Pro-prion, as a membrane adaptor protein for E3 ligase c-Cbl, facilitates the ubiquitination of IGF-1R, promoting melanoma metastasis.

Aberrant activation of receptor tyrosine kinase (RTK) is usually a result of mutation and plays important roles in tumorigenesis. How RTK without mutation affects tumorigenesis remains incompletely understood. Here we show that in human melanomas pro-prion (pro-PrP) is an adaptor protein for an E3 ligase c-Cbl, enabling it to polyubiquitinate activated insulin-like growth factor-1 receptor (IGF-1R), leading to enhanced melanoma metastasis. All human melanoma cell lines studied here express pro-PrP, retaining its glycosylphosphatidylinositol-peptide signal sequence (GPI-PSS). The sequence, PVILLISFLI in the GPI-PSS of pro-PrP, binds c-Cbl, docking c-Cbl to the inner cell membrane, forming a pro-PrP/c-Cbl/IGF-1R trimeric complex. Subsequently, IGF-1R polyubiquitination and degradation are augmented, which increases autophagy and tumor metastasis. Importantly, the synthetic peptide PVILLISFLI disrupts the pro-PrP/c-Cbl/IGF-1R complex, reducing cancer cell autophagy and mitigating tumor aggressiveness in vitro and in vivo. Targeting cancer-associated GPI-PSS may provide a therapeutic approach for treating human cancers expressing pro-PrP.

Integration of molecular pathology with histopathology to accurately evaluate the biological behaviour of WHO grade 2 meningiomas and patient prognosis.

PURPOSE: A molecular pathological grading method was tested in WHO grade 2 meningiomas to judge whether this molecular grading can more accurately evaluate meningioma biological behaviour. METHODS: The medical records and paraffin-embedded tissues of surgically resected WHO grade 2 meningioma patients in our department from January 1, 2010, to December 31, 2020, were collected. The molecular pathological risk grading suggested by Sahm et al. was adopted and the patients were graded as low, intermediate and high risk. Progression-free survival (PFS), malignant progression-free survival (MPFS) and overall survival (OS) were analysed. Univariate and multivariate analysis were performed to determine the relationship between molecular risk grading and patient survival. RESULTS: Of the 98 patients, 13 (13.2%) were graded as low risk, 63 patients (64.3%) were graded as intermediate risk, and 22 patients (22.4%) were graded as high risk. With increasing molecular risk grade, the rates of tumour recurrence, malignant progression and mortality increased significantly (P < 0.05). Multivariate analysis showed that molecular risk grading was negatively associated with PFS (HR 0.018, 95% CI 0.003-0.092), MPFS (HR 0.040, 95% CI 0.006-0.266) and OS (HR 0.088, 95% CI 0.016-0.472) (P < 0.01), and gross total resection (Simpson grade I-III) significantly prolonged PFS (HR 5.882, 95% CI 2.538-13.699) and OS (HR 2.611, 95% CI 1.117-7.299) (P < 0.05). CONCLUSION: Sahm et al.'s molecular risk grading can further refine the classification of WHO grade 2 meningiomas and more accurately evaluate their biological behaviour and patient prognosis.

Worenine Prevents Solar Ultraviolet-Induced Sunburn by Inhibiting JNK2.

Excessive solar ultraviolet (SUV) radiation often causes dermatitis, photoaging, and even skin cancer. In the pathological processes of SUV-induced sunburn, JNK is activated by phosphorylation, and it in turn phosphorylates its downstream transcription factors, such as ATF2 and c-jun. The transcription factors further regulate the expression of pro-inflammatory genes, such as IL-6 and TNF-α, which ultimately leads to dermatitis. Therefore, inhibiting JNK may be a strategy to prevent dermatitis. In this study, we screened for worenine as a potential drug candidate for inhibiting sunburn. We determined that worenine inhibited the JNK-ATF2/c-jun signaling pathway and the secretion of IL-6 and TNF-α in cell culture and in vivo, confirming the role of worenine in inhibiting sunburn. Furthermore, we determined that worenine bound and inhibited JNK2 activity in vitro through the MST, kinase, and in vitro kinase assays. Therefore, worenine might be a promising drug candidate for the prevention and treatment of SUV-induced sunburn.

