Colorectal cancer (CRC) cells often express Tn antigen, a tumor-associated truncated immature O-glycan (GalNAcα-O-Ser/Thr) that can promote tumor progression. Immunotherapies against Tn antigen have ...been developed and are being evaluated in clinical trials. Tn antigen can also be considered a novel immune checkpoint that induces immunosuppressive signaling through glycan-biding lectins to lead effector T cell apoptosis. We evaluated the correlation of Tn antigen expression by immunohistochemistry with mismatch-repair (MMR) status, tumor-infiltrating lymphocytes, tumor cell PD-L1 expression, and clinicopathological characteristics in 507 CRC patients. Although 91.9% of CRCs showed negative or weak Tn antigen staining (Tn-negative/weak), we identified a small subset of CRCs (8.1%) that displayed particularly intense and diffuse distribution of Tn antigen immunoreactivity (Tn-strong) that closely related to deficient MMR (dMMR). Moreover, 40 dMMR CRCs were stratified into 24 Tn-negative/weak dMMR tumors (60.0%) exhibiting dense CD8+ lymphocyte infiltrate concomitant with a high rate of PD-L1 positivity, and 16 Tn-strong dMMR tumors (40.0%) that demonstrated CD8+ T cell exclusion and a lack of PD-L1 expression, which was comparable to those of proficient MMR. Our finding suggests that the immune cold subset of patients with Tn-strong dMMR CRC may be effectively treated with immune checkpoint blockade therapy or cellular immunotherapy targeting Tn antigen.
Nuclear pore complexes are massive multiprotein channels responsible for traffic between the nucleus and cytoplasm, and are composed of approximately 30 proteins, termed nucleoporins (Nup). Our ...recent studies indicated that the nucleoporins Rae1 and Tpr play critical roles in maintaining the spindle bipolarity during cell division. In the present study, we found that another nucleoporin, Nup88, was localized on the spindles together with Nup214 during mitosis. Nup88 expression is linked to the progression of carcinogenesis, Nup88 has been proposed as a tumor marker. Overexpression of Nup88 enhanced multinucleated cell formation. RNAi-mediated knockdown of Nup88 disrupted Nup214 expression and localization and caused multipolar spindle phenotypes. Our data indicate that proper expression of Nup88 is critical for preventing aneuploidy formation and tumorigenesis.
The effect of soil exchangeable potassium (K) and cesium (Cs) levels on Cs uptake and accumulation in different parts of rice (Oryza sativa L.) plants were examined using paddy soils with diverse ...exchangeable K and Cs in pot experiments. Aboveground Cs uptake decreased with higher exchangeable K and was linearly correlated with exchangeable Cs/K ratios, indicating competitive absorption of these elements by roots. Variation in Cs concentration in brown rice among soils was also related to the exchangeable Cs/K ratio. The exchangeable Cs/K ratio was positively reflected in the Cs/K concentration ratio in each plant part, with a specific slope, suggesting that Cs transport was coordinated with K transport and that there were regulated discriminations of Cs against K in the translocation process among parts. The Cs/K ratio was higher in brown rice and dead leaves than in active leaves, stems and husks. The distribution of Cs accumulation in brown rice was 14.5% on average, but it was variable and negatively related to K concentration in the stem. The Cs distribution in aboveground plant parts also decreased with higher K concentration in the root. These results imply the importance of the competitiveness with K in the root absorption and translocation of Cs within the plant. Based on the observed relationship between Cs and K, effective K management and other measures to control Cs accumulation in plant parts are discussed.
We assessed whether lung sound analysis (LSA) is a valid measure of airway obstruction and inflammation in patients with bronchial asthma during treatment with inhaled corticosteroids (ICSs).
63 good ...adherence patients with bronchial asthma and 18 poor adherence patients were examined by LSA, spirometry, fractional exhaled nitric oxide (FeNO), and induced sputum. The expiration-to-inspiration lung sound power ratio at low frequencies between 100 and 200 Hz (E/I LF) obtained by LSA was compared between healthy volunteers and bronchial asthma patients. Next, post-ICS treatment changes were compared in bronchial asthma patients between the good adherence patients and the poor adherence patients.
