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Rechallenge of immunotherapy beyond progression in patients with extensive-stage small-cell lung cancer.

Jian-Ti-Kang-Yi decoction alleviates poly(IC)-induced pneumonia by inhibiting inflammatory response, reducing oxidative stress, and modulating host metabolism.

Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(IC)), a mimic of viral dsRNA, was used to induce pneumonia in mice the therapeutic effects of JTKY on poly(IC)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory effects of JTKY in poly(IC)-induced pneumonia model mice were studied using untargeted metabolomics. Our results showed that JTKY treatment decreased the wet-to-dry ratio in the lung tissue, total protein concentration, and total cell count of the bronchoalveolar lavage fluid (BALF). Hematoxylin and Eosin (HE) and Masson staining indicated that the JTKY treatment alleviated the pathological changes and decreased the fibrotic contents in the lungs. JTKY treatment also decreased the expression of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) and increased the levels of immunomodulatory cytokines (IL-4 and IL-10) in the BALF and serum. Flow cytometry analysis showed that the JTKY treatment lowered the ratio of CD86

An unusual location for metastasis - Breast cancer in the bladder.

Metastatic breast cancer is the second most common cancer related death amongst women in the United States. The common locations for metastases-lymph nodes, bone, lung, liver, brain - are well reported. Rarely, breast cancer metastasizes to the bladder. We present a case of primary hormone positive, HER2 unamplified breast cancer, thirteen years in remission, with triple negative metastases to the bladder. Urologists should consider breast metastases in patients with even a remote history of breast cancer who present with gross hematuria to avoid delays in treatment.

An extensive surgical resection in stage T4 small cell lung cancer with cardiac invasion A case report and literature review.

We report a rare case of a patient with a mass involving both the hilum and the heart, but its specific nature could not be determined. SCLC was confirmed by postoperative pathology. It revealed that radical surgical resection for T4 SCLC should be considered an important part of multimodality treatment. A 49-year-old gentleman complained of mild chest tightness for a week. Two large mass lesions were detected on CECT in the left atrium and left hilum. After an MDT discussion, an extended resection was recommended. Postoperative pathology denoted a complete excision with no residuals and negative lymph nodes. Due to the rarity of lung metastases to the heart, it is vital to determine the homology between the hilar mass and the cardiac mass. Based on this, simultaneous surgical treatment is done and it is very beneficial for patients by eliminating those hazards, such as acute mechanical cardiac obstruction, and cardiac embolism. Our literature review demonstrates that the SCLC tumour progresses rapidly after cardiac metastasis, limiting the chance of a complete resection. Furthermore, complete resection of T4 tumours in NSCLC has been attempted many times, so it should also be tried on SCLC. It is common for SCLC tumours to progress rapidly once they havemetastasized to the heart. An aggressive operation such as radical resection can reduce tumor burdens, minimize the risk of sudden acute death and improve patient follow-up treatment, all of which may prolong the survival of patients.

Calcinosis universalis and breast cancer A distinctive association.

Calcinosis universalis (CU) is characterised by diffuse deposition of insoluble calcium salt in the skin, subcutaneous tissue or organs. Calcium deposits in the breast may be associated with an increased risk for developing breast cancer. We present a case of a 65-year-old woman diagnosed with CU secondary to undifferentiated connective tissue disease. She developed progressive calcification of her skin, which did not improve with oral medications aimed at reducing the calcification. Investigations to look for possible causes of calcification were all unremarkable. During follow-up, calcification was also found in both her breasts. Initial mammography was reported as fibroadenoma. However, 3 years later, she returned with metastatic breast cancer which presented with a massive pleural effusion of the right lung. Calcinosis universalis should now be considered as a risk factor for breast cancer.

Nodules, nodes and non-functioning macrophages A risk with ibrutinib therapy.

We describe the case of a 70-year-old never smoker with chronic lymphocytic leukaemia, treated with single agent ibrutinib therapy. Chest imaging noted nodular change and mediastinal lymphadenopathy, which showed avid uptake on positron emission tomography and guided subsequent biopsies (bronchoscopy using endobronchial ultrasound, mediastinoscopy). Despite negative aspergillus blood immunology tests, he was found to have invasive aspergillosis, which is a known risk with ibrutinib therapy. He has since been successfully treated with antifungal therapy.

Design and synthesis of novel quinazolinone-based derivatives as EGFR inhibitors with antitumor activity.

Nineteen new quinazolin-4(3

Early-Onset Pulmonary Events with Combined Brigatinib and Afatinib Treatment of L858cisT790McisC797S NSCLC A Case Report.

BACKGROUND Brigatinib is used for anaplastic lymphoma kinase (ALK)-positive lung cancer treatment, and some research showed it was useful in treating triple-mutant epidermal growth factor receptor lung cancer. Clinical trials have shown some potential pulmonary toxicities of brigatinib. The early-onset pulmonary events (EOPEs) of brigatinib are associated with high dosage and older age. The successful treatment of EOPEs with steroids was reported. We present the case of a patient with epidermal growth factor receptor L858Rcis-T790Mcis-C797S triple mutations who developed EOPEs after using brigatinib together with afatinib, and the patient was successfully treated with high-dose steroids. CASE REPORT A 54-year-old woman with underlying stage IV lung adenocarcinoma, ECOG score of 0, was treated with brigatinib and afatinib due to disease progression secondary to L858Rcis-T790Mcis-C797S triple mutations. After starting brigatinib and afatinib, she developed dyspnea and dry cough within 2 days and was intubated due to hypercapnic respiratory failure. The chest X-ray showed bilateral interstitial infiltrates while chest computed tomography (CT) showed bilateral ground-glass opacities. EOPEs were suspected and methylprednisolone was prescribed. The oxygenation of the patient improved and her chest CT showed complete resolution after 2 weeks of steroid treatment. CONCLUSIONS This is the first reported case in which brigatinib combined with afatinib induced EOPEs in a patient with triple-mutant epidermal growth factor receptors of lung cancer. Use of doubled tyrosine kinase inhibitors may result in increased risk of pulmonary toxicities that require high alertness, and the respiratory symptoms should be monitored closely after prescription. The early treatment of EOPEs with high-dose steroids resulted in remarkable improvement.

Image Recovery from Synthetic Noise Artifacts in CT Scans Using Modified U-Net.

Computed Tomography (CT) is commonly used for cancer screening as it utilizes low radiation for the scan. One problem with low-dose scans is the noise artifacts associated with low photon count that can lead to a reduced success rate of cancer detection during radiologist assessment. The noise had to be removed to restore detail clarity. We propose a noise removal method using a new model Convolutional Neural Network (CNN). Even though the network training time is long, the result is better than other CNN models in quality score and visual observation. The proposed CNN model uses a stacked modified U-Net with a specific number of feature maps per layer to improve the image quality, observable on an average PSNR quality score improvement out of 174 images. The next best model has 0.54 points lower in the average score. The score difference is less than 1 point, but the image result is closer to the full-dose scan image. We used separate testing data to clarify that the model can handle different noise densities. Besides comparing the CNN configuration, we discuss the denoising quality of CNN compared to classical denoising in which the noise characteristics affect quality.

An Interpretable Two-Phase Modeling Approach for Lung Cancer Survivability Prediction.

