Forkhead box P3-positive (Foxp3 + )-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1–mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1–mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1–mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF–mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.

PURPOSE: To describe the MRI findings in the bronchial anthracofibrosis mimicking lung cancer on CT examination. MATERIALS AND METHODS: Ten patients, who showed CT findings mimicking lung cancer, were selected among fifty patients of bronchial anthracofibrosis proven by bronchoscopic biopsy, consisting of two men and eight women, ranging in age from 58 to 79 years old (average age, 68 years old). CT scan and MRI were performed in all patients(n=10). Percutaneous lung biopsy on mass was performed in one patient. MRI findings were analyzed with the emphasis on the signal intensity of the mass (n=4), collapsed lung (n=4) and lymph node (n=10) on axial T1 and T2-weighted images by two radiologists in consensus. No contrast enhancement was used in all cases. RESULTS: CT scan revealed mass(n=4), atelectasis with obstructive pneumonia(n=4) and bronchial wall thickening(n=2). All patients showed enlarged medistinal lymph nodes(n=10). The mass showed low signal intensity on T1WI and T2WI (n=4). The collapsed lung in patients with atelectasis indicated intermediate signal intensity on T1WI and low signal intensity on T2WI (n=4). Nine patients showed low signal intensity of lymph node on T1WI and T2WI, except one patient who showed central high signal intensity with peripheral rim of low signal intensity in right lower paratracheal lymph node on T2WI. CONCLUSION: Low signal intensity of a mass, collapsed lung, and lymph nodes on T2WI in anthracofibrosis patients may be helpful in differentiation of the lesion from lung cancer.
Aged ; Biopsy ; Consensus ; Female ; Humans ; Lung Neoplasms* ; Lung* ; Lymph Nodes ; Magnetic Resonance Imaging* ; Male ; Pulmonary Atelectasis ; Tomography, X-Ray Computed

It was reported that cancer in humans and animals infected with microbial pathogens was regressed about 100 years ago. Bacteria are able to trigger apoptosis by a variety of mechanisms including the secretion of protein synthesis inhibitors, pore forming proteins, molecules activating the endogenous death machinery in the infected cell. This study was conducted in order to investigate whether extracellular products of Psuedomonas aeruginosa (EPPA) induce apoptosis in human oral carcinoma cells (OSC9). The EPPA showed cytotoxic effect on OSC9 cells in dose and time-dependent manner. The cell death was demonstrated to be due to apoptosis characterized by chromatin condensation and nuclear fragment. EPPA treatment induced cleavage of caspase-3 and caspase-6. The caspase substrates, PARP, DFF45 and lamin A were cleaved during EPPA-induced apoptosis. Taken together, EPPA induces apoptosis on human oral squamous carcinoma cells in caspase-dependent manner. Our data therefore provide that EPPA contains a novel antitumor agent for human oral squamous carcinoma.
Animals ; Apoptosis* ; Bacteria ; Carcinoma, Squamous Cell* ; Caspase 3 ; Caspase 6 ; Cell Death ; Chromatin ; Humans* ; Lamin Type A ; Protein Synthesis Inhibitors ; Pseudomonas aeruginosa* ; Pseudomonas*

Chronic neutrophilic leukemia(CNL) is a rare disorder characterized by persistent neutrophilia of mature cell type without evidence of infection, hepatosplenomegaly, elevated neutrophil alkaline phosphatase score and the absence of Philadelphia chromosome We report a typical case of CNL with multiple myeloma(IgG-lambda type) in 68 years old female. Many neutrophils had toxic granule and vacuole. The peripheral blood smear showed neutrophlic leukocytosis(50,940/microliter, neutrophil 94%) with rare immature form. The cytogenetic study showed normal karyotype without Philadelphia chromosome. She was diagnosed as multiple myeloma with paraproteinemia, lytic bone lesion of skull, and immature plasma cells in bone marrow.
Aged ; Alkaline Phosphatase ; Bone Marrow ; Cytogenetics ; Female ; Humans ; Karyotype ; Leukemia, Neutrophilic, Chronic* ; Multiple Myeloma* ; Neutrophils ; Paraproteinemias ; Philadelphia Chromosome ; Plasma Cells ; Skull ; Vacuoles

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3 +induced Treg (iTreg) differentiation in ovalbumin-specific CD4 + T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.

PURPOSE: Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. RESULTS: A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology. CONCLUSION: Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.
Biomarkers ; Carcinoma, Non-Small-Cell Lung* ; Disease-Free Survival ; Drug Therapy* ; Humans ; Immunohistochemistry ; Lung Neoplasms ; Multivariate Analysis ; Platinum ; Prognosis ; Reactive Oxygen Species* ; Smoke ; Smoking