E/I LF was significantly higher in bronchial asthma patients (0.62 ± 0.21) than in healthy volunteers (0.44 ± 0.12, p < 0.001). The good adherence patients demonstrated a significant reduction in E/I LF from pre-treatment to post-treatment (0.55 ± 0.21 to 0.46 ± 0.16, p = 0.002), whereas the poor adherence patients did not show a significant change. The decrease of E/I LF correlated with the improvement of FEV1/FVC ratio during the ICS treatment (r = −0.26, p = 0.04). The subjects with higher pre-treatment E/I LF values had significantly lower FEV1/FVC and V50,%pred (p < 0.001), and significantly higher FeNO and sputum eosinophil percentages (p = 0.008 and p < 0.001, respectively).
The E/I LF measurement obtained by LSA is useful as an indicator of changes in airway obstruction and inflammation and can be used for monitoring the therapeutic course of bronchial asthma patients.
Background:Laparoscopic and endoscopic cooperative surgery (LECS) is a well-recognized surgical procedure for gastric gastrointestinal stromal tumor (GIST). In this report, we describe the clinical ...outcomes of LECS procedures for gastric GIST in our institution.Methods:We performed LECS procedures, including classical LECS, inverted LECS, closed LECS, and combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET), in 40 gastric intraluminal and intramural type GIST patients, whose tumors were ≤ 50 mm in diameter, between September 2012 and December 2020. The patient background, surgical outcomes, postoperative morbidity and mortality, as well as the tumors’ clinicopathological characteristics were analyzed retrospectively.Results:Pathological findings showed that most patients had a low or very low risk of tumor recurrence, while one patient had a high risk according to the modified-Fletcher’s classification. The median length of postoperative hospital stay was 7 days. Only one patient had severe postoperative grade III complications according to the Clavien-Dindo (C-D) classification, after closed LECS, but was treated successfully with endoscopic hemostasis for postoperative hemorrhage. The remaining patients treated with LECS did not have severe complications. During the follow-up period (median, 31 months), all patients were disease-free, with no tumor recurrence or metastases.Conclusion:LECS is a safe surgical procedure for gastric intraluminal and intramural type GIST ≤ 50 mm in diameter, with good clinical outcomes.
GI24, an immunoglobulin superfamily member, has been cloned from a placenta cDNA library as a gene product that promoted activation of matrix metalloproteinase (MMP)‐2 mediated by membrane type (MT) ...1–MMP. Co‐expression of GI24 with MT1‐MMP in HEK293T cells increased the cell‐surface level of MT1‐MMP concomitant with the cleavage of the GI24 at the juxtamembrane site to shed the extracellular domain. HT1080 fibrosarcoma cells stably transfected with the GI24 gene expressed a higher level of MT1‐MMP and showed more invasive ability in collagen gel than the control cells. GI24 was cleaved in HT1080 cells, which was blocked by the administration of MMP inhibitor BB94 or transfection of small interfering RNA (siRNA) targeting MT1‐MMP. GI24 expression is relatively high in some squamous carcinoma and hepatocarcinoma cell lines. Transfection of siRNA for GI24 into oral squamous carcinoma‐derived HSC‐4 cells, which express GI24 and MT1‐MMP genes reduced the expression of not only GI24 but also MT1‐MMP, and attenuated invasive growth in the collagen matrix. These results suggest that GI24 contributes to tumor‐invasive growth in the collagen matrix by augmenting cell surface MT1‐MMP. (Cancer Sci 2010; 101: 2368–2374)
Desmoid-type fibromatosis (DF) is a rare, locally infiltrative, and fibroblastic proliferative disease. DF usually arises from abdominal fascial tissue, but in rare cases, it can occur in ...extra-abdominal areas. A 73-year-old Japanese male complained of a painless, left anterior neck mass of 3-month duration. Computed tomography revealed the mass measured 9 × 7 × 6 cm and extended to the anterior mediastinum, with invasion of the left clavicle. En bloc resection of the tumor with the left sternoclavicular joint and the medial portion of the left clavicle was performed by cervico-thoracic approach with L-shaped partial sternotomy. Histopathologic examination showed fascicular growth of spindle-shaped cells separated by abundant collagen. Immunohistologic examination revealed nuclear staining of β-catenin and cytoplasmic staining of vimentin. Genetic analysis of 160 cancer-related genes by next-generation sequencing (NGS) demonstrated only a missense mutation in the CTNNB1 gene (c.133T>C, p.S45P). DF extending from the neck to the anterior mediastinum is rare. We report the complete resection of a large-sized DF with the clavicular invasion. A low-frequency CTNNB1 mutation of DF was identified. Genetic analysis with NGS was beneficial for the diagnosis.
