Camrelizumab combined with apatinib and nanoparticle albumin-bound paclitaxel in lung adenocarcinoma (CAPAP-lung): a single-arm phase II study.

Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma. Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations received a rational-based combination of camrelizumab (200 mg intravenously, day one), apatinib (250 mg, q.d., five continuous days per week), and nab-paclitaxel (135 mg/m2 intravenously, days one and eight) every three weeks for four to six cycles in China. Patients with controlled disease were maintained with camrelizumab and apatinib. The primary end point was progression-free survival (PFS). This trial is registered with ClinicalTrials.gov (No. NCT04459078). Findings: Between August 26, 2020 and May 20, 2022, 64 patients were enrolled. The median PFS was 14.3 (95% CI: 9.9, not reached) months. The confirmed objective response rate was 64.1% (95% CI: 51.1, 75.7). The grade 3-4 hematologic treatment-related adverse events (TRAEs) were decreased neutrophil count (14.1%), decreased white blood cell count (7.8%), and anemia (3.1%). The most common non-hematologic TRAEs of grade 3-4 were increased alanine transaminase (18.8%) and aspartate transaminase (15.6%). No treatment-related death occurred. The quality of life was on average not clinically meaningful worse through treatment cycle 14. Interpretation: Nab-paclitaxel plus camrelizumab and apatinib showed clinically meaningful anti-tumor activity and manageable safety, with few hematologic toxicities, and might be a potential treatment option in patients with advanced lung adenocarcinoma lacking EGFR/ALK mutations. Funding: Heath Research Foundation of Chinese Society of Clinical Oncology, Hunan Provincial Natural Science Foundation of China, Hunan Cancer Hospital Climb Plan, Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center, The Science and Technology Innovation Program of Hunan Province, and Suzhou Sheng Diya Biomedical Co., Ltd, a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Shanghai, China).

The Evaluation of Prognostic Value and Immune Characteristics of Ferroptosis-Related Genes in Lung Squamous Cell Carcinoma.

Background The purpose of our study was to construct a prognostic model based on ferroptosis-related gene signature to improve the prognosis prediction of lung squamous carcinoma (LUSC). Methods The mRNA expression profiles and clinical data of LUSC patients were downloaded. LUSC-related essential differentially expressed genes were integrated for further analysis. Prognostic gene signatures were identified through random forest regression and univariate Cox regression analyses for constructing a prognostic model. Finally, in a preliminary experiment, we used the reverse transcription-quantitative polymerase chain reaction assay to verify the relationship between the expression of three prognostic gene features and ferroptosis. Results Fifty-six ferroptosis-related essential genes were identified by using integrated analysis. Among these, three prognostic gene signatures (HELLS, POLR2H, and POLE2) were identified, which were positively affected by LUSC prognosis but negatively affected by immune cell infiltration. Significant overexpression of immune checkpoint genes occurred in the high-risk group. In preliminary experiments, we confirmed that the occurrence of ferroptosis can reduce three prognostic gene signature expression. Conclusions The three ferroptosis-related genes could predict the LUSC prognostic risk of antitumor immunity.

Inhibition Effect of KHCO3 and KH2PO4 on Ethylene Explosion.

The explosion risk of ethylene (C2H4) seriously hinders safe development of its production and processing. To reduce the harm caused by C2H4 explosion, an experimental study was conducted to assess the explosion inhibition characteristics of KHCO3 and KH2PO4 powders. The experiments were conducted based on the explosion overpressure and flame propagation of the 6.5% C2H4-air mixture in a 5 L semi-closed explosion duct. Both the physical and chemical inhibition characteristics of the inhibitors were mechanistically assessed. The results showed that the 6.5% C2H4 explosion pressure (P ex) decreases by increasing the concentration of KHCO3 or KH2PO4 powder. The inhibition effect of KHCO3 powder on the C2H4 system explosion pressure was better than that of the KH2PO4 powder under similar concentration conditions. Both powders significantly affected the flame propagation of the C2H4 explosion. Compared with KH2PO4 powder, KHCO3 powder had a better inhibition effect on the flame propagation speed, but its ability to reduce the flame luminance was less than KH2PO4 powder. Finally, the inhibition mechanism(s) of KHCO3 and KH2PO4 powders were revealed based on the powders' thermal characteristics and gas-phase reaction.

