Intratumoral injections of recombinant heat shock protein (Hsp)70 were explored for feasibility in patients with brain tumors. Patients aged 4.5–14 years with untreated newly diagnosed tumors (n=12) were enrolled. After tumor resection, five injections of recombinant Hsp70 (total 2.5 mg) were administered into the resection cavity through a catheter. Before administration of Hsp70 and after the last injection, specific immune responses to the autologous tumor lysate were evaluated using the delayed-type hypersensitivity test. Further, peripheral blood was monitored to identify possible changes in lymphocyte subpopulations, cytokine levels, and the cytolytic activity of natural killer cells. The follow-up period in this trial was 12 months. Intratumoral injections of Hsp70 were well tolerated by patients. One patient had a complete clinical response documented by radiologic findings and one patient had a partial response. A positive delayed-type hypersensitivity test was observed in three patients. In peripheral blood, there was a shift from cytokines provided by Th2 cells toward cytokines of a Th1-cell-mediated response. These data corresponded to changes in lymphocyte subpopulations. Immunosuppressive T-regulatory cell levels were also reduced after injection of Hsp70, as well as production of interleukin-10. The cytolytic activity of natural killer cells was unchanged. The present study demonstrates the feasibility of intratumoral delivery of recombinant Hsp70 in patients with cancer. Further randomized clinical trials are recommended to assess the optimum dose of the chaperone, the treatment schedule, and clinical efficacy.
Objective: This study is to analyze fluorescence sensitivity in the diagnosis of brain and spinal cord tumors.Material and methods: The authors conducted a multicenter retrospective analysis of data on 653 cases in 641 patients: 553 of them had brain tumors and 88 spinal cord tumors. Brain tumor resection was performed in 523 patients, of whom 484 were adults and 39 children. The analyzed series was presented by 320 gliomas, 101 meningiomas, and 72 metastases. A stereotactic biopsy was performed in 20 patients and endoscopic surgery in 10 patients. In all cases, 20 mg/kg of 5–Aminolaevulinic acid was administered orally 2-h before surgery. All surgical interventions were performed with a microscope BLUE 400 to visualize fluorescence, while endoscopic surgery—with an endoscope equipped with a fluorescent module. Fluorescence spectroscopy was conducted in 20 cases of stereotactic biopsies and in 88 cases of spinal cord tumors.Results: Among adult brain tumors operated by microsurgical techniques, meningiomas showed the highest 5-ALA fluorescence sensitivity 94% (n = 95/101), brain metastases 84.7% (n = 61/72), low-grade gliomas 46.4% (n = 26/56), and high-grade gliomas 90.2% (n = 238/264). In children the highest 5-ALA visible fluorescence was observed in anaplastic astrocytomas 100% (n = 4/4) and in anaplastic ependymomas 100% (n = 4/4); in low-grade gliomas it made up 31.8% (n = 7/22). As for the spinal cord tumors in adults, the highest sensitivity was demonstrated by glioblastomas 100% (n = 4/4) and by meningiomas 100% (n = 4/4); Fluorescence was not found in gemangioblastomas (n = 0/6) and neurinomas (n = 0/4). Fluorescence intensity reached 60% (n = 6/10) in endoscopic surgery and 90% (n = 18/20) in stereotactic biopsy.Conclusion: 5-ALA fluorescence diagnosis proved to be most sensitive in surgery of HGG and meningioma (90.2 and 94.1%, respectively). Sensitivity in surgery of intracranial metastases and spinal cord tumors was slightly lower (84.7 and 63.6%, correspondingly). The lowest fluorescence sensitivity was marked in pediatric tumors and LGG (50 and 46.4%, correspondingly). Fluorescence diagnosis can also be used in transnasal endoscopic surgery of skull base tumors and in stereotactic biopsy.
The study demonstrated the correlation of the neuroradiological parameters with morphological changes. The abnormality of the FA and ADC parameters in the obstructive hydrocephalus represents a significant implication for the diagnostics and management of hydrocephalus in patients.
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