Dual-Responsive Supramolecular Polymeric Nanomedicine for Self-Cascade Amplified Cancer Immunotherapy.

Insufficient tumor immunogenicity and immune escape from tumors remain common problems in all tumor immunotherapies. Recent studies have shown that pyroptosis, a form of programmed cell death that is accompanied by immune checkpoint inhibitors, can induce effective immunogenic cell death and long-term immune activation. Therapeutic strategies to jointly induce pyroptosis and reverse immunosuppressive tumor microenvironments are promising for cancer immunotherapy. In this regard, a dual-responsive supramolecular polymeric nanomedicine (NCSNPs) to self-cascade amplify the benefits of cancer immunotherapy is designed. The NCSNPs are formulated by ß-cyclodextrin coupling nitric oxide (NO) donor, a pyroptosis activator, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, and self-assembled through host-guest molecular recognition and hydrophobic interaction to obtain nanoparticles. NCSNPs possess excellent tumor accumulation and bioavailability attributed to ingenious supramolecular engineering. The study not only confirms the occurrence of NO-triggered pyroptosis in tumors for the first time but also reverses the immunosuppressive microenvironment in tumor sites via an IDO inhibitor by enhancing the infiltration of cytotoxic T lymphocytes, to achieve remarkable inhibition of tumor proliferation. Thus, this study provides a novel strategy for cancer immunotherapy.

Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines.

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.

Supramolecular Lipid Nanoparticles Based on Host-Guest Recognition: A New Generation Delivery System of mRNA Vaccines For Cancer Immunotherapy.

Dendritic cell (DC) maturation is a crucial process for antigen presentation and the initiation of T cell-mediated immune responses. Toll-like receptors play pivotal roles in stimulating DC maturation and promoting antigen presentation. Here, a novel message RNA (mRNA) cancer vaccine is reported that boosts antitumor efficacy by codelivering an mRNA encoding tumor antigen and a TLR7/8 agonist (R848) to DC using supramolecular lipid nanoparticles (SMLNP) as a delivery platform, in which a new ionizable lipid (N2-3L) remarkably enhances the translation efficiency of mRNA and a ß-cyclodextrin (ß-CD)-modified ionizable lipid (Lip-CD) encapsulates R848. The incorporation of R848 adjuvant into the mRNA vaccine through noncovalent host-guest complexation significantly promotes DC maturation and antigen presentation after vaccination, thus resulting in superior antitumor efficacy in vivo. Moreover, the antitumor efficacy is further boosted synergized with immune checkpoint blockade by potentiating the anticancer capability of cytotoxic T lymphocytes infiltrated in tumor sites. This work indicates that SMLNP shows brilliant potential as next-generation delivery system in the development of mRNA vaccines with high efficacy.

Development of Mannosylated Lipid Nanoparticles for mRNA Cancer Vaccine with High Antigen Presentation Efficiency and Immunomodulatory Capability.

Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNAOVA ) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.

Drug-initiated poly(thiocitc acid) polymer incorporating host-guest interaction for cancer combination chemotherapy.

Combination chemotherapy has shown considerable promise for cancer therapy. However, the hydrophobicity of chemotherapeutic agents and the difficulties of precise drug co-administration severely hinder the development of combination chemotherapy. Herein, we develop a polymeric drug delivery system (D-PTA-CD) to provide robust loading capacity, glutathione-responsive drug release, and precise combination therapy. The vehicle is prepared based on poly(thioctic acid) (PTA) polymers using DM1, a chemotherapeutic agent, as the initiator to endow the vehicle with cancer-inhibiting activity. ß-cyclodextrins are incorporated into the side chains to enhance drug loading capacity via host-guest interactions. Attributing to the sufficient disulfide bond on the backbone, D-PTA-CD exhibits accelerated drug release triggered by elevated glutathione levels. Doxorubicin (DOX) and camptothecin (CPT) are encapsulated by D-PTA-CD to afford the combination chemotherapy nanoparticles (NP), DOX-NP, and CPT-NP, respectively, which exhibit significant synergetic anti-cancer effects, highlighting the enormous potential of D-PTA-CD as a versatile drug delivery platform for cancer combination chemotherapy.

Separation of benzene and toluene associated with vapochromic behaviors by hybrid[4]arene-based co-crystals.

