BackgroundGastric cancer is one of the major causes of cancer-related mortality worldwide. Most of patients presenting with inoperable gastric cancers rely on systemic chemotherapy for prolongation of survival. Doxorubicin (DOX) is one of the important agents against gastric cancer. Acquired DOX-resistance severely impedes the chemotherapeutic effect, invariably leading to poor prognosis. Resveratrol (RES) as a kind of phytoalexin has demonstrated anti-tumor functions in breast cancer and myeloid leukemia, but its function and mechanism are still unknown in gastric cancer treatment.MethodsCCK8 assay was used to detect the cytotoxicity of DOX and RES to gastric cancer cells. DOX-resistant subclone cell line (SGC7901/DOX) was derived from SGC7901 cells exposed to stepwise increasing concentrations of DOX treatment. We measured the migratory capabilities of SGC7901/DOX cells by Cell scratch test and Transwell assay. SGC7901/DOX cells were treated with DOX, RES, neither or both. Then we analyzed cell survival by CCK8 assay, colony formation by Colony-forming assay, cell apoptosis by Annexin-V-FITC and PI dual staining assay and cell migration by Cell scratch test and Transwell assay. Western blotting was conducted to detect the protein expressions of PTEN/Akt signaling pathway and EMT-related markers. Immunofluorescence was performed to confirm the EMT-related markers expressions. The xenograft model was used to assess the effect of DOX and RES in vivo. The key molecules associated with proliferation, apoptosis and EMT were evaluated by immunohistochemistry in tumor specimens.ResultsSGC7901/DOX cells acquired drug resistance and enhancive migratory capability. RES enabled SGC7901/DOX cells to regain DOX sensitivity, mitigated the aggressive biological features, promoted cell apoptosis in vitro and inhibited tumor growth in vivo. Mechanistic studies revealed that SGC7901/DOX cells underwent epithelial-mesenchymal transition (EMT) which was induced by Akt activation, and through activating PTEN, RES inhibited the Akt pathway, and then achieved the reversion of EMT.ConclusionRES serves as a novel solution to reverse the DOX-resistance of gastric cancer via preventing EMT by modulating PTEN/Akt signaling pathway. DOX-RES combined treatment provides a promising future for gastric cancer patients to postpone drug resistance and prolong survival.

BackgroundColorectal cancer (CRC) is one of the most common malignancies worldwide with poor prognosis. Studies have showed that abnormal microRNA (miRNA) expression can affect CRC pathogenesis and development through targeting critical genes in cellular system. However, it is unclear about which miRNAs play central roles in CRC’s pathogenesis and how they interact with transcription factors (TFs) to regulate the cancer-related genes.ResultsTo address this issue, we systematically explored the major regulation motifs, namely feed-forward loops (FFLs), that consist of miRNAs, TFs and CRC-related genes through the construction of a miRNA-TF regulatory network in CRC. First, we compiled CRC-related miRNAs, CRC-related genes, and human TFs from multiple data sources. Second, we identified 13,123 3-node FFLs including 25 miRNA-FFLs, 13,005 TF-FFLs and 93 composite-FFLs, and merged the 3-node FFLs to construct a CRC-related regulatory network. The network consists of three types of regulatory subnetworks (SNWs): miRNA-SNW, TF-SNW, and composite-SNW. To enhance the accuracy of the network, the results were filtered by using The Cancer Genome Atlas (TCGA) expression data in CRC, whereby we generated a core regulatory network consisting of 58 significant FFLs. We then applied a hub identification strategy to the significant FFLs and found 5 significant components, including two miRNAs (hsa-miR-25 and hsa-miR-31), two genes (ADAMTSL3 and AXIN1) and one TF (BRCA1). The follow up prognosis analysis indicated all of the 5 significant components having good prediction of overall survival of CRC patients.ConclusionsIn summary, we generated a CRC-specific miRNA-TF regulatory network, which is helpful to understand the complex CRC regulatory mechanisms and guide clinical treatment. The discovered 5 regulators might have critical roles in CRC pathogenesis and warrant future investigation.Electronic supplementary materialThe online version of this article (10.1186/s12859-017-1796-4) contains supplementary material, which is available to authorized users.

WTX (Wilms' tumor suppressor X chromosome) is a novel putative tumor suppressor gene in Wilms' tumor of kidney, its expression and function in other human cancers had not been explored. This study detected the expression of WTX in 459 cases of 15 organs of cancers and adjacent normal tissues by using immunohistochemical staining (IHC), and validated them by in situ hybridization (ISH) and quantitative real-time reverse transcription PCR (qRT-PCR). IHC and ISH data showed that WTX protein was generally expressed in normal tissues, but reduced expression in corresponding cancers. This study demonstrated that WTX downregulation is a common phenomenon in human cancers, WTX might be a general tumor-suppressor gene and biological marker of multiple cancer tissues. Apart from kidney, stomach is another target tissue of WTX gene. The germline and somatic mutations of WTX were screened in 12 gastric cancer patients and identified in one cases (8.3%). Mutation in the WTX gene might be one of the reasons of WTX loss in gastric cancer patients.

