Dual-layer spectral detector CT (SDCT) can improve the detection of mixed ground-glass lung nodules.

BACKGROUND: Mixed ground-glass lung nodules are a high-risk factor for lung adenocarcinoma. This study aimed to analyze the value of SDCT electron density imaging in the detection of mixed ground-glass lung nodules (GGNs). METHOD: 150 patients with GGNs confirmed by chest SDCT and surgical pathology were retrospectively analyzed. GGNs were screened by two senior radiologists by the double-blind method based on conventional CT and SDCT electron density images. Average CT values and electron density (ED) values of GGNs were measured for all, solid and ground-glass. RESULT: Thirty pGGN cases determined by conventional CT were found to be mGGN on electron density images, including 23 in the invasive adenocarcinoma group (detection rate of 35.38%), which was significantly higher than that of the PGL group (14.89%, P < 0.05). In electron density images, average CT values and ED values in the PGL and invasive adenocarcinoma groups with pGGNs were no difference. The average CT value and ED value were significantly higher in the mGGN invasive adenocarcinoma group compared with the PGL group (P < 0.05). Meanwhile, ROC curve analysis of average CT value and ED value revealed AUC values for mGGN infiltration of 0.759 and 0.752. CONCLUSION: SDCT can improve GGN visualization and increase the detection rate of mGGN compared with conventional CT. Attention should be paid to invasive adenocarcinoma for lung GGNs detected as mGGNs with high average CT value or ED value.

A rare multiple primary sarcomatoid carcinoma (SCA) of small intestine harboring driver gene mutations: a case report and a literature review.

Primary sarcomatoid carcinoma (SCA) is a type of rare tumor consisting of both malignant epithelial and mesenchymal components. Only 32 cases of SCA of the small bowel have been reported in the literature to date. Due to its rarity and complexity, this cancer has not been genetically studied and its diagnosis and treatment remain difficult. Here we report a 54-year-old male underwent emergency surgical resection in the small intestine due to severe obstruction and was diagnosed with multiple SCA based on postoperative pathological examination. Over 100 polypoid tumors scattered along his whole jejunum and proximal ileum. Chemotherapy (IFO+Epirubicin) was performed after surgery while the patient died two months after the surgery due to severe malnutrition. Whole-exome sequencing was performed for the tumor tissue with normal tissue as the control. Important cancer-related gene mutations, including KRAS (c.37G>T, p.G13C), TP53 (c.871A>T, p.K291*), EGFR (c.1351C>T, p.R451C), and CDKN2A (c.104_138del, p.G35fs), were found among 286 nonsynonymous somatic mutations (SNV and Indel). Copy-number amplified genes mainly gathered in chromosome 6, 7, 16 and 20. Mutation clustering analysis showed that main genetic abnormalities included DNA methylation, DNA alkylation, cellular homeostasis, and shared similarities with melanoma, glioma, prostate cancer, bladder cancer, non-small cell lung cancer, and pancreatic cancer. In summary, the genomic features of the small intestine SCA were explored at whole-exome level for the first time, and over 200 somatic mutations were identified in the tumor tissue. Key tumor driver gene mutations were revealed, as well as several aberrant functional pathways. These results contribute to further understanding of the pathogenesis and molecular mechanism of this rare tumor.

Blockage of TGF-α Induced by Spherical Silica Nanoparticles Inhibits Epithelial-Mesenchymal Transition and Proliferation of Human Lung Epithelial Cells.

