Effects of angiotensin II combined with asparaginase and dexamethasone on the femoral head in mice: A model of steroid-induced femoral head osteonecrosis.

Background: To study the pathogenesis of steroid-induced femoral head osteonecrosis, an ideal animal model is very important. As experimental animals, mice are beneficial for studying the pathogenesis of disease. However, there are currently few mouse models of steroid-induced femoral head osteonecrosis, and there are many questions that require further exploration and research. Purposes: The purpose of this study was to establish a new model of osteonecrosis in mice using angiotensin II (Ang II) combined with asparaginase (ASP) and dexamethasone (DEX) and to study the effects of this drug combination on femoral head osteonecrosis in mice. Methods: Male BALB/c mice (n = 60) were randomly divided into three groups. Group A (normal control, NC) was treated with physiological saline and given a normal diet. Group B (DEX + ASP, DA) was given free access to food and water (containing 2 mg/L DEX) and subjected to intraperitoneal injection of ASP (1200 IU/kg twice/week for 8 weeks). Group C (DEX + ASP + Ang II, DAA) was treated the same as group B, it was also given free access to food and water (containing 2 mg/L DEX) and subjected to intraperitoneal injection of ASP (1200 IU/kg twice/week for 8 weeks), but in the 4th and 8th weeks, subcutaneous implantation of a capsule osmotic pump (0.28 mg/kg/day Ang II) was performed. The mice were sacrificed in the 4th and 8th weeks, and the model success rate, mouse mortality rate, body weight, blood lipids, coagulation factors, histopathology, and number of local vessels in the femoral head were evaluated. Results: DAA increased the model success rate [4th week, 30% (DA) vs. 40% (DAA) vs. 0% (NC); 8th week, 40% (DA) vs. 70% (DAA) vs. 0% (NC)]. There was no significant difference in mortality rate between the groups [4th week, 0% (DA) vs. 0% (DAA) vs. 0% (NC); 8th week, 5% (DA) vs. 10% (DAA) vs. 0% (NC)]. DAA affected mouse body weight and significantly affected blood lipids and blood coagulation factors. DAA reduces the number of blood vessels in the femoral head and destroys the local blood supply. Conclusion: Angiotensin II combined with asparaginase and dexamethasone can obviously promote the necrosis of femoral head and provide a new idea for the model and treatment of osteonecrosis.

Exploring the pathological relationships between adamantinomatous craniopharyngioma and contiguous structures with tumor origin.

PURPOSE: Identifying relationships between craniopharyngiomas (CPs) and contiguous structures, and tumor origin are crucial for treatments. This study attempted to explore the relationships and tumor origin. METHODS: CPs that underwent endoscopic surgeries were enrolled. The interfacial specimens of CPs attaching the hypothalamus, pituitary stalk (PS), pituitary grand (PG), optic chiasma (OC) and brain tissue (BT) were pathologically examined. Boundaries between CPs and these structures were observed during operations. Expression of ß-catenin and stem cell markers were analyzed to explore the tumor origin. Outcomes of patients were assessed. RESULTS: A total of 34 CPs were categorized into two groups based on the locations of finger-like protrusions (FP). Group A comprised 18 CPs with FP only present in the specimens attaching to hypothalamus. The surface of these CPs was fused with hypothalamus under endoscopic videos. However, the specimens attaching to the PS, PG, OC, and BT showed no FP. Clear boundaries was observed between these CPs and these structures. Group B comprised 16 CPs with FP only present in the specimens attaching to PS. The tumor surface was fused with PS. Specimens attaching to the hypothalamus, PG, OC and BT showed no FP. Clear boundary was observed among these CPs with these structures. These results implied CPs only invaded a certain part of hypothalamic-pituitary axis. ß-catenin and stem cells markers mainly distributed in the FP tissues of both groups. Patients in group B achieved better outcomes than group A. CONCLUSIONS: CPs only invade the hypothalamic-pituitary axis with FP and the FP would be the tumor origin.

The eagle sign: a new preoperative MRI-based tool for predicting topographic correlation between craniopharyngioma and hypothalamus.

PURPOSE: Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological-surgical-pathological-outcome analysis. MATERIALS AND METHODS: Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named "eagle sign" was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. RESULTS: A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of "eagle sign". Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical-pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of "eagle sign" were more than 90%. CONCLUSION: "Eagle sign" is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.