Introduction Biologic markers that predict development of invasive breast cancer (IBC) in patients diagnosed with ductal carcinoma in-situ (DCIS) are needed to improve personalized therapy. In this study, we examined the incidence of early IBC in DCIS subgroups defined by immunophenotype. Methods Clinical and histologic materials of 143 patients with radiographically suggesting DCIS without obvious evidence of IBC were reviewed. All patients underwent initial biopsy followed by short-term subsequent resection. The presence of IBC, histopathologic features of DCIS and IBC, when present, and their estrogen receptor (ER), progesterone receptor (PR) and HER2 phenotypes were evaluated. Results Early IBC was identified on initial biopsy in 6 (4%) and subsequent resection in 24 (17%) patients. HER2 positivity in DCIS was the dominant factor associated with IBC. There was also a significant association between ER/PR/HER2+ DCIS and the presence of IBC. The ER/PR/HER2+ DCIS appeared to be the most unstable precursor, because of the highest invasion rate and frequent association with a discordant phenotype. Conclusions HER2 positivity and ER/PR/HER2 phenotype may be used to identify DCIS patients at higher risk of harboring or potentially developing IBC. Strategies targeting HER2 in DCIS may be of potential benefit in preventing IBC in patients with DCIS.

Background: Due to lack of country-specifi c norms in China, we established the reference range of plasma amino acids for younger Chinese children by reverse phase high-performance liquid chromatography (HPLC). Methods: Plasma proteins were precipitated with ethanol. L -Norvaline served as an internal standard. This HPLC method was based on automated precolumn derivatization using o -phthalaldehyde 3-mercaptopropionic acid for primary amino acids and 9-fl uorenylmethyl chloroformate for secondary amino acids. Twenty-three amino acid derivatives were separated by a Zorbax Eclipse AAA column and detected fl uorometrically. Plasma amino acids were measured in 108 healthy Chinese children (ages 0 -5 years, 59 boys and 49 girls). Results: The assay was linear from 7.2 to 925.0 µ mol/L for all amino acids. Recovery of amino acids added to plasma samples was 93 % -107 % . Within-and between-run reproducibility was 0.18 % -6.27 % and 2.94 % -16.15 % , respectively. Sex-and age-specifi c plasma amino acid reference range for younger Chinese children was established. In our study, the boys had signifi cantly higher levels of glutamine, citrulline, and tryptophan than girls (p < 0.05), and the girls had a signifi cantly higher level of alanine than boys (p < 0.05). Compared with the 0-to 1-year group, the 1-to 5-year group had signifi cantly higher levels of citrulline, valine, phenylalanine, isoleucine, and sarcosine and lower levels of aspartate, glutamate, serine, threonine, alanine, methionine, and tryptophan (p < 0.05). Conclusions: This study validates the HPLC method described here as a simple, rapid, and reliable assay. The reference range of plasma amino acids for younger Chinese children is different from that for Caucasian children and will facilitate our clinical diagnosis in the future.Chemicals 9-Fluorenylmethyl chloroformate, o -phthalaldehyde 3-mercaptopropionic acid (OPA-3MPA), and borate buffer were obtained from Brought to you by |

Background: To report the outcomes of hepatoblastoma resected in our institution. Methods: We diagnosed 135 children with hepatoblastoma at our institution between January 2010 and December 2017. Patients who underwent liver resection were included for analysis. However, patients who abandoned treatment after diagnosis were excluded from analysis, but their clinical characteristics were provided in the supplementary material. Results: Forty-two patients abandoned treatment, whereas 93 patients underwent liver resection and were included for statistical analysis. Thirty-six, 23, 3, and 31 patients had PRETEXT stages II, III, IV, and unspecified tumours, respectively. Seven patients had ruptured tumour; 9 had lung metastasis (one patient had portal vein thrombosis concurrently). Sixteen patients underwent primary liver resection; 22, 25, and 30 patients received cisplatin-based neoadjuvant chemotherapy and delayed surgery, preoperative transarterial chemoembolization (TACE) and delayed surgery, and a combination of cisplatin-based neoadjuvant chemotherapy, TACE, and delayed surgery, respectively. Forty patients had both PRETEXT and POST-TEXT information available for analysis. Twelve patients were down-staged after preoperative treatment, including 2, 8, and 2 patients from stages IV to III, III to II, and II to I, respectively. Ten patients with unspecified PRETEXT stage were confirmed to have POST-TEXT stages II (n = 8) and I (n = 2) tumours. Seven tumours were associated with positive surgical margins, and 12 patients had microvascular involvement. During a median follow-up period of 30.5 months, 84 patients survived without relapse, 9 experienced tumour recurrence, and 4 died. The 2-year event-free survival (EFS) and overall survival (OS) rates were 89.4 ± 3.4%, and 95.2 ± 2.4%, respectively; they were significantly better among patients without metastasis (no metastasis vs metastasis: EFS, 93.5 ± 3.7% vs 46.7 ± 19.0%, adjusted p = 0.002. OS, 97.6 ± 2.4% vs 61.0 ± 18.1%, adjusted p = 0.005), and similar among patients treated with different preoperative strategies (chemotherapy only vs TACE only vs Both: EFS, 94.7 ± 5.1% vs 91.7 ± 5.6% vs 85.6 ± 6.7%, p = 0.542. OS, 94.1 ± 5.7% vs 95.7 ± 4.3% vs 96.7 ± 3.3%, p = 0.845).

Cardiac PEComa is very rare. We reported two cases of epithelioid PEComas, one in an adult and one in a 2-year-old child. Both tumors were composed of sheets of epithelioid cells with coagulation necrosis. In addition, the adult case showed marked nuclear atypia and high mitotic activity with atypical mitosis and the pediatric case showed unusual clear cell features. Immunohistochemically, both tumors were positive for HMB-45 and SMA and negative for S100 and cytokeratin. Electron microscopy was performed in the pediatric case and showed premelanosomes. The adult patient developed extensive metastasis indicating malignant behavior. Prior to the two cases, only 5 other cases of cardiac PEComa were reported and the literatures are reviewed.

Confirmatory Sanger sequencing of whole exome sequencing first identified a somatic and germline FOXP3 mosaicism with two different mutational events of c.210 + 1G > T and c.210 + 1G > A in the mother of a boy with IPEX syndrome.