Lung Carcinoma Research Articles

Novel circular RNA hsa_circ_0036683 suppresses proliferation and migration by mediating the miR-4664-3p/CDK2AP2 axis in non-small cell lung cancer.

The aim of the present study was to investigate the function of novel circular RNA hsa_circ_0036683 (circ-36683) in non-small cell lung cancer (NSCLC). RNA sequencing was used to screen out differentially expressed miRNAs. Expression levels of miR-4664-3p and circ-36683 were evaluated in lung carcinoma cells and tissues by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The effects of miR-4664-3p and circ-36683 on proliferation and migration were assessed using cell counting kit-8 (CCK-8), wound healing and transwell migration assays and xenograft experiments. The targeting relationship of circ-36683/miR-4664-3p/CDK2AP2 was assessed by luciferase reporter assays, western blot, qRT-PCR and argonaute2-RNA immunoprecipitation (AGO2 RIP). Co-immunoprecipitation (Co-IP), 5-ethynyl-2'-deoxyuridine (EdU) staining and CCK-8 were used to validate the indispensable role of CDK2AP2 in suppressing cell proliferation as a result of CDK2AP1 overexpression. By RNA sequencing, miR-4664-3p was screened out as an abnormally elevated miRNA in NSCLC tissues. Transfection of miR-4664-3p could promote cell proliferation, migration and xenograft tumor growth. As a target of miR-4664-3p, CDK2AP2 expression was downregulated by miR-4664-3p transfection and CDK2AP2 overexpression could abolish the proliferation promotion resulting from miR-4664-3p elevation. Circ-36683, derived from back splicing of ABHD2 pre-mRNA, was attenuated in NSCLC tissue and identified as a sponge of miR-4664-3p. The functional study revealed that circ-36683 overexpression suppressed cell proliferation, migration and resulted in G0/G1 phase arrest. More importantly, the antioncogenic function of circ-36683 was largely dependent on the miR-4664-3p/CDK2AP2 axis, through which circ-36683 could upregulate the expression of p53/p21/p27 and downregulate the expression of CDK2/cyclin E1. The present study revealed the antioncogenic role of circ-36683 in suppressing cell proliferation and migration and highlighted that targeting the circ-36683/miR-4664-3p/CDK2AP2 axis is a promising strategy for the intervention of NSCLC.

2D TiO2 Nanosheets Decorated Via Sphere-Like BiVO4: A Promising Non-Toxic Material for Liquid Phase Photocatalysis and Bacterial Eradication.

An in-depth investigation was conducted on a promising composite material (BiVO4/TiO2), focusing on its potential toxicity, photoinduced catalytic properties, as well as its antibiofilm and antimicrobial functionalities. The preparation process involved the synthesis of 2D TiO2 using the lyophilization method, which was subsequently functionalized with sphere-like BiVO4 through wet impregnation. Finally, we developed BiVO4/TiO2 S-scheme heterojunctions which can greatly promote the separation of electron-hole pairs to achieve high photocatalytic performance. The evaluation of concentration- and time-dependent viability inhibition was performed on human lung carcinoma epithelial A549 cells. This assessment included the estimation of glutathione levels and mitochondrial dehydrogenase activity. Significantly, the BiVO4/TiO2 composite demonstrated minimal toxicity towards A549 cells. Impressively, the BiVO4/TiO2 composite exhibited notable photocatalytic performance in the degradation of rhodamine B (k=0.135 min-1) and phenol (k=0.016 min-1). In terms of photoinduced antimicrobial performance, the composite effectively inactivated both gram-negative E. coli and gram-positive E. faecalis bacteria upon 60 minutes of UV-A light exposure, resulting in a significant log 6 (log 10 CFU/mL) reduction in bacterial count. In addition, a 49 % reduction of E. faecalis biofilm was observed. These promising results can be attributed to the unique 2D morphology of TiO2 modified by sphere-like BiVO4, leading to an increased generation of (intracellular) hydroxyl radicals, which plays a crucial role in the treatments of both organic pollutants and bacteria. This research has significant potential for various applications, particularly in addressing environmental contamination and microbial infections.

