Objective: To examine the effect of SiO2 exposure on the airway surface microenvironment and NIMA-related kinase 7 (NEK7)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in rats. Methods: Twenty-four specific pathogen-free male rats of the SD strain were randomly divided into the control group and the model group, of 12 rats in each group. Rats in the model group were given SiO2 suspensions through disposable tracheal intubation perfusion to model silicosis in rats, while rats in the control group was perfused with the same amount of physiological saline. The pH value and glucose level were measured in the rat bronchoalveolar lavage fluid (BALF) 14 and 28 days after modeling. Lung tissues were stained with HE and Masson and the distribution of inflammatory cells and the deposition of pulmonary interstitial collagens were observed in lung tissues under a light microscope. The expression of transforming growth factor β1 (TGF-β1), collagen type Ⅰ(ColⅠ), collagen type Ⅲ (Col Ⅲ), interleukin-1β (IL-1β), NLRP3, N-terminal domain of Gasdermin D (GSDMD-NT), caspase-1, and NEK7 was quantified in lung specimens using immunohistochemistry. Results: Lower pH values were measured in rat BALF in the model group than in the control group 14 [(6.38±0.05) vs. (6.68±0.08), P<0.05] and 28 days after modeling [(6.63±0.14) vs. (6.86±0.05), P<0.05], while higher glucose levels were seen in the model group than in the control group 14 [(0.39±0.06) vs. (0.31±0.04) mg/dL, P<0.05] and 28 days after modeling [(0.39±0.08) vs. (0.31±0.06) mg/dL, P<0.05]. HE and Masson staining showed mild to moderate alveolitis and pulmonary fibrosis in rats 14 days post-exposure to SiO2, and showed moderate to severe alveolitis and pulmonary fibrosis 28 days post-exposure. Immunohistochemistry detected higher TGF-β1, ColⅠ, Col Ⅲ, IL-1β, NLRP3, GSDMD-NT, caspase-1 and NEK7 expression in rat lung tissues in the model group than in the control group (all P<0.05). Conclusions SiO2 exposure may cause changes in rat airway surface microenvironment, including BALF acidification and elevated glucose. Pyroptosis induced by activation of NEK7-associated NLRP3 inflammasome may be an important mechanism of pulmonary fibrosis caused by silicosis.

Adult ; Female ; Humans ; Immunohistochemistry ; methods ; Male ; Meningeal Neoplasms ; immunology ; ultrastructure ; Meningioma ; immunology ; ultrastructure ; Microscopy, Electron ; Middle Aged ; Paraganglioma ; physiopathology

Adenoma ; pathology ; Brain Neoplasms ; secondary ; Chromogranin A ; metabolism ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Pituitary Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Reoperation ; Synaptophysin ; metabolism ; Temporal Lobe ; pathology

Adult ; Brain Neoplasms ; pathology ; Glioblastoma ; pathology ; Humans ; Male ; Pineal Gland ; pathology

Base Sequence ; DNA, Neoplasm ; genetics ; DNA-Binding Proteins ; metabolism ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Genes, Immunoglobulin Heavy Chain ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Interferon Regulatory Factors ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; Molecular Sequence Data ; Neprilysin ; metabolism ; Proto-Oncogene Proteins c-bcl-6

OBJECTIVETo explore the inhibition of Hedyotis diffusa Willd Injection (HDI) on the proliferation of RPMI 8226 cells and its mechanisms.

METHODSThe inhibition of HDI on the proliferation of RPMI 8226 cells was detected by MTT and the drug concentrations for further researches were screened out. The apoptosis rate was detected using Annexin V-PI of flow cytometry. The cell cycle distribution was detected by PI. The expressions of adhesion molecule FITC-CD44 and PE-CD49d were detected. The IL-6 and VEGF concentrations of cell supernatants were tested by ELISA. The mRNA expressions of Bax, Bcl-2, Caspase-3, Survivin, IL-6, and VEGF were detected by RT-PCR.

RESULTSHDI could inhibit the proliferation of RPMI 8226 cells. Meanwhile, it induced their early apoptosis, arresting them at G1 phase in a concentration-dependent manner. The VEGF concentrations were down-regulated after acted by 0, 20, 40, and 60 microL/mL HDI in a dose-dependent manner (P< 0.01). The IL-6 content increased (P<0.01). The expressions of CD44 and CD49d were up-regulated in a concentration-dependent manner. After acted by 40 microL/mL HDI, the Survivin mRNA level was significantly downregulated (P<0.01), the mRNA levels of Bcl-2, IL-6, and VEGF were significantly up-regulated (P<0.01), but the up-regulation of Bax and Caspase-3 mRNA levels were not so obvious (P>0.05).

CONCLUSIONSHDI could inhibit the proliferation of RPMI 8226 cells. Its mechanisms might be correlated with early apoptosis induction, G1 phase arresting, VEGF secretion lowering, and Survivin mRNA transcription level down-regulating.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Hedyotis ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Interleukin-6 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo study the clinicopathologic features, treatment response and prognosis of pleomorphic xanthoastrocytoma (PXA).

