A series of highly emissive three-coordinate copper(I) complexes, (dtpb)CuIX X = Cl (1), Br (2), I (3); dtpb =1,2-bis(o-ditolylphosphino)benzene, were synthesized and investigated in prototype ...organic light-emitting diodes (OLEDs). 1–3 showed excellent photoluminescent performance in both degassed dichloromethane solutions quantum yield (Φ) = 0.43–0.60; lifetime (τ) = 4.9–6.5 μs and amorphous films (Φ = 0.57–0.71; τ = 3.2–6.1 μs). Conventional OLEDs containing 2 in the emitting layer exhibited bright green luminescence with a current efficiency of 65.3 cd/A and a maximum external quantum efficiency of 21.3%.
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IJS, KILJ, NUK, PNG, UL, UM
A series of highly emissive sublimable copper(i) complexes with tetrahedral geometries, Cu(dppb)(pz sub(2)Bph sub(2)) 1, Cu(dppb-F)(pz sub(2)Bph sub(2)) 2, and Cu(dppb-CF sub(3))(pz sub(2)Bph sub(2)) ...3 dppb = 1,2-bis(diphenylphosphino)benzene, dppb-F = 1,2-bisbis(3,5-difluorophenyl)phosphinobenzene, and dppb-CF sub(3) = 1,2-bisbis3,5-bis(trifluoromethyl)phenylphosphinobenzene, pz sub(2)Bph sub(2) super(-) = diphenyl-bis(pyrazol-1-yl)borate, were synthesized and investigated as luminescent guest molecules in prototype organic light-emitting diodes. Thermogravimetric analysis of 1-3 under vacuum revealed that introduction of F or CF sub(3) substituents to the metapositions of the four peripheral phenyl groups in the dppb skeleton increased the ability of the copper(i) complexes to be sublimed. 1-3 exhibited strong green emission in amorphous films at 293 K with maximum emission wavelengths of 523-544 nm, quantum yields of 0.50-0.68, and decay times of 3.6-8.2 mu s. Molecular orbital calculations indicated that the origin of green phosphorescence from 1-3 was a mixture of sigma arrow right pi * and pi arrow right pi * transitions. Conventional bottom-emitting devices with three-layer structures containing 1-3 produced bright green luminescence with maximum external quantum efficiencies of 11.9, 16.0, and 17.7% for 1, 2 and 3, respectively.
Tetrahedral gold(I) complexes containing the diphosphane ligand (dppb=1,2‐bis(diphenylphosphino)benzene), Au(dppb)2X X=Cl (1), Br (2), I (3), NO3 (4), BF4 (5), PF6 (6), B(C6H4F‐4)4 (7), and the ...ethanol and methanol adducts of complex 4, 8, and 9, were prepared to analyze their unique photophysical properties. These complexes are classified into two categories on the basis of their crystal structures. In Category I, the complexes (1–5) have relatively‐small counter anions and two dppb ligands are symmetrically coordinated to the central AuI atom, and display an intense blue phosphorescence. Alternatively, the complexes (6–9) in Category II have large counter anions and two dppb ligands asymmetrically coordinated to AuI atom, and display a yellow or yellow orange phosphorescence. The difference in the phosphorescence color of the complexes between the Category I and II is ascribed to the change in the structure of the cationic moiety in the complex. According to DFT calculations, the symmetry reduction caused by the large counter anion of the complex in Category II gives the destabilization of HOMO (σ*) levels, leading to the red‐shift of the emission peak. We have demonstrated that the symmetry reductions are responsible for the phosphorescence color alteration caused by external stimuli (volatile organic compounds and mechanical grinding).
Phosphorescence color alteration: A small conformational change of two 1,2‐bis(diphenylphosphino)benzene (dppb) ligands in tetrahedral AuI complexes is caused by changing the counter anion or by external stimuli (volatile organic compounds and mechanical grinding), giving rise to the remarkable phosphorescence color alteration (see scheme).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Immune checkpoint inhibitor has greatly altered the standard of care for patients with advanced non–small-cell lung cancer (NSCLC). This prospective study reported the benefits of nivolumab in a ...routine clinical practice. Furthermore, neutrophil-to-lymphocyte ratio was identified as a candidate of predictive markers in nivolumab-treated NSCLC patients.
The immune checkpoint inhibitor nivolumab is entering routine oncologic practice. We investigated the safety and efficacy of nivolumab in the real world and alternative predictive factors for survival in patients with advanced non–small-cell lung cancer (NSCLC).
We performed a prospective observational study to evaluate the activity of nivolumab treatment for chemotherapy-refractory NSCLC. Patients were treated with nivolumab once every 2 weeks, and the efficacy was assessed every 8 ± 2 weeks.