Uncommon threads: pneumopericardium complexity following liver catheter removal in pancreatic cancer

Pneumopericardium, the presence of air within the pericardial sac, is a rare but critical condition that can lead to severe complications such as tension pneumopericardium and cardiac tamponade, causing hemodynamic instability and necessitating immediate intervention. Various etiologies include congenital defects, post-surgical complications, infections, and trauma. Malignancies, such as advanced esophageal cancer or lung carcinoma, can also cause pneumopericardium via fistula formation. Multimodal imaging, including chest X-ray, echocardiography, and computed tomography (CT), is essential for diagnosis. This case report discusses a 65-year-old male with advanced pancreatic adenocarcinoma who developed pneumopericardium following the removal of a left lobe liver drainage catheter. Initial CT imaging revealed liver lesions suspicious for metastatic disease or abscess, leading to drainage procedures. Following the removal of the drainage tube, the patient experienced respiratory distress and hypotension, and computed tomography pulmonary angiogram (CTPA) revealed pneumopericardium, likely due to a fistula formed between the abscess and pericardium. Despite no echocardiographic signs of tamponade, the patient’s persistent hypotension warranted CT-guided pericardiocentesis, resulting in gradual blood pressure improvement. This case highlights the intricate interplay between malignancy, infection, and procedural complications in developing pneumopericardium. It emphasizes the need for a multidisciplinary approach and the importance of considering both the quantity and rate of air accumulation when assessing the risk of hemodynamic compromise. The patient’s hemodynamic instability and subsequent improvement following pericardiocentesis underscore the critical role of timely intervention in managing this condition.

Lung Cancer Classification Using Combination Of Efficientnet And Visual Geometry Group Algorithm

Lung cancer is one of the leading causes of mortality All around the world. It is classified into three main types: Adenocarcinoma of the lung (ACA), Non-small cell lung cancer (N), and Squamous Cell Carcinoma of the lung (SCC). Lung Cancer Classification is crucial on development of effective treatments. This study aims to improve the accuracy of lung cancer classification through the integration of a hybrid model, which combines two Convolutional Neural Networks architectures, namely EfficientNet-B7 and VGG-16. A set of histopathology images was subjected to testing, with the data split into three categories: 60% for training, 30% for validation, and 10% for testing. Prior to use, each image underwent a preprocessing process, wherein it was resized to 256x256 pixels. The model test results achieved an accuracy, precision, recall, and F1-score of 98.73%, which is superior to the EfficientNet-B7 base model. The findings of this study demonstrate the potential of hybrid models to improve accuracy in lung cancer classification. The utilization of hybrid models has the potential to contribute significantly to the beginning diagnosis and appropriate Lung Cancer Therapies. Future research will focus on improving the model through the application of image segmentation techniques and expanding the scope of classification to other types of lung cancer. Optimization of the hybrid model architecture using novel techniques such as the attention mechanism or transfer learning will be conducted to improve the efficiency and accuracy of the model. Additionally, a system that can be integrated into clinical practice will be developed

3-Aminobenzamide-linked multifunctional nanoparticles enhances anticancer activity of low-dose cisplatin chemotherapy in lung adenocarcinoma

Chemotherapy is one of the main treatment methods for cancer patients, but its effectiveness is limited by drug resistance. Combining a chemotherapeutic agent with targeted molecular therapy may improve the curative effect of the chemotherapeutic agent. In this study, we investigate the efficacy of combining a 3-Aminobenzamide (3AB)-linked multifunctional platform with low-dose cisplatin chemotherapy aiming to modulate poly [ADP-ribose] polymerase 1 (PARP1) function in DNA repair to increase cytotoxic activity of the platinum-based cisplatin. The structure of the synthesized nanoplatforms was characterized by several physicochemical techniques, including dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and an in vitro pH-dependent release study. Cellular uptake experiments demonstrated preferentially targeted delivery of nanoparticles in lung carcinoma A549 cells, whereas the cellular uptake capacity was minimal in normal lung BEAS-2B cells. On the other hand, cytotoxicity experiments showed a reduction of cancer cell viability compared to free formulations. Furthermore, the combination treatment was examined by detecting the loss of mitochondrial membrane potential and the apoptotic cell population, confirming the treatment's functional involvement in apoptosis. Soft agar colony formation and cell invasion tests were also performed to detect the cancer cell's tumorigenic potential, confirming the synergistic effect of this combination in the reduction of tumorigenicity. Moreover, we analyzed the expression profiles of three candidate genes, which play important roles in cancer initiation, promotion and progression. Cell biology experiments indicated that this novel combination treatment possesses significant synergy between 3AB and low-dose cisplatin and is promising for development as an antitumor treatment for lung cancer.

