Clinical Treatment Of Lung Cancer Research Articles

Synergistic chemotherapy and photothermal therapy of lung cancer using MoS2 nanosheets co-loaded with silybin and doxorubicin

The active ingredient in traditional Chinese medicine, silybin (SBN), is known to inhibit the proliferation of cancer cells and synergistically enhance the anticancer effects of the chemotherapy drug doxorubicin (DOX). However, the combination of SBN and DOX faces challenges such as a lack of targeting, short half-lives, different administration routes, and pharmacokinetic processes, which prevent the drug combination from effectively targeting tumors and diminish their synergistic potential, thereby limiting their in vivo antitumor effects. In response, this study proposes the development of a novel nanocarrier system based on molybdenum disulfide (MoS₂) modified with polyethylene glycol (PEG) and sialic acid (SA) to co-deliver SBN and DOX. This system is designed to trigger the release of the drugs in response to dual stimuli of pH and near-infrared light, increasing the intracellular concentration of the drugs and enhancing their synergistic interaction. The MoS₂-LPN-SBN/DOX nanosystem circulates within the body and specifically accumulates at tumor sites due to the enhanced permeability and retention (EPR) effect and SA-mediated active targeting. Upon exposure to near-infrared light, the system provides combined chemo- and photothermal therapy, leading to significant tumor suppression. This research offers a new approach and strategy for the clinical treatment of lung cancer, suggesting a promising pathway for enhancing the efficacy of traditional therapies.

Jmjd2c maintains the ALDHbri+ cancer stemness with transcription factor SOX2 in lung squamous cell carcinoma

ABSTRACT Lung squamous cell carcinoma (LSCC) is a deadly cancer in the world. Histone demethylase Jmjd2c is a key epigenetic regulator in various tumors, while the molecular mechanism underlying Jmjd2c regulatory in LSCC is still unclear. We used the aldehyde dehydrogenasebright (ALDHbri+) subtype as a research model for cancer stem cells (CSCs) in LSCC and detected the sphere formation ability and the proportion of ALDHbri+ CSCs with Jmjd2c interference and caffeic acid (CA) treatment. Additionally, we carried out bioinformatic analysis on the expression file of Jmjd2c RNAi mice and performed western blotting, qRT-PCR, Co-IP and GST pull-down assays to confirm the bioinformatic findings. Moreover, we generated Jmjd2c-silenced and Jmjd2c-SOX2-silenced ALDHbri+ tumor-bearing BALB/c nude mice to detect the effects on tumor progression. The results showed that Jmjd2c downregulation inhibited the sphere formation and the proportion of ALDHbri+ CSCs. The SOX2 decreased expression significantly in Jmjd2c RNAi mice, and they were positively co-expressed according to the bioinformatic analysis. In addition, SOX2 expression decreased in Jmjd2c shRNA ALDHbri+ CSCs, Jmjd2c and SOX2 proteins interacted with each other. Furthermore, Jmjd2c interference revealed significant blocking effect, and Jmjd2c-SOX2 interference contributed even stronger inhibition on ALDHbri+ tumor progression. The Jmjd2c and SOX2 levels were closely related to the development and prognosis of LSCC patients. This study indicated that Jmjd2c played key roles on maintaining ALDHbri+ CSC activity in LSCC by interacting with transcription factor SOX2. Jmjd2c might be a novel molecule for therapeutic targets and biomarkers in the diagnosis and clinical treatment of lung cancer.

Exosomal microRNAs in lung cancer: a narrative review.

