Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer cells via miR-145-5p-mediated regulation of AKAP12.

Our present work was aimed to study on the regulatory role of MALAT1/miR-145-5p/AKAP12 axis on docetaxel (DTX) sensitivity of prostate cancer (PCa) cells. The microarray data (GSE33455) to identify differentially expressed lncRNAs and mRNAs in DTX-resistant PCa cell lines (DU-145-DTX and PC-3-DTX) was retrieved from the Gene Expression Omnibus (GEO) database. QRT-PCR analysis was performed to measure MALAT1 expression in DTX-sensitive and DTX-resistant tissues/cells. The human DTX-resistant cell lines DU145-PTX and PC3-DTX were established as in vitro cell models, and the expression of MALAT1, miR-145-5p and AKAP12 was manipulated in DTX-sensitive and DTX-resistant cells. Cell viability was examined using MTT assay and colony formation methods. Cell apoptosis was assessed by TUNEL staining. Cell migration and invasion was determined by scratch test (wound healing) and Transwell assay, respectively. Dual-luciferase assay was applied to analyse the target relationship between lncRNA MALAT1 and miR-145-5p, as well as between miR-145-5p and AKAP12. Tumour xenograft study was undertaken to confirm the correlation of MALAT1/miR-145-5p/AKAP12 axis and DTX sensitivity of PCa cells in vivo. In this study, we firstly notified that the MALAT1 expression levels were up-regulated in clinical DTX-resistant PCa samples. Overexpressed MALAT1 promoted cell proliferation, migration and invasion but decreased cell apoptosis rate of PCa cells in spite of DTX treatment. We identified miR-145-5p as a target of MALAT1. MiR-145-5p overexpression in PC3-DTX led to inhibited cell proliferation, migration and invasion as well as reduced chemoresistance to DTX, which was attenuated by MALAT1. Moreover, we determined that AKAP12 was a target of miR-145-5p, which significantly induced chemoresistance of PCa cells to DTX. Besides, it was proved that MALAT1 promoted tumour cell proliferation and enhanced DTX-chemoresistance in vivo. There was an lncRNA MALAT1/miR-145-5p/AKAP12 axis involved in DTX resistance of PCa cells and provided a new thought for PCa therapy.

Invasive aspergillosis presenting as hilar masses with stenosis of bronchus: A case report.

BACKGROUND: Hilar masses with stenosis of the bronchus occur mainly due to malignant diseases, such as lung cancer. Hilar masses resulting from invasive aspergillosis are extremely rare and occur mostly in severely immunosuppressed patients. CASE SUMMARY: In the current case report, we have documented a unique case of invasive aspergillosis presenting as a mass in the hilum and bronchial stenosis under bronchoscopy mimicking lung cancer in a 54-year-old man with diabetes mellitus. The histological analysis of bronchial membrane biopsy demonstrated fungal elements of 45° branching hyphae with positive Periodic Acid-Schiff and Grocott staining. After 3 mo of antifungal therapy, the symptoms, computed tomography scan and bronchoscopy manifestations all showed improvement. CONCLUSION: We highlight that clinicians should consider a diagnosis of invasive aspergillosis when radiological examination shows pseudotumor appearance in diabetes mellitus patients.

Disseminated Talaromyces marneffei And Mycobacterium avium Infection Accompanied Sweet's Syndrome In A Patient With Anti-Interferon-γ Autoantibodies: A Case Report.

BACKGROUND: Patients with high-titer anti-IFN-γ autoantibodies present disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections. Due to its rare occurrence and non-specific symptoms, this syndrome is difficult to diagnose during early disease stages. Here, we report a case with high-concentrations of serum anti-IFN-γ autoantibodies who presented with disseminated Talaromyces marneffei and NTM disease accompanied Sweet's syndrome. CASE PRESENTATION: A 62-year-old Chinese woman with no previous history was admitted to our hospital in August 2016 due to intermittent fever for 2 years, left chest wall redness, and swelling for 3 months. During hospitalization, the patient was confirmed with disseminated T. marneffei and successfully treated with antifungal therapy. In July 2017, upon second admission, Mycobacterium avium intracellular (MAC) pulmonary infection was established after positive cultures from the right lung tissue. The patient failed treatment after 1 month of anti-NTM therapy due to side effects. In May 2018, she was confirmed as having disseminated MAC disease accompanied by hand rashes, which was considered as Sweet's syndrome. High-level anti-IFN-γ antibodies in the patient serum were detected upon comparison with normal controls (2.85-fold increase). Following anti-NTM therapy, both symptoms and pulmonary infiltration gradually improved, and joint destruction and lymphadenitis remained. CONCLUSIONS: Patients with anti-interferon-γ autoantibodies should be considered for severe, recurrent infections in adults in the absence of other known risk factors. Sweet's syndrome is a common skin manifestation of the syndrome.

