LncRNA MITA1 promotes gefitinib resistance by inducing autophagy in lung cancer cells.

Lung cancer is a major health challenge worldwide. Gefitinib, a tyrosine kinase inhibitor (TKI), is the common therapeutic drug used in advanced non-small-cell lung cancer (NSCLC). However, it is eventually bound to face the problem of acquired drug resistance. In this work, we investigated the role of lncRNA MITA1 in the acquisition of gefitinib resistance in NSCLC and uncovered the possible underlying molecular mechanism of the same. Experiments were carried out using the HCC827 and HCC827GR cells. These were transfected with pcDNA-MITA1 or si-MITA1 and treated with gefitinib. Subsequently, lncRNA MITA1 mediated effect on cell viability and apoptosis were studied using the MTT and flow cytometry assays. Furthermore, using qRT-PCR, Western blotting, and immunofluorescence assays, the regulatory association between lncRNA MITA1 and markers of autophagy (LC3, Beclin-1, and p62) were examined by estimating their cellular protein levels. Also, these results were verified in the presence of an autophagy inhibitor bafilomycin A1. We found that MITA1 was highly upregulated in the gefitinib-resistant NSCLC cells, indicating the regulatory role of MITA1 in gefitinib resistance. Mechanistically, upregulated MITA1 led to gefitinib resistance by suppressing apoptosis, increasing cell viability, and inducing autophagy. Furthermore, these results were true when tested in the presence of bafilomycin A1. Our results suggest that MITA1 by inducing autophagy could be a key regulator of gefitinib resistance in NSCLC.

Isolated interrupted aortic arch in an adult: A case report.

BACKGROUND: Interrupted aortic arch (IAA) is a rare congenital heart disease defined by an interruption of the lumen and anatomical continuity between the ascending and descending major arteries. It is usually found within a few hours or days of birth. Without surgery, the chances of survival are low. If IAA patients have an effective collateral circulation established, they can survive into adulthood. However, IAA in adults is extremely rare, with few reported cases. CASE SUMMARY: A 27-year-old woman presented with a 6-year history of progressively worsening shortness of breath and chest tightness on exertion. She had cyanotic lips and clubbing of the fingers. A transthoracic echocardiogram revealed an enlarged heart and dilation of the main pulmonary artery. There was an abnormal 9 mm passage between the descending aorta and pulmonary artery. The ventricular septal outflow tract had a 14 mm defect. Doppler ultrasound suggested a patent ductus arteriosus and computed tomographic angiography showed the absence of the aortic arch. The diagnoses were ventricular septal defect, patent ductus arteriosus, and definite interruption of the aortic arch. Although surgical correction was recommended, the patient declined due to the surgical risks and was treated with medications to reduce pulmonary artery pressure and treat heart failure. Her condition has been stable for 12 mo of follow-up. CONCLUSION: Although rare, IAA should be considered in adults with refractory hypertension or unexplained congestive heart failure.

Erythroblastic islands in the bone marrow of patients with immune-related pancytopenia.

BACKGROUND: Immune-related pancytopenia (IRP) is characterized by pancytopenia caused by autoantibody-mediated bone marrow destruction or suppression. The bone marrows of IRP patients have remarkably increased erythroblastic islands (EIs). METHODOLOGY AND PRINCIPAL FINDINGS: We determined the immunoglobulin G (IgG) autoantibodies in some parts of EIs of IRP patients using immunofluorescence to investigate the biological function of EIs with IgG in the pathophysiology of IRP. The dominant class of autoantibodies detected in mononuclear cells was IgG (CD34 IgG, CD15 IgG, and GlycoA IgG), specifically IgG on GlycoA-positive cells (GlycoA IgG). Results show that extravascular hemolysis occurred in IRP through IgG autoantibodies in the EIs. These data included a high percentage of reticulocytes in the peripheral blood, hypererythrocytosis in the bone marrow, and high serum bilirubin. Furthermore, we examined the macrophages in the bone marrow of IRP patients. The results show that the number of activated macrophages relatively increased, and the phagocytic activity of macrophages significantly increased. CONCLUSIONS AND SIGNIFICANCE: Increased EIs with IgG were the sites of erythroblast phagocytosis by the activated macrophages, rather than erythropoietic niches. The IgG autoantibodies in the EIs possibly functioned as adhesion molecules for a ring of erythroblasts around the macrophages, thereby forming morphologic EIs.

[Preliminary study of "erythroblast island" in the bone marrow of hematocytopenic patients with positive BMMNC-Coombs test].