The combination of macrocyclic chemistry with co-crystal engineering has promoted the development of materials with vapochromic behaviors in supramolecular science. Herein, we develop a macrocycle co-crystal based on hybrid[4]arene and 1,2,4,5-tetracyanobenzene that is able to construct vapochromic materials. After the capture of benzene and toluene vapors, activated hybrid[4]arene-based co-crystal forms new structures, accompanied by color changes from brown to yellow. However, when hybrid[4]arene-based co-crystal captures cyclohexane and pyridine, neither structures nor colors change. Interestingly, hybrid[4]arene-based co-crystal can separate benzene from a benzene/cyclohexane equal-volume mixture and allow toluene to be removed from a toluene/ pyridine equal-volume mixture with purities reaching 100%. In addition, the process of adsorptive separation can be visually monitored. The selectivity of benzene from a benzene/cyclohexane equal-volume mixture and toluene from a toluene/ pyridine equal-volume mixture is attributed to the different changes in the charge-transfer interaction between hybrid[4]arene and 1,2,4,5-tetracyanobenzene when hybrid[4]arene-based co-crystal captures different vapors. Moreover, hybrid[4]arene-based co-crystal can be reused without losing selectivity and performance. This work constructs a vapochromic material for hydrocarbon separation.

Engineering Clinically Relevant Probiotics with Switchable "Nano-Promoter" and "Nano-Effector" for Precision Tumor Therapy.

Probiotics have the potential as biotherapeutic agents for cancer management in preclinical models and human trials by secreting antineoplastic or immunoregulatory agents in the tumor microenvironment (TME). However, current probiotics lack the ability to dynamically respond to unique TME characteristics, leading to limited therapeutic accuracy and efficacy. Although progress has been made in customizing controllable probiotics through synthetic biology, the engineering process is complex and the predictability of production is relatively low. To address this, here, for the first time, this work adopts pH-dependent peroxidase-like (POD-like) artificial enzymes as both an inducible "nano-promoter" and "nano-effector" to engineer clinically relevant probiotics to achieve switchable control of probiotic therapy. The nanozyme initially serves as an inducible "nano-promoter," generating trace amounts of nonlethal reactive oxygen species (ROS) stress to upregulate acidic metabolites in probiotics. Once metabolites acidify the TME to a threshold, the nanozyme switches to a "nano-effector," producing a great deal of lethal ROS to fight cancer. This approach shows promise in subcutaneous, orthotopic, and colitis-associated colorectal cancer tumors, offering a new methodology for modulating probiotic metabolism in a pathological environment.

Poly(ethyl ethylene phosphate): Overcoming the "Polyethylene Glycol Dilemma" for Cancer Immunotherapy and mRNA Vaccination.

Polyethylene glycol conjugation (PEGylation) is the most successful strategy to promote the stability, pharmacokinetics, and efficacy of therapeutics; however, anti-PEG antibodies induced by repeated treatments raise serious concerns about the future of PEGylated therapeutics. In order to solve the "PEG dilemma", polymers with excellent water solubility and biocompatibility are urgently desired to attenuate the generation of anti-PEG antibodies. Here, poly(ethyl ethylene phosphate) (PEEP) with excellent degradability and stealth effects is used as an alternative to PEG to overcome the "PEG dilemma". PEEPylated liposomes exhibit lower immunogenicity and generate negligible anti-PEEP antibodies (IgM and IgG) after repeated treatments. In vivo studies confirm that PEEPylated liposomes loaded with oxaliplatin (PEEPlipo@OxPt) show better pharmacokinetics compared to PEGlipo@OxPt, and they exhibit potent antitumor performances, which can be further promoted with checkpoint blockade immunotherapy. In addition, PEEPylated lipid nanoparticle is also used to develop an mRNA vaccine with the ability to evoke a potent antigen-specific T cell response and achieve excellent antitumor efficacy. PEEP shows promising potentials in the development of next-generation nanomedicines and vaccines with higher safety and efficacy.

Fabrication of An Immunostimulatory Supramolecular Nanomedicine for Potent Cancer Chemoimmunotherapy.