Interferon regulatory factor-1 regulates cisplatin-induced apoptosis and autophagy in A549 lung cancer cells.

This study aimed to investigate the expression and function of interferon regulatory factor-1 (IRF-1) in non-small cell lung cancer (NSCLC). IRF-1 expression and its prognostic value were investigated through bioinformatic analysis. The protein expression levels of IRF-1, cleaved caspase 3, and LC3-I/II were analyzed by western blotting. A lentiviral vector was used to overexpress or knockdown IRF-1 in vitro. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed by JC-1 and DCFH-DA staining, respectively. ATP, SOD, MDA, cell viability, LDH release, and caspase 3 activity were evaluated using commercial kits. Compared to the levels in normal tissues, IRF-1 expression was significantly lower in lung cancer tissues and was a prognostic factor for NSCLC. Cisplatin treatment-induced IRF-1 activation, ROS production, ATP depletion, SOD consumption, and MDA accumulation in A549 lung cancer cells. IRF-1 overexpression promoted mitochondrial depolarization, oxidative stress, and apoptotic cell death and inhibited autophagy in A549 cells, and these effects could be reversed by IRF-1 knockdown. These data suggest that IRF-1 regulates apoptosis, autophagy and oxidative stress, which might be served as a potential target for increasing chemotherapy sensitivity of lung cancer.

Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma.

PURPOSE: The prognostic value of an N6-methyladenosine (m6A) methylation-related immune gene signature for lung adenocarcinoma (LUAD) was investigated. PATIENTS AND METHODS: Gene expression and clinical phenotype data of LUAD patients were downloaded from The Cancer Genome Atlas database. A list of immune-related genes was retrieved from the InnateDB database. Correlation analysis, survival analysis, and univariate and multivariate Cox regression analyses were performed. After allocating patients into a high-risk or a low-risk group, the corresponding survival rates, immune microenvironment, expression of immune checkpoint genes, and modulation of Kyoto Encyclopedia of Genes and Genomes pathways were examined. Finally, the expression levels of prognostic biomarkers were assessed in the GSE126044 dataset. RESULTS: Seven m6A-related immune prognostic genes were identified. High expression of PSMD10P1, DIDO1, ABCA5, and CIITA was associated with high survival rates, while that of PRC1, ZWILCH, and ANLN was associated with low survival rates. The high- and low-risk groups showed significant differences in terms of the abundance of six tumor-infiltrating immune cell types and expression of 12 immune checkpoint genes. The risk group acted as an independent prognostic factor (hazard ratio = 0.398, 95% confidence interval = 0.217-0.729, P = 0.003). Finally, the developed nomogram could predict most efficiently the 1-, 2-, and 3-year survival probability of LUAD patients with a C-index of 0.833. CONCLUSION: A seven-gene risk signature, associated with the immune microenvironment in LUAD, showed independent prognostic value.

Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy.