METHODSAmongst a total of 6 287 patients with central nervous system tumors encountered in Nanjing General Hospital of PLA during the period from 1980 to 2004, 15 cases of PXA were found. Two additional cases of PXA were also retrieved from the authors' consultation files. The clinicopathologic features of the 17 cases were studied. Follow-up information was available in 10 patients.

RESULTSThe age of the patients ranged from 12 to 55 years (mean = 30.8 years). The male-to-female ratio was 6:11. Commonest clinical symptoms included seizures, headaches and dizziness. The tumors in 16 patients were located in the superficial cerebral cortex (94.1%). Seven cases (41.2%) involved the temporal lobe. The size of the tumors varied from 2 to 7 cm (mean = 4.3 cm). Cystic degeneration was noted in 9 cases. For those in-house cases, total tumor excision was performed in 12 patients and subtotal tumor excision was performed in 3 patients. Amongst the 10 patients with follow-up information available, 8 were alive. The post-operative survival ranged from 10 months to more than 13 years (mean survival = 6 years). Classic histopathologic features included an admixture of mononuclear cells, bizarre multinucleated giant cells, spindled cells and lipid-rich vacuolated cells. The tumor cells were associated with abundant lymphocytes and reticulin fibers. They showed little tumor necrosis or mitotic activity. Immunohistochemical study demonstrated diffuse positive staining for glial fibrillary acidic protein, vimentin and S-100 protein. Seventy-seven percent of the cases also showed positive staining for CD34. One case had anaplastic transformation, with increased mitotic activity (mitotic count >or= 5 per 10 high power fields). The tumor cells infiltrated the underlying cerebral cortex with extension into perivascular spaces in 2 cases. Radiologic examination revealed tumor recurrence with diffuse leptomeningeal spread in 1 case.

CONCLUSIONSPXA is low-grade glial tumor, corresponding to WHO grade II. Cases with typical pathologic features and total tumor excision carry favorable prognosis. Local recurrence or anaplastic transformation may occur in rare examples. Histologically, PXA can be mistaken as WHO grade IV giant cell glioblastoma, as both entities possess tumor giant cells. PXA however harbors lipiodized astrocytes and lacks coagulative tumor necrosis and high mitotic activity. Frequent expression of CD34 in PXA is also helpful in differential diagnosis.

Adolescent ; Adult ; Brain Neoplasms ; metabolism ; pathology ; ultrastructure ; Child ; Female ; Follow-Up Studies ; Glial Fibrillary Acidic Protein ; analysis ; Glioblastoma ; metabolism ; pathology ; ultrastructure ; Humans ; Immunohistochemistry ; Male ; Microscopy, Electron ; Middle Aged ; S100 Proteins ; analysis ; Young Adult

OBJECTIVETo study clinicopathologic features, diagnosis, treatment and prognosis of von Hippel-Lindau (VHL) syndrome-related and sporadic hemangioblastomas of the central nervous system (CNS-HB).

METHODSHistopathological, ultrastructural, immunohistochemical (EnVision method) and clinical features of 21 VHL syndrome and 63 sporadic CNS-HB cases were studied with correlation of the available follow-up information.

RESULTSTwenty-one VHL patients accompanied with a total of 87 CNS-HBs, including one patient of developing 12 HBs within 13 years. There were 10 patients presenting other lesions related to VHL, including 6 retinal HBs, 4 pancreatic tumors (endocrine tumor and microcystic cystadenoma), 1 clear renal cell carcinoma, 4 renal cysts and 1 endolymphatic sac tumor. One patient developed 5 different tumors related to VHL within a period of 4 years. In the 63 cases of sporadic CNS-HB (34 male and 29 female), the mean age was 43.0 years. Among the 18 VHL syndrome patients with available follow-up information, 14 were still alive and within them, 4 became disabled and 11 had developed new lesions. The other 4 patients died. Among the 42 patients of sporadic HB with follow-up information, 39 were alive including 3 disabled cases, and the other 3 died. Histologically, the tumors showed large and vacuolated stromal cells. Some tumors showed atypical nuclei. Involvement of the brain tissue was seen in 32 cases, among which, 21 patients with available follow-up information were learnt to be alive. Tumor cells of HB stained positive for vimentin, EGFR, Inhibin alpha and D2-40, but negative for CD34 and CD68. In 3 cases of HB, some stromal cells were positive for GFAP. All cases showed a low expression for Ki-67, except 2 cases with 2% and 1 case with 5% Ki-67 indices.

CONCLUSIONSVHL syndrome is a multisystem disorder with a poor prognosis and a high rate of missed diagnosis. The syndrome is characterized by development of various benign and malignant tumors. The most common tumor is CNS-HB, which occurs predominantly in the cerebellum. Patients with VHL syndrome tend to present at a younger age than patients with sporadic CNS-HBs, and VHL related HB occurs more predominantly in the brain stem and spinal cord. Prognosis of CNS-HB patients is not correlated with the nuclear atypicality, expression for Ki-67 and involvement of the brain tissue. Because new lesions may develop during the patient's lifetime. So that, regular clinical inspection is recommended in order to check up the development of any new lesions.