Chemoimmunotherapy can boost strong antitumor immune responses by triggering immunogenic cell death (ICD), which highlights a promising prospect in clinical applications. However, current chemoimmunotherapy shows limited efficacy due to the low delivery efficiency and insufficient immunogenicity of available chemotherapeutic drugs. A supramolecular polymeric nanomedicine (Pt-Tu@NP) is herein reported using cucurbit[7]uril-based host-guest recognition and noncovalent self-assembly. Pt-Tu@NPs have excellent biodistribution and strongly evoke the endoplasmic reticulum stress-mediated ICD of tumor cells, triggering potent antitumor immune responses by promoting dendritic cell (DC) maturation and cytotoxic T cell infiltration. The coordinated butyrate promotes a positive feedback regulation between DCs and CD8+ T cells. Pt-Tu@NPs stimulate immune cold tumors into hot ones, working in synergy with an immune checkpoint blockade to effectively suppress tumor growth and metastasis, which suggests a promising approach for cancer chemoimmunotherapy.

Supramolecular Biomaterials for Cancer Immunotherapy.

Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with feeble immune responses and serious adverse effects still cannot be neglected due to the complicated multifactorial etiology and pathologic microenvironment in tumors. The rapid development of nanomedical science and material science has facilitated the advanced progress of engineering biomaterials to tackle critical issues. The supramolecular biomaterials with flexible and modular structures have exhibited unparalleled advantages of high cargo-loading efficiency, excellent biocompatibility, and diversiform immunomodulatory activity, thereby providing a powerful weapon for cancer immunotherapy. In past decades, supramolecular biomaterials were extensively explored as versatile delivery platforms for immunotherapeutic agents or designed to interact with the key moleculars in immune system in a precise and controllable manner. In this review, we focused on the crucial role of supramolecular biomaterials in the modulation of pivotal steps during tumor immunotherapy, including antigen delivery and presentation, T lymphocyte activation, tumor-associated macrophage elimination and repolarization, and myeloid-derived suppressor cell depletion. Based on extensive research, we explored the current limitations and development prospects of supramolecular biomaterials in cancer immunotherapy.

Supramolecular Modulation of Tumor Microenvironment through Pillar[5]arene-Based Host-Guest Recognition to Synergize Cancer Immunotherapy.

Despite the tremendous breakthrough of immunotherapy, the low response rate and resistance of immune checkpoint inhibitors (ICIs) toward solid tumors occur frequently. A highly hypoxic tumor microenvironment (TME) provides tumor cells with high concentrations of HIF-1α and polyamines to evade immune cell destruction. Reprogramming of an immunogenic TME has exhibited a brilliant future to boost immunotherapeutic performances. Herein, a supramolecular nanomedicine (TAPP) is developed on the basis of host-guest molecular recognition and metal coordination, showing the capability to remodel the immunosuppressive TME. Tamoxifen (Tmx) and Fe3+ are encapsulated into TAPP to achieve the combination of chemotherapy and chemodynamic therapy (CDT). Tmx directly downregulates HIF-1α, and a pillar[5]arene-based macrocyclic host successfully eliminates polyamines in tumors. Enhanced immunogenic cell death is achieved by Tmx and Fe3+, and the therapeutic efficacy is further synergized by immune checkpoint blockade (ICB) therapy. This supramolecular reprogramming modality encourages cytotoxic T lymphocyte infiltration, achieving pre-eminent immune response and long-term tumor suppression.

Drug-eluting beads bronchial arterial chemoembolization vs. conventional bronchial arterial chemoembolization in the treatment of advanced non-small cell lung cancer.

