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Brachytherapy is one mainstay treatment for lung cancer. However, a great challenge in brachytherapy is radio-resistance, which is caused by severe hypoxia in solid tumors. In this research, we have developed a PEGylated

Carvacrol and HP-β-Cyclodextrin Complexes Extensive Characterization and Potential Cytotoxic Effect in Human Colorectal Carcinoma Cells.

The aim of this study was to obtain solid carvacrol-cyclodextrin (CD) complexes for use in the pharmaceutical industry. To this end, the complexation of carvacrol at different pH values was studied in detail, to determine the type of CD and the reaction environment that supported the highest amount of encapsulated carvacrol. Evidence of the capability of hydroxypropyl-β-cyclodextrins (HP-β-CD) to form inclusion complexes with carvacrol (K

Chlorotoxin and Lung Cancer A Targeting Perspective for Drug Delivery.

In the generational evolution of nano-based drug delivery carriers, active targeting has been a major milestone for improved and selective drug accumulation in tissues and cell types beyond the existing passive targeting capabilities. Among the various active targeting moieties, chlorotoxin, a peptide extracted from scorpions, demonstrated promising tumor cell accumulation and selection. With lung cancer being among the leading diagnoses of cancer-related deaths in both men and women, novel therapeutic methodologies utilizing nanotechnology for drug delivery emerged. Given chlorotoxins promising biological activity, we explore its potential against lung cancer and its utilization for active targeting against this cancers tumor cells. Our analysis indicates that despite the extensive chlorotoxins research against glioblastoma, lung cancer research with the molecule has been limited, despite some promising early results.

Encorafenib Acts as a Dual-Activity Chemosensitizer through Its Inhibitory Effect on ABCC1 Transporter In Vitro and Ex Vivo.

Encorafenib (LGX818, trade name Braftovi), a novel BRAF inhibitor, has been approved for the treatment of melanoma and colorectal cancer. In the present work, we evaluated encorafenibs possible antagonistic effects on the pharmacokinetic mechanisms of multidrug resistance (MDR), as well as its perpetrator role in drug interactions. Firstly, encorafenib potently inhibited the efflux function of the ABCC1 transporter in drug accumulation assays, while moderate and null interaction levels were recorded for ABCB1 and ABCG2, respectively. In contrast, the mRNA expression levels of all the tested transporters were not altered by encorafenib. In the drug combination studies, we found that daunorubicin and topotecan resistances were synergistically attenuated by the encorafenib-mediated interaction in A431-ABCC1 cells. Notably, further experiments in ex vivo patient-derived explants confirmed the MDR-modulating ability of encorafenib. Advantageously, the overexpression of tested drug efflux transporters failed to hinder the antiproliferative activity of encorafenib. In addition, no significant modulation of the CYP3A4 enzymes activity by encorafenib was observed. In conclusion, our work indicated that encorafenib can act as an effective chemosensitizer targeting the ABCC1-induced MDR. Our in vitro and ex vivo data might provide valuable information for designing the novel effective scheme applicable in the clinical pharmacotherapy of

Isotopic Radiolabeling of Crizotinib with Fluorine-18 for In Vivo Pet Imaging.

Crizotinib is a tyrosine kinase inhibitor approved for the treatment of non-small-cell lung cancer, but it is inefficient on brain metastases. Crizotinib is a substrate of the P-glycoprotein, and non-invasive nuclear imaging can be used to assess the brain penetration of crizotinib. Positron emission tomography (PET) imaging using fluorine-18-labeled crizotinib would be a powerful tool for investigating new strategies to enhance the brain distribution of crizotinib. We have synthesized a spirocyclic hypervalent iodine precursor for the isotopic labeling of crizotinib in a 2.4% yield. Because crizotinib is an enantiomerically pure drug, a chiral separation was performed to afford the

Human Lung Cancer (A549) Cell Line Cytotoxicity and Anti-

Lung cancer and cutaneous leishmaniasis are critical diseases with a relatively higher incidence in developing countries. In this research, the activity of

Cytotoxic Labdane Diterpenes, Norlabdane Diterpenes and Bis-Labdanic Diterpenes from the Zingiberaceae A Systematic Review.

Over the years, labdane diterpenes, norlabdane diterpenes, and bis-labdanic diterpenes with cytotoxic activities have been identified across various families in the plant kingdom including the Zingiberaceae. The present review discusses the distribution of these labdane-type diterpenes within the Zingiberaceae their extraction, isolation, and characterization from the respective Zingiberaceae species the structural similarities and differences within each group and between the different groups of the labdane-type diterpenes and their cytotoxic activities against breast, cervical, liver, colorectal, pancreatic, lung and prostate cancer cell lines. The review will also provide insight into how the cytotoxic activities of the labdane-type diterpenes are influenced by their structural features.

Targeting the DNA Damage Response Machinery for Lung Cancer Treatment.

Lung cancer is considered the most commonly diagnosed cancer and one of the leading causes of death globally. Despite the responses from small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients to conventional chemo- and radiotherapies, the current outcomes are not satisfactory. Recently, novel advances in DNA sequencing technologies have started to take off which have provided promising tools for studying different tumors for systematic mutation discovery. To date, a limited number of DDR inhibition trials have been conducted for the treatment of SCLC and NSCLC patients. However, strategies to test different DDR inhibitor combinations or to target multiple pathways are yet to be explored. With the various biomarkers that have either been recently discovered or are the subject of ongoing investigations, it is hoped that future trials would be designed to allow for studying targeted treatments in a biomarker-enriched population, which is defensible for the improvement of prognosis for SCLC and NSCLC patients. This review article sheds light on the different DNA repair pathways and some of the inhibitors targeting the proteins involved in the DNA damage response (DDR) machinery, such as ataxia telangiectasia and Rad3-related protein (ATR), DNA-dependent protein kinase (DNA-PK), and poly-ADP-ribose polymerase (PARP). In addition, the current status of DDR inhibitors in clinical settings and future perspectives are discussed.

Cyclooxygenase-2 (COX-2) as a Target of Anticancer Agents A Review of Novel Synthesized Scaffolds Having Anticancer and COX-2 Inhibitory Potentialities.

Cancer is a serious threat to human beings and is the second-largest cause of death all over the globe. Chemotherapy is one of the most common treatments for cancer however, drug resistance and severe adverse effects are major problems associated with anticancer therapy. New compounds with multi-target inhibitory properties are targeted to surmount these challenges. Cyclooxygenase-2 (COX-2) is overexpressed in cancers of the pancreas, breast, colorectal, stomach, and lung carcinoma. Therefore, COX-2 is considered a significant target for the synthesis of new anticancer agents. This review discusses the biological activity of recently prepared dual anticancer and COX-2 inhibitory agents. The most important intermolecular interactions with the COX-2 enzyme have also been presented. Analysis of these agents in the active area of the COX-2 enzyme could guide the introduction of new lead compounds with extreme selectivity and minor side effects.

Nanoparticles in Drug Delivery From History to Therapeutic Applications.

Current research into the role of engineered nanoparticles in drug delivery systems (DDSs) for medical purposes has developed numerous fascinating nanocarriers. This paper reviews the various conventionally used and current used carriage system to deliver drugs. Due to numerous drawbacks of conventional DDSs, nanocarriers have gained immense interest. Nanocarriers like polymeric nanoparticles, mesoporous nanoparticles, nanomaterials, carbon nanotubes, dendrimers, liposomes, metallic nanoparticles, nanomedicine, and engineered nanomaterials are used as carriage systems for targeted delivery at specific sites of affected areas in the body. Nanomedicine has rapidly grown to treat certain diseases like brain cancer, lung cancer, breast cancer, cardiovascular diseases, and many others. These nanomedicines can improve drug bioavailability and drug absorption time, reduce release time, eliminate drug aggregation, and enhance drug solubility in the blood. Nanomedicine has introduced a new era for drug carriage by refining the therapeutic directories of the energetic pharmaceutical elements engineered within nanoparticles. In this context, the vital information on engineered nanoparticles was reviewed and conferred towards the role in drug carriage systems to treat many ailments. All these nanocarriers were tested in vitro and in vivo. In the coming years, nanomedicines can improve human health more effectively by adding more advanced techniques into the drug delivery system.

Evaluation of In Vitro Cytotoxic Potential of Avarol towards Human Cancer Cell Lines and In Vivo Antitumor Activity in Solid Tumor Models.

The goal of this study was to determine the activity in vitro and in vivo of avarol, a sesquiterpene hydroquinone originating from the

The Role of Hydrogen Sulfide in the Development and Progression of Lung Cancer.

Lung cancer is one of the 10 most common cancers in the world, which seriously affects the normal life and health of patients. According to the investigation report, the 3-year survival rate of patients with lung cancer is less than 20%. Heredity, the environment, and long-term smoking or secondhand smoke greatly promote the development and progress of the disease. The mechanisms of action of the occurrence and development of lung cancer have not been fully clarified. As a new type of gas signal molecule, hydrogen sulfide (H

Target Identification of 22-(4-Pyridinecarbonyl) Jorunnamycin A, a Tetrahydroisoquinoline Derivative from the Sponge

A dysregulation of the cell-death mechanism contributes to poor prognosis in lung cancer. New potent chemotherapeutic agents targeting apoptosis-deregulating molecules have been discovered. In this study, 22-(4-pyridinecarbonyl) jorunnamycin A (22-(4py)-JA), a synthetic derivative of bistetrahydroisoquinolinequinone from the Thai blue sponge, was semisynthesized by the Steglich esterification method, and its pharmacological mechanism in non-small-cell lung cancer (NSCLC) was elucidated by a network pharmacology approach. All predicted targets of 22-(4py)-JA and genes related to NSCLC were retrieved from drug-target and gene databases. A total of 78 core targets were identified, and their associations were analyzed by STRING and Cytoscape. Gene ontology and KEGG pathway enrichment analyses revealed that molecules in mitogen-activated protein kinase (MAPK) signaling were potential targets of 22-(4py)-JA in the induction of NSCLC apoptosis. In silico molecular docking analysis displayed a possible interaction of ERK12 and MEK1 with 22-(4py)-JA. In vitro anticancer activity showed that 22-(4py)-JA has strong cytotoxic and apoptosis-inducing effects in H460, H292 and A549 NSCLC cells. Furthermore, immunoblotting confirmed that 22-(4py)-JA induced apoptotic cell death in an ERKMEKBcl-2-dependent manner. The present study demonstrated that 22-(4py)-JA exhibited a potent anticancer effect that could be further developed for clinical application and showed that network pharmacology approaches are a powerful tool to illustrate the molecular pathways of new drugs or compounds.

Axl, Immune Checkpoint Molecules and HIF Inhibitors from the Culture Broth of

Two compounds

Quinoxalinones as A Novel Inhibitor Scaffold for EGFR (L858RT790MC797S) Tyrosine Kinase Molecular Docking, Biological Evaluations, and Computational Insights.

Combating acquired drug resistance of EGFR tyrosine kinase (TK) is a great challenge and an urgent necessity in the management of non-small cell lung cancers. The advanced EGFR (L858RT790MC797S) triple mutation has been recently reported, and there have been no specific drugs approved for this strain. Therefore, our research aimed to search for effective agents that could impede the function of EGFR (L858RT790MC797S) TK by the integration of in silico and in vitro approaches. Our in-house quinoxalinone-containing compounds were screened through molecular docking and their biological activity was then verified by enzyme- and cell-based assay. We found that the four quinoxalinone-containing compounds including CPD4, CPD15, CPD16, and CPD21 were promising to be novel EGFR (L858RT790MC797S) TK inhibitors. The IC

Effect of Copper Chelators via the TGF-β Signaling Pathway on Glioblastoma Cell Invasion.

Glioblastoma multiforme (GBM) is a fast-growing and aggressive type of brain cancer. Unlike normal brain cells, GBM cells exhibit epithelial-mesenchymal transition (EMT), which is a crucial biological process in embryonic development and cell metastasis, and are highly invasive. Copper reportedly plays a critical role in the progression of a variety of cancers, including brain, breast, and lung cancers. However, excessive copper is toxic to cells. D-penicillamine (DPA) and triethylenetetramine (TETA) are well-known copper chelators and are the mainstay of treatment for copper-associated diseases. Following treatment with copper sulfate and DPA, GBM cells showed inhibition of proliferation and suppression of EMT properties, including reduced expression levels of N-cadherin, E-cadherin, and Zeb, which are cell markers associated with EMT. In contrast, treatment with copper sulfate and TETA yielded the opposite effects in GBM. Genes, including

Precious Gene The Application of RET-Altered Inhibitors.