Fifty-two patients were enrolled after nivolumab approval in Japan. These patients received a median of 4 (range, 1-43) cycles of nivolumab. Overall objective response was observed in 12 patients (23.1%). Median progression-free survival was 2.1 (95% confidence interval, 1.0-3.2) months, and 1-year overall survival rate was 59.9%. A total of 23 immune-related adverse events occurred in 20 patients, as follows: 7 cases of pneumonitis, 6 of oral mucositis, 5 of hypothyroidism, 2 of colitis, 2 of liver dysfunction, and 1 of arthritis. All patients recovered after appropriate management. A pretreatment neutrophil-to-lymphocyte ratio (NLR) of ≥ 5 was significantly associated with poor prognosis compared to NLR < 5 (hazard ratio, 4.52; 95% confidence interval, 1.84-11.14; P = .013), independently.
Nivolumab showed promising activity with a manageable safety profile in clinical practice, consistent with effects of previous clinical trials. This drug could affect a specific population of patients with advanced NSCLC, and pretreatment NLR was a candidate for surrogate markers for survival benefit of patients with NSCLC treated with nivolumab.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abnormal expressions of extracellular matrix (ECM) proteins are correlated with increased tumor progression, an advanced histologic grade, and metastasis. LCN1 cells derived from a pulmonary large ...cell neuroendocrine carcinoma were grown to form an Aegagropila-shaped conglomeration on a suspension culture dish (LCN1-sus). In contrast, LCN1 cells cultured in a type I collagen dish were adherent and tended to grow as spindle-shaped individual cells (LCN1-co). In this study, aiming at the discovery of predictive markers for tumor invasion, we performed protein profiling between LCN1-sus and LCN1-co cells using two-dimensional gel electrophoresis. Twenty-six protein spots with >1.2-fold quantitative differences between LCN1-sus and LCN1-co cells were detected. Among the identified proteins, we focused on and immunohistochemically investigated G6PD in lung cancer. G6PD expression was significantly associated with a higher pathological TNM stage (p = 0.0024), lymph node metastasis (p = 0.0187), poorer differentiation (p = 0.0046), pleural invasion (p = 0.0197), vascular invasion (p < 0.0001), lymphatic invasion (p = 0.0200) and poorer prognosis (p = 0.0005) in adenocarcinoma. Especially, G6PD-positive patients with overexpression at the invasive front had significantly poorer survival than those without overexpression (p = 0.0058). Moreover, multivariable analysis revealed that G6PD expression was an independent adverse-prognostic factor. These results suggest that G6PD may be a novel predictive prognostic marker for lung adenocarcinoma.
•G6PD expression was significantly correlated with clinicopathological factors.•Overexpression of G6PD at the invasive front meant significantly poorer survival.•G6PD expression was an independent prognostic factor by multivariable analysis.•G6PD may be a novel predictive prognostic marker for lung adenocarcinoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer chemotherapy indications for patients with poor performance status and advanced lung cancer are limited. Molecular targeted drugs, including epidermal growth factor receptor (EGFR)-tyrosine ...kinase inhibitors, can be used in patients with poor performance status owing to their high efficacy and safety. The third-generation EGFR-tyrosine kinase inhibitor osimertinib has demonstrated effectiveness in the initial treatment of advanced EGFR mutation-positive non-small cell lung cancer in patients with good performance status; however, no evidence exists of the drug's effectiveness in patients with poor performance status in a prospective study. We designed a study that aims to investigate the efficacy and safety of first-line osimertinib treatment in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations and with poor performance status.
The OPEN/TORG2040 study is a multicenter, single-arm, phase II trial for patients with unresectable, advanced EGFR mutation-positive non-small cell lung cancer with a poor performance status (≥ 2). Eligible patients will receive osimertinib until disease progression or unacceptable toxicity. The primary endpoint is the objective response rate of the first-line osimertinib treatment. Considering a threshold value of 45%, expected value of 70% for objective response rate, one-sided significance level of 5%, statistical power of 80%, and ineligible patients, the sample size was set to 30. The secondary endpoints are disease control rate, performance status improvement rate, and safety and patient-reported outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Quality of Life Questionnaire and Lung Cancer 13. Time to treatment failure, progression-free survival, and overall survival will also be assessed.
Our study can determine the clinical benefits of osimertinib treatment in patients with poor performance status, since the clinical outcomes of patients with EGFR mutation-positive non-small cell lung cancer with poor performance status treated with this drug as a first-line treatment have not been sufficiently evaluated.