Purpose: To compare the effectiveness and safety of drug-eluting bead bronchial artery chemoembolization (DEB-BACE) with conventional bronchial artery chemoembolization (cBACE) and provide a novel treatment option for advanced non-small cell lung cancer (NSCLC). Methods: Patients with advanced NSCLC underwent DEB-BACE or cBACE and were screened retrospectively. Progression-free survival (PFS) and overall survival (OS) were the primary outcome indicators, while technical success rate, objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were the secondary ones. Results: A total of 41 patients were enrolled in the study, 12 in the DEB-BACE group and 29 in the cBACE group, according to the treatment regimen. No patient achieved complete response. Eighteen patients achieved partial response (9 in each group), 15 patients achieved stable disease (3 in the DEB-BACE group and 12 in the cBACE group), and eight patients achieved progressive disease (all in the cBACE group) when treated for 2 months. The overall ORR and DCR were 43.9% (18/41) and 80.5% (33/41), respectively. ORR and DCR in the DEB-BACE group were 50.0% (9/12) and 100.0% (12/12), respectively, while ORR and DCR in the cBACE group were 31.0% (9/29) and 72.4% (21/29), respectively. Compared to cBACE, the ORR and DCR of DEB-BACE were significantly improved (p < 0.05). The median PFS was better in the DEB-BACE group than in the cBACE group (6.95 months vs. 3.20 months, respectively, Hazard Ratio [HR] = 0.416; p = 0.005). Furthermore, the median OS was significantly better in the DEB-BACE group than in the cBACE group (28.5 months vs. 22.5 months, respectively, HR = 0.316; p = 0.020). Conclusion: DEB-BACE has a good safety and therapeutic profile in advanced NSCLC and is superior to cBACE. DEB-BACE can be used as an alternative treatment option for advanced NSCLC, even in elderly patients.

Lymph node-targeting adjuvant/neoantigen-codelivering vaccines for combination glioblastoma radioimmunotherapy.

Glioblastoma multiforme (GBM) is the most common and lethal type of adult brain cancer. Current GBM standard of care, including radiotherapy, often ends up with cancer recurrence, resulting in limited long-term survival benefits for GBM patients. Immunotherapy, such as immune checkpoint blockade (ICB), has thus far shown limited clinical benefit for GBM patients. Therapeutic vaccines hold great potential to elicit anti-cancer adaptive immunity, which can be synergistically combined with ICB and radiotherapy. Peptide vaccines are attractive for their ease of manufacturing and stability, but their therapeutic efficacy has been limited due to poor vaccine co-delivery and the limited ability of monovalent antigen vaccines to prevent tumor immune evasion. To address these challenges, here, we report GBM radioimmunotherapy that combines radiotherapy, ICB, and multivalent lymph-node-targeting adjuvant/antigen-codelivering albumin-binding vaccines (AAco-AlbiVax). Specifically, to codeliver peptide neoantigens and adjuvant CpG to lymph nodes (LNs), we developed AAco-AlbiVax based on a Y-shaped DNA scaffold that was site-specifically conjugated with CpG, peptide neoantigens, and albumin-binding maleimide-modified Evans blue derivative (MEB). As a result, these vaccines elicited antitumor immunity including neoantigen-specific CD8+ T cell responses in mice. In orthotopic GBM mice, the combination of AAco-AlbiVax, ICB, and fractionated radiation enhanced GBM therapeutic efficacy. However, radioimmunotherapy only trended more efficacious over radiotherapy alone. Taken together, these studies underscore the great potential of radioimmunotherapy for GBM, and future optimization of treatment dosing and scheduling would improve the therapeutic efficacy.

Dynamically assembled nanomedicine based on host-guest molecular recognition for NIR laser-excited chemotherapy and phototheranostics.

Nanomedicines combining multimodal therapeutic modalities supply opportunities to eliminate tumors in a safe and efficient manner. However, the rigid encapsulation and covalent conjugation of different therapeutic reagents suffer from the complicated preparation process, premature drug leakage and severe adverse events. Herein, we report a self-enhanced supramolecular nanomedicine (SND) based on the host-guest molecular recognition between ß-cyclodextrin (ß-CD) and camptothecin (CPT) for trimodal synergistic chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT) using a single 670 nm near-infrared (NIR) laser. Thioketal bond and polyethylene glycol (PEG) segment are introduced into the structure of CPT-tk-PEG prodrug, thus the premature release of CPT is efficiently inhibited and the specific drug release is realized at tumor site where singlet oxygen (1O2)-generated PDT is performed. A boron dipyrromethene (BODIPY) theranostic agent is anchored onto ß-CD, endowing SND with capabilities of fluorescence imaging, PDT and PTT. Benefiting from the supramolecular assembly, not only the solubility of CPT is improved by 40 times, but also the blood circulation time and tumor accumulation of SND are greatly promoted. In vivo, SND can effectively induce the immunogenic cell death (ICD) of tumor cells, thus performing prominent inhibition against both primary and distal tumors, and even anti-metastasis effect against liver without causing obvious systemic toxicity. STATEMENT OF SIGNIFICANCE: Although nanomedicines supply opportunities to eliminate tumors in an efficient manner, they usually suffer from premature drug leakage, complicated preparation process and severe side effects owing to the rigid encapsulation or covalent conjugation. Based on the host-guest molecular recognition, we developed a self-enhanced SND for synergistic chemotherapy, photodynamic therapy and photothermal therapy. Introduction of thioketal bond in CPT prodrug avoided the premature drug release, and the specific drug release was realized in the tumor cells. Profiting from the facile supramolecular assembly strategy, SND not only displayed a primary anticancer efficacy with a low systemic toxicity, but also efficiently inhibited the growth of distal tumors, contributing a vaccine-like function to eradicate the recurrent and metastatic tumors.