The well-known proto-oncogene rearrangement during transfection (RET), also known as ret proto-oncogene Homo sapiens (human), is a rare gene that is involved in the physiological development of some organ systems and can activate various cancers, such as non-small cell lung cancer, thyroid cancer, and papillary thyroid cancer. In the past few years, cancers with RET alterations have been treated with multikinase inhibitors (MKIs). However, because of off-target effects, these MKIs have developed drug resistance and some unacceptable adverse effects. Therefore, these MKIs are limited in their clinical application. Thus, the novel highly potent and RET-specific inhibitors selpercatinib and pralsetinib have been accelerated for approval by the Food and Drug Administration (FDA), and clinical trials of TPX-0046 and zetletinib are underway. It is well tolerated and a potential therapeutic for RET-altered cancers. Thus, we will focus on current state-of-the-art therapeutics with these novel RET inhibitors and show their efficacy and safety in therapy.

Recent Trends and Opportunities for the Targeted Immuno-Nanomaterials for Cancer Theranostics Applications.

The targeted delivery of cancer immunotherapies has increased noticeably in recent years. Recent advancements in immunotherapy, particularly in blocking the immune checkpoints (ICs) axis, have shown favorable treatment outcomes for multiple types of cancer including melanoma and non-small-cell lung cancer (NSLC). Engineered micromachines, including microparticles, and nanoplatforms (organic and inorganic), functionalized with immune agonists can effectively deliver immune-targeting molecules to solid tumors. This review focuses on the nanomaterial-based strategies that have shown promise in identifying and targeting various immunological markers in the tumor microenvironment (TME) for cancer diagnosis and therapy. Nanomaterials-based cancer immunotherapy has improved treatment outcomes by triggering an immune response in the TME. Evaluating the expression levels of ICs in the TME also could potentially aid in diagnosing patients who would respond to IC blockade therapy. Detecting immunological checkpoints in the TME using noninvasive imaging systems via tailored nanosensors improves the identification of patient outcomes in immuno-oncology (IO). To enhance patient-specific analysis, lab-on-chip (LOC) technology is a rapid, cost-effective, and accurate way of recapitulating the TME. Such novel nanomaterial-based technologies have been of great interest for testing immunotherapies and assessing biomarkers. Finally, we provide a perspective on the developments in artificial intelligence tools to facilitate ICs-based nano theranostics toward cancer immunotherapy.

Metabolomic Analysis of Renal Cell Carcinoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Clinical, Laboratory, Histological, Radiological, and Metabolic Features and Prognosis of Malignant Pleural Mesothelioma.

Exploring the Potential Use of Wearable Devices as a Prognostic Tool among Patients in Hospice Care.

Changes in Body Weight, Body Composition, Phase Angle, and Resting Metabolic Rate in Male Patients with Stage IV Non-Small-Cell Lung Cancer Undergoing Therapy.

Novel Carboxymethyl Cellulose-Based Hydrogel with Core-Shell Fe

A nanocomposite composed of carboxymethyl cellulose (CMC) and core-shell nanoparticles of Fe

Eco-Friendly Preparation of Silver Nanoparticles and Their Antiproliferative and Apoptosis-Inducing Ability against Lung Cancer.

In the present study, the anti-proliferative and apoptotic potential of

Potential Role of Tumor-Derived Exosomes in Non-Small-Cell Lung Cancer in the Era of Immunotherapy.

Lung cancer, of which non-small-cell lung cancer (NSCLC) represents about 80% of all cases, is the second most common cancer diagnosed in the general population and one of the major causes of cancer-related deaths worldwide. Overall, the outcomes of patients with advanced NSCLC are still disappointing despite advances in diagnosis and treatment. In recent years immune-checkpoint inhibitors (ICIs), administered alone or in combination with chemotherapy, have revolutionized the treatment landscape of patients with advanced non-small-cell lung cancer. However, until now, tissue expression of PD-L1 and tumor mutation burden represent the only available biomarkers for NSCLC patients treated with ICIs. A growing body of evidence showed that tumor-derived exosomes (TDEs) have the PD-L1 protein on their surface and that they are involved in angiogenesis, tumor growth, invasion, metastasis and immune escape. This review focused on the potential clinical applications of TDEs in NSCLC, including their possible role as a biomarker for prognosis and disease monitoring in patients undergoing immunotherapy.

Baseline Ang-2 Serum Levels as a Predictive Factor for Survival in NSCLC and SCLC.

Angiopoietin-2 (Ang-2) has been implicated in the development of several types of cancer, including lung malignancy. In the present study, we examined the impact of Ang-2 serum concentration on the development, dissemination, and 5-year overall survival of NSCLC and SCLC. A total of 99 patients with lung cancer were tested. The OS of NSCLC and SCLC patients was estimated using Kaplan-Meier curves and compared through log-rank test. The median serum level of Ang-2 at baseline in both NSCLC and SCLC patients was significantly higher than that of controls (

Chemical Composition of Volatile Extracts from Black Raspberries, Blueberries, and Blackberries and Their Antiproliferative Effect on A549 Non-Small-Cell Lung Cancer Cells.

Berry volatiles are responsible for the berry aroma but there is limited information available on the health-promoting activities of berry volatiles. The objectives of this study were to evaluate the chemical composition of volatile extracts from black raspberries, blueberries, and blackberries and investigate their antiproliferative effect and apoptotic mechanisms on A549 lung cancer cells. The chemical composition of three berry volatile extracts (BVEs) was identified by using gas chromatography-mass spectrometry. Cells were treated with different dilutions of three BVEs for 48 h and determined for cell proliferation and apoptosis. Total volatiles in BVEs were 1.6-3.2 mgL. Two-fold diluted BVEs significantly inhibited cell proliferation after 48 h, inducing apoptosis (

Quantitative Assessment of Asbestos Fibers in Normal and Pathological Peritoneal Tissue-A Scoping Review.

Peritoneal tissue is the second most affected site by malignant mesothelioma linked to asbestos exposure. This scoping review aims to summarize the findings of the studies in which asbestos fibers in the peritoneum were quantified by electron microscopy, occasionally associated with spectroscopy, both in neoplastic and non-neoplastic tissue. The 9 studies selected comprised 62 cases, out of whom 100 samples were analyzed. Asbestos fibers were detected in 58 samples (58%). In addition, 28 cases had diagnosis of peritoneal mesothelioma. For 32 cases, a lung tumor sample was available 2832 samples analyzed presented asbestos fibers 1832 reported amphiboles with a range from not detected to 14.2 million fibers per gram of dry tissue (mfgdt) 1832 reported chrysotile, with a range of 0 to 90 mfgdt. The studies were heterogeneous for type of samples, analytical technology, and circumstances of exposure to asbestos. To evaluate asbestos fibers in the peritoneum and to better understand the association between asbestos exposure and malignant peritoneal mesothelioma, it is desirable that the search for asbestos fibers becomes a routine process every time peritoneal tissue is accessible.

Efficacy and Failure Patterns of Early SBRT to the Primary Tumor in Advanced EGFR-Mutation-Positive Lung Cancer with EFGR-TKI Treatment A Prospective, Single Arm, Phase II Study.

Early stereotactic body radiation therapy (SBRT) to the primary tumor combined with epidermal growth factor receptor tyrosine kinase inhibitor (EFGR-TKI) treatment may increase progression-free survival (PFS) by delaying resistance in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). In this prospective, single arm, phase II study, patients with advanced NSCLC were treated with EGFR-TKI (icotinib 125 mg tid or gefitinib 250 mg qd) for one month followed by SBRT (40-60 Gy5-8 F5-10 d) to the primary tumor with concurrent EGFR-TKI until disease progression. The primary endpoint was PFS and the patterns of failure. Overall survival (OS) and adverse effects (AEs) were secondary endpoints. Overall, 41 advanced NSCLC patients with EGFR mutations received treatment with 24.42 months of median follow-up time. On average, SBRT was initiated 1.49 months after EGFR-TKI administration. Tumors were found to have an average shrinkage rate of 42.50%. Median PFS was 15.23 months (95% CI 13.10-17.36), while median OS was 27.57 months (95% CI 23.05-32.09). Thirty-three patients were found to have disease progression, of which new site failure (NF) (22 patients, 66.66%) was the most common pattern, followed by original site failure (OF) (7 patients, 21.21%) and simultaneous OFNF (ONF) (4 patients, 12.12%). There were no Aes equal to or greater than grade 3, with the most frequent AE being radiation pneumonitis. Therefore, administering therapy targeted at the primary tumor using early SBRT after EGFR-TKI initiation is a new potentially safe and effective approach to treat EGFR-mutant advanced NSCLC.

Identification of Potential microRNA Panels for Male Non-Small Cell Lung Cancer Identification Using Microarray Datasets and Bioinformatics Methods.

Novel Potential Therapeutic Targets of PTPN Families for Lung Cancer.

Despite the treatment of lung adenocarcinoma (LUAD) having partially improved in recent years, LUAD patients still have poor prognosis rates. Therefore, it is especially important to explore effective biomarkers and exploit novel therapeutic developments. High-throughput technologies are widely used as systematic approaches to explore differences in expressions of thousands of genes for both biological and genomic systems. Recently, using big data analyses in biomedicine research by integrating several high-throughput databases and tools, including The Cancer Genome Atlas (TCGA), cBioportal, Oncomine, and Kaplan-Meier plotter, is an important strategy to identify novel biomarkers for cancer therapy. Here, we used two different comprehensive bioinformatics analysis and revealed protein tyrosine phosphatase non-receptor type (PTPN) family genes, especially PTPN1 and PTPN22, were downregulated in lung cancer tissue in comparison with normal samples. The survival curves indicated that LUAD patients with high transcription levels of PTPN5 were significantly associated with a good prognosis. Meanwhile, Gene Ontology (GO) and MetaCore analyses indicated that co-expression of the PTPN1, PTPN5, and PTPN21 genes was significantly enriched in cancer development-related pathways, including GTPase activity, regulation of small GTPase-mediated signal transduction, response to mechanical stimuli, vasculogenesis, organ morphogenesis, regulation of stress fiber assembly, mitogen-activated protein kinase (MAPK) cascade, cell migration, and angiogenesis. Collectively, this study revealed that PTPN family members are both significant prognostic biomarkers for lung cancer progression and promising clinical therapeutic targets, which provide new targets for treating LUAD patients.

Myocardial Injury Is Associated with the Incidence of Major Adverse Cardiac Events in Patients with Severe Trauma.

Severe trauma potentially results in end-organ damage such as myocardial injury. Data suggest that myocardial injury is associated with increased mortality in this cohort, but the association with the incidence of in-hospital major adverse cardiac events (MACE) remains undetermined. Retrospective cohort study including adult patients with severe trauma treated at the University Hospital Duesseldorf between January 2016 and December 2019. The main exposure was myocardial injury at presentation. Endpoints were in-hospital incidence of MACE and incidence of acute kidney injury (AKI) within 72 h. Discrimination of hsTnT for MACE and AKI was examined by the receiver operating characteristic curve (ROC) and the area under the curve (AUC). We conducted multivariate logistic regression analysis. We included 353 patients in our final analysis (72.5% male (256353), age 55 ± 21 years). The AUC for hsTnT and MACE was 0.68 95% confidence interval (CI) 0.59-0.78. The AUC for hsTnT and AKI was 0.64 95% (CI) 0.55-0.72. The adjusted odds ratio (OR) for myocardial injury and MACE was 2.97 95% (CI) 1.31-6.72, and it was 2.14 95% (CI) 1.03-4.46 for myocardial injury and AKI. Myocardial injury at presentation in patients with severe trauma is independently associated with the incidence of in-hospital MACE and AKI.

A Simulation Study of Tolerance of Breathing Amplitude Variations in Radiotherapy of Lung Cancer Using 4DCT and Time-Resolved 4DMRI.