Case report and literature review: thyroid carcinoma showing intrathyroid thymic carcinoma.

Background: Intrathyroid thymic carcinoma (ITTC) is a rare malignancy of the thyroid gland with histological and immunophenotypic resemblance to thymic carcinoma. Surgery combined with adjuvant radiotherapy improves the survival of patients with ITTC. However, for patients with extensive metastases, there is currently no effective treatment. Chemotherapy is an option but has not demonstrated improved patient survival. Methods and results: A female patient presented with metastases to the pleura, lung, and bone 16 years after surgery for ITTC. As radiotherapy and chemotherapy failed to control the recurrent disease, lenvatinib treatment was initiated. After 3 months, positron emission tomography/computed tomography showed a substantial reduction of all metastatic lesions and decreased tumor metabolism. The patient continues to receive lenvatinib and remains well and symptom-free. Conclusion: For patients with ITTC who have progressive, life-threatening metastases, lenvatinib represents a valuable salvage therapy that may offer a sustained reduction in tumor burden and maintenance of quality of life.

A survival analysis of surgically treated incidental low-grade glioma patients.

To evaluate the surgical effect on survival in patients with incidental low-grade glioma (LGG) through comparison between asymptomatic and symptomatic patients. The medical records of surgically treated adult cerebral incidental LGG (iLGG) patients in our department between January 2008 and December 2015 were retrospectively reviewed. The survival of patients was calculated starting from the initial imaging diagnosis. Factors related to progression-free survival (PFS), overall survival (OS) and malignant progression-free survival (MPFS) were statistically analyzed. Seventy-five iLGG patients underwent surgery: 49 in the asymptomatic group, who underwent surgery in the asymptomatic period, and 26 in the symptomatic group, who underwent surgery after the tumor had grown and the patients had developed tumor-related symptoms. Significantly more tumors were initially located adjacent to the functional area in the symptomatic group than in the asymptomatic group (P < 0.05), but there was no significant difference in the total resection rate between the two groups. The incidence of postoperative complications (15.4%) and postoperative epilepsy (23.1%) was higher in the symptomatic group than in the asymptomatic group (4.1% and 10.2%, respectively). Multivariate analysis showed that surgical timing, namely, surgery performed before or after symptom occurrence, had no significant effect on PFS, OS or MPFS, while total resection significantly prolonged PFS, OS and MPFS, and the pathology of oligodendroglioma was positively correlated with PFS and OS (P < 0.05). Surgical timing for iLGGs should facilitate total resection. If total resection can be achieved, even after symptom occurrence, patients can achieve comparable survival benefits to those treated with surgery in the asymptomatic phase.

TOPK inhibits autophagy by phosphorylating ULK1 and promotes glioma resistance to TMZ.

ULK1, the upper-most protein of the ULK1 complex, is emerging as a crucial node in autophagy induction. However, the regulation of ULK1 is not fully understood. In this study, we identified TOPK (T-LAK cell-originated protein kinase), an oncokinase, as a novel upstream kinase to phosphorylate ULK1. We found that TOPK could directly bind with and phosphorylate ULK1 at Ser469, Ser495, and Ser533. The phosphorylation of ULK1 at Ser469, Ser495, and Ser533 by TOPK decreased the activity and stability of ULK1. In addition, we want to examine the initiation of autophagy because the reduction activity of ULK1 reduces the occurrence of autophagy. We demonstrated that TOPK could inhibit the initiation and progression of autophagy in glioma cells. Furthermore, TOPK inhibition increased the sensitivity of glioma cells to temozolomide (TMZ). This discovery provides insight into the problem of TMZ-resistance in GBM treatment.

Solitary Fibrous Tumor/Hemangiopericytoma of Spinal Cord: A Retrospective Single-Center Study of 16 Cases.

