We performed a pathological study to identify the locus of production of protoporphyrin IX (PPIX) in human metastatic brain tumors. Patients with metastatic brain tumors (n = 11) received 1 g of 5-aminolevulinic acid (5-ALA) perorally 2 h before undergoing surgery. The target region was exposed to laser light with a peak wavelength of 405 +/- 1 nm and an output of 40 mW. Tissue samples from the tumor bulk and surrounding areas were examined by histological and fluorescence methods. Of the 11 tumors, 9 manifested PPIX fluorescence in the tumor bulk and peritumoral brain tissue. Our findings indicate that PPIX fluorescence can be observed in peritumoral edematous areas that are free of neoplastic cells, because PPIX produced by neoplastic cells leaks into the surrounding edematous area.
Lignin conversion to value-added products is one of the most attractive challenges to develop a complete system for lignocellulosic biomass utilization. The objective of this study was cis,cis-muconic acid (ccMA) production from lignin, in particular, without sugar. Here, two bacterial strains were developed that can synthesize ccMA from lignin without using glucose. One is applicable to softwood lignin (mostly guaiacyllignin), and the other is applicable to hardwood lignin (mostly syringyl-and guaiacyl-lignins). The engineered Pseudomonas putida KT2440-based strain produced ccMA from a mixture of vanillic acid (a guaiacyl-lignin model) and 4-hydroxybenzoic acid (a p-hydroxyphenyl-lignin model) with ∼20% yield (mol/mol) without supplement of glucose. The dissolved oxygen concentration of 5−10% was effective to produce ccMA with a higher yield. The Sphingobium sp. SYK-6-based strain produced ccMA from vanillic acid with ∼45% yield (mol/mol) while growing on syringic acid (a syringyl-lignin model). These ccMAproducing strains can synthesize ccMA from lignin extracts of Japanese cedar and birch without using glucose.
The response of nonfluorescing infiltrating tumors that had been exposed to 5-aminolevulinic acid and irradiated using a laser at a wavelength of 405 nm was analyzed intraoperatively using spectroscopy. Histological analyses demonstrated that neoplastic cells were present in the tissue region that displayed a peak at 636 nm, whereas no neoplastic cells were present in the region that exhibited only the excitation light peak. The authors conclude that the intraoperative use of laser spectroscopy can allow the diagnosis of infiltrating tumor and the detection of boundaries of the infiltrate when standard fluorescence techniques fail.
The aim of this study is to review the different histological and clinical characteristics of glioblastoma multiforme (GBM) with and without cysts (cystic and noncystic GBM, respectively). Thirty-seven GBM were collected; these were tumors for which more than 80% of the volume was surgically resected, including a portion of the peripheral parenchyma of the brain. Based on preoperative magnetic resonance (MR) imaging studies, tumors were tentatively classified as cystic GBM if more than 50% of their volume appeared to be liquid; otherwise, they were considered to be noncystic GBM. Tumor volumes were estimated from contrast-enhanced T1-weighted MR images. Edema was deduced from the maximum width of contrast-enhanced edges. Peritumoral pathological analysis showed distinct margins, indicating little or no infiltration of tumor cells into white matter. Five cases were classified as cystic and 32 were noncystic GBMs. There was a statistically significant difference in age (Mann-Whitney U test; P < 0.05) between the patients with cystic tumors (median, 44 years; range, 26-59 years) and those with noncystic tumors (median, 54 years; range, 26-81 years). Four of the cystic tumors and eight of the noncystic tumors were more than 5 cm in maximum diameter. Cystic GBMs had a well-defined tumor interface and less than 2-cm-thick peritumoral edema compared to the noncystic GBMs (Fisher's exact test; P < 0.05). For patients with cystic GBMs, median survival time after surgery was 19.8 months and the 2-year survival rate was 50%. Patients with noncystic GBMs had a median survival time of 12.8 months and a 2-year survival rate of only 17%. Median time to tumor recurrence was 13.3 months for patients harboring cystic GBMs and 8.5 months for those with noncystic GBMs (log-rank test; P < 0.05). Thus, the prognosis for cystic GBM was significantly better than that for noncystic GBM, possibly because cystic GBMs showed comparatively little infiltration of the peritumoral brain parenchyma.
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