As patient breathing irregularities can introduce a large uncertainty in targeting the internal tumor volume (ITV) of lung cancer patients, and thereby affect treatment quality, this study evaluates dose tolerance of tumor motion amplitude variations in ITV-based volumetric modulated arc therapy (VMAT). A motion-incorporated planning technique was employed to simulate treatment delivery of 10 lung cancer patients clinical VMAT plans using original and three scaling-up (by 0.5, 1.0, and 2.0 cm) motion waveforms from single-breath four-dimensional computed tomography (4DCT) and multi-breath time-resolved 4D magnetic resonance imaging (TR-4DMRI). The planning tumor volume (PTV ITV 5 mm margin) dose coverage (PTV D95%) was evaluated. The repeated waveforms were used to move the isocenter in sync with the clinical leaf motion and gantry rotation. The continuous VMAT arcs were broken down into many static beam fields at the control points (2°-interval) and the composite plan represented the motion-incorporated VMAT plan. Eight motion-incorporated plans per patient were simulated and the plan with the native 4DCT waveform was used as a control. The first (D95% ≤ 95%) and second (D95% ≤ 90%) plan breaching points due to motion amplitude increase were identified and analyzed. The PTV D95% in the motion-incorporated plans was 99.4 ± 1.0% using 4DCT, closely agreeing with the corresponding ITV-based VMAT plan (PTV D95% 100%). Tumor motion irregularities were observed in TR-4DMRI and triggered D95% ≤ 95% in one case. For small tumors, 4 mm extra motion triggered D95% ≤ 95%, and 6-8 mm triggered D95% ≤ 90%. For large tumors, 14 mm and 21 mm extra motions triggered the first and second breaching points, respectively. This study has demonstrated that PTV D95% breaching points may occur for small tumors during treatment delivery. Clinically, it is important to monitor and avoid systematic motion increase, including baseline drift, and large random motion spikes through threshold-based beam gating.

Factors Associated with Early Discharge after Thoracoscopic Lobectomy Results from the Italian VATS Group Registry.

There are limited data for estimating the risk of early discharge following thoracoscopic lobectomy. The objective was to identify the factors associated with a short length of stay and verify the influence of these variables in uncomplicated patients. We reviewed all lobectomies reported to the Italian VATS Group between January 2014 and January 2020. Patients and perioperative characteristics were divided into two subgroups based on whether or not they met the target duration of stay (≤ or gt4 days). The association between preoperative and intraoperative variables and postoperative length of stay (LOS) ≤4 days was assessed using a stepwise multivariable logistic regression analysis to identify factors independently associated with LOS and factors related to LOS in uncomplicated cases. Among 10,240 cases who underwent thoracoscopic lobectomy, 37.6% had a hospital stay ≤4 days. Variables associated with LOS included age, hospital surgical volume, Diffusion Lung CO % (81 69-94 vs. 85 73-98), Forced Expiratory Volume (FEV1) % (92 79-106 vs. 96 82-109), operative time (180 141-230 vs. 160 125-195), uniportal approach (571 9% vs. 713 18.5%), bioenergy sealer use, and pain control through intercostal block or opioids ( Demographic, clinical, and surgical variables are associated with early discharge after thoracoscopic lobectomy. This study indicates that these characteristics are associated with early discharge. This result can be used in association with clinical judgment to identify appropriate patients for fast-track protocols.

Malignancies in Patients with Interstitial Lung Diseases A Single Center Observational Study.

Current studies focus on the prevalence rate of lung cancer in idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease (CTD-LID). Our aim was to investigate the prevalence of malignancies in patients with various subtypes of ILD. A total of 5350 patients diagnosed with ILD between January 2015 and December 2021 were retrospectively included. The prevalence of different malignancies and different ILDs was assessed using complete follow-up data. A total of 248 patients (139 males 65-IQR, 57 to 72-years) out of 5350 patients with ILD were confirmed with malignancies. A total of 69% of patients with ILD and malignances were older than 60 years old. The prevalence of malignancies in ILD patients was 4.6%, and lung cancer had the most common incidence of 1.9%, followed by malignancies in the digestive system of 0.9%. Among the different ILD subtypes, the prevalence of malignancies such as organizing pneumonia (OP), idiopathic pulmonary fibrosis (IPF), anti-neutrophil cytoplasmic antibodies-associated vasculitis-related ILD(AAV-ILD), nonspecific interstitial pneumonia (NSIP), CTD-ILD, hypersensitivity pneumonitis (HP), sarcoidosis, and other types of ILD was 6.8%, 5.0%, 4.7%, 4.3%, 2.5%, 2.2%, 1.2%, and 6.9%, respectively. The incidence of lung cancer as the most common tumor in IPF was 3.9%, with adenocarcinoma predominating (1.7%). The highest rate of malignancy occurring in RA of CTD-ILD was 2.4%. Older patients with ILD (≥60 years) including OP, IPF, AAV-ILD, NSIP, CTD-ILD, and HP, were associated with a higher incidence of malignancy, especially males aged from 60 to 69 years. These epidemiological results indicate that it is essential for physicians to pay more attention to the screening of and management strategies for different malignancies, according to the specific ILD subtypes.

Performance of Scoring Systems in Predicting Clinical Outcomes of Patients with Emphysematous Pyelonephritis A 14-Year Hospital-Based Study.

Emphysematous pyelonephritis (EPN) is a rare but severe necrotizing infection causing there to be gas in the pelvicalyceal system, renal parenchyma, and perirenal or pararenal space. Physicians should attend to EPN because of its life-threatening septic complications. The overall mortality rate has been reported to be as high as 20-40%. In addition, most patients had diabetes mellitus (DM) and obstructive uropathy. The most common isolated microorganism is We collected the data of patients with EPN in this single hospital-based retrospective study from the electronic medical records of Taichung Veterans General Hospital between January 2007 and December 2020. Radiological investigations of abdominal computed tomography (CT) confirmed the diagnosis of EPN. In addition, we analyzed demographics, clinical characteristics, and laboratory data. Finally, we used various scoring systems to predict clinical outcomes. A total of fifty patients with EPN, whose diagnoses were confirmed through CT, were enrolled in the study. There were 18 males (36%) and 32 females (64%), with a mean age of 64.3 ± 11.3 years. The in-hospital mortality rate was 16%. A DM of 34 (68%) patients was the most common comorbidity. Fever was the most common symptom, found in 25 (50%) patients. The Mortality in Emergency Department Sepsis (MEDS) score was 4.64 ± 3.67 for survivors and 14.25 ± 5.34 for non-survivors ( MEDS, REMS, and NEWS could be prognostic tools for the prediction of the clinical outcomes of patients with EPN. MEDS showed the best sound performance. In those with higher scores in MEDS (≥12), REMS (≥10), and NEWS (≥8), we recommended aggressive management and appropriate antimicrobial therapy as soon as possible to reduce mortality. Further large-scale studies are required to gain a deep understanding of this disease and to ensure patient safety.

Microbial Biomarkers for Lung Cancer Current Understandings and Limitations.

As our hidden organ, microbes widely co-exist at various sites on the human body. These microbes are collectively referred to as the microbiome. A considerable number of studies have already proven that the microbiome has significant impacts on human health and disease progression, including cancers. The recent discovery of cancer-specific microbiomes renders these cancer-associated microbes as potential biomarkers and therapeutic targets. While at low biomass levels, the lung microbiome still dramatically influences the initiation, progression and treatment of lung cancers. However, research on lung cancer-associated microbiomes is emerging, and most profiling studies are performed within three years. Unfortunately, there are substantial inconsistencies across these studies. Variations in microbial diversity were observed, and different microbial biomarkers for lung cancer have been proposed. In this review, we summarized the current findings of lung cancer microbiome studies and attempt to explain the potential reasons for the dissimilarities. Other than lung microbiomes, oral and airway microbiomes are highly related to lung microbiomes and are therefore included as well. In addition, several lung cancer-associated bacterial genera have been detected by different independent studies. These bacterial genera may not be perfect biomarkers, but they still serve as promising risk factors for lung cancers and show great prognostic value.

Sleep Characteristics and Cancer-Related Outcomes An Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies.

Sleep is closely related to various diseases. Several meta-analyses have provided evidence of sleep and cancer, and yet the credibility of this evidence has not been comprehensively quantified. Thus, we conducted an umbrella review to quantify the evidence for systematic reviews and meta-analyses of observational studies on sleep characteristics (sleep duration, sleep quality, napping, bedtime, and wake-up time) and cancer-related outcomes. PubMed, Web of Science (Core Collection), and Embase databases were searched from inception until 29 July 2022. Assessment of Multiple Systematic Reviews, version 1, was used to evaluate the methodological quality of each eligible systematic review or meta-analysis. For each association, the summary effect with a 95% confidence interval was evaluated by fixed and random effects models. The 95% prediction interval, heterogeneity, small-study effects, and excess significance bias were also evaluated. Evidence of the associations from systematic reviews and meta-analyses was ranked based on the established criteria of published literature as convincing, highly suggestive, suggestive, weak, or non-significant. The umbrella review identified thirty meta-analyses on the aforementioned associations from six articles. The methodological quality of five articles was high or moderate. Suggestive evidence was found for associations between long sleep duration and a 21% increased risk of colorectal cancer, a 9% increased all-cancer mortality and a 65% increased mortality of lung cancer, and associations between short sleep duration and a 21% increased mortality of lung cancer. Additionally, the evidence of associations between short sleep duration and lung cancer mortality was upgraded to convincing, and between long sleep duration and lung cancer mortality was upgraded to highly suggestive, among the population reporting 24 h sleep duration. Abnormal sleep duration might be linked to several adverse cancer-related outcomes.

DNA Methylation Alterations in Fractionally Irradiated Rats and Breast Cancer Patients Receiving Radiotherapy.

Radiation-Induced CardioVascular Disease (RICVD) is an important concern in thoracic radiotherapy with complex underlying pathophysiology. Recently, we proposed DNA methylation as a possible mechanism contributing to RICVD. The current study investigates DNA methylation in heart-irradiated rats and radiotherapy-treated breast cancer (BC) patients. Rats received fractionated whole heart X-irradiation (0, 0.92, 6.9 and 27.6 Gy total doses) and blood was collected after 1.5, 3, 7 and 12 months. Global and gene-specific methylation of the samples were evaluated and gene expression of selected differentially methylated regions (DMRs) was validated in rat and BC patient blood. In rats receiving an absorbed dose of 27.6 Gy, DNA methylation alterations were detected up to 7 months with differential expression of cardiac-relevant DMRs. Of those,

Advances in Imaging of Inflammation, Fibrosis, and Cancer in the Gastrointestinal Tract.

Gastrointestinal disease is prevalent and broad, manifesting itself in a variety of ways, including inflammation, fibrosis, infection, and cancer. However, historically, diagnostic technologies have exhibited limitations, especially with regard to diagnostic uncertainty. Despite development of newly emerging technologies such as optoacoustic imaging, many recent advancements have focused on improving upon pre-existing modalities such as ultrasound, computed tomography, magnetic resonance imaging, and endoscopy. These advancements include utilization of machine learning models, biomarkers, new technological applications such as diffusion weighted imaging, and new techniques such as transrectal ultrasound. This review discusses assessment of disease processes using imaging strategies for the detection and monitoring of inflammation, fibrosis, and cancer in the context of gastrointestinal disease. Specifically, we include ulcerative colitis, Crohns disease, diverticulitis, celiac disease, graft vs. host disease, intestinal fibrosis, colorectal stricture, gastric cancer, and colorectal cancer. We address some of the most recent and promising advancements for improvement of gastrointestinal imaging, including unique discussions of such advancements with regard to imaging of fibrosis and differentiation between similar disease processes.

Anticancer Effects of Fucoxanthin through Cell Cycle Arrest, Apoptosis Induction, Angiogenesis Inhibition, and Autophagy Modulation.

Cancer accounts for one in seven deaths worldwide and is the second leading cause of death in the United States, after heart disease. One of the standard cancer treatments is chemotherapy which sometimes can lead to chemoresistance and treatment failure. Therefore, there is a great need for novel therapeutic approaches to treat these patients. Novel natural products have exhibited anticancer effects that may be beneficial in treating many kinds of cancer, having fewer side effects, low toxicity, and affordability. Numerous marine natural compounds have been found to inhibit molecular events and signaling pathways associated with various stages of cancer development. Fucoxanthin is a well-known marine carotenoid of the xanthophyll family with bioactive compounds. It is profusely found in brown seaweeds, providing more than 10% of the total creation of natural carotenoids. Fucoxanthin is found in edible brown seaweed macroalgae such as

B7-H3CD276 Inhibitors Is There Room for the Treatment of Metastatic Non-Small Cell Lung Cancer

The striking clinical outcomes of antibody-based immunotherapy, through the inhibitors of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and the programmed cell death protein-1 (PD-1) and its ligand (PD-L1) axis, have driven research aimed at identifying further clinically relevant tumor antigens that can serve as targets in solid tumors. B7 homolog 3 protein (B7-H3, also known as CD276) is a member of the B7 family overexpressed in tumor tissues, including non-small cell lung cancer (NSCLC), while showing limited expression in normal tissues, becoming an attractive and promising target for cancer immunotherapy. B7-H3 expression in tumors has been demonstrated to be associated with poor prognosis. In addition to its role in immune modulation, B7-H3 also promotes pro-tumorigenic functions such as tumor migration, invasion, metastases, resistance, and metabolism. In this review, we will provide an overview of this newly characterized immune checkpoint molecule and its development in the management of metastatic NSCLC.

