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ObjectiveTo provide an accurate assessment of the prevalence of breast fibroadenoma in a large population and to confirm the diagnostic accuracy of ultrasound for fibroadenoma.DesignThis was a cross-sectional survey.SettingThis research was conducted at Nanfang Hospital, Guangzhou, Guangdong, China.ParticipantsA total of 11 898 women aged 18–40 years who underwent breast screening between 1 January 2019 and 31 December 2019 were included in the fibroadenoma prevalence study. From 1 June 2019 to 31 December 2019, 342 breast lesions with pathology reports and preoperative ultrasound images were collected for diagnostic fibroadenoma testing (vs histological diagnostic testing).Primary outcome measuresPearson’s χ2 test was performed to compare the prevalence of different lesions between age groups, and descriptive statistics were used to report the clinical characteristics of fibroadenoma. For ultrasound diagnosis, fibroadenoma was defined as a well-circumscribed lesion with round or oval shape, consisting of a homogeneously hypoechoic or isoechoic solid mass, located parallel to the chest wall with a smooth margin and no posterior shadowing. Diagnostic test results for breast fibroadenoma were stratified by diagnostic type (histological vs ultrasound).ResultsOf the women aged 18–40 years, 27.6% (3285/11 898) had an ultrasound diagnosis offibroadenoma. Of these, the prevalence of fibroadenoma was stable across age groups (p=0.14) and did not differ between the left and right sides of the breast. Almost two-thirds of women presented with a single fibroadenoma, and most fibroadenomas did not exceed 1 cm in size. The sensitivity and specificity for fibroadenoma were 97.0% (95% CI for sensitivity: 93.7% to 98.8%) and 91.4% (95% CI for specificity: 85.4% to 95.5%) for ultrasonography, respectively.ConclusionsThe prevalence of fibroadenoma in South China is as high as 27.6%, and ultrasound could be used as a tool to diagnose fibroadenoma.

Cetuximab resistance is a key barrier in treating metastatic colorectal cancer (mCRC). Targeting of metabolic resources import could resensitize drug-resistant cancer cells to anticancer treatments. Here we showed that the expression of the glutamine transporter solute carrier 1 family member 5 (SLC1A5) in clinical CRC samples of patients resisted to cetuximab was significantly higher than in those of patients responded to cetuximab. Inhibition of SLC1A5 by shRNA-mediated gene silencing or pharmacological inhibitor significantly suppressed the growth of CRC. Moreover, inhibition of SLC1A5 significantly enhanced the inhibitory efficacy of cetuximab on CRC proliferation both in vitro and in vivo. Mechanistically, SLC1A5 inhibition facilitated EGFR degradation through the ubiquitin-proteasome pathway, and decreased the expression of nuclear EGFR, both of which might have contribution to the improved response to cetuximab. This study provides the metabolic molecule SLC1A5 as a potential therapeutic target to increase the efficacy of cetuximab on CRC.

Interferon-induced transmembrane proteins (IFITMs) are expressed in some types of cancer. However, their precise roles in tumor progression remain unclear. The present study investigated the function of IFITM2 in gastric cancer (GC) progression. A retrospective analysis of a public database and 167 GC patients revealed that IFITM2 expression was upregulated in gastric tumor samples, which was positively correlated with disease progression, more frequent postoperative recurrence, and higher mortality rate. IFITM2 knockdown decreased GC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition in vitro. We also found that IFITM2 expression was in part induced by insulin-like growth factor (IGF) 1 via IGF1 receptor/signal transducer and activator of transcription 3 signaling. Furthermore, IFITM2 regulated interleukin-6 expression and secretion, which in turn increased IFITM2 expression. Silencing of IFITM2 expression suppressed tumor growth and lung metastasis in vivo. These results suggest that IFITM2 is a novel prognostic biomarker and regulator of GC progression.

Treatment for advanced gastric cancer is challenging. Epidermal growth factor receptor (EGFR) contributes to the proliferation and development of gastric cancer (GC), and its overexpression is associated with unfavorable prognosis in GC. Cetuximab, a monoclonal antibody targeting EGFR, failed to improve the overall survival of gastric cancer patients indicated in phase III randomized trials. Glutamine is a vital nutrient for tumor growth and its metabolism contributes to therapeutic resistance, making glutamine uptake an attractive target for cancer treatment. The aim of the present study was to investigate whether intervention of glutamine uptake could improve the effect of cetuximab on GC. The results of MTT assay showed that by glutamine deprivation or inhibition of glutamine uptake, the viability of gastric carcinoma cells was inhibited more severely than that of human immortal gastric mucosa epithelial cells (GES-1). The expression of the key glutamine transporter alanine-serine-cysteine (ASC) transporter 2 (ASCT2; SLC1A5) was significantly higher in gastric carcinoma tissues and various gastric carcinoma cell lines than in normal gastric tissues and cells, as shown by immunohistochemistry and western blotting, while silencing ASCT2 significantly inhibited the viability and proliferation of gastric carcinoma cells. Consistent with previous studies, it was shown herein by MTT and EdU assays that cetuximab had a weak inhibitory effect on the cell viability of gastric carcinoma cells. However, inhibiting glutamine uptake by blockade of ASCT2 with l-γ-glutamyl- p-nitroanilide (GPNA) significantly enhanced the inhibitory effect of cetuximab on suppressing the proliferation of gastric cancer both in vitro and in vivo. Moreover, combining cetuximab and GPNA induced cell apoptosis considerably in gastric carcinoma cells, as shown by flow cytometry, and had a higher depressing effect on gastric cancer proliferation both in vitro and in vivo, as compared to either treatment alone. The present study suggested that inhibition of glutamine uptake may be a promising strategy for improving the inhibitory efficacy of cetuximab on advanced gastric cancer.

