Surgery Outcomes for Pulmonary Metastases from Renal Cell Carcinoma

Pulmonary metastatic resection is a standard therapy for renal cell carcinoma (RCC). Although patients with pulmonary metastases who do not undergo any treatment have poor prognoses, it has been reported that resection for pulmonary metastases yields good clinical outcomes. We investigated the prognoses of the 10 Japanese patients (eight males, two females) who underwent a surgical resection of pulmonary metastasectomy from RCC at our institution between April 1, 2012 and March 31, 2020 and analyzed the prognostic factors. We determined the prognoses and calculated the 5-year overall survival (OS) and disease-free survival (DFS) rates. To identify prognostic factors, we compared the median DFS duration for each factor. Elderly patients (median age, 75.5 years) were more predominant compared to previous studies, and all 10 patients underwent a complete resection. The 5-year DFS rate was 30.5% (95%CI: 0.045-0.63) and the 5-year OS rate was 80% (95%CI: 0.20-0.97). The following factors were associated with better prognosis: female, disease-free interval≥36 months, and metastases size<12 mm. These results indicate that complete resection for pulmonary metastases from RCC resulted in good clinical outcomes, particularly for patients with better prognostic factors

Recognition of 2′-hydroxyl groups by Escherichia coli ribonuclease HI

AbstractIn order to investigate the hydrogen-bonding interactions between Escherichia coli ribonuclease HI and the 2′-hydroxyl functions of the substrate, oligonucleotide duplexes containing 2′-amino-2′-deoxyuridine or 2′-fluoro-2′-deoxyuridine at a specific site were used, and their affinities for the enzyme were determined by kinetic analyses. The results indicate that the hydroxyl groups of the nucleoside 3′-adjacent to the cleaved phosphodiester linkage and the second nucleoside 5′ to the cleaved phosphodiester act as both a proton donor and an acceptor and as a proton acceptor, respectively, in the enzyme-substrate complex. A molecular model was constructed using the interactions derived from the results

Thoracoscopic Localization of Small Peripheral Pulmonary Lesions Using Percutaneous Computed Tomography-guided Pleural Dye Marking: A Retrospective Analysis

Small pulmonary lesions are often difficult to localize during thoracoscopic surgery. We describe a new com-puted tomography (CT)-guided pleural dye-marking method for small peripheral pulmonary lesions that does not involve a visceral pleural puncture. We used this technique for 23 lesions (22 patients) who underwent tho-racoscopic partial lung resection (Nov. 2016-Jan. 2018). With the patient in the lateral decubitus position, pre-operative CT-guided marking on the skin over the lesion was performed. During the surgery, we marked the visceral pleura with a skin marker directly or with an infant-size nutrition catheter with crystal violet at the tip through a venous indwelling needle inserted perpendicular to the skin marking. We localized and resected the lesions in all cases, without complications. The median nodule size measured histopathologically was 8 (4-20) mm overall, and 7 (0-20) mm of the solid part; the median distance from the visceral pleura to the nodule was 9 (1-33) mm. The median operation time was 67 (37-180) min. The median postoperative hospital stay was 3 (3-11) days. Our CT-guided pleural dye-marking method is useful and safe for the localization of small periph-eral pulmonary lesions in thoracoscopic partial lung resections

Impact of the day of the week on the discontinuation of broad-spectrum antibiotic prescriptions; a multi-centered observational study

