Chemoradiotherapy combined with immunotherapy in stage III non-small cell lung cancer: a systematic review and meta-analysis of efficacy and safety outcomes.

Background Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies. Methods We searched all the relevant studies in PubMed, Embase and Cochrane Library databases. We also reviewed abstracts of relevant conferences, to prevent omissions. The meta-analysis was performed using Stata version 16.0. Results Chemoradiotherapy combined with immunotherapy can improve PFS (HR: 0.60, 95%CI :0.55-0.60) and OS (HR: 0.59, 95%CI :0.53-0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5%-52.7%) and 71.3% (95% CI, 67.3%-75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95%CI, 51.0%-70.3%) and 77.4% (95%CI, 73.2%-81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95%CI, 31.3%-39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95%CI, 31.9%-51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95%CI, 5.0%-8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95%CI, 3.1%-6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95%CI, 2.9%-7.3%). Conclusions Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit.

Aspirin enhances the therapeutic efficacy of cisplatin in oesophageal squamous cell carcinoma by inhibition of putative cancer stem cells.

BACKGROUND: Cancer stem cells (CSCs) are related to the patient's prognosis, recurrence and therapy resistance in oesophageal squamous cell carcinoma (ESCC). Although increasing evidence suggests that aspirin (acetylsalicylic acid, ASA) could lower the incidence and improve the prognosis of ESCC, the mechanism(s) remains to be fully understood. METHODS: We investigated the role of ASA in chemotherapy/chemoprevention in human ESCC cell lines and an N-nitrosomethylbenzylamine-induced rat ESCC carcinogenesis model. The effects of combined treatment with ASA/cisplatin on ESCC cell lines were examined in vitro and in vivo. Sphere-forming cells enriched with putative CSCs (pCSCs) were used to investigate the effect of ASA in CSCs. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed to determine the alterations in chromatin accessibility caused by ASA in ESCC cells. RESULTS: ASA inhibits the CSC properties and enhances cisplatin treatment in human ESCC cells. ATAC-seq indicates that ASA treatment results in remarkable epigenetic alterations on chromatin in ESCC cells, especially their pCSCs, through the modification of histone acetylation levels. The epigenetic changes activate Bim expression and promote cell death in CSCs of ESCC. Furthermore, ASA prevents the carcinogenesis of NMBzA-induced ESCC in the rat model. CONCLUSIONS: ASA could be a potential chemotherapeutic adjuvant and chemopreventive drug for ESCC treatment.

Radiosensitivity nomogram based on circulating neutrophils in thoracic cancer.

AIM: To evaluate the prediction ability of neutrophils and develop a nomogram on radiosensitivity in thoracic cancer patients. METHODS: We retrospectively reviewed 398 lung and esophageal cancers patients who received external-beam radiotherapy or concurrent chemoradiotherapy as first-line therapy. RESULTS: Logistic regression model showed that patients with low levels of neutrophil counts and/or TGF-ß1 exhibited better radiation sensitivity. Furthermore, a nomogram was created to predict radiotherapy sensitivity. The combination of neutrophil count and TGF-ß1 level was an independent prognostic factor for lung and esophageal cancers patients. CONCLUSION: The study developed a nomogram based on the levels of circulating neutrophils and TGF-ß1. The prediction value in radiosensitivity and protumorigenic effect of neutrophils might owe to N2 tumor-associated neutrophils.

A new insight into the thermodynamical criterion for the preparation of semiconductor and metal nanocrystals using a polymerized complexing method.