Adolescent ; Adult ; Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Central Nervous System Neoplasms ; metabolism ; pathology ; surgery ; Child ; Female ; Follow-Up Studies ; Glial Fibrillary Acidic Protein ; metabolism ; Hemangioblastoma ; metabolism ; pathology ; surgery ; Humans ; Inhibins ; metabolism ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Pancreatic Neoplasms ; metabolism ; pathology ; surgery ; Receptor, Epidermal Growth Factor ; metabolism ; Retinal Neoplasms ; metabolism ; pathology ; surgery ; Survival Analysis ; Vimentin ; metabolism ; Young Adult ; von Hippel-Lindau Disease ; metabolism ; pathology ; surgery

OBJECTIVETo study clinicopathologic features, treatment and prognosis of pilocytic astrocytoma (PA).

METHODSHistopathological, ultrastructural, immunohistochemical (EnVision method) and clinical features of 68 cases of PA were studied by microscopic investigation with correlation of clinical follow-up information when available.

RESULTSThirty-five male patients and 33 female patients were studied. The patient's age ranged from 3 to 66 years (mean = 20.1 years). The mean time from symptom onset to surgery was 371 days (range, 3 days to 14 years). Cystic degeneration was noted in 41 cases (60.3%), and enhancement of the tumor was noted in 43 cases (87.8%). On postcontrast imaging examination there were 33 cases involving the cerebellum (48.5%). Total tumor excision was performed in 35 patients, subtotal tumor excision was performed in 31 patients, and the procedures of other 2 patients were not clear. Among 51 patients with follow-up information, 44 were alive, 7 had recurrent tumor, and 7 died. The post-operative survival ranged from 2 months to 124 months (mean survival = 48.1 months). Five years and ten years survival rates were 89%, respectively. Tumors with classic histopathology demonstrated biphasic pattern of growth, consisting of compact elongated bipolar astrocytes associated with rosenthal fibers, and less cellular areas of multipolar cells with granular bodies and microcyst. Some cases showed atypia of nuclei, and occasional mitoses. Involvement of subarachnoid space was seen in 17 cases. One case had anaplastic features. All cases showed diffuse positive staining for GFAP and low expression for Ki-67, except 1 anaplastic tumor with 10% Ki-67 indices. Tumors with subarachnoid space involvement showed positive reticular fiber staining and negative EMA staining.

CONCLUSIONSPA is a benign, WHO grade I tumor with favorable prognosis, and does not require radiotherapy after total resection. The tumor can be mistaken as higher-grade astrocytoma when involving the subarachnoid space, and with cytological atypia, leading to unnecessary radiotherapy after surgery. Recurrence rate is increased when only partial resection is achieved. The outcome for patients with brainstem tumor or anaplastic PA is poor.

Astrocytoma ; diagnosis ; genetics ; Brain Neoplasms ; diagnosis ; genetics ; Cell Nucleus ; pathology ; Female ; Glial Fibrillary Acidic Protein ; genetics ; Humans ; Male ; Prognosis ; Recurrence ; Treatment Outcome

OBJECTIVETo investigate the clinicopathological characteristics, diagnosis and differential diagnoses of proximal-type epithelioid sarcoma (PES).

METHODSFive cases of PES were retrieved from pathology files. Clinical, pathologic and immunohistochemical features of the tumors were reviewed.

RESULTSOne patient was female and 4 were male. Ages of the patients ranged from 19 to 46 years. The sites of the tumor involvement were vulvar (2 cases), hypogastric zone (1 case), anterosuperior iliac spine (1 case) and buttock (1 case). Clinically, the tumor masses were painless and progressive solitary nodules. Microscopically, the tumor cell growth was infiltrative in nature, nodular in appearance with degenerative and necrotic cells at the central areas. The tumors consisted of relatively uniform epithelioid cells with round or oval nuclei and eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for vimentin (5/5), CK (4/5), EMA (4/5), beta-catenin (3/5), CD34 (3/5), and S-100 protein (1/5), but were negative for SMA, MyoD1, Desmin, HMB-45, CK7 and CK20.

CONCLUSIONDefinitive diagnosis of PES relies on its histopathological characteristics in conjunction with appropriate immunohistochemical findings.

Adult ; Chemotherapy, Adjuvant ; Epithelioid Cells ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Neoplasm Recurrence, Local ; Pelvic Neoplasms ; metabolism ; pathology ; surgery ; Radiotherapy, Adjuvant ; Sarcoma ; metabolism ; pathology ; surgery ; Soft Tissue Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism ; Vulvar Neoplasms ; metabolism ; pathology ; surgery ; Young Adult ; beta Catenin ; metabolism