Adhesion molecules can initiate intracellular signaling. Engagement of CD44 either by its natural ligand hyaluronan or a speci¢c antibody on a cell line induced tyrosine phosphorylation and activation of focal adhesion kinase (FAK), which then associated with phosphatidylinositol 3-kinase (PI3K) and activated mitogen-activated protein kinase at its downstream. However, the introduction of dominant negative Rho into the cells inhibited the CD44-stimulated FAK phosphorylation. Cells expressing CD44 were signi¢cantly resistant to etoposide-induced apoptosis. This anti-apoptotic e¡ect was cancelled by the inhibition of either Rho, FAK or PI3K. These results may indicate a signaling pathway from CD44 to mediate the resistance against drug-induced apoptosis in cancer cells. ß
Adsorption of sulfuric acid anion (HSO4
- or SO4
2-) was studied using IRAS (infrared reflection absorption
spectroscopy) on Pt(S)-[n(111) × (111)] and Pt(S)-[n(100) × (111)] electrodes in 0.05 M H2SO4. Pt(S)-[n(111) × (111)] electrodes give two IRAS bands. One is from a sulfuric acid anion adsorbed on the terrace
with 3-fold symmetry (∼1200 cm-1), and another is from that on the step with 2-fold symmetry (∼1200
cm-1 and ∼1100 cm-1). Relative band intensity from the 2-fold sulfuric acid anion (∼1100 cm-1) gets higher
with the increase of step atom density. Pt(S)-[n(100) × (111)] electrodes also show two IRAS bands around
1200 and 1100 cm-1 which originate from the sulfuric acid anion adsorbed on the terrace and the step with
2-fold symmetry. The relative intensity of the lower frequency band increased with the increase of the step
atom density.
Objective Although lung squamous cell carcinoma (SCC) accounts for 20-30% of lung cancer cases, new treatment options are limited. The CA031 study showed that nanoparticle albumin-bound-paclitaxel (nab-PTX) plus carboplatin produced a significantly higher overall response rate (41%) than solvent-based paclitaxel plus carboplatin in patients with lung SCC. However, the safety and efficacy of combination chemotherapy of nab-PTX and carboplatin has not yet been established for patients with concurrent lung SCC and idiopathic interstitial pneumonias (IIPs). The aim of this study was to assess the safety and efficacy profiles of nab-PTX and carboplatin in patients with lung SCC and concurrent IIPs. Methods Eight patients with inoperable-stage lung SCC and IIPs were treated with nab-PTX plus carboplatin in a first-line setting between June 2013 and December 2016. One of the eight was a woman, and the median age was 77 (range=72-80) years. Their clinical outcomes, including chemotherapy-associated acute exacerbation of IIPs, were retrospectively investigated. Results The overall response rate was 50%, the median progression-free survival time was 5.6 months, and the median overall survival time was 8.1 months. No patients experienced chemotherapy-related exacerbation of IIPs in the first-line treatment with nab-PTX plus carboplatin. However, IIPs worsened in two of four patients who received second-line chemotherapy. Conclusion Combination chemotherapy of nab-PTX and carboplatin may be an effective and safe treatment option for patients with inoperable lung SCC with IIPs. To confirm this, a large-scale prospective study is needed.
Objective
Pembrolizumab has benefited patients with advanced non-small-cell lung cancer (NSCLC) with a programmed death-ligand (PD-L)1 high expression, but little information is available regarding its safety for patients with interstitial lung disease (ILD). The aim of this study was to assess the efficacy and tolerability of pembrolizumab for patients with advanced NSCLC and preexisting ILD.
Methods
We retrospectively reviewed the medical records of five patients with advanced NSCLC and preexisting ILD who received pembrolizumab monotherapy in a first-line setting.
Patients
All patients had mild ILD and pulmonary emphysema with a forced vital capacity within the normal range. Pembrolizumab was administered at a dose of 200 mg/body on day 1 every 3 weeks.
Results
The overall response rate was 60%. Four patients developed pembrolizumab-induced lung injury, which was improved in all cases by corticosteroid therapy. One patient received pembrolizumab for two years, did not experience lung injury and achieved a complete response.
Conclusion
Pembrolizumab has a high risk of inducing lung injury in patients with preexisting ILD, although it may be very effective in NSCLC patients with a high PD-L1 expression, even concurrent with preexisting ILD. Further large-scale studies are needed to determine risk factors of pembrolizumab-induced lung injury in such patients.
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