Although lung cancer survival status and survival length predictions have primarily been studied individually, a scheme that leverages both fields in an interpretable way for physicians remains elusive. We propose a two-phase data analytic framework that is capable of classifying survival status for 0.5-, 1-, 1.5-, 2-, 2.5-, and 3-year time-points (phase I) and predicting the number of survival months within 3 years (phase II) using recent Surveillance, Epidemiology, and End Results data from 2010 to 2017. In this study, we employ three analytical models (general linear model, extreme gradient boosting, and artificial neural networks), five data balancing techniques (synthetic minority oversampling technique (SMOTE), relocating safe level SMOTE, borderline SMOTE, adaptive synthetic sampling, and majority weighted minority oversampling technique), two feature selection methods (least absolute shrinkage and selection operator (LASSO) and random forest), and the one-hot encoding approach. By implementing a comprehensive data preparation phase, we demonstrate that a computationally efficient and interpretable method such as GLM performs comparably to more complex models. Moreover, we quantify the effects of individual features in phase I and II by exploiting GLM coefficients. To the best of our knowledge, this study is the first to (a) implement a comprehensive data processing approach to develop performant, computationally efficient, and interpretable methods in comparison to black-box models, (b) visualize top factors impacting survival odds by utilizing the change in odds ratio, and (c) comprehensively explore short-term lung cancer survival using a two-phase approach.

Biological Assay-Guided Fractionation and Mass Spectrometry-Based Metabolite Profiling of

A Review of Non-Invasive Drug Delivery through Respiratory Routes.

With rapid and non-invasive characteristics, the respiratory route of administration has drawn significant attention compared with the limitations of conventional routes. Respiratory delivery can bypass the physiological barrier to achieve local and systemic disease treatment. A scientometric analysis and review were used to analyze how respiratory delivery can contribute to local and systemic therapy. The literature data obtained from the Web of Science Core Collection database showed an increasing worldwide tendency toward respiratory delivery from 1998 to 2020. Keywords analysis suggested that nasal and pulmonary drug delivery are the leading research topics in respiratory delivery. Based on the results of scientometric analysis, the research hotspots mainly included therapy for central nervous systems (CNS) disorders (Parkinsons disease, Alzheimers disease, depression, glioblastoma, and epilepsy), tracheal and bronchial or lung diseases (chronic obstructive pulmonary disease, asthma, acute lung injury or respiratory distress syndrome, lung cancer, and idiopathic pulmonary fibrosis), and systemic diseases (diabetes and COVID-19). The study of advanced preparations contained nano drug delivery systems of the respiratory route, drug delivery barriers investigation (blood-brain barrier, BBB), and chitosan-based biomaterials for respiratory delivery. These results provided researchers with future research directions related to respiratory delivery.

Exposure-Response Analysis of Osimertinib in Patients with Advanced Non-Small-Cell Lung Cancer.

High interindividual variability (IIV) of the clinical response to epidermal growth factor receptor (EGFR) inhibitors such as osimertinib in non-small-cell lung cancer (NSCLC) might be related to the IIV in plasma exposure. The aim of this study was to evaluate the exposure-response relationship for toxicity and efficacy of osimertinib in unselected patients with advanced EGFR-mutant NSCLC. This retrospective analysis included 87 patients treated with osimertinib. Exposure-toxicity analysis was performed in the entire cohort and survival analysis only in second-line patients (

Conjugation of a Cationic Cell-Penetrating Peptide with a Novel Kunitzin-like Trypsin Inhibitor New Insights for Enhancement of Peptide Bioactivities.

Cationic cell-penetrating peptides (CPPs), such as transactivator of transcription (TAT) peptide, have been proposed as effective drug carriers to improve intracellular delivery of biological macromolecules. Amphibian skin-derived Kunitz-type trypsin inhibitors (KTIs), short counterparts of KTIs from plant sources, were found to possess potent serine protease inhibitory activity. However, poor transmembrane permeability of these molecules has largely hindered the study of the full spectrum of their biological actions. As a result, this study aimed to extend the biological activities of amphibian KTIs by their conjugation to cationic CPPs. Herein, a novel peptide (kunitzin-OV

In Silico Pharmacokinetic Profiling of the Identified Bioactive Metabolites of

The in vitro cytotoxic efficacy of plant latex from

P-Glycoprotein (MDR1ABCB1) Restricts Brain Accumulation of the Novel EGFR Inhibitor EAI045 and Oral Elacridar Coadministration Enhances Its Brain Accumulation and Oral Exposure.

EAI045 is a fourth-generation allosteric tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR). It targets T790M and C797S EGFR mutants in the treatment of non-small cell lung cancer (NSCLC). EAI045 and cetuximab combined induce tumor regression in mouse models of EGFR-mutant lung cancer. We investigated the pharmacokinetic roles of the multidrug efflux and uptake transporters ABCB1 (P-gp), ABCG2 (BCRP), and OATP1A1B, and of the drug-metabolizing enzyme CYP3A in plasma and tissue distribution of EAI045 and its metabolites, using genetically modified mouse models. In vitro, EAI045 was a good transport substrate of human ABCB1. In vivo, oral EAI045 (20 mgkg) was rapidly absorbed. Relative to wild-type mice, EAI045 brain-to-plasma ratios were increased 3.9-fold in

Plasma Pharmacokinetics and Tissue Distribution of Doxorubicin in Rats following Treatment with Astragali Radix.

Doxorubicin (DOX) is an essential component in chemotherapy, and Astragali Radix (AR) is a widely used tonic herbal medicine. The combination of DOX and AR offers widespread, well-documented advantages in treating cancer, e.g., reducing the risk of adverse effects. This study mainly aims to uncover the impact of AR on DOX disposition in vivo. Rats received a single intravenous dose of 5 mgkg DOX following a single-dose co-treatment or multiple-dose pre-treatment of AR (10 gkg × 1 or × 10). The concentrations of DOX in rat plasma and six tissues, including heart, liver, lung, kidney, spleen, and skeletal muscle, were determined by a fully validated LC-MSMS method. A network-based approach was further employed to quantify the relationships between enzymes that metabolize and transport DOX and the targets of nine representative AR components in the human protein-protein interactome. We found that short-term (≤10 d) AR administration was ineffective in changing the plasma pharmacokinetics of DOX in terms of the area under the concentration-time curve (AUC, 1303.35 ± 271.74 μgLh versus 1208.74 ± 145.35 μgLh,

Evaluation of Novel Inhibitors of Tryptophan Dioxygenases for Enzyme and Species Selectivity Using Engineered Tumour Cell Lines Expressing Either Murine or Human IDO1 or TDO2.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is commonly expressed by cancers as a mechanism for evading the immune system. Preclinical and clinical studies have indicated the potential of combining IDO1 inhibitors with immune therapies for the treatment of cancer, strengthening an interest in the discovery of novel dioxygenase inhibitors for reversing tumour-mediated immune suppression. To facilitate the discovery, development and investigation of novel small molecule inhibitors of IDO1 and its hepatic isozyme tryptophan dioxygenase (TDO2), murine tumour cells were engineered to selectively express either murine or human IDO1 and TDO2 for use as tools to dissect both the species specificity and isoenzyme selectivity of newly discovered inhibitors. Lewis lung carcinoma (LLTC) lines were engineered to express either murine or human IDO1 for use to test species selectivity of the novel inhibitors in addition, GL261 glioma lines were engineered to express either human IDO1 or human TDO2 and used to test the isoenzyme selectivity of individual inhibitors in cell-based assays. The 20 most potent inhibitors against recombinant human IDO1 enzyme, discovered from a commissioned screening of 40,000 compounds in the Australian WEHI compound library, returned comparable IC

Identification of Novel Aryl Carboxamide Derivatives as Death-Associated Protein Kinase 1 (DAPK1) Inhibitors with Anti-Proliferative Activities Design, Synthesis, In Vitro, and In Silico Biological Studies.

Death-associated protein kinase 1 (DAPK1) is a serinethreonine protein kinase involved in diverse fundamental cellular processes such as apoptosis and autophagy. DAPK1 isoform plays an essential role as a tumor suppressor and inhibitor of metastasis. Consequently, DAPK1 became a promising target protein for developing new anti-cancer agents. In this work, we present the rational design and complete synthetic routes of a novel series of eighteen aryl carboxamide derivatives as potential DAPK1 inhibitors. Using a custom panel of forty-five kinases, a single dose of 10 µM of the picolinamide derivative

Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases.

Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug therapies for the management and treatment of CRDs only address the symptoms and fail to reverse or recover the chronic-inflammation-mediated structural and functional damage of the respiratory tract. In addition, the low efficacy and adverse effects of these drugs have directed the attention of researchers towards nutraceuticals in search of potential treatment strategies that can not only ameliorate CRD symptoms but also can repair and reverse inflammatory damage. Hence, there is a growing interest toward investigating the medicinal benefits of nutraceuticals, such as rutin, curcumin, zerumbone, and others. Nutraceuticals carry many nutritional and therapeutic properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, and anti-obesity properties, and usually do not have as many adverse effects, as they are naturally sourced. Recently, the use of nanoparticles has also been increasingly studied for the nano drug delivery of these nutraceuticals. The discrete size of nanoparticles holds great potential for the level of permeability that can be achieved when transporting these nutraceutical compounds. This review is aimed to provide an understanding of the use of nutraceuticals in combination with nanoparticles against CRDs and their mechanisms involved in slowing down or reversing the progression of CRDs by inhibiting pro-inflammatory signaling pathways.

Biomineralized Manganese Oxide Nanoparticles Synergistically Relieve Tumor Hypoxia and Activate Immune Response with Radiotherapy in Non-Small Cell Lung Cancer.

Radiotherapy (RT) is currently considered as an essential treatment for non-small cell lung cancer (NSCLC) it can induce cell death directly and indirectly via promoting systemic immune responses. However, there still exist obstacles that affect the efficacy of RT such as tumor hypoxia and immunosuppressive tumor microenvironment (TME). Herein, we report that the biomineralized manganese oxide nanoparticles (Bio-MnO

Bioactive Potential A Pharmacognostic Definition through the Screening of Four

In this work, we propose a general methodology to assess the bioactive potential (BP) of extracts in the quest of vegetable-based drugs. To exemplify the method, we studied the anticancer potential (AP) of four endemic species of genus

Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts.

Dimethylaminoethyl MethacrylateDiethylene Glycol Dimethacrylate Grafted onto Folate-Esterified Bagasse XylanAndrographolide Composite Nanoderivative Synthesis, Molecular Docking and Biological Activity.

As a biocompatible biomaterial, bagasse xylan (BX) has been widely used in the biomedical field. The low biological activity of andrographolide (AD) restricts its development, so AD with certain anticancer activity is introduced. We use chemical modification methods such as grafting and esterification to improve the biological activity and make a novel anticancer nanomaterial. On the basis of the esterification of a mixture of BX and AD with folic acid (FA), a novel anticancer nanoderivative of bagasse xylanandrographolide folate-g-dimethylaminoethyl methacrylate (DMAEMA)diethylene glycol dimethacrylate (DEGDMA) nanoparticles (FA-BXAD-g-DMAEMADEGDMA NPs) was synthesized by introducing DMAEMA and DEGDMA monomers through a graft copolymerization and nanoprecipitation method. The effects of reaction temperature, reaction time, the initiator concentration and the mass ratio of FA-BXAD to mixed monomers on the grafting rate (

Low Temperature Plasma Suppresses Lung Cancer Cells Growth via VEGFVEGFR2RASERK Axis.

Low temperature plasma (LTP) is a promising cancer therapy in clinical practice. In this study, dielectric barrier discharge plasma with helium gas was used to generate LTP. Significant increases in extracellular and intracellular reactive species were found in lung cancer cells (CALU-1 and SPC-A1) after LTP treatments. Cells viability and apoptosis assays demonstrated that LTP inhibited cells viability and induced cells death, respectively. Moreover, Western blotting revealed that the growth of CALU-1 cells was suppressed by LTP via the VEGFVEGFR2RASERK axis for the first time. The results showed that LTP-induced ROS and RNS could inhibit the growth of lung cancer cells via VEGFVEGFR2RASERK axis. These findings advance our understanding of the inhibitory mechanism of LTP on lung cancer and will facilitate its clinical application.

Polyphenols as Lung Cancer Chemopreventive Agents by Targeting microRNAs.

Lung cancer is the second leading cause of cancer-related death worldwide. In recent decades, investigators have found that microRNAs, a group of non-coding RNAs, are abnormally expressed in lung cancer, and play important roles in the initiation and progression of lung cancer. These microRNAs have been used as biomarkers and potential therapeutic targets of lung cancer. Polyphenols are natural and bioactive chemicals that are synthesized by plants, and have promising anticancer effects against several kinds of cancer, including lung cancer. Recent studies identified that polyphenols exert their anticancer effects by regulating the expression levels of microRNAs in lung cancer. Targeting microRNAs using polyphenols may provide a novel strategy for the prevention and treatment of lung cancer. In this review, we reviewed the effects of polyphenols on oncogenic and tumor-suppressive microRNAs in lung cancer. We also reviewed and discussed the potential clinical application of polyphenol-regulated microRNAs in lung cancer treatment.

New Anticancer Theobromine Derivative Targeting EGFR

Based on the pharmacophoric features of EGFR inhibitors, a new semisynthetic theobromine-derived compound was designed to interact with the catalytic pocket of EGFR. Molecular docking against wild (EGFR

A Comprehensive Analysis of Microflora and Metabolites in the Development of Ulcerative Colitis into Colorectal Cancer Based on the Lung-Gut Correlation Theory.

The lungs and large intestine can co-regulate inflammation and immunity through the lung-gut axis, in which the transportation of the gut microbiota and metabolites is the most important communication channel. In our previous study, not only did the composition of the gut microbiota and metabolites related to inflammation change significantly during the transition from ulcerative colitis (UC) to colorectal cancer (CRC), but the lung tissues also showed corresponding inflammatory changes, which indicated that gastrointestinal diseases can lead to pulmonary diseases. In order to elucidate the mechanisms of this lung-gut axis, metabolites in bronchoalveolar lavage fluid (BALF) and lung tissues were detected using UHPLC-Q-TOF-MSMS technology, while microbiome characterization was performed in BALF using 16S rDNA sequencing. The levels of pulmonary metabolites changed greatly during the development of UC to CRC. Among these changes, the concentrations of linoleic acid and 7-hydroxy-3-oxocholic acid gradually increased during the development of UC to CRC. In addition, the composition of the pulmonary microbiota also changed significantly, with an increase in the

Sarcoconvolutums F and G Polyoxygenated Cembrane-Type Diterpenoids from

Natural products and chemical analogues are widely used in drug discovery, notably in cancer and infectious disease pharmacotherapy.

Cranberry Ingestion Modulated Drug Transporters and Metabolizing Enzymes Gefitinib Used as a Probe Substrate in Rats.

Cranberry, a polyphenol-rich functional food, is commonly used for the prophylaxis of urinary tract infections. Gefitinib, an anticancer agent clinically prescribed to treat non-small-cell lung cancer, is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and metabolized mainly by cytochrome P450 (CYP) 3A4 and CYP2D6. This study used gefitinib as a probe substrate to investigate the modulation of cranberry on P-gp, BCRP, CYP3A4 and CYP2D6. Rats were administered gefitinib with and without 5.0 gkg of cranberry as juice (CJ). The concentration of gefitinib in serum was determined by LC-MSMS. The results showed that CJ significantly increased the C

Do Bacteria Provide an Alternative to Cancer Treatment and What Role Does Lactic Acid Bacteria Play

Cancer is one of the leading causes of mortality and morbidity worldwide. According to 2022 statistics from the World Health Organization (WHO), close to 10 million deaths have been reported in 2020 and it is estimated that the number of cancer cases world-wide could increase to 21.6 million by 2030. Breast, lung, thyroid, pancreatic, liver, prostate, bladder, kidney, pelvis, colon, and rectum cancers are the most prevalent. Each year, approximately 400,000 children develop cancer. Treatment between countries vary, but usually includes either surgery, radiotherapy, or chemotherapy. Modern treatments such as hormone-, immuno- and antibody-based therapies are becoming increasingly popular. Several recent reports have been published on toxins, antibiotics, bacteriocins, non-ribosomal peptides, polyketides, phenylpropanoids, phenylflavonoids, purine nucleosides, short chain fatty acids (SCFAs) and enzymes with anticancer properties. Most of these molecules target cancer cells in a selective manner, either directly or indirectly through specific pathways. This review discusses the role of bacteria, including lactic acid bacteria, and their metabolites in the treatment of cancer.