Immune checkpoint inhibitors (ICIs) significantly improve the survival of patients with non-small-cell lung cancer (NSCLC), but only some patients obtain clinical benefits. Predictive biomarkers for ICIs can accurately identify people who will benefit from immunotherapy. Lipid metabolism signaling plays a key role in the tumor microenvironment (TME) and immunotherapy. Hence, we aimed to explore the association between the mutation status of the lipid metabolism pathway and the prognosis of patients with NSCLC treated with ICIs. We downloaded the mutation data and clinical data of a cohort of patients with NSCLC who received ICIs. Univariate and multivariate Cox regression models were used to analyze the association between the mutation status of the lipid metabolism signaling and the prognosis of NSCLC receiving ICIs. Additionally, The Cancer Genome Atlas (TCGA)-NSCLC cohort was used to explore the relationships between the different mutation statuses of lipid metabolism pathways and the TME. Additionally, we found that patients with high numbers of mutations in the lipid metabolism pathway had significantly enriched macrophages (M0- and M1-type), CD4 + T cells (activated memory), CD8 + T cells, Tfh cells and gamma delta T cells, significantly increased expression of inflammatory genes [interferon-γ (IFNG), CD8A, GZMA, GZMB, CXCL9, and CXCL10] and enhanced immunogenic factors [neoantigen loads (NALs), tumor mutation burden (TMB), and DNA damage repair pathways]. In the local-NSCLC cohort, we found that the group with a high number of mutations had a significantly higher tumor mutation burden (TMB) and PD-L1 expression. High mutation status in the lipid metabolism pathway is associated with significantly prolonged progression-free survival (PFS) in NSCLC, indicating that this marker can be used as a predictive indicator for patients with NSCLC receiving ICIs.

Effect of Metal Foam Mesh on Flame Propagation of Biomass-Derived Gas in a Half-Open Duct.

The effect of metal foam mesh on flame propagation of biomass-derived gas in a half-open duct was studied. The explanations are based essentially on the experimental investigations of premixed biomass-derived gas explosions carried out in a rectangular half-open combustion chamber. The initial temperature T 0 and pressure P 0 were 300 K and 1.0 atm, respectively. The key parameters of explosive characteristics, such as flame propagation images and explosive overpressure, were analyzed by changing the porosity, the pore density of porous metal foams, and the gas components. The results show that the use of porous metal foam has a significant inhibitory effect on the gas explosion. Although the combustion structure of the flames is similar, the action of the porous metal foam during the experiment also shows the characteristics consistent with the obstacles. When the porosity of the porous foam is 97%, the flame can be stimulated to produce turbulence, and then the shock-flame interaction generated by the reflection of the lead shock wave can enhance the explosion propagation and promote the explosion escalation. However, with the increase of hole density, the existence of the porous metal foam by momentum loss and heat loss to curb the spread of the explosion not only hindered the flow of not flammable but also extracted energy from the expansion of the combustion products at the same time. This study also confirms that the biological hydrogen and methane component has a vital role in the flame, and a reasonable hydrogen and methane ratio can improve the flame burning to get more economic value.

Comprehensive analysis of genomic alterations detected by next-generation sequencing-based tissue and circulating tumor DNA assays in Chinese patients with non-small cell lung cancer.

While tumor genotyping is the standard treatment for patients with non-small cell lung cancer (NSCLC), spatial and temporal tumor heterogeneity and insufficient specimens can lead to limitations in the use of tissue-based sequencing. Circulating tumor DNA (ctDNA) fully encompasses tumor-specific sequence alterations and offers an alternative to tissue sample biopsies. However, few studies have evaluated whether the frequency of multiple genomic alterations observed following ctDNA sequencing is similar to that observed following tissue sequencing in NSCLC. Therefore, in the present study, targeted next-generation sequencing (NGS) was performed on tissue and plasma ctDNA samples in 99 patients with NSCLC. Overall, the frequencies of genetic alterations detected in ctDNA were positively correlated with those detected via tissue profiling (r=0.812; P=0.022). Genomic data revealed significant mutual exclusivity between alterations in epidermal growth factor receptor (EGFR) and tumor protein 53 (TP53; P=0.020), and between alterations in EGFR and KRAS (P=0.008), as well as potential mutual exclusivity between alterations in EGFR and Erb-B2 receptor tyrosine kinase 2 (P=0.059). Furthermore, the EGFR mutant allele frequency (MAF) was positively correlated with the TP53 MAF in individual tumors (r=0.773; P=0.005), and there was a marked difference in the EGFR MAF between patients with and without the TP53 mutation (P=0.001). Levels of the tumor serum marker CA242 in patients with ctDNA-detectable mutations were higher compared with those in patients without ctDNA-detectable mutations. The data from the present study highlight the importance of tissue and plasma ctDNA screening by NGS to guide personalized therapy and promote the clinical management of patients with NSCLC.

