浸潤性発育を示した後腹膜孤立線維性腫瘍の1例

56歳女.悪性後腹膜孤立性線維性腫瘍であり, 主訴は腹部腫瘤触知で, 腹部CT及びMRI検査にて左腎下方に接して, Gerota筋膜に沿うように発育する境界不明瞭な腫瘤を認めた.手術所見では後腹膜腔にゼラチン状の腫瘍を認め, 下行結腸周囲の脂肪組織やGerota筋膜周囲の脂肪組織に浸潤していた.Gerota筋膜内への浸潤は認めなかったので左腎は温存した.病理組織像では間質の膠原線維は著明に増殖し, hemangiopericytoma様のくちばし状を呈する血管も豊富に認められた.腫瘍組織内に腫瘍細胞密度の増加しているところや核異型度が強く分裂像を認める組織が混在しており, また周囲脂肪組織内に浸潤している所見を認めた.以上より, 悪性後腹膜孤立性線維性腫瘍と診断した.治療は外科的切除のみを行い, 2年4ヵ月を経過しても再発無く生存中であるSolitary fibrous retroperitoneal tumor is rare. We present a case with infiltrative growth in a 56-year-old female patient whose initial symptom was palpable tumor in the lower abdomen. Computed tomography and magnetic resonance imaging indicated a mass in the retroperitoneum under the left kidney with a poorly demarcated infiltrative growth. Surgical findings revealed a gelatinous tumor in the retroperitoneum, which had invaded up to the fatty tissue surrounding the Gerota's fascia and to the fatty tissue surrounding the descending colon. However, as there was no invasion into the Gerota's fascia, it was possible to preserve the left kidney. Pathohistological examination revealed increased cellularity in the tumor tissues as well as tissues with atypical nuclei of the tumor cells with some cell division. Due to these findings, it was diagnosed as malignant solitary fibrous tumor. Only surgical treatment was performed and the patient is alive without recurrence 2 years and 4 months after surgery

An enhancer peptide for membrane-disrupting antimicrobial peptides

<p>Abstract</p> <p>Background</p> <p>NP4P is a synthetic peptide derived from a natural, non-antimicrobial peptide fragment (pro-region of nematode cecropin P4) by substitution of all acidic amino acid residues with amides (i.e., Glu → Gln, and Asp → Asn).</p> <p>Results</p> <p>In the presence of NP4P, some membrane-disrupting antimicrobial peptides (ASABF-α, polymyxin B, and nisin) killed microbes at lower concentration (e.g., 10 times lower minimum bactericidal concentration for ASABF-α against <it>Staphylococcus aureus</it>), whereas NP4P itself was not bactericidal and did not interfere with bacterial growth at ≤ 300 μg/mL. In contrast, the activities of antimicrobial agents with a distinct mode of action (indolicidin, ampicillin, kanamycin, and enrofloxacin) were unaffected. Although the membrane-disrupting activity of NP4P was slight or undetectable, ASABF-α permeabilized <it>S. aureus </it>membranes with enhanced efficacy in the presence of NP4P.</p> <p>Conclusions</p> <p>NP4P selectively enhanced the bactericidal activities of membrane-disrupting antimicrobial peptides by increasing the efficacy of membrane disruption against the cytoplasmic membrane.</p

Generation of novel cationic antimicrobial peptides from natural non-antimicrobial sequences by acid-amide substitution

<p>Abstract</p> <p>Background</p> <p>Cationic antimicrobial peptides (CAMPs) are well recognized to be promising as novel antimicrobial and antitumor agents. To obtain novel skeletons of CAMPs, we propose a simple strategy using acid-amide substitution (i.e. Glu→Gln, Asp→Asn) to confer net positive charge to natural non-antimicrobial sequences that have structures distinct from known CAMPs. The potential of this strategy was verified by a trial study.</p> <p>Methods</p> <p>The pro-regions of nematode cecropin P1-P3 (P1P-P3P) were selected as parent sequences. P1P-P3P and their acid-amide-substituted mutants (NP1P-NP3P) were chemically synthesized. Bactericidal and membrane-disruptive activities of these peptides were evaluated. Conformational changes were estimated from far-ultraviolet circular dichroism (CD) spectra.</p> <p>Results</p> <p>NP1P-NP3P acquired potent bactericidal activities via membrane-disruption although P1P-P3P were not antimicrobial. Far-ultraviolet CD spectra of NP1P-NP3P were similar to those of their parent peptides P1P-P3P, suggesting that NP1P-NP3P acquire microbicidal activity without remarkable conformational changes. NP1P-NP3P killed bacteria in almost parallel fashion with their membrane-disruptive activities, suggesting that the mode of action of those peptides was membrane-disruption. Interestingly, membrane-disruptive activity of NP1P-NP3P were highly diversified against acidic liposomes, indicating that the acid-amide-substituted nematode cecropin pro-region was expected to be a unique and promising skeleton for novel synthetic CAMPs with diversified membrane-discriminative properties.</p> <p>Conclusions</p> <p>The acid-amide substitution successfully generated some novel CAMPs in our trial study. These novel CAMPs were derived from natural non-antimicrobial sequences, and their sequences were completely distinct from any categories of known CAMPs, suggesting that such mutated natural sequences could be a promising source of novel skeletons of CAMPs.</p

Autonomous right-screw rotation of growth cone filopodia drives neurite turning

The clockwise turning of neurites is caused by the rotations of filopodia as they extend and sweep across the substratum

Optical IFU Observations of GOALS Sample with KOOLS-IFU on Seimei Telescope: Initial results of 9 U/LIRGs at z<z < 0.04

