Objective: To investigate the clinicopathological characteristics, immunophenotype, and molecular signatures of oncocytic papillary renal cell carcinoma (OPRCC), and to compare these findings with those in type 1 papillary renal cell carcinoma (PRCC 1). Methods: The clinicopathologic data of 19 patients with OPRCC from the Affiliated Hospital of Qingdao University (16 patients) and the 971 Hospital of People's Liberation Army Navy (3 patients) from October 2003 to February 2021 were collected. Histologic, immunohistochemical (IHC) and molecular analyses, together with a control group of 15 cases of PRCC I diagnosed in the same period, were assessed. Results: The cohort included 15 males and 4 females, with a median age of 61 years (range, 47-78 years). In 13 patients the tumors were found at physical examination; four presented with painless gross hematuria and two with low back pain. As for the pathologic stage, 14 patients were pT1, one patient was pT2a, three patients were pT3a and one patient was pT4. The tumor size ranged from 1.7-14.0 cm, with clear boundary and soft texture. The cut surface was grayish-yellow and grayish-red. Microscopically, the tumor cells were mainly arranged in papillary (10%-100%) and acinar (tubular) patterns, with strongly eosinophilic cytoplasm, round or irregular nuclei, and prominent nucleoli (WHO/ISUP grade Ⅲ). Two cases showed sarcomatoid differentiation. Stromal foamy macrophages were visible in all cases. IHC staining showed diffuse strong positivity for AMACR in all cases. RCC (18/19), CD10 (17/19), vimentin (16/19) and PAX8 (17/19) were positive in most tumors. CK7 was expressed in about 50% of cases. Fluorescence in situ hybridization identified trisomy 7 in eight patients, trisomy 17 in seven patients, and the two aberrations occurred simultaneously in seven cases. Eight of 13 men had Y chromosome deletion. All patients were followed up for 8-120 months. Three patients died of metastases at 8, 62 and 82 months postoperatively, respectively, and one patient relapsed 36 months after surgery. Compared with PRCC1, OPRCC tended to have higher nuclear grade, and stromal foam cell aggregation was more commonly found (P<0.05). The expression of CD10 and EMA were different (P<0.01). There was no significant difference in the survival rate between the two groups (P=0.239). Conclusions: OPRCC has unique morphologic features, and its immunophenotype overlaps but differs from PRCC1. The molecular results support that it belongs to a morphologic variation of PRCC. This tumor has similar biologic behavior to PRCC1, and has a poor prognosis when sarcomatoid differentiation occurs.
Aged ; Biological Products ; Biomarkers, Tumor/analysis* ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kidney Neoplasms/genetics* ; Male ; Middle Aged ; Neprilysin/analysis* ; Vimentin/analysis*