Exosomes are nanoscale extracellular vesicles secreted by cells, which can release bioactive macromolecules, such as microRNA (miRNA) to receptor cells. Exosomes can efficiently penetrate various biological barriers which mediate intercellular communication. MiRNA are a class of non-coding RNA that primarily regulate messenger RNA (mRNA) at the post-transcriptional level. MiRNA is abundant in exosomes, which plays an important role by being transported and released through exosomes secreted by lung cancer cells. This review aims to elucidate the roles of exosome-derived miRNAs in lung cancer. We focused on the roles of exosome-derived miRNAs in cancer occurrence and development, including angiogenesis, cell proliferation, invasion, metastasis, immune escape, drug resistance, and their clinical value as new diagnostic and prognostic markers for lung cancer. Exosomal miRNA can not only affect angiogenesis of lung cancer, induce epithelial-mesenchymal transformation, and promote reprogramming of tumor microenvironment, but also affect immune regulation and drug resistance transmission and participate in regulating lung cancer cell proliferation. Therefore, understanding the regulatory roles of exosomal miRNAs in tumor invasion and metastasis can provide new ideas for the treatment of lung cancer. Exosomal miRNA can provide some unique ideas on how to improve the efficiency of diagnosis and treatment of lung cancer in the future. Targeting tumor-specific exosomal miRNA represents a new strategy for clinical treatment of lung cancer, which can provide potential non-invasive biomarkers in the early diagnosis of lung cancer. Investigation of the involvement of exosomal miRNAs in the occurrence and progression of tumors can yield new opportunities for the clinical diagnosis and treatment of lung cancer.

Keratin 6A (KRT6A) promotes radioresistance, invasion, and metastasis in lung cancer via p53 signaling pathway.

It is reported that the incidence rate and mortality of lung cancer are very high. Therefore, early diagnosis and identification of specific biomarkers are crucial for the clinical treatment of lung cancer. This study aims to comprehensively investigate the prognostic significance of KRT6A in human lung cancer. The GEO2R online tool was utilized to analyze the differential expression of mRNA between lung carcinoma tissues and radioresistant tissues in the GSE73095 and GSE197236 datasets. DAVID database was used to perform GO and KEGG enrichment analyses on target genes. The Kaplan-Meier plotter tool was used to analyze the impact of key messenger ribonucleic acid on the survival status of lung cancer. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to investigate the impact of key genes on the phenotype of lung cancer cells. After the knockout, we conducted cell migration and CCK-8 experiments to detect their effects on cell proliferation and invasion. 40 differentially expressed genes (DEGs) were chosen from GSE73095 and 118 DEGs were chosen from GSE197236. Kaplan-Meier map analysis showed that the overall cancer survival rate of the high-expression KRT6A group was higher than that of the low-expression group (P < 0.05). Besides, cell experiments have shown that when the KRT6A gene is downregulated, the proliferation and invasion ability of lung cancer cells is weakened. Our research concluded that KRT6A may take part in the radioresistance and progression of lung cancer and can be a potential biomarker for lung cancer patients.

Out-of-set association analysis of lung cancer drugs and symptoms based on clinical case data mining.

There are 1.8 million lung cancer deaths worldwide, accounting for 18% of global cancer deaths, including 710,000 in China, accounting for 23.8% of all cancer deaths in China. To explore the out-of-set association rules of lung cancer symptoms and drugs through text mining of traditional Chinese medicine (TCM) treatment of lung cancer, and form medical case analysis to analyze the experience of TCM syndrome differentiation in its treatment. The medical records of all patients diagnosed with lung cancer in Nanjing Chest Hospital from January to December 2018 were collected, and the out-of-set association analysis was performed using the MedCase v5.2 TCM clinical scientific research auxiliary platform based on the frequent pattern growth enhanced association analysis algorithm. In terms of TCM treatment of lung cancer, the clinical symptoms with high correlation included cough, expectoration, chest distress, and white phlegm; and the drugs with high correlation included Pinellia ternata, licorice root, white Atractylodes rhizome, and Radix Ophiopogonis; with the prescriptions based on Erchen and Maimendong decoctions. This analytical study of the medical cases of TCM treatment for lung cancer was performed using data mining techniques, and the out-of-set association rules between clinical symptoms and drugs were analyzed, including the understanding of lung cancer in TCM. Moreover, the essence of experience in drug use was gathered, providing significant scientific guidance for the clinical treatment of lung cancer.

PDGFRβ-Antagonistic Affibody-Mediated Tumor-Targeted Tumor Necrosis Factor-Alpha for Enhanced Radiotherapy in Lung Cancer.