Intravesicular Genomic DNA Enriched by Size Exclusion Chromatography Can Enhance Lung Cancer Oncogene Mutation Detection Sensitivity.

Extracellular vesicles (EVs) are cell-derived structures surrounded by a lipid bilayer that carry RNA and DNA as potential templates for molecular diagnostics, e.g., in cancer genotyping. While it has been established that DNA templates appear on the outside of EVs, no consensus exists on which nucleic acid species inside small EVs (lt200 nm, sEVs) are sufficiently abundant and accessible for developing genotyping protocols. We investigated this by extracting total intravesicular nucleic acid content from sEVs isolated from the conditioned cell medium of the human NCI-H1975 cell line containing the epidermal growth factor (

Inhibition of TIGAR Increases Exogenous p53 and Cisplatin Combination Sensitivity in Lung Cancer Cells by Regulating Glycolytic Flux.

The metabolism and apoptosis of tumor cells are important factors that increase their sensitivity to chemotherapeutic drugs. p53 and cisplatin not only induce tumor cell apoptosis, but also regulate the tumor cell metabolism. The TP53-induced glycolysis and apoptosis regulator (TIGAR) can inhibit glycolysis and promote more glucose metabolism in the pentose phosphate pathway. We speculate that the regulation of the TIGAR by the combination therapy of p53 and cisplatin plays an important role in increasing the sensitivity of tumor cells to cisplatin. In this study, we found that the combined treatment of p53 and cisplatin was able to inhibit the mitochondrial function, promote mitochondrial pathway-induced apoptosis, and increase the sensitivity. Furthermore, the expression of the TIGAR was inhibited after a combined p53 and cisplatin treatment, the features of the TIGAR that regulate the pentose phosphate pathway were inhibited, the glucose flux shifted towards glycolysis, and the localization of the complex of the TIGAR and Hexokinase 2 (HK2) on the mitochondria was also reduced. Therefore, the combined treatment of p53 and cisplatin may modulate a glycolytic flux through the TIGAR, altering the cellular metabolic patterns while increasing apoptosis. Taken together, our findings reveal that the TIGAR may serve as a potential therapeutic target to increase the sensitivity of lung cancer A549 cells to cisplatin.

99-Metastabil Technetium (

Computational Prediction of Resistance Induced Alanine-Mutation in ATP Site of Epidermal Growth Factor Receptor.

Epidermal growth factor receptor (EGFR) resistance to tyrosine kinase inhibitors can cause low survival rates in mutation-positive non-small cell lung cancer patients. It is necessary to predict new mutations in the development of more potent EGFR inhibitors since classical and rare mutations observed were known to affect the effectiveness of the therapy. Therefore, this research aimed to perform alanine mutagenesis scanning on ATP binding site residues without COSMIC data, followed by molecular dynamic simulations to determine their molecular interactions with ATP and erlotinib compared to wild-type complexes. Based on the result, eight mutations were found to cause changes in the binding energy of the ATP analogue to become more negative. These included G779A, Q791A, L792A, R841A, N842A, V843A, I853A, and D855A, which were predicted to enhance the affinity of ATP and reduce the binding ability of inhibitors with the same interaction site. Erlotinib showed more positive energy among G779A, Q791A, I853A, and D855A, due to their weaker binding energy than ATP. These four mutations could be anticipated in the development of the next inhibitor to overcome the incidence of resistance in lung cancer patients.

The Educational Program of Macrophages toward a Hyperprogressive Disease-Related Phenotype Is Orchestrated by Tumor-Derived Extracellular Vesicles.

Hyperprogressive disease (HPD), an aggressive acceleration of tumor growth, was observed in a group of cancer patients treated with anti-PD1PDL1 antibodies. The presence of a peculiar macrophage subset in the tumor microenvironment is reported to be a sort of immunological prerequisite for HPD development. These macrophages possess a unique phenotype that it is not clear how they acquire. We hypothesized that certain malignant cells may promote the induction of an HPD-related phenotype in macrophages. Bone-marrow-derived macrophages were exposed to the conditioned medium of five non-small cell lung cancer cell lines. Macrophage phenotype was analyzed by microarray gene expression profile and real-time PCR. We found that human NSCLC cell lines, reported as undergoing HPD-like tumor growth in immunodeficient mice, polarized macrophages towards a peculiar pro-inflammatory phenotype sharing both M1 and M2 features. Lipid-based factors contained in cancer cell-conditioned medium induced the over-expression of several pro-inflammatory cytokines and the activation of innate immune receptor signaling pathways. We also determined that tumor-derived Extracellular Vesicles represent the main components involved in the observed macrophage re-education program. The present study might represent the starting point for the future development of diagnostic tools to identify potential hyperprogressors.

Cell Therapy with Human Reprogrammed CD8

Using a model of Lewis lung carcinoma (LLC) in vitro and in vivo, we previously demonstrated increased antitumor activity in CD8

Enhanced Therapeutic Effect of Optimized Melittin-dKLA, a Peptide Agent Targeting M2-like Tumor-Associated Macrophages in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by a high possibility of metastasis. M2-like tumor-associated macrophages (TAMs) are the main components of the tumor microenvironment (TME) and play a key role in TNBC metastasis. Therefore, TAMs may be a potential target for reducing TNBC metastasis. Melittin-dKLA, a peptide composed of fused melittin and pro-apoptotic peptide d(KLAKLAK)2 (dKLA), showed a potent therapeutic effect against cancers by depleting TAMs. However, melittin has a strong adverse hemolytic effect. Hence, we attempted to improve the therapeutic potential of melittin-dKLA by reducing toxicity and increasing stability. Nine truncated melittin fragments were synthesized and examined. Of the nine peptides, the melittin-dKLA8-26 showed the best binding properties to M2 macrophages and discriminated M0M1M2. All fragments, except melittin, lost their hemolytic effects. To increase the stability of the peptide, melittin-dKLA8-26 fragment was conjugated with PEGylation at the amino terminus and was named PEG-melittin-dKLA8-26. This final drug candidate was assessed in vivo in a murine TNBC model and showed superior effects on tumor growth, survival rates, and lung metastasis compared with the previously used melittin-dKLA. Taken together, our study showed that the novel PEG-melittin-dKLA8-26 possesses potential as a new drug for treating TNBC and TNBC-mediated metastasis by targeting TAMs.

Preferred Migration of Mitochondria toward Cells and Tissues with Mitochondrial Damage.

Mitochondria are organelles that play a vital role in cellular survival by supplying ATP and metabolic substrates via oxidative phosphorylation and the Krebs cycle. Hence, mitochondrial dysfunction contributes to many human diseases, including metabolic syndromes, neurodegenerative diseases, cancer, and aging. Mitochondrial transfer between cells has been shown to occur naturally, and mitochondrial transplantation is beneficial for treating mitochondrial dysfunction. In this study, the migration of mitochondria was tracked in vitro and in vivo using mitochondria conjugated with green fluorescent protein (MT

Integrated Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Unravels the Influences of SARS-CoV-2 Infections to Cancer Patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious and pathogenic coronavirus that emerged in late 2019 and caused a pandemic of respiratory illness termed as coronavirus disease 2019 (COVID-19). Cancer patients are more susceptible to SARS-CoV-2 infection. The treatment of cancer patients infected with SARS-CoV-2 is more complicated, and the patients are at risk of poor prognosis compared to other populations. Patients infected with SARS-CoV-2 are prone to rapid development of acute respiratory distress syndrome (ARDS) of which pulmonary fibrosis (PF) is considered a sequelae. Both ARDS and PF are factors that contribute to poor prognosis in COVID-19 patients. However, the molecular mechanisms among COVID-19, ARDS and PF in COVID-19 patients with cancer are not well-understood. In this study, the common differentially expressed genes (DEGs) between COVID-19 patients with and without cancer were identified. Based on the common DEGs, a series of analyses were performed, including Gene Ontology (GO) and pathway analysis, protein-protein interaction (PPI) network construction and hub gene extraction, transcription factor (TF)-DEG regulatory network construction, TF-DEG-miRNA coregulatory network construction and drug molecule identification. The candidate drug molecules (e.g., Tamibarotene CTD 00002527) obtained by this study might be helpful for effective therapeutic targets in COVID-19 patients with cancer. In addition, the common DEGs among ARDS, PF and COVID-19 patients with and without cancer are TNFSF10 and IFITM2. These two genes may serve as potential therapeutic targets in the treatment of COVID-19 patients with cancer. Changes in the expression levels of TNFSF10 and IFITM2 in CD14CD16 monocytes may affect the immune response of COVID-19 patients. Specifically, changes in the expression level of TNFSF10 in monocytes can be considered as an immune signature in COVID-19 patients with hematologic cancer. Targeting N

Natural Taxanes From Plant Composition to Human Pharmacology and Toxicity.

Biologically active taxanes, present in small- to medium-sized evergreen conifers of various

De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity.

Despite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their effectiveness on a variety of molecular targets, along with high selectivity and specificity for cancer cells. In the present study, a novel ACP was de novo designed using in silico methods, and its functionality and molecular mechanisms of action were explored. AC-P19M was discovered through functional prediction and sequence modification based on peptide sequences currently available in the database. The peptide exhibited anticancer activity against lung cancer cells, A549 and H460, by disrupting cellular membranes and inducing apoptosis while showing low toxicity towards normal and red blood cells. In addition, the peptide inhibited the migration and invasion of lung cancer cells and reversed epithelial-mesenchymal transition. Moreover, AC-P19M showed anti-angiogenic activity through the inhibition of vascular endothelial growth factor receptor 2 signaling. Our findings suggest that AC-P19M is a novel ACP that directly or indirectly targets cancer cells, demonstrating the potential development of an anticancer agent and providing insights into the discovery of functional substances based on an in silico approach.

Immunomodulation of HDAC Inhibitor Entinostat Potentiates the Anticancer Effects of Radiation and PD-1 Blockade in the Murine Lewis Lung Carcinoma Model.

Although the combination of radiotherapy and immunotherapy has proven to be effective in lung cancer treatment, it may not be sufficient to fully activate the antitumor immune response. Here, we investigated whether entinostat, a histone deacetylase inhibitor, could improve the efficacy of radiotherapy and anti-PD-1 in a murine syngeneic LL2 tumor model. A total of 12 Gy of X-rays administered in two fractions significantly delayed tumor growth in mice, which was further enhanced by oral entinostat administration. Flow cytometry-aided immune cell profiling revealed that entinostat increased radiation-induced infiltration of myeloid-derived suppressor cells and CD8

Mebendazole Increases Anticancer Activity of Radiotherapy in Radiotherapy-Resistant Triple-Negative Breast Cancer Cells by Enhancing Natural Killer Cell-Mediated Cytotoxicity.

Breast cancer is the most commonly diagnosed cancer worldwide and ranks first in terms of both prevalence and cancer-related mortality in women. In this study, we aimed to evaluate the anticancer effect of mebendazole (MBZ) and radiotherapy (RT) concomitant use in triple-negative breast cancer (TNBC) cells and elucidate the underlying mechanisms of action. Breast cancer mouse models and several types of breast cancer cells, including TNBC-derived RT-resistant (RT-R) MDA-MB-231 cells, were treated with MBZ andor RT. In mice, changes in body weight, renal and liver toxicity, tumor volume, and number of lung metastases were determined. In cells, cell viability, colony formation, scratch wound healing, Matrigel invasion, and protein expression using western blotting were determined. Our findings showed that MBZ and RT combined treatment increased the anticancer effect of RT without additional toxicity. In addition, we noted that cyclin B1, PH2AX, and natural killer (NK) cell-mediated cytotoxicity increased following MBZ RT treatment compared to unaided RT. Our results suggest that MBZ RT have an enhanced anticancer effect in TNBC which acquires radiation resistance through blocking cell cycle progression, initiating DNA double-strand breaks, and promoting NK cell-mediated cytotoxicity.

Elevation of Anticancer Drug Toxicity by Caffeine in Spheroid Model of Human Lung Adenocarcinoma A549 Cells Mediated by Reduction in Claudin-2 and Nrf2 Expression.