Inverted Sandwich-Type e-LCR Aided by Lambda Exonuclease-RecJf Combination Enables Ultrasensitive Detection of Low-Frequency EGFR-L858R Mutation in NSCLC.

Highly sensitive detection of low-frequency EGFR-L858R mutation is particularly important in guiding targeted therapy of nonsmall-cell lung carcinoma (NSCLC). To this end, a ligase chain reaction (LCR)-based electrochemical biosensor (e-LCR) with an inverted sandwich-type architecture was provided by combining a cooperation of lambda exonuclease-RecJf exonuclease (λ-RecJf exo). In this work, by designing a knife-like DNA substrate (an overhang ssDNA part referred to the "knife arm") and introducing the λ-RecJf exo, the unreacted DNA probes in the LCR were specially degraded while only the ligated products were preserved, after which the ligated knife-like DNA products were hybridized with capture probes on the gold electrode surface through the "knife arms", forming the inverted sandwich-type DNA structure and bringing the methylene blue-label close to the electrode surface to engender the electrical signal. Finally, the sensitivity of the e-LCR could be improved by 3 orders of magnitude with the help of the λ-RecJf exo, and due to the mutation recognizing in the ligation site of the employed ligase, this method could detect EGFR-L858R mutation down to 0.01%, along with a linear range of 1 fM-10 pM and a limit detection of 0.8 fM. Further, the developed method could distinguish between L858R positive and negative mutations in cultured cell samples, tumor tissue samples, and plasma samples, whose accuracy was verified by the droplet digital PCR, holding a huge potential in liquid biopsy for precisely guiding individualized-treatment of NSCLC patients with advantages of high sensitivity, low cost, and adaptability to point-of-care testing.

Polyallylamine antiviral activity against influenza and acute respiratory viral infection in various cell cultures

Acute respiratory viral infections, including influenza, comprise the most common group of seasonal viral infections. Influenza is the most common and dangerous viral infection. The only way to control it is influenza vaccination. Regarding infections caused by parainfluenza and respiratory syncytial virus, only symptomatic treatment is available. Influenza virus quickly bypasses post-vaccination immunity due to its ability to antigenic drift and genetic reassortment. Available antiviral drugs quickly lose effectiveness, especially in relation to highly contagious influenza virus strains. The aim of the study was to create chemotherapeutic agent with a multi-layered effect on all viral structures: surface proteins, lipid membrane and ribonucleoprotein. Such drugs include polyelectrolytes (PE), particularly, polyallylamine (PAA), which showed strong virus-inhibiting effect in combination with low cytotoxicity against several influenza strains in MDCK cell culture and as well as measles virus in Vero cell culture. Materials and methods. In this work, an extended study on PAA antiviral activity and cytotoxicity was carried out using three influenza virus strains in A549 cell line, parainfluenza virus type 3 (HPIV-3) and respiratory syncytial virus (RSV) in A549, HEp-2, Vero, L-41, MA-104 cell lines. Results. It was shown that influenza and RSV were the most sensitive to PAA,so that virus activity decreased by 3 orders of magnitude in human lung carcinoma cells A549. The lowest antiviral activity was registered in Vero cells, which may be because it lacks interferon production system. Based on the results of in vitro experiments, PAA can be considered as a broad-spectrum antiviral drug not only against influenza, but also other human respiratory viruses.

Repeat Next-Generation Sequencing (15-Gene Panel) in Unifocal, Synchronous, and Metachronous Non-Small-Cell Lung Cancer-A Single-Center Experience.

