Lymphocytic interstitial pneumonia presenting with a ground glass nodule: A case report and literature review.

RATIONALE: Lymphocytic interstitial pneumonia (LIP) is a rare benign lymphoproliferative disorder, often associated with autoimmune diseases. Most LIPs present with multiple bronchial cysts and diffuse interstitial infiltration. It is histologically characterized by widespread diffuse lymphocytic infiltration of the pulmonary interstitium, and the enlargement and widening of the alveolar septum. PATIENT CONCERNS: A 49-year-old woman was admitted to hospital for finding pulmonary nodules for more than 2 months. 3D imaging chest computed tomography (CT) examination of both lungs showed that there was a middle lobe of the right lung with a size of about 1.5 cm × 1.1 cm ground-glass nodules. DIAGNOSES: A single operating port thoracoscopic wedge resection biopsy of a right middle lung nodule was performed. The pathology showed diffuse lymphocytic infiltration with varying numbers of small lymphocytes, plasma cells, macrophages and histiocytes infiltrating the alveolar septa, widened and enlarged alveolar septa, and scattered lymphoid follicles. Immunohistochemically, CD20 positive in follicular area, CD3 positive in interfollicular area. LIP was considered. INTERVENTIONS: The patient was regularly followed without any specific treatment. OUTCOMES: Follow-up chest CT showed no significant abnormalities in the lungs 6 months after surgery. LESSONS: To the best of our knowledge, our case may be the second reported case of a patient with LIP presenting with a ground glass nodule on chest CT, and it is speculated that the ground glass nodule may be an early manifestation of idiopathic LIP.

CircPVT1 Promoted the Progression of Breast Cancer by Regulating MiR-29a-3p-Mediated AGR2-HIF-1α Pathway.

BACKGROUND: Breast cancer (BC) is a great contributor to cancer-related death. Mounting studies have identified that circular RNAs (circRNAs) play vital roles in cancer cell proliferation, apoptosis and invasion. Here, we explored the effect of circPVT1 on BC development as well as its downstream mechanisms. METHODS: qRT-PCR was used to determine the relative expression levels of circPVT1 and miR-29a-3p in BC tissue samples and cell lines. We also analyzed the relevance between pathological indexes and circPVT1 expression level. Human breast cancer cell lines MCF-7 and MDA-MB-231 were taken as cell models. Gain- or loss-of-functional assays of circPVT1 and miR-29a-3p were conducted in BC cell lines to investigate their effects on the cell proliferation, apoptosis, migration and invasion. The protein levels of AGR2, HIF-1α, Bax, Bcl2 and Caspase3 were determined by Western blot. Furthermore, dual-luciferase reporter assay and RNA fluorescence in situ hybridization (FISH) were used to confirm the targeted relationships between circPVT1 and miR-29a-3p, miR-29a-3p and anterior gradient 2 (AGR2). RESULTS: CircPVT1 was highly expressed while miR-29a-3p was lowly expressed in BC tissues and cell lines. Inhibition of circPVT1 or overexpression of miR-29a-3p remarkably suppressed BC cell proliferation, invasion and migration while promoted cell apoptosis. By contrast, circPVT1 upregulation or miR-29a-3p inhibition led to mitigate malignant behaviours of BC cells. Functionally, circPVT1 bound to miR-29a-3p, and AGR2 was a target gene of miR-29a-3p. Overexpressed circPVT1 promoted AGR2 and HIF-1α expression by repressing miR-29a-3p. More importantly, overexpressing AGR2 enhances HIF-1α expression, accompanied with accelerated proliferation, invasion and migration of BC cells. CONCLUSION: CircPVT1 acts as an oncogene in BC via promoting the growth, invasion, migration and inhibiting apoptosis through miR-29a-3p-mediated AGR2-HIF-1α axis.

Microarray data analysis reveals gene expression changes in response to ionizing radiation in MCF7 human breast cancer cells.