OBJECTIVE: In this study, we retrospectively reviewed our experience in the surgical management of solitary fibrous tumor (SFT)/hemangiopericytomas (HPCs) of the spinal cord. METHODS: Sixteen patients with SFT/HPCs of the spinal cord were enrolled in this study. Data on clinical presentation, radiologic findings, histopathologic features, surgical treatment, adjuvant therapy, and prognosis were retrospectively reviewed. Kaplan-Meier curves and log-rank tests were used to identify the prognostic factors for recurrence and overall survival (OS). RESULTS: Our series included 6 men and 10 women, with a male/female ratio of 1:1.7. Magnetic resonance imaging (MRI) showed slightly hyperintense lesions on T2-weighted images for all 16 patients. All tumors showed positive immunohistochemical staining for signal transducer and activator of transcription 6. Statistical analysis of clinical data showed that age, gender, tumor location, tumor size, medullary compartment location, and Ki-67 index were not associated with recurrence and OS (P > 0.05). However, World Health Organization grade III was significantly associated with recurrence (P < 0.01). Gross total resection (GTR) and postoperative radiotherapy significantly reduced recurrence (P < 0.01 and P < 0.05), but only GTR showed remarkable benefits to improve OS (P < 0.05). CONCLUSIONS: SFT/HPCs of spinal cord are rare neoplasms with a propensity to recur. Hyperintensity on T2-weighted magnetic resonance imaging combined with positive immunohistochemical staining for signal transducer and activator of transcription 6 are important clues for classification and differentiation of these tumors. The extent of resection, World Health Organization grade, and postoperative radiotherapy might be predictive factors for recurrence. Complete tumor resection should be sought whenever possible, and adjuvant radiotherapy is recommended after surgical resection. Moreover, regular and long-term follow-up is mandatory to monitor recurrence.

CD2-Associated Protein Contributes to Hepatitis C, Virus Propagation and Steatosis by Disrupting Insulin Signaling.

Chronic hepatitis C virus (HCV) infection can result in steatosis, a condition displaying aberrant accumulation of neutral lipid vesicles, the component of lipid droplets (LDs), which are essential for HCV assembly. However, the interplay between HCV infection and steatosis remains unclear. Here, we show that HCV-infected cells have higher levels of CD2-associated protein (CD2AP), which plays two distinct, yet tightly linked, roles in HCV pathogenesis: Elevated CD2AP binds to nonstructural protein 5A (NS5A) and participates in the transport of NS5A to LDs to facilitate viral assembly; Up-regulated CD2AP also interacts with casitas B-lineage lymphoma (b) (Cbl/Cbl-b) E3 ligases to degrade insulin receptor substrate 1 (IRS1), which, in turn, disrupts insulin signaling and increases LD accumulation through the IRS1/protein kinase B (Akt)/adenosine monophosphate-activated protein kinase (AMPK)/hormone-sensitive lipase (HSL) signaling axis to accommodate viral assembly. In the HCV-infected mouse model, CD2AP expression is up-regulated during the chronic infection stage and this up-regulation correlates well with liver steatosis. Importantly, CD2AP up-regulation was also detected in HCV-infected human liver biopsies showing steatosis compared to non-HCV-infected controls. Conclusion: CD2AP is indicated as a protein up-regulated by HCV infection, which, in turn, stimulates HCV propagation and steatosis by disrupting insulin signaling; targeting CD2AP may offer an opportunity for alleviating HCV infection and its associated liver pathology. (Hepatology 2018;XX:XXX-XXX.).

T-lymphokine-activated killer cell-originated protein kinase (TOPK) as a prognostic factor and a potential therapeutic target in glioma.

