Background: Lactate greatly contributes to the regulation of intracellular communication within the tumor microenvironment (TME). However, the role of lactate in pituitary adenoma (PA) invasion is unclear. In this study, we aimed to clarify the effects of lactate on the TME and the effects of TME on PA invasion. Methods: To explore the correlation between TME acidosis and tumor invasion, LDHA and LAMP2 expression levels were quantified in invasive (n = 32) and noninvasive (n = 32) PA samples. The correlation between immune cell infiltration and tumor invasion was evaluated in 64 PAs. Critical chemokine and key signaling pathway components were detected by qPCR, Western blotting, siRNA knockdown, and specific inhibitors. The functional consequences of CCR4 signaling inhibition were evaluated in vitro and in vivo. Results: Lactate was positively associated with PA invasion. Of the 64 PA tissues, invasive PAs were related to high infiltration of M2-like tumor-associated macrophages (TAMs) (P < 0.05). Moreover, lactate secreted from PA cells facilitated M2 polarization via the mTORC2 and ERK signaling pathways, while activated TAMs secreted CCL17 to promote PA invasion via the CCL17/CCR4/mTORC1 axis. According to univariate analysis of clinical data, high CCL17 expression was associated with larger tumor size (P = 0.0438), greater invasion (P = 0.0334), and higher susceptibility to postoperative recurrence (P = 0.0195) in human PAs. Conclusion: This study illustrates the dynamics between PA cells and immune TME in promoting PA invasion via M2 polarization. CCL17 levels in the TME are related to the PA invasiveness and clinical prognosis, and the CCL17/CCR4/mTOCR1 axis may serve as potential therapeutic targets for Pas.
Abstract Background Trigeminal neuralgia (TN) is a common cause of craniofacial pain. The retrosigmoid approach is usually used to treat TN, but no cases of endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) were used to undergo operation for TN. Case presentation Two patients were presented with severe facial pain and preliminary diagnosis was TN. Preoperative magnetic resonance imaging revealed that a superior cerebellar artery (SCA) compressed the trigeminal nerve in case 1, and a tumor located in the petrous apex extending into the Meckel’s cave compressed the trigeminal nerve in case 2. Operations were achieved through the EF-SCITA. The pain was totally relieved with no postsurgical complications in both cases. Conclusions We present the first two case reports of EF-SCITA to relieve classical and secondary TN successfully. The EF-SCITA can be a promising approach for treating TN.
Cabergoline is a dopamine agonist that has been used as the first-line treatment option for prolactin-secreting pituitary adenomas for several decades. It not only suppresses hormone production from these prolactinomas, but also causes tumour shrinkage. Recent studies revealed some novel mechanisms by which cabergoline suppresses tumour cell proliferation and induces cell death. In this article, we review the most recent findings in cabergoline studies, focusing on its anti-tumour function. These studies suggest the potential broader clinical use of cabergoline in the treatment of other tumours such as breast cancer, pancreatic neuroendocrine tumours, and lung cancer.
Rho-associated protein kinase 1 (ROCK1), a serine/threonine kinase, has previously been shown to be over-expressed in various types of human malignant tumors and to play an important role in cancer development and progression. Although ROCK1 has gained growing prominence as an important protein kinase in cancer biology, its potential as a predictive biomarker and a therapeutic target in papillary thyroid carcinoma (PTC) remains unknown. In the present study, ROCK1 expression was examined in 356 formalin-fixed, paraffin-embedded papillary thyroid carcinoma tissues using immunohistochemistry, and its clinical implications and prognostic significance were analyzed. Our results showed that ROCK1 expression was significantly increased in PTC compared with normal tissues, and was significantly associated with tumor size, lymphatic metastasis, distant organ metastasis, extrathyroid invasion, vascular invasion and tumor, node and metastasis (TNM) stage. Patients with strong ROCK1 expression had lower overall survival, disease-free survival, lymph node recurrence-free survival and distant recurrence-free survival rates than those with weak expression. Furthermore, overexpression of ROCK1 in papillary thyroid carcinoma cells was found to increase their invasiveness. Silencing ROCK1 by siRNA, however, caused an inhibition of cell invasion. Knockdown of ROCK1 decreased the volume and weight of the xenograft tumors, while overexpression of ROCK1 showed a proliferative tendency with significantly greater tumor volume and weight in vivo. Moreover, the upregulation of ROCK1 increased the expression of MMP-9, and levels of MMP-9 positively correlated with the ROCK1 levels in PTC tissues, implicating that MMP-9 may be involved in the mechanism of ROCK1 in the development and progression of PTC. These data suggest that ROCK1 might be a potential prognostic marker and therapeutic target for the treatment of PTC.
