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Background Pituitary neuroendocrine tumors (PitNETs) are common intracranial tumors that are classified into seven histological subtypes, including lactotroph, somatotroph, corticotroph, thyrotroph, gonadotroph, null cell, and plurihormonal PitNETs. However, the molecular characteristics of these types of PitNETs are not completely clear. Methods A total of 180 consecutive cases of PitNETs were collected to perform RNA sequencing. All subtypes of PitNETs were distinguished by unsupervised clustering analysis. We investigated the regulation of TPIT by TRIM65 and its effects on ACTH production and secretion in ACTH-secreting pituitary cell lines, as well as in murine models using biochemical analyses, confocal microscopy, and luciferase reporter assays. Results A novel subtype of PitNETs derived from TPIT lineage cells was identified as with normal TPIT transcription but with lowered protein expression. Furthermore, for the first time, TRIM65 was identified as the E3 ubiquitin ligase of TPIT. Depending on the RING domain, TRIM65 ubiquitinated and degraded the TPIT protein at multiple Lys sites. In addition, TRIM65-mediated ubiquitination of TPIT inhibited POMC transcription and ACTH production to determine the fate of the novel subtype of PitNETs in vitro and in vivo. Conclusion Our studies provided a novel classification of PitNETs and revealed that the TRIM65-TPIT complex controlled the fate of the novel subtype of PitNETs, which provides a potential therapy target for Cushing’s disease.

OX40 signaling pathway occupies a vital place in anti-tumor immunity; however, the role of tumor-infiltrating OX40A total of 325 sequential PDAC patients who received curative tumor resection between January 2014 and December 2016 were enrolled. Tissues of these patients were immunohistochemically assessed for tumor infiltration of CD4Our results showed that higher OX40This study demonstrated that intratumoral infiltration by a high number of OX40

BACKGROUND: To investigate the role of (99m)Tc-labeled sestamibi ((99m)Tc-MIBI) retention level in the assessment of malignant potential of parathyroid lesions. METHODS: Twenty patients with parathyroid carcinomas and forty controls with benign parathyroid lesions who underwent preoperatively (99m)Tc-MIBI dual-phase planar and SPECT/CT imaging were retrospectively enrolled in this study. The mean and peak of retention index (RI(mean) and RI(peak)) were measured for evaluating the retention level of (99m)Tc-MIBI in the parathyroid lesions. Diagnostic accuracies of RI for differentiating malignant parathyroid lesions from benign ones were assessed by receiver operating characteristic analyses (area under the curve; AUC). RESULTS: RI(peak) (AUC =0.87, P

Purpose To evaluate the predictive and prognostic value of tumor‐infiltrating lymphocytes (TILs) before and after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Patients and methods Consecutive breast cancer patients treated with NAC between August 2008 and November 2019 were retrospectively analyzed. TIL levels were evaluated of invasive tumor samples, and high expression was defined as TILs >10%. Total pathological complete response (pCR) was defined as no invasive tumor in the breast or lymph nodes. Univariate and multivariate analyses were used to assess factors associated with pCR rate, disease‐free survival (DFS), and overall survival. Results A total of 461 patients were included. The mean pre‐NAC TIL level was higher among patients with pCR than among patients without pCR (24.28% ± 2.34% vs. 11.34% ± 0.60%, respectively, p

Mutations in the EGFR gene are biomarkers that guide the targeted therapy of Non-Small Cell Lung Cancer (NSCLC). When the mutation assay was performed on small Formalin-Fixed, Paraffin-Embedded (FFPE) biopsies in which only a limited number of tumor cells were obtained, determining Limit of detection of cell number (LODCN) was helpful for quality control. An NCL-H1975 cell block was used to determine the range of LODCN for EGFR mutations. The in-house LODCN was set based on the results of 10 samples with known EGFR mutations. The other 35 samples were assayed to validate the LODCN value. The consistency of 35 clinical validated samples was 100% in samples with more than 70 tumor cells. LODCN could be a useful quality control parameter for mutation assays on small FFPE samples with a very limited number of tumor cells.

