Wilms' tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90.

BACKGROUND: Wilms' tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. Furthermore, in various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), however, remains unclear. METHODS: Immunohistochemistry was applied to evaluate the levels of WTAP expression in DLBCL tissues and normal lymphoid tissues. Overexpression and knock-down of WTAP in DLBCL cell lines, verified on mRNA and protein level served to analyze cell proliferation and apoptosis in DLBCL cell lines by flow cytometry. Finally, co-immunoprecipitation (Co-IP), IP, and GST-pull down assessed the interaction of WTAP with Heat shock protein 90 (Hsp90) and B-cell lymphoma 6 (BCL6) as well as determined the extend of its ubiquitinylation. RESULTS: WTAP protein levels were consistently upregulated in DLBCL tissues. WTAP promoted DLBCL cell proliferation and improved the ability to confront apoptosis, while knockdown of WTAP in DLBCL cell lines allowed a significant higher apoptosis rate after treatment with Etoposide, an anti-tumor drug. The stable expression of WTAP was depended on Hsp90. In line, we demonstrated that WTAP could form a complex with BCL6 via Hsp90 in vivo and in vitro. CONCLUSION: WTAP is highly expressed in DLBCL, promoting growth and anti-apoptosis in DLBCL cell lines. WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL. Down-regulation of WTAP could improve the chemotherapeutic treatments in DLBCL.

[Relationship between CT findings and immunohistochemical types of gastrointestinal stromal tumors].

OBJECTIVE: To evaluate the relationship between CT findings and immunohistochemical types of gastrointestinal stromal tumors (GIST). METHODS: CT imaging and clinicopathological data of 85 patients with GIST were analyzed retrospectively. The CT findings of GIST including lesion location, size, contour, boundary, tumor growth pattern, degree of enhancement, necrosis and calcification, were summarized and compared with the immunohistochemical types of the GIST. RESULTS: Of the 85 patients, smooth muscle differentiation was in 26 cases (30.6%), neural differentiation in 20 (23.5%) , both smooth muscle and neural differentiation in 10 (11.8%) and no obvious differentiation in 29 (34.1%) cases. GISTs occurred in the duodenum were more frequently seen in muscle type than in any other types, GIST with smooth muscle differentiation had higher prevalence of huge mass (larger than 10 cm), distinctive enhancement and extensive necrosis than other types (P < 0.05). There was no significant difference in the relationships of immunohistochemical types with tumor contour, boundary, growth pattern and calcification among the four groups of GIST (P > 0.05). CONCLUSIONS: CT scan is the most important and effective method for diagnosis of GIST. Analyzing CT signs has some potential value in judgmet of immunohistochemical types of GIST.

Ki67 increase after core needle biopsy associated with worse disease outcome in HER2-negative breast cancer patients.

Ki67 would change after core needle biopsy (CNB) in invasive breast cancer. However, whether Ki67 alteration (ΔKi67) influences disease outcomes remains unclear. Here we aim to evaluate the prognostic value of ΔKi67. Patients with paired CNB and open excision biopsy (OEB) samples between January 2009 and June 2016 were retrospectively analyzed. ΔKi67 was calculated as the absolute difference between Ki67 level in CNB and OEB samples, and the median value of 5% was adopted to category patients into high- and low ΔKi67 groups. Disease-free survival (DFS) and overall survival (OS) were compared between different ΔKi67 groups. Overall, 2173 invasive breast cancer patients were included. Median Ki67 was higher in OEB than CNB samples: 25.00% versus 20.00% (P < 0.001). Axillary nodal status, STI, histological grading, and molecular subtype were independently associated with ΔKi67 (P < 0.05). In the whole population, patients with low ΔKi67 showed superior 5-year DFS (89.6% vs 87.0%, P = 0.026), but similar OS (95.8% vs 94.3%, P = 0.118) compared to those with high ΔKi67. HER2 status at surgery was the only significant factor interacting with ΔKi67 on both DFS (P = 0.026) and OS (P = 0.007). For patients with HER2-negative disease, high ΔKi67 was associated with worse 5-year DFS (87.2% vs 91.2%, P = 0.004) as well as impaired 5-year OS (93.9% vs 96.8%, P = 0.010). ΔKi67 had no significant impact on survival of HER2-positive patients. Ki67 increase after CNB was significantly associated with worse disease outcomes in HER2-negative, but not in HER2-positive patients, which warrants further study.