A Combination of Two Probiotics,

Cancer remains a leading cause of death worldwide and, even though several advances have been made in terms of specific treatment, the late-stage detection and the associated side effects of the conventional drugs sustain the search for better treatment alternatives. Probiotics are live microorganisms that have been proven to possess numerous health benefits for human hosts, including anticancer effects. In the present study, the in vitro effect of the association of two probiotic strains (PBT),

Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part II Applications to the Diagnosis and Prognostic Monitoring of Oral and Systemic Cancers.

Human saliva offers many advantages over other biofluids regarding its use and value as a bioanalytical medium for the identification and prognostic monitoring of human diseases, mainly because its collection is largely non-invasive, is relatively cheap, and does not require any major clinical supervision, nor supervisory input. Indeed, participants donating this biofluid for such purposes, including the identification, validation and quantification of surrogate biomarkers, may easily self-collect such samples in their homes following the provision of full collection details to them by researchers. In this report, the authors have focused on the applications of metabolomics technologies to the diagnosis and progressive severity monitoring of human cancer conditions, firstly oral cancers (e.g., oral cavity squamous cell carcinoma), and secondly extra-oral (systemic) cancers such as lung, breast and prostate cancers. For each publication reviewed, the authors provide a detailed evaluation and critical appraisal of the experimental design, sample size, ease of sample collection (usually but not exclusively as whole mouth saliva (WMS)), their transport, length of storage and preparation for analysis. Moreover, recommended protocols for the optimisation of NMR pulse sequences for analysis, along with the application of methods and techniques for verifying and resonance assignments and validating the quantification of biomolecules responsible, are critically considered. In view of the authors specialisms and research interests, the majority of these investigations were conducted using NMR-based metabolomics techniques. The extension of these studies to determinations of metabolic pathways which have been pathologically disturbed in these diseases is also assessed here and reviewed. Where available, data for the monitoring of patients responses to chemotherapeutic treatments, and in one case, radiotherapy, are also evaluated herein. Additionally, a novel case study featured evaluates the molecular nature, levels and diagnostic potential of

Clinical Outcomes of Stereotactic Ablative Radiotherapy for All Stages of Non-Small Cell Lung Cancer Definitive versus Consolidative.

A Life-Threatening Infection after Endobronchial Ultrasound Transbronchial Lung Biopsy with Guide Sheath A Case Report.

Endobronchial ultrasound transbronchial lung biopsy with guide sheath (EBUS-GS-TBLB) has been regarded as a reasonable diagnostic method with an acceptable diagnostic yield. In addition, EBUS-GS-TBLB is considered safer and less invasive compared to percutaneous needle biopsy and thoracoscopic surgery. However, we encountered a case of life-threatening procedure-related fatal infection, which was successfully managed. A 61-year-old man with a 30 pack-year smoking history was referred to our clinic with a necrotic lung mass in the right middle lobe on a chest computed tomography scan. EBUS-GS-TBLB was performed for a pathological diagnosis without immediate complications. Eight days after the procedure, the patient visited the hospital with sudden hemoptysis and severe dyspnea with fever. A chest computed tomography revealed a ruptured lung abscess and pneumonia, developed after EBUS-GS-TBLB. Extracorporeal membrane oxygenation (ECMO) and mechanical ventilation were initiated to manage refractory hypoxia. While maintaining ECMO, video-assisted thoracoscopic surgery was performed at the patients bedside in the intensive care unit. After surgery, the patients vital signs gradually improved, and a chest computed tomography revealed a reduction in the extent of the lung abscess. Although EBUS-GS-TBLB is minimally invasive and relatively safe when used for the diagnosis of peripheral lung lesions, pulmonary physicians should be aware of this rare but critical complication. We suggest that the careful prescription of prophylactic antibiotics before EBUS-GS-TBLB would be wise if the mass featured a necrotic, cavitary, or cystic lesion.

Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy.

Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients daily treatment for nonmalignant-associated pathology and have known, light toxicity profiles. It is quite common for a given patients daily administration schedule to include two or three of these drugs for the duration of their treatment. We chose to review the latest literature concerning metformin, employed as a first-line treatment for type 2 diabetes mebendazole, as an anthelmintic atorvastatin, as a cholesterol-lowering drug propranolol, used in cardiovascular diseases as a nonspecific inhibitor of beta-1 and beta-2 adrenergic receptors. At the same time, certain key action mechanisms make them feasible antitumor agents such as for mitochondrial ETC inhibition, activation of the enzyme adenosine monophosphate-activated protein kinase, amelioration of endogenous hyperinsulinemia, inhibition of selective tyrosine kinases (i.e., VEGFR2, TNIK, and BRAF), and mevalonate pathway inhibition. Despite the abundance of results from in vitro and in vivo studies, the only solid data from randomized clinical trials confirm metformin-related oncological benefits for only a small subset of nondiabetic patients with HER2-positive breast cancer and early-stage colorectal cancer. At the same time, clinical studies confirm metformin-related detrimentallack of an effect for lung, breast, prostate cancer, and glioblastoma. For atorvastatin we see a clinical oncological benefit in patients and head and neck cancer, with a trend towards radioprotection of critical structures, thus supporting the role of atorvastatin as a promising agent for concomitant association with radiotherapy. Propranolol-related increased outcomes were seen in clinical studies in patients with melanoma, breast cancer, and sarcoma.

Localization Technique Using Mixture of Indigo Carmine and Lipiodol of Pulmonary Nodule via Bronchoscopic Navigation.

What Is Different in Acute Hematologic Malignancy-Associated ARDS An Overview of the Literature.

Impacts of Outdoor Particulate Matter Exposure on the Incidence of Lung Cancer and Mortality.

Alpha-Mangostin Reduces Pericellular Fibronectin on Suspended Tumor Cells and Therapeutically, but Not Prophylactically, Suppresses Distant Metastasis.

Major cancer deaths can be ascribed to distant metastasis to which the assembly of pericellular fibronectin (periFN) on suspended tumor cells (STCs) in the bloodstream that facilitate endothelial attachment can lead. Even though mangosteen pericarps (MP) extracts and the major component α-mangostin (α-MG) exhibit potent cancer chemopreventive properties, whether they can prophylactically and therapeutically be used as dietary nutraceuticals to prevent distant metastasis by suppressing periFN assembly on STCs within the circulation remains obscure. Immunofluorescence staining, MTT assays, flow cytometric assays, immunoblotting, and experimental metastasis mouse models were used to detect the effects of MP extracts or α-MG on periFN on STCs, tumor cell proliferation and apoptosis, the AKT activity, and tumor lung metastasis. The periFN assembly on STCs was significantly diminished upon treatments of STCs with either α-MG or MP extracts in a dose-dependent manner without inhibiting cell proliferation and viability due to increased AKT activity. Pretreatment of STCs with α-MG appeared to suppress tumor lung metastasis and prolong mouse survival rates. Oral gavage with MP extracts could therapeutically, but not prophylactically, prevent lung metastasis of STCs. We concluded that MP extracts or the major component α-MG may therapeutically serve as a potent anti-metastatic nutraceutical.

Sputum Microbiome Composition in Patients with Squamous Cell Lung Carcinoma.