Background. Xuanwei City in Yunnan province has been one of the towns with highest lung cancer mortality in China. The high content of amorphous silica in the bituminous coal from Xuanwei of Yunnan is mainly present as irregular and spherical silica nanoparticles (SiNPs). It has been reported that silica nanoparticles in bituminous coal correlated with the high incidence of lung cancer in Xuanwei. To explore the role and mechanism of SiNPs in the tumorigenesis of lung cancer in Xuanwei, human mononuclear cells (THP-1) and human bronchial epithelial cells (BEAS-2B) were cocultured in a transwell chamber. Combined with Benzo[a]pyrene-7, 8-dihydrodiol-9, and 10-epoxide (BPDE), SiNPs could significantly promote the proliferation and Epithelial-Mesenchymal Transition (EMT) and inhibit apoptosis of BEAS-2B cells and induce the release of TGF-α from THP-1 cells. After neutralizing TGF-α with antibody, the proliferation and EMT were decreased and enhanced apoptosis of BEAS-2B cells. Furthermore, the results showed that TGF-α in the sera of patients with lung adenocarcinoma in Xuanwei were significantly higher than in patients with benign pulmonary lesions in Xuanwei and those with lung adenocarcinoma in outside of Xuanwei of Yunnan. Taken together, our study found that SiNPs promoted the proliferation and EMT of BEAS-2B cells by inducing the release of TGF-α from THP-1 cells.

Spherical silica nanoparticles promote malignant transformation of BEAS-2B cells by stromal cell-derived factor-1α (SDF-1α).

OBJECTIVE: This study aimed to examine the role of spherical silica nanoparticles (SiNPs) on human bronchial epithelial (BEAS-2B) cells through inflammation. METHODS: Human mononuclear (THP-1) cells and BEAS-2B cells were co-cultured in transwell chambers and treated with 800 mmol/L benzo[ a]pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE) and 12.5 µg/mL SiNPs for 24 hours. For controls, cells were treated with BPDE alone. Subcutaneous tumorigenicity and epithelial-mesenchymal transition (EMT) of BEAS-2B cells were measured. The cells were blocked with a stromal cell-derived factor-1α (SDF-1α)-specific antibody. EMT was analyzed in cells treated with 800 mmol/L BPDE and 12.5 µg/mL SiNPs relative to matched control cells and xenografts in vivo. Serum SDF-1α levels were measured in 23 patients with lung adenocarcinoma in Xuanwei, in 25 with lung adenocarcinoma outside Xuanwei, and in 22 with benign pulmonary lesions in Xuanwei. RESULTS: SiNPs significantly promoted tumorigenesis and EMT, induced the release of SDF-1α, and activated AKT (ser473) in BEAS-2B cells. EMT and phosphorylated AKT (ser473) and glycogen synthase kinase-3ß levels were decreased when blocked by SDF-1α antibody in BEAS-2B cells. SDF-1α was mainly secreted by THP-1 cells. CONCLUSION: SiNPs combined with BPDE promote EMT of BEAS-2B cells via the AKT pathway by inducing release of SDF-1α from THP-1 cells.

Clinical associations between ASCT2 and p­mTOR in the pathogenesis and prognosis of epithelial ovarian cancer.

Alanine serine cysteine­preferring transporter 2 (ASCT2; also known as SLC1A5) is an important glutamine transporter, and it serves a crucial role in tumor growth and progression. ASCT2 is highly expressed in numerous types of cancer, but the pathological significance of its expression in epithelial ovarian cancer (EOC) remains unclear. The mechanistic target of rapamycin (mTOR) level is hyperelevated in a number of tumor types, including ovarian cancer. The aim of the present study was to elucidate the prognostic role of ASCT2 and phosphorylated (p)­mTOR in EOC. The levels of ASCT2 and p­mTOR/mTOR were detected in normal ovarian tissues, benign ovarian tumors, borderline ovarian tumors and EOC tissues by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot assays. The protein levels of ASCT2 and p­mTOR in EOC patients were then detected by immunohistochemistry (IHC). Furthermore, EOC tumor sections were stained for Ki­67 and cluster of differentiation 34 (CD34) to assess proliferation and microvessel density by IHC. The results of RT­qPCR and western blot analysis demonstrated that ASCT2 and p­mTOR protein levels were significantly higher in EOC tissues compared with those in other groups. IHC analysis of 104 EOC tissues suggested that ASCT2 expression was associated with clinicopathological parameters, including International Federation of Gynecology and Obstetrics stage, pathological grade, serum cancer antigen 125 level, Ki­67 status and CD34 status. Kaplan­Meier survival curve analysis indicated that high expression of ASCT2 and p­mTOR were important factors predicting a poor prognosis for patients with EOC. The expression levels of ASCT2 and p­mTOR in EOC were positively correlated (r=0.385, P<0.001). This positive correlation between ASCT2 and p­mTOR indicates that they have a synergistic effect on the growth and development of early EOC. The combined detection of ASCT2 and p­mTOR may serve as a potential marker to inform diagnosis, postoperative follow­up requirements and targeted therapy options for patients with early­stage EOC, but not for terminal­stage patients.