This work reports the intrinsic thermodynamical criterion for the preparation of metal and semiconductor nanocrystals using a polymerized complexing method. The basic principle of this method is the formation of a polymerized complexing structure between mono-, binary-, or ternary-metallic ions and bonding agents in aqueous or ethylene glycol solutions by evaporation of the solvents. Heat treatment of the complexing structure under N2 atmosphere produces H2 and CH4 gases, which can reduce the oxide crystalline nuclei to semiconductor and metallic nanocrystals. Experimental results show that Te, CdTe, Ag2Te, CuTe, NiTe1.5, CoTe1.5, Bi2Te3, Sb2Te3, Bi-Sb, In2Te3, Ni2.9SnTe2, CuGaTe2, and CuInS2 semiconductors and Bi, Sb, Ag, Cu, and Ni metallic nanocrystals can be prepared by this method. Transmission electron microscopy observations show that the obtained Bi, Ag2Te, Bi2Te3, Sb2Te3, CdTe, and NiTe1.5 nanocrystals have grain sizes in the nanometer range. The types of metallic and semiconductor phase that can be obtained by this method are explained by the thermodynamical criterion based on calculations of the Gibbs free energy and electrode potential. It is proposed that the crystalline phase of the final product is controlled by the change of the Gibbs free energies of the reactions of the metal oxide with reducing gases and the metal oxide redox electrode potentials, not the metal redox standard electrode potentials and electronegativities of the elements. Furthermore, a prediction is presented for the preparation of other kinds of binary and ternary compound based on the thermodynamical criterion. Our results provide new insight into facile and green preparation of semiconductor and metal nanocrystals.

The effect of granulocyte and granulocyte-macrophage colony stimulating factors on tumor promotion.

GM-CSF and G-CSF are capable to regulate the maturation of undifferentiated multipotent stem cells into mature granulocytes, macrophages and T cells in the bone marrow. Thereby, clinicians correct neutropenia induced by chemotherapy or radiation routinely with recombinant G- or GM-CSFs in clinical practice. However, relevant studies found that treatment for cancer patients with adjuvant G-/GM-CSF would occasionally enhance the progression of tumors. Besides, constitutive production of G-CSF or GM-CSF by lung cancer cells could stimulate the growth or the invasion of tumor and result in protecting the tumor against unfavorable environment. These findings convinced researchers that G-/GM-CSF overexpression has a positive effect on malignant tumor progression. The purpose of this article was to explore the most recent research and the mechanisms of GM-CSF and G-CSF-induced tumor promotion and their clinical therapeutic applications.

The relationship between vasculogenic mimicry and epithelial-mesenchymal transitions.

Vasculogenic mimicry (VM) is a vascular-like structure which can mimic the embryonic vascular network pattern to nourish the tumour tissue. As a unique perfusion way, VM is correlated with tumour progression, invasion, metastasis and lower 5-year survival rate. Notably, epithelial-mesenchymal transition (EMT) regulators and EMT-related transcription factors are highly up-regulated in VM-forming tumour cells, which demonstrated that EMT may play a crucial role in VM formation. Therefore, the up-regulation of EMT-associated adhesion molecules and other factors can also make a contribution in VM-forming process. Depending on these discoveries, VM and EMT can be utilized as therapeutic target strategies for anticancer therapy. The purpose of this article is to explore the advance research in the relationship of EMT and VM and their corresponding mechanisms in tumorigenesis effect.

Vasculogenic mimicry and tumor metastasis.

Vasculogenic mimicry (VM), a microvascular channel made up of nonendothelial cells, has been accepted as a new model of neovascularization in aggressive tumors, owning to the specific capacity of malignant cells to form vessel-like networks which provide sufficient blood supply for tumor growth. Multiple molecular mechanisms, especially vascular endothelial (VE)-cadherin, erythropoietin-producing hepatocellular receptor A2 (EphA2), phosphatidyl inositol 3-kinase (PI3K), matrix metalloproteinases (MMPs), vascular endothelial growth factor receptor (VEGFR1), and hypoxia inducible factor (HIF)-1a, have been reported to participate in VM formation which is associated with tumor migration and invasion. In addition, hypoxia, cancer stem cells (CSCs) and epithelial-mesenehymal transition (EMT) are regarded as significant factors in VM formation and tumor metastasis. Due to the important effects of VM on tumor progression, a review was carried out in the present study, to synthetically analyze the relationship between VM and tumor metastasis.

The management of patients with esophageal cancer and coronary artery stenosis undergoing radiotherapy or concurrent chemoradiotherapy: a single-center experience.

