4 expression on invasion, we performed migration and invasion assays after transfection with siRNA specific for MCT1 or MCT4. Knockdown of MCT1 or MCT4 did not influence cell migration but reduced invasion; this was also observed for knockdown of the lactate transporter-associated protein basigin. We also demonstrated that both expression and activity of MMP9 and MMP2 were not correlated with invasion activity and not regulated by MCT1, MCT4 and basigin. Furthermore, the addition of lactate did not increase migration and invasion activity, but low concentration of 4,4¢-diisothiocyanatostilbene-2,2¢-disulphonic acid (DIDS), a general anion channel blocker, as well as other MCT inhibitors quercetin and simvastatin, inhibited cell invasion without influencing migration activity and the cellular expression of MCT1 and MCT4. This is the first report suggesting that lactate transporters are involved in human cancer cell invasiveness. As such, these proteins may be promising targets for the prevention of cancer invasion and metastasis. (Cancer Sci 2011; 102: 1007-1013 M onocarboxylates, such as lactate and pyruvate, play a central role in cellular metabolism and metabolic communication between tissues.(1) In cancer cells, a steady source of metabolic energy is required to continue the uncontrolled growth and proliferation of these cells.(2) Most cancer cells rely on a high rate of aerobic glycolysis, a phenomenon termed ''the Warburg effect'', to obtain sufficient ATP in a hypoxic microenvironment.(3) As a result of the Warburg effect, lactate is abundantly synthesized from pyruvate, (4) but lactic acid induces cellular acidosis, which triggers apoptosis. To avoid apoptosis, cancer cells must transport the lactate out of the cell. On the other hand, lactate is not just a waste product: it was recently identified as a major energy fuel in tumors.(4) Lactate is transported by monocarboxylate anion transporters (MCT; also called the solute carrier family 16 [SLC16]).(1) It is known that MCT4 (SLC16A3) transports lactate out of the cell (5) and MCT1 (SLC16A1) regulates the entry of lactate into tumor cells. (4) Migration and invasion are two of the most important aspects of the malignant cancer phenotype; if they could be inhibited, the cancer prognosis would improve. Hypoxia and acidosis create a nurturing environment for tumor progression and the evolution of metastases, and invasiveness is abetted by acidosis, the result of shifting to an anaerobic glycolytic metabolism.(6) Basigin (BSG; also called EMMPRIN and CD147) is a multifunctional glycoprotein ...
Background and Purpose-The role of interleukin (IL)-1 remains unknown in early brain injury (EBI) after subarachnoid hemorrhage (SAH), although IL-1 has been repeatedly reported to increase in the brain and cerebrospinal fluid. The aim of this study is to examine the effects of IL-1 inactivation on EBI after SAH in mice. Methods-The endovascular perforation model of SAH was produced and 112 mice were assigned to sham, SAHϩ vehicle, and SAHϩ N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-CMK, 6 and 10 mg/kg) groups. Ac-YVAD-CMK, a selective inhibitor of IL-1 converting enzyme, or vehicle was administered intraperitoneally 1 hour post-SAH. EBI was assessed in terms of mortality within 24 hours, neurological scores, brain water content at 24 and 72 hours, Evans blue dye extravasation and Western blot for IL-1, c-Jun N-Terminal kinase (JNK), matrix metalloproteinase (MMP)-9, and zonula occludens (ZO)-1 at 24 hours after SAH. Results-High-dose (10 mg/kg) but not low-dose (6 mg/kg) treatment group significantly improved neurological scores, mortality, brain water content, and Evans blue dye extravasation compared with the vehicle group. Although both dosages of Ac-YVAD-CMK attenuated the mature IL-1 induction, only high-dose treatment group significantly inhibited the phosphorylation of JNK, MMP-9 induction, and ZO-1 degradation. Conclusion-IL-1
Programmed cell death protein 4 (PDCD4) has recently been shown to be involved in both transcription and translation, and to regulate cell growth. However, the mechanisms underlying PDCD4 function are not well understood. In this study, we show that PDCD4 interacts directly with the transcription factor Twist1 and leads to reduced cell growth through the down-regulation of the Twist1 target gene Y-box binding protein-1 (YB-1). PDCD4 interacts with the DNA binding domain of Twist1, inhibiting its DNA binding ability and YB-1 expression. Immunohistochemical analysis showed that an inverse correlation between nuclear PDCD4 and YB-1 expression levels was observed in 37 clinical prostate cancer specimens. Growth suppression by PDCD4 expression was completely recovered by either Twist1 or YB-1 expression. Moreover, PDCD4-overexpressing cells are sensitive to cisplatin and paclitaxel but not to etoposide or 5-fluorouracil. In summary, PDCD4 negatively regulates YB-1 expression via its interaction with Twist1 and is involved in cancer cell growth and chemoresistance. [Cancer Res 2009;69(7):3148-56]
BACKGROUND AND PURPOSE:Preoperative evaluation of pituitary macroadenoma tumor consistency is important for neurosurgery. Thus, we aimed to retrospectively assess the role of contrast-enhanced FIESTA in predicting the tumor consistency of pituitary macroadenomas.
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