Search

Glioblastoma is the most lethal primary malignant brain tumor in adults. Simplified two-dimensional (2D) cell culture and neurospheres in vitro models fail to recapitulate the complexity of the tumor microenvironment, limiting its ability to predict therapeutic response. Three-dimensional (3D) scaffold-based models have emerged as a promising alternative for addressing these concerns. One such 3D system is gelatin methacrylate (GelMA) hydrogels, which can be used for modeling the glioblastoma microenvironment. We characterized the phenotype of patient-derived glioma cells cultured in GelMA hydrogels (3D-GMH) for their tumorigenic properties using invasion and chemoresponse assays. In addition, we used integrated single-cell and spatial transcriptome analysis to compare cells cultured in 3D-GMH to cells in vivo. Finally, we assessed tumor-immune cell interactions with a macrophage infiltration assay and a cytokine array. We show that cells cultured in 3D-GMH develop a mesenchymal-like cellular phenotype found in perivascular and hypoxic regions present in the core of the tumor, and recruit macrophages by secreting cytokines in contrast to the cells grown as neurospheres that match the phenotype of cells of the infiltrative edge of the tumor.

Gliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade 3 and grade 4 or GBM) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high-grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, IDH-wild type) or grade 3 IDH-mutant gliomas. We observe that neutrophils are highly heterogeneous among individuals with glioma, and are different from healthy controls. We also show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade 3 IDH-mutant glioma tissue, and a larger proportion of granulocytic myeloid-derived suppressor cells are present in grade 3 IDH-mutant gliomas when compared to GBM. Finally, we demonstrate that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor and suggest that these may be used as possible markers for prognosis.

Gliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade III and IV) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, grade IV) or grade III gliomas. Our data show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade III glioma tissue. In addition, we observe that neutrophils are highly heterogeneous among individuals with glioma, and a greater proportion of granulocytic myeloid-derived suppressor cells are present in grade III gliomas when compared to GBM. Finally, we show that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor, and suggest that these may be used as possible markers for prognosis.

A novel natural hydroxyapatite (HAp) bioceramic was extracted from the ostrich cortical bone by the thermal decomposition method. HAp was characterized by different analytical tools such as thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). Removal of organic impurities from the bone powder was confirmed by TGA analysis. FTIR spectra of HAp confirmed the presence of the major functional groups such as phosphate (PO43−), hydroxyl (OH−), and carbonate (CO32−) in the bioceramic. The XRD data revealed that the HAp was the crystalline phase obtained by calcination of the bone powder at 950°C, and the SEM analyses confirmed the typical plate-like texture of the nanosized HAp crystals.

Craniofacial resection is the technique of choice for tumors of the oral cavity or paranasal sinus extending close to the skull base of middle cranial fossa. Here we would like to describe a new technique of approaching these tumors through the facial incision itself. All patients treated with this technique at our institute were included in this retrospectively analyzed case series. The pathological clearance margins, complications and outcomes were studied. A total of nine patients underwent resection of tumor with the subcranial approach. There were seven males and two female patients. Mean age was 50.66 years (22–72 years). The diagnosis was squamous cell carcinoma in five patients, adenoid cystic carcinoma in three patients and alveolar soft part sarcoma in one patient. A lip split incision and mandibulotomy/mandibulectomy was done in seven patients; a Weber–Fergusson incision was used in one patient and details were not available in one other patient. Reconstruction was done with anterolateral thigh flaps with or without titanium mesh for all the patients. One patient developed thalamic infarct and was managed conservatively. None of the other patients had complications related to the craniotomy. The infratemporal fossa margin was close/involved in two patients (22.22%). Eight patients received adjuvant therapy without delay. One patient, who had received radiation previously, did not receive adjuvant radiation. This technique aims to reduce morbidity without compromising on the oncological outcomes for tumors extending short of or up to the skull base.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) has become a prevalent cause of spinal cord dysfunction among the aging population worldwide. Although great strides have been made in spine surgery in past decades, the optimal timing and surgical strategy to treat CSM have remained controversial. In this article the authors aimed to analyze the current trends in studies of CSM and to summarize the recent advances of surgical techniques in its treatment. METHODS: The PubMed database was searched using the keywords pertaining to CSM in human studies that were published between 1975 and 2018. Analyses of both the bibliometrics and contents, including the types of papers, authors, affiliations and countries, number of patients, and the surgical approaches were conducted. A systematic review of the literature was also performed with emphasis on the diagnosis and treatment of mild CSM. RESULTS: A total of 1008 papers published during the span of 44 years were analyzed. These CSM studies mainly focused on the natural history, diagnosis, and treatment, and only a few prospective randomized trials were reported. For the authors and affiliations, there was a shift of clustering of papers toward Asian countries in the past decades. Regarding the treatment for CSM, there was an exponential growth of surgical series published, and there was a trend toward slightly more anterior than posterior approaches through the past decade. Patients with CSM had increased risks of neurological deterioration or spinal cord injury with nonoperative management. Because surgery might reduce the risks, and early surgery was likely to be correlated with better outcomes, there was a trend toward attention to mildly symptomatic CSM. CONCLUSIONS: There is emerging enthusiasm for research on CSM worldwide, with more publications originating in Asian countries over the past few decades. The surgical management of CSM is evolving continuously toward early and anterior approaches. More prospective investigations on the optimal timing and choices of surgery are therefore needed. info:eu-repo/semantics/publishedVersion