BACKGROUND: The aim of this study was to identify potential therapeutic target genes for breast cancer (BC) by the investigation of gene expression changes after ionizing radiation (IR) in BC cells. Gene expression profile GSE21748, including BC cell line MCF-7 samples at different time points after IR treatment, were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified in different time points following IR compared with cell samples before IR, respectively. Gene ontology functions and The Kyoto Encyclopedia of Genes and Genomes pathways of the overlapping DEGs were enriched using DAVID. Transcription factor (TFs)-encoding genes were identified from the overlapping DEGs, followed by construction of transcriptional regulatory network and co-expression network. RESULTS: A total of 864 overlapping DEGs were identified, which were significantly enriched in regulation of cell proliferation and apoptosis, and cell cycle process. We found that FOXD1, STAT6, XBP1, STAT2, LMO2, TFAP4, STAT3, STAT1 were hub nodes in the transcriptional regulatory network of the overlapping DEGs. The co-expression network of target genes regulated by STAT3, STAT1, STAT6 and STAT2 included some key genes such as BCL2L1. CONCLUSION: STAT1, STAT2, STAT3, STAT6, XBP1, BCL2L1, CYB5D2, ESCO2, and PARP2 were significantly affected by IR and they may be used as therapeutic gene targets in the treatment of BC.

Magnolin Inhibits Proliferation and Invasion of Breast Cancer MDA-MB-231 Cells by Targeting the ERK1/2 Signaling Pathway.

The aim of this study was to evaluate the effects of Magnolin (MGL) on inhibition of human breast cancer cells, and explore the underlying molecular mechanisms. The viability of the treated cells was assessed with the Cell Counting Kit-8 (CCK-8) assay, and the proliferation was analyzed in terms of EdU uptake, colony formation, and flow cytometry. The in vitro invasion and migration were determined by the transwell and wound healing assays respectively. The mRNA and protein levels of relevant factors was evaluated by quantitative real-time PCR and Western blotting respectively. MGL significantly decreased the viability and promoted apoptosis of MDA-MB-231 cells, along with reducing EdU incorporation rate as well as the colony forming capacity compared to the untreated control cells. In addition, the in vitro invasion and migration were also significantly inhibited by MGL. Furthermore, MGL suppressed the phosphorylation of MEK1/2, extracellular signal-regulated kinase (ERK)1/2 and significantly downregulated the expression of cyclin-dependent kinase 1 (CDK1), the anti-apoptotic B-cell lymphoma 2 (BCL2) and metastasis-associated matrix metalloproteases (MMPs) 2 & 9, and upregulated the cleaved caspases 3 and 9. After ERK was completely inhibited with the small interfering RNA (siRNA), MGL had no effect on these factors, indicating that ERK is essential for MGL action in breast cancer. In conclusion, MGL inhibits proliferation and invasion of and induces apoptosis in breast cancer cells through the ERK pathway.

MiR-654-5p attenuates breast cancer progression by targeting EPSTI1.

MicroRNAs (miRNAs) dysregulation is a common event in a variety of human diseases including breast cancer. However, clinical relevance and biological role of miR-654-5p in the progression of breast cancer remain greatly elusive. Herein, the expression levels of miR-654-5p were aberrantly downregulated in human breast cancer specimens and four breast cancer cell lines. Low expression of miR-654-5p was strongly associated with advanced TNM stage and lymph node metastasis as well as a poor survival. Functional analysis showed that miR-654-5p overexpression inhibited cell growth and invasion, and induced cell apoptosis in two aggressive breast cancer cells. Further studies demonstrated that Epithelial stromal interaction 1 (EPSTI1) was a direct target gene of miR-654-5p and showed an inverse correlation with miR-654-5p expression. Forced expression of EPSTI1 could abrogate the inhibitory effect of miR-654-5p on the growth and invasion of breast cancer cells as well as apoptosis-induced ability. In conclusion, the present study highlights that miR-654-5p acts as a tumor suppressor in breast cancer through directly targeting EPSTI1, and their functional regulation may open a novel avenue with regard to the therapeutic target for breast cancer.

Adipose-derived mesenchymal stem cells inhibit activation of hepatic stellate cells in vitro and ameliorate rat liver fibrosis in vivo.