No Alteration Between Intrinsic Connectivity Networks by a Pilot Study on Localized Exposure to the Fourth-Generation Wireless Communication Signals.

Neurophysiological effect of human exposure to radiofrequency signals has attracted considerable attention, which was claimed to have an association with a series of clinical symptoms. A few investigations have been conducted on alteration of brain functions, yet no known research focused on intrinsic connectivity networks, an attribute that may relate to some behavioral functions. To investigate the exposure effect on functional connectivity between intrinsic connectivity networks, we conducted experiments with seventeen participants experiencing localized head exposure to real and sham time-division long-term evolution signal for 30 min. The resting-state functional magnetic resonance imaging data were collected before and after exposure, respectively. Group-level independent component analysis was used to decompose networks of interest. Three states were clustered, which can reflect different cognitive conditions. Dynamic connectivity as well as conventional connectivity between networks per state were computed and followed by paired sample t-tests. Results showed that there was no statistical difference in static or dynamic functional network connectivity in both real and sham exposure conditions, and pointed out that the impact of short-term electromagnetic exposure was undetected at the ICNs level. The specific brain parcellations and metrics used in the study may lead to different results on brain modulation.

Contrast-enhanced CT imaging for the assessment of lymph node status in patients with colorectal cancer.

The aim of the present study was to identify a novel strategy that predicts the metastatic status of lymph nodes (LNs) in patients diagnosed with colorectal cancer, using detailed characteristics of contrast-enhanced CT scan images. A total of 284 preoperative CT scans derived from patients diagnosed with colorectal cancer at Second Affiliated Hospital, Zhejiang University School of Medicine between January 2013 and July 2018 were retrospectively reviewed. A total of 794 LNs were assessed for size, margins, morphology and subtle internal enhancements in the equilibrium phase. Imaging features were analyzed by two abdominal radiologists (Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine and Departments of Radiology; Shaoxing Second Hospital Departments of Radiology, Shaoxing Second Hospital) in a blind manner. If the conclusions were not concordant, the final score was determined by a senior radiologist who specialized in abdominal radiology for ≥30 years. According to the histopathology results, 27.3% (217/794) of LNs were metastatic (LN+). In addition, LNs >10 mm in size demonstrated sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) of 47.0, 80.9, 48.1 and 80.2%, respectively [odds ratio (OR), 3.77; 95% confidence interval (CI), 2.69-5.28]. LNs in the shape of a kidney bean (middle fat depression like kidney) and/or those with an oblong shape were more likely to be metastasis negative LNs (LN-), while lobulated and irregular LNs were more likely to be LN+. In magnified images, internal enhancement characteristics of LN- were defined as homogeneous, spotted, striped and core enhancing. By contrast, rim and heterogeneity enhancement features for LN+ demonstrated sensitivity, specificity, PPVs and NPVs of 46.5, 89.9, 63.5 and 81.7%, respectively (OR, 7.79; 95% CI, 5.33-11.40). The results demonstrated that the internal enhancement features of LNs may be used as a predictor of metastasis. The detailed benign characteristics, such as homogeneity, spotted, striped and core enhancement of LNs may facilitate the identification of LN- in patients with colorectal cancer.

LITAF is a potential tumor suppressor in pancreatic cancer.