PURPOSE: The incidence of esophageal cancer (EC) patients with coronary artery stenosis presents particular challenges. The aim of this retrospective study was to evaluate the efficiency of management on patients with both diseases treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS: Fifty-three patients with both EC and coronary artery stenosis from June 2009 to August 2012 were retrospectively analyzed. The patients received RT or CCRT with coronary artery stenosis management. Cardiac treatments often prescribed included aspirin, ß-blockers, statins etc. The adverse effects, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: Most of the patients were 40-70 years old. There were 25 patients in the CCRT group and 28 patients in the RT group. The complete response (CR) rate was higher in the patients in the CCRT group than in those in the RT group (48.0 vs 21.4%; p=0.041). The median PFS was 15.9 months in the CCRT group and 11.6 months in the RT group (p=0.025). OS was 22.4 months in the CCRT group and 15.8 months in the RT group (p=0.013). Though adverse effects were less in the RT group, no significance differences in grade 3-4 toxicity were observed. CONCLUSION: With the appropriate of coronary artery stenosis management, RT and CCRT were both tolerable and effective in EC patients with coronary artery stenosis.

Nanoporous nonwoven fibril-like morphology by cooperative self-assembly of poly(ethylene oxide)-block-poly(ethyl acrylate)-block-polystyrene and phenolic resin.

Cooperative self-assembly of block copolymers with (in)organic precursors effectively generates ordered nanoporous films, but the porosity is typically limited by the need for a continuous (in)organic phase. Here, a network of homogeneous fibrous nanostructures (≈20 nm diameter cylinders) having high porosity (≈ 60%) is fabricated by cooperative self-assembly of a phenolic resin oligomer (resol) with a novel, nonfrustrated, ABC amphiphilic triblock copolymer template, poly(ethylene oxide)-block-poly(ethyl acrylate)-block-polystyrene (PEO-b-PEA-b-PS), via a thermally induced self-assembly process. Due to the high glass transition temperature (Tg) of the PS segments, the self-assembly behavior is kinetically hindered as a result of competing effects associated with the ordering of the self-assembled system and the cross-linking of resol that suppresses segmental mobility. The balance in these competing processes reproducibly yields a disordered fibril network with a uniform fibril diameter. This nonequilibrium morphology is dependent on the PEO-b-PEA-b-PS to resol ratio with an evolution from a relatively open fibrous structure to an apparent poorly ordered mixed lamellae-cylinder morphology. Pyrolysis of these former films at elevated temperatures yields a highly porous carbon film with the fibril morphology preserved through the carbonization process. These results illustrate a simple method to fabricate thin films and coatings with a well-defined fiber network that could be promising materials for energy and separation applications.

Ground movement analysis based on stochastic medium theory.

In order to calculate the ground movement induced by displacement piles driven into horizontal layered strata, an axisymmetric model was built and then the vertical and horizontal ground movement functions were deduced using stochastic medium theory. Results show that the vertical ground movement obeys normal distribution function, while the horizontal ground movement is an exponential function. Utilizing field measured data, parameters of these functions can be obtained by back analysis, and an example was employed to verify this model. Result shows that stochastic medium theory is suitable for calculating the ground movement in pile driving, and there is no need to consider the constitutive model of soil or contact between pile and soil. This method is applicable in practice.

Repair Effect of Umbilical Cord Mesenchymal Stem Cells Embedded in Hydrogel on Mouse Insulinoma 6 Cells Injured by Streptozotocin.

Umbilical cord mesenchymal stem cells (UC-MSCs) possess the capabilities of differentiation and immune modulation, which endow them with therapeutic potential in the treatment of type 2 diabetes mellitus (T2DM). In this study, to investigate the repair mechanism of UC-MSCs in hydrogel on pancreatic ß-cells in diabetes, mouse insulinoma 6 (MIN-6) cells damaged by streptozotocin (STZ) in vitro were used in co-culture with UC-MSCs in hydrogel (UC-MSCs + hydrogel). It was found that UC-MSCs + hydrogel had a significant repair effect on injured MIN-6 cells, which was better than the use of UC-MSCs alone (without hydrogel). After repair, the expression of superoxide dismutase (SOD) and catalase (CAT) as well as the total antioxidant capacity (T-AOC) of the repaired MIN-6 cells were increased, effectively reducing the oxidative stress caused by STZ. In addition, UC-MSCs + hydrogel were able to curb the inflammatory response by promoting the expression of anti-inflammatory factor IL-10 and reducing inflammatory factor IL-1ß. In addition, the expression of both nuclear antigen Ki67 for cell proliferation and insulin-related genes such as Pdx1 and MafA was increased in the repaired MIN-6 cells by UC-MSCs + hydrogel, suggesting that the repair effect promotes the proliferation of the injured MIN-6 cells. Compared with the use of UC-MSCs alone, UC-MSCs + hydrogel exhibit superior antioxidant stress resistance against injured MIN-6 cells, better proliferation effects and a longer survival time of UC-MSCs because the porous structure and hydrophilic properties of the hydrogel could affect the growth of cells and slow down their metabolic activities, resulting in a better repair effect on the injured MIN-6 cells.