TOPK is overexpressed in various types of cancer and associated with poor outcomes in different types of cancer. In this study, we first found that the expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was significantly higher in Grade III or Grade IV than that in Grade II in glioma (P = 0.007 and P < 0.001, respectively). Expression of TOPK was positively correlated with Ki67 (P < 0.001). Knockdown of TOPK significantly inhibited cell growth, colony formation and increased sensitivities to temozolomide (TMZ) in U-87 MG or U-251 cells, while TOPK overexpression promoted cell growth and colony formation in Hs 683 or A-172 cells. Glioma patients expressing high levels of TOPK have poor survival compared with those expressing low levels of TOPK in high-grade or low-grade gliomas (hazard ratio = 0.2995; 95% CI, 0.1262 to 0.7108; P = 0.0063 and hazard ratio = 0.1509; 95% CI, 0.05928 to 0.3842; P < 0.0001, respectively). The level of TOPK was low in TMZ-sensitive patients compared with TMZ-resistant patients (P = 0.0056). In TMZ-resistant population, patients expressing high TOPK have two months' shorter survival time than those expressing low TOPK. Our findings demonstrated that TOPK might represent as a promising prognostic and predictive factor and potential therapeutic target for glioma.

Clinical, radiological, and histological features and treatment outcomes of supratentorial extraventricular ependymoma: 14 cases from a single center.

OBJECTIVE Reports on supratentorial extraventricular ependymoma (STE) are relatively rare. The object of this study was to analyze the clinical, radiological, and histological features and treatment outcomes of 14 patients with STE. METHODS Overall, 227 patients with ependymoma underwent surgical treatment in the authors' department between January 2010 and June 2015; 14 of these patients had STE. Data on clinical presentation, radiological studies, histopathological findings, surgical strategies, and treatment outcomes in these 14 cases were retrospectively analyzed. RESULTS The patients consisted of 6 women and 8 men (sex ratio 0.75). Mean age at diagnosis was 24.5 ± 13.5 years (range 3-48 years). Tumors were predominantly located in the frontal and temporal lobes (5 and 4 cases, respectively). Typical radiological features were mild to moderate heterogeneous tumor enhancements on contrast-enhanced MRI. Other radiological features included well-circumscribed, "popcorn" enhancement and no distinct adjoining brain edema. Gross-total resection was achieved in 12 patients, while subtotal removal was performed in 2. Radiotherapy was administered in 7 patients after surgery. Seven tumors were classified as WHO Grade II and the other 7 were verified as WHO Grade III. The mean follow-up period was 22.6 months (range 8-39 months). There were 3 patients with recurrence, and 2 of these patients died. CONCLUSIONS Supratentorial extraventricular ependymoma has atypical clinical presentations, various radiological features, and heterogeneous histological forms; therefore, definitive diagnosis can be difficult. Anaplastic STE shows malignant biological behavior, a higher recurrence rate, and a relatively poor prognosis. Gross-total resection with or without postoperative radiotherapy is currently the optimal treatment for STE.

Primary extraskeletal myxoid chondrosarcoma in cerebellum: A case report with literature review.

RATIONALE: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm of which intracranial EMC is the rarest. PATIENT CONCERNS: We present an unusual case report of a 41-year-old woman who was sent to the emergency department for a sudden headache and other symptoms related to increased intracranial pressure. INTERVENTIONS: Emergent CT revealed an occupying lesion in the left cerebellum with surrounding edema. A complete surgical excision of the lesion through a transcortical approach was performed. After the operation, this patient received adjuvant radiotherapy and temozolomide treatment. DIAGNOSES: Pathology diagnosis was an intracranial EMC. OUTCOMES: The patient survives with no tumor recurrence as of the last follow-up. Progression-free survival exceeded 20 months. LESSONS: We have reviewed the literature and here summarize the diagnosis and treatment options for intracranial EMC. Diagnosis and treatment options of this rare disease are discussed.

Analyses of prognosis-related factors of intracranial solitary fibrous tumors and hemangiopericytomas help understand the relationship between the two sorts of tumors.

