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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.

Congenital hyperinsulinism (CHI) is a severe heterogeneous disorder due to dysregulation of insulin secretion from the pancreatic β-cells leading to severe hypoglycemia in infancy. 18-fluoro-l-3,4-dihydroxyphenylalanine positron emission tomography ((18)F‑DOPA‑PET)/CT is a useful tool in distinguishing between focal and diffuse disease preoperatively. But recent studies have suggested that the scanning may not be accurate as initially estimated. In this study we characterize a case of CHI with a compound heterozygous mutation of ABCC8 gene. The results of clinical investigation, gene mutation analysis, (18)F‑DOPA‑PET/CT scan, and pathological examination showed some new characteristics that have never been reported. The patient was unresponsive to medical therapy with diazoxide and received pancreatectomy twice. Genetic analysis identified a compound heterozygous mutation in ABCC8 genes. Imaging with (18)F‑DOPA‑PET/CT indicated a focal lesion in the head of the pancreas. The pathological diagnosis was an atypical form of CHI. The patient presented with a phenotype of atypical CHI unresponsive to diazoxide. It is considered that a relationship existed between the compound heterozygous mutation and the atypical form. (18)F‑DOPA‑PET/CT is a useful tool in distinguishing between focal and diffuse forms preoperatively but the accuracy is not 100%. The scan result is best combined with genetic analysis and intra-operative biopsy to confirm the histological subtypes. The combination will provide the optimal strategy for the surgical treatment of patients with CHI.

Background Colorectal 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. Results To 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. Conclusions In 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 material The online version of this article (10.1186/s12859-017-1796-4) contains supplementary material, which is available to authorized users.

SUMMARY Thyroid transcription factor-1 (TTF-1) is a 38-kd nuclear protein, and a member of the NKx2 family of homeodomain transcription factors. It is highly expressed in normal and neoplastic thyroid and lung tissues, and is considered a reliable marker for lung adenocarcinoma and thyroid carcinoma. Recently, expression of TTF-1 has also been reported in ovarian, endometrial, and endocervical epithelial neoplasms. Little is known about TTF-1 immunoreactivity in normal gynecologic tissues. In this study, TTF-1 expression in various non-neoplastic gynecologic tissues was investigated by standard immunohistochemistry. One hundred and eight samples of benign gynecologic tissues from adult patients who had no known history of neoplastic condition were collected. Twenty-eight endometria (12 proliferative, 11 secretory, and 5 inactive), 26 fallopian tubes, 28 cervixes (14 endocervical and 14 ectocervical), 14 myometria, and 12 ovaries were studied. In addition, 4 normal fallopian tubes and 2 ovaries from 5 pediatric patients (aged from 3 mo to 11-yr old) were evaluated. Variable TTF-1 nuclear reactivity was identified in 25 of 26 (96%) fallopian tubes (extent of positivity ranged from 2% to 60%, median 25%), 15 of 28 (54%) endometria (1% to 10%, median 5%), and 6 of 14 (43%) endocervical samples (

Background Gastric 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. Methods CCK8 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. Results SGC7901/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. Conclusion RES 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.