Recent findings indicate that the host microbiome can have a significant impact on the development of lung cancer by inducing an inflammatory response, causing dysbiosis, and generating genome damage. The aim of this study was to search for bacterial communities specifically associated with squamous cell carcinoma (LUSC). In this study, the taxonomic composition of the sputum microbiome of 40 men with untreated LUSC was compared with that of 40 healthy controls. Next-Generation sequencing of bacterial 16S rRNA genes was used to determine the taxonomic composition of the respiratory microbiome. There were no differences in alpha diversity between the LUSC and control groups. Meanwhile, differences in the structure of bacterial communities (β diversity) among patients and controls differed significantly in sputum samples (pseudo-F 1.53 Among other candidates,

Decreased TSPAN14 Expression Contributes to NSCLC Progression.

Tspan14 is a transmembrane protein of the tetraspanin (Tspan) protein family. Different members of the Tspan family can promote or suppress tumor progression. The exact role of Tspan14 in tumor cells is unknown. Earlier, mutational inactivation of the TSPAN14 gene has been proposed to coincide with a low survival rate in NSCLC patients. This study aimed to investigate the correlation of TSPAN14 lack of function with clinicopathological features of NSCLC patients, and to elucidate the role TSPAN14 might have in NSCLC progression. TSPAN14 expression was lower in tumor cells than non-tumor cells in NSCLC patients samples. The decreased gene expression was correlated with a low survival rate of patients and was more frequent in patients with aggressive, invasive tumor types. Additionally, the role of decreased TSPAN14 expression in the metastatic potential of cancer cells was confirmed in NSCLC cell lines. The highly invasive NSCLC cell line (NCI-H661) had the lowest TSPAN14 gene and protein expression, whereas the NSCLC cell line with the highest TSPAN14 expression (NCI-H460) had no significant metastatic potential. Finally, silencing of TSPAN14 in these non-metastatic cancer cells caused an increased expression of matrix-degrading enzymes MMP-2 and MMP-9, followed by an elevated capacity of cancer cells to degrade gelatin. The results of this study propose TSPAN14 expression as an indicator of NSCLC metastatic potential and progression.

Adoption of Robotic Core Technology in Minimally Invasive Lung Segmentectomy Review.

A recent randomized trial demonstrated the survival superiority of lung segmentectomy over lobectomy in patients with early stage, small-sized lung cancer. Hence, there is a pressing need for thoracic surgeons to gain familiarity with lung segmentectomy. However, lung segmentectomy, especially via minimally invasive surgery, is a technically challenging thoracic surgical procedure. The robotic surgery platform helps surgeons to improve their operative performance based on its core technological features improved dexterity, precision, and visualization. Herein, we have discussed the key issues related to robotic lung segmentectomy, explicitly focusing on the technical features of complex segmentectomy under difficult conditions. We have also introduced our preferred surgical strategy for robotic lung segmentectomy with specific maneuvers.

Retrospective Analysis for Dose Reduction to Organs at Risk with New Personalized Breast Holder (PERSBRA) in Left Breast IMRT.

This study evaluated dose differences in normal organs at risk, such as the lungs, heart, left anterior descending artery (LAD), right coronary artery, left ventricle, and right breast under personalized breast holder (PERSBRA), when using intensity-modulated radiation therapy (IMRT). This study evaluated the radiation protection offered by PERSBRA in left breast cancer radiation therapy. Here, we retrospectively collected data from 24 patients with left breast cancer who underwent breast-conserving surgery as well as IMRT radiotherapy. We compared the dose differences in target coverage and organs at risk with and without PERSBRA. For target coverage, tumor prescribed dose 95% coverage, conformity index, and homogeneity index were evaluated. For organs at risk, we compared the mean heart dose, mean left ventricle dose, LAD maximum and mean dose, mean left lung receiving 20 Gy, 10 Gy, and 5 Gy of left lung volume, maximum and mean coronary artery of the right, maximum of right breast, and mean dose. Good target coverage was achieved with and without PERSBRA. When PERSBRA was used with IMRT, the mean dose of the heart decreased by 42%, the maximum dose of LAD decreased by 26.4%, and the mean dose of LAD decreased by 47.0%. The mean dose of the left ventricle decreased by 54.1%, the volume (V

Different Machine Learning Approaches for Implementing Telehealth-Based Cancer Pain Management Strategies.

The most effective strategy for managing cancer pain remotely should be better defined. There is a need to identify those patients who require increased attention and calibrated follow-up programs. Machine learning (ML) models were developed using the data prospectively obtained from a single-center program of telemedicine-based cancer pain management. These models included random forest (RF), gradient boosting machine (GBM), artificial neural network (ANN), and the LASSO-RIDGE algorithm. Thirteen demographic, social, clinical, and therapeutic variables were adopted to define the conditions that can affect the number of teleconsultations. After ML validation, the risk analysis for more than one remote consultation was assessed in target individuals. The data from 158 patients were collected. In the training set, the accuracy was about 95% and 98% for ANN and RF, respectively. Nevertheless, the best accuracy on the test set was obtained with RF (70%). The ML-based simulations showed that young age (lt55 years), lung cancer, and occurrence of breakthrough cancer pain help to predict the number of remote consultations. Elderly patients (gt75 years) with bone metastases may require more telemedicine-based clinical evaluations. ML-based analyses may enable clinicians to identify the best model for predicting the need for more remote consultations. It could be useful for calibrating care interventions and resource allocation.

Deep Ensemble Learning for the Automatic Detection of Pneumoconiosis in Coal Workers Chest X-ray Radiography.

Globally, coal remains one of the natural resources that provide power to the world. Thousands of people are involved in coal collection, processing, and transportation. Particulate coal dust is produced during these processes, which can crush the lung structure of workers and cause pneumoconiosis. There is no automated system for detecting and monitoring diseases in coal miners, except for specialist radiologists. This paper proposes ensemble learning techniques for detecting pneumoconiosis disease in chest X-ray radiographs (CXRs) using multiple deep learning models. Three ensemble learning techniques (simple averaging, multi-weighted averaging, and majority voting (MVOT)) were proposed to investigate performances using randomised cross-folds and leave-one-out cross-validations datasets. Five statistical measurements were used to compare the outcomes of the three investigations on the proposed integrated approach with state-of-the-art approaches from the literature for the same dataset. In the second investigation, the statistical combination was marginally enhanced in the ensemble of multi-weighted averaging on a robust model, CheXNet. However, in the third investigation, the same model elevated accuracies from 87.80 to 90.2%. The investigated results helped us identify a robust deep learning model and ensemble framework that outperformed others, achieving an accuracy of 91.50% in the automated detection of pneumoconiosis.

Prognostic Significance of Organ-Specific Metastases in Patients with Metastatic Upper Tract Urothelial Carcinoma.

Existing data on metastatic upper tract urothelial carcinoma (mUTUC) are limited. In this study, we investigated the prognostic value of site-specific metastases in patients with mUTUC and its association with survival outcomes. We retrospectively collected data from the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2016. Kaplan-Meier analysis with a log-rank test was used for survival comparisons. Multivariate Cox regression was employed to predict overall survival (OS) and cancer-specific survival (CSS). 633 patients were selected in this study cohort. The median follow-up was 6 months (IQR 2-13) and a total of 584 (92.3%) deaths were recorded. Within the population presenting with a single metastatic organ site, the most common metastatic sites were distant lymph nodes, accounting for 36%, followed by lung, bone and liver metastases, accounting for 26%, 22.8% and 16.2%, respectively. In patients with a single metastatic organ site, the Kaplan-Meier curves showed significantly worse OS for patients with liver metastases vs. patients presenting with metastases in a distant lymph node ( A distant lymph node was the most common site of single-organ metastases for mUTUC. Patients with liver metastases and patients with multiple organ metastases exhibited worse survival outcomes. Lastly, CHT administration and RNU were revealed to be predictors of better survival outcomes in the mUTUC cohort.

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors A Systematic Review.

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the bodys own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.

Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Lung Cancer.

