Overexpression of FRAT1 protein is closely related to triple-negative breast cancer.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients. Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. Results: The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features: T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion: FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.

Solitary fibrous tumor of the lesser omentum mimicking stomach gastrointestinal stromal tumor.

Solitary fibrous tumor (SFT) is a mesenchymal tumor that rarely occurs in the abdomen. We report a very rare case of an abdominal SFT in the lesser omentum. A 39-year-old Korean man was referred to our center for management of a 9 cm incidental mass in the abdominal space found on a chest computed tomography (CT) during a routine medical examination. He had no symptoms, and there were no specific findings on physical examination. A contrast enhancement CT was performed, and an extraluminal gastrointestinal stromal tumor in the stomach or a pancreatic origin mass was suspected. Surgery was performed and an enclosed mass in the lesser omentum was observed, which was resected completely. The postoperative course was uneventful. Based on microscopy, the omental tumor was diagnosed as SFT.

Secreted tyrosine kinase Vlk negatively regulates Hedgehog signaling by inducing lysosomal degradation of Smoothened.

Vlk is a secreted tyrosine kinase that plays crucial roles during vertebrate embryonic development including skeletal formation. Genetic studies suggest that Vlk can modulate the Hedgehog signaling pathway during skeletal development. Despite its potential roles as an extracellular regulator of signaling pathways, little is known regarding the molecular functions of Vlk. Here we show that Vlk can negatively regulate the Hedgehog signaling pathway. We found that Vlk can induce lysosomal degradation of Smoothened, a crucial transmembrane signal transducer of the Hedgehog pathway, through the interaction with the extracellular domain of Smoothened (Smo-ECD). In addition, we observed that Vlk can attenuate Hedgehog signaling-induced ciliary localization of Smoothened. Furthermore, Vlk-mediated suppression of Hedgehog signaling can be diminished by tyrosine-to-phenylalanine substitutions in Smo-ECD. Taken together, these results suggest that Vlk may function as a signaling regulator in extracellular space to modulate the Hedgehog pathway.

Discovery of gastric cancer specific biomarkers by the application of serum proteomics.

Current diagnostic markers for gastric cancer are not sufficiently specific or sensitive for use in clinical practice. The aims of this study are to compare the proteomes of serum samples from patients with gastric cancers and normal controls, and to develop useful tumor markers of gastric cancer by quantitative proteomic analysis. We identified a total of 388 proteins with a ≤1% FDR and with at least two unique peptides from the sera of each group. Among them, 215, 251, and 260 proteins were identified in serum samples of patients in an advanced cancer group, early cancer group, and normal control group, respectively. We selected differentially expressed proteins in cancer patients compared with those of normal controls via semiquantitative analyses comparing the spectral counts of identified proteins. These differentially expressed proteins were successfully verified using an MS-based quantitative assay, multiple reactions monitoring analysis. Four proteins (vitronectin, clusterin isoform 1, thrombospondin 1, and tyrosine-protein kinase SRMS) were shown to have significant changes between the cancer groups and the normal control group. These four serum proteins were able to discriminate gastric cancer patients from normal controls with sufficient specificity and selectivity.

Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters.

PURPOSE: In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. MATERIALS AND METHODS: A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped. RESULTS: In univariate survival analysis, tumor grade (p < 0.0001), extent (p < 0.0001), size (p < 0.0001), lymph node metastasis (p=0.0063), and L-cell phenotype (p < 0.0001) showed significant correlation with the prognosis of rectal NENs; however, none of these markers achieved independent significance in multivariate analysis. The 10-year OS of tumors of NET grade 1, < 10 mm, the mucosa/submucosa was 97.58%, 99.47%, and 99.03%, respectively. L-Cell marker, glucagon II (GLP-1&2), with a cut off score of > 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. CONCLUSION: From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.

The relationship between somatic symptoms and depression.

