FAM83H overexpression predicts worse prognosis and correlates with less CD8+ T cells infiltration and Ras-PI3K-Akt-mTOR signaling pathway in pancreatic cancer.

BACKGROUND: Family with sequence similarity 83 members H (FAM83H) is one member of Family with sequence similarity 83 (FAM83) family, which possess oncogenic properties in several types of cancer. However, the potential function of FAM83H in pancreatic cancer (PC) still remain unknown. AIM: This study aims to explore the role of FAM83H during pancreatic carcinogenesis and the regulation of immune infiltration in PC. METHODS: In the current study, the clinical significance and potential biological of FAM83H were evaluated by bioinformatics analysis. Possible associations between FAM83H expression and tumor immunity were analyzed using ESTIMATE algorithm and single-sample gene set enrichment analysis (ssGSEA). RESULTS: FAM83H expression was significantly upregulated in tumor tissues, and positively associated with higher histologic grade, tumor recurrence, and worse prognosis. FAM83H overexpression is notably associated with KRAS activation. And functional enrichment analysis demonstrated that FAM83H may be involved in positive regulation of cell proliferation and migration, Ras protein signal transduction, regulation of cell-matrix adhesion, epithelial to mesenchymal transition (EMT), TGF-ß receptor signaling in EMT, and activated NOTCH transmits signal to the nucleus. ESTIMATE algorithm and ssGSEA demonstrated that FAM83H overexpression suppressed the infiltration and antitumor activity of tumor-infiltrating lymphocytes (TILs), especially for CD8+ T cells. Besides, FAM83H overexpression significantly correlated with low expression of TIL-related gene markers (e.g. CD8A, CD8B, CD2, CD3D, and CD3E). CONCLUSION: The study suggests that FAM83H overexpression predicts poor prognosis and correlates with less CD8+ T cells infiltration and Ras-PI3K-Akt-mTOR signaling pathway in PC.

Altered expression of metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in cervical disc herniation patients.

The aim of the current study was to examine matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) expression in patients with cervical disc herniation (CDH). A total of 127 specimens from CDH patients undergoing posterior spinal surgery were obtained for the case group, which was divided into three subgroups: lateral protrusion (N = 102), median protrusion (N = 18), and paramedian protrusion (N = 7). Another 55 specimens from subjects who had cervical spine trauma and underwent spinal canal decompression were obtained for the control group. Routine hematoxylin and eosin staining was performed for pathological diagnosis. Immunohistochemical (IHC) analysis was used to determine MMP-2 and TIMP-2 expression. Under light microscopy, MMP-2-positive cells presented brown-yellow or dark brown staining in the cell membrane or cytoplasm. MMP-2 expression in the case group was significantly higher than that in controls (P < 0.05). Furthermore, MMP-2 expression in the lateral and median protrusion groups was significantly higher compared to that in the paramedian protrusion group (both P < 0.05), while there was no apparent difference in MMP-2 expression between the lateral and median protrusion groups (P > 0.05). IHC results showed that TIMP-2 expression in cases was significantly lower than that in controls (P < 0.05). Spearman correlation analysis indicated that MMP- 2 was negatively correlated with TIMP-2 expression (r = -0.418, P < 0.001). In conclusion, MMP-2 expression increased, whereas TIMP- 2 expression decreased in CDH patients, suggesting that MMP-2 and TIMP-2 expression may contribute to CDH development.

[Does semi-quantitative analysis of FDG-PET have any additional value in the diagnosis of mesial temporal sclerosis?]. / Qual o valor da análise semi-quantitativa dos exames de FDG-PET no diagnóstico da esclerose mesial temporal?

UNLABELLED: The aim of this study was to compare qualitative visual analysis with semi-quantitative analysis in the diagnosis of mesial temporal sclerosis (MTS) using FDG-PET. METHODS: This study included 21 patients with histopathological confirmation of MTS. FDG-PET visual analysis data were based on clinical reports generated soon after the completion of the scan. FDG-PET images were semi-quantitatively analyzed using regions of interest (ROIs) in 19 slices perpendicular to the longest axis of the temporal lobe. These ROIs divided each temporal lobe into three regions (lateral, inferior and medial). An asymmetry index was calculated for each region. RESULTS: The visual analysis of the FDG-PET studies demonstrated asymmetric hypometabolism in all patients. All but 1 patient underwent standard lobectomy of the same side described as hypometabolic by the PET report. Using an asymmetry index equal or greater than 9% in at least one of the regions as a threshold, the FDG-PET semi-quantitative analysis showed significant asymmetry in 18 patients. These also matched the side of lobectomy and were confirmed as sclerotic in all but one patient (same patient as above). CONCLUSION: The semi-quantitative analysis did not provide additional information over visual interpretation in this series of patients.

[Brain hypometabolism in patients with mesial-temporal sclerosis demonstrated by FDG-PET]. / Hipometabolismo cerebral em pacientes com esclerose mesial temporal demonstrado pelo FDG-PET.

UNLABELLED: The purpose of this study was to evaluate the extent of brain hypometabolism in patients with mesial-temporal sclerosis (MTS). METHOD: This retrospective study included 21 patients who had medically refractory complex partial seizures and were selected for surgical therapy after a comprehensive evaluation which included surface EEG recordings and neuroimaging studies (PET, SPECT and MRI). All patients were subjected to surgical intervention and had an histopathological confirmation of MTS. A semi-quantitative analysis of the PET images was performed using regions of interest in the following structures: frontal, parietal and occipital lobes, basal ganglia, thalami, cerebellum and three different regions in the temporal lobes, which included medial, inferior and lateral cortices. An asymmetry index (AI) was calculated, comparing the counts per pixel in the homologous structures in both brain hemispheres. The AI of the different structures were then correlated. RESULTS: A significant correlation was demonstrated between the AI of the medial temporal cortices and the frontal lobe, parietal lobe, basal ganglia and thalami (r = 0.72, 0.62, 0.47 and 0.47 respectively with p < 0.05 ). Within the temporal lobe, highly significant correlations were demonstrated among the structures (as high as 0.86 between temporo-medial and temporo-inferior). CONCLUSION: These data indicated that hypometabolism extends beyond the epileptogenic focus in the temporal lobe in patients with complex partial seizure related to MTS. The metabolism in the medial portion of the temporal lobe is more correlated with the metabolism in the frontal lobe than with those of the others brain structures outside the temporal lobe. The pathophysiological mechanisms of hypometabolism remain controversial.