Objective: To investigate the clinicopathologic features,diagnosis and prognosis of pericytic tumor of the kidney. Methods: Three cases of pericytic tumor of the kidney (two cases were diagnosed as glomangiomyomas and one case as pericytic tumor,unclassified) were collected from the affiliated Hospital of Qingdao University between January 2014 to May 2021; the clinical and morphologic features, immunohistochemical and molecular characteristics were analyzed and the relevant literature was reviewed. Results: The three patients included one male and two females, with ages ranging from 21 to 70 years. In two patients the tumors were detected incidentally at physical examination and one patient presented with low back discomfort. Imaging showed a rounded nodular soft tissue density shadow in renal parenchyma, and enhancement scan showed uneven delayed enhancement. Grossly, two tumors were located in the renal hilum and one in the renal parenchyma; all were nodular. The tumors were measured in size from 1.6 cm to 5.1 cm (mean 4.1 cm) and showed gray or gray-red cut surface. Histologic examination showed the tumor cells were arranged in solid sheets or small nodules, closely related to vascular wall. Tumor cells were mostly epithelial-like with abundant cytoplasm, light eosinophilia, obscure boundary and round nuclei with visible nucleoli. Vague bundles and fascicular arrangements of smooth muscle component were noted in some areas, with transition of both components. There was no necrosis. By immunohistochemistry, the tumor cells strongly and diffusely expressed vimentin, SMA and collagen Ⅳ, two cases expressed CD34, all three cases expressed PDGFRB to varying extent, and the Ki-67 index was 2%-3%. PCR tests showed absent K-RAS, BRAF V600E gene mutation in all three cases. PDGFRB mutations in exons 3 and 18, respectively were found in two of the three cases by high-throughput sequencing, and no NOTCH 1/2/3 gene fusions were found in any of them. Follow-up information (range: 6-92 months) showed no evidence of local recurrence or distant metastasis in all three patients. Conclusions: Pericytic tumor of the kidney is a rare mesenchymal tumor originating in the kidney with differentiation to smooth muscle, most commonly glomus tumor. The mild pleomorphism, close relationship with vascular wall and spindled smooth muscle components suggest the diagnosis of the tumor. Expression of both epithelial and muscle-associated markers aids the diagnosis. PDGFRB gene mutations may have an important role in the development of this tumor. Most patients have a good prognosis, and a few cases have malignant biological behavior.
Adult ; Aged ; Biomarkers, Tumor/analysis* ; Collagen ; Diagnosis, Differential ; Female ; Glomus Tumor/pathology* ; Humans ; Ki-67 Antigen ; Kidney/pathology* ; Kidney Neoplasms/pathology* ; Male ; Middle Aged ; Neoplasms, Connective and Soft Tissue ; Proto-Oncogene Proteins B-raf ; Receptor, Platelet-Derived Growth Factor beta ; Vimentin ; Young Adult

PURPOSE: This study was designed to identify novel fusion transcripts (FTs) and their functional significance in colorectal cancer (CRC) lines. MATERIALS AND METHODS: We performed paired-end RNA sequencing of 28 CRC cell lines. FT candidates were identified using TopHat-fusion, ChimeraScan, and FusionMap tools and further experimental validation was conducted through reverse transcription-polymerase chain reaction and Sanger sequencing. FT was depleted in human CRC line and the effects on cell proliferation, cell migration, and cell invasion were analyzed. RESULTS: One thousand three hundred eighty FT candidates were detected through bioinformatics filtering. We selected six candidate FTs, including four inter-chromosomal and two intrachromosomal FTs and each FT was found in at least one of the 28 cell lines. Moreover, when we tested 19 pairs of CRC tumor and adjacent normal tissue samples, NFATC3–PLA2G15 FT was found in two. Knockdown of NFATC3–PLA2G15 using siRNA reduced mRNA expression of epithelial–mesenchymal transition (EMT) markers such as vimentin, twist, and fibronectin and increased mesenchymal–epithelial transition markers of E-cadherin, claudin-1, and FOXC2 in colo-320 cell line harboring NFATC3–PLA2G15 FT. The NFATC3–PLA2G15 knockdown also inhibited invasion, colony formation capacity, and cell proliferation. CONCLUSION: These results suggest that that NFATC3–PLA2G15 FTs may contribute to tumor progression by enhancing invasion by EMT and proliferation.
Cadherins ; Cell Line* ; Cell Movement ; Cell Proliferation ; Claudin-1 ; Colorectal Neoplasms* ; Computational Biology ; Fibronectins ; Humans ; RNA* ; RNA, Messenger ; RNA, Small Interfering ; Sequence Analysis, RNA* ; Vimentin

ObjectiveTo investigate the effects of Qiangjing Tablets (QJT) on sperm quality and the MAPK signaling pathway in the SD rat model of asthenospermia (AS).

