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Background: Non-small cell lung cancers (NSCLC) harboring Human Epidermal Growth Factor Receptor 2 (HER2) mutations represent a distinct subset with unique therapeutic challenges. Although immune checkpoint inhibitors (ICIs) have been transformative in lung cancer treatment, the efficacy of ICIs in HER2-mutated NSCLC remains to be established. Methods: We systematically searched for real-world studies investigating the use of ICIs in treating HER2-mutated NSCLC, sourced from the PubMed, Cochrane Library, and Embase databases. Outcomes including objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were extracted for further analysis. Results: Twelve studies involving 260 patients were enrolled in this meta-analysis. Pooled data revealed an ORR of 0.26 (95% CI 0.17–0.34), a DCR of 0.68 (95% CI 0.55–0.81), and a median PFS (mPFS) of 5.36 months (95% CI 3.50–7.21). Notably, in the subgroup receiving combined immune and chemotherapy, the ORR increased to 0.37 (95% CI 0.26–0.49), the DCR to 0.79 (95% CI 0.70–0.87), and the mPFS to 7.10 months (95% CI 5.21–8.99). Conclusions: ICIs demonstrate promising anti-tumor activity and safety in patients with HER2-mutated NSCLC. Furthermore, the combined regimen of ICIs and chemotherapy may provide a significant therapeutic option for this patient population. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the correlation between tumor-infiltrating lymphocytes (TILs) and immunotherapy efficacy in patients with advanced non-small cell lung cancer (NSCLC). Eighty-nine patients with advanced NSCLC who received immune checkpoint inhibitors (ICIs) monotherapy were retrospectively enrolled in this study. The density of TILs in paraffin-embedded pathological tissues taken before receiving ICIs was quantitatively analyzed by immunohistochemical staining. The density of TILs was treated as a dichotomous variable using the median as the cutoff value. The Kaplan–Meier analysis was used to assess survival differences between groups. Univariate and multivariate Cox analyses were applied to screen out independent prognostic factors and further construct a nomogram prediction model to predict survival. Survival analysis showed that CD8+ TILs, CD4+ TILs, and IFN-γ+ Th1 were significant positive indicators for predicting progression-free survival (PFS) and overall survival (OS) (p < 0.05), whereas Foxp3+ Treg were a significant negative predictor (p < 0.05). The predictive role of IL-4+ Th2 was not apparent in this study and requires further investigation and exploration (p > 0.05). The nomogram prediction model exhibited good discriminative ability, with C-index values of 0.723 (95% CI 0.682-0.764) and 0.793 (95% CI, 0.738-0.848) in the training cohort and validation cohort, respectively. The AUC values indicated that the nomogram prediction model had high predictive value and the calibration curve presented good prediction accuracy. TILs could predict the efficacy of immunotherapy and may become a promising predictor. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have transformed the treatment paradigm for patients with ALK-positive non-small cell lung cancer (NSCLC). Yet the differential efficacy between alectinib and crizotinib in treating patients with NSCLC and central nervous system (CNS) metastases has been insufficiently studied. A retrospective analysis was conducted of clinical outcomes of patients with ALK-positive NSCLC and CNS metastases treated at the Shandong Cancer Centre. Based on their initial ALK-TKI treatment, patients were categorised into either the crizotinib group or the alectinib group. Efficacy, progression-free survival (PFS), intracranial PFS and overall survival (OS) were evaluated. A total of 46 eligible patients were enrolled in the present study: 33 patients received crizotinib and 13 patients received alectinib. The median OS of the entire group was 66.8 months (95% CI: 48.5–85.1). Compared with the patients in the crizotinib group, the patients in the alectinib group showed a significant improvement in both median (m)PFS (27.5 vs. 9.5 months; P=0.003) and intracranial mPFS (36.0 vs. 10.8 months; P<0.001). However, there was no significant difference in OS between the alectinib and crizotinib groups (not reached vs. 58.7 months; P=0.149). Furthermore, there were no significant differences between patients receiving TKI combined with radiotherapy (RT) vs. TKI alone with respect to mPFS (11.0 vs. 11.7 months, P=0.863) as well as intracranial mPFS (12.5 vs. 16.9 months, P=0.721). In the present study, alectinib exhibited superior efficacy to crizotinib for treating patients with ALK-positive NSCLC and CNS metastases, especially in terms of delaying disease progression and preventing CNS recurrence. Moreover, the results demonstrated that it might be beneficial to delay local RT for patients with ALK-positive NSCL and CNS metastases. [ABSTRACT FROM AUTHOR]