OBJECTIVE: We investigated the influence of somatic symptoms on the severity and clinical outcomes in female Korean patients with major depressive disorder (MDD) in routine practice. METHODS: Two hundred and seven female patients with MDD were prospectively recruited. Patients with somatic symptoms (PSS) was defined as a total score ≥ 10 on the Patient Health Questionnaire-15 (PHQ-15), others were classified as non PSS (NPSS). The PHQ-9 for de-pression, the Generalized Anxiety Disorder Scale (GAD-7) for anxiety, the Clinical Global Impression-Severity (CGI-S) for clinical status, and the Visual Analogue Scale (VAS) for health status were utilised. RESULTS: Of 207 participants, 126 (60.9%) were PSS and 81 (39.1%) were classified as NPSS. The proportion of patients showing severe symptoms (65.1% vs. 24.7%) and recurrence of depression (74.6% vs. 49.4%), the CGI-S (4.6 vs. 4.1), the PHQ-9 (16.8 vs. 11.1), and the GAD-7 (8.3 vs 6.7) scores were significantly higher in PSS than in NPSS, while the VAS (39.4 vs. 51.2) was significantly lower in PSS than in NPSS. The improvement of depressive symptoms (-1.3 vs. -2.0) measured by the changes in CGI-S was also significantly less in PSS than in NPSS after 6 months treatment. CONCLUSION: Our findings have shown the significant impact of somatic symptoms on the symptomatology as well as treatment outcomes in Korean female patients with MDD, indicating that clinicians should carefully evaluate somatic symptoms in patients with MDD in routine clinical practice. Due to the methodological shortcomings of the present study, further adequately powered and well-designed investigations are necessary.

Intra-abdominal fibromatosis after gastrectomy for gastric cancer.

Intra-abdominal fibromatosis (IAF) may arise either sporadically or in association with familial adenomatous polyposis. The characteristics of fibromatosis are slow-growth, benign histological features, and aggressive local invasion. Surgery remains a reasonable first treatment option. Here, we report 2 cases of a phenomenon rarely described in published literature, IAF after gastrectomy for gastric cancer. Intra-abdominal masses were found during the routine follow-up period in a 50-year-old man who had received a radical subtotal gastrectomy for early gastric cancer. Two mesenteric masses were detected in the upper abdomen by CT and were excised completely along with segments of the jejunum. Another intra-abdominal mass was found in 60-year-old man who had received a radical total gastrectomy for advanced gastric cancer. A 4.2-cm-sized mass was detected in the periumbilical region by follow-up CT and was excised completely along with a segment of the ileum.

Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy.

ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision repair cross-complementation group 2) as genes have been known to be belonged to the nucleotide excision repair pathway and therefore related to DNA repair. Polymorphisms in these genes have been rarely evaluated in terms of predicting cancer patient survival. We investigated whether these polymorphisms have an effect on response to chemotherapy and survival in 109 patients with non-small-cell lung cancer treated with cisplatin combination chemotherapy. Polymorphisms of ERCC1 Asn118Asn (C --> T), XPD Lys751Gln (A --> C) and Asp312Asn (G --> A) were evaluated using a SNaPshot kit. As for chemotherapy response, treatment response did not show statistically significant differences between the wild genotypes and the variant genotypes for the ERCC1 and XPD gene. The median survival time of all patients was 376 days (95% CI, 291-488). As for survival rate according to the polymorphism of codon 118 in ERCC1, median survival time in patients showing C/C genotype was 486 days (95% CI, 333-x), which was significantly different from the 281 days (95% CI, 214-376) of patients with the variant genotype (T/T or C/T) (P = 0.0058). Using the Cox-proportional hazards model, the polymorphism of codon 118 in ERCC1, response to chemotherapy, weight loss and performance status effected overall survival significantly (P = 0.0001, 0.0001, 0.0028 and 0.0184, respectively). However, polymorphisms of codons 751 and 312 in the XPD gene did not affect patient survival (P = 0.4711 and 0.4542, respectively). Therefore, we suggest that the C/C genotype in codon 118 of ERCC1 is a surrogate marker for predicting better survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy.

The implication of elevated carcinoembryonic antigen level in pleural fluid of patients with non-malignant pleural effusion.