METHODSA total of 100 male SD rats were randomly divided into five groups of equal number, blank control, AS model control, high-dose QJT, medium-dose QJT, and low-dose QJT. All the rats were intragastrically administered ORN at 200 mg/kg/d for establishment of the AS model except those in the blank control group, which were given 1% CMC sodium solution at 1 ml/100 g by gavage. Meanwhile the animals of the high-, medium-, and low-dose QJT groups were gavaged with QJT at 6700, 3300 and 1700 mg/kg/d, respectively, qd 6 days a week for 20 days. Then the testis issue and the apoptosis of the testicular cells were observed under the electron microscope, the expression of vimentin in the testis was determined with the immunohistochemical SP method, that of ERK1/2 detected by Western blot, and the concentration of TGF-β1 in the semen measured by ELISA.

RESULTSThe AS model controls showed round nuclei of spermatocytes, homogeneously distributed chromatins, broken or lost mitochondria, and expanded rough endoplasmic reticulum in the testis tissue. In comparison, the rats of the high-, medium-, and low-dose QJT groups exhibited round nuclei of spermatocytes, homogeneously distributed chromatins, and well-structured mitochondria, rough endoplasmic reticulum and ribosome, which were all similar those of the blank controls. Compared with the blank controls, the AS model rats manifested significantly increased expressions of ERK1/2 (1.00 ± 0.00 vs 1.26 ± 0.10, P<0.01) and vimentin (0.16 ± 0.01 vs 0.17 ± 0.01, P<0.01) and apoptosis rate of cells in the testis tissue (［9.20 ± 3.07］ vs ［42.20 ± 9.17］ %, P<0.01), but decreased level of TGF-β1 in the semen (［627.67 ± 26.07］ vs ［566.73 ± 68.44］ ng/ml, P<0.05). In comparison with the model controls, the rats of the high- and medium- -dose QJT groups presented remarkably down-regulated expressions of ERK1/2 (1.26 ± 0.10 vs 1.14 ± 0.08, P<0.01; 1.26 ± 0.10 vs 1.18 ± 0.05, P<0.05) and vimentin (0.17 ± 0.01 vs 0.16 ± 0.01, P<0.01; 0.17 ± 0.01 vs 0.17 ± 0.09, P<0.05) and decreased rate of cell apoptosis (［42.20 ± 9.17］ vs ［21.60 ± 5.94］ %, P<0.01; ［42.20 ± 9.17］ vs ［33.95 ± 6.39］ %, P<0.05). The concentration of TGF-β1 in the semen was markedly lower in the high-dose QJT than in the AS model control group (［621.78 ± 30.80］ vs ［566.73 ± 68.44］ ng/ml, P < 0.05).

CONCLUSIONSQiangjing Tablets could improve semen quality in asthenospermia rats by acting against oxidative stress.

Animals ; Apoptosis ; Asthenozoospermia ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Mitogen-Activated Protein Kinases ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Semen ; Semen Analysis ; Signal Transduction ; Spermatozoa ; Testis ; metabolism ; ultrastructure ; Transforming Growth Factor beta1 ; metabolism ; Vimentin ; metabolism

OBJECTIVETo investigate the molecular mechanism of action of BET bromodomain inhibitor JQ1 in treating airway remodeling in asthmatic mice.

METHODSA total of 24 mice were randomly divided into control group, ovalbumin (OVA)-induced asthma group (OVA group), and JQ1 intervention group (JQ1+OVA group), with 8 mice in each group. OVA sensitization/challenge was performed to establish a mouse model of asthma. At 1 hour before challenge, the mice in the JQ1+OVA group were given intraperitoneal injection of JQ1 solution (50 μg/g). Bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected at 24 hours after the last challenge, and the total number of cells and percentage of eosinophils in BALF were calculated. Pathological staining was performed to observe histopathological changes in lung tissue. RT-PCR and Western blot were used to measure the mRNA and protein expression of E-cadherin and vimentin during epithelial-mesenchymal transition (EMT).