Early diagnosis of pancreatic cancer, one of the most deadly cancers with low survival rates, is difficult, and effective biomarkers are urgently needed. Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) has been recently proposed as a potential tumor suppressor gene in several types of cancer. Here, we analyzed the biological function of LITAF in pancreatic cancer. The LITAF gene and protein levels were decreased in pancreatic tumor tissues compared with their paired adjacent non-cancerous tissues. In addition, patients with the lower LITAF protein expression had lower disease-free survival rates. The decreased LITAF expression correlated with LITAF promoter hypermethylation in pancreatic cancer cells and tissues. Moreover, promoter demethylation dose-dependently increased the LITAF transcription. Importantly, LITAF demethylation suppressed proliferation and cell cycle progression, and enhanced apoptosis of pancreatic cancer cells. Together, our results indicate that LITAF functions as a tumor suppressor gene in pancreatic cancer cells, and might serve as a novel biomarker for early diagnosis of pancreatic cancer.

Lymphoepithelioma-like hepatocellular carcinoma without Epstein-Barr virus infection: A case report and a review of the literature.

Lymphoepithelioma-like carcinoma (LELC) of the liver is uncommon, only 20 cases have been reported in the English-language literature so far, and the majority has been identified as cholangiocarcinomas, only four cases were hepatocellular LELC. Here we described a rare case of lymphoepithelioma-like hepatocellular carcinoma (HCC). A 42-year-old Chinese female who was incidentally found to have a liver-occupying lesion during a routine medical examination. Ultrasonography revealed a 47 mm × 33 mm × 36 mm hypoechoic mass in the left lobe. Computed tomography and magnetic resonance imaging displayed a nodular lesions in the left liver lobe. The patient underwent a left-side hepatectomy. Histopathological examination of the resected specimen revealed an undifferentiated carcinoma with a dense lymphocytic infiltrate, predominantly composed of CD3(+) T cells, morphologically similar to nasopharyngeal carcinoma. Immunohistochemically, the tumor cells were positive for CK, EMA, Glypican-3 and hepatocyte, but negative for alpha-fetoprotein, CK19, CK7 and CK20. Epstein-Barr virus (EBV) in situ hybridization was negative. The final histopathological diagnosis was lymphoepithelioma-like HCC without EBV infection.

Overexpression of CD151 predicts prognosis in patients with resected gastric cancer.

PURPOSE: The tetraspanin CD151 acts as a promoter of metastasis and invasion in several tumors. However, the role of CD151 in human gastric cancer (HGC) remains unclear. METHODS: Twenty HGC specimens and matched nontumor samples, human gastric epithelial cells (HGEC), and four gastric cancer cell lines were used to analyze CD151 expression. Short hairpin RNA-mediated downregulation of CD151 expression in HGC cells was performed to examine the role of CD151 in the proliferation and metastasis/invasion of HGC cells in vivo and in vitro. The relationship of CD151 with integrin α3 in HGC cells was investigated by silencing integrin α3 followed by co-immunoprecipitation and immunofluorescence staining. Finally, the prognostic value of CD151 and integrin α3 was evaluated by immunohistochemistry in tissue microarrays of 76 HGC patients. RESULTS: CD151 was expressed at higher levels in HGC tissues and HGC cells than in nontumor tissues and HGEC cells. Down-regulation of CD151 by vshRNA-CD151 impaired metastasis and invasion of HGC-27 cells, but did not affect cell proliferation. CD151 formed a complex with integrin α3 in HGC cells. CD151-cDNA transfection rescued the metastatic potential and invasiveness of HGC-27-vshCD151 cells, but not those of HGC-27-vshintegrin α3 cells in vitro. Clinically, CD151 overexpression was significantly correlated with high TNM stage, depth of invasion and positive lymph node involvement (p<0.05), and high levels of integrin α3 were associated with large tumor size, high TNM stage, depth of invasion and lymph node involvement (p<0.05). Importantly, the postoperative 5-year overall survival of patients with CD151(low) and/or integrin α3(low) was higher than that of patients with CD151(high) and/or integrin α3(high). CONCLUSION: CD151 is positively associated with the invasiveness of HGC, and CD151 or the combination of CD151 and integrin α3 is a novel marker for predicting the prognosis of HGC patients and may be potential therapeutic targets.