Enhancing crop yield response to elevated CO2 concentrations (E-CO2) is an important adaptation measure to climate change. A high-yielding indica rice cultivar "Takanari" has recently been identified ...as a potential candidate for high productivity in E-CO2 resulting from its large sink and source capacities. To fully utilize these traits, nitrogen should play a major role, but it is unknown how N levels influence the yield response of Takanari to E-CO2. We therefore compared grain yield and quality of Takanari with those of Koshihikari, a standard japonica cultivar, in response to Free-Air CO2 enrichment (FACE, +200 μmol mol-1) under three N levels (0, 8, and 12 g m-2) over three seasons. The biomass of both cultivars increased under E-CO2 at all N levels; however, the harvest index decreased under E-CO2 in the N-limited treatment for Koshihikari but not for Takanari. The decreased harvest index of Koshihikari resulted from limited enhancement of spikelet number under N-limitation. In contrast, spikelet number increased in E-CO2 in Takanari even without N application, resulting in significant yield enhancement, averaging 18% over 3 years, whereas Koshihikari exhibited virtually no increase in yield in E-CO2 under the N-limited condition. Grain appearance quality of Koshihikari was severely reduced by E-CO2, most notably in N-limited and hot conditions, by a substantial increase in chalky grain, but chalky grain % did not increase in E-CO2 even without N fertilizer. These results indicated that Takanari could retain its high yield advantage over Koshihikari with limited increase in chalkiness even under limited N conditions and that it could be a useful genetic resource for improving N use efficiency under E-CO2.Enhancing crop yield response to elevated CO2 concentrations (E-CO2) is an important adaptation measure to climate change. A high-yielding indica rice cultivar "Takanari" has recently been identified as a potential candidate for high productivity in E-CO2 resulting from its large sink and source capacities. To fully utilize these traits, nitrogen should play a major role, but it is unknown how N levels influence the yield response of Takanari to E-CO2. We therefore compared grain yield and quality of Takanari with those of Koshihikari, a standard japonica cultivar, in response to Free-Air CO2 enrichment (FACE, +200 μmol mol-1) under three N levels (0, 8, and 12 g m-2) over three seasons. The biomass of both cultivars increased under E-CO2 at all N levels; however, the harvest index decreased under E-CO2 in the N-limited treatment for Koshihikari but not for Takanari. The decreased harvest index of Koshihikari resulted from limited enhancement of spikelet number under N-limitation. In contrast, spikelet number increased in E-CO2 in Takanari even without N application, resulting in significant yield enhancement, averaging 18% over 3 years, whereas Koshihikari exhibited virtually no increase in yield in E-CO2 under the N-limited condition. Grain appearance quality of Koshihikari was severely reduced by E-CO2, most notably in N-limited and hot conditions, by a substantial increase in chalky grain, but chalky grain % did not increase in E-CO2 even without N fertilizer. These results indicated that Takanari could retain its high yield advantage over Koshihikari with limited increase in chalkiness even under limited N conditions and that it could be a useful genetic resource for improving N use efficiency under E-CO2.
The pathological role of snoring independent of obstructive sleep apnea remains under debate. The authors hypothesized that snoring sound intensity, as assessed by mean tracheal sound energy (Leq) ...during sleep, is related to daytime blood pressure.
Retrospective analysis of clinical records and polysomnography data.
Sleep laboratory at a national hospital in Japan.
Consecutive patients who underwent diagnostic polysomnography with suspicion of sleep apnea between January 2005 and December 2009 (n = 1,118).
Not applicable.
Leq was calculated from tracheal sound spectra recorded every 0.2 sec during polysomnography. Daytime high blood pressure (HBP) was defined as taking antihypertensive drugs or having a systolic blood pressure ≥ 140 mm Hg or a diastolic blood pressure ≥ 90 mmHg at the patient's first clinical visit. Patient age, sex, body mass index, apnea-hypopnea index, alcohol consumption, and smoking were considered as confounders. Leq during sleep was associated with HBP after adjusting for all confounding factors (n = 1,074, P = 0.00019). This association was demonstrated even in nonapneic nonobese patients (n = 232, P = 0.012).
The association between snoring intensity, as assessed by mean sound energy, and blood pressure suggests a pathological role for heavy snoring. Further study in a general population is warranted.
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