RESULTSCompared with the control group, the OVA group had marked infiltration of inflammatory cells in the airway, thickening of the airway wall, increased secretion of mucus, and increases in the total number of cells and percentage of eosinophils in BALF (P<0.01). Compared with the OVA group, the JQ1+OVA group had significantly alleviated airway inflammatory response and significant reductions in the total number of cells and percentage of eosinophils in BALF (P<0.01). Compared with the control group, the OVA group had significant reductions in the mRNA and protein expression of E-cadherin and significant increases in the mRNA and protein expression of vimentin (P<0.01); compared with the OVA group, the JQ1+OVA group had significant increases in the mRNA and protein expression of E-cadherin and significant reductions in the mRNA and protein expression of vimentin (P<0.01); there were no significant differences in these indices between the JQ1+OVA group and the control group (P>0.05).

CONCLUSIONSMice with OVA-induced asthma have airway remodeling during EMT. BET bromodomain inhibitor JQ1 can reduce airway inflammation, inhibit EMT, and alleviate airway remodeling, which provides a new direction for the treatment of asthma.

Airway Remodeling ; drug effects ; Animals ; Asthma ; drug therapy ; Azepines ; pharmacology ; Cadherins ; analysis ; genetics ; Epithelial-Mesenchymal Transition ; Female ; Mice ; Nuclear Proteins ; antagonists & inhibitors ; Ovalbumin ; immunology ; RNA, Messenger ; analysis ; Transcription Factors ; antagonists & inhibitors ; Triazoles ; pharmacology ; Vimentin ; analysis ; genetics

PURPOSE: The biological function of long non-coding RNAs (lncRNAs) is only partially understood; therefore, in this study, we investigated the expression of the novel HOXA11 antisense (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC). MATERIALS AND METHODS: HOXA11as expression was examined in 129 SOC tissue samples by real time reverse transcription polymerase chain reaction. Clinicopathological factors and patient survival were compared between the high (n=27) and low HOXA11as expression group (n=102). To investigate the role of HOXA11as in cell proliferation, invasion, and migration, HOXA11as expression in ovarian cancer cells was knocked down using RNA interference. RESULTS: HOXA11as expression in cancer tissue was 77-fold higher than that of noncancerous tissue (p < 0.05). Higher HOXA11as expression was significantly correlated with histological grade (p=0.017) and preoperative cancer antigen 125 (p=0.048). HOXA11as overexpression in SOC cells led to increased cell proliferation, invasion, and migration. Moreover, HOXA11as was associated with the expression of genes involved in cell invasion, migration, and epithelial-mesenchymal transition (EMT), including vascular endothelial growth factor, matrix metalloproteinase 9 (MMP-9), B-catenin, E-cadherin, Snail, Twist, and vimentin. Multivariate analysis revealed that HOXA11as was a prognostic factor of progressive disease and mortality (hazard ratio [HR], 1.730; p=0.043 and HR, 2.170; p=0.033, respectively). Progression-free and overall survival were significantly shorter in patients with high HOXA11as expression. CONCLUSION: These findings highlight the clinical significance of HOXA11as to predicting the prognosis of SOC patients and suggest its potential in promoting tumor aggressiveness via regulation of vascular endothelial growth factor (VEGF), MMP-9, and EMT-related mechanisms.
Cadherins ; Cell Proliferation* ; Epithelial-Mesenchymal Transition ; Humans ; Matrix Metalloproteinase 9 ; Mortality ; Multivariate Analysis ; Ovarian Neoplasms* ; Polymerase Chain Reaction ; Prognosis* ; Reverse Transcription ; RNA Interference ; RNA, Long Noncoding* ; Snails ; Vascular Endothelial Growth Factor A ; Vimentin