BACKGROUND/PURPOSE: Previous studies suggested that mesenchymal stem cells may ameliorate fibrogenesis through the inhibition of hepatic stellate cells (HSCs) activation. This study aimed to investigate whether adipose derived mesenchymal stem cells (ADSCs) could modulate the activation of HSCs and contribute to the recovery of liver fibrogenesis. METHODS: ADSCs and HSCs were isolated from Sprague-Dawley rats and co-cultured using a transwells insert. Cell proliferation, apoptosis and smooth muscle α-actin (α-SMA) expression in HSCs were examined. Rats were injected with CCl4 to induce liver fibrogenesis. After injection of ADSCs through portal vein, the rats were examined for pathological changes in the liver. α-SMA expression and hydroxyproline content in the liver and serum levels of collagen III and hyaluronic acid was detected. RESULTS: After co-culturing for 72 h, the proliferation and activation of HSCs was inhibited by ADSCs and the apoptosis of HSCs was promoted by ADSCs. Transplantation of ADSCs inhibited liver fibrogenesis in the rats. CONCLUSION: ADSCs inhibit the proliferation and activation of HSCs in vitro and inhibit liver fibrogenesis in rat model, suggesting the potential application of ADSCs in liver fibrogenesis therapy.

Relationship between CIP2A expression, and prognosis and MDR-related proteins in patients with advanced gastric cancer.

CIP2A is highly expressed in a variety of malignancies. We determined the expression and clinical significance of CIP2A in patients with advanced gastric cancer. CIP2A protein was expressed in 25 of 37 cancer tissue specimens. There was no correlation between CIP2A and PGP, GST-π, Topo-II, and LRP expression. Survival analysis showed significant differences between the survival rate of the CIP2A protein-positive and -negative groups (χ(2)=4.509, P=0.034), but the degree of positive expression was unrelated to survival time (χ(2)=4.639, P=0.098). CIP2A expression may have no prospective value for optimizing chemotherapy regimens, but it can be an indicator for patient prognosis.

Prophylactic Lamivudine to Improve the Outcome of Breast Cancer Patients With HBsAg Positive During Chemotherapy: A Meta-Analysis.

CONTEXT: Raising the chemotherapy-induced HBV reactivation is parallel to the increment of chemotherapy treatments in breast cancer patients. This meta-analysis aims to evaluate the efficacy of prophylactic use of lamivudine in breast cancer patients with HBsAg positive during chemotherapy. EVIDENCE ACQUISITION: MEDLINE, Pubmed, Ovid and Embase were used to search for clinical studies comparing with or without prophylactic use of lamivudine for HBV reactivation in breast cancer patients receiving chemotherapy. Outcomes of interest were the rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis attributable to HBV reactivation, severity of hepatitis and severity of hepatitis attributable to HBV reactivation, the rate of chemotherapy disruption, and the rate of chemotherapy disruption attributable to HBV reactivation, overall mortality, and mortality attributable to HBV reactivation. RESULTS: Four studies with 285 patients were included in this meta-analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis related to HBV reactivation were reduced by use of prophylactic lamivudine compared to control group. Pooled Odds Ratios (ORs) were 0.09 (95% confidence intervals [CI] 0.03-0.26; P < 0.0001), 0.23 (95% CI 0.06-0.92; P = 0.04), and 0.10 (95% CI 0.03-0.32; P < 0.0001) respectively. There was a reduction in chemotherapy disruption related to HBV reactivation by use of prophylactic lamivudine (pooled OR = 0.11; 95% CI 0.02-0.58; P = 0.01). Chemotherapy disruption, overall mortality, and mortality attributable to HBV reactivation were not significantly different between two groups. Pooled ORs were 0.42 (95% CI 0.11-1.58; P = 0.20), 0.37 (95% CI 0.07-2.04; P = 0.25), and 0.25 (95% CI 0.01-6.82; P = 0.41) respectively. Lamivudine was well-tolerated, and no additional toxicity was observed. CONCLUSIONS: Use of prophylactic lamivudine may have positive effect on the outcome of breast cancer patients with HBsAg positive during chemotherapy.