The morbidity and mortality of lung cancer are still the highest among all malignant tumors. Radiotherapy plays an important role in clinical treatment of lung cancer. However, the effect of radiotherapy is not ideal due to the radiation resistance of tumor tissues. Abnormalities in tumor vascular structure and function affect blood perfusion, and oxygen transport is impeded, making tumor microenvironment hypoxic. Tumor hypoxia is the major cause of radiotherapy resistance. By promoting tumor vessel normalization and enhancing vascular transport function, tumor hypoxia can be relieved to reduce radiotherapy resistance and increase tumor radiotherapy sensitivity. In our previous study, a pericytes-targeted tumor necrosis factor alpha (named Z-TNFα) was first constructed and produced by genetically fusing the platelet-derived growth factor receptor β (PDGFRβ)-antagonistic affibody (ZPDGFRβ) to the TNFα, and the Z-TNFα induced normalization of tumor vessels and improved the delivery of doxorubicin, enhancing tumor chemotherapy. In this study, the tumor vessel normalization effect of Z-TNFα in lung cancer was further clarified. Moreover, the tumor hypoxia improvement and radiosensitizing effect of Z-TNFα were emphatically explored in vivo. Inspiringly, Z-TNFα specifically accumulated in Lewis lung carcinoma (LLC) tumor graft and relieved tumor hypoxia as well as inhibited HIF-1α expression. As expected, Z-TNFα significantly increased the effect of radiotherapy in mice bearing LLC tumor graft. In conclusion, these results demonstrated that Z-TNFα is also a promising radiosensitizer for lung cancer radiotherapy.

Mechanisms predictive of Tibetan Medicine Sophora moorcroftiana alkaloids for treatment of lung cancer based on the network pharmacology and molecular docking

BackgroundLeguminous Sophora moorcroftiana (SM) is a genuine medicinal material in Tibet. Many research results have reveal the Sophora moorcroftiana alkaloids (SMA), as the main active substance, have a wide range of effects, such as antibacterial, antitumor and antiparasitic effects. However, there are few reports on the inhibition of lung cancer (LC) and its inhibitory mechanism, and the pharmacological mechanism of SMA is still unclear, Therefore, exploring its mechanism of action is of great significance.MethodsThe SMA active components were obtained from the literature database. Whereas the corresponding targets were screened from the PubChem and PharmMapper database, UniProt database were conducted the correction and transformation of UniProt ID on the obtained targets. The GeneCards and OMIM databases identified targets associated with LC. Venny tools obtained the intersection targets of SMA and LC. R language and Cytoscape software constructed the visual of SMA - intersection targets – LC disease network. The intersection targets protein-protein interaction (PPI) network were built by the STRING database. The functions and pathways of the common targets of SMA and LC were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking And A549 cells vitro experiment were performed to further validate our finding.ResultsWe obtained six kinds of alkaloids in SM, 635 potential targets for these compounds, and 1,303 genes related to LC. SMA and LC intersection targets was 33, including ALB, CCND1, ESR1, NOTCH1 and AR. GO enrichment indicated that biological process of SMA was mainly involved in the positive regulation of transcription and nitric oxide biosynthetic process, and DNA-templated, etc. Biological functions were mainly involved in transcription factor binding and enzyme binding, etc. Cell components were mainly involved in protein complexes, extracellular exosome, cytoplasm and nuclear chromatin, etc., Which may be associated with its anti-LC effects. KEGG enrichment analysis showed that main pathways involved in the anti-LC effects of SMA, including pathway in cancer, non small-cell lung cancer, p53, PI3K-Akt and FOXO signaling pathways. Molecular docking analyses revealed that the six active compounds had a good binding activity with the main therapeutic targets 2W96, 2CCH and 1O96. Experiments in vitro proved that SMA inhibited the proliferation of LC A549 cells.ConclusionsResults of the present study, we have successfully revealed the SMA compounds had a multi-target and multi-channel regulatory mechanism in treatment LC, These findings provided a solid theoretical reference of SMA in the clinical treatment of LC.