Increasing evidence has suggested a close relationship between solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) in the central nervous system (CNS). However, CNS SFTs differentiate from HPCs in their clinical behavior and patient prognoses. Analyses of prognosis-related factors can help clarify the relationship between SFT and HPC. The intracranial SFT and HPC cases treated in our departments from January 2002 to December 2012 were retrospectively reviewed. The SFT and HPC cases were also combined into an SFT/HPC group. The factors associated with patient progression-free survival (PFS) and overall survival (OS) were statistically analyzed using uni- and multivariate analyses. Fifty-eight intracranial SFT/HPC patients including 38 SFT patients and 20 HPC patients were treated during this period. The "Marseille grading" evaluated upon the histological aggressive phenotypes was applied in this study. The grading reflected a malignant progression ranging from "conventional" SFTs (grade I) to WHO III HPCs (grade III), and grade was negatively correlated with the PFS and OS of the SFT, HPC and SFT/HPC patients (P < 0.05).The multivariate analyses revealed that gross total resection (GTR) was significantly positively correlated with PFS and OS in the SFT, HPC and SFT/HPC patients and that radiotherapy was significantly positively correlated with PFS in the HPC and SFT/HPC patients (P < 0.05). In conclusion, the intracranial SFTs and HPCs share common prognostic factors including extent of surgery and pathology, moreover, the histological grading of the aggressive phenotypes supports the unifying of the CNS SFT and HPC into one tumor entity of SFT/HPC.

Meningeal Ewing Sarcoma/Peripheral PNET: Clinicopathological, Immunohistochemical and FISH study of four cases.

Meningeal Ewing Sarcoma (ES)/peripheral primitive neuroectodermal tumor (pPNET) is a rare diagnostically challenging small round cell tumor in the CNS. This study investigates the clinical pathological features of four cases of this tumor from archives of 6 years in our hospital. Patients were within the median age of 21.5 years and male to female ratio was 1:1. The tumors distributed at the supra-tentorial location, posterior fossa and lumbar vertebral canal, usually presenting as the dura-sited nodule or having close connection with the meninges within the cranium or vertebral canal. Histopathologically, small round undifferentiated tumor cells with hypercellularities, scant cytoplasm and inconspicuous nucleoli were observed, although some components such as atypical larger vesicular nuclei, prominent nucleoli of tumor cells, necrotic foci and mesenchymal collagen proliferation forming the lobular structure, were also appreciated. Immunohistochemally, tumor cells displayed membranous positivity of CD99 (4/4), nuclear positivity of FLI-1 (4/4) and NKX2.2 (4/4), negativity of EMA, GFAP and synaptophysin expression. The histochemical PAS staining showed weak positivity in one case. Fluorescence in situ hybridization (FISH) test using EWSR1 (22q12) dual color break apart rearrangement probe showed positive results in two cases. Results suggest that using a panel of immunohistochemical markers, including NKX2.2, CD99, FLI-1, EMA, GFAP and synaptophysin, combined with the supplementary EWSR1 FISH test, helps to define the diagnosis of meningeal ES/pPNET of CNS.

Salidroside suppresses solar ultraviolet-induced skin inflammation by targeting cyclooxygenase-2.

Solar ultraviolet (SUV) irradiation causes skin disorders such as inflammation, photoaging, and carcinogenesis. Cyclooxygenase-2 (COX-2) plays a key role in SUV-induced skin inflammation, and targeting COX-2 may be a strategy to prevent skin disorders. In this study, we found that the expression of COX-2, phosphorylation of p38 or JNKs were increased in human solar dermatitis tissues and SUV-irradiated human skin keratinocyte HaCaT cells and mouse epidermal JB6 Cl41 cells. Knocking down COX-2 inhibited the production of prostaglandin E2 (PGE2), the phosphorylation of p38 or JNKs in SUV-irradiated cells, which indicated that COX-2 is not only the key enzyme for PGs synthesis, but also an upstream regulator of p38 or JNKs after SUV irradiation. The virtual ligand screening assay was used to search for natural drugs in the Chinese Medicine Database, and indicated that salidroside might be a COX-2 inhibitor. Molecule modeling indicated that salidroside can directly bind with COX-2, which was proved by in vitro pull-down binding assay. Ex vivo studies showed that salidroside has no toxicity to cells, and inhibits the production of PGE2, phosphorylation of p38 or JNKs, and secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) caused by SUV irradiation. In vivo studies demonstrated that salidroside attenuates the skin inflammation induced by SUV. In brief, our data provided the evidences for the protective role of salidroside against SUV-induced inflammation by targeting COX-2, and salidroside might be a promising drug for the treatment of SUV-induced skin inflammation.

Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase.

Skin inflammation, and skin cancer induced by excessive solar ultraviolet (SUV) is a great threat to human health. SUV induced skin inflammation through activating p38 mitogen-activated protein kinase (p38) and c-Jun N-termeinal kinases (JNKs). T-LAK cell-originated protein kinase (TOPK) plays an important role in this process. Herein, the clinical data showed TOPK, phospho-p38, phospho-JNKs were highly expressed in human solar dermatitis. Ex vivo studies showed that SUV induced the phosphorylation of p38 and JNKs in HaCat and JB6 cells in a dose and time dependent manner. Molecule docking model indicated cefradine, an FDA-approved cephalosporin antibiotic, directly binds with TOPK. The result of in vitro binding assay verified cefradine can directly bind with TOPK. In vitro kinase results showed cefradine can inhibit TOPK activity. Ex vivo studies further showed cefradine inhibited SUV-induced the phosphorylation level of p38, JNKs and H2AX through inhibiting TOPK activity in a dose and time dependent manner, and cefradine inhibited the secretion of IL6 and TNF-α in HaCat and JB6 cells. In vivo studies showed that cefradine down-regulated SUV-induced the phosphorylation of p38, JNKs and H2AX and inhibited the secretion of IL6 and TNF-α in Babl/c mice. These results indicated that cefradine can inhibit SUV-induced skin inflammation by blocking TOPK signaling pathway, and TOPK is an effective target for suppressing inflammation induced by SUV irradiation.

Surgical Treatment of Giant Liver Hemangioma Larger Than 10 cm: A Single Center's Experience With 86 Patients.

The ideal surgical treatment of giant liver hemangioma is still controversial. This study aims to compare the outcomes of enucleation with those of resection for liver hemangioma larger than 10 cm in different locations of the liver and establish the preoperative predictors of increased intraoperative blood loss.Eighty-six patients underwent enucleation or liver resection for liver hemangioma larger than 10 cm was retrospectively reviewed. Patient demographic, tumor characteristics, surgical indications, the outcomes of both surgical treatment, and the clinicopathological parameters influencing intraoperative blood loss were analyzed.Forty-six patients received enucleation and 40 patients received liver resection. Mean tumor size was 14.1 cm with a range of 10-35 cm. Blood loss, blood product usage, operative time, hepatic vascular occlusion time and frequency, complications and postsurgical hospital stay were similar between liver resections and enucleation for right-liver and left-liver hemangiomas. There was no surgery-related mortality in either group. Bleeding was more related to adjacency of major vascular structures than the size of hemangioma. Adjacency to major vascular structures and right or bilateral liver hemangiomas were independently associated with blood loss >550 mL (P = 0.000 and 0.042, respectively).Both enucleation and liver resection are safe and effective surgical treatments for liver hemangiomas larger than 10 cm. The risk of intraoperative blood loss is related to adjacency to major vascular structures and the location of hemangioma.

(18)F-FDG PET/CT in Patients with Nodular Pulmonary Amyloidosis: Case Report and Literature Review.