Despite the significant progress made towards comprehending the deregulated signatures in lung cancer, these vary from study to study. We reanalyzed 25 studies from the Gene Expression Omnibus (GEO) to detect and annotate co-deregulated signatures in lung cancer and in single-gene or single-drug perturbation experiments. We aimed to decipher the networks that these co-deregulated genes (co-DEGs) form along with their upstream regulators. Differential expression and upstream regulators were computed using Characteristic Direction and Systems Biology tools, including GEO2Enrichr and X2K. Co-deregulated gene expression profiles were further validated across different molecular and immune subtypes in lung adenocarcinoma (TCGA-LUAD) and lung adenocarcinoma (TCGA-LUSC) datasets, as well as using immunohistochemistry data from the Human Protein Atlas, before being subjected to subsequent GO and KEGG enrichment analysis. The functional alterations of the co-upregulated genes in lung cancer were mostly related to immune response regulating the cell surface signaling pathway, in contrast to the co-downregulated genes, which were related to S-nitrosylation. Networks of hub proteins across the co-DEGs consisted of overlapping TFs (SOX2, MYC, KAT2A) and kinases (MAPK14, CSNK2A1 and CDKs). Furthermore, using Connectivity Map we highlighted putative repurposing drugs, including valproic acid, betonicine and astemizole. Similarly, we analyzed the co-DEG signatures in single-gene and single-drug perturbation experiments in lung cancer cell lines. In summary, we identified critical co-DEGs in lung cancer providing an innovative framework for their potential use in developing personalized therapeutic strategies.

Pathogenesis of Tobacco-Associated Lung Adenocarcinoma Is Closely Coupled with Changes in the Gut and Lung Microbiomes.

Microbial dysbiosis has emerged as a modulator of oncogenesis and response to therapy, particularly in lung cancer. Here, we investigate the evolution of the gut and lung microbiomes following exposure to a tobacco carcinogen. We performed 16S rRNA-Seq of fecal and lung samples collected prior to and at several timepoints following (nicotine-specific nitrosamine ketoneNNK) exposure in

Resveratrol Affects Sphingolipid Metabolism in A549 Lung Adenocarcinoma Cells.

Resveratrol is a naturally occurring polyphenol which has various beneficial effects, such as anti-inflammatory, anti-tumor, anti-aging, antioxidant, and neuroprotective effects, among others. The anti-cancer activity of resveratrol has been related to alterations in sphingolipid metabolism. We analyzed the effect of resveratrol on the enzymes responsible for accumulation of the two sphingolipids with highest functional activity-apoptosis promoting ceramide (CER) and proliferation-stimulating sphingosine-1-phosphate (S1P)-in human lung adenocarcinoma A549 cells. Resveratrol treatment induced an increase in CER and sphingosine (SPH) and a decrease in sphingomyelin (SM) and S1P. Our results showed that the most common mode of CER accumulation, through sphingomyelinase-induced hydrolysis of SM, was not responsible for a CER increase despite the reduction in SM in A549 plasma membranes. However, both the activity and the expression of CER synthase 6 were upregulated in resveratrol-treated cells, implying that CER was accumulated as a result of stimulated de novo synthesis. Furthermore, the enzyme responsible for CER hydrolysis, alkaline ceramidase, was not altered, suggesting that it was not related to changes in the CER level. The enzyme maintaining the balance between apoptosis and proliferation, sphingosine kinase 1 (SK1), was downregulated, and its expression was reduced, resulting in a decrease in S1P levels in resveratrol-treated lung adenocarcinoma cells. In addition, incubation of resveratrol-treated A549 cells with the SK1 inhibitors DMS and fingolimod additionally downregulated SK1 without affecting its expression. The present studies provide information concerning the biochemical processes underlying the influence of resveratrol on sphingolipid metabolism in A549 lung cancer cells and reveal possibilities for combined use of polyphenols with specific anti-proliferative agents that could serve as the basis for the development of complex therapeutic strategies.

Analysis of Circulating Tumor and Cancer Stem Cells Provides New Opportunities in Diagnosis and Treatment of Small Cell Lung Cancer.

Current methods for diagnosis and treatment of small cell lung cancer (SCLC) have only a modest efficacy. In this pilot study, we analyzed circulating tumor cells (CTCs) and cancer stem cells (CSCs) in patients with SCLC to search for new diagnostic and prognostic markers and novel approaches to improve the treatment of the disease. In other forms of lung cancer, we showed a heterogeneity of blood CTCs and CSCs populations, as well as changes in other cell populations (ALDH

Identification of AGR2 Gene-Specific Expression Patterns Associated with Epithelial-Mesenchymal Transition.

The TGF-β signaling pathway is involved in numerous cellular processes, and its deregulation may result in cancer development. One of the key processes in tumor progression and metastasis is epithelial to mesenchymal transition (EMT), in which TGF-β signaling plays important roles. Recently, AGR2 was identified as a crucial component of the cellular machinery responsible for maintaining the epithelial phenotype, thereby interfering with the induction of mesenchymal phenotype cells by TGF-β effects in cancer. Here, we performed transcriptomic profiling of A549 lung cancer cells with CRISPR-Cas9 mediated

Multiple Parallel Fusion Network for Predicting Protein Subcellular Localization from Stimulated Raman Scattering (SRS) Microscopy Images in Living Cells.

Stimulated Raman Scattering Microscopy (SRS) is a powerful tool for label-free detailed recognition and investigation of the cellular and subcellular structures of living cells. Determining subcellular protein localization from the cell level of SRS images is one of the basic goals of cell biology, which can not only provide useful clues for their functions and biological processes but also help to determine the priority and select the appropriate target for drug development. However, the bottleneck in predicting subcellular protein locations of SRS cell imaging lies in modeling complicated relationships concealed beneath the original cell imaging data owing to the spectral overlap information from different protein molecules. In this work, a multiple parallel fusion network, MPFnetwork, is proposed to study the subcellular locations from SRS images. This model used a multiple parallel fusion model to construct feature representations and combined multiple nonlinear decomposing algorithms as the automated subcellular detection method. Our experimental results showed that the MPFnetwork could achieve over 0.93 dice correlation between estimated and true fractions on SRS lung cancer cell datasets. In addition, we applied the MPFnetwork method to cell images for label-free prediction of several different subcellular components simultaneously, rather than using several fluorescent labels. These results open up a new method for the time-resolved study of subcellular components in different cells, especially cancer cells.

Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media.

In comparing two human lung cancer cells, we previously found lower levels of acetylcholinesterase (AChE) and intact amyloid-β4042 (Aβ), and higher levels of mature brain-derived neurotrophic factor (mBDNF) in the media of H1299 cells as compared to A549 cell media. In this study, we hypothesized that the levels of soluble amyloid precursor protein α (sAPPα) are regulated by AChE and mBDNF in A549 and H1299 cell media. The levels of sAPPα were higher in the media of H1299 cells. Knockdown of AChE led to increased sAPPα and mBDNF levels and correlated with decreased levels of intact Aβ4042 in A549 cell media. AChE and mBDNF had opposite effects on the levels of Aβ and sAPPα and were found to operate through a mechanism involving α-secretase activity. Treatment with AChE decreased sAPPα levels and simultaneously increased the levels of intact Aβ4042 suggesting a role of the protein in shifting APP processing away from the non-amyloidogenic pathway and toward the amyloidogenic pathway, whereas treatment with mBDNF led to opposite effects on those levels. We also show that the levels of sAPPα are regulated by protein kinase C (PKC), extracellular signal-regulated kinase (ERK)12, phosphoinositide 3 Kinase (PI3K), but not by protein kinase A (PKA).

Malignant Transformation of Giant Cell Tumour of Bone A Review of Literature and the Experience of a Referral Centre.

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1-9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.