Analysis of the Effect of Bevacizumab as An Anti-VEGFR Pathway Drug in the Clinical Treatment of Lung Cancer

Objective To analyze the effect of treatment with bevacizumab, an anti-VEGFR pathway drug, in patients with lung cancer. Methods 60 patients with lung cancer were used as samples, from October 2021 to February 2023, and random number table method was used to divide them into groups. Group A was treated with bevacizumab + paclitaxel protein-binding protein combined with carboplatin + cisplatin, and Group B was treated with paclitaxel protein-binding combined with carboplatin + cisplatin. Compare the differences in curative effect, tumor marker levels, immune function, toxic and side effects between the two groups. Results Lung cancer therapy in group A was higher than that in group B, P&lt;0.05; serum tumor markers such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125) in group A were significantly higher than those in group B Low, P&lt;0.05; CD4 + , CD8 + , CD4 + /CD8 + and other immune indicators in group A were better than those in group B, P&lt;0.05; the incidence of toxic and side effects in patients with lung cancer in group A was not different from that in group B, P&gt;0.05. Conclusion Bevacizumab, an anti-VEGFR pathway drug, is effective and feasible in the treatment of lung cancer, which can inhibit the progression of cancer, regulate the body's immune function, reduce toxic and side effects, and prolong the survival of patients.

Salvianolic acid F suppresses KRAS-dependent lung cancer cell growth through the PI3K/AKT signaling pathway

BackgroundKRAS mutation is a common driver of NSCLC, and there is a high proportion of lung cancer patients with KRAS G12C and G12D mutation. KRAS was previously considered an "undruggable" target, but the first KRAS G12C mutation-targeted drug AMG510, entered the market in 2021. However, treatments for G12D mutant tumors remain to be discovered. Salvianolic acid F (SalF), a monomer derived from the traditional Chinese medicine Salvia miltiorrhiza (SM), and KRAS had high binding affinity, especially for KRAS G12D. There is an urgent need to investigate effective and safe novel targeted therapies against KRAS G12D-driven NSCLC. MethodsTo evaluate the anticancer effect of SalF, we used KRAS-overexpressing lung cancer cells in vitro, a subcutaneous transplant tumor model, and KRAS G12D mice model in vivo. Then, the binding effect of SalF and KRAS was investigated using molecular docking, proteolytic assays and protein thermal shift assays. More critically, the PI3K/AKT signaling pathway in the lung was investigated utilizing RT-qPCR and Western Blotting. ResultsThis is the first study to evaluate the anticancer effect of SalF on KRAS-overexpressing lung cancer cells or KRAS G12D lung tumors in vivo. We demonstrated that SalF inhibits OE-KRAS A549 cell migration, proliferation and promotes apoptosis in vitro. In addition, we used a subcutaneous transplant tumor model to show that SalF suppresses the growth of lung cancer cells in vivo. Interestingly, our group found that SalF was strongly bound to G12D and could decrease the stability and promoted the degradation of the KRAS G12D mutant through molecular docking, proteolytic assays and protein thermal shift assays. Further research demonstrated that in the KrasG12D mice model, after SalF treatment, the number and size of mouse lung tumors were significantly reduced. More importantly, SalF can promote apoptosis by inhibiting downstream PI3K/AKT signaling pathway activation. ConclusionSalF activated apoptosis signaling pathways, suppressed anti-apoptotic genes, and inhibited lung cancer cell growth. These datas suggested that SalF could effectively inhibit the growth of lung tumors with KRAS G12D mutation. SalF may be a novel inhibitor against KRAS G12D, providing a strong theoretical basis for the clinical treatment of lung cancer with KRAS mutations.

Analysis of the cluster efficacy and prescription characteristics of traditional Chinese medicine intervention for non-small cell lung cancer based on a clustering algorithm.