To encourage and guide antimicrobial stewardship team (AST) activity and promote appropriate antibiotic use, we studied the impact of day of the week on the initiation and discontinuation of antibiotic administration. This was a multicenter observational study conducted at 8 Japanese hospitals from April 1 to September 30, 2019, targeting patients who underwent treatment with broad-spectrum antibiotics, such as anti-methicillin-resistant Staphylococcus aureus agents and anti-pseudomonal agents. We compared the weekly numbers of initiations and discontinuations of antibiotic prescription on each day of the week or on the days after a holiday. There was no statistical difference in the number of antibiotic initiations on both weekdays and the day after a holiday. However, antibiotic discontinuation was significantly higher from Tuesday onward than Monday and from the second day than the first day after a holiday. Similar trends were observed regardless of the categories of antibiotics, hospital and admission ward, and AST activity. This study suggests that broad-spectrum antibiotics tend to be continued during weekends and holidays and are most likely to be discontinued on Tuesday or the second day after a holiday. This was probably due to behavioral factors beyond medical indications, requiring further antimicrobial stewardship efforts in the future

Mechanistic Analysis of Resistance to REIC/Dkk-3-induced Apoptosis in Human Bladder Cancer Cells

We have recently shown that a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC) is effective against various human cancers, including those of prostate, testis and breast origins. The aim of the present study was to examine the sensitivity of bladder cancers to Ad-REIC and to clarify the molecular mechanisms that determine sensitivity/resistance. We found that 2 human bladder cancer cell lines, T24 and J82, are resistant to Ad-REIC. In T24 and J82 cells, the ER stress response and activation of JNK were observed in a manner similar to that in the sensitive PC3 cells. Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells. Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines. Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis. The results indicate that some human bladder cancers are resistant to apoptosis induced by overexpression of REIC/Dkk-3, which is at least in part due to up-regulation of Bcl-2. These results provide a basis for possible use of Bcl-2 as a marker of sensitive cancers and to try to sensitize resistant cancers to Ad-REIC by down-regulation of Bcl-2.</p

Brain pericytes among cells constituting the blood-brain barrier are highly sensitive to tumor necrosis factor-α, releasing matrix metalloproteinase-9 and migrating in vitro

<p>Abstract</p> <p>Background</p> <p>Increased matrix metalloproteinase (MMP)-9 in the plasma and brain is associated with blood-brain barrier (BBB) disruption through proteolytic activity in neuroinflammatory diseases. MMP-9 is present in the brain microvasculature and its vicinity, where brain microvascular endothelial cells (BMECs), pericytes and astrocytes constitute the BBB. Little is known about the cellular source and role of MMP-9 at the BBB. Here, we examined the ability of pericytes to release MMP-9 and migrate in response to inflammatory mediators in comparison with BMECs and astrocytes, using primary cultures isolated from rat brains.</p> <p>Methods</p> <p>The culture supernatants were collected from primary cultures of rat brain endothelial cells, pericytes, or astrocytes. MMP-9 activities and levels in the supernatants were measured by gelatin zymography and western blot, respectively. The involvement of signaling molecules including mitogen-activated protein kinases (MAPKs) and phosphoinositide-3-kinase (PI3K)/Akt in the mediation of tumor necrosis factor (TNF)-α-induced MMP-9 release was examined using specific inhibitors. The functional activity of MMP-9 was evaluated by a cell migration assay.</p> <p>Results</p> <p>Zymographic and western blot analyses demonstrated that TNF-α stimulated pericytes to release MMP-9, and this release was much higher than from BMECs or astrocytes. Other inflammatory mediators [interleukin (IL)-1β, interferon-γ, IL-6 and lipopolysaccharide] failed to induce MMP-9 release from pericytes. TNF-α-induced MMP-9 release from pericytes was found to be mediated by MAPKs and PI3K. Scratch wound healing assay showed that in contrast to BMECs and astrocytes the extent of pericyte migration was significantly increased by TNF-α. This pericyte migration was inhibited by anti-MMP-9 antibody.</p> <p>Conclusion</p> <p>These findings suggest that pericytes are most sensitive to TNF-α in terms of MMP-9 release, and are the major source of MMP-9 at the BBB. This pericyte-derived MMP-9 initiated cellular migration of pericytes, which might be involved in pericyte loss in the damaged BBB.</p

Review Article : Feudalism or Absolute Monarchism?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68809/2/10.1177_009770049001600304.pd