Claudin-2 (CLDN2), a component of tight junctions, is abnormally expressed in human lung adenocarcinoma tissue. CLDN2 contributes to chemoresistance in human lung adenocarcinoma-derived A549 cells, and it may be a target for cancer therapy. Here, we found that coffee ingredients, namely caffeine and theobromine, decreased the protein level of CLDN2 in human lung adenocarcinoma-derived A549 cells. In contrast, other components, such as theophylline and chlorogenic acid, had no effect. These results indicate that the 7-methyl group in methylxanthines may play a key role in the reduction in CLDN2 expression. The caffeine-induced reduction in the CLDN2 protein was inhibited by chloroquine, a lysosome inhibitor. In a protein-stability assay using cycloheximide, CLDN2 protein levels decreased faster in caffeine-treated cells than in vehicle-treated cells. These results suggest that caffeine accelerates the lysosomal degradation of CLDN2. The accumulation and cytotoxicity of doxorubicin were dose-dependently increased, which was exaggerated by caffeine but not by theophylline in spheroids. Caffeine decreased nuclear factor-erythroid 2-related factor 2 (Nrf2) levels without affecting hypoxia-inducible factor-1α levels. Furthermore, caffeine decreased the expression of Nrf2-targeted genes. The effects of caffeine on CLDN2 expression and anticancer-drug-induced toxicity were also observed in lung adenocarcinoma RERF-LC-MS cells. We suggest that caffeine enhances doxorubicin-induced toxicity in A549 spheroids mediated by the reduction in CLDN2 and Nrf2 expression.

Systematic Review of Smoking Cessation Inventions for Smokers Diagnosed with Cancer.

The detrimental impact of smoking on health and wellbeing are irrefutable. Additionally, smoking is associated with the development of cancer, a reduction treatment outcomes and poorer health outcomes. Nevertheless, a significant number of people continue to smoke following a cancer diagnosis. Little is understood of the smoking cessation services provided to smokers with cancer or their engagement with them. This systematic review aimed to identify existing smoking cessation interventions for this cohort diagnosed with breast, head and neck, lung and cervical cancers (linked to risk). Systematic searches of Pubmed, Embase, Psych Info and CINAHL from 1 January 2015 to 15 December 2020 were conducted. Included studies examined the characteristics of smoking cessation interventions and impact on referrals and quit attempts. The impact on healthcare professionals was included if reported. Included studies were restricted to adults with a cancer diagnosis and published in English. No restriction was placed on study designs, and narrative data synthesis was conducted due to heterogeneity. A review protocol was registered on PROSPERO CRD 42020214204, and reporting adheres to PRISMA reporting guidelines. Data were screened, extracted in duplicate and an assessment of the quality of evidence undertaken using Mixed Methods Assessment Tool. 23 studies met the inclusion criteria, representing USA, Canada, England, Lebanon, Australia and including randomized controlled trials (9), observational studies (10), quality improvement (3), and one qualitative study. Hospital and cancer clinics including a dental clinic were the settings for all studies. 43% (1023) of studies reported interventions for smokers diagnosed with head and neck cancer, 13% (323) for smokers diagnosed with lung cancer, one study provides evidence for breast cancer, and the remaining nine studies (39%) report on multiple cancers including the ones specified in this review. Methodological quality was variable. There were limited data to identify one optimal intervention for this cohort. Key elements included the timing and frequency of quit conversations, use of electronic records, pharmacotherapy including extended use of varenicline, increased counselling sessions and a service embedded in oncology departments. More studies are required to ensure tailored smoking cessation pathways are co-developed for smokers with a diagnosis of cancer to support this population.

Pathogenic Potential of Respirable Spodumene Cleavage Fragments following Application of Regulatory Counting Criteria for Asbestiform Fibres.

Health risks from exposure to lithium-bearing spodumene cleavage fragments are unknown. While asbestiform fibres can lead to fibrosis, mesothelioma and lung cancer, controversy remains whether non-asbestiform cleavage fragments, having equivalent dimensions, elicit similar pathologic responses. The mineralogy of respirable particles from two alpha (α)-spodumene concentrate grades (chemical and technical) were characterised using semi-quantitative X-ray diffraction (XRD). Particles were measured using scanning electron microscopy (SEM) and the dimensions (length L, diameter D, aspect ratio AR) applied to regulatory counting criteria for asbestiform fibres. Application of the current World Health Organization (WHO) and National Occupational Health and Safety Commission (NOHSC) counting criteria, L ˃ 5 µm, D ˂ 3 µm, AR ˃ 31, to 10 SEM images of each grade identified 47 countable particles in the chemical and 37 in the technical concentrate test samples. Of these particles, 17 and 16 in the chemical and technical test samples, respectively, satisfied the more rigorous, previously used

Smoking Behavior and Smoking Cessation Because of and during the COVID-19 Pandemic A Brief Online Survey 12 Months into the Pandemic and during the Second Wave in Europe.

Smoking is considered a major preventable cause of cardiovascular and lung diseases, as well as cancer. During the COVID-19 pandemic, there was extensive discussion about the influence of nicotine use ultimately, smoking was considered a major risk factor for poor disease progression. Therefore, in April 2021, we conducted an anonymous cross-sectional online survey on smoking and vaping behavior, as well as smoking cessation, in four different countries in Europe (the United Kingdom, Germany, Spain, and Italy). A total of 3605 participants completed a questionnaire on their smoking and vaping behaviors and smoking cessation because of and during the COVID-19 pandemic. Fear of COVID-19 infection, a high percentage of quarantine stays (44.9% Italy and 52.1% Spain), and high infection (75.5% Italy and 52.4% Spain) and death (42% Italy) rates in respondents personal circles were observed mostly in the surveyed populations of Italy and Spain. Smoking cessation attempts and success were mainly seen in the Italian population and were linked to psychological distress, while the same effects were shown for vaping in Spain. In summary, health anxiety was detected in all cohorts. Despite these findings, smoking as a risk factor for severe outcomes of COVID-19 infection did not lead to a higher rate of smoking cessation attempts.

Comorbidity and Cancer Disease Rates among Those at High-Risk for Alzheimers Disease A Population Database Analysis.

(1) Importance Alzheimers disease (AD) is complex and only partially understood. Analyzing the relationship between other more treatable or preventable diseases and AD may help in the prevention and the eventual development of treatments for AD. Risk estimation in a high-risk population, rather than a population already affected with AD, may reduce some bias in risk estimates. (2) Objective To examine the rates of various comorbidities and cancers in individuals at high-risk for AD, but without a clinical diagnosis, relative to individuals from the same population with normal AD risk. (3) Design, Setting, and Participants We conducted a study using data from the Utah Population Database (UPDB). The UPDB contains linked data from the Utah Cancer Registry, Utah death certificates, the Intermountain Health patient population, and the University of Utah Health patient population. Subjects were selected based on the availability of ancestral data, linked health information, and self-reported biometrics. (4) Results In total, 75,877 participants who were estimated to be at high risk for AD based on family history, but who did not have an active AD diagnosis, were analyzed. A lower incidence of diabetes (RR 0.95, 95% CI 0.92,0.97,

The Direct and Indirect Costs of Breast Cancer in Poland Estimates for 2017-2019.

In Poland, breast cancer (BC) is the most frequently diagnosed cancer in women and the second most common cause of death after lung cancer. This disease has important economic implications for patients, public payers, and the whole Polish economy. This study aimed to estimate the total National Health Fund (NHF) expenditures on the diagnosis and treatment of patients with breast cancer. In addition, the costs of productivity losses were also calculated. Cost estimation was prepared using a top-down approach. Direct cost calculations were based on data reported by NHF for patients with the diagnosis of breast cancer. Medical care costs included the following components screening program, oncological package, surgical treatment, hospitalization, drug program, chemotherapy, radiotherapy, and outpatient care. Indirect costs in the form of absenteeism costs were calculated based on data from Statistics Poland (gross domestic product, number of employees) and the Social Insurance Institution database (the number of sick leave days). Total expenditures for BC including direct costs and indirect costs amounted to EUR 305,371, EUR 332,998, and EUR 344,649, respectively in 2017, 2018, and 2019. Total healthcare costs in 2019 were EUR 4114 lower than in 2018, which resulted from the reduction in expenditure on the drug program (decrease of EUR 13,527), despite the observed increase in all remaining resources. From direct costs, the highest expense was spent on the drug program (nearly 50% of total direct costs), but this expense dropped significantly in 2019. For the remaining parameters, the costs increased year by year, of which the most expensive were surgical treatment (15%), radiotherapy (12%), and the screening program (10%). BC generated over EUR 120 thousand of social costs in 2019 and compared to 2017, there was an increase in productivity loss by 26%. Our results from 2017-2019 demonstrated that total expenditure for BC in Poland increased from year to year. Breast cancer generated almost EUR 345 thousand expenses in 2019, which translates into a significant burden on the public payers budget and the society in Poland.

Improved Complementary Pulmonary Nodule Segmentation Model Based on Multi-Feature Fusion.

Accurate segmentation of lung nodules from pulmonary computed tomography (CT) slices plays a vital role in the analysis and diagnosis of lung cancer. Convolutional Neural Networks (CNNs) have achieved state-of-the-art performance in the automatic segmentation of lung nodules. However, they are still challenged by the large diversity of segmentation targets, and the small inter-class variances between the nodule and its surrounding tissues. To tackle this issue, we propose a features complementary network according to the process of clinical diagnosis, which made full use of the complementarity and facilitation among lung nodule location information, global coarse area, and edge information. Specifically, we first consider the importance of global features of nodules in segmentation and propose a cross-scale weighted high-level feature decoder module. Then, we develop a low-level feature decoder module for edge feature refinement. Finally, we construct a complementary module to make information complement and promote each other. Furthermore, we weight pixels located at the nodule edge on the loss function and add an edge supervision to the deep supervision, both of which emphasize the importance of edges in segmentation. The experimental results demonstrate that our model achieves robust pulmonary nodule segmentation and more accurate edge segmentation.

Last Resort Antibiotics Costs and Reimbursement Analysis of Real-Life ICU Patients with Pneumonia Caused by Multidrug-Resistant Gram-Negative Bacteria in Germany.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) cause serious infections and aggravate disease progression. Last resort antibiotics are effective against MDR-GNB and are reimbursed by flat rates based on German diagnosis-related groups (G-DRG). From a hospital management perspective, this analysis compared hospital reimbursement for last resort antibiotics with their acquisition costs to outline potential funding gaps. Retrospective analyses based on medical charts and real-life reimbursement data included patients with pneumonia due to MDR-GNB treated in intensive care units (ICU) of a German tertiary care hospital (University Hospital Cologne) between January 2017 and December 2020. Drug-associated hospital reimbursement of G-DRG was compared with drug acquisition costs based on preliminarily approved last resort antibiotics (cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-cilastatin-relebactam) according to label. Funding gaps were determined for the treatment of

Dietary Antioxidants and Lung Cancer Risk in Smokers and Non-Smokers.

Smoking is considered a major risk factor in the development of lung diseases worldwide. Active smoking and secondhand (passive) smoke (SHS) are related to lung cancer (LC) risk. Oxidative stress (OS) andor lipid peroxidation (LP) induced by cigarette smoke (CS) are found to be involved in the pathogenesis of LC. Meta-analyses and other case-controlprospective cohort studies are inconclusive and have yielded inconsistent results concerning the protective role of dietary vitamins C and E, retinol, and iron intake against LC risk in smokers andor non-smokers. Furthermore, the role of vitamins and minerals as antioxidants with the potential in protecting LC cells against CS-induced OS in smokers and non-smokers has not been fully elucidated. Thus, this review aims to summarize the available evidence reporting the relationships between dietary antioxidant intake and LC risk in smokers and non-smokers that may be used to provide suggestions for future research.

The Impact of Popular Science Articles by Physicians on Their Performance on Online Medical Platforms.

The public demand for popular science knowledge regarding health is increasing, and physicians popular science practices on online medical platforms are becoming frequent. Few studies have been conducted to address the relationship between specific characteristics of popular science articles by physicians and their performance. This study explored the impact of the characteristics of popular science articles on physicians performance based on the elaboration likelihood model (ELM) from the central path (topic focus and readability) and the peripheral path (form diversity). Data on four diseases, namely, lung cancer, brain hemorrhage, hypertension, and depression, were collected from an online medical platform, resulting in relevant personal data from 1295 doctors and their published popular science articles. Subsequently, the independent variables were quantified using thematic analysis and formula calculation, and the research model and hypotheses proposed in this paper were verified through empirical analysis. The results revealed that the topic focus, readability, and form diversity of popular science articles by physicians had a significant positive effect on physicians performance. This study enriches the research perspective on the factors influencing physicians performance, which has guiding implications for both physicians and platforms, thereby providing a basis for patients to choose physicians and enabling patients to receive popular science knowledge regarding health in an effective manner.

RNA Epigenetics in Chronic Lung Diseases.

