Promising preclinical models for lung cancer research-lung cancer organoids: a narrative review.

Background and Objective: Traditional cell line models are the commonly used preclinical models for lung cancer research. However, cell lines cannot recapitulate the complex tumor heterogeneity and cannot mimic the microenvironment of human cancer. Recently, 3D multicellular in vitro self-assembled models called "organoids" have been developed at a fast pace in the field of research, which can mimic the actual primary tumor. At present, several studies have reported on protocols of lung cancer organoids (LCOs) generation, and using LCOs can provide novel insight into the basic and translational research of lung cancer. However, the establishment of the LCO models remains challenging due to the complexity of lung cancer and the immaturity of organoid technology, so it is necessary to understand the influences of different methodologies on LCO generation and review the applications and limitations of LCO models. Methods: In this review, we searched the literature in the recent ten years in the field of LCOs. Key Content and Findings: We summarized the methodology, the problems, and the solutions in the LCOs generation, its application and limitations, as well as proposing future challenges and perspectives. Conclusions: Currently, LCOs are successfully generated via exploring the methodology by the researchers. Though there are still challenges in clinical application, LCOs are applied in some cancer studies including investigation of anti-cancer treatment response in vitro, modeling tumor immune microenvironment, and construction of organ chips, which are forging a promising path towards precision medicine.

New progress of tuberculosis scar carcinoma.

It has been demonstrated that scar tissue and fibrosis may increase the likelihood of developing malignancies. Specifically, scar tissue has been linked to the occurrence and progression of lung cancer (LC), though the precise mechanisms necessitate further research for explanation. Lung scarring can stem from various causes, with carcinogenesis on scarring lesions in pulmonary tuberculosis (PTB) being the most frequent (accounting for approximately 75% of cases). Notably, having previously cured, PTB is the second most common risk factor for LC after smoking, with approximately 3% of PTB patients experiencing LC as a secondary condition. This essay will delve into the mechanisms, treatment, and prognosis of tuberculosis scar carcinoma (TSC).

Smoking related environmental microbes affecting the pulmonary microbiome in Chinese population.

BACKGROUND: Smoking is a serious public health problem that affects human health conditions. Although there is evidence that microorganisms are associated with smoking-related lung diseases, the relationship between the rich lung microbiome of upper respiratory tract groups and smoking has not been studied. OBJECTIVE: In this study, we investigated the effects of smoking on environmental microbes and lung microbiome in the Chinese population and provided clues for the role of smoking in the development of respiratory disease. METHODS: Bronchoalveolar lavage fluid samples were collected from 55 individuals with a history of smoking. Microbial gene sequencing was carried out through NGS technology. We analyzed and compared the diversity, community structure, and species abundance of bronchoalveolar lavage microbiome between smokers and nonsmokers, to speculate the effects of smoking on the lung microbiome. RESULTS: Smoking hardly affected the α diversity of microbial groups of bronchoalveolar lavage, but it had a huge influence on the microbiome composition. The relative abundance of Rothia, Actinomycetes, Haemophilus, Porphyrins, Neisseria, Acinetobacter, and Streptococcus genera had a remarkable increase in the smoking group. On the other hand, the relative abundance of Plusella and Veronella decreased significantly. CONCLUSION: Smoking may change the environmental microbes and then alter the structure of the lung microbiome, which may lead to smoking-related diseases.

Update on lymphocyte-activation gene 3 (LAG-3) in cancers: from biological properties to clinical applications.

ABSTRACT: Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, however, is limited, emphasizing the need to potentiate the efficacy of these regimens. The functions of immune cells are modulated by multiple stimulatory and inhibitory molecules, including lymphocyte activation gene 3 (LAG-3). LAG-3 is co-expressed together with other inhibitory checkpoints and plays key roles in immune suppression. Increasing evidence, particularly in the last 5 years, has shown the potential of LAG-3 blockade in anti-tumor immunity. This review provides an update on the biological properties and clinical applications of LAG-3 in cancers.

Progress and future prospective of FDG-PET/CT imaging combined with optimized procedures in lung cancer: toward precision medicine.

With a 5-year overall survival of approximately 20%, lung cancer has always been the number one cancer-specific killer all over the world. As a fusion of positron emission computed tomography (PET) and computed tomography (CT), PET/CT has revolutionized cancer imaging over the past 20 years. In this review, we focused on the optimization of the function of 18F-flurodeoxyglucose (FDG)-PET/CT in diagnosis, prognostic prediction and therapy management of lung cancers by computer programs. FDG-PET/CT has demonstrated a surprising role in development of therapeutic biomarkers, prediction of therapeutic responses and long-term survival, which could be conducive to solving existing dilemmas. Meanwhile, novel tracers and optimized procedures are also developed to control the quality and improve the effect of PET/CT. With the continuous development of some new imaging agents and their clinical applications, application value of PET/CT has broad prospects in this area.

Percutaneous Microwave Coagulation Therapy: A Promising Therapeutic Method for Breaking the Barrier of the Intertumor Heterogeneity.