Antitumour effects of artesunate via cell cycle checkpoint controls in human oesophageal squamous carcinoma cells.

Artesunate (ART), an effective antimalarial semisynthetic derivative of artemisinin, exhibits antitumour properties, but the mechanism(s) involved remain elusive. In this study, we investigated the antitumour effects of ART on human oesophageal squamous cell carcinoma (ESCC) cell lines. Treatment of ESCC cell lines with ART resulted in the production of excessive reactive oxygen species (ROS) that induced DNA damage, reduced cell proliferation and inhibited clonogenicity via G1-S cell cycle arrest and/or apoptosis in vitro. The administration of ART to nude mice with ESCC cell xenografts inhibited tumour formation in vivo. However, the cytotoxicity of ART strongly differed among the ESCC cell lines tested. Transcriptomic profiling revealed that although the expression of large numbers of genes in ESCC cell lines was affected by ART treatment, these genes could be functionally clustered into pathways involved in regulating cell cycle progression, DNA metabolism and apoptosis. We revealed that p53 and Cdk4/6-p16-Rb cell cycle checkpoint controls were critical determinants required for mediating ART cytotoxicity in ESCC cell lines. Specifically, KYSE30 cells with p53Mut/p16Mut were the most sensitive to ART, KYSE150 and KYSE180 cells with p53Mut/p16Nor exhibited intermediate responses to ART, and Eca109 cells with p53Nor/p16Nor exhibited the most resistance to ATR. Consistently, perturbation of p53 expression using RNA interference (RNAi) and/or Cdk4/6 activity using the inhibitor palbociclib altered ART cytotoxicity in KYSE30 cells. Given that the p53 and Cdk4/6-cyclin D1-p16-Rb genes are commonly mutated in ESCC, our results potentially shed new light on neoadjuvant chemotherapy strategies for ESCC.

An effective two-stage NMBzA-induced rat esophageal tumor model revealing that the FAT-Hippo-YAP1 axis drives the progression of ESCC.

Rat model of N-nitrosomethylbenzylamine (NMBzA)-induced esophageal squamous cell carcinoma (ESCC) is routinely used to study ESCC initiation, progression and new therapeutic strategies. However, the model is time-consuming and malignant tumor incidences are low. Here, we report the usage of multi-kinase inhibitor sorafenib as a tumor promoter to establish an efficient two-stage NMBzA-induced rat ESCC carcinogenesis model, resulting in increments of tumor incidences and shortened tumor formation times. By establishing the model and applying whole-genome sequencing, we discover that benign papillomas and malignant ESCCs harbor most of the "driver" events found in rat ESCCs (e.g. recurrent mutations in Ras family, the Hippo and Notch pathways and histone modifier genes) and the mutational landscapes of rat and human ESCCs overlap extensively. We generate tumor cell lines derived from NMBzA-induced papillomas and ESCCs, showing that papilloma cells retain more characteristics of normal epithelial cells than carcinoma cells, especially their exhibitions of normal rat cell karyotypes and inabilities of forming tumors in immunodeficient mice. Three-dimensional (3-D) organoid cultures and single cell RNA sequencing (scRNA-seq) indicate that, when compared to control- and papilloma-organoids, ESCC-organoids display salient abnormalities at tissue and single-cell levels. Multi-omic analyses indicate that NMBzA-induced rat ESCCs are accompanied by progressive hyperactivations of the FAT-Hippo-YAP1 axis and siRNA or inhibitors of YAP1 block the growth of rat ESCCs. Taken together, these studies provide a framework of using an effective rat ESCC model to investigate multilevel functional genomics of ESCC carcinogenesis, which justify targeting YAP1 as a therapeutic strategy for ESCC.