Chronic lung diseases are highly prevalent worldwide and cause significant mortality. Lung cancer is the end stage of many chronic lung diseases. RNA epigenetics can dynamically modulate gene expression and decide cell fate. Recently, studies have confirmed that RNA epigenetics plays a crucial role in the developing of chronic lung diseases. Further exploration of the underlying mechanisms of RNA epigenetics in chronic lung diseases, including lung cancer, may lead to a better understanding of the diseases and promote the development of new biomarkers and therapeutic strategies. This article reviews basic information on RNA modifications, including

Proposing Specific Neuronal Epithelial-to-Mesenchymal Transition Genes as an Ancillary Tool for Differential Diagnosis among Pulmonary Neuroendocrine Neoplasms.

Pulmonary neuroendocrine neoplasms (PNENs) are currently classified into four major histotypes, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). This classification was designed to be applied to surgical specimens mostly anchored in morphological parameters, resulting in considerable overlapping among PNENs, which may result in important challenges for clinicians decisions in the case of small biopsies. Since PNENs originate from the neuroectodermic cells, epithelial-to-mesenchymal transition (EMT) gene expression shows promise as biomarkers involved in the genotypic transformation of neuroectodermic cells, including mutation burden with the involvement of chromatin remodeling genes, apoptosis, and mitosis rate, leading to modification in final cellular phenotype. In this situation, additional markers also applicable to biopsy specimens, which correlate PNENs subtypes with systemic treatment response, are much needed, and current potential candidates are neurogenic EMT genes. This study investigated EMT genes expression and its association with PNENs histotypes in tumor tissues from 24 patients with PNENs. PCR Array System for 84 EMT-related genes selected 15 differentially expressed genes among the PNENs, allowing to discriminate TC from AC, LCNEC from AC, and SCLC from AC. Functional enrichment analysis of the EMT genes differentially expressed among PNENs subtypes showed that they are involved in cellular proliferation, extracellular matrix degradation, regulation of cell apoptosis, oncogenesis, and tumor cell invasion. Interestingly, four EMT genes (

Identification of an Amino Acid Metabolism-Related Gene Signature for Predicting Prognosis in Lung Adenocarcinoma.

Dysregulation of amino acid metabolism (AAM) is an important factor in cancer progression. This study intended to study the prognostic value of AAM-related genes in lung adenocarcinoma (LUAD).

Optimal microRNA Sequencing Depth to Predict Cancer Patient Survival with Random Forest and Cox Models.

(1) Background tumor profiling enables patient survival prediction. The two essential parameters to be calibrated when designing a study based on tumor profiles from a cohort are the sequencing depth of RNA-seq technology and the number of patients. This calibration is carried out under cost constraints, and a compromise has to be found. In the context of survival data, the goal of this work is to benchmark the impact of the number of patients and of the sequencing depth of miRNA-seq and mRNA-seq on the predictive capabilities for both the Cox model with elastic net penalty and random survival forest. (2) Results we first show that the Cox model and random survival forest provide comparable prediction capabilities, with significant differences for some cancers. Second, we demonstrate that miRNA andor mRNA data improve prediction over clinical data alone. mRNA-seq data leads to slightly better prediction than miRNA-seq, with the notable exception of lung adenocarcinoma for which the tumor miRNA profile shows higher predictive power. Third, we demonstrate that the sequencing depth of RNA-seq data can be reduced for most of the investigated cancers without degrading the prediction abilities, allowing the creation of independent validation sets at a lower cost. Finally, we show that the number of patients in the training dataset can be reduced for the Cox model and random survival forest, allowing the use of different models on different patient subgroups.

Mechanisms of EGFR-TKI-Induced Apoptosis and Strategies Targeting Apoptosis in EGFR-Mutated Non-Small Cell Lung Cancer.

Homeostasis is achieved by balancing cell survival and death. In cancer cells, especially those carrying driver mutations, the processes and signals that promote apoptosis are inhibited, facilitating the survival and proliferation of these dysregulated cells. Apoptosis induction is an important mechanism underlying the therapeutic efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-small cell lung cancer (NSCLC). However, the mechanisms by which EGFR-TKIs induce apoptosis have not been fully elucidated. A deeper understanding of the apoptotic pathways induced by EGFR-TKIs is essential for the developing novel strategies to overcome resistance to EGFR-TKIs or to enhance the initial efficacy through therapeutic synergistic combinations. Recently, therapeutic strategies targeting apoptosis have been developed for cancer. Here, we review the state of knowledge on EGFR-TKI-induced apoptotic pathways and discuss the therapeutic strategies for enhancing EGFR-TKI efficiency. We highlight the great progress achieved with third-generation EGFR-TKIs. In particular, combination therapies of EGFR-TKIs with anti-vascular endothelial growth factorreceptor inhibitors or chemotherapy have emerged as promising therapeutic strategies for patients with EGFR-mutated NSCLC. Nevertheless, further breakthroughs are needed to yield an appropriate standard care for patients with EGFR-mutated NSCLC, which requires gaining a deeper understanding of cancer cell dynamics in response to EGFR-TKIs.

Expression Analysis of Five Different Long Non-Coding Ribonucleic Acids in Nonsmall-Cell Lung Carcinoma Tumor and Tumor-Derived Exosomes.

Long non-coding ribonucleic acids (LncRNAs) are recently known for their role in regulating gene expression and the development of cancer. Controversial results indicate a correlation between the tissue expression of LncRNA and LncRNA content of extracellular vesicles. The present study aimed to evaluate the expression of different LncRNAs in non-small cell lung cancer (NSCLC) patients in tumor tissue, adjacent non-cancerous tissue (ANCT), and exosome-mediated lncRNA. Tumor and ANCT, as well as serum samples of 168 patient with NSCLC, were collected. The GHSROS, HNF1A-AS1, HOTAIR, HMlincRNA717, and LINCRNA-p21 relative expressions in tumor tissue, ANCT, and serum exosomes were evaluated in NSCLC patients. Among 168 NSCLC samples, the expressions of GHSROS (REx 3.64,

When Pulmonologists Are Novice to Navigational Bronchoscopy, What Predicts Diagnostic Yield

Predicting factors of diagnostic yield in electromagnetic navigation bronchoscopy (ENB) have been explored in a number of previous studies based on data from experienced operators. However, little is known about predicting factors when the procedure is carried out by operators in the beginning of their learning curve. We here aim to identify the role of operators experience as well as lesion- and procedure characteristics on diagnostic yield of ENB procedures in the hands of novice ENB operators. Four operators from three centers without prior ENB experience were enrolled. The outcome of consecutive ENB procedures was assessed and classified as either diagnostic or non-diagnostic and predicting factors of diagnostic yield were assessed. A total of 215 procedures were assessed. A total of 122 (57%) of the ENB procedures resulted in diagnostic biopsies. Diagnostic ENB procedures were associated with a minor yet significant difference in tumor size compared to non-diagnosticinconclusive ENB procedures (28 mm vs. 24 mm

The Genetic and Epigenetic Footprint in Idiopathic Pulmonary Fibrosis and Familial Pulmonary Fibrosis A State-of-the-Art Review.

Idiopathic pulmonary fibrosis (IPF) is a rare disease of the lung with a largely unknown etiology and a poor prognosis. Intriguingly, forms of familial pulmonary fibrosis (FPF) have long been known and linked to specific genetic mutations. There is little evidence of the possible role of genetics in the etiology of sporadic IPF. We carried out a non-systematic, narrative literature review aimed at describing the main known genetic and epigenetic mechanisms that are involved in the pathogenesis and prognosis of IPF and FPF. In this review, we highlighted the mutations in classical genes associated with FPF, including those encoding for telomerases (

Breast Cancer Detection Using Automated Segmentation and Genetic Algorithms.

Breast cancer is the most common cancer among women worldwide, after lung cancer. However, early detection of breast cancer can help to reduce death rates in breast cancer patients and also prevent cancer from spreading to other parts of the body. This work proposes a new method to design a bio-marker integrating Bayesian predictive models, pyRadiomics System and genetic algorithms to classify the benign and malignant lesions. The method allows one to evaluate two types of images The radiologist-segmented lesion, and a novel automated breast cancer detection by the analysis of the whole breast. The results demonstrate only a difference of 12% of effectiveness for the cases of calcification between the radiologist generated segmentation and the automatic whole breast analysis, and a 25% of difference between the lesion and the breast for the cases of masses. In addition, our approach was compared against other proposed methods in the literature, providing an AUC 0.86 for the analysis of images with lesions in breast calcification, and AUC 0.96 for masses.

Quantitative Airway Assessment of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) on CT as a Novel Biomarker.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) occurs due to abnormal proliferation of pulmonary neuroendocrine cells. We hypothesized that performing a quantitative analysis of airway features on chest CT may reveal differences to matched controls, which could ultimately help provide an imaging biomarker. A retrospective quantitative analysis of chest CTs in patients with DIPNECH and age matched controls was carried out using semi-automated post-processing software. Paired segmental airway and artery diameters were measured for each bronchopulmonary segment, and the airwayartery (AA) ratio, airway wall thicknessartery ratio (AWTA ratio) and wall area percentage (WAP) calculated. Nodule number, size, shape and location was recorded. Correlation between CT measurements and pulmonary function testing was performed. 16 DIPNECH and 16 control subjects were analysed (all female, mean age 61.7 - 11.8 years), a combined total of 425 bronchopulmonary segments. The mean AwtA ratio, AA ratio and WAP for the DIPNECH group was 0.57, 1.18 and 68.8%, respectively, compared with 0.38, 1.03 and 58.3% in controls ( Quantitative CT airway analysis in patients with DIPNECH demonstrates increased airway wall thickness and airwayartery ratio compared to controls. Quantitative CT measurement of airway wall thickening offers a potential imaging biomarker for treatment response.

Real-World Patterns and Decision Drivers of Radiotherapy for Lung Cancer Patients in Romania RADIO-NET Study Results.

Radiotherapy (RT) plays a crucial role in all stages of lung cancer. Data on recent real-world RT patterns and main drivers of RT decisions in lung cancer in Romania is scarce we aimed to address these knowledge gaps through this physician-led medical chart review in 16 RT centers across the country. Consecutive patients with lung cancer receiving RT as part of their disease management between May-October 2019 (pre-COVID-19 pandemic) were included. Descriptive statistics were generated for all variables. This cohort included 422 patients median age 63 years, males 76%, stages I-II 6%, III 43%, IV 50%, mostly adeno- and squamous cell carcinoma (76%), ECOG 0-1 50% at the time of RT. Curative intent RT was used in 36% of cases, palliative RT in 64%. Delays were reported in 13% of patients, mostly due to machine breakdown (67%). Most acute reported RT toxicity was esophagitis (19%). Multiple disease-, patient-, physician- and context-related drivers counted in the decision-making process. This is the first detailed analysis of RT use in lung cancer in Romania. Palliative RT still dominates the landscape. Earlier diagnosis, coordinated multidisciplinary strategies, and the true impact of the multimodal treatments on survival are strongly needed to improve lung cancer outcomes.

The Feasibility of Using the Artery Sign for Pre-Procedural Planning in Navigational Bronchoscopy for Parenchymal Pulmonary Lesion Sampling.

Electromagnetic navigation bronchoscopy (ENB) and robotic-assisted bronchoscopy (RAB) systems are used for pulmonary lesion sampling, and utilize a pre-procedural CT scan where an airway, or bronchus sign, is used to map a pathway to the target lesion. However, up to 40% of pre-procedural CTs lack a bronchus sign partially due to surrounding emphysema or limitation in CT resolution. Recognizing that the branches of the pulmonary artery, lymphatics, and airways are often present together as the bronchovascular bundle, we postulate that a branch of the pulmonary artery (artery sign) could be used for pathway mapping during navigation bronchoscopy when a bronchus sign is absent. Herein we describe the navigation success and safety of using the artery sign to create a pathway for pulmonary lesion sampling. We reviewed data on consecutive cases in which the artery sign was used for pre-procedural planning for conventional ENB (superDimension™, Medtronic) and RAB (Monarch™, Johnson Johnson). Patients who underwent these procedures from July 2020 until July 2021 at the University of Minnesota Medical Center and from June 2018 until December 2019 at the University of Chicago Medical Center were included in this analysis (IRB 19-0011 for the University of Chicago and IRB 00013135 for the University of Minnesota). The primary outcome was navigation success, defined as successfully maneuvering the bronchoscope to the target lesion based on feedback from the navigation system. Secondary outcomes included navigation success based on radial EBUS imaging, pneumothorax, and bleeding rates. A total of 30 patients were enrolled in this analysis. The median diameter of the lesions was 17 mm. The median distance of the lesion from the pleura was 5 mm. Eleven lesions were solid, 15 were pure ground glass, and 4 were mixed. All cases were planned successfully using the artery sign on either the superDimension™ ENB (n 15) or the Monarch™ RAB (n 15). Navigation to the target was successful for 29 lesions (96.7%) based on feedback from the navigation system (virtual target). Radial EBUS image was acquired in 27 cases (90%) eccentric view in 13 (43.33%) and concentric view in 14 patients (46.66%), while in 3 cases (10%) no r-EBUS view was obtained. Pneumothorax occurred in one case (3%). Significant airway bleeding was reported in one case (3%). We describe the concept of using the artery sign as an alternative for planning EMN and RAB procedures when bronchus sign is absent. The navigation success based on virtual target or r-EBUS imaging is high and safety of sampling of such lesions compares favorably with prior reports. Prospective studies are needed to assess the impact of the artery sign on diagnostic yield.