Constructing novel near-infrared (NIR) fluorophores with an aggregation-induced emission (AIE) character is of particular interest but remains challenging. In this work, we linked two propeller-shaped alkoxyl-substituted tetraphenylethylene (TPE) to the short axis of a pyrrolopyrrole aza-BODIPY (PPAB) core by a phenylene spacer to form three novel NIR dyes (PPAB-TPE1–PPAB-TPE3). Due to the butterfly-shaped conformation and non-planar molecular structure, three dyes exhibited typical AIE characteristics with up to 390-fold fluorescence enhancement in the aggregated state. The structural effects on their photophysical properties and solvatochromic behavior via experimental and theoretical approaches were studied. The results indicated that attaching an AIE rotor along the short axis of PPAB is an efficient and facile strategy to construct AIE-active NIR dyes. Taking PPAB-TPE1 as an example, the resulting nanoparticles encapsulated by an amphiphilic copolymer F-127 had a small size and NIR emission, which showed potential application to bioimaging in HeLa cells. Moreover, PPAB-TPE1 showed sensitive and selective detection of diamine/polyamine with an over 210 nm hypsochromic shift in the absorption maximum and ratiometric fluorescence "turn on" process. The limit of detection was up to 0.053 μM. Visual putrescine gas detection with colorimetric and ratiometric fluorescent modes was also demonstrated. [ABSTRACT FROM AUTHOR]

Biogenic amines (BAs) are important biomarkers to monitor meat spoilage. However, the design of efficient BA fluorescent probes with distinct colorimetric and ratiometric fluorescent dual-channels is still a critical challenge because of similar chemical properties and basicity between BAs and other amines. Herein, pyrrolopyrrole cyanine (PPCy-1) is reported to display distinctly high reactivity toward BAs through an ultrasensitive irreversible chromophore reaction for the first time. The reaction mechanism is ascribed to synergistic aza-Michael addition and B–N detachment, followed by hydrolysis to produce low-conjugated diketopyrrolopyrrole and heteroaromatic acetonitrile compounds. As a result, colorimetric and ratiometric fluorescent dual-channel (Δλab = 188 nm and Δλem = 151 nm) signals and a limit of detection up to 62.1 nM level for BA solution are acquired. In addition, the colorimetric detection of volatile amine vapor using the PPCy-1-loaded filter paper, showing a color change from green to yellow, is feasible. A simple and cost-effective fluorescence "turn on" method using the filter paper or the CAD-40 resin loaded with PPCy-1 to detect TVB (total volatile bases) originating from shrimp spoilage is further demonstrated. [ABSTRACT FROM AUTHOR]

Aim: This study was conducted to evaluate the efficacy of immune checkpoint inhibitors (ICIs) plus anlotinib versus anlotinib alone to provide guidance for clinical treatment of non-small-cell lung cancer. Patients & methods: The records of 139 patients with advanced non-small-cell lung cancer who received at least one dose of ICIs plus anlotinib (IA group) or single-agent anlotinib (AA group) were retrospectively reviewed. The efficacy of the treatments, survival outcomes and adverse events were analyzed. The primary end point was investigator-assessed progression-free survival (PFS). Result: The IA group had a significantly prolonged median PFS (mPFS: 5.8 vs 4.2 months; p = 0.022) compared with the AA group (hazard ratio: 0.68; 95% CI: 0.68-0.97). In patients with brain metastases, the IA group exhibited improved efficacy (mPFS: 6.0 vs 3.8 months; p = 0.034) compared with the AA group (hazard ratio: 0.49; 95% CI: 0.23-1.05). Conclusion: ICIs plus anlotinib significantly improved efficacy compared with anlotinib alone and showed substantial potential for the control of intracranial lesions. [ABSTRACT FROM AUTHOR]

Immunotherapy against cancer, through immune checkpoint inhibitors targeting the programmed cell death‐1/programmed cell death‐ligand 1 axis, is particularly successful in tumors by relieving the immune escape. However, interindividual responses to immunotherapy are often heterogeneous. Therefore, it is essential to screen out predictive tumor biomarkers. In this study, we analyzed the commensal microbiota in stool samples and paired sputum samples from 75 metastatic non‐small‐cell lung cancer (NSCLC) patients at baseline and during treatment with immune checkpoint inhibitors. Results showed distinct microbes' signatures between the gut microbiota and paired respiratory microbiota. The alpha diversity between the gut and respiratory microbiota was uncorrelated, and only the gut microbiota alpha diversity was associated with anti‐programmed cell death‐1 response. Higher gut microbiota alpha diversity indicated better response and more prolonged progression‐free survival. Comparison of bacterial communities between responders and nonresponders showed some favorable/unfavorable microbes enriched in responders/nonresponders, indicating that commensal microbiota had potential predictive value for the response to immune checkpoint inhibitors. Generally, some rare low abundance gut microbes and high abundance respiratory microbes lead to discrepancies in microbial composition between responders and nonresponders. A significant positive correlation was observed between the abundance of Streptococcus and CD8+ T cells. These results highlighted the intimate relationship between commensal microbiota and the response to immunotherapy in NSCLC patients. Gut microbiota and respiratory microbiota are promising biomarkers to screen suitable candidates who are likely to benefit from immune checkpoint inhibitor‐based immunotherapy. [ABSTRACT FROM AUTHOR]