Inert nanoparticle suppression of gas explosion in the presence of obstacles.

The suppressing effects of inert nanoparticles on methane-air explosion, in an obstructed chamber with internal dimensions of 150 mm × 150 mm × 500 mm, were experimentally investigated. To this end, the flame behaviors in the presence of obstacles as well as overpressure transients during the explosions with and without nanoparticles were compared. Additionally, the effects of density, diameter, and material of nanoparticles on the suppressing behaviors were analyzed as well. The results showed that the methane-air deflagrating flame remains generally light blue if the nanoparticles are added. In particular, the flame obstacle interaction may enhance the suppression effect of the nanoparticles, and the flame acceleration rate and the peak overpressure decrease significantly. Increasing explosion suppression is seen up to about 100 g m-3 particle density, but further increase in particle density, up to 150 g m-3, yields no further increase in the explosion suppression ability. And as the particle size decreases, the suppressing effect is more evident. The experiments also showed that Al(OH)3, Mg(OH)2, and SiO2 all can be used to suppress the flame propagation and overpressure. However, the metal hydroxides suppress the methane explosions even more efficiently than SiO2 particles; Al(OH)3 particles have a slightly better inhibiting effect than Mg(OH)2. Mechanisms for the observed phenomena were discussed.

[Effect of informing the diagnosis on depressive state in patients with non-small cell lung cancer of stage III.].

BACKGROUND: As other tumors, unresectabe lung cancer can cause many psychological problems to the patients, such as depression and anxiety. The present paper aims to evaluate the status of depression before and after knowing the state of illness in patients with non-small cell lung cancer of stage III. METHODS: 43 cases of newly diagnosed non-small cell lung cancer (NSCLC) with stage III were enrolled in the study. All the patients were distributed into three groups and given different intervention, that was completely unknowing the state of illness (group A), partly knowing the state of illness (group B) and completely knowing the state of illness (group C). Before and after knowing the state of illness, the depression status was assessed with the Hamilton depression rating scale for depression (HAMD). RESULTS: The mean total score of HAMD was unchanged both in group A and C, while significantly reduced in group B. The scores of anxiety somatization, cognitive disorder, retardation and feeling of despair were all significant lower in the group B after the patients partly knowing the state of illness, while the scores of sleep disorder was obviously higher in group C after the patients completely knowing the state of illness. The hypochondriasis was much severer in the group A, and in the group C, the score of suicidal idea became significantly higher after the patient knowing the diagnosis. CONCLUSIONS: Depression is very common in the NSCLC patients with stage III. Partly knowing the state of illness can obviously ameliorate the symptoms of depression, while completely knowing or completely unknowing the state of illness have no effect on relieving the patients' depression.

[Therapeutic efficacy of chemotherapy combined with radiotherapy in 527 patients with stage III and IV non-small cell lung cancer].