Establishment of a NIR-based methodology for tracking the blend homogeneity of HTPB propellant slurry in the mixing process.

The hydroxyl-terminated polybutadiene (HTPB) propellants with high level of solid loadings from 80 wt% to 90 wt% consist of aluminum (Al) powder, ammonium perchlorate (AP) and HTPB. The Al/AP/HTPB adhesive system full of solid grains appears high viscosity against flow. Therefore, the mixing is a crucial procedure in the production as it directly affects the structural integrity of the finished product. This work focused on the feasibility of tracking the blend homogeneity of Al/AP/HTPB adhesive system in the mixing process through using the near-infrared (NIR) spectroscopy and orthogonal partial least squares discrimination analysis (OPLS-DA). The OPLS-DA classification models were created by variable selection, spectral pretreatment and latent variables (LVs) optimization. It had been demonstrated that the developed models presented an excellent predictability with the root mean square error of cross-validation (RMSECV) for slurries in Ⅰ, Ⅱ groups of 0.1261 and 0.0789, respectively. Meanwhile, the well-fitted models for slurries in Ⅰ, Ⅱ groups with the squared correlation coefficient (R2) of 0.806 and 0.980, exhibited separately an acceptable predictive capability with the predictive squared correlation coefficient (Q2) > 0.5. Furthermore, Euclidean distance and move block standard deviation (MBSD) as reference methods were used to validate the predictive performance of the developed models with respect to the blend homogeneity of HTPB propellant slurry. The experimental results showed that the terminal time for each batch of slurry reaching to ideal uniformity predicted by Euclidean distance/MBSD and OPLS-DA were both at 26-30 min. Therefore, it had been proved that the method we proposed was a potential tool to monitor the variation of the uniform state of HTPB propellant slurry in the mixing process.

An approach to detecting diphenylamine content and assessing chemical stability of single-base propellants by near-infrared reflectance spectroscopy.

Diphenylamine (DPA) as a stabilizer component plays an important role in maintaining the chemical stability of single-base propellants (SBPs). This work investigated the feasibility of rapidly detecting the content of DPA in SBP by near-infrared reflectance spectroscopy (NIRS). The quantitative NIR model was developed by intervals selection, spectral pretreatment and factor number optimization. The optimal spectral intervals were determined to be 1081 nm âˆ¼ 1280 nm and 1378 nm âˆ¼ 1602 nm based on the characteristic spectral peaks of DPA. By comparing the performance of the developed models with different preprocessing methods, the best preprocessing method was standard normal variate transformation (SNV) + de-trending (Dr) + Smoothing. The optimal number of factors was 6 for DPA model. Partial least squares (PLS) regression was used to establish the calibration models of DPA. For the developed model, the determination coefficients of calibration and prediction (Rc2, Rp2) were 0.9907 and 0.9884, respectively. The root mean square errors of calibration and prediction (RMSEC, RMSEP) were 0.0310 and 0.0342, respectively. The samples in the prediction set were predicted by the developed model, and the average absolute error of the proposed and reference method was only 0.0265. The developed model can be applied in rapid monitor the content of DPA in SBP. In addition, vieille test have demonstrated that the chemical stability of SBP became worse with the decrease of DPA content. The content of DPA contained in the SBP with qualified chemical stability is not less than 0.8753%. Thus, the developed model can be used to judge whether the chemical stability of SBP is qualified or unqualified.

