Rare primary malignant mixed Müllerian tumor of the mediastinum: A case report.

RATIONALE: Malignant mixed Müllerian tumor (MMMT) of extragenital organs is rare, especially in male. To our knowledge, this is the first reported case of primary MMMT at the mediastinum in male. PATIENT CONCERNS: A 54-year-old male was admitted to the hospital due to repeated stimulating dry cough for 2 years. His systemic examination was unremarkable. Laboratory workup revealed that all blood indicators were within normal limits. But subsequent computerized tomography (CT) scans of chest showed an abnormal soft tissue density in the area of its left, measuring approximately 4 cm in anterior-posterior dimension and 7 cm in maximum transverse dimension. DIAGNOSES AND INTERVENTIONS: The pathogenesis of these tumors remains controversial. The diagnosis is combined with biopsy and immunohistochemical staining. So, the patient underwent radical surgical resection and pathologic examination of the excised specimen was consistent with the diagnosis of MMMT. After surgery, he was treated by sequential chemoradiotherapy. OUTCOMES: The patient died from tumor recurrence 16 months later. LESSONS: MMMT is a rare, highly aggressive tumor associated with interesting embryological origin, a definite diagnosis of which is only confirmed on pathological assessment. Due to its high degree of malignancy and high rate of recurrence, complete macroscopic excision of the tumor is recommended as soon as possible.

Sorafenib induced alteration of protein glycosylation in hepatocellular carcinoma cells.

Sorafenib is a multikinase inhibitor and is effective in treating hepatocellular carcinoma (HCC). However, it remains unknown whether sorafenib induces the alteration of protein glycosylation. The present study treated HCC MHCC97L and MHCC97H cells with a 50% inhibitory concentration of sorafenib. Following this treatment, alteration of protein glycosylation was detected using a lectin microarray. Compared with the controls, the binding capacity of glycoproteins extracted from sorafenib-treated HCC cells to the lectins Bauhinia purpurea lectin, Dolichos biflorus agglutinin, Euonymus europaeus lectin, Helix aspersa lectin, Helix pomatia lectin, Jacalin, Maclura pomifera lectin and Vicia villosa lectin were enhanced; while, the binding capacities to the lectins Caragana arborescens lectin, Lycopersicon esculentum lectin, Limulus polyphemus lectin, Maackia amurensis lecin I, Phaseolus vulgaris leucoagglutinin, Ricinus communis agglutinin 60, Sambucus nigra lectin and Solanum tuberosum lectin were reduced (spot intensity median/background intensity median ≥2, P<0.05). This difference in glycoprotein binding capacity indicates that cells treated with sorafenib could increase α-1,3GalNAc/Gal, ß-1,3 Gal, GalNAcα-Ser/Thr(Tn) and α-GalNAc structures and decrease GlcNAc, sialic acid, tetra-antennary complex-type N-glycan and ß-1,4Gal structures. These results were additionally confirmed by lectin blotting. Expression levels of signaling molecules including erythroblastosis 26-1 (Ets-1), extracellular signal-related kinases (ERK) and phosphorylated-ERK were measured by western blotting. There was a reduction in the expression of Ets-1 and ERK phosphorylation in sorafenib or 1,4-Diamino-2,3-dicyano-1,4-bis (2-aminophenylthio) butadiene treated cells suggesting that sorafenib may reduce the expression levels of Ets-1 by blocking the Ras/Raf/mitogen activated protein kinase signaling pathway. In the present study, it was clear that sorafenib could inhibit the proliferation of HCC cells and alter protein glycosylation. The findings of this study may lead to providing a novel way of designing new anti-HCC drugs.

Discovering potential serological biomarker for chronic Hepatitis B Virus-related hepatocellular carcinoma in Chinese population by MAL-associated serum glycoproteomics analysis.