In advanced non-squamous non-small-cell lung cancer (NSCLC), routine testing with next-generation sequencing (NGS) is recommended to identify actionable genomic alterations (AGAs). The therapeutic implications of repeated NGS testing on synchronous and metachronous tumors are unclear. Between February 2017 and October 2020, NSCLC samples from a single institution were reflex-tested using a targeted 15-gene NGS panel (TruSight Tumor 15, Illumina). Thirty-eight patients were identified with multiple NGS results from 82 samples: 11% were from single unifocal, 51% were from synchronous, and 38% were from metachronous tumors. Changes in EGFR, KRAS, PI3KCA, and TP53 variants were found in 22 patients' samples (58%). No changes were seen with longitudinal testing of multiple samples from single unifocal tumors, while changes were observed in 60% of synchronous and 71% of metachronous tumors. Of these, 26% of patients had AGA differences between samples. Acknowledging the limited sample size, a significant difference in overall survival was observed between synchronous separate primaries and metastasis. Repeat NGS testing of synchronous and metachronous NSCLC tumors may identify differing variants in >50% of patients. These changes may reflect separate primary lung carcinomas, tumor heterogeneity among intrapulmonary metastases, and clonal evolution. NGS testing of multiple tumors may enhance the identification of therapeutic targets for treatment decisions.

Surgically resected sarcomatoid carcinoma of the lung: a nationwide retrospective study in 2010

BackgroundSarcomatoid carcinoma of the lung is a rare histological type of non-small cell lung cancer with a poor prognosis. We aimed to investigate the clinicopathological characteristics and prognostic factors of surgically resected sarcomatoid carcinoma of the lung.MethodsWe retrospectively reviewed 14999 patients who underwent surgical resection for non-small cell lung cancer accumulated by the Japanese Joint Committee of Lung Cancer Registry in 2010. Clinicopathological characteristics and survival were compared between the sarcomatoid carcinoma and other non-small cell cancer groups. The prognostic factors in the sarcomatoid carcinoma group were identified using a multivariate Cox proportional hazard model.ResultsPatients with sarcomatoid carcinoma comprised 1.4% of all patients. The sarcomatoid carcinoma group demonstrated a more aggressive pathology with presentation at more advanced stages, requiring more frequent extensive surgical resections. The sarcomatoid carcinoma group had remarkably poorer overall and recurrence-free survival than the other non-small cell lung cancer group. Adjuvant chemotherapy was associated with improved survival for pathological stage II–III sarcomatoid carcinoma cases rather than for pathological stage I disease. In the multivariate analysis, larger tumor size, lymphatic permeation, and no adjuvant chemotherapy were associated with the sarcomatoid carcinoma group’s overall and recurrence-free survival.ConclusionsSurgically resected sarcomatoid carcinoma of the lung has a higher aggressive and metastatic potential and a worse prognosis than other non-small cell lung cancers. Adjuvant chemotherapy, which was associated with enhanced survival in patients with pathological stage II–III of the disease, could be considered for treating patients with pathological stage II–III sarcomatoid carcinoma of the lung.

Abstract Mo019: Angiotensin II Links Cardiovascular Disease With Enhanced Cancer Growth