Hedychium flavum flower essential oil: Chemical composition, anti-inflammatory activities and related mechanisms in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Hedychium flavum, an ornamental, edible, and medicinal plant, is extensively cultivated as a source of aromatic essential oils (EO). Its flower is a traditional Chinese medicine for treating inflammation-related diseases like indigestion, diarrhea, and stomach pain. In particular, H. flavum flower EO has been used in cosmetics and as an aromatic stomachic to treat chronic gastritis in China. AIM OF THE STUDY: This research aimed to analyze H. flavum flower EO's chemical composition and explore its anti-inflammatory activities and related mechanisms in vitro and in vivo. MATERIALS AND METHODS: EO's chemical composition was determined by GC-FID/MS analysis. For in vitro test, the anti-inflammatory activity of EO was demonstrated by measuring the LPS-induced release of NO, PGE2, IL-1ß, TNF-α, and IL-6 in RAW264.7 macrophages, and then its related mechanisms were explored using qRT-PCR, western blot, and immunofluorescent staining analysis. Next, EO's in vivo anti-inflammatory potential was further evaluated using a xylene-induced ear edema model, in which ear swelling and TNF-α, IL-6, and IL-1ß levels in serum and tissue were examined. RESULTS: The main components of EO were ß-pinene (20.2%), α-pinene (9.3%), α-phellandrene (8.3%), 1,8-cineole (7.1%), E-nerolidol (5.4%), limonene (4.4%), borneol (4.1%), and ß-caryophyllene (3.7%). For the anti-inflammatory activities in vitro, EO dramatically reduced the LPS-stimulated NO and PGE2 release by suppressing the mRNA and protein expression of iNOS and COX-2. Meanwhile, it remarkably decreased IL-6, TNF-α, and IL-1ß production by inhibiting their mRNA levels. Related mechanism studies indicated that it not only inhibited IκBα phosphorylation and degradation, leading to blockade of NF-κB nuclear transfer but also suppressed MAPKs (ERK, p38, and JNK) phosphorylation in LPS-stimulated RAW264.7 cells. Further in vivo assay showed that EO ameliorated xylene-induced ear edema in mice and reduced TNF-α, IL-6, and IL-1ß levels in serum and tissue. CONCLUSIONS: H. flavum EO exerted significant anti-inflammatory activity in vivo and in vitro, and its mechanism of action is related to the inhibition of MAPK and NF-κB activation. Thus, H. flavum EO could be considered a novel and promising anti-inflammatory agent and possess high potential for utilization in the pharmaceutical field.

Advances in anti-tumor based on various anaerobic bacteria and their derivatives as drug vehicles.

Cancer therapies, such as chemotherapy and radiotherapy, are often unsatisfactory due to several limitations, including drug resistance, inability to cross biological barriers, and toxic side effects on the body. These drawbacks underscore the need for alternative treatments that can overcome these challenges and provide more effective and safer options for cancer patients. In recent years, the use of live bacteria, engineered bacteria, or bacterial derivatives to deliver antitumor drugs to specific tumor sites for controlled release has emerged as a promising therapeutic tool. This approach offers several advantages over traditional cancer therapies, including targeted drug delivery and reduced toxicity to healthy tissues. Ongoing research in this field holds great potential for further developing more efficient and personalized cancer therapies, such as E. coli, Salmonella, Listeria, and bacterial derivatives like outer membrane vesicles (OMVs), which can serve as vehicles for drugs, therapeutic proteins, or antigens. In this review, we describe the advances, challenges, and future directions of research on using live bacteria or OMVs as carriers or components derived from bacteria of delivery systems for cancer therapy.

Serum ferritin level is an effective prognostic factor for lung cancer immunotherapy.

Immunotherapy of lung cancer has achieved promising clinical results. However, it is urgent to develop predictive biomarkers for effective immunotherapy. While ferroptosis plays a critical role in immunotherapy efficacy, ferritin is an important regulatory factor. We, therefore, hypothesize that basal serum ferritin levels before immunotherapy and their corresponding changes during immunotherapy can be useful predictors of immunotherapy response in patients with lung cancer. We measured serum ferritin levels in 107 patients with lung cancer before and during immune checkpoint blockade treatments and studied the correlation between ferritin levels, response rate, and survival. Moreover, the correlation between basal ferritin and PD-L1 expression, tumor stages and pathological types was also analyzed. Patients with lower basal serum ferritin levels before immunotherapy had longer progression-free survival (PFS) (median 7 vs 4 months, P = .023) and higher disease control rate (DCR) (X2 = 4.837, P = .028), those with downregulated serum ferritin levels during immunotherapy correlated with longer PFS (median 9.5 vs 4 months, P < .001) and higher DCR (X2 = 6.475, P = .011). However, the "integrated factor", which was calculated as the combination of lower basal serum ferritin levels before immunotherapy and downregulated serum ferritin levels during immunotherapy, correlated with prolonged PFS (P < .001). Multivariate analyses revealed that the basal serum ferritin levels before immunotherapy and the corresponding changes during immunotherapy were both strong independent prognostic factors (hazard ratio (HR) = 1.60, P = .041; HR = 2.65, P = .001). These findings suggest that serum ferritin levels can be used as a prognostic biomarker for lung cancer in predicting immunotherapy efficacy.