Integrated Analysis of Genome-Wide Copy Number Alterations and Gene Expression Profiling of Lung Cancer in Xuanwei, China.

OBJECTIVES: Lung cancer in Xuanwei (LCXW), China, is known throughout the world for its distinctive characteristics, but little is known about its pathogenesis. The purpose of this study was to screen potential novel "driver genes" in LCXW. METHODS: Genome-wide DNA copy number alterations (CNAs) were detected by array-based comparative genomic hybridization and differentially expressed genes (DEGs) by gene expression microarrays in 8 paired LCXW and non-cancerous lung tissues. Candidate driver genes were screened by integrated analysis of CNAs and DEGs. The candidate genes were further validated by real-time quantitative polymerase chain reaction. RESULTS: Large numbers of CNAs and DEGs were detected, respectively. Some of the most frequently occurring CNAs included gains at 5p15.33-p15.32, 5p15.1-p14.3, and 5p14.3-p14.2 and losses at 11q24.3, 21q21.1, 21q22.12-q22.13, and 21q22.2. Integrated analysis of CNAs and DEGs identified 24 candidate genes with frequent copy number gains and concordant upregulation, which were considered potential oncogenes, including CREB3L4, TRIP13, and CCNE2. In addition, the analysis identified 19 candidate genes with a negative association between copy number change and expression change, considered potential tumor suppressor genes, including AHRR, NKD2, and KLF10. One of the most studied oncogenes, MYC, may not play a carcinogenic role in LCXW. CONCLUSIONS: This integrated analysis of CNAs and DEGs identified several potential novel LCXW-related genes, laying an important foundation for further research on the pathogenesis of LCXW and identification of novel biomarkers or therapeutic targets.

Translocation of microbes and changes of immunocytes in the gut of rapid- and slow-progressor Chinese rhesus macaques infected with SIVmac239.

Human/simian immunodeficiency virus (HIV/SIV) infection can cause severe depletion of CD4(+) T cells in both plasma and mucosa; it also results in damage to the gut mucosa barrier, which makes the condition more conducive to microbial translocation. In this study, we used SIV-infected Chinese rhesus macaques to quantify the extent of microbial translocation and the function of immune cells in the entire gastrointestinal tract and to compare their differences between rapid and slow progressors. The results showed that in the slow progressors, microbial products translocated considerably and deeply into the lamina propria of the gut; the tissue macrophages had no significant differences compared with the rapid progressors, but there was a slightly higher percentage of mucosal CD8(+) T cells and a large amount of extracellular microbial products in the lamina propria of the intestinal mucosa of the slow progressors. The data suggested that although microbial translocation increased markedly, the mucosal macrophages and CD8(+) T cells were insufficient to clear the infiltrated microbes in the slow progressors. Also, therapies aimed at suppressing the translocation of microbial products in the mucosa could help to delay the progression of SIV disease.

Pathogenesis sequences in Gejiu miners with lung cancer: an introduction.