Introduction: It has been demonstrated that CVD promote tumor growth in mouse models of breast, lung, and colon cancer, suggesting a causal relationship between both diseases. Cancer and CVD share several risk factors and pathophysiological mechanisms, e.g. inflammation and oxidative stress, that could explain why patients with CVD are prone to develop cancer. Recent reports also suggest a link between hypertension, hypertrophy and lung cancer. Angiotensin II (ANGII) is a hormone involved in blood pressure regulation, vascular hemostasis and hypertrophy development. Moreover, ANGII is cancerogenic by increasing proliferation of several cancer cell types. Hence, ANGII could be a link in CVD-induced enhancement of cancer growth. Hypothesis: We hypothesized that ANGII treatment, and subsequent hypertension and cardiac hypertrophy, could promote cancer growth. Methods: ANGII (2000 ng.kg -1 .min -1 ; 4w) was administered to 10w old C57B6/J mice using osmotic minipumps. After 4w, pumps were removed and 5*10 5 Lewis lung carcinoma (LLC) cells injected onto the right flank. To study the direct impact of the ANGII peptide on the cancer growth mice were treated with ANGII as mentioned above and LLC cells were injected after 3w to allow concomitant ANGII treatment and cancer growth. A similar experiment was performed by injecting 2*10 5 MC38 colon cancer cells. Tumor growth was monitored for 21d after which the mice were sacrificed. Results are expressed as mean ± SEM. Results: ANGII treatment concomitantly with cancer growth resulted in significantly larger tumors as shown by post-mortem tumor volume (881 ± 111 control vs. 1467 ± 154 mm^3 ANGII, P=0.013). In contrast, no increased tumor growth was observed when ANGII was administered non-concomitant with cancer growth. Interestingly, MC38 tumor growth significantly decreased in the ANGII treated group as portrayed by tumor volume (462 ± 65 control vs. 227 ± 81 mm^3 ANGII). Conclusion: Our data suggest a role for ANGII in CVD-enhanced cancer growth, but also that this effect is not universal, illustrated by a differential effect of ANGII on distinct cancer types. Although further investigation is required to unravel the role of ANGII, screening cancer patients with CVD comorbidities for ANGII involvement might be warranted.

RETRACTION: Elevated GAPDH expression is associated with the proliferation and invasion of lung and esophageal squamous cell carcinomas.

Hao, L., Zhou, X., Liu, S., Sun, M., Song, Y., Du, S., Sun, B., Guo, C., Gong, L., Hu, J., Guan, H., Shao, S. (2015). Elevated GAPDH expression is associated with the proliferation and invasion of lung and esophageal squamous cell carcinomas, Proteomics, 15(17), 3087-3100. https://doi.org/10.1002/pmic.201400577 The above article, published online on May 6, 2015 in Wiley Online Library (wileyonlinelibrary.com), and a corresponding correction (https://doi.org/10.1002/pmic.202070084; published May 25, 2020) have been retracted by agreement between the journal Editor-in-Chief, Lucie Kalvodova; and Wiley-VCH GmbH, Weinheim. The retraction has been agreed following concerns raised by the authors; the same shVector panel was used in two of the figures, suggesting the same control data was used for different experiments.

Biosensor Based on Zif-8-905% Metal-organic Nanocomposite and Carbon Nanotubes Associated with Concanavalin a for Detection of Alpha-fetoprotein

Introduction:: Lung carcinoma presents an aggressive evolution, with its carriers having reduced survival. Late diagnosis is one of the main factors of death. In the neoplasia in question, there is an established correlation with increases in Alpha-Fetoprotein (AFP) serum concentrations. Methos: Commonly used diagnostic methods are invasive or inaccessible. Therefore, a low-cost, non-invasive method would be extremely promising, and biomarkers can be used to achieve this goal. Electrochemical biosensors are a promising approach for detecting analytes of clinical interest using innovative bioreceptors. In this work, we obtained an electrochemical biosensor based on a hybrid ligand metal-organic structure (ZIF-8-905%) and functionalized carbon nanotubes (MWCNTs- COOH) in association with the lectin Concanavalin A (ConA), as a biorecognition element for detecting AFP in human serum from patients with lung carcinoma. Cyclic Voltammetry (CV), Square Wave Voltammetry (SWV), and Electrochemical Impedance Spectroscopy (EIS) were used to characterize the development of this biosensor. Microscopic analysis through Atomic Force Microscopy (AFM) revealed the formation of ConA-AFP complexes, pointing out the sensor's ability to identify the target analyte. Results: The blocking electron transfer effect in the electrode-redox pair interface assessed AFP detection. The ZIF-8-905%/MWCNTs-COOH/ConA platform exhibited a limit of detection (LOD) of 7.98 ng/mL, and a limit of quantification (LOQ) of 23.78ng/mL was also estimated. In addition, the biosensor showed excellent selectivity towards interfering biomolecules. Conclusion:: Therefore, the biosensor represents an efficient form of detection, contributing to research that aims to detect tumor biomarkers and ensure better prognoses.

SMAC Mimetics for the Treatment of Lung Carcinoma: Present Development and Future Prospects.