In recent years, malignant tumors have gradually become one of the main causes of death for Chinese residents, of which lung cancer ranks first in both the incidence and mortality in China. To mine the text of traditional Chinese medicine (TCM) clinical medical cases after data cleaning, analyze it, and study the experience of TCM doctors in treating non-small cell lung cancer (NSCLC). The applied approach was based on the data mining methods of decentralized and hierarchical system clustering of data from a drug and prescription database. This study involved 215 patients, 287 cases, and 147 types of clinical drugs. The data analysis of the clinical treatment of NSCLC in TCM showed that Erchen Decoction was the main method for the treatment of non-small cell lung cancer in clinical treatment of non-small cell lung cancer. Junjian recipes were close to each other, with Banzhilian, Lobelia, Shanci Mushroom, Hedyotis diffusa to anticancer and detoxify. This study analyzed the core TCM prescription for NSCLC by collecting the empirical essence and characteristics of specific medications. It has some guiding scientific significance for the clinical treatment of lung cancer.

Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer

BackgroundNon-small cell lung cancer (NSCLC) is a worldwide health threat with high annual morbidity and mortality. Chemotherapeutic drugs such as paclitaxel (PTX) have been widely applied clinically. However, systemic toxicity due to the non-specific circulation of PTX often leads to multi-organ damage, including to the liver and kidney. Thus, it is necessary to develop a novel strategy to enhance the targeted antitumor effects of PTX.MethodsHere, we engineered exosomes derived from T cells expressing the chimeric antigen receptor (CAR-Exos), which targeted mesothelin (MSLN)-expressing Lewis lung cancer (MSLN-LLC) through the anti-MSLN single-chain variable fragment (scFv) of CAR-Exos. PTX was encapsulated into CAR-Exos (PTX@CAR-Exos) and administered via inhalation to an orthotopic lung cancer mouse model.ResultsInhaled PTX@CAR-Exos accumulated within the tumor area, reduced tumor size, and prolonged survival with little toxicity. In addition, PTX@CAR-Exos reprogrammed the tumor microenvironment and reversed the immunosuppression, which was attributed to infiltrating CD8+ T cells and elevated IFN-γ and TNF-α levels.ConclusionsOur study provides a nanovesicle-based delivery platform to promote the efficacy of chemotherapeutic drugs with fewer side effects. This novel strategy may ameliorate the present obstacles to the clinical treatment of lung cancer.

ISG15 targets glycosylated PD-L1 and promotes its degradation to enhance antitumor immune effects in lung adenocarcinoma

BackgroundImmunocheckpoint inhibitors (ICIs) have been widely used in the clinical treatment of lung cancer. Although clinical studies and trials have shown that patients can benefit significantly after PD-1/PD-L1 blocking therapy, less than 20% of patients can benefit from ICIs therapy due to tumor heterogeneity and the complexity of immune microenvironment. Several recent studies have explored the immunosuppression of PD-L1 expression and activity by post-translational regulation. Our published articles demonstrate that ISG15 inhibits lung adenocarcinoma progression. Whether ISG15 can enhance the efficacy of ICIs by modulating PD-L1 remains unknown.MethodsThe relationship between ISG15 and lymphocyte infiltration was identified by IHC. The effects of ISG15 on tumor cells and T lymphocytes were assessed using RT-qPCR and Western Blot and in vivo experiments. The underlying mechanism of PD-L1 post-translational modification by ISG15 was revealed by Western blot, RT-qPCR, flow cytometry, and Co-IP. Finally, we performed validation in C57 mice as well as in lung adenocarcinoma tissues.ResultsISG15 promotes the infiltration of CD4+ T lymphocytes. In vivo and in vitro experiments demonstrated that ISG15 induces CD4+ T cell proliferation and invalidity and immune responses against tumors. Mechanistically, we demonstrated that the ubiquitination-like modifying effect of ISG15 on PD-L1 increased the modification of K48-linked ubiquitin chains thus increasing the degradation rate of glycosylated PD-L1 targeting proteasomal pathway. The expression of ISG15 and PD-L1 was negatively correlated in NSCLC tissues. In addition, reduced accumulation of PD-L1 by ISG15 in mice also increased splenic lymphocyte infiltration as well as promoted cytotoxic T cell infiltration in the tumor microenvironment, thereby enhancing anti-tumor immunity.ConclusionsThe ubiquitination modification of PD-L1 by ISG15 increases K48-linked ubiquitin chain modification, thereby increasing the degradation rate of glycosylated PD-L1-targeted proteasome pathway. More importantly, ISG15 enhanced the sensitivity to immunosuppressive therapy. Our study shows that ISG15, as a post-translational modifier of PD-L1, reduces the stability of PD-L1 and may be a potential therapeutic target for cancer immunotherapy.

