Aberrant expression of CD133 protein correlates with Ki-67 expression and is a prognostic marker in gastric adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The relationships between the expression of CD133, Ki-67 and prognosis in gastric adenocarcinoma are unknown and needs exploring.</p> <p>Methods</p> <p>The samples of gastric adenocarcinoma from 336 Chinese patients with follow-up were analyzed for CD133 and Ki-67 protein expressions by immunohistochemical method.</p> <p>Results</p> <p>CD133 was expressed in up to 57.4% (193/336) of this group of gastric carcinoma. The expression of CD133 was significantly higher in carcinoma than in normal (<it>P </it>= 0.0001) and dysplastic mucosas (<it>P </it>= 0.004). CD133 was positive corresponded with the tumour size, grade, infiltrative depth and clinical stage (all <it>P </it>< 0.05). The overall mean survival time of the patients with CD133 positive expression was shorter than that of patients with negative expression (<it>P </it>= 0.0001). The expression of CD133 has a positive correlation with that of Ki-67 (r = 0.188, <it>P </it>= 0.001) in gastric adenocarcinoma. CD133 was an independent prognostic indicator. (<it>P </it>= 0.0001).</p> <p>Conclusions</p> <p>It is suggested that CD133 may play an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for the prognosis.</p

Development and validation of a preoperative MRI-based radiomics nomogram to predict progression-free survival in patients with clival chordomas

ObjectivesThe aim of this study was to establish and validate a MRI-based radiomics nomogram to predict progression-free survival (PFS) of clival chordoma.MethodsA total of 174 patients were enrolled in the study (train cohort: 121 cases, test cohort: 53 cases). Radiomic features were extracted from multiparametric MRIs. Intraclass correlation coefficient analysis and a Lasso and Elastic-Net regularized generalized linear model were used for feature selection. Then, a nomogram was established via univariate and multivariate Cox regression analysis in the train cohort. The performance of this nomogram was assessed by area under curve (AUC) and calibration curve.ResultsA total of 3318 radiomic features were extracted from each patient, of which 2563 radiomic features were stable features. After feature selection, seven radiomic features were selected. Cox regression analysis revealed that 2 clinical factors (degree of resection, and presence or absence of primary chordoma) and 4 radiomic features were independent prognostic factors. The AUC of the established nomogram was 0.747, 0.807, and 0.904 for PFS prediction at 1, 3, and 5 years in the train cohort, respectively, compared with 0.582, 0.852, and 0.914 in the test cohort. Calibration and risk score stratified survival curves were satisfactory in the train and test cohort.ConclusionsThe presented nomogram demonstrated a favorable predictive accuracy of PFS, which provided a novel tool to predict prognosis and risk stratification. Our results suggest that radiomic analysis can effectively help neurosurgeons perform individualized evaluations of patients with clival chordomas

PitNETs and the gut microbiota: potential connections, future directions

The role of the gut microbiome has been widely discussed in numerous works of literature. The biggest concern is the association of the gut microbiome with the central nervous system through the microbiome-brain-gut axis in the past ten years. As more and more research has been done on the relationship between the disease of the central nervous system and gut microbes. This fact is being revealed that gut microbes seem to play an important role from the onset and progression of the disease to clinical symptoms, and new treatments. As a special tumor of the central nervous system, pituitary neuroendocrine tumors (PitNETs)are closely related to metabolism, endocrinology, and immunity. These factors are the vectors through which intestinal microbes interact with the central nervous system. However, little is known about the effects of gut microbes on the PitNET. In this review, the relationship of gut microbiota in PitNETs is introduced, the potential effects of the gut-brain axis in this relationship are analyzed, and future research directions are presented

Melatonin modulates the effects of diethylstilbestrol (DES) on the anterior pituitary of the female Wistar rat.

We studied the anti-tumorigenic effect of melatonin in diethylstilbestrol (DES)-treated anterior pituitaries in rats. Twenty-one female Wistar rats were randomly allocated into three groups: vehicle control rats, DES-treated rats, and DES-treated rats co-administrated with melatonin beginning at week 13. At the end of 16 weeks, rats were weighed and decapitated for morphological studies, including an H+E staining-based score evaluation in regard to cell proliferation, angiogenesis, immunostaining for VEGF, MMP-9, and AQP-1, and electron microscopy. Compared with vehicle, long-term treatment of DES significantly reduced rat body weight and increased H+E score, both of which were counteracted by melatonin. Administration of melatonin also reduced the expression of VEGF and MMP-9, although no changes were detected in AQP-1 expression. In rats cotreated with melatonin, the RER loosened and accumulated more secretion granules. We thus concluded that melatonin can modulate the effects of DES on the rat anterior pituitary by downregulating expression of VEGF and MMP-9 and suppressing the release of secretion granules, suggesting a therapeutic potential in estrogen-induced pituitary malfunctions