Uncontrolled cell growth and proliferation, which originate from lung tissue often lead to lung carcinoma and are more likely due to smoking as well as inhaled environmental toxins. It is widely recognized that tumour cells evade the ability of natural programmed death (apoptosis) and facilitates tumour progression and metastasis. Therefore investigating and targeting the apoptosis pathway is being utilized as one of the best approaches for decades. This review describes the emergence of SMAC mimetic drugs as a treatment approach, its possibilities to synergize the response along with current limitations as well as future perspective therapy for lung cancer. Articles were analysed using search engines and databases namely Pubmed and Scopus. Under cancerous circumstances, the level of Inhibitor of Apoptosis Proteins (IAPs) gets elevated, which suppresses the pathway of programmed cell death, plus supports the proliferation of lung cancer. As it is a major apoptosis regulator, natural drugs that imitate the IAP antagonistic response like SMAC mimetic agents/Diablo have been identified to trigger cell death. SMAC i.e. second mitochondria activators of caspases is a molecule produced by mitochondria, stimulates apoptosis by neutralizing/inhibiting IAP and prevents its potential responsible for the activation of caspases. Various preclinical data have proven that these agents elicit the death of lung tumour cells. Apart from inducing apoptosis, these also sensitize the cancer cells toward other effective anticancer approaches like chemo, radio, or immunotherapies. There are many SMAC mimetic agents such as birinapant, BV-6, LCL161, and JP 1201, which have been identified for diagnosis as well as treatment purposes in lung cancer and are also under clinical investigation. SMAC mimetics acts in a restorative way in the prevention of lung cancer.

Aloe and coconut extracts mediated CuInS2 nanoparticles induce apoptosis in non-small lung cancer cells (A549)

The most prevalent type of cancer found in the world is lung cancer. Furthermore, chemotherapeutic intervention for lung carcinomas is frequently associated with severe off-target effects. As a result, there is a worldwide push to investigate alternative medicines with superior tolerance profiles, such as natural compounds, to substitute routinely used chemotherapeutics. The purpose of this study is to examine the anticancer potential of aloe (S1) and coconut (S2) extract-mediated CuInS2 (CIS) nanoparticles against non-small cell lung carcinoma (A549) cells. S1 and S2 both efficiently showed a dose-proportionate cytotoxic effect on A549 cells, while causing negligible toxic effects on normal healthy lung cells (WI-38), indicating their safety against healthy cells. Reduced cell viability was validated by acridine orange and ethidium bromide double staining, demonstrating that apoptosis was induced in A549 cells treated with both nanoparticles. In addition, the mitochondrial membrane potential was reduced by both nanoparticles, leading to an increase in ROS generation. Both nanoparticles increased caspase-3, caspase-9, and caspase-8 levels in A549 cells. To summarize, both nanoparticles induced apoptotic cell damage in A549 cells by targeting mitochondria, causing increased ROS production, activating the caspase cascade, and inducing apoptosis. Aloe (S1) and coconut (S2) extract-mediated CIS nanoparticles may represent viable therapeutic options for lung cancer management.

Dihydroartemisinin restores the immunogenicity and enhances the anticancer immunosurveillance of cisplatin by activating the PERK/eIF2α pathway