Ferritin in cancer therapy: A pleiotropic tumoraffin nanocage-based transport.

BACKGROUND: Ferritin, a ubiquitously distributed iron storage protein, can specifically target tumor cells through transferrin receptor 1. Due to its rearrangeable nanocage structure, ferritin can be loaded with anticancer drugs. Combined with amino acid modifications on the outer- and/or inner-spaces of the nanocage, ferritins can be further coupled with antigens, antibodies, and nucleotide sequences. Since ferritin is naturally presented in the human body, when used in vivo, ferritin exhibits good biocompatibility, and no immunogenic response occurs. These makes ferritin an ideal nanocarrier which shows broad application prospects in cancer therapy. METHODS: In this study, to find articles, a search was made in PubMed with the keywords ferritin, drug delivery, drug delivery, and cancer treatment. RESULTS: According to the investigation, some studies suggest that ferritin can be loaded with drugs and targeted for delivery to tumor tissue. Therefore, ferritin nanocarriers loaded with drugs can be used in chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT) and immunotherapy. Importantly, the specific targeting of ferritin nanocarriers to tumor cells increases the effectiveness of related therapies and reduces side effects. CONCLUSIONS: We conclude in this paper that the superior properties of ferritin nanocarriers as an emerging drug delivery system make them a promising cancer treatment strategy. In the future, it is worth conducting clinical trials to further investigate the safety and efficacy of ferritin nanocarriers in patients.

Targeting complement C5a to improve radiotherapy sensitivity in non-small cell lung cancer.

Background: Tumor local and distant relapse recurrence after radiotherapy (RT) is one of the critical factors leading to poor prognosis. The effective antitumor effects of RT are dependent upon the participation of innate and adaptive components of the immune system. C5a/C5aR1 signaling can regulate antitumor immune effect in the tumor microenvironment (TME). Thus, exploring the changes and mechanism in the TME induced by RT-mediated complement activation may provide a novel perspective for reversing radioresistance. Methods: First, fractionated radiation of 8 Gy ×3 fractions were targeted at Lewis lung carcinoma (LLC) tumor-bearing female mice to measure the infiltration of CD8+ T cell and analyze the RNA sequencing (RNA-seq) in RT-recruited CD8+ T cells. Second, tumor growth was measured in LLC tumor-bearing mice treated with RT either with or without C5aR1 inhibitor to clarify the antitumor effect of RT combined with C5aR1 inhibitor. Third, we detected the expression of C5a/C5aR1 and their signaling pathways on radiated tumor tissues. Furthermore, we investigated the expression of C5a in tumor cells at different time points after different doses of RT. Results: In our system, RT induced the increased infiltration of CD8+ T cells and local activation of complement C5a/C5aR. Concurrent administration of RT and blocking of C5aR improved radiosensitivity and tumor-specific immune response, which was reflected by high C5aR expression in CD8+ T cells. The AKT/NF-κB pathway was found to be an important signaling pathway in C5a/C5aR axis mediation by RT. Conclusions: RT promotes the release of C5a from tumor cells and leads to up-regulation of C5aR1 expression via the AKT/NF-κB pathway. Inhibition of the combination of complement C5a and C5aR could improve RT sensitivity. Our work provides evidence that the combination of RT and C5aR blockade opens a new window of opportunity to promote anti-tumor therapeutic effects in lung cancer.