Mutations and expressions of breast cancer 1/2 in lung cancer.

Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) tumor suppressor genes play crucial roles in DNA repair and regulation of transcription. Mutations in these genes are closely associated with the occurrence of cancers. However, the mutation status of BRCA gene in central south Chinese lung cancer patients remains unclear, and its expression levels in lung cancer also need to be further explored. In this study, we use next-generation sequencing (NGS) technology to analyze the BRCA genes mutations in 462 central south Chinese lung cancer patients. Public databases including cBioportal, Catalogue Of Somatic Mutations In Cancer (COSMIC), The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and Expression Profiling Interactive Analysis (GEPIA) are also applied to explore the expression level and mutation status of BRCA in lung cancer patients and their relationships with the prognosis. We found that the mutation rate of BRCA1/2 in central south Chinese lung cancer patients is 4.3% and 6.5% respectively, and missense mutations account for the majority in both BRCA1/2, which are similar to the international status of BRCA1/2 from public databases. In addition, 45 novel mutations of BRCA1/2 in lung cancer are reported in this study. Furthermore, we find that the BRCA2 mutations are negatively correlated with overall survival rate in lung cancer using cBioportal. Last, we demonstrate that both of the mRNA and protein levels of BRCA1/2 are upregulated in lung cancer, and the elevated mRNA expression levels are positively linked with poor prognosis. In general, our study better complements knowledge of the BRCA1/2 mutation status in the Chinese lung cancer patients, and firstly reveals the association between BRCA1/2 expression levels and prognosis of lung cancer patients, which may provide great value for the early diagnosis and clinical treatment of lung cancer.

The Tian-Men-Dong decoction suppresses the tumour-infiltrating G-MDSCs via IL-1β-mediated signalling in lung cancer

Ethnopharmacological relevanceThe traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown. Aim of the studyThis study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs). Materials and methodsAn orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT–qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1β/TD + IL-1β in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1β-mediated apoptosis of G-MDSCs. ResultsTD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1β-mediated NF-κB signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8+ T-cell infiltration, which was supported by both the depletion and adoptive transfer of G-MDSCs assays. In addition, TD also showed minimal cytotoxicity both in vivo and in vitro. ConclusionThis study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1β-mediated NF-κB signalling pathway, reshaping the tumour microenvironment and demonstrating antitumour effects. These findings provide a scientific foundation the clinical treatment of lung cancer with TD.

Risk Factors for Operation Complications of High Dose Rate 3-Dimensional Interstitial Brachytherapy for Lung Cancer

BackgroundThe risk factors for operation complications of high-dose-rate dimensional (3D) interstitial brachytherapy for lung malignant tumors are still unclear. We aimed to provide a reliable reference for the preoperative safety assessment of interstitial brachytherapy. Patients and MethodsWe analyzed the degree and incidence of operational complications in 120 eligible patients with lung carcinoma who underwent computed tomography (CT)-guided HDR interstitial brachytherapy. Univariate and multivariate analyses were used to study the relationships between patient-related factors, tumor-related factors, operation-related factors, and operational complications. ResultsThe most frequent complications of CT-guided HDR interstitial brachytherapy were pneumothorax and hemorrhage. In univariate analysis, smoking, emphysema, distance of implanted needles through the normal lung tissue, number of implanted needle adjustments, and distance of the lesion from the pleura were the risk factors for pneumothorax; the tumor size, distance of the tumor from the pleura, number of implanted needle adjustments, and distance of the implanted needle through the normal lung tissue were risk factors for hemorrhage. In multivariate analysis, the depth of the implanted needle through the normal lung tissue and distance of the lesion from the pleura were independent risk factors for pneumothorax. Tumor size, number of implanted needle adjustments, and distance through normal lung tissue were independent risk factors for hemorrhage. ConclusionThis study provides a reference for the clinical treatment of lung cancer by analyzing the risk factors for complications of interstitial brachytherapy.