BackgroundImmunosurveillance is pivotal in the effectiveness of anticancer therapies and tumor control. The ineffectiveness of cisplatin in activating the immunosurveillance is attributed to its lack of adjuvanticity resulting from its inability to stimulate endoplasmic reticulum stress. Dihydroartemisinin demonstrates the anti-tumor effects through various mechanisms, including the activation of the endoplasmic reticulum stress. This study aimed to develop a novel strategy to enhance the immunogenicity of dying tumor cells by combining cisplatin with dihydroartemisinin, thereby triggering effective anti-tumor immunosurveillance and improving the efficacy of cisplatin in clinical practice.MethodsLewis lung carcinoma (LLC) and CT26 colon cancer cell lines and subcutaneous tumor models were used in this study. The importance of immunosurveillance was validated in both immunocompetent and immunodeficient mouse models. The ability of dihydroartemisinin and cisplatin therapy to induce immunogenic cell death and tumor growth control in vivo was validated by prophylactic tumor vaccination and therapeutic tumor models. The underlying mechanism was elucidated through the pharmaceutical or genetic intervention of the PERK/eIF2α pathway in vitro and in vivo.ResultsDihydroartemisinin enhanced the generation of reactive oxygen species in cisplatin-treated LLC and CT26 cancer cells. The combination treatment of dihydroartemisinin with cisplatin promoted cell death and ensured an optimal release of damage-associated molecular patterns from dying cancer cells, promoting the phagocytosis of dendritic cells. In the tumor vaccination model, we confirmed that dihydroartemisinin plus cisplatin treatment induced immunogenic cell death. Utilizing immunocompetent and immunodeficient mouse models, we further demonstrated that the combination treatment suppressed the tumor growth of CT26 colon cancer and LLC lung cancer, leading to an improved prognosis through the restoration of cytotoxic T lymphocyte responses and reinstatement of anti-cancer immunosurveillance in vivo. Mechanistically, dihydroartemisinin restored the immunogenicity of cisplatin by activating the adjuvanticity of damage-associated molecular patterns, such as calreticulin exposure, through the PERK/eIF2α pathway. Additionally, the inhibition of eIF2α phosphorylation attenuated the anti-tumor efficiency of C + D in vivo.ConclusionsWe highlighted that dihydroartemisinin acts as an immunogenic cell death rescuer for cisplatin, activating anticancer immunosurveillance in a PERK/eIF2α-dependent manner and offering a strategy to enhance the anti-tumor efficacy of cisplatin in clinical practice.

A gene set enrichment analysis for the cancer hallmarks

The "hallmarks of cancer" concept provides a valuable framework for understanding fundamental organizing principles common to various cancers. However, without a consensus gene set for cancer hallmarks, data comparison and integration result in diverse biological interpretations across studies. Therefore, we aimed to form a consensus cancer hallmark gene set by merging data from available mapping resources and establishing a framework for mining these gene sets. By consolidating data from seven projects, 6,763 genes associated with ten cancer hallmarks were identified. A cancer hallmarks enrichment analysis was performed for prognostic genes associated with overall survival across twelve types of solid tumors. "Tissue invasion and metastasis" was most prominent in cancers of the stomach (P = 2.2×10−11), pancreas (P = 4.2×10−9), bladder (P = 3.3×10−8), and ovaries (P = 0.0007), aligning with their heightened potential to spread. "Sustained angiogenesis" was most prominent in squamous cell carcinomas of the lung (P = 2.5×10−7), while "genome instability" showed strong enrichment in lung adenocarcinomas (P = 1.5×10−8) and cancers of the liver (P = 5.5×10−10), pancreas (P = 2.1×10−5), and kidney (P = 0.018). Pancreatic cancers displayed the highest enrichment of hallmarks, emphasizing the disease's complexity, while in melanomas, and cancers of the liver, prostate, and kidney, a single hallmark was enriched among the prognostic markers of survival. Additionally, an online tool (www.cancerhallmarks.com) that allows the identification of cancer-associated hallmarks from new gene sets was established. In summary, our aim of establishing a consensus list of cancer hallmark genes was achieved. Furthermore, the analysis of survival-associated genes revealed a unique pattern of hallmark enrichment with potential pharmacological implications in different tumor types.

Pathological Diagnostic Testing and Biomarkers for Perioperative System Therapy

Optimal personalized treatment planning for resectable lung cancer requires quality-assured, standardized and prompt processing of tissue samples in pathological laboratories, as well as the determination of relevant predictive and prognostic biomarkers. Pathological diagnostic testing includes histological tumor typing, staging and tumor grading, resection status and, if necessary, regression grading after neoadjuvant systemic therapy. Histopathological typing is performed according to the current WHO classification and includes adenocarcinomas, squamous cell carcinomas, other non-small cell lung carcinomas (NSCLCs), carcinoids, small cell and large cell neuroendocrine carcinomas. Standardized tumor grading currently plays an important role in invasive non-mucinous adenocarcinoma in particular and enables prognostic risk assessment. The R classification and regression grading are also prognostically relevant. In the early stages of NSCLC, molecular biomarkers such as EGFR, ALK and PD-L1, are relevant for decisions on individual treatment. Testing is performed on FFPE tissue samples and must be carried out in a quality-assured manner and in accordance with international standards.