Japan Registry of Clinical Trials: jRCTs041200100 (registration date: February 12, 2021).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Our aim was to develop a serodiagnostic marker for lung cancer. Monoclonal antibodies were generated, and one antibody designated as KU-Lu-1, recognizing cytoskeleton-associated protein 4 (CKAP4), ...was studied further. To evaluate the utility of KU-Lu-1 antibody as a serodiagnostic marker for lung cancer, reverse-phase protein array analysis was performed with sera of 271 lung cancer patients and 100 healthy controls. CKAP4 was detected in lung cancer cells and tissues, and its secretion into the culture supernatant was also confirmed. The serum CKAP4 levels of lung cancer patients were significantly higher than those of healthy controls (P < 0.0001), and the area under the curve of receiver-operating characteristic curve analysis was 0.890, with 81.1% sensitivity and 86.0% specificity. Furthermore, the serum CKAP4 levels were also higher in patients with stage I adenocarcinoma or squamous cell carcinoma than in healthy controls (P < 0.0001). Serum CKAP4 levels may differentiate lung cancer patients from healthy controls, and they may be detected early even in stage I non–small cell lung cancer. Serum CKAP4 levels were also significantly higher in lung cancer patients than in healthy controls in the validation set (P < 0.0001). The present results provide evidence that CKAP4 may be a novel early serodiagnostic marker for lung cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Oligometastasis is a state in which cancer patients have a limited number of metastatic tumors; patients with oligometastases survive longer than those with polymetastases. Extensive disease ...(ED)-small cell lung cancer (SCLC) is considered a systemic disease and a poor survival. This study investigated whether the concept of oligometastases is prognostic factor also applicable to patients with ED-SCLC.
We performed a retrospective study of 141 consecutive patients with ED-SCLC between 2008 and 2016. The patients were divided into four subgroups: group 1; patients with solitary metastatic site in one organ (n = 31), group 2; patients with 2-5 metastatic sites in one organ (n = 18), group 3; patients with over 6 metastases in one organ (n = 15), and group 4; patients with 2 or more metastatic organs (n = 77).
It was identified that 49 patients with ED-SCLC had oligometastases (groups 1 + 2) and 92 had polymetastases (groups 3 + 4). The prognoses of patients with ED-SCLC and oligometastases, defined as ≤5 metastases in a single organ, were significantly superior to those of patients with polymetastases 16.0 (95% CI, 11.0-21.0) months vs. 6.9 (95% CI, 6.0-7.8) months; p<0.001. 43 of 49 patients with ED-SCLC and oligometastases were relapsed after initial chemotherapy, and 38 (88%) experienced local recurrence.
Patients with ED-SCLC and oligometastases may have improved survival than those with polymetastases. As oligometastatic ED-SCLC tends to recur locally, local therapy combined with systemic chemotherapy may be a treatment option.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
. The optimal second and subsequent lines of chemotherapy for patients with non-small cell lung cancer (NSCLC) who have preexisting interstitial lung disease (ILD) are unclear. ...Hence, we examined the clinical efficacy and safety of second-line chemotherapy in such patients, including any exacerbation of preexisting ILD.
Methods.
The medical records of patients with NSCLC and preexisting ILD who received both first- and second-line chemotherapy were retrospectively reviewed.
Results.
Twenty-four patients with a median age of 71 years who were treated between April 2013 and March 2021 were included. The response rate after second-line chemotherapy with S-1 (n = 13), docetaxel (n = 8), pemetrexed (n = 2), or docetaxel plus ramucirumab (n = 1) was 12.5%, with a median progression-free survival (2nd line PFS) of 3.8 months. The overall survival from a start of first-line chemotherapy (1
st
line OS) and post-progression survival (PPS) post-first-line chemotherapy were 18.7 and 9.7 months, respectively. Spearman rank correlation and linear regression analyses showed that PPS was strongly correlated with 1st line OS (R = 0.85, P < 0.00001). Importantly, the 2nd line PFS was also significantly correlated with 1st line OS (R = 0.71, P = 0.0001). While second-line chemotherapy-related acute exacerbation of ILD was observed in 7 patients (29.2%), there were no treatment-related fatalities.
Conslusions.
Second-line chemotherapy has a strong positive impact on the OS of patients with NSCLC who have preexisting ILD. Given the findings of this study, second-line chemotherapy may be valuable in terms of prolonging long-term OS.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Objective
. The clinical outcomes of poor performance status (PS) patients with
epidermal growth factor receptor
(
EGFR
)-mutated non-small cell lung cancer (NSCLC) who are treated with ...osimertinib as a first-line treatment have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in chemotherapy-naive and poor PS (2 or more) patients with NSCLC harboring sensitive
EGFR
mutations.
Materials and Methods.
We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in
EGFR
. All patients were administered osimertinib (80 mg/day) as the initial treatment.
Results.
Sixteen patients (nine women and seven men) who were treated between August 2018 and July 2021 were included in this study; their median age was 78 years. The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5 months and the PS score improved in 8 of 16 patients (50%). The most common adverse event was acneiform rash (42%), followed by diarrhea (36%) and paronychia (36%); none of these were of grade ≥ 3. Interstitial lung disease occurred in 2 patients (12.5%); however, no treatment-related deaths occurred.
Conclusion.
Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive
EGFR
mutations. To obtain conclusive results, further studies with larger cohorts are warranted.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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