Background and importance Metastasis to the pituitary gland is uncommon in patients with systemic disseminated cancer. Individual articles have reported cases of pituitary metastasis mimicking a prolactinoma, but no case of a prolactin-secreting tumor metastasizing to the pituitary mimicking a prolactinoma has been reported so far. Clinical presentation This article reports a 67-yr-old man with a recent onset of headaches, ophthalmoplegia, hypopituitarism, and hyperprolactinemia who was initially diagnosed with prolactinoma and given bromocriptine in the local hospital. Because of vomiting after taking drugs, he was transferred to our hospital for further diagnosis and treatment. Serum prolactin was elevated up to 1022 ng/mL, and pituitary magnetic resonance imaging revealed a 2.9 × 2.8 × 2.3 cm sellar mass with pituitary apoplexy, for which endoscopic transsphenoidal surgery was performed. Postoperative pathology and western blotting disclosed a prolactin-positive metastatic lung adenocarcinoma. Whole exome sequencing revealed a number of gene mutations including KRAS, PIK3CA, ALK, and CTNNB1. The patient died of deterioration of the lung disease 3 mo after the initial diagnosis. Conclusion To the best of our knowledge, this is the first report of a prolactin-secreting tumor metastasizing to the pituitary mimicking a prolactinoma as confirmed by both immunohistochemistry and western blot. Prolactin secretion is rare and elusive, and may associate with specified gene mutations.

Background: Idiopathic nonspecific interstitial pneumonia (INSIP) presents with varying degrees of interstitial inflammation and fibrosis exhibiting a uniform appearance. Lack of knowledge on the underlying mechanisms of INSIP has contributed to few effective treatment strategies. Our study is designed to explore aberrantly expressed cytokines involvement in INSIP development. Methods: Oligo GEArray was employed to detect the expression of cytokines in INSIP patients, and idiopathic pulmonary fibrosis (IPF) was setup as isotype control. Real-time PCR and immunohistochemistry analysis were used to further confirm the expression of abnormally expressed cytokines. The correlationship between cytokines expression and overall survival rate of patients with IPF and INSIP were analyzed. Results: From microarray detection, transforming growth factor-beta-1 (TGF-β1), fibroblast growth factor 10 (FGF10), and platelet derived growth factor (PDGF) were predominantly up-regulated in patients with INSIP. Real-time PCR and immunohistochemistry also showed these cytokines was abnormally expressed in INSIP. In addition to, the clinical relevance analysis demonstrated relatively lower expression of PDGF patients had longer overall survival rate than those with higher expression of PDGF. Conclusions: Our study suggests that TGF-β1, FGF10, and PDGF are required for the pathogenesis of INSIP, and may therefore be ideal targets in INSIP treatment. Moreover, INSIP patients with lower expression of PDGF had better survival rate.

Objective: To clarify the clinicopathologic and ultrastructural features of primary pulmonary cryptococcosis (PC).Methods: 43 cases of PC were observed by light microscopy and histochemical staining, including mucicarmine (MC), Alcian blue (AB), periodic acid–Schiff (PAS), and Grocott methenamine–silver (GMS). Transmission electron microscopy (TEM) was performed on 11 fresh and 8 formalin-fixed specimens.Results: The detective rate of Cryptococcus neoformans (CN) by MC, AB, PAS, GMS staining, and TEM was 61.3% (19/31), 62.2% (23/37), 85.7% (30/35), 79.1% (34/43), and 89.5% (17/19), respectively. All CN detected by TEM had a capsule. Most of them possessed simple structure with undeveloped cellular organelles.Conclusion: Electron microscopy has a high rate of detecting CN. A combination of histochemical staining and electron microscopy can make an accurate diagnosis of PC.