Antioxidant properties and bioactivity of three marine microalgae on human cancer cell lines

ABSTRACT Marine microalgae offer significant potential as sustainably cultivable microorganisms for the biorefining of a diverse array of functional metabolites. In this study, three species of marine microalgae, Tetraselmis chuii Butcher CCAP 66/21B (Chlorophyte), Phaeodactylum tricornutum Bohlin CCAP 1052/1 (Diatom) and Amphidinium carterae Hulburt CCAP 1102/8 (Dinoflagellate), were batch cultivated and their biomass retrieved for analysis in terms of pigment and fatty acid composition as well as bioactivity potential. Sequential solvent maceration of the biomass returned extracts was used to determine antioxidant capacity and assess their growth inhibition potential against A549 (a human lung carcinoma) and MCF-7 (a breast carcinoma) cell lines. The extracts of A. carterae showed higher antioxidant capacity (≤ 33.5 μmol Trolox Equivalent mg Recovered Dried Material‒1) compared to the other extracts. No major cytotoxic activity nor production of reactive oxygen species was observed using the extracts of T. chuii and P. tricornutum. However, the methanolic extraction of A. carterae inhibited the growth of both A549 and MCF-7 cells (< 4%) at 25, 50 and 100 µg ml−1 concentrations, as determined using the MTS assay and AO/PI cell staining. Microalgal metabolites have the potential for practical applications in a variety of industrial sectors. The absence of toxicity and substantial antioxidant potential of extracts of T. chuii and P. tricornutum confirm their suitability for incorporation into animal feeds or human nutrition supplements. A. carterae also appears to be a promising source of bioactives that can be further valorized via multi-compound biorefinery pipelines.

Sublobar Resection vs Lobectomy for High-Risk Stage I Non–Small Cell Lung Carcinoma

Sublobar Resection vs Lobectomy for High-Risk Stage I Non–Small Cell Lung Carcinoma

Selenium nanoparticles enhance the anti-tumor immune responses of anti-4-1BB antibody and alleviate the adverse effects on mice

4-1BB agonists for cancer immunotherapy have shown good preliminary efficacy in clinical trials, but several of the first-generation 4-1BB agonistic antibodies entering the clinic have failed due to safety issues. Selenium nanoparticles (SeNPs) exhibit anti-inflammatory, anti-tumor, antioxidant, and immune-modulating properties. In addition, they have been shown to have detoxifying effects and prevent oxidative liver damage. In this study, we used an anti-4-1BB antibody in combination with SeNPs to evaluate the anti-lung cancer effects in in vitro and in vivo experiments and explore the underlying mechanisms by pathological analyses, quantitative PCR, and enzyme-linked immunoassay. We found that 5 μmol·L–1 anti-4-1BB antibody combined with 1 μmol·L–1 SeNPs increased the expression of IFN-γ and promoted the killing effects of peripheral blood mononuclear cells on Lewis lung carcinoma cells, with a lethality rate up to 56.88 %. Experiments in tumor-bearing mice showed that the tumor inhibition rate was 58.61 % after treatment with 3.5 mg/kg anti-4-1BB antibody combined with 0.25 mg/kg SeNPs, and the liver function index returned to normal. When the combined treatment was compared with the antibody treatment alone, detection of immune relevant factors demonstrated that the expression of FOXP3, IL-2, IL-12, and TNF-α in the spleen was downregulated, whereas the expression of IFN-γ in the spleen, serum, and tumor was upregulated, accompanied by increased Fas ligand expression in the tumor tissues. Based on these findings, we get the conclusion that anti-4-1BB antibody combined with SeNPs may alleviate the immunosuppression of regulatory T cells, promote the immune cell proliferation and metastasis to synergistically kill tumor cells. This combination also reduces the inflammatory damage to normal tissues and slows overstimulation of the splenic immune response.