BACKGROUND: Chemotherapy is very important in treatment of advanced non-small cell lung cancer (NSCLC), and the third-generation cisplatin-based chemotherapy regimens have been the standard treatment for advanced NSCLC. The aim of this study is to compare the efficacy and toxicity among four different chemotherapeutic regimens combined with radiotherapy in patients with stage III/IV NSCLC. METHODS: A total of 527 patients with stage III/IV NSCLC were enrolled, among whom there were 243 patients received cisplatin/vinorelbine (NP group), 163 patients for cisplatin/paclitaxel (TP group), 65 patients for cisplatin/gemcitabine (GP group) and 56 patients for cisplatin/docetaxel (DP group). The efficacy, side effects, median time to progression (TTP), median survival time (MST), 1- and 2-year survival rate were compared. RESULTS: The response rate was 46.9% in the NP arm, 44.8% in the TP arm, 47.7% in the GP arm and 42.9% in the DP arm (P > 0.05). The response rate of patients with radiochemotherapy was 69.9%, and 40.8% for those with chemotherapy alone (P < 0.05). In group NP, TP, GP and DP, median TTP was 5.7, 5.3, 5.9 and 5.5 months (P > 0.05) respectively, MST was 10.4, 10.6, 11.5 and 10.4 months (P > 0.05) respectively, 1-year survival rate was 41.9%, 41.1%, 43.1% and 42.9% (P > 0.05) respectively, and 2-year survival rate was 21.3%, 19.4%, 23.1% and 23.2% (P > 0.05) respectively. CONCLUSIONS: The third-generation cisplatin-based chemotherapy regimens may be the standard treatment for advanced NSCLC, and their combination with radiotherapy may improve the therapeutic efficacy and prolong the survival of patients.

[Clinical study of shenqi fuzheng injection and chemotherapy in CHOP protocol in treating malignant lymphoma].

OBJECTIVE: To compare the efficacy and adverse reaction of chemotherapy in CHOP protocol (CT-CHOP) alone or compared with Shenqi Fuzheng injection (SFI) for treatment of moderate malignant non-Hodgkin's lymphoma. METHODS: Sixty patients were divided into 2 groups, the treated group (n = 32) treated with CT-CHOP plus SFI for 5.7 cycles on average and the control group (n = 28) treated with CT-CHOP alone for 5.6 cycles on average. RESULTS: In the treated group, 18 patients were completely remitted (CR), 4 were partially remitted (PR), 7 were unchanged (NC), 3 were progressively deteriorated (PD), with the total remission rate of 68.8%, while in the control group, 13 were CR, 4 PR, 7 NC and 4 PD, the total remission rate being 60.7%. After treatment, the levels of CD3, CD4 and CD4/CD8 increased and CD8 decreased significantly in the treated group (P <0.05). Patients' quality of life (QOL) in the treated group was improved more obviously than that in the control group (P < 0.01), and the incidence rate of adverse reaction as leucopenia, neurotoxicity, and cardiac toxicity were lower in the treated group than those in the control group (P<0.01). CONCLUSION: Shenqi Fuzheng injection combined with CT-CHOP on malignant non-Hodgkin's lymphoma can reduce the adverse reaction of chemotherapy, ameliorate the compliance of patients to chemotherapy, and improve the immune function and QOL of patients.

[Preliminary result of advanced soft tissue sarcoma treated by MAID regimen].

BACKGROUND & OBJECTIVES: Chemotherapy combined with other therapeutic modalities is the main option for advanced and metastatic soft tissue sarcoma(STS). So far there is no standard regimen for STS yet. Adrimycin, ifosfamide, and dacarbazine are the most effective agents at present. The purpose of this clinical trial was to evaluate the efficacy and toxicity of MAID regimen (mesna/ifosfamide + Adriamycin + dacarbazine) in the treatment of advanced soft tissue sarcoma. METHODS: Twenty-two patients with advanced STS were treated by MAID(Adriamycin 60 mg/m2, ifosfamide 6,000 mg/m2, and dacarbazine 1,000 mg/m2). These drugs were administered as continuous intravenous infusion for 72 hours while mesna was infused continuously for 96 hours. RESULTS: Partial response rate was 36.4% without complete remission. The duration of response ranged from 2-10 months with median of 4.6 months. Main toxicities were myelosuppression, gastrointestinal toxicity and alopecia. Percentage of leucopenia, nausea/vomiting, and alopecia in WHO grade III and IV were 63.6%, 27.3%, and 50%, respectively. CONCLUSIONS: The response rate of MAID for advanced STS was not satisfactory with evident myelosuppression. Further study on new anti-cancer agents and regimen are needed.