Effectiveness and safety of preoperative percutaneous transhepatic cholangiodrainage with bile re-infusion in patients with hilar cholangiocarcinoma: a retrospective controlled study.

BACKGROUND: Extensive controversies exist over the use of preoperative biliary drainage preceding radical resection of hilar cholangiocarcinoma. This study assessed the effectiveness and safety of percutaneous transhepatic cholangiodrainage (PTCD) with bile re-infusion in the preoperative optimization of hilar cholangiocarcinoma patients. METHODS: Eligible hilar cholangiocarcinoma patients received preoperative PTCD with bile re-infusion (treatment group, n = 56) through a nasoduodenal tube for 2 weeks, and the control group (n = 60) received conservative treatment alone. Operable patients were assigned to undergo either a radical or palliative resection. The outcome measures included the overall resection rate, R0 resection rate, surgical morbidity rate and 1-year and 5-year overall survival rates. RESULTS: The treatment group exhibited a significant decrease in serum bilirubin levels after PTCD with bile re-infusion. The overall resection rate was significantly higher in the treatment group than in the control group (85.5% vs. 65.0%, P < 0.05), and the palliative resection rate was also significantly higher in the treatment group (53.5% vs. 35.0%, P < 0.05). However, the R0 resection rate was comparable between the 2 groups (32.1% vs. 30.0%, P > 0.05). The morbidity rate was significantly lower in the treatment group than in the control group (29.1% vs. 51.3%, P < 0.05). One-year and 5-year survival rates were similar between the 2 groups (69.6% vs. 66.7%, P > 0.05; 5.3% vs. 3.6%, P > 0.05). CONCLUSIONS: Preoperative PTCD with bile re-infusion improves the resection rate and shows a good safety profile in patients with hilar cholangiocarcinoma.

Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate cells results in decreased secretion of IL-6.

AIM: To investigate the mechanism of interleukin (IL)-6 secretion through blocking the IL-17A/IL-17A receptor (IL-17RA) signaling pathway with a short hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro. METHODS: HSCs were derived from the livers of adult male Sprague-Dawley rats. IL-6 expression was evaluated using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay. The phosphorylation activity of p38 mitogen activated protein kinases (MAPK) and extracellular regulated protein kinases (ERK) 1/2 upon induction by IL-17A and suppression by IL-17RA shRNA were examined using Western blotting. RESULTS: IL-6 expression induced by IL-17A was significantly increased compared to control in HSCs (P < 0.01 in a dose-dependent manner). Suppression of IL-17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by IL-17A compared to group with only IL-17A treatment (1.44 ± 0.17 vs 4.07 ± 0.43, P < 0.01). IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5 min exposure, and showed the strongest levels of phosphorylation of p38 MAPK and ERK1/2 at 15 min in IL-17A-treated HSCs. IL-6 mRNA expression induced by IL-17A (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups without inhibitors preincubation (1.67 ± 0.24, 2.01 ± 0.10 vs 4.08 ± 0.59, P < 0.01). Moreover, Lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced IL-6 mRNA expression compared to random shRNA in HSCs (1.44 ± 0.17 vs 3.98 ± 0.68, P < 0.01). Lentiviral-mediated IL-17RA shRNA 1 inhibited phosphorylation of p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure. CONCLUSION: Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs. Suppression of IL-17RA expression may be a strategy to reduce the inflammatory response induced by IL-17A in the liver.

Inhibition of hepatic stellate cell activation and liver fibrosis by fat-specific protein 27.

