271 research outputs found

    X-Ray Topographic Observation of Strain Generated by Thin Film (TiN) on Silicon Surface

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    The strain in Si substrate induced by locally ion-plated thin film of TiN was observed by X-ray topograph (Lang technique). Circular TiN film was deposited on one side of the Si surface. In all topographs the highest blackness attributed to kinematical diffraction effect occurred at the film edge. Rosette pattern with four-lobes was observed around the film. Blackness as a whole increased with the film thickness. Strain was observed in the depth direction of substrate by limited projection method. When the slit width was narrowed, the kinematical images disappeared, and white images appeared at the film edge. All the contrast disappeared when the TiN film was completely removed in boiling HNO(3). The strain induced by the film deposition was proved to be elastic

    Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22

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    During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis

    The depletion of donor macrophages reduces ischaemia-reperfusion injury after mouse lung transplantation†

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    OBJECTIVES Macrophages (M) are one of the most important cells of the innate immune system for first line defense. Upon transplantation (Tx), M play a prominent role during lung ischaemia reperfusion (I/R) injury. Here, we hypothesize that the depletion of donor M ameliorates the post-transplant lung I/R injury. METHODS Orthotopic single-lung Tx was performed between syngeneic BALB/c mice after a cold ischaemic time of 8 h and a reperfusion time of 10 h. Prior to graft implantation, alveolar macrophages of donor lungs were selectively depleted applying the ‘suicide technique' by intratracheal application of clodronate liposomes (experimental, n = 6) vs the application of empty liposomes (control, n = 6). Cell count (number of F4/80+-macrophages) and graft injury were evaluated by histology and immunohistochemistry, and levels of lactat dehydrogenase (LDH) (apoptosis assay), enzyme linked immunosorbent assay for nuclear protein high-mobility-group-protein B1 (HMGB1), tumor necrosis factor alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in plasma were analysed. RESULTS Clodronate liposomes successfully reduced 70% of M from donor lungs when compared with grafts treated with empty liposome only. M-depleted transplants showed improved histology and revealed considerably less graft damage when compared with control recipients (LDH, P = 0.03; HMGB1, P = 0.3). Oxygenation capacity was ameliorated in M-depleted transplants, if not significant (P = 0.114); however, wet/dry ratio did not differ between groups (P = 0.629). The inflammatory response was significantly reduced in M-depleted mice when compared with control recipients (TNF-α, P = 0.042; TGF-β1, P = 0.039). CONCLUSIONS The selective depletion of M in donor lung transplants can be successfully performed and results in a sustained anti-inflammatory response upon I/R-injury. The beneficial effect of this preconditioning method should be further evaluated as a promising tool for the attenuation of I/R prior to graft implantation in clinical T

    Strategy for lung parenchyma-sparing bronchial resection: a case series report

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    Lung parenchyma-sparing bronchial resection is uncommon, and the operative procedure depends on the cause and location of the stenosis. We present 6 cases and discuss the different surgical strategies for sleeve resection of the central airway without lung resection. Bronchoplasty for the main bronchus and truncus intermedius was performed with a posterolateral approach. We resected the right main bronchus including the right lateral wall of the lower trachea and half of the carina obliquely and performed an anastomosis. The tumour in the left lobar bronchus was exposed and removed by transient division of the accompanying pulmonary artery. Although post-transplant stenosis and malacia can pose a challenge, bronchoplasty can be used as a definitive treatment in experienced centres

    Biased IL-2 signals induce Foxp3-rich pulmonary lymphoid structures and facilitate long-term lung allograft acceptance in mice

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    Transplantation of solid organs can be life-saving in patients with end-stage organ failure, however, graft rejection remains a major challenge. In this study, by pre-conditioning with interleukin-2 (IL-2)/anti-IL-2 antibody complex treatment biased toward IL-2 receptor α, we achieved acceptance of fully mismatched orthotopic lung allografts that remained morphologically and functionally intact for more than 90 days in immunocompetent mice. These allografts are tolerated by the actions of forkhead box p3 (Foxp3)+^{+} regulatory T (Treg) cells that home to the lung allografts. Although counts of circulating Treg cells rapidly return to baseline following cessation of IL-2 treatment, Foxp3+^{+} Treg cells persist in peribronchial and peribronchiolar areas of the grafted lungs, forming organized clusters reminiscent of inducible tertiary lymphoid structures (iTLS). These iTLS in lung allografts are made of Foxp3+^{+} Treg cells, conventional T cells, and B cells, as evidenced by using microscopy-based distribution and neighborhood analyses. Foxp3-transgenic mice with inducible and selective deletion of Foxp3+^{+} cells are unable to form iTLS in lung allografts, and these mice acutely reject lung allografts. Collectively, we report that short-term, high-intensity and biased IL-2 pre-conditioning facilitates acceptance of vascularized and ventilated lung allografts without the need of immunosuppression, by inducing Foxp3-controlled iTLS formation within allografts

    Difference between carbohydrate antigen 19-9 and fluorine-18 fluorodeoxyglucose positron emission tomography in evaluating the treatment efficacy of neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma: Results of a dual-center study

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    kita, H, Takahashi, H, Eguchi, H, et al. Difference between carbohydrate antigen 19‐9 and fluorine‐18 fluorodeoxyglucose positron emission tomography in evaluating the treatment efficacy of neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma: Results of a dual‐center study. Ann Gastroenterol Surg. 2020; 00: 1– 9. https://doi.org/10.1002/ags3.12418

    Epidermal growth factor receptor (EGFR)—tyrosine kinase inhibitors as a first-line treatment for postoperative recurrent and EGFR-mutated non-small-cell lung cancer

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    [OBJECTIVES] To clarify survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) as first-line treatment for postoperative recurrence. [METHODS] A retrospective chart review was performed to identify consecutive patients who received EGFR-TKIs as first-line treatment for postoperative recurrence of non-small-cell lung cancer (NSCLC) harbouring EGFR gene mutations at our institution between August 2002 and October 2020. Therapeutic response, adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using the Kaplan–Meier analysis. The Cox proportional hazards model was used for univariable and multivariable analyses. [RESULTS] Sixty-four patients were included in the study. The objective response and disease control rates were 53% and 92%, respectively. Grade 3 or greater adverse events were noted in 4 (6.3%) patients, including 1 patient (1.6%) of interstitial pneumonia. The median follow-up period was 28.5 months (range 3–202 months). The total number of events was 43 for PFS and 23 for OS, respectively. The median PFS was 18 months, and the median OS was 61 months after EGFR-TKI treatment. In multivariable analysis, osimertinib showed a tendency to prolong PFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.12–1.1; P = 0.071], whereas the micropapillary component was significantly associated with shorter OS (HR 2.1, 95% CI 1.02–6.9; P = 0.045). [CONCLUSIONS] EGFR-TKIs as first-line treatment appeared to be a reasonable treatment option in selected patients with postoperative recurrent EGFR-mutated NSCLC. Osimertinib and the micropapillary component may be prognostic factors
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