The performance of serum cryptococcal capsular polysaccharide antigen test, histopathology and culture of the lung tissue for diagnosis of pulmonary cryptococcosis in patients without HIV infection.

BACKGROUND: Clinicians may fail to make an early diagnosis of pulmonary cryptococcosis (PC) without HIV infection. Serum cryptococcal capsular polysaccharide antigen (CrAg) test, histopathology and culture of lung tissue play different roles in diagnosis of PC. OBJECTIVE: To investigate the performance of serum CrAg test, histopathology and culture of the lung tissue in diagnosis of PC without HIV infection. PATIENTS/METHODS: From January 2011 to September 2017, patients with proven PC were recruited from a teaching hospital in southern China. Those patients with HIV infection, PC confirmed by surgery or PC with probable or possible diagnosis were excluded from the study. Latex agglutination test and CrAg lateral flow assay were used for detection of serum CrAg. Lung biopsy and needle aspiration were performed under computed tomography guidance. RESULTS: Eighty-nine patients with proven PC including 41 male (46.1%) and 48 female (53.9%) were enrolled. Fifty-one (57.3%) patients had underlying disease. Positive CrAg test was found in 83 (93.3%) cases. Among six cases with negative CrAg test, PC was confirmed by histology in two cases and positive culture in four cases. The histopathological results of 77 (86.5%) cases revealed cryptococcal granuloma and 12 cases showed chronic inflammation, which was confirmed by positive culture. Among 65 cases, the diseased tissue of 46 (70.8%) cases presented Cryptococcus neoformans in the culture and one case was diagnosed with lung cancer coexisting with PC. CONCLUSION: Our findings showed that serum CrAg test is rapid and sensitive in diagnosing PC, histology is important for confirming PC and culture plays a complementary role. Biopsied lung tissue should be submitted for cultures whenever feasible.

Diagnosis of tuberculous pleurisy with combination of adenosine deaminase and interferon-γ immunospot assay in a tuberculosis-endemic population: A prospective cohort study.

The aim of this study was to identify the optimal cut-off value of T cell enzyme-linked immunospot assay for tuberculosis (T-SPOT.TB) and evaluate its diagnostic performance alone (in the peripheral blood) or in combination with the adenosine deaminase (ADA) activity test (in peripheral blood and the pleural fluid) in patients with tuberculous pleurisy.Adult patients presenting with pleural effusion were included in this prospective cohort study. Tuberculous pleurisy was diagnosed by T-SPOT.TB in peripheral blood and a combination of T-SPOT.TB and ADA activity test in pleural fluid and peripheral blood. Receiver operating characteristic (ROC) curve in combination with multivariate logistic regression was used to evaluate the diagnostic performance of the assays.Among a total of 189 patients with suspected tuberculous pleurisy who were prospectively enrolled in this study, 177 patients were validated for inclusion in the final analysis. ROC analysis revealed that the area under the ROC curve (AUC) for T-SPOT.TB in pleural fluid and peripheral blood was 0.918 and 0.881, respectively, and for the ADA activity test in pleural fluid was 0.944. In addition, 95.5 spot-forming cells (SFCs)/2.5 × 10 cells were determined as the optimal cut-off value for T-SPOT.TB in pleural fluid. Parallel combination of T-SPOT.TB and ADA activity test in pleural fluid showed increased sensitivity (96.9%) and specificity (87.5%), whereas serial combination showed increased specificity (97.5%). The combination of 3 assays had the highest sensitivity at 97.9%, with an AUC value of 0.964.T-SPOT.TB in pleural fluid performed better than that in peripheral blood and the ADA activity test in pleural fluid for tuberculous pleurisy diagnosis. The optimal cut-off value of T-SPOT.TB in pleural fluid was 95.5 SFCs/2.5 × 10 cells. Combination of 3 assays might be a promising approach for tuberculous pleurisy diagnosis.