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Glioblastoma (GBM), the most aggressive and fatal brain malignancy, is largely driven by a subset of tumor cells known as cancer stem cells (CSCs). CSCs possess stem cell-like properties, including self-renewal, proliferation, and differentiation, making them pivotal for tumor initiation, invasion, metastasis, and overall tumor progression. The regulation of CSCs is primarily controlled by transcription factors (TFs) which regulate the expressions of genes involved in maintaining stemness and directing differentiation. This review aims to provide a comprehensive overview of the role of TFs in regulating CSCs in GBM. The discussion encompasses the definitions of CSCs and TFs, the significance of glioma stem cells (GSCs) in GBM, and how TFs regulate GSC self-renewal, proliferation, differentiation, and transformation. The potential for developing TF-targeted GSC therapies is also explored, along with future research directions. By understanding the regulation of GSCs by TFs, we may uncover novel diagnostic and therapeutic strategies against this devastating disease of GBM.

Objectives: This study aimed to evaluate the feasibility of monitoring fetal intracranial volume using three‐dimensional ultrasound virtual organ computer‐aided analysis (VOCAL) technology and to analyze normal fetal brain growth. Methods: This multi‐center prospective cross‐sectional study included 821 pregnant women (18–40 gestational weeks) divided into 23 groups according to gestational week. We used transabdominal three‐dimensional ultrasound VOCAL to monitor fetal intracranial volume; explore the correlation between intracranial volume and gestational age, biparietal diameter (BPD), and head circumference (HC); and analyze the proportion of brain weight to body weight. Results: The intracranial volume of normal fetuses conformed to the normal distribution, gradually increased with gestational age, and was highly correlated with gestational age (r = 0.977), BPD (r = 0.975), and HC (r = 0.953; p < 0.001). The median percentage of brain weight (BW) to estimated fetal weight (EFW) was between 13% and 21%, and the BW/EFW ratio showed a significant downward trend in the third trimester. The VOCAL technology monitored the fetal intracranial volume with good repeatability. Conclusions: VOCAL technology is feasible for monitoring the fetal intracranial volume, and the intracranial volume increases more than 10‐times in the second and third trimesters. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive form of cancer with a low survival rate. A successful treatment strategy should not be limited to targeting cancer cells alone, but should adopt a more comprehensive approach, taking into account other influential factors. These include the extracellular matrix (ECM) and immune microenvironment, both of which are integral components of the tumor microenvironment. The present review describes the roles of pancreatic stellate cells, differentiated cancer-associated fibroblasts and the interleukin family, either independently or in combination, in the progression of precursor lesions in pancreatic intraepithelial neoplasia and PDAC. These elements contribute to ECM deposition and immunosuppression in PDAC. Therapeutic strategies that integrate interleukin and/or stromal blockade for PDAC immunomodulation and fibrogenesis have yielded inconsistent results. A deeper comprehension of the intricate interplay between fibrosis, and immune responses could pave the way for more effective treatment targets, by elucidating the mechanisms and causes of ECM fibrosis during PDAC progression. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most malignant and aggressive glioma, which has a very poor prognosis. Temozolomide (TMZ) is still a first‐line treatment, but resistance is inevitable even in MGMT‐deficient glioblastoma cells. The aims of this study were to comprehend the effect of TMZ on nucleus and the underlying mechanism of acquired TMZ resistance in MGMT‐deficient GBM. We show the changes of nuclear proteome in the MGMT‐deficient GBM U87 cells treated with TMZ for 1 week. Label‐free–based quantitative proteomics were used to investigate nuclear protein abundance change. Subsequently, gene ontology function annotation, KEGG pathway analysis, protein‐protein interaction (PPI) network construction analysis of DAPs, and immunofluorescence were applied to validate the quality of proteomics. In total, 457 (455 gene products) significant DAPs were identified, of which 327 were up‐regulated and 128 were down‐regulated. Bioinformatics analysis uncovered RAD50, MRE11, UBR5, MSH2, MSH6, DDB1, DDB2, RPA1, RBX1, CUL4A, and CUL4B mainly enriched in DNA damage repair related pathway and constituted a protein‐protein interaction network. Ribosomal proteins were down‐regulated. Cells were in a stress‐responsive state, while the entire metabolic level was lowered. Significance of the study: In U87 cell treated with TMZ for 1 week, which resulted in DNA damage, we found various proteins dysregulated in the nucleus. Some proteins related to the DNA damage repair pathway were up‐regulated, and there was a strong interaction. We believe this is the potential clues of chemotherapy resistance in tumour cells. These proteins can be used as indicators of tumour resistance screening in the future. [ABSTRACT FROM AUTHOR]