Immune Infiltration of MMP14 in Pan Cancer and Its Prognostic Effect on Tumors.

BACKGROUND: Matrix metalloproteinase 14 (MMP14) is a member of the MMP family, which interacts with tissue inhibitors of metalloproteinase (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis, and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 across cancers. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, and immune checkpoint genes. METHODS: In this study, we used bioinformatics to analyze data from multiple databases, including The Cancer Genome Atlas (TCGA), ONCOMINE, and Kaplan-Meier plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene MMR, MSI, TMB, DNA methylation, and immune checkpoint genes. RESULTS: MMP14 expression is highly associated with the prognosis of a variety of cancers and tumor immune invasion and has important effects on pan oncologic MMR, MSI, TMB, DNA methylation, and immune checkpoint genes. CONCLUSION: MMP14 is highly correlated with tumor prognosis and immune invasion and affects the occurrence and progression of many tumors. All of these results fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis, and treatment of many tumors and provide new ideas and direction for subsequent tumor immune research and treatment strategies.

Invasive Corridor of Clivus Extension in Pituitary Adenoma: Bony Anatomic Consideration, Surgical Outcome and Technical Nuances.

BACKGROUND: It is well known that the clivus is composed of abundant cancellous bone and is often invaded by pituitary adenoma (PA), but the range of these cancellous bone corridors is unknown. In addition, we found that PA with clivus invasion is sometimes accompanied by petrous apex invasion, so we speculated that the petrous apex tumor originated from the clivus cancellous bone corridor. The aim of this study was to test this hypothesis by investigating the bony anatomy associated with PA with clival invasion and its clinical significance. METHODS: Twenty-two cadaveric heads were used in the anatomical study to research the bony architecture of the clivus and petrous apex, including six injected specimens for microsurgical dissection and sixteen cadavers for epoxy sheet plastination. The surgical videos and outcomes of PA with clival invasion in our single center were also retrospectively reviewed. RESULTS: The hypoglossal canal and internal acoustic meatus are composed of bone canals surrounded by cortical bone. The cancellous corridor within clivus starts from the sellar or sphenoid sinus floor and extends downward, bypassing the hypoglossal canal and finally reaching the occipital condyle and the medial edge of the jugular foramen. Interestingly, we found that the cancellous bone of the clivus was connected with that of the petrous apex through petroclival fissure extending to the medial margin of the internal acoustic meatus instead of a separating cortical bone between them as it should be. It is satisfactory that the anatomical outcomes of the cancellous corridor and the path of PA with clival invasion observed intraoperatively are completely consistent. In the retrospective cohort of 49 PA patients, the clival component was completely resected in 44 (89.8%), and only five (10.2%) patients in the early-stage had partial residual cases in the inferior clivus. CONCLUSION: The petrous apex invasion of PA is caused by the tumor invading the clivus and crossing the petroclival fissure along the cancellous bone corridor. PA invade the clivus along the cancellous bone corridor and can also cross the hypoglossal canal to the occipital condyle. This clival invasion pattern presented here deepens our understanding of the invasive characteristics of PA.

MMP12 is a potential therapeutic target for Adamantinomatous craniopharyngioma: Conclusions from bioinformatics analysis and in vitro experiments.

Adamantinomatous craniopharyngioma (ACP) is considered a benign intracranial tumor, but it can also exhibit aggressive characteristics. Due to its unique location in the suprasellar, which brings it close to important nerves and vascular structures, ACP can often lead to significant neuroendocrine diseases. The current treatments primarily include surgical intervention, radiation therapy or a combination of the two, but these can lead to serious complications and adversely affect the quality of life of patients. Thus, it is important to identify effective and safe alternatives. Recently, studies have focused on the tumor genome, transcriptome and proteome in an attempt to identify potential therapeutic targets for clinical use. However, studies on this region of the CP are limited; thus, the present study focused on this region. The GSE94349 and GSE68015 datasets were downloaded from the Gene Expression Omnibus database and analyzed. In the in vitro studies, the effect of the matrix metalloproteinase (MMP)12 inhibitor, MMP408, on cell proliferation and protein expression was assessed. The results demonstrated that MMP408 effectively inhibited cell proliferation and migration of ACP cells, and decreased the expression levels of the related proteins. Thus, MMP12 may be used as a potential therapeutic target for the treatment of ACP.