An Axis between the Long Non-Coding RNA

Long non-coding RNAs (lncRNAs) play critical roles in human cancers. HOXA11 anti-sense RNA (

Identification of

Changes in DNA methylation identified by epigenome-wide association studies (EWAS) have been recently linked to increased lung cancer risk. However, the cellular effects of these differentially methylated positions (DMPs) are often unclear. Therefore, we investigated top differentially methylated positions identified from an EWAS study. This included a putative regulatory region of

Circulating

The Sympathetic Nervous System Contributes to the Establishment of Pre-Metastatic Pulmonary Microenvironments.

Emerging evidence suggests that neural activity contributes to tumor initiation and its acquisition of metastatic properties. More specifically, it has been reported that the sympathetic nervous system regulates tumor angiogenesis, tumor growth, and metastasis. The function of the sympathetic nervous system in primary tumors has been gradually elucidated. However, its functions in pre-metastatic environments andor the preparation of metastatic environments far from the primary sites are still unknown. To investigate the role of the sympathetic nervous system in pre-metastatic environments, we performed chemical sympathectomy using 6-OHDA in mice and observed a decrease in lung metastasis by attenuating the recruitment of myeloid-derived suppressor cells. Furthermore, we note that neuro-immune cell interactions could be observed in tumor-bearing mouse lungs in conjunction with the decreased expression of Sema3A. These data indicate that the sympathetic nervous system contributes to the preparation of pre-metastatic microenvironments in the lungs, which are mediated by neuro-immune cell interactions.

Comparison between Immunocytochemistry, FISH and NGS for

The detection of

FGFR1-4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer.

While fibroblast growth factor receptors (FGFRs) are involved in several biological pathways and FGFR inhibitors may be useful in the treatment of squamous non-small cell lung cancer (Sq-NSCLC), FGFR aberrations are not well characterized in Sq-NSCLC. We comprehensively evaluated FGFR expression, fusions, and variants in 40 fresh-frozen primary Sq-NSCLC (stage IA3-IV) samples and tumor-adjacent normal tissues using real-time PCR and next-generation sequencing (NGS). Protein expression of FGFR1-3 and amplification of

Potent Chlorambucil-Platinum(IV) Prodrugs.

The DNA-alkylating derivative chlorambucil was coordinated in the axial position to atypical cytotoxic, heterocyclic, and non-DNA coordinating platinum(IV) complexes of type,

Histidine-Rich Glycoprotein Suppresses the S100A8A9-Mediated Organotropic Metastasis of Melanoma Cells.

The dissection of the complex multistep process of metastasis exposes vulnerabilities that could be exploited to prevent metastasis. To search for possible factors that favor metastatic outgrowth, we have been focusing on secretory S100A8A9. A heterodimer complex of the S100A8 and S100A9 proteins, S100A8A9 functions as a strong chemoattractant, growth factor, and immune suppressor, both promoting the cancer milieu at the cancer-onset site and cultivating remote, premetastatic cancer sites. We previously reported that melanoma cells show lung-tropic metastasis owing to the abundant expression of S100A8A9 in the lung. In the present study, we addressed the question of why melanoma cells are not metastasized into the brain at significant levels in mice despite the marked induction of S100A8A9 in the brain. We discovered the presence of plasma histidine-rich glycoprotein (HRG), a brain-metastasis suppression factor against S100A8A9. Using S100A8A9 as an affinity ligand, we searched for and purified the binding plasma proteins of S100A8A9 and identified HRG as the major protein on mass spectrometric analysis. HRG prevents the binding of S100A8A9 to the B16-BL6 melanoma cell surface via the formation of the S100A8A9 complex. HRG also inhibited the S100A8A9-induced migration and invasion of A375 melanoma cells. When we knocked down HRG in mice bearing skin melanoma, metastasis to both the brain and lungs was significantly enhanced. The clinical examination of plasma S100A8A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis.

Impact of Baseline Versus Intercurrent Steroids Administration on Upfront Chemo-Immunotherapy for Advanced Non-Small Cell Lung Cancer (NSCLC).

The impact of baseline versus intercurrent steroids on the efficacy of upfront chemotherapy plus pembrolizumab (CT-ICI) for advanced non-small cell lung cancer (NSCLC) patients is unclear. We conducted a retrospective study on metastatic NSCLC patients treated with upfront CT-ICI at our institution between March 2020 and December 2021. The use of steroids was considered as the administration of at least 10 mg of prednisone equivalent. Of 101 patients, 36 (35.6%) received steroid therapy at baseline, and 18 (17.8%) started steroids on treatment. Overall, median progression-free survival (mPFS) was 6.5 months (95% CI, 5.9-8.9) and median overall survival (mOS) was 18.2 months (95% CI, 8.9-NR). Patients taking baseline steroids had significantly shorter survival than those not taking them and those assuming intercurrent steroids (mPFS 5.0 vs. 9.2 vs. 7.3 months,

Challenges and Suggestions in Management of Lung and Liver Cancer in Uzbekistan The Second Report of the Uzbekistan-Korea Oncology Consortium.

The health burden of cancer increases in Uzbekistan as the country develops and the life expectancy increases. Management of such a burden requires efficient screening, treatment optimization, and investigation of the causes of cancer. The Ministry of Health of Uzbekistan formed an advisory consortium, including clinical oncology and healthcare management experts from Uzbekistan and South Korea, to design a strategy for cancer management. Our consortium has analyzed six cancer types with high morbidity and mortality in Uzbekistan by classifying them into three categories (breast, cervical (gynecologic cancers), lung, liver (cancer common in men), stomach, and colorectal cancers (gastrointestinal cancers)). Lung and liver cancers are common causes of death in men after middle age-they can yield a serious health burden on the country and ruin the livelihood of families. In this review, we will analyze the oncologic literature and suggest practical recommendations for the treatment and prevention of lung and liver cancer in Uzbekistan. Data from South Korea, which has conducted nationwide screening for two decades and made progress in improving prognosis, will be discussed as a comparative control.

Global Research Trends of Artificial Intelligence on Histopathological Images A 20-Year Bibliometric Analysis.

Cancer has become a major threat to global health care. With the development of computer science, artificial intelligence (AI) has been widely applied in histopathological images (HI) analysis. This study analyzed the publications of AI in HI from 2001 to 2021 by bibliometrics, exploring the research status and the potential popular directions in the future. A total of 2844 publications from the Web of Science Core Collection were included in the bibliometric analysis. The countryregion, institution, author, journal, keyword, and references were analyzed by using VOSviewer and CiteSpace. The results showed that the number of publications has grown rapidly in the last five years. The USA is the most productive and influential country with 937 publications and 23,010 citations, and most of the authors and institutions with higher numbers of publications and citations are from the USA. Keyword analysis showed that breast cancer, prostate cancer, colorectal cancer, and lung cancer are the tumor types of greatest concern. Co-citation analysis showed that classification and nucleus segmentation are the main research directions of AI-based HI studies. Transfer learning and self-supervised learning in HI is on the rise. This study performed the first bibliometric analysis of AI in HI from multiple indicators, providing insights for researchers to identify key cancer types and understand the research trends of AI application in HI.

Association between Air Pollution and Squamous Cell Lung Cancer in South-Eastern Poland.

Air pollution is closely associated with the development of respiratory illness. The aim of the present study was to assess the relationship between long-term exposure to PM2.5, PM10, NO

Two-Dose Vaccination Significantly Prolongs the Duration from Symptom Onset to Death A Retrospective Study Based on 173,894 SARS-CoV-2 Cases in Khyber Pakhtunkhwa, Pakistan.

This research was carried out to quantify the duration from symptom onset to recoverydeath (SORSOD) during the first four waves and the AlphaDelta period of the epidemic in Khyber Pakhtunkhwa, Pakistan, and identify the associated factors. A total of 173,894 COVID-19 cases were admitted between 16 March 2020 and 30 November 2021, including 458 intensive care unit (ICU) cases. The results showed that the case fatality rate (CFR) increased with age, and females had a higher CFR. The median SOR of ICU cases was longer than that of non-ICU cases (27.6 vs. 17.0 days), while the median SOD was much shorter (6.9 vs. 8.4 days). The SOR and SOD in the Delta period were slightly shortened than the Alpha period. Age, cardiovascular diseases, chronic lung disease, diabetes, fever, breathing issues, and ICU admission were risk factors that were significantly associated with SOD (

Availability of Financial and Medical Resources for Screening Providers and Its Impact on Cancer Screening Uptake and Intervention Programs.