Recent Progress of Supramolecular Chemotherapy Based on Host-Guest Interactions.

Chemotherapy is widely recognized as an effective approach for treating cancer due to its ability to eliminate cancer cells using chemotherapeutic drugs. However, traditional chemotherapy suffers from various drawbacks, including limited solubility and stability of drugs, severe side effects, low bioavailability, drug resistance, and challenges in tracking treatment efficacy. These limitations greatly hinder its widespread clinical application. In contrast, supramolecular chemotherapy, which relies on host-guest interactions, presents a promising alternative by offering highly efficient and minimally toxic anticancer drug delivery. In this review, an overview of recent advancements in supramolecular chemotherapy based on host-guest interactions is provided. The significant role it plays in guiding cancer therapy is emphasized. Drawing on a wealth of cutting-edge research, herein, a timely and valuable resource for individuals interested in the field of supramolecular chemotherapy or cancer therapy, is presented. Furthermore, this review contributes to the progression of the field of supramolecular chemotherapy toward clinical application.

A possible combined appraisal pattern: predicting the prognosis of patients after esophagectomy.

OBJECTIVE: To investigate the predictive merit of combined preoperative nutritional condition and systemic inflammation on the prognosis of patients receiving esophagectomy, with the assessment of model construction to extract a multidisciplinary phantom having clinical relevance and suitability. METHODS: The software of R 4.1.2 was utilized to acquire the survival optimal truncation value and the confusion matrix of survival for the continuity variables. SPSS Statistics 26 was employed to analyze the correlation of parameters, where including t-test, ANOVA and the nonparametric rank sum test shall. Pearson chi-square test was used for categorical variables. The survival curve was retrieved by Kaplan-Meier method. Univariate analysis of overall survival (OS) was performed through log-rank test. Cox analysis was for survival analyze. The performance of the prediction phantom through the area under curve (AUC) of receiver operating characteristic curve (ROC), decision curve analysis (DCA), nomogram and clinical impact curve (CIC) was plotted by R. RESULTS: The AUC value of albumin-globulin score and skeletal muscle index (CAS) is markedly superior. Patients with diminished AGS and greater SMI were associated with improved overall survival (OS) and recurrence-free survival (RFS) (P < 0.01). The CAS composite evaluation model was calibrated with better accuracy and predictive performance. The DCA and CIC indicated a relatively higher net revenue for the prediction model. CONCLUSIONS: The prediction model including the CAS score has excellent accuracy, a high net revenue, and favorable prediction function.

Self-Assembly of Selenium-Doped Carbon Quantum Dots as Antioxidants for Hepatic Ischemia-Reperfusion Injury Management.

Hepatic ischemia-reperfusion injury (HIRI) is a critical complication after liver surgery that negatively affects surgical outcomes of patients with the end-stage liver-related disease. Reactive oxygen species (ROS) are responsible for the development of ischemia-reperfusion injury and eventually lead to hepatic dysfunction. Selenium-doped carbon quantum dots (Se-CQDs) with an excellent redox-responsive property can effectively scavenge ROS and protect cells from oxidation. However, the accumulation of Se-CQDs in the liver is extremely low. To address this concern, the fabrication of Se-CQDs-lecithin nanoparticles (Se-LEC NPs) is developed through self-assembly mainly driven by the noncovalent interactions. Lecithin acting as the self-assembly building block also makes a pivotal contribution to the therapeutic performance of Se-LEC NPs due to its capability to react with ROS. The fabricated Se-LEC NPs largely accumulate in the liver, effectively scavenge ROS and inhibit the release of inflammatory cytokines, thus exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.