The human microbiome: A promising target for lung cancer treatment.

Lung cancer is the leading cause of cancer-related deaths worldwide, and insights into its underlying mechanisms as well as potential therapeutic strategies are urgently needed. The microbiome plays an important role in human health, and is also responsible for the initiation and progression of lung cancer through its induction of inflammatory responses and participation in immune regulation, as well as for its role in the generation of metabolic disorders and genotoxicity. Here, the distribution of human microflora along with its biological functions, the relationship between the microbiome and clinical characteristics, and the role of the microbiome in clinical treatment of lung cancer were comprehensively reviewed. This review provides a basis for the current understanding of lung cancer mechanisms with a focus on the microbiome, and contributes to future decisions on treatment management.

Fbxo45-mediated NP-STEP46 degradation via K6-linked ubiquitination sustains ERK activity in lung cancer.

Lung cancer is one of the most threatening malignant tumors to human health. Epidermal growth factor receptor (EGFR)‐targeted therapy is a common and essential means for the clinical treatment of lung cancer. However, drug resistance has always affected the therapeutic effect and survival rate in non‐small cell lung cancer (NSCLC). Tumor heterogeneity is a significant reason, yielding various drug resistance mechanisms, such as EGFR‐dependent or ‐independent extracellular signal‐regulated kinase 1 and/or 2 (ERK1/2) activation in NSCLC. To examine whether this aberrant activation of ERK1/2 is related to the loss of function of its specific phosphatase, a series of in vitro and in vivo assays were performed. We found that F‐box/SPRY domain‐containing protein 1 (Fbxo45) induces ubiquitination of NP‐STEP46 , an active form of striatal‐enriched protein tyrosine phosphatase, with a K6‐linked poly‐ubiquitin chain. This ubiquitination led to proteasome degradation in the nucleus, which then sustains the aberrant level of phosphorylated‐ERK (pERK) and promotes tumor growth of NSCLC. Fbxo45 silencing can significantly inhibit cell proliferation and tumor growth. Moreover, NSCLC cells with silenced Fbxo45 showed great sensitivity to the EGFR tyrosine kinase inhibitor (TKI) afatinib. Here, we first report this critical pERK maintenance mechanism, which might be independent of the upstream kinase activity in NSCLC. We propose that inhibiting Fbxo45 may combat the issue of drug resistance in NSCLC patients, especially combining with EGFR‐TKI therapy.

Research Progress in Immunotherapy of NSCLC With EGFR-Sensitive Mutations.

Lung cancer is a malignant tumor with high incidence and mortality across the world. The use of immune checkpoint inhibitors for lung cancer has improved the prognosis of some lung cancer patients to a greater extent and provided a new direction for the clinical treatment of lung cancer. Immunotherapy still has limitations in terms of its appropriate population and adverse reactions. Particularly for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation, there has been no major breakthrough in current immunotherapy. Whether immunotherapy can bring new benefits after drug resistance is induced by tyrosine kinase inhibitor-targeted therapy and whether the combination of immunotherapy with other treatments can improve the prognosis remain to be studied in depth. In this article, we provide a detailed review of the relevant characteristics of the tumor microenvironment of NSCLC with EGFR mutation and the current research on immunotherapy for NSCLC with EGFR mutation.

System analysis of FHIT in LUAD and LUSC: The expression, prognosis, gene regulation network, and regulation targets.