A 62-year-old woman was found to have multiple bilateral pulmonary nodules showing different (18)F-fluorodeoxyglucose (FDG) uptakes on positron-emission tomography/computed tomography (PET/CT). Only the largest nodule in the left lower lobe showed an increased (18)F-FDG uptake on PET/CT. Three nodules were surgically resected from different lobes of the left lung. Two lobes were benign and showed amyloid deposition. The largest nodule in the left lower lobe showed adenocarcinoma and a heavy amyloid deposition. Pulmonary amyloidosis should be added to the differential diagnosis for cases with multiple pulmonary nodules that show different (18)F-FDG uptakes on PET/CT. To the best of our knowledge, this is the second reported case of a lung nodule consisting of adenocarcinoma and amyloid deposition.

Extraventricular neurocytoma in pediatric populations: A case report and review of the literature.

Extraventricular neurocytomas (EVNs) are rare neuronal tumors included in the definition of neoplasms in the 2007 World Health Organization classification of tumors of the central nervous system. Although a small case series of EVNs in adults has been previously reported, EVNs in pediatric populations are extremely rare. The current case report presents the clinicopathological features of an EVN in a 2-year-old female who presented with nausea and vomiting that had lasted for five days. In addition, an analysis of the imaging features, histology, treatment and prognosis of these reported rare lesions is presented. Immunohistochemically, EVNs are characterized by the robust expression of synaptophysin, but with a lack of oligodendrocyte transcription factor 2, isocitrate dehydrogenase enzyme isoform 1 (IDH1) R132/IDH2 R172 mutations and p53 immunoexpression. The treatment for EVNs in pediatric and adult populations is gross total resection, with post-operative radiation reserved for subtotal resection or recurrent disease. In addition, drop metastasis must be carefully avoided.

[Identification and management of intra-operative suspicious tissues in 20 transsphenoidal surgery cases].

OBJECTIVE: To determine appropriate protocols for the identification and management of intra operative suspicious tissues during transsphenoidal surgery. METHODS: Clinical data and pathological reports of 20 patients with intra-operative suspicious tissues during transsphenoidal surgeries were analyzed retrospectively. The methods for discriminating between adenoma and normal pituitary tissues were reviewed. RESULTS: The postoperative pathological reports revealed that adenoma and normal pituitary tissues coexisted in 9 samples, while 5 samples were identified as normal pituitary tissues, 2 as adenoma tissues, and 4 as other tissues. Adenomas were distinguished from normal pituitary tissues on the basis of intra-operative appearance, texture, blood supply and possible existence of boundary. CONCLUSION: If decisions are difficult to made during surgeries from the appearance of the suspicious tissues, pathological examinations are advised as a guidance for the next steps.

Quantitative analysis of aberrant fatty acid composition of zebrafish hepatic lipids induced by organochlorine pesticide using stable isotope-coded transmethylation and gas chromatography-mass spectrometry.

Organochlorine pesticides have been extensively used worldwide for agricultural purposes. Due to their resistance to metabolism, a major public health concern has been raised. Aberrant hepatic lipid composition has been a hallmark of many liver diseases associated with exposure to various toxins and chemicals. And thus lots of efforts have been focused on the development of analytical techniques that can rapidly and quantitatively determine the changes in fatty acid composition of hepatic lipids. In this work, changes in fatty acid composition of hepatic lipids in response to DDT (dichlorodiphenyltrichloroethane) exposure were quantitatively analyzed by a gas chromatography-mass spectrometric approach based on stable isotope-coded transmethylation. It has been quantitatively demonstrated that polyunsaturated fatty acids including C20:3n3, C20:4n6, and C22:6n3 decrease in response to DDT exposure. However, saturated long chain fatty acids including C16:0, C18:0, as well as monounsaturated long chain fatty acid C18:1n9 consistently increase in a DDT-concentration-dependent manner. In particular, much higher changes in the level of hepatic C16:0 and C18:0 for male fish were observed than that for female fish. These experimental results are in accordance with qualitative histopathological analysis that revealed liver morphological alterations. The stable isotope-coded mass spectrometric approach provides a reliable means for investigating hepatotoxicity associated with fatty acid synthesis, desaturation, mitochondrial beta-oxidation, and lipid mobilization. It should be useful in elucidation of hepatotoxic mechanisms and safety assessment of environmental toxins.