Abstract Background Our previous study shows that LINC01278 inhibits the malignant proliferation and invasion of papillary thyroid carcinoma (PTC) cells by regulating the miR-376c-3p/DNM3 axis. However, the regulation mechanism of LINC01278 expression in PTC cells is still unclear. Methods The luciferase reporter and ChIP assays were used to confirm the binding of LEF-1 to the putative promoter site of LINC01278 gene. The RNA immunoprecipitation and RNA pulldown were used to determine the enrichment of LINC01278 in β-catenin protein. The proteasome inhibitors (MG132) was used for detecting the β-catenin ubiquitination-proteasome degradation. Wnt/β-catenin specific agonists (LiCI), inhibitors (WiKI4) and TOP/FOP-flash reporter assay were used for detecting the activation of Wnt/β-catenin signal. Western blot was used to detected the expression of target proteins. Results The online PROMO algorithm determines a putative LEF-1 binding site on LINC01278 promoter, the LEF-1 binds to the putative promoter site of LINC01278 gene, and β-catenin enhances the binding of LEF-1 to the LINC01278 gene promoter. Furthermore, LINC01278 negatively regulated the protein accumulation of β-catenin in the cytoplasm, into nucleus, and ultimately inhibited the transcription of downstream target genes activated by Wnt/β-catenin signal. The results of RNA immunoprecipitation and RNA pulldown proved the direct binding of LINC01278 to β-catenin protein. In addition, the combination of LINC01278 and β-catenin promotes the β-catenin ubiquitination-proteasome degradation. Conclusion In summary, we found the transcriptional activation of LINC01278 by the β-catenin/LEF-1 transcription factor, and the negative feedback regulation of LINC01278 onβ-catenin signal.
Study Design. A retrospective data analysis was performed. Objective. The aim of this study is to explore the significant prognostic factors and propose new nomograms to facilitate clinical decision-making. Summary of Background Data. Chordoma is a rare bone tumor. The clinical features and optimal therapeutic strategies are still uncertain. Methods. Chordoma patients treated in four medical centers of mainland China before January 2015 were included. The predictors for local relapse-free survival (LRFS) and overall survival (OS) were identified by the Lasso regression and Cox proportional hazards regression model. Then the nomograms were developed. Their discrimination, calibration, and accuracy were evaluated by the C -index, calibration curve, and receiver operating characteristic curve (ROC), respectively. Results. A total of 341 patients were identified and full prognostic variable data were available for 276 patients. A total of 179 patients (64.9%) experienced recurrence and 122 patients (44.2%) died of all causes with a median follow-up time of 57.5 (range, 1–325) months. We identified recurrence-relevant factors of tumor size, tumor location, histology subtype and resection method, and death-relevant factors of tumor size, tumor location, resection method, complication, and postoperative recurrence. The constructed LRFS and OS nomograms showed good calibration and discriminative ability (C index 0.79 and 0.76, respectively). The ROCs suggested decent prediction ability with the 5-year area under curve (AUC) value of 0.868 and 0.786, respectively. Conclusion. Based on the multicenter case series of chordoma with a relative long follow-up, we proposed two nomograms to predict the prognosis on the basis of recurrence- and death-relevant factors. These findings could be referenced in the clinical decision-making process and provide additional prognostic information for risk stratification. Level of Evidence: 4
Macrophages are one of the most common infiltrating immune cells and an essential component of tumor microenvironment. Macrophages and the soluble cytokines and chemokines produced play an important role in tumorigenesis, progression, invasion and metastasis in solid tumors. Despite the multiple studies in other solid tumors, there is little known about macrophages in pituitary adenomas. Recently, studies about pituitary adenoma-infiltrated macrophages have been emerging, including the immunohistochemical and immunophenotypic analysis of the pituitary adenomas and further studies into the mechanism of the crosstalk between macrophages and tumor cells in vivo and in vitro . These studies have offered us new insights into the polarization of macrophages and its role in tumorigenesis, progression and invasion of pituitary adenomas. This review describes the advances in the field of pituitary adenoma-infiltrated macrophages and the prospect of targeting macrophages as cancer therapy in pituitary adenoma.
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