OBJECTIVE: The aim of this study was to evaluate the false positive rate for pleural fluid carcinoembryonic antigen (CEA) level in non-malignant pleural effusions and to determine whether the falsely elevated CEA level has any relation to other biochemical parameters of pleural effusions. METHODOLOGY: We performed a retrospective analysis of 654 consecutive patients with a pleural effusion admitted to the pulmonary department of a tertiary referral teaching hospital from March 1997 to March 1999. The aetiology of the pleural effusions were classified as tuberculosis (n = 262), malignancy (n = 204), pneumonia (n = 145), exudates of other origin (n = 28) and transudate (n = 1). RESULTS: A false positive result for pleural fluid CEA level (> 5 ng/mL) was registered in 13.8% of non-malignant pleural effusion cases: empyema (38.6%), parapneumonic effusion (14.7%), exudates of other origin (14.3%), tuberculosis (7.3%) and transudate (6.7%). In analysis of the subgroup with false positive results for pleural fluid CEA level, the CEA level of non-malignant pleural effusion showed a significant relationship to the severity of pleural inflammation in terms of the following variables: LDH (rs = 0.4201, P= 0.001), adenosine deaminase (ADA) (rs = 0.4440, P= 0.0004), white blood cell count (rs = 0.4266, P= 0.0004), polymorphonuclear cell percentage (rs = 0.5080, P= 0.0001), and polymorphonuclear cell count (rs = 0.5095, P= 0.0002). In the parapneumonic effusion and empyema groups, the changes in pleural fluid CEA level exhibited a positive association with the changes in the pleural fluid ADA level (rs = 0.8143, P= 0.0002). CONCLUSIONS: The results from our series indicated that false positive results for pleural fluid CEA level were most commonly observed in patients with empyema and parapneumonic effusion and the CEA level showed a significant correlation to the indices of pleural inflammation. The serial measurement of pleural fluid CEA level may be useful as a means of monitoring resolution of pleural inflammation and excluding the possibility of a malignant pleural effusion.

Acute respiratory distress syndrome induced by adenovirus in an otherwise healthy woman.

Acute respiratory distress syndrome (ARDS) caused by adenovirus is a rare event in healthy adults, especially in non- military settings. Although treatment with intravenous ribavirin has been reported, supportive care, including mechanical ventilation, is known to be the main stay in the treatment of ARDS caused by adenovirus, with high-dose steroid treatment having rarely been reported. We report our experience with a 41-year-old, otherwise healthy, woman with ARDS, treated with high-dose steroid and mechanical ventilatory support.

Effect of p38 mitogen-activated protein kinase on the replication of encephalomyocarditis virus.

Cellular phosphorylation events during viral infection are necessary for effective viral replication. Encephalomyocarditis (EMC) virus has been used for studies on the molecular mechanisms of viral replication, but little is known about the cellular signaling pathways involved. This investigation was initiated to determine whether mitogen-activated protein kinases (MAPKs), which are central components of signal transduction pathways in the regulation of cell proliferation, play a role in the replication of EMC virus. We examined the phosphorylation of MAPKs, including extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and stress-activated protein kinase 1/c-Jun NH(2)-terminal kinase (SAPK/JNK) in EMC virus-infected L929 cells and found that p38 MAPK and SAPK-JNK, but not ERK1/2, were activated during viral infection. We then examined the effect of these kinases on the replication of EMC virus in L929 cells by using specific inhibitors, including genistein or herbimycin A for tyrosine kinase, SB203580 or SB202190 for p38 MAPK, and PD98059 for ERK1/2. We found that the tyrosine kinase and p38 MAPK inhibitors, but not the ERK1/2 inhibitor, suppressed viral replication and that the inhibitory effect was primarily on viral protein synthesis. Finally, we examined whether p38 MAPK is involved in the translation of EMC viral transcripts by using L929 cells transfected with a gene construct containing the internal ribosomal entry site (IRES) of EMC virus and a luciferase reporter gene. We found that the p38 MAPK inhibitor suppressed the translation of EMC viral RNA. On the basis of these observations, we conclude that p38 MAPK plays a critical role in the replication of EMC virus, probably in the translation of viral RNA.

Extraskeletal chondroma of the fallopian tube.

Extraskeletal chondroma can occur in the hands, feet, head and neck. This tumor usually presents as a small solitary nodule. The histogenesis of the tumor is controversial, but some have suggested a metaplastic origin. Chondroma of the fallopian tube is very rare. There is only one report in English literature. The origin of this tumor can be subcoelomic mesenchyme of the tubal serosa or mesenchyme of the myosalpinx. We describe a case of chondroma arising from the serosal surface of the fallopian tube with a review of literature. A 30-yr-old woman visited hospital due to left adnexal mass. On operating finding, 2 x 3 cm sized nodular mass was noted on the left tubal serosal area. The excised mass showed multilobulated appearance covered with thin fibrous membrane. The cut surface was solid, grayish yellow, and myxoid with a focal gelatinous area. The microscopic finding showed islands and elongated lobules of mature benign cartilage without cytologic atypia.