Radiofrequency ablation has become an increasingly common therapeutic technique for patients with hepatocellular carcinoma or metastatic liver tumors. However, reports on the effect of percutaneous radiofrequency ablation (PRFA) on circulating tumor cells (CTCs) are limited. The present study aimed to further investigate the impacts of PRFA on the numbers and phenotypes of CTCs in patients with hepatocellular carcinoma or metastatic liver tumors. A total of 43 patients with hepatocellular carcinoma or 7 types of metastatic liver tumors were treated with PRFA. A total of 5 ml blood per sample were collected from the peripheral circulation 30 min before and 3 days after PRFA. The total number of CTCs significantly increased 3 days after PRFA, and the mesenchymal phenotype CTCs, which also increased significantly, significantly contributed to the overall increase in CTCs. Furthermore, the lymphocyte levels were significantly decreased following PRFA, and the CTC level was significantly higher in patients with decreased lymphocyte levels compared with those with increased lymphocyte levels. Liver tumor PRFA may increase the level of mesenchymal phenotype CTCs, which is significantly associated with the lymphocyte count. Factors pertaining to the performance of PRFA were also investigated in the present research, but no significant results were identified.

Cetuximab resistance is a key barrier in treating metastatic colorectal cancer (mCRC). Targeting of metabolic resources import could resensitize drug-resistant cancer cells to anticancer treatments. Here we showed that the expression of the glutamine transporter solute carrier 1 family member 5 (SLC1A5) in clinical CRC samples of patients resisted to cetuximab was significantly higher than in those of patients responded to cetuximab. Inhibition of SLC1A5 by shRNA-mediated gene silencing or pharmacological inhibitor significantly suppressed the growth of CRC. Moreover, inhibition of SLC1A5 significantly enhanced the inhibitory efficacy of cetuximab on CRC proliferation both in vitro and in vivo. Mechanistically, SLC1A5 inhibition facilitated EGFR degradation through the ubiquitin-proteasome pathway, and decreased the expression of nuclear EGFR, both of which might have contribution to the improved response to cetuximab. This study provides the metabolic molecule SLC1A5 as a potential therapeutic target to increase the efficacy of cetuximab on CRC.

This study developed a kind of magnetic-polymer nanocarrier with folate receptor-targeting and pH-sensitive multifunctionalities to carry doxorubicin (DOX) for treatment of advanced gastric cancer (AGC). Folate-conjugated, pH-sensitive, amphiphilic poly(β-aminoester) self-assembled with hydrophobic oleic acid-modified iron oxide nanoparticles, and the resulting hydrophobic interaction area is a reservoir for lipophilic DOX (F-P-DOX). Confocal microscopy illustrated that F-P-DOX treatment could keep higher DOX accumulation in cells than P-DOX (without folate conjugation), and therefore get a higher efficiency of DOX internalization at pH 6.5 than at pH 7.4. Electron microscope characterization and real-time polymerase chain reaction revealed cell apoptosis promoted by F-P-DOX. The better efficacy of F-P-DOX on GC than free DOX and P-DOX was determined by MTT assay and xenograft model. Moreover, the accumulation of F-P-DOX in the tumor site was detected by magnetic resonance imaging (MRI). All those observations suggest F-P-DOX could be a promising theranostic candidate for AGC treatment.