Recent Development of Supramolecular Cancer Theranostics Based on Cyclodextrins: A Review.

With the development of personalized medical demands for precise diagnosis, rational management and effective cancer treatment, supramolecular theranostic systems have received widespread attention due to their reversibly switchable structures, sensitive response to biological stimuli and integration ability for multiple capabilities in a single platform with a programmable fashion. Cyclodextrins (CDs), benefiting from their excellent characteristics, such as non-toxicity, easy modification, unique host-guest properties, good biocompatibility, etc., as building blocks, serve as an all-purpose strategy for the fabrication of a supramolecular cancer theranostics nanodevice that is capable of biosafety, controllability, functionality and programmability. This review focuses on the supramolecular systems of CD-bioimaging probes, CD-drugs, CD-genes, CD-proteins, CD-photosensitizers and CD-photothermal agents as well as multicomponent cooperation systems with regards to building a nanodevice with functions of diagnosis and (or) therapeutics of cancer treatment. By introducing several state-of-the-art examples, emphasis will be placed on the design of various functional modules, the supramolecular interaction strategies under the fantastic topological structures and the hidden "bridge" between their structures and therapeutic efficacy, aiming for further comprehension of the important role of a cyclodextrin-based nanoplatform in advancing supramolecular cancer theranostics.

Non­diagnostic electromagnetic navigation bronchoscopy biopsy: Predictive factors and final diagnoses.

The present study aimed to explore the final diagnosis of pulmonary nodules with an initial non-diagnostic result on electromagnetic navigation bronchoscopy (ENB) biopsy and the predictive factors for a non-diagnostic result. A total of 198 nodules from 194 patients that were suspected to be malignant tumors were included in the present study. The initial biopsy pathology results were divided into two groups: The diagnostic group and the non-diagnostic group. The diagnostic group was defined as a successful initial biopsy to obtain a diagnosis, including malignant and benign diagnoses. The non-diagnostic group was defined as a non-specific benign diagnosis, normal lung tissue or an unsuccessful biopsy. Among the 198 nodules, 139 (70.2%) were in the diagnostic group and 59 (29.8%) were in the non-diagnostic group. Predictive factors for a non-diagnostic biopsy included nodule size ≤1.5 cm [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.03-4.09], non-solid nodules (OR, 2.71; 95% CI, 1.33-5.64) and nodules in the left lung (OR, 2.50; 95% CI, 1.27-4.92). Of the 59 non-diagnostic biopsies, 46 were finally confirmed to be malignant by surgery. Notably, non-diagnostic biopsies with non-solid nodules (OR, 7.64; 95% CI, 3.11-18.76) were more likely to be malignant. In conclusion, the predictive factors for a non-diagnostic biopsy were nodule size ≤1.5 cm and non-solid nodules. It was not rare for patients to finally be diagnosed with a malignancy in the non-diagnostic group. Therefore, care should be taken when the results of an ENB are non-diagnostic to prevent misdiagnosis.

TEDC2 correlated with prognosis and immune microenvironment in lung adenocarcinoma.

Tubulin epsilon and delta complex 2 (TEDC2) is a protein coding gene whose functions are poorly identified yet. This study aimed to identify the role of TEDC2 in prognosis and immune microenvironment of lung adenocarcinoma (LUAD). Through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, the mRNA expression of TEDC2 was upregulated in LUAD tissues compared to normal tissues. The protein level of TEDC2 was also higher in LUAD in the Human Protein Atlas. The receiver operating characteristic (ROC) curve showed that high TEDC2 level could distinguish LUAD patients from normal subjects. In addition, the impact of TEDC2 expression on prognosis was evaluated by Kaplan-Meier and Cox regression analyses, and the results suggested that high TEDC2 expression was significantly associated with poor prognosis and was the independent prognostic factor in LUAD. GO and KEGG pathway analyses indicated the co-expressed genes of TEDC2 were mainly related to mitotic cell cycle processes. Importantly, high expression of TEDC2 indicated low infiltration of immune cells, especially dendritic cells and B cells. TEDC2 was also positively correlated with immune checkpoints such as PDCD1, LAG3 and CD276. Taken together, this study preliminarily revealed the clinical significance of TEDC2 in LUAD and provided novel insights into the role of TEDC2 in immune microenvironment.