Application of “mosiac sign” on T2-WI in predicting the consistency of pituitary neuroendocrine tumors

PurposeTumor consistency is important for pituitary neuroendocrine tumors (PitNETs) resection to improve surgical outcomes. In this study, we evaluated the T2-WI of PitNETs and defined a specific T2-WI signaling manifestation, the “Mosaic sign,” to predict tumor consistency and resection of PitNETs.DesignA retrospective review of MRI and tumor histology of 137 consecutive patients who underwent endoscopic endonasal resection for PitNETs was performed.MethodsThe “Mosaic sign” was defined by the ratio of the tumor itself T2-WI signals, and characterized by multiple intratumor hyperintense dots. The degree of tumor resection was an assessment by postoperative MRI examination. The presence of the “Mosaic sign” was compared with patients' basic information, tumor consistency, tumor pathological staining, and surgical result. To determine whether the presence or absence of “Mosaic sign” could predict tumor consistency and guide surgical resection of tumors.ResultsStatistical analysis showed that the consistency of the tumor and the degree of resection were correlated with the “Mosaic sign”. In the 137 cases of T2-WI, 43 had “Mosaic sign”, 39 cases had soft tumor consistency, and 4 were classified as fibrous, of which 42 were completely resected and 1 was subtotal resected. Of the 94 patients without “Mosaic sign”, the consistency of tumor of 54 cases were classified as soft, the remaining 40 cases were fibrous, 80 cases were completely resected, and 14 cases were subtotal resected. Postoperative cerebrospinal fluid leakage occurred in 1 patient. The number of corticotroph adenomas in the group of “Mosaic sign” was higher, with the statistical difference between the two groups (P = 0.0343).ConclusionsThe presence of the “Mosaic sign” in T2-WI may provide preoperative information for pituitary adenomas consistency and effectively guide surgical approaches

Somatic SF3B1 hotspot mutation in prolactinomas.

The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase&nbsp;chain&nbsp;reaction (PCR) analysis of tissue samples from 227 prolactinomas. We identify the same hotspot somatic mutation in splicing factor 3 subunit B1 (SF3B1R625H) in 19.8% of&nbsp;prolactinomas. These patients with mutant prolactinomas display higher prolactin (PRL) levels (p = 0.02) and shorter progression-free survival (PFS) (p = 0.02) compared to patients without the mutation. Moreover, we identify that the SF3B1R625H mutation causes aberrant splicing of estrogen related receptor gamma (ESRRG), which results in stronger binding of pituitary-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion. Thus our study validates an important mutation and elucidates a potential mechanism underlying the pathogenesis of prolactinomas that may lead to the development of targeted therapeutics

LRP16 Integrates into NF-κB Transcriptional Complex and Is Required for Its Functional Activation

BACKGROUND: Nuclear factor κB (NF-κB)-mediated pathways have been widely implicated in cell survival, development and tumor progression. Although the molecular events of determining NF-κB translocation from cytoplasm to nucleus have been extensively documented, the regulatory mechanisms of NF-κB activity inside the nucleus are still poorly understood. Being a special member of macro domain proteins, LRP16 was previously identified as a coactivator of both estrogen receptor and androgen receptor, and as an interactor of NF-κB coactivator UXT. Here, we investigated the regulatory role of LRP16 on NF-κB activation. METHODOLOGY: GST pull-down and coimmunoprecipitation (CoIP) assays assessed protein-protein interactions. The functional activity of NF-κB was assessed by luciferase assays, changes in expression of its target genes, and its DNA binding ability. Annexin V staining and flow cytometry analysis were used to evaluate cell apoptosis. Immunohistochemical staining of LRP16 and enzyme-linked immunosorbent assay-based evaluation of active NF-κB were performed on primary human gastric carcinoma samples. RESULTS: We demonstrate that LRP16 integrates into NF-κB transcriptional complex through associating with its p65 component. RNA interference knockdown of the endogenous LRP16 in cells leads to impaired NF-κB activity and significantly attenuated NF-κB-dependent gene expression. Mechanistic analysis revealed that knockdown of LRP16 did not affect tumor necrosis factor α (TNF-α)-induced nuclear translocation of NF-κB, but blunted the formation or stabilization of functional NF-κB/p300/CREB-binding protein transcription complex in the nucleus. In addition, knockdown of LRP16 also sensitizes cells to apoptosis induced by TNF-α. Finally, a positive link between LRP16 expression intensity in nuclei of tumor cells and NF-κB activity was preliminarily established in human gastric carcinoma specimens. CONCLUSIONS: Our findings not only indicate that LRP16 is a crucial regulator for NF-κB activation inside the nucleus, but also suggest that LRP16 may be an important contributor to the aberrant activation of NF-κB in tumors