// Na Huang 1 , Zhenzhen Wu 1 , Li Lin 1 , Minyu Zhou 1 , Lin Wang 1 , Huanrong Ma 1 , Jianling Xia 1 , Jianping Bin 2 , Yulin Liao 2 and Wangjun Liao 1 1 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China 2 Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China Correspondence to: Wangjun Liao, email: // Keywords : gastric cancer; miR-338-3p; ZEB2; MACC1; epithelial-mesenchymal transition Received : December 14, 2014 Accepted : March 26, 2015 Published : April 14, 2015 Abstract MicroRNAs (miRNAs) are involved in the epithelial-mesenchymal transition (EMT) process and are associated with metastasis in gastric cancer (GC). MiR-338-3p has been reported to be aberrantly expressed in GC. In the present study, we show that miR-338-3p inhibited the migration and invasion of GC cells in vitro . Knocking down miR-338-3p in GC cells led to mesenchymal-like changes. MiR-338-3p influenced the expression of the EMT-associated proteins by upregulating the epithelial marker E-cadherin and downregulating the mesenchymal markers, N-cadherin, fibronectin, and vimentin. In terms of mechanism, miR-338-3p directly targeted zinc finger E-box-binding protein 2 (ZEB2) and metastasis-associated in colon cancer-1 (MACC1). MiR-338-3p repressed the Met/Akt pathway after MACC1 inhibition. Reintroduction of ZEB2 and MACC1 reversed miR-338-3p-induced EMT suppression. Consistently, inverse correlations were also observed between the expression of miR-338-3p and ZEB2 or MACC1 in human GC tissue samples. In conclusion, miR-338-3p inhibited the EMT progression in GC cells by targeting ZEB2 and MACC1/Met/Akt signaling.

e15556 Background: Chemotherapy based on DNA-damaging anti-cancer drugs remains the most predominant treatment for advanced gastric cancer. The predictors for their sensitivity are under development. Our data showed that sperm-associated antigen 5 (Spag5) contributed to cancer cell proliferation and decreased DNA-damaging drug sensitivity in vivo and vitro. Methods: Spag5 mRNA expression were compared in The Cancer Genome Atlas (TCGA) and GEO datasets (GSE56807, GSE63089, GSE65801), while protein level were detected in 52 patients diagnosed with gastric cancer in Nanfang Hospital by immunohistochemistry. BGC-823 and MGC-803 were transfected with spag5 and control siRNA and then subjected to MTT and EDU assay to verify proliferation rate. Cell viability and apoptosis were tested in spag5-silenced BGC-823 and MGC-803 treated with oxaliplatin, epirubicin and 5-fluorouracil independently. DNA-damaged were detected by comet assay and yH2ax level with western blot. Treatment of oxaliplatin was given intraperitoneally to nude mice carrying xerographs of Shspag5 or control BGC-823 cells every three days. Results: Spag5 mRNA level was significantly upregulated in cancer tissues compared with paired normal tissues in all of the datasets. Immunohistochemistry shows higher protein level of spag5 in paired cancer tissue. Knockdown of Spag5 BGC-823 and MGC-803 showed a significantly decreased proliferation in both MTT and EDU assay. Spag5 silencing led to increase vulnerability to oxaliplatin, epirubicin and 5-fluorouracil, thus less cell viability and more apoptosis. Spag5 knockdown BGC-823 and MGC-803 subjected to DNA-damaging drugs showed upregulated yH2ax level and increased DNA damage in comet assay. Tumor growth rate were significantly reduced in shspag5 group and treatment of oxaliplatin led to relatively higher inhibition of tumor growth. Conclusions: Spag5 serves as a candidate to predict proliferation and chemosensitivity to DNA-damaging chemotherapy.

e17050 Background: Flotillin microdomains, essential part of plain lipid raft domains in cell membranes, have been demonstrated to participate in several intracellular signal pathways. Recent studi...

e15054 Background: Cancer cells mainly metabolize by glycolysis (the Warburg effect) and are better adapted to resist metabolic stress. Metastasis-associated in colon cancer-1 (MACC1) is an oncogen...

4042 Background: Metastasis-associated in colon cancer-1 (MACC1), a new oncogene predominantly expressed in several solid tumors including gastric cancer (GC), is associated with cancer lymph node ...

e15052 Background: Vasculogenic mimicry (VM) as a blood supplyment pattern is strongly associated with tumor progression. In a previous study, metastasis-associated in colon cancer-1 (MACC1) upregu...

e22010 Background: AberrantmicroRNAs (miRNAs) expression is involved in carcinogensis and tumor progression in gastric cancer (GC). Recently, microRNA-338-3p (miR-338-3p) has been proved to down-regulate in GC patients with deeper local invasion and advanced TNM stage. However, the underlying mechanism has not been well explored. Epithelial-mesenchymal transition (EMT) is well-known as a key step for tumor cell invasion and metastasis. Increasing evidence indicates that miRNAs play an important part in modulating EMT in many cancers. Here, we investigated the role and mechanism of miR-338-3p on EMT in GC. Methods: Cell migration and invasion ability were detected by wound-healing and transwell invasion assay.Western blot analysis was preformed to assess E-cadherin, N-cadherin, Fibronectin, Vimentin, c-Met, Akt and GSK-3β expression in GC cells. 3D cell culture system was carried out to observe the morphological changes in GC cells. Dual-luciferase assay was conducted to verify that miR-338-3p targeting ZE...