Registered Clinical Trials for Artificial Intelligence in Lung Disease A Scoping Review on ClinicalTrials.gov.

Clinical trials are the most effective tools to evaluate the advantages of various diagnostic and treatment modalities. AI used in medical issues, including screening, diagnosis, and treatment decisions, improves health outcomes and patient experiences. This studys objective was to investigate the traits of registered trials on artificial intelligence for lung disease. Clinical studies on AI for lung disease that were present in the ClinicalTrials.gov database were searched, and fifty-three registered trials were included. Forty-six (72.1%) were observational trials, compared to seven (27.9%) that were interventional trials. Only eight trials (15.4%) were completed. Thirty (56.6%) trials were accepting applicants. Clinical studies often included a large number of cases for example, 24 (32.0%) trials included samples of 100-1000 cases, while 14 (17.5%) trials included samples of 1000-2000 cases. Of the interventional trials, twenty (15.7%) were retrospective studies and twenty (65.7%) were prospective studies.

A Survey on AI Techniques for Thoracic Diseases Diagnosis Using Medical Images.

Thoracic diseases refer to disorders that affect the lungs, heart, and other parts of the rib cage, such as pneumonia, novel coronavirus disease (COVID-19), tuberculosis, cardiomegaly, and fracture. Millions of people die every year from thoracic diseases. Therefore, early detection of these diseases is essential and can save many lives. Earlier, only highly experienced radiologists examined thoracic diseases, but recent developments in image processing and deep learning techniques are opening the door for the automated detection of these diseases. In this paper, we present a comprehensive review including types of thoracic diseases examination types of thoracic images image pre-processing models of deep learning applied to the detection of thoracic diseases (e.g., pneumonia, COVID-19, edema, fibrosis, tuberculosis, chronic obstructive pulmonary disease (COPD), and lung cancer) transfer learning background knowledge ensemble learning and future initiatives for improving the efficacy of deep learning models in applications that detect thoracic diseases. Through this survey paper, researchers may be able to gain an overall and systematic knowledge of deep learning applications in medical thoracic images. The review investigates a performance comparison of various models and a comparison of various datasets.

The Potential Role of MUC16 (CA125) Biomarker in Lung Cancer A Magic Biomarker but with Adversity.

Lung cancer is the second most commonly diagnosed cancer in the world. In terms of the diagnosis of lung cancer, combination carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) detection had higher sensitivity, specificity, and diagnostic odds ratios than CEA detection alone. Most individuals with elevated serum CA125 levels had lung cancer that was either in stage 3 or stage 4. Serum CA125 levels were similarly elevated in lung cancer patients who also had pleural effusions or ascites. Furthermore, there is strong evidence that human lung cancer produces CA125 in vitro, which suggests that other clinical illnesses outside of ovarian cancer could also be responsible for the rise of CA125. MUC16 (CA125) is a natural killer cell inhibitor. As a screening test for lung and ovarian cancer diagnosis and prognosis in the early stages, CA125 has been widely used as a marker in three different clinical settings. MUC16 mRNA levels in lung cancer are increased regardless of gender. As well, increased expression of mutated MUC16 enhances lung cancer cells proliferation and growth. Additionally, the CA125 serum level is thought to be a key indicator for lung cancer metastasis to the liver. Further, CA125 could be a useful biomarker in other cancer types diagnoses like ovarian, breast, and pancreatic cancers. One of the important limitations of CA125 as a first step in such a screening technique is that up to 20% of ovarian tumors lack antigen expression. Each of the 10 possible serum markers was expressed in 29-100% of ovarian tumors with minimal or no CA125 expression. Therefore, there is a controversy regarding CA125 in the diagnosis and prognosis of lung cancer and other cancer types. In this state, preclinical and clinical studies are warranted to elucidate the clinical benefit of CA125 in the diagnosis and prognosis of lung cancer.

Bronchoalveolar Lavage Fluid-Isolated Biomarkers for the Diagnostic and Prognostic Assessment of Lung Cancer.

Lung cancer is considered one of the most fatal malignant neoplasms because of its late detection. Detecting molecular markers in samples from routine bronchoscopy, including many liquid-based cytology procedures, such as bronchoalveolar lavage fluid (BALF), could serve as a favorable technique to enhance the efficiency of a lung cancer diagnosis. BALF analysis is a promising approach to evaluating the tumor progression microenvironment. BALFs cellular and non-cellular components dictate the inflammatory response in a cancer-proliferating microenvironment. Furthermore, it is an essential material for detecting clinically significant predictive and prognostic biomarkers that may aid in guiding treatment choices and evaluating therapy-induced toxicities in lung cancer. In the present article, we have reviewed recent literature about the utility of BALF analysis for detecting markers in different stages of tumor cell metabolism, employing either specific biomarker assays or broader omics approaches.

A Framework for Lung and Colon Cancer Diagnosis via Lightweight Deep Learning Models and Transformation Methods.

Among the leading causes of mortality and morbidity in people are lung and colon cancers. They may develop concurrently in organs and negatively impact human life. If cancer is not diagnosed in its early stages, there is a great likelihood that it will spread to the two organs. The histopathological detection of such malignancies is one of the most crucial components of effective treatment. Although the process is lengthy and complex, deep learning (DL) techniques have made it feasible to complete it more quickly and accurately, enabling researchers to study a lot more patients in a short time period and for a lot less cost. Earlier studies relied on DL models that require great computational ability and resources. Most of them depended on individual DL models to extract features of high dimension or to perform diagnoses. However, in this study, a framework based on multiple lightweight DL models is proposed for the early detection of lung and colon cancers. The framework utilizes several transformation methods that perform feature reduction and provide a better representation of the data. In this context, histopathology scans are fed into the ShuffleNet, MobileNet, and SqueezeNet models. The number of deep features acquired from these models is subsequently reduced using principal component analysis (PCA) and fast Walsh-Hadamard transform (FHWT) techniques. Following that, discrete wavelet transform (DWT) is used to fuse the FWHTs reduced features obtained from the three DL models. Additionally, the three DL models PCA features are concatenated. Finally, the diminished features as a result of PCA and FHWT-DWT reduction and fusion processes are fed to four distinct machine learning algorithms, reaching the highest accuracy of 99.6%. The results obtained using the proposed framework based on lightweight DL models show that it can distinguish lung and colon cancer variants with a lower number of features and less computational complexity compared to existing methods. They also prove that utilizing transformation methods to reduce features can offer a superior interpretation of the data, thus improving the diagnosis procedure.

A Pilot Analysis of Circulating cfRNA Transcripts for the Detection of Lung Cancer.

Lung cancers are the leading cause of cancer-related deaths worldwide. Studies have shown that non-small cell lung cancer (NSCLC), which constitutes the majority of lung cancers, is significantly more responsive to early-stage interventions. However, the early stages are often asymptomatic, and current diagnostic methods are limited in their precision and safety. The cell-free RNAs (cfRNAs) circulating in plasma (liquid biopsies) offer a non-invasive detection of spatial and temporal changes occurring in primary tumors since the early stages. To address gaps in the current cfRNA knowledge base, we conducted a pilot study for the comprehensive analysis of transcriptome-wide changes in plasma cfRNA in NSCLC patients. Total cfRNA was extracted from archived plasma collected from NSCLC patients (N 12), cancer-free former smokers (N 12), and non-smoking healthy volunteers (N 12). Plasma cfRNA expression levels were quantified by using a tagmentation-based library preparation and sequencing. The comparisons of cfRNA expression levels between patients and the two control groups revealed a total of 2357 differentially expressed cfRNAs enriched in 123 pathways. Of these, 251 transcripts were previously reported in primary NSCLCs. A small subset of genes (N 5) was validated in an independent sample (N 50) using qRT-PCR. Our study provides a framework for developing blood-based assays for the early detection of NSCLC and warrants further validation.

AP-2δ Is the Most Relevant Target of AP-2 Family-Focused Cancer Therapy and Affects Genome Organization.

Formerly hailed as undruggable proteins, transcription factors (TFs) are now under investigation for targeted therapy. In cancer, this may alter, inter alia, immune evasion or replicative immortality, which are implicated in genome organization, a process that accompanies multi-step tumorigenesis and which frequently develops in a non-random manner. Still, targeting-related research on some TFs is scarce, e.g., among AP-2 proteins, which are known for their altered functionality in cancer and prognostic importance. Using public repositories, bioinformatics tools, and RNA-seq data, the present study examined the ligandability of all AP-2 members, selecting the best one, which was investigated in terms of mutations, targets, co-activators, correlated genes, and impact on genome organization. AP-2 proteins were found to have the conserved TFAP-2 domain, but manifested different binding characteristics and evolution. Among them, AP-2δ has not only the highest number of post-translational modifications and extended strands but also contains a specific histidine-rich region and cleft that can receive a ligand. Uterine, colon, lung, and stomach tumors are most susceptible to AP-2δ mutations, which also co-depend with cancer hallmark genes and drug targets. Considering AP-2δ targets, some of them were located proximally in the spatial genome or served as co-factors of the genes regulated by AP-2δ. Correlation and functional analyses suggested that AP-2δ affects various processes, including genome organization, via its targets this has been eventually verified in lung adenocarcinoma using expression and immunohistochemistry data of chromosomal conformation-related genes. In conclusion, AP-2δ affects chromosomal conformation and is the most appropriate target for cancer therapy focused on the AP-2 family.

KLK6PAR1 Axis Promotes Tumor Growth and Metastasis by Regulating Cross-Talk between Tumor Cells and Macrophages.

Kallikrein-related peptidase (KLK)6 is associated with inflammatory diseases and neoplastic progression. KLK6 is aberrantly expressed in several solid tumors and regulates cancer development, metastatic progression, and drug resistance. However, the function of KLK6 in the tumor microenvironment remains unclear. This study aimed to determine the role of KLK6 in the tumor microenvironment. Here, we uncovered the mechanism underlying KLK6-mediated cross-talk between cancer cells and macrophages. Compared with wild-type mice, KLK6-- mice showed less tumor growth and metastasis in the B16F10 melanoma and Lewis lung carcinoma (LLC) xenograft model. Mechanistically, KLK6 promoted the secretion of tumor necrosis factor-alpha (TNF-α) from macrophages via the activation of protease-activated receptor-1 (PAR1) in an autocrine manner. TNF-α secreted from macrophages induced the release of the C-X-C motif chemokine ligand 1 (CXCL1) from melanoma and lung carcinoma cells in a paracrine manner. The introduction of recombinant KLK6 protein in KLK6-- mice rescued the production of TNF-α and CXCL1, tumor growth, and metastasis. Inhibition of PAR1 activity suppressed these malignant phenotypes rescued by rKLK6 in vitro and in vivo. Our findings suggest that KLK6 functions as an important molecular link between macrophages and cancer cells during malignant progression, thereby providing opportunities for therapeutic intervention.

FUT2 Facilitates Autophagy and Suppresses Apoptosis via p53 and JNK Signaling in Lung Adenocarcinoma Cells.

Lung cancer is the most common cancer with high morbidity and mortality worldwide. Our previous studies showed that fucosyltransferase 2 (FUT2) is highly expressed in lung adenocarcinoma (LUAD) and plays a vital role in the tumorigenesis of LUAD. However, the underlying mechanism is not fully understood. Autophagy has recently attracted increasing attention due to its pro-survival role in cancer progression and metastasis. Here, we found that FUT2 was up-regulated and had an AUC (Area Under Curve) value of 0.964 in lung adenocarcinoma based on the TCGA dataset. Knockdown of FUT2 weakened the autophagy response, as evidenced by a degradation of LC3-II and Beclin1. The phosphorylation levels of AMPK, ULK1, and PI3K III were significantly reduced by FUT2 knockdown. FUT2 promoted the translocation of p53 from the cytoplasm into the nucleus, which triggered the DRAM1 pathway and enhanced autophagy. Meanwhile, the knockdown of FUT2 increased the phosphorylation of JNK and promoted mitochondrial-mediated apoptosis. Furthermore, the knockdown of FUT2 inhibited the autophagy induced by Z-VAD-FMK and promoted the apoptosis suppressed by rapamycin. The autophagy and apoptosis regulated by FUT2 antagonized each other. Taken together, these findings provide a mechanistic understanding of how FUT2 mediated the crosstalk between autophagy and apoptosis, which determine lung cancer cell death and survival, leading to the progression of lung adenocarcinoma.