Interventions for residents and medicalfinancial resources available to screening providers can improve cancer screening rates. Yet the mechanisms by which the interactions of these factors affect the screening rates remain unknown. This study employed structural equation modeling to analyze the mechanisms underlying these factors. Data for Japanese municipalities medicalfinancial status, their implementation of screening interventions, and the number of municipality-based cancer screening appointments from April 2016 to March 2017 were obtained from an open database. Five cancer screenings were included gastric, lung, colorectal, breast, and cervical cancer screening all are nationally recommended for population screening in Japan. We defined two latent variables, namely, intervention for residents and medicalfinancial resources, and then analyzed the relationships between these variables and screening rates using structural equation modeling. Models were constructed for gastric, lung, and breast cancer screening, and similar relationships were observed. With these cancer types, medicalfinancial resources affected the intervention for residents, directly affecting screening rates. One limitation of this study is that it only included screening by municipalities, which may cause selection bias. In conclusion, financial pressures and lack of medical resources may cause a reduction in screening intervention programs, leading to stagnant screening rates. Ensuring consistent implementation of interventions for residents may improve local and regional cancer screening rates.

Radon Progeny Adsorption on Facial Masks.

The radioactive noble gas radon and its short-living progeny are inhaled during respiration, depositing their decay energies in the lungs. These progeny are considered responsible for more than 95% of the total effective dose and are, together with radon, classified as carcinogenic for lung cancer. Consequently, filtration of the progeny could reduce the dose to the lungs. In our study, we investigated the filtration properties of FFP2 versus surgical masks (II R) for radon and its decay products. The masks were attached to a measurement device, which enabled determination of the size distribution of radon progeny, ranging from unattached to clustered progeny. In parallel, it measured the radon activity concentration during experiments. By comparing background measurements without mask and experiments with masks, the percentage of retained unattached radon progeny was determined for FFP2 (98.8 ± 0.6%) and II R masks (98.4 ± 0.7%). For clustered progeny, the retained fraction was 85.2 ± 18.1% for FFP2 and 79.5 ± 22.1% for II R masks while radon was not filtered. We can show that masks are effective in filtering radon progeny and thus are capable of reducing the total effective dose to the lungs.

An Innovative Tool to Control Occupational Radon Exposure.

After smoking, indoor radon is the main contributor to lung cancer in many countries. The European Union (EU) Directive 201359Euratom establishes a maximum reference level of 300 Bqm

Detection and Visualisation of Pneumoconiosis Using an Ensemble of Multi-Dimensional Deep Features Learned from Chest X-rays.

Pneumoconiosis is a group of occupational lung diseases induced by mineral dust inhalation and subsequent lung tissue reactions. It can eventually cause irreparable lung damage, as well as gradual and permanent physical impairments. It has affected millions of workers in hazardous industries throughout the world, and it is a leading cause of occupational death. It is difficult to diagnose early pneumoconiosis because of the low sensitivity of chest radiographs, the wide variation in interpretation between and among readers, and the scarcity of B-readers, which all add to the difficulty in diagnosing these occupational illnesses. In recent years, deep machine learning algorithms have been extremely successful at classifying and localising abnormality of medical images. In this study, we proposed an ensemble learning approach to improve pneumoconiosis detection in chest X-rays (CXRs) using nine machine learning classifiers and multi-dimensional deep features extracted using CheXNet-121 architecture. There were eight evaluation metrics utilised for each high-level feature set of the associated cross-validation datasets in order to compare the ensemble performance and state-of-the-art techniques from the literature that used the same cross-validation datasets. It is observed that integrated ensemble learning exhibits promising results (92.68% accuracy, 85.66% Matthews correlation coefficient (MCC), and 0.9302 area under the precision-recall (PR) curve), compared to individual CheXNet-121 and other state-of-the-art techniques. Finally, Grad-CAM was used to visualise the learned behaviour of individual dense blocks within CheXNet-121 and their ensembles into three-color channels of CXRs. We compared the Grad-CAM-indicated ROI to the ground-truth ROI using the intersection of the union (IOU) and average-precision (AP) values for each classifier and their ensemble. Through the visualisation of the Grad-CAM within the blue channel, the average IOU passed more than 90% of the pneumoconiosis detection in chest radiographs.

How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma

Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices-such as population-level screening for lung cancer-are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens.

Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway.

Aging has been recently reported to promote lung cancer initiation and progression. Senescent fibroblasts gain a cancer-associated fibroblast (CAF) phenotype, and exert a powerful influence on cancer behavior, such as tumor cell growth and metastasis. However, mechanisms linking fibroblast senescence with CAF activation remain poorly understood. Our study shows that senescent fibroblasts displayed CAF properties, including the highly expressed CAF markers, α-SMA and Vimentin, and CAF-specific factors, CXCL12, FGF10, IL6 and COL1A1, which significantly increased collagen contractile activity and promoted the migration and invasion of lung cancer cells, H1299 and A549. We were further able to show that CAF characteristics in senescent fibroblasts could be regulated by the Stat3 pathway. Intracellular ROS accumulation activates the Stat3 pathway during senescence. Thus, our findings indicate that senescent fibroblasts mediate a CAF function with the Stat3 pathway. We further propose a novel Stat3 dependent targetable mechanism, which is instrumental in mediating the migration and invasion of lung cancer cells.

Diagnosis and Pattern Identification of Intrathoracic Malignant Melanoma Metastasis A Retrospective Single Center Analysis.

The lung is a frequent site of secondary malignancies. Melanoma is a malignant tumor originating from melanocytes, that accounts for the majority of death related to skin cancers. In advanced stages, it can also present with intrathoracic metastasis, particularly in the lungs, but infrequent intrathoracic manifestations are possible. A retrospective analysis of the cases referred to the pulmonary endoscopy unit of the hospital of Reggio Emilia in the last 10 years (since December 2012) was carried out, discovering 17 cases of melanoma metastasis with thoracic localizations, either with or without a diagnosis of primary melanoma. Four repetitive patterns of clinical-radiological presentation have been identified and described through the same number of paradigmatic clinical cases nodal involvement (35%), lung mass(es) (41%), diffuse pulmonary involvement (12%), and pleural involvement (12%). These different presentations imply the use of different diagnostic techniques, with an overall high diagnostic yield (87.5%). Finally, a brief analysis of survival based on the pattern of presentation has been performed, finding no statistically significant differences between the four groups at metastasis diagnosis (

Deep Learning Using Endobronchial-Ultrasound-Guided Transbronchial Needle Aspiration Image to Improve the Overall Diagnostic Yield of Sampling Mediastinal Lymphadenopathy.

Lung cancer is the biggest cause of cancer-related death worldwide. An accurate nodal staging is critical for the determination of treatment strategy for lung cancer patients. Endobronchial-ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has revolutionized the field of pulmonology and is considered to be extremely sensitive, specific, and secure for lung cancer staging through rapid on-site evaluation (ROSE), but manual visual inspection on the entire slide of EBUS smears is challenging, time consuming, and worse, subjective, on a large interobserver scale. To satisfy ROSEs needs, a rapid, automated, and accurate diagnosis system using EBUS-TBNA whole-slide images (WSIs) is highly desired to improve diagnosis accuracy and speed, minimize workload and labor costs, and ensure reproducibility. We present a fast, efficient, and fully automatic deep-convolutional-neural-network-based system for advanced lung cancer staging on gigapixel EBUS-TBNA cytological WSIs. Each WSI was converted into a patch-based hierarchical structure and examined by the proposed