BACKGROUND: Aquaporin 1 (AQP1) overexpression has been shown to be associated with uncontrolled cell replication, invasion, migration, and tumor metastasis. We aimed to evaluate AQP1 expression in lung adenocarcinomas and to examine its association with clinicopathological features and prognostic significance. We also investigated the association between AQP1 overexpression and epithelial-mesenchymal transition (EMT) markers. METHODS: We examined AQP1 expression in 505 cases of surgically resected lung adenocarcinomas acquired at the Seoul National University Bundang Hospital from 2003 to 2012. Expression of AQP1 and EMT-related markers, including Ecadherin and vimentin, were analyzed by immunohistochemistry and tissue microarray. RESULTS: AQP1 overexpression was associated with several aggressive pathological parameters, including venous invasion, lymphatic invasion, and tumor recurrence. AQP1 overexpression tended to be associated with higher histological grade, advanced pathological stage, and anaplastic lymphoma kinase (ALK) translocation; however, these differences were not statistically significant. In addition, AQP1 overexpression positively correlated with loss of E-cadherin expression and acquired expression of vimentin. Lung adenocarcinoma patients with AQP1 overexpression showed shorter progression-free survival (PFS, 46.1 months vs. 56.2 months) compared to patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter PFS (hazard ratio, 1.429; 95% confidence interval, 1.033 to 1.977; p=.031). CONCLUSIONS: AQP1 overexpression was thereby concluded to be an independent factor of poor prognosis associated with shorter PFS in lung adenocarcinoma. These results suggested that AQP1 overexpression might be considered as a prognostic biomarker of lung adenocarcinoma.
Adenocarcinoma* ; Aquaporin 1* ; Cadherins ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Humans ; Immunohistochemistry ; Lung* ; Lymphoma ; Multivariate Analysis ; Neoplasm Metastasis ; Phosphotransferases ; Prognosis* ; Recurrence ; Seoul ; Tissue Array Analysis ; Vimentin

To investigate the effect of a novel EZH2 inhibitor GSK126 on cell growth, apoptosis and migration of prostate cancer cells.Prostate cancer PC-3 and DU145 cells were treated with GSK126 at different doses. Cell growth was detected by sulforhodamine assay. Cell apoptosis was assayed by Annexin V-/PI kit. Transwell chamber and wound healing assays were conducted to detect cell migration. The mRNA level was detected by quantitative PCR, and protein expression was detected by Western blot analysis.GSK126 showed significant effect on cell growth and apoptosis when the dose was higher than 50 μmol/L. Wound healing assay revealed that scratch space in PC-3 cells was significantly increased in a dose-dependent manner in GSK126-treated groups[(247.2±24.4),(347.2±19.2) and (410.5±18.1) μm in low, medium and high dose (5.0, 20.0, 50.0 μmol/L), respectively] as compared with the control group[(171.3±17.8) μm](all<0.05). Transwell assay showed that migrated PC-3 cells in control group was 322.0±17.9,while those in GSK126-treated groups were 198.3±15.4 (low),82.7±6.2 (medium) and 30.2±4.1 (high), and the differences between the control group and GSK126-treated groups were significant(all<0.05). In addition, GSK126 up-regulated E-cadherin mRNA expression and down-regulated N-cadherin and Vimentin mRNA expression, whereas had no significant effect on Snail, Fibronectin and VEGF-A mRNA expression. The protein expression of E-cadherin was elevated but VEGF-A protein did not change in GSK126-treated groups. Similar results were exhibited in DU145 cell.GSK126 can significantly inhibit cell migration and invasion in prostate cancer PC-3 and DU145 cells, which may be resulted from its effect on epithelial-mesenchymal transition. GSK126 may be used as a potential anti-prostate cancer dug in clinic.
Apoptosis ; drug effects ; Cadherins ; analysis ; drug effects ; metabolism ; Cell Line, Tumor ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Down-Regulation ; drug effects ; Drug Screening Assays, Antitumor ; methods ; Enhancer of Zeste Homolog 2 Protein ; analysis ; drug effects ; metabolism ; Fibronectins ; analysis ; drug effects ; metabolism ; Humans ; Indoles ; pharmacology ; Male ; Prostatic Neoplasms ; chemistry ; genetics ; physiopathology ; Pyridones ; pharmacology ; RNA, Messenger ; Up-Regulation ; drug effects ; Vascular Endothelial Growth Factor A ; analysis ; drug effects ; Vimentin ; analysis ; drug effects ; metabolism

OBJECTIVETo study the clinicopathologic features of tuberous sclerosis complex (TSC).