To investigate the expressions of cytokines in idiopathic pulmonary fibrosis (IPF) and in idiopathic nonspecific interstitial pneumonia (INSIP); To discuss expressions and meanings of bone morphogenetic protein 7 (BMP-7) and transforming growth factor beta (TGF-β) in IPF and IPF.Selected 47 cases of idiopathic interstitial pneumonia (IIP), which were diagnosed by clinical-radiologic-pathologic (CRP), and classified into two groups which were group IPF (25 IPF) and group INSIP (22 INSIP, including 6 cellular pattern and 16 fibrosing pattern). The normal lung tissues were collected as the control group: The fresh tissues were made to detect more than 114 kinds of cytokines' expressions via Oligo GEArray gene microarray technology. Made a tissue microarray which applied EnVision immunohistochemistry technology to detect the expressions of BMP-7 and TGF-β in both kinds of IIPs. The two groups of patients were followed-up visited around 5 to 8 years and the survival curves were evaluated by Kaplan-Meier method.According to gene microarray results, these two groups were up-expression in TGF family,IL family and TNF family. Most of BMP members were down-expression, in comparison with the control group, except BMP-5,BMP-8B and BMP-15. As the tissue microarray results demonstrated, compared with normal lung tissues,BMP-7 expressed decreasingly in IPF and INSIP groups (t1 = 27.618, P0.001; t2 = -12.404, P0.001). The expression of IPF were lower than INSIP (t = 5.387, P0.05); In INSIP group, patients of cellular pattern expressed BMP-7 more than fibrosing pattern's (t = -5.341, P0.001). There were dramatically increasing expressions of TGF-β in IPF and INSIP, when compared with the control group (t1 = 23.393, P0.001; t2 = -13.445, P0.001) and it presented negative correlation with BMP-7(group IPF: r = -0.771, P0.001; group INSIP: r = -0.729, P0.001). (3) Clinical follow-up data showed, the stability(improvement), deterioration and death rates of the group IPF and the group INSIP were, respectively, 0(0%), 2 (8%), 23 (92%) and 15 (68.1%), 3 (13.6%), 4 (18.2%). The results were statistically significant (all P0.05). The median survival time of the part with higher BMP-7 expression and the part with relatively lower BMP-7 expression, in the group IPF, were 110.8 and 66.4 months (t = -2.686, P0.05); In the group INSIP, were 146.4 and 74.9 months (t = -3.037, P0.05).Cellular cytokines presented different expression profiles in IPF and INSIP patients. Differently with highly activated TGF-β, BMP-7 was inhibited in IIP patients, which would remind the degree of fibrosis and prognosis of IIP. BMP-7 would be expected to be a novel target for IIP pathogenesis and prognostic research.

To construct tumor-targeted nanometer particles as a negative magnetic resonance imaging (MRI) contrast agent. Ultra-small superparamagnetic iron oxide (USPIO) nanometer particles were prepared by one-step chemical precipitation. The covalent bond between cyclic RGD (cRGD) containing an Arg-Gly-Asp sequence targeting integrin-alphavbeta3, and USPIO was conducted by chemical crosslinking. The physico-chemical property of cRGD-USPIO was detected. Prussian blue staining was applied to detect the specific binding capacity of cRGD-USPIO and USPIO to human pulmonary adenocarcinoma A549 cells and human umbilical vein endothelial cells. Subsequently, A549 xenografts in nude mice were established, and intravenous injections of USPIO and cRGD-USPIO into the vena caudalis were performed. The enhancement of cRGD-USPIO against tumor MRI signal was evaluated. The mean hydrodynamic diameter of cRGD-USPIO was 43.97 +/- 10.10 nm and the size of the ferric oxide core was 5-10 nm. The specific saturation magnetization was 59.94 A x m2 x Kg(-1). The cell conjugation assay results indicated that the positive staining of the cRGD-USPIO group was significantly enhanced. The in vivo MRI diagnosis indicated that the cRGD-USPIO tumor signal was significantly reduced compared to that of the USPIO group (P < 0.01). The targeted superparamagnetic iron oxide nanometer particle can be a novel MRI negative contrast agent for more specific tumor early diagnosis.