Intertumor heterogeneity is common in various cancers and has been widely accepted as the primary cause of the diversity and variation of the effect of the same treatment on patients with the same type of tumor. Percutaneous microwave coagulation therapy (PMCT) is a minimally invasive and effective approach for destroying tumors by microwave beam under image guidance, which has been applied in lung cancer. However, no previous study has investigated the capability of PMCT solving intertumor heterogeneity. Here, we performed a component analysis of four lung cancer patients' tumor microenvironment (TME) via single-cell RNA sequencing (scRNA-seq) and treated all four cases with PMCT. One patient's TME could be classified into a hot tumor, mainly proinflammatory cytokines, and T cell infiltration. The other three patients' TMEs were cold tumors, where immunosuppressive cells occupied a large proportion, including tumor-associated macrophages and cancer cells. Despite a high level of heterogeneity among their tumor microenvironment compositions, disease type and stage, and basic physical conditions, all four patients presented a stable disease (SD) without any cancer cell detected in the TME of cancer tissues after PMCT. In conclusion, this report uniquely contributed to the knowledge of the PMCT adaptation to tumor heterogeneity. Therefore, PMCT is promising to demonstrate a stable and robust antitumor efficacy in unresectable lung cancers with various TMEs.

The Angiotensin-Converting Enzyme Inhibitory State Promotes the Transformation of Non-Small Cell Lung Cancer Blood Supply Pattern Toward Vasculogenic Mimicry Formation.

Tumor microenvironment plays an important role in tumor proliferation, metastasis, and angiogenesis. Local RAS is a key factor to tumor proliferation and metastasis in NSCLC microenvironment, but its role on angiogenesis and VM formation remains unclear. Although overwhelming majority of previous studies suggested that VM is well established in aggressive tumor and facilitates tumor growth and metastasis, we put forward different views from another angle. We proved that status of tumor blood supply patterns, including VM channels and endothelial vessels, can dynamically exchange with each other along with local RAS fluctuations in microenvironment. Quantitatively, ACE2/ACEI promotes VM formation via Nodal/Notch4 activation; while structurally, ACE2/ACEI leads to a strong and solid structure of VM via inhibition of VE-cadherin internalization. These changes induced by ACE2/ACEI relate to relatively low metastasis rate and comforting prognoses of NSCLC patients.

The role of angiotensin-(1-7) on acquired platinum resistance-induced angiogenesis in non-small cell lung cancer in vitro and in vivo.

Renin-angiotensin system (RAS) signaling has been implicated in the development of cancer. The new RAS ACE2/Ang-(1-7)/Mas axis antagonizes the classical ACE/Ang II/AT1R axis. Ang-(1-7) has pleiotropic roles in lung cancer including suppressing proliferation, angiogenesis, and metastasis. This research was designed to investigate the effect of Ang-(1-7) on tumor-associated angiogenesis in DDP-resistant lung cancer cell lines. We first established acquired DDP-resistant cell lines A549 (A549-DDP) and LLC (LLC-DDP). We next performed RT-qPCR, western blot, ELISA, tube formation, microvessel density detection, immunohistochemistry, and tumor formation assays. The results showed that the mRNA and protein levels of RAS components and vascular endothelial growth factor A (VEGFa) were lessened in the A549/LLC-DDP+Ang-(1-7) group compared with the A549/LLC-DDP group. This effect could be blocked by the MAS receptor antagonist A779. The data revealed that Ang-(1-7) could perform its antiangiogenic function by PI3K/AKT and MAPK pathways. Furthermore, the impact of Ang-(1-7) on tumor-associated angiogenesis has been confirmed in lung cancer xenograft model with acquired DDP resistance. These results provide a theoretical basis for designing therapeutic strategies for targeting Ang-(1-7) in the treatment of NSCLC.

Application of ordinal logistic regression analysis to identify the determinants of illness severity of COVID-19 in China.

Corona Virus Disease 2019 (COVID-19) has presented an unprecedented challenge to the health-care system across the world. The current study aims to identify the determinants of illness severity of COVID-19 based on ordinal responses. A retrospective cohort of COVID-19 patients from four hospitals in three provinces in China was established, and 598 patients were included from 1 January to 8 March 2020, and divided into moderate, severe and critical illness group. Relative variables were retrieved from electronic medical records. The univariate and multivariate ordinal logistic regression models were fitted to identify the independent predictors of illness severity. The cohort included 400 (66.89%) moderate cases, 85 (14.21%) severe and 113 (18.90%) critical cases, of whom 79 died during hospitalisation as of 28 April. Patients in the age group of 70+ years (OR = 3.419, 95% CI: 1.596-7.323), age of 40-69 years (OR = 1.586, 95% CI: 0.824-3.053), hypertension (OR = 3.372, 95% CI: 2.185-5.202), ALT >50 µ/l (OR = 3.304, 95% CI: 2.107-5.180), cTnI >0.04 ng/ml (OR = 7.464, 95% CI: 4.292-12.980), myohaemoglobin>48.8 ng/ml (OR = 2.214, 95% CI: 1.42-3.453) had greater risk of developing worse severity of illness. The interval between illness onset and diagnosis (OR = 1.056, 95% CI: 1.012-1.101) and interval between illness onset and admission (OR = 1.048, 95% CI: 1.009-1.087) were independent significant predictors of illness severity. Patients of critical illness suffered from inferior survival, as compared with patients in the severe group (HR = 14.309, 95% CI: 5.585-36.659) and in the moderate group (HR = 41.021, 95% CI: 17.588-95.678). Our findings highlight that the identified determinants may help to predict the risk of developing more severe illness among COVID-19 patients and contribute to optimising arrangement of health resources.