Platelet-derived growth factor-C functions as a growth factor in mouse embryonic stem cells and human fibrosarcoma cells

Abstract Background Platelet-derived growth factor-C (PDGF-C) has been shown to be involved in several biological processes, such as embryonic development, wound healing and angiogenesis, as well as in diseases including tumor formation and fibrotic diseases. However, its role in fibrosarcoma and embryonic stem (ES) cells has not been elucidated. Methods The expression level of PDGF-C was measured using RT-PCR. The activity of PDGF-C was suppressed using RNA interference or a neutralizing antibody and the effect on cell growth was examined using the WST and soft agar assays. Results In the tumor cell lines studied, the highest level of PDGF-C expression was in human HT1080 fibrosarcoma cells. In ES cells, it was highly expressed in the self-renewal state but not in the differentiated state. PDGF-C knockdown suppressed anchorage-dependent and -independent growth of HT1080 and ES cells. In addition, the suppression of PDGF-C activity by a neutralizing antibody retarded ES cell growth. Conclusion Our results suggest that PDGF-C plays an important role in the proliferation of fibrosarcoma and ES cells

Two Cases of Mucinous Cystadenoma of the Appendix Successfully Treated by Laparoscopy

Two cases of mucinous cystadenoma of the appendix successfully treated by laparoscopy are reported. An 81-year-old woman with lower right back pain was diagnosed with mucinous cystadenoma of the appendix or appendiceal carcinoma and underwent elective laparoscopic surgery. The other case involved a 70-year-old man with hematochezia who was diagnosed with mucinous cystadenoma. He also underwent elective laparoscopic surgery. In these two cases, gauze was folded around the tumors rather than grasping them directly. The postoperative courses were uneventful, and these patients had no recurrent disease at 2-year follow-up. In such cases, surgical excision of the tumor without rupture is of paramount importance because rupture of the lesion can cause pseudomyxoma peritonei. Though appendiceal mucinous cystadenoma has been considered a contraindication of laparoscopic resection, it was possible to achieve this by using a laparoscopic procedure with a gauze technique

Modular Redox Switching of Dinuclear Organometallic Molecular Junctions

Molecular switch is one of the essential functional units of molecular electronics. Here, we report development of new molecular switches based on the electron-rich diruthenium complexes with the (2,5-di-R-substituted 1,4-diethynylbenzene)diyl linkers. The dinuclear molecular switches, {µ-p-C≡C-(2,5-R2-C6H2)-C≡C}{Ru(dppe)2(C≡C-C6H4-p-SMe)}2 1R (R= OMe, H, CF3), with various substituents (R) on the bridging phenylene rings showed two successive reversible 1e-oxidation waves, indicating stability of 1e-oxidized mixed-valence species. The solid-state structure of [1H]+ showed the charge-localized Robin-Day class II nature, while that of [1OMe]+ revealed the fully charge-delocalized class III nature. These characters were also evident from the spectroscopic data in solutions. Single-molecule conductance measurements by the scanning tunneling microscope break junction method revealed a significant dependence of the conductance on R, i.e. 1OMe turned out to be >100-times more conductive than 1H and 1CF3, whereas the substituent effect of the monocationic complexes was within a fold-change of 2. As a result, the ON/OFF ratios (the ratios of the conductance of the cationic species [1R]+ to that of the neutral species 1R) were critically dependent on R (as large as 191 when R = CF3) and even reversed (0.4 when R = OMe). Furthermore, the neutral and monocationic complexes 1H and [1H]+ fabricated into the nanogap devices showed in situ ON/OFF switching behavior. The present study demonstrates not only the rare examples of the mixed-valence complexes which were subjected to the break junction measurements but also the first examples of molecular switch, the ON/OFF ratio of which was controlled by tuning the organic linker parts

Photoinduced Generation of Acyl Radicals from Simple Aldehydes, Access to 3‑Acyl-4-arylcoumarin Derivatives, and Evaluation of Their Antiandrogenic Activities

A novel photocatalysis to construct the 3-acyl-4-arylcoumarin framework from simple aldehyde with ynoate is described. The reaction proceeded through an acyl radical intermediate generated by hydrogen atom abstraction from aldehyde, followed by reaction with ynoate and then cyclization to afford coumarins. This valuable radical cyclization reaction gave over 20 coumarin derivatives in moderate to good yields with inexpensive 2-^<i>t</i>Bu-anthraquinone as a catalyst. In addition, synthetic coumarins were investigated for 5α-dihydrotestosterone (DHT)-induced secretion of prostate-specific antigen (PSA) levels and cell proliferation of androgen-dependent CWR22Rv1 cells

Efficacy and safety of nanoparticle albumin‐bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non‐small cell lung cancer: A multicenter Phase 2 clinical trial

Abstract Background Whether immunotherapy improves the efficacy or worsens adverse events of subsequent chemotherapy remains unclear. We performed a Phase 2 study to evaluate the efficacy and safety of nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) as a treatment for advanced non‐small cell lung cancer (NSCLC) after treatment with programmed cell death 1 or programmed death ligand 1 [PD‐(L)1] inhibitor failure. Methods Nab‐paclitaxel (100 mg/m2) was administered on Days 1, 8, and 15 of a 28‐day cycle to patients with advanced NSCLC within 12 weeks after the failure of PD‐(L)1 inhibitor treatment. The primary endpoint was objective response rate (ORR) in all patients; the secondary endpoints were disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. Results Thirty cases were registered, and 29 cases were included in the analysis. The ORR was 55.2% (95% confidence interval [CI]: 28.1%–79.6%) and the DCR was 86.2% (95% CI: 65.9%–97.0%). The median PFS was 5.6 months (95% CI: 4.4–6.7 months), and PFS rates at 1‐ and 2‐year timepoints were 34.5% and 13.3%, respectively. The median OS was 11.9 months (95% CI: 0.8–23.0 months). Good performance status and responder of previous PD‐(L)1 inhibitor therapy were independent predictors of PFS. Grade 3 or higher toxicities included leukopenia (27.6%), neutropenia (31.0%), peripheral sensory neuropathy (6.9%), increased alanine aminotransferase and aspartate aminotransferase levels (3.4%), and interstitial lung disease (3.4%). Conclusions Nab‐paclitaxel therapy improved ORR after PD‐(L)1 inhibitor treatment failure with a durable response of 13% and acceptable toxicities in patients with advanced NSCLC