Molecular Detection of Lymph Node Metastases in Lung Cancer Patients Using the One-Step Nucleic Acid Amplification MethodClinical Significance and Prognostic Value.

The one-step nucleic acid amplification (OSNA) method allows for the quantitative evaluation of the tumor burden in resected lymph nodes (LNs) in patients with lung cancer. This technique enables to detect macro and micrometastases, facilitating the correct classification of patients for appropriate follow-up of the disease after surgery. Of 160 patients with resectable lung cancer whose LNs were examined by OSNA, HE and CK19 IHC between July 2015 and December 2018, 110 patients with clinical stages from IA1 to IIIB were selected for follow-up. LN staging in lung cancer by pathological study led to understaging in 13.64% of the cases studied. OSNA allowed to quantify the tumor burden and establish a prognostic value. Patients with a total tumor load of ≥1650 cCPuL were associated with a significantly increased likelihood of recurrence. Moreover, the survival of patients with <4405 cCPuL was significantly higher than patients with ≥4405 cCPuL. The OSNA assay is a rapid and accurate technique for quantifying the tumor burden in the LNs of lung cancer patients and OSNA quantitative data could allow to establish prognostic values for recurrence-free survival and overall survival in this type of malignancy.

Inhibition of EZH2 Ameliorates Sepsis Acute Lung Injury (SALI) and Non-Small-Cell Lung Cancer (NSCLC) Proliferation through the PD-L1 Pathway.

(1) Background Both sepsis acute lung injury (SALI) and non-small-cell lung cancer (NSCLC) are life-threatening diseases caused by immune response disorders and inflammation, but the underlining linking mechanisms are still not clear. This study aimed to detect the shared gene signature and potential molecular process between SALI and NSCLC. (2) Methods RNA sequences and patient information on sepsis and NSCLC were acquired from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to build a co-expression network associated with sepsis and NSCLC. Protein-protein interaction (PPI) analysis of shared genes was intuitively performed by the Search Tool for the Retrieval of Interacting GenesProteins (STRING) database. The involvement of

Naturally Occurring Functional Ingredient from Filamentous Thermophilic Cyanobacterium

Cyanobacteria are rich in phytochemicals, which have beneficial impacts on the prevention of many diseases. This study aimed to comprehensively characterize phytochemicals and evaluate multifunctional bioactivities in the ethanolic extract of the cyanobacterium

Chemical Profiling, Antiproliferative and Antimigratory Capacity of

A Systems Biology and LASSO-Based Approach to Decipher the Transcriptome-Interactome Signature for Predicting Non-Small Cell Lung Cancer.

The lack of precise molecular signatures limits the early diagnosis of non-small cell lung cancer (NSCLC). The present study used gene expression data and interaction networks to develop a highly accurate model with the least absolute shrinkage and selection operator (LASSO) for predicting NSCLC. The differentially expressed genes (DEGs) were identified in NSCLC compared with normal tissues using TCGA and GTEx data. A biological network was constructed using DEGs, and the top 20 upregulated and 20 downregulated hub genes were identified. These hub genes were used to identify signature genes with penalized logistic regression using the LASSO to predict NSCLC. Our models development involved the following steps (i) the dataset was divided into 80% for training (TR) and 20% for testing (TD1) (ii) a LASSO logistic regression analysis was performed on the TR with 10-fold cross-validation and identified a combination of 17 genes as NSCLC predictors, which were used further for development of the LASSO model. The models performance was assessed on the TD1 dataset and achieved an accuracy and an area under the curve of the receiver operating characteristics (AUC-ROC) of 0.986 and 0.998, respectively. Furthermore, the performance of the LASSO model was evaluated using three independent NSCLC test datasets (GSE18842, GSE27262, GSE19804) and achieved high accuracy, with an AUC-ROC of gt0.99, gt0.99, and 0.95, respectively. Based on this study, a web application called

High-Risk Human Papillomavirus Infection in Lung Cancer Mechanisms and Perspectives.

Lung cancer is a very prevalent and heterogeneous group of malignancies, and most of them are etiologically associated with tobacco smoking. However, viral infections have been detected in lung carcinomas, with high-risk human papillomaviruses (HR-HPVs) being among them. The role of HR-HPVs in lung cancer has been considered to be controversial. This issue is due to the highly variable presence of this virus in lung carcinomas worldwide, and the low viral load frequently that is detected. In this review, we address the epidemiological and mechanistic findings regarding the role of HR-HPVs in lung cancer. Some mechanisms of HR-HPV-mediated lung carcinogenesis have been proposed, including (i) HPV works as an independent carcinogen in non-smoker subjects (ii) HPV cooperates with carcinogenic compounds present in tobacco smoke (iii) HPV promotes initial alterations being after cleared by the immune system through a hit and run mechanism. Additional research is warranted to clarify the role of HPV in lung cancer.

Ivermectin Affects Neutrophil-Induced Inflammation through Inhibition of Hydroxylysine but Stimulation of Cathepsin G and Phenylalanine Secretion.

The invasion and integrin-dependent adhesion of neutrophils to lung tissues and their secretion lead to the development of pneumonia in various pulmonary pathologies, including acute respiratory distress syndrome in coronavirus disease. We studied the effect of ivermectin, a possible therapeutic agent for inflammation and cancer, on integrin-dependent neutrophil adhesion to fibronectin and the concomitant secretion. Ivermectin did not affect the attachment of neutrophils to the substrate and the reactive oxygen species production but sharply inhibited the adhesion-induced release of hydroxylysine and stimulated the release of phenylalanine and cathepsin G. Hydroxylysine is a product of lysyl hydroxylase, which is overexpressed in tumor cells with an increased ability to invade and metastasize. The inhibition of hydroxylysine release by ivermectin, by analogy, may indicate the suppression of neutrophil invasion into tissue. The increase in the release of phenylalanine in our experiments coincided with the secretion of cathepsin G, which indicates the possible role of this enzyme in the cleavage of phenylalanine. What is the substrate in such a reaction is unknown. We demonstrated that exogenously added angiotensin II (1-8) can serve as a substrate for phenylalanine cleavage. Mass spectrometry revealed the formation of angiotensin II (1-7) in the secretion of neutrophils, which attached to fibronectin in the presence of ivermectin and exogenous angiotensin II (1-8), indicating a possible involvement of ivermectin in the inactivation of angiotensin II.

Epidemiological, Clinical, and Genomic Profile in Head and Neck Cancer Patients and Their Families.

Inherited cancer predisposition genes are described as risk factors in head and neck cancer (HNC) families. To explore the clinical and epidemiological data and their association with a family history of cancer, we recruited 74 patients and 164 relatives affected by cancer. The germline copy number alterations were evaluated in 18 patients using array comparative genomic hybridization. Two or more first-degree relatives with HNC, tobacco-associated tumor sites (lung, esophagus, and pancreas), or other related tumors (breast, colon, kidney, bladder, cervix, stomach carcinomas, and melanoma) were reported in 74 families. Ten index patients had no exposure to any known risk factors. Family members presented tumors of 19 topographies (30 head and neck, 26 breast, 21 colon). In first-degree relatives, siblings were frequently affected by cancer (

TIGIT Expression on Intratumoral Lymphocytes Correlates with Improved Prognosis in Oral Squamous Cell Carcinoma.

(1) Background T-cell immunoglobulin and ITIM domain (TIGIT) is a potential immunotherapeutic target in a variety of malignant entities, and antibody-based treatments are currently under investigation in clinical trials. While promising results were observed in patients with lung cancer, the role of TIGIT in oral squamous cell carcinoma (OSCC) as a biomarker as well as a therapeutic target remains elusive. Therefore, we evaluated the role of TIGIT as a prognostic factor in OSCC. (2) Methods Here, we describe the results of a retrospective tissue microarray (TMA) OSCC cohort. Using immunohistochemistry, TIGIT expression was correlated with overall and recurrence-free survival (OAS and RFS, respectively). Additionally, in silico analysis was performed based on the TCGA Head and Neck Squamous Cell Carcinoma (HNSCC) cohort in order to correlate patients survival with TIGIT and CD274 (encoding for PD-L1) gene expression levels. (3) Results Database analysis revealed a beneficial outcome in OAS for tumor patients with high intraepithelial CD3-TIGIT-expression (

Identification of the Transcriptional Regulatory Role of RUNX2 by Network Analysis in Lung Cancer Cells.

The use of a new bioinformatics pipeline allowed the identification of deregulated transcription factors (TFs) coexpressed in lung cancer that could become biomarkers of tumor establishment and progression. A gene regulatory network (GRN) of lung cancer was created with the normalized gene expression levels of differentially expressed genes (DEGs) from the microarray dataset GSE19804. Moreover, coregulatory and transcriptional regulatory network (TRN) analyses were performed for the main regulators identified in the GRN analysis. The gene targets and binding motifs of all potentially implicated regulators were identified in the TRN and with multiple alignments of the TFs target gene sequences. Six transcription factors (E2F3, FHL2, ETS1, KAT6B, TWIST1, and RUNX2) were identified in the GRN as essential regulators of gene expression in non-small-cell lung cancer (NSCLC) and related to the lung tumoral process. Our findings indicate that RUNX2 could be an important regulator of the lung cancer GRN through the formation of coregulatory complexes with other TFs related to the establishment and progression of lung cancer. Therefore, RUNX2 could become an essential biomarker for developing diagnostic tools and specific treatments against tumoral diseases in the lung after the experimental validation of its regulatory function.

How to Manage a Patient with Ocular Metastases

Ocular metastases are the most frequent ocular malignant tumors their prevalence is estimated around 5-10% and is even higher in patients with breast or lung cancer. They represent various clinical situations, but they share the same hierarchical multidisciplinary therapeutic challenge with respect to the way systemic and local therapies should be selected in combination or sequentially in the personalized medical history of a patient. The challenges include tumor control, eye preservation, and the minimization of iatrogenic damage to sensitive tissues surrounding the tumor in order to preserve vision. These aims should further contribute to maintaining quality of life in patients with metastases. Many patients with choroidal metastases have systemic molecular treatment for their primary tumor. However, secondary resistance to systemic treatment is common and may ultimately be associated with cancer relapse, even after an initial response. Therefore, it makes sense to propose local treatment concomitantly or after systemic therapy to provide a more sustainable response. The aim of this review is to present current therapeutic strategies in ocular metastases and discuss how to tailor the treatment to a specific patient.

Aberrant Expression and Prognostic Potential of IL-37 in Human Lung Adenocarcinoma.

Interleukin-37 (IL-37) is a relatively new IL-1 family cytokine that, due to its immunoregulatory properties, has lately gained increasing attention in basic and translational biomedical research. Emerging evidence supports the implication of this protein in any human disorder in which immune homeostasis is compromised, including cancer. The aim of this study was to explore the prognostic andor diagnostic potential of IL-37 and its receptor SIGIRR (single immunoglobulin IL-1-related receptor) in human tumors. We utilized a series of bioinformatics tools and -omics datasets to unravel possible associations of IL-37 and SIGIRR expression levels and genetic aberrations with tumor development, histopathological parameters, distribution of tumor-infiltrating immune cells, and survival rates of patients. Our data revealed that amongst the 17 human malignancies investigated, IL-37 exhibits higher expression levels in tumors of lung adenocarcinoma (LUAD). Moreover, the expression profiles of IL-37 and SIGIRR are associated with LUAD development and tumor stage, whereas their high mRNA levels are favorable prognostic factors for the overall survival of patients. What is more,

Attempting to Identify Bacterial Allies in Immunotherapy of NSCLC Patients.

Factors other than PD-L1 (Programmed Death Ligand 1) are being sought as predictors for cancer immuno- or chemoimmunotherapy in ongoing studies and long-term observations. Despite high PD-L1 expression on tumor cells, some patients do not benefit from immunotherapy, while others, without the expression of this molecule, respond to immunotherapy. Attention has been paid to the composition of the gut microbiome as a potential predictive factor for immunotherapy effectiveness. Our study enrolled 47 Caucasian patients with stage IIIB or IV non-small cell lung cancer (NSCLC). They were eligible for treatment with first- or second-line immunotherapy or chemoimmunotherapy. We collected stool samples before the administration of immunotherapy. We performed next-generation sequencing (NGS) on DNA isolated from the stool sample and analyzed bacterial V3 and V4 of the We found that bacteria from the families The