Fragile histidine triad (FHIT) is a strong tumor suppressor gene, and cells deficient in FHIT are prone to acquiring cancer-promoting mutations. Due to its location, deletions within FHIT are common in cancer. Over 50% of cancers show loss of FHIT expression. However, to date, expression levels, gene regulatory networks, prognostic value, and target prediction of FHIT in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) have not been fully reported. Therefore, systematic analysis of FHIT expression, gene regulatory network, prognostic value, and targeted prediction in patients with LUAD and LUSC has important guiding significance, providing new therapeutic targets and strategies for clinical treatment of lung cancer to further improve the therapeutic effect of lung cancer. Multiple free online databases were used for the abovementioned analysis in this study, including cBioPortal, TRRUST, Human Protein Atlas, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, and TIMER. FHIT was upregulated in patients with LUAD, and downregulated in patients with LUSC. Genetic alterations of FHIT were found in patients with LUAD (7%), and LUSC (10%). The promoter methylation of FHIT was lower in patients with LUAD and LUSC. FHIT expression significantly correlated with LUSC pathological stages. Furthermore, patients with LUAD and LUSC having low FHIT expression levels had a longer survival than those having high FHIT expression levels. FHIT and its neighboring genes (the 50 most frequently altered neighboring genes of FHIT) functioned in the regulation of protein kinase and DNA binding in patients with LUAD, as well as cell channels and membrane potential in patients with LUSC. Gene ontology enrichment analysis revealed that the functions of FHIT and its neighboring genes are mainly related to disordered domain-specific binding, protein kinase binding, and ion gated channel activity in patients with LUAD, as well as calcium ion binding and intracellular ligand-gated ion channel activity in patients with LUSC. Transcription factor targets of FHIT and its neighboring genes in patients with lung cancer were found: USF1, SOX6, USF2, SIRT1, VHL, LEF1, EZH2, TP53, HDAC1, ESR1, EGR1, YY1, MYC, RELA, NFKB1, and E2F1 in LUAD; and HDAC1, DNMT1, and E2F1 in LUSC. We further explored the FHIT-associated kinase (PRKCQ, AURKB and ATM in LUAD as well as PLK3 in LUSC) and FHIT-associated miRNA targets (MIR-188, MIR-323, and MIR-518A-2 in LUAD). Furthermore, the following genes had the strongest correlation with FHIT expression in patients with lung cancer: NICN1, HEMK1, and BDH2 in LUAD, and ZMAT1, TTC21A, and NICN1 in LUSC. FHIT expression was positively associated with immune cell infiltration (B cell) in patients with LUAD, as well as B cell, CD8 + T, CD4 + T cells, macrophages, and dendritic cells in patients with LUSC. Nevertheless, FHIT expression was negatively associated with CD8 + T cells and neutrophils in patients with LUAD. The expression, gene regulatory network, prognostic value and targeted prediction of FHIT in patients with LUAD and LUSC were systematically analyzed and revealed in this study, thereby laying a foundation for further research on the role of FHIT in LUAD and LUSC occurrence. This study provides new LUAD and LUSC therapeutic targets and prognostic biomarkers as a reference for fundamental and clinical research.

Anaerobic bacteria mediated ‘smart missile’ targeting tumor hypoxic area enhances the therapeutic outcome of lung cancer

Tumor hypoxia is associated with a negative impact on the clinical treatment of lung cancer. Traditional therapeutic agents cannot be efficiently transported to tumor tissues, resulting in a reduced efficacy and serious toxic side effects. Therefore, the aim of this study is to propose a novel drug delivery strategy to solve this problem. The anaerobic Bifidobacterium infantis (B. infantis, Bi) is implanted in the hypoxic area of the tumor as the pre-implanted target. The bacterial antibody decorated nano-drug missile (Ab-DOX-s-s-NPS) actively targets the interior of tumor tissue, and enriches therapeutic drug doxorubicin into tumor hypoxic area through bacterial recruitment. The study confirms that the increased concentration of Ab-DOX-s-s-NPS in tumor tissues through the recruitment of B. infantis plays an excellent anti-tumor effect, while the systemic side effects are significantly reduced, suggesting the good therapeutic effect of the B. infantis-mediated drug delivery strategy against lung cancer. Therefore, this work provides an elegant platform for the in vivo delivery of chemotherapeutic drugs to the hypoxic area of the tumor, representing a novel strategy potentially effective in the treatment of solid tumors.