Tin miners in Gejiu, Yunnan Province, China are at high risk of developing lung cancer with significant occupational characteristics. Tissue samples from these miners presented pathological characteristics, such as fibroplasia in carcinomas, peri-cancerous tissue in lung cancers, and hyperplasia and dysplasia of epithelial cells in peri-cancerous tissue. Carcinomas induced by Yunnan tin mine dust in the animal experiment underwent inflammation, fibroplasia, hyperplasia, dysplasia, and carcinogenesis of epithelial cells. A correlated and synergistic relationship was observed between bronchial epithelial cell transformation and fibroblast activation in vitro induced by mine dust. Fibroblast hyperplasia and activation are important factors that promote the transformation and carcinogenesis of epithelial cells. Our findings suggested that pulmonary fibrosis may increase the risk and promote the occurrence of lung cancer, which can lead to lung fiber hyperplasia.

Malignant adenomyoepithelioma combined with adenoid cystic carcinoma of the breast: a case report and literature review.

BACKGROUND: Malignant adenomyoepithelioma and adenoid cystic carcinoma are both rare malignant epithelial-myoepithelial tumors of the breast. We report a very rare case with a malignant adenomyoepithelioma combining with adenoid cystic carcinoma in a single mass. CASE PRESENTATION: A 61-year-old female presented with a palpable painless mass in the right breast. Mammography revealed a large irregular dense shadow without obvious internal calcification. A simple lumpectomy was performed, and a 1.6cm well-circumscribed pale-tan nodule was presented. Histologically, the nodule was composed of two obscure lobules. One exhibited typical histological image of adenoid cystic carcinoma, the other one showed the image of epithelial-myoepithelial carcinoma of salivary gland, and support the diagnosis of biphasic malignant adenomyoepithelioma. Transition between the two lobules was gradual. Immunohistochemically, CK18 and P63 highlighted the epithelial and myoepithelial cells respectively in both lesions. CD117 was positive in the epithelial cells of adenoid cystic carcinoma, but was totally negative in malignant adenomyoepithelioma. CONCLUSION: This report is, to our knowledge, the first case that combines these two tumors in a single mass. In addition, we present a review of the literature. The histogenesis of these tumors is also discussed. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://med.motic.com/MoticGallery/Slide?id=D562817E-23C2-4F72-9823-86EF6DA40005&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025 and http://med.motic.com/MoticGallery/Slide?id=38BB7126-6FFB-4B66-A208-B8C0F528DCA8&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025.

Semaphorin 5A promotes gastric cancer invasion/metastasis via urokinase-type plasminogen activator/phosphoinositide 3-kinase/protein kinase B.

BACKGROUND: Semaphorin 5A, a member of the semaphorin family, was originally identified as an axonal guidance factor functioning during neuronal development. Previously, we showed that the expression of semaphorin 5A might contribute to the metastasis of gastric cancer. However, less information is currently available as to the involvement of uPA in the semaphorin 5A-induced metastasis and invasion of gastric cancer cells. AIM: The present study was designed to test whether semaphorin 5A mediates the invasion and metastasis of gastric cancer via PI3K/Akt/uPA signaling. METHODS: The semaphorin 5A-overexpressing cell was established from the gastric cancer cell line AGS. The effect of semaphorin 5A on the expression of uPA was evaluated by ELISA and Western blotting as well as RT-PCR assays, respectively. Synthetic or natural inhibitors and dominant-negative mutants were used to determine the hierarchical relationship between semaphorin 5A, PI3K/Akt and uPA in the invasion and metastasis of gastric cancer. RESULTS: Overpression of semaphorin 5A enhanced the expression of uPA, and synthetic or natural inhibitors of uPA abolished semaphorin 5A-induced cell migration and invasion. Semaphorin 5A overexpression promoted the phosphorylation of Akt. Blocking effects of PI3K/Akt using pharmacologic inhibitors, dominant-negative mutants abolished the ability of semaphorin 5A to induce uPA expression and cell invasion and migration. CONCLUSION: Semaphorin 5A could promote invasion and metastasis of gastric cancer through the PI3K/Akt/uPA signal transduction pathway. Semaphorin 5A and its regulated molecules could be the potential targets for cancer therapy.