Background: To study in vitro the effects of anlotinib combined with radiotherapy on the lung cancer H520 cell cycle and apoptosis. Methods: The log growth period H520 cells were divided into the control group, anlotinib group (A group), radiotherapy group (RT group) and combined group (A + RT group). Cell cycle and apoptosis were detected by flow cytometry and changes in H520 cell cycle and apoptosis were analyzed in each group. Results: Anlotinib was determined to significantly inhibit cell growth in all groups, both alone, or in combination with radiotherapy. After receiving corresponding treatments, the proportions of G2/M‐phase cells in the control group, A group, RT group and A + RT group were different, and statistically significant (F = 32.086, P < 0.001). The apoptotic cell statistics of H520 cells in the control group, A group, RT group and A + RT group were significantly different (F = 44.537, P < 0.01). The relative expression of CDK1 in each group of cells was 0.04 ± 0.02, 0.07 ± 0.12, 0.81 ± 0.11, and 0.56 ± 0.16, respectively. There were differences between the groups by analysis of variance which were statistically significant (F = 58.36, P < 0.0001). The relative expression of cycle B in each group of cells was 0.27 ± 0.05, 0.40 ± 0.16, 0.65 ± 0.14, and 0.57 ± 0.13, respectively. There were differences between the groups by analysis of variance which were statistically significant (F = 10.77, P = 0.0002). Conclusions: Anlotinib had an inhibitory effect on lung cancer H520 cell proliferation. A higher rate of apoptosis and G2/M phase block was observed in the anlotinib‐radiotherapy combined group. Anlotinib combined with radiotherapy was able to synergistically inhibit tumor cell growth. Key points: Anrotinib combined with radiotherapy can synergistically inhibit tumor cell growth. [ABSTRACT FROM AUTHOR]

Reversible oxygen conversion is important for various green energy technologies. Herein we synthesize a series of bimetallic coordination polymers by varying the Ni/Co ratio and using HITP (HITP=2,3,6,7,10,11‐hexaiminotriphenylene) as the ligand, to interrogate the role of metal centres in modulating the activity of the oxygen reduction reaction (ORR). Co3HITP2 and Ni3HITP2 are compared. Unpaired 3d electrons in Co3HITP2 result in less coplanarity but more radical character. Thus, despite of a reduced crystallinity and conductivity, the best ORR activity, comparable to 20 % Pt/C, is obtained for Co3HITP2, showing the 3d orbital configuration of the metal centre promotes ORR. Experimental and DFT studies show a transition of ORR pathway from four‐electron for Co3HITP2 to two‐electron for Ni3HITP2. Rechargeable zinc–air batteries using Co3HITP2 as the air cathode catalyst demonstrate excellent energy efficiency and stability. [ABSTRACT FROM AUTHOR]

Background: This study was designed to assess the clinical efficacy and toxicity of apatinib (YN968D1) as third or subsequent‐line treatment for stage III/IV non‐small cell lung cancer (NSCLC). Methods: A total of 100 patients with advanced NSCLC who were treated with apatinib at a daily dose of 250/425/500 mg at Shandong Cancer Hospital from January 2016 to June 2018 were enrolled in our study. The objective response, disease control, and median progression‐free survival rates were reviewed and evaluated. Univariate and multivariate analyses were performed to determine the prognostic factors. The main adverse events were evaluated per the Common Terminology Criteria for Adverse Events version 4.0. Results: All patients were assessable for response. No complete responses were observed, 11 patients achieved a partial response, and 56 showed stable disease. The objective response rate was 11.0%, the disease control rate was 67.0%, and the median progression‐free survival was 2.93 months (95% confidence interval 2.07–3.87). In Cox regression analysis, the Eastern Cooperative Oncology Group performance status score (hazard ratio 1.799; P < 0.05) and smoking history (hazard ratio 1.958; P < 0.05) were predictive indicators for apatinib treatment efficacy. Treatment‐related adverse events were tolerated, predictable, reversible, and controllable. Conclusion: Apatinib was found to be both effective and safe in advanced NSCLC patients without a genetic driver mutation who experienced progression after two or more lines of chemotherapy treatment. [ABSTRACT FROM AUTHOR]

Described as a Btk inhibitor, ibrutinib also potently inhibits Bmx and EGFR, two good targets for lung cancer. Owing to its high CLogP (4.07) and low aqueous solubility (<0.01 mg/ml), resulting in unfavorable bioavailability, ibrutinib requires high dosages to achieve good clinical response in the treatment of non-small cell lung cancer (NSCLC). In our effort to improve the CLogP of ibrutinib by structural optimization led to the discovery of a potent anti-cancer agent B6 , with beneficial physicochemical parameters (CLogP = 2.56, solubility in water ≈ 0.1 mg/ml) meeting the principles of oral drugs. B6 exhibited anti-proliferation activities against EGFR-expressing cells, especially the mutant ones, such as H1975 (L858R/T790M, IC 50 = 0.92 ± 0.19 μM) and HCC827 (Del119 IC 50 = 0.014 ± 0.01 μM). Moreover, B6 significantly slowed down H1975 tumor growth with anti-tumor rate of 73.9% ( p < 0.01). Enzyme potencies assay demonstrated B6 moderately selectively inhibited Bmx (IC 50 = 35.7 ± 0.1 nM) over other kinases. So, as a potent Bmx inhibitor, B6 has the potential to be an efficacious treatment for NSCLC with acquired drug resistance. [ABSTRACT FROM AUTHOR]