METHODSThe clinicopathologic data of the patients diagnosed as TSC with refractory epilepsy and resection of epileptic focus were retrospectively analyzed.

RESULTSFourteen cases were included, the mean age was (15.8±12.9) years, with a male predominance (male to female ratio=10:4). Frontal lobe was the most common (13/14) site of involvement. MRI showed multiple patchy long T1 and long T2 signals. CT images showed multiple subependymal high density calcified nodules in nine cases. Histology showed mild to severe disruption of the cortical lamination, cortical and subcortical tubers with giant cells and/or dysmorphic neurons. The giant cells showed strong immunoreactivity for vimentin and nestin, while the dysmorphic neurons partially expressed MAP2 and NF. Vimentin also stained strongly the "reactive" astrocytes. Thirteen cases had follow-up information: Engel class I in six cases, Engel class II in six cases, and Engel class III in one case.

CONCLUSIONSDiagnosis of TSC relies on combined pathologic, clinical and neuroradiological features. Immunohistochemical staining can be helpful. Resection of epileptic focus is an effective method to treat refractory epilepsy in TSC.

Adolescent ; Astrocytes ; chemistry ; pathology ; Child ; Drug Resistant Epilepsy ; surgery ; Epilepsy ; complications ; metabolism ; pathology ; Epilepsy, Frontal Lobe ; complications ; metabolism ; pathology ; Female ; Giant Cells ; chemistry ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Nestin ; analysis ; Neurons ; metabolism ; pathology ; Retrospective Studies ; Tuberous Sclerosis ; complications ; metabolism ; pathology ; Vimentin ; analysis

OBJECTIVETo investigate the diagnostic role of STAT6 immunohistochemistry in solitary fibrous tumors (SFT)/meningeal hemangiopericytomas (HPC).

METHODEvaluated the expression of STAT6, vimentin, CD34, EMA, PR, S-100, CD56, GFAP and Ki-67 in a cohort of 37 SFT/meningeal HPC, 30 meningiomas and 30 schwannomas by immunohistochemistry staining.

RESULTSAll SFT/meningeal HPC demonstrated nuclear positivity for STAT6, and the proportion of positive tumor cells ranged from 60% to 95%, with no significant difference cases.Vimentin was strongly positive in all cases. CD34, EMA and PR positivity was found in 32 cases, 1 case and 4 cases, respectively.S-100 protein, CD56 and GFAP were negative; Ki-67 labeling index was 1%-8%. However, the meningiomas and schwannomas were negative for STAT6.

CONCLUSIONSSTAT6 is a relatively specific biomarker for SFT/meningeal HPC, and may be used in the diagnosis and differential diagnosis of SFT/meningeal HPC, especially for the atypical cases, and allows the precise pathologic diagnosis of SFT/meningeal HPC.

Antigens, CD ; analysis ; Antigens, CD34 ; analysis ; Antigens, Differentiation, T-Lymphocyte ; analysis ; Biomarkers, Tumor ; analysis ; Diagnosis, Differential ; Glial Fibrillary Acidic Protein ; analysis ; Hemangiopericytoma ; chemistry ; diagnosis ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; analysis ; Meningeal Neoplasms ; chemistry ; diagnosis ; Meningioma ; chemistry ; diagnosis ; Neurilemmoma ; chemistry ; diagnosis ; S100 Proteins ; analysis ; STAT6 Transcription Factor ; analysis ; Solitary Fibrous Tumors ; chemistry ; diagnosis ; Vimentin ; analysis