OBJECTIVE: To explore the mechanism of 'erythroblast island (EI)' formation in the bone marrow of patients with immun-related hemocytopenia (IRP). METHODS: The category of BM-auto antibody (au Ab) in 48 patients with IRP was detected with FCM. The BM-au Ab in the 'EI' of these cases were explored with immuonhistofluorescence (IF). Clinical and laboratory characteristics of these cases were also analyzed retrospectively. RESULTS: IgG could be detected in the 'EI' on the BM smear of 14 cases (29.17%), BM-au Ab mainly deposited at the edge/membranes between macrophage and erythroblasts rather than cyto plasm. Positive reaction were seen in all the cases with GlycoAIgG. The red blood cell count [(1.8 ± 0.5) × 10(12)/L] and hemoglobin level [(59.6 ± 16.2)g/L] were significantly lower than that in the IF(-) group [(2.5 ± 0.9) × 10(12)/L and (83.4 ± 25.0) g/L] (P < 0.05). The percentage of reticulocyte [(2.0 ± 0.8)%], serum level of IBIL [(9.4 ± 4.7) µmol/L], percentage of erythroblats in sternum BM (0.441 ± 0.139) and response rate to therapy (85.7%) in IF(+) group were significantly higher than that in IF(-)group [(1.3 ± 1.0)%, (6.6 ± 6.7)µmol/L, 0.298 ± 0.082, 61.3%, respectively] (P < 0.05). CONCLUSION: Macrophage was connected with erythroblasts through autologous IgG in the 'EI's of some patients with IRP. 'EI' were the places where macrophages devoured and destroyed erythroblasts rather than erythroid development and differentiation. The pathogenetic mechanism of IRP might be associated with macrophages phagocytosing and destroying BM hematopoietic cells.

[Study on the dendritic cell subsets in peripheral blood and its relationship with the expressions of T-bet and GATA-3 in lymphocytes in severe aplastic anemia].

OBJECTIVE: To investigate the relationship between the dendritic cell (DC) subsets and transcriptive factors, T-bet, GATA-3, and immune imbalance in acquired severe aplastic anemia (SAA). METHODS: The DC1 (HLA-DR+Lin-CD11c+) and DC2 (HLA-DR+Lin-CD123+) in peripheral blood mononuclear cells (PBMNC) were measured with flow cytometry (FCM), the expressions of T-bet mRNA and GATA-3 mRNA in PBMNC with semiquantitative RT-PCR and the plasma level of IFN gamma and IL-4 with ELISA in 29 SAA patients and 16 healthy controls. RESULTS: The percentages of DC1 in PBMNC were (0.44 +/- 0.24)% and (0.73 +/- 0.30)% in untreated and recovered SAA patients respectively, both were higher than that in controls (0.29 +/- 0.10)% (P < 0.05). The percentage of DC2 in the untreated cases was lower than that of recovered ones or controls [(0.18 +/- 0.14)% vs (0.28 +/- 0.20)% and (0.29 +/- 0.13)%] (P < 0.05). DC1/DC2 ratios were 3.45 +/- 2.71 and 2.90 +/- 0.95 in untreated and recovered groups respectively, both were higher than that in controls (1.15 +/- 0.56) (P < 0.05). No statistic difference in DC1/DC2 ratio was found between untreated and recovered patients (P < 0.05). The relative mRNA expression levels of transcriptive factor T-bet were 0.37 +/- 0.07, 0.20 +/- 0.07 and 0.17 +/- 0.05 in the above 3 groups, respectively, untreated group being higher than that of recovered group or healthy controls (P < 0.05). There was no statistic difference of GATA-3 expression among the 3 groups (P > 0.05). T-bet/GATA-3 ratio was 0.72 +/- 0.13 in untreated group, being higher than that of recovered group (0.33 +/- 0.08) or controls (0.35 +/- 0.11). The plasma level of IFN gamma in the untreated group was (50.9 +/- 1.1) ng/L, which was higher than that of recovered group [(49.7 +/- 0.9) ng/L] or controls [(49.7 +/- 0.7) ng/L]. There was significant positive correlations between T-bet and DC1/DC2 ratio (r = 0.445, P < 0.01), as well as between T-bet and IFN gamma (r = 0.402, P < 0.01). CONCLUSION: Either DC1/DC2 or T-bet/GATA-3 ratio might become an index to estimate immune imbalance. High-expressed T-bet was related to the progress of SAA. In patients with SAA, DC1/DC2 ratio returns to normal range later than that of routine blood test does, indicating that immunosuppressive therapy should not be withdrawn too earlier.