The accuracy of current biomarkers for the diagnosis of hepatocellular carcinoma (HCC), especially chronic Hepatitis B Virus (HBV)-related HCC, is limited. Recent progress in glycoproteomics has provided a novel platform for screening novel serological biomarkers of HCC. In this study, lectin affinity chromatography by Maackia amurensis lectin (MAL) and iTRAQ combined with mass spectrometric analysis were performed to enrich and identify the glycoprotein fractions in serum samples from HBV-related HCC patients and from healthy controls. Seventeen differential MAL-associated glycoproteins were identified. Among them, Galectin 3 binding protein (Gal-3BP) was selected for further evaluated by ELISA analysis and showed a high diagnostic potential of HBV-related HCC, with the AUC of 0.898 and a sensitivity, specificity and accuracy of 80.00%, 93.75% and 86.88%, respectively. Moreover, we constructed a predictive model through the combined use of serum Gal-3BP and Alpha Fetoprotein (AFP), which improved the sensitivity (from 87.5% to 95%), specificity (from 93.75% to 95%) and accuracy (from 90.63% to 95%) of diagnosing early HCC. These data suggested serum Gal-3BP level is a promising biomarker to identify HBV-related HCC and the combined use of serum Gal-3BP and AFP improves the diagnostic potential of HBV-HCC compared with AFP alone in current clinical practice.

Novel interacting proteins identified by tandem affinity purification coupled to nano LC-MS/MS interact with ribosomal S6 protein kinase 4 (RSK4) and its variant protein (RSK4m).

Ribosomal S6 protein kinase 4 (RSK4) is an important novel tumor suppressor that inhibits breast cancer cell growth and induces senescence. However, RSK4m, which is a variant of RSK4 resulting from alternative splicing, may play distinct roles in some aspects. Knowledge about the mechanisms of RSK4 or RSK4m activity has been lacking. Analysis of the RSK4 and RSK4m interactome could provide insight into their specific functions and integrative mechanisms. Using tandem affinity purification, we obtained protein complexes that interacted with RSK4 or RSK4m. Mass spectrum analysis was performed to identify the obtained protein complexes, and bioinformatics analysis was performed. In this study, we isolated and identified 82 RSK4-associated proteins and 137 RSK4m-associated proteins using two STREP II and a single Flag tag-based tandem affinity purification (SF-TAP) coupled with nano LC-MS/MS in MDA-MB-231 cells. Gene Ontology and Ingenuity Pathway Analysis analyses provided functional annotations and protein-protein interaction networks of the protein interactome of RSK4 and RSK4m. Functional annotations of these proteins by bioinformatics analyses highlight the essential role of RSK4 and RSK4m in coordination with their interacting partners to mediate multiple biological processes, especially cell senescence. Moreover, after comparing the interactome of RSK4 and RSK4m, we found that RSK4m is involved in more molecular functions than RSK4.

The high expressed serum soluble neural cell adhesion molecule, a high risk factor indicating hepatic encephalopathy in hepatocelular carcinoma patients.

OBJECTIVE: To investigate whether the expression of serum soluble neural cell adhesion molecule (sNCAM) is associated with hepatic encephalopathy (HE) in hepatocelular carcinoma (HCC) patients. MATERIALS AND METHODS: The Oncomine Cancer Microarray database was used to determine the clinical relevance of NCAM expression in different kinds of human cancers. Sera from 75 HCC cases enrolled in this study were assessed for expression of sNCAM by enzyme linked immunosorbent assay (ELISA). RESULTS: Dependent on the Oncomine Cancer Microarray database analysis, NCAM was down regulated in 10 different kinds of cancer, like bladder cancer, brain and central nervous system cancer, while up-regulated in lung cancer, uterine corpus leiomyoma and sarcoma, compared to normal groups. Puzzlingly, NCAM expression demonstrated no significant difference between normal and HCC groups. However, we found by quantitative ELISA that the level of sNCAM in sera from HCC patients with HE (347.4±151.9 ng/ml) was significantly more up-regulated than that in HCC patients without HE (260.3±104.2 ng/ml), the p-value being 0.008. sNCAM may be an important risk factor of HE in HCC patients, the correlation coefficients was 0.278 (P< 0.05) on rank correlation analysis. CONCLUSIONS: This study highlights that up-regulated level of serum sNCAM is associated with HE in HCC patients and suggests that the high expression can be used as an indicator.