Heterogeneity is regarded as the major factor leading to the poor outcomes of glioblastoma (GBM) patients. However, conventional two‐dimensional (2D) analysis methods, such as immunohistochemistry and immunofluorescence, have limited capacity to reveal GBM spatial heterogeneity. Thus, we sought to develop an effective analysis strategy to increase the understanding of GBM spatial heterogeneity. Here, 2D and three‐dimensional (3D) analysis methods were compared for the examination of cell morphology, cell distribution and large intact structures, and both types of methods were employed to dissect GBM spatial heterogeneity. The results showed that 2D assays showed only cross‐sections of specimens but provided a full view. To visualize intact GBM specimens in 3D without sectioning, the optical tissue clearing methods CUBIC and iDISCO+ were used to clear opaque specimens so that they would become more transparent, after which the specimens were imaged with a two‐photon microscope. The 3D analysis methods showed specimens at a large spatial scale at cell‐level resolution and had overwhelming advantages in comparison to the 2D methods. Furthermore, in 3D, heterogeneity in terms of cell stemness, the microvasculature, and immune cell infiltration within GBM was comprehensively observed and analysed. Overall, we propose that 2D and 3D analysis methods should be combined to provide much greater detail to increase the understanding of GBM spatial heterogeneity. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most malignant type of primary brain tumor in adults and can diffusely infiltrate adjacent normal tissue. GBM is therefore rarely cured by surgery or radiation therapy. Matrix metalloproteinases (MMPs) are involved in tissue remodeling and numerous other physiological progresses. The MMPs MMP-2 and MMP-9 are associated with the invasion ability of GBM. PT93 is a novel caffeic acid amide derivative that was first synthesized in 2013. In the present study, the human GBM T98G, U87 and U251 cell lines and the normal mouse neuron HT22 cell line were used to investigate the anticancer and cytotoxic effects of PT93 in vitro . The cytotoxicity of PT93 was measured using MTT and lactate dehydrogenase assays. The anti-proliferation effect was tested using a cell colony formation assay. Gelatin zymography analysis and a scratch test were used to investigate the anti-migration mechanism of PT93. Western blot analysis was used to measure the expression of MMP-2/-9. The experimental results showed that PT93 suppressed the proliferation of T98G cells, and showed cytotoxicity effects at high concentration in T98G, U87, U251 and HT22 cell lines. Furthermore, PT93 limited the migration ability of the cells and inhibited the extracellular MMP-2 and MMP-9 activity of T98G and U251 cells. Finally, the present study confirmed that PT93 affects the level of MMP-2/-9 expression in T98G cells in a concentration-dependent manner. The present study indicates that PT93, as a novel caffeic acid amide derivative, may be used in the treatment of GBM.