We present ionized gas properties of 9 local ultra/luminous infrared galaxies (U/LIRGs) at $z <$ 0.04 through IFU observations with KOOLS-IFU on Seimei Telescope. The observed targets are drawn from the Great Observatories All-sky LIRG Survey (GOALS), covering a wide range of merger stages. We successfully detect emission lines such as H$\beta$, [OIII]$\lambda$5007, H$\alpha$, [NII]$\lambda\lambda$6549,6583, and [SII]$\lambda\lambda$6717,6731 with a spectral resolution of $R$ = 1500-2000, which provides (i) spatially-resolved ($\sim$200-700 pc) moment map of ionized gas and (ii) diagnostics for active galactic nucleus (AGN) within the central $\sim$3--11 kpc in diameter for our sample. We find that [OIII] outflow that is expected to be driven by AGN tends to be stronger (i) towards the galactic center and (ii) as a sequence of merger stage. In particular, the outflow strength in the late-stage (stage D) mergers is about 1.5 times stronger than that in the early-state (stage B) mergers, which indicates that galaxy mergers could induce AGN-driven outflow and play an important role in the co-evolution of galaxies and supermassive black holes.Comment: 12 pages, 8 figures, and 2 tables, accepted for publication in PAS

Hyperbaric oxygen therapy for painful bladder syndrome/interstitial cystitis resistant to conventional treatments: long-term results of a case series in Japan

<p>Abstract</p> <p>Background</p> <p>There is no confirmed strategy for treating painful bladder syndrome/interstitial cystitis (PBS/IC) with unclear etiology. Therefore, a pilot study was carried out to evaluate the efficacy and safety of hyperbaric oxygen (HBO) therapy in treatment-resistant PBS/IC patients.</p> <p>Methods</p> <p>HBO treatment (2.0 ATA for 60 minutes/day × 5 days/week for 2 or 4 weeks) was performed on 11 patients with severe symptoms that had not been improved by previous therapy regimens between December 2004 and July 2009.</p> <p>Results</p> <p>Seven of the 11 patients demonstrated persistent improvement in symptoms during the 12 months after HBO treatment. These responders demonstrated a decrease in the pelvic pain scale and urgency scale from 7.7 ± 1.0 and, 6.6 ± 0.9 to 3.4 ± 2.5 and 4.3 ± 2.4 after 12 months, respectively (p < 0.05). The total score of the interstitial cystitis symptom index and 24-hour urinary frequency demonstrated a significant sustained decrease from the baseline. Two responders, who received an additional course of HBO 12 and 13 months after initial treatment, respectively, did not suffer impairment for more than two years. There was one case of transient eustachian tube dysfunction and three cases of reversible exudative otitis media as a consequence of HBO treatment.</p> <p>Conclusions</p> <p>HBO is a potent treatment for PBS/IC patients resistant to conventional therapy. It was well tolerated and provided maintained amelioration of pain, urgency and urinary frequency for at least 12 months.</p

Health-related Quality of Life Analysis from KEYNOTE-426: Pembrolizumab plus Axitinib Versus Sunitinib for Advanced Renal Cell Carcinoma

The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitinib monotherapy in patients with advanced renal cell carcinoma

Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial

Background The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitinib monotherapy in patients with advanced renal cell carcinoma. Methods In the ongoing, randomised, open-label, phase 3 KEYNOTE-426 study, adults (≥18 years old) with treatmentnaive, advanced renal cell carcinoma with clear cell histology were enrolled in 129 sites (hospitals and cancer centres) across 16 countries. Patients were randomly assigned (1:1) to receive 200 mg pembrolizumab intravenously every 3 weeks for up to 35 cycles plus 5 mg axitinib orally twice daily or 50 mg sunitinib monotherapy orally once daily for 4 weeks per 6-week cycle. Randomisation was done using an interactive voice response system or integrated web response system, and was stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk status and geographical region. Primary endpoints were overall survival and progression-free survival in the intentionto-treat population. Since the primary endpoints were met at the first interim analysis, updated data are reported with nominal p values. This study is registered with ClinicalTrials.gov, NCT02853331. Findings Between Oct 24, 2016, and Jan 24, 2018, 861 patients were randomly assigned to receive pembrolizumab plus axitinib (n=432) or sunitinib monotherapy (n=429). With a median follow-up of 30·6 months (IQR 27·2–34·2), continued clinical benefit was observed with pembrolizumab plus axitinib over sunitinib in terms of overall survival (median not reached with pembrolizumab and axitinib vs 35·7 months [95% CI 33·3–not reached] with sunitinib); hazard ratio [HR] 0·68 [95% CI 0·55–0·85], p=0·0003) and progression-free survival (median 15·4 months [12·7–18·9] vs 11·1 months [9·1–12·5]; 0·71 [0·60–0·84], p<0·0001). The most frequent (≥10% patients in either group) treatmentrelated grade 3 or worse adverse events were hypertension (95 [22%] of 429 patients in the pembrolizumab plus axitinib group vs 84 [20%] of 425 patients in the sunitinib group), alanine aminotransferase increase (54 [13%] vs 11 [3%]), and diarrhoea (46 [11%] vs 23 [5%]). No new treatment-related deaths were reported since the first interim analysis. Interpretation With extended study follow-up, results from KEYNOTE-426 show that pembrolizumab plus axitinib continues to have superior clinical outcomes over sunitinib. These results continue to support the first-line treatment with pembrolizumab plus axitinib as the standard of care of advanced renal cell carcinoma

Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Results from 42-month follow-up of KEYNOTE-426

https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.450