In order to explore the effects of fat-specific protein 27 (Fsp27) on regulation of hepatic stellate cell (HSC) activation and liver fibrosis. HSCs were isolated from rat liver tissues and cultivated in vitro for gene expression and lentivirus infection. CCK-8 cell viability assay, immunofluorescence staining, qRT-PCR, and western blot assays were used to assess phenotypic changes and gene expression in HSCs. The rat liver fibrosis model was produced by intraperitoneal injection of carbon tetrachloride for assessing the effects of Fsp27 in the rat liver. Gene expression was then detected by immunohistochemistry and ELISA assays. The results of the study showed that Fsp27 was constitutively expressed in primary quiescent HSCs, but was absent in activated HSCs. Ectopic expression of Fsp27 significantly inhibited HSC proliferation and activation, as well as expression of α-smooth muscle actin. Fsp27 expression also significantly reduced collagen I production and matrix metalloproteinases 2 protein levels, and to a lesser degree, reduced tissue inhibitors of metalloproteinases 1 expression. In vivo data showed that ectopic expression of Fsp27 protein significantly reduced levels of hydroxyproline in liver tissue, and decreased serum levels of collagen III and hyaluronic acid, which in turn, suppressed liver fibrosis in rats. From these findings, it can be concluded that Fsp27 expression suppressed HSC activation in vitro and liver fibrogenesis in vivo. Further studies are needed to explore whether expression of Fsp27 can be selected as a potential novel strategy for anti-fibrotic therapy against liver fibrosis.

Is the TissueLink dissecting sealer a better liver resection device than clamp-crushing? A meta-analysis and system review.

BACKGROUND/AIMS: Liver resection is the most effective treatment for selected patients with primary or metastatic hepatic tumor and many liver resection techniques have tried to minimize blood loss. The objective of the present study was to examine whether TissueLink dissection sealer (DS) was superior to clamp-crushing (CC) technique for liver transection or not. METHODOLOGY: MEDLINE, Pubmed, Ovid and Cochrane Library electronic databases were used to search for studies without language and time period restrictions. RESULTS: Four clinical trials with 276 patients were involved. We evaluated intraoperative blood loss, postoperative morbidity, postoperative biliary leakage, transfusion rate, operation time,hospital stay duration, postoperative mortality,transection time, blood loss in liver transection and pertran section area, transection speed, AST and TBIL and found no statistical differences between the DS and CC groups. Sensitive analysis showed transection time was longer in the former group. In addition, there was no apparent publication bias concerning intraoperative blood loss. CONCLUSIONS: In summary, we could not draw a firm conclusion that DS is superior to CC in liver resection of transection and the advantage of TissueLink dissecting sealer should be evaluated

The combined treatment of CT-guided percutaneous 125I seed implantation and chemotherapy for non-small-cell lung cancer.

PURPOSE: Gemcitabine plus cisplatin (GP) is a first-line treatment for advanced non-small-cell lung cancer (NSCLC). In this study, we evaluated the efficacy and safety of a combined treatment consisting of CT-guided percutaneous (125)I seed implantation with GP chemotherapy for advanced NSCLC. METHODS: Fifty-three patients with advanced NSCLC were enrolled in a nonrandomized, two-armed clinical trial. Of these patients, 24 received a combination treatment of CT-guided percutaneous (125) I seed implantation and GP (the combo group), while 29 were treated with GP only (the control group). RESULTS: Patients in the combo group received (125)I seed implantation with prescription dose of 100-140 Gy and a total of 55 cycles of GP, and patients in the control group received a total of 73 cycles of GP. The overall response rate was 79.2% in the combo group and 41.4% in the control group. The median overall survival time was 13.5 ± 1.5 months in the combo group and 9.0 ± 1.8 months in the control group. The progression-free survival time was 8.0 ± 1.2 months in the combo group and 5.0 ± 0.8 months in the control group. The 1- and 2-year survival rates were 62.5 and 16.7% in the combo group, respectively, and 41.4 and 13.8% in the control group. The interventional complications in the combo group included 5 cases of pneumothorax and 4 cases of hemoptysis. There were no complications due to radiation pneumonia or radiation esophagitis in the combo group, and no patients had lethal hemoptysis or esophagotracheal fistula. Chemotherapy treatment-related toxicities, including Grade 3/4 myelosuppression and Grade 3 gastrointestinal toxicity, were similar in both groups. CONCLUSIONS: Our initial experience showed that combined CT-guided (125)I radioactive seed implantation and GP chemotherapy are effective and safe for treating advanced NCSLC.