Glioblastoma (GBM) is the most common brain tumor with high abilities of proliferation, migration and invasion. As is well-known, the peritumoral excitotoxic neuronal cell loss caused by glutamate, secreted by GBM cells, through activated N-methyl-D aspartate receptor (NMDAR) of neuronal cell. What's more, glutamate benefits the migration of GBM cells. However, the glutamate will not kill the GBM cells itself, which may be due to the deficiency of NMDAR. Fasudil, a ROCK inhibitor, was applied for subarachnoid hemorrhage (SAH) in clinic for many years. And it was found to be of potential to inhibit the proliferation, migration and invasion of GBM cells. In present study, we applied fasudil on the primary human GBM cells to further investigate the reduction of cell viability combined with glutamate. Combination treatment of glutamate and fasudil could significantly decrease the cell viability and elevate the level of LDH compared with fasudil treatment alone. What's more, MK-801, a NMDAR antagonist, could partially abolish this death caused by combination treatment. Further study found that the expression level of NMDAR-2B was elevated after treatment with fasudil in GBM cells. These results demonstrated fasudil could increase the expression level of NMDAR, which is necessary for glutamate to work. In a word, our research has provided a new sight of medicine combination in the treatment of GBM.

Objectives: The aim of this study was to compare the diagnostic yield of TBNA and EBUS-TBNA in the patients with suspected stage I and II sarcoidosis in the case of the same number of needle aspiration lymph nodes and the same lymph nodes needle aspiration times., Methods: A total of 62 patients with suspected stage I and II sarcoidosis were randomly divided into TBNA group and EBUS-TBNA group, based on the clinical and radiologic manifestations. Biopsy specimens of each patient in both groups were taken from two lymph nodes with two needle passes per lymph node. The diagnostic yields of subgroup were separately calculated including the 4th and 7th lymph nodes (referred to as group A), in other stations (group B), greater than 15 mm and less than 15 mm in the shortest diameter., Results: The diagnostic yield of TBNA and EBUS-TBNA for sarcoidosis was 64% and 93%, respectively (χ2=7.12, P<0.05). Subgroup analysis showed that the percentages of positive pathological diagnosis in group A for TBNA and EBUS-TBNA were 79% and 95% (χ2=3.47, P>0.05). The percentages of positive pathological diagnosis greater than 15 mm in the shortest diameter were 78% and 94% (χ2=2.29, P>0.05)., Conclusion: The overall diagnostic yield of EBUS-TBNA for stage I and II sarcoidosis was higher than TBNA. However, Conventional TBNA has very high diagnostic yield similar to EBUS-TBNA, if the lymph nodes located on the 4th and 7th group or the shortest diameter was greater than 15 mm.

Background: There have been several studys about transbronchial needle aspiration (TBNA) combined with rapid on-site evaluation (ROSE) so far at home and abroad, yet few studys were especially for patients with lung cancer. The aim of our study is to investigate the effect of TBNA combined with ROSE in the diagnosis of lung cancer., Methods: The data of the patients from December 2012 to December 2013, who were performed with TBNA and ultimately diagnosed with lung cancer in the People's Hospital of Binzhou City, were retrospectively analyzed. The patients were divided into two groups, ROSE group (rapid on-site evaluation group) and no-ROSE group (the group without rapid on-site evaluation). Among these patients, 37 patients were in the ROSE group and 32 patients were in the no-ROSE group. The result of ROSE and HE stain, the diagnostic yields and needle passes of each lymph node, the complication and cytology diagnostic cost of TBNA with ROSE and without ROSE were compared., Results: The coherence of ROSE and HE stain was 94.1% (32/34). The diagnostic yields of TBNA were 91.9% (34/37) and 78.1% (25/32) in ROSE group and no-ROSE group respectively, no significant differences were found. But the median number of needle passes of each lymph node and the percentage of the complication in ROSE group and no-ROSE group was significantly lower (t=29.5, P<0.05 and χ(2)=4.4, P<0.05, respectively). The cytopathological diagnostic cost of ROSE group was significantly lower compared with no-Rose group (t=10.9, P<0.05)., Conclusions: TBNA combined with ROSE has good concordance with HE stain in the diagnosis of lung cancer, and could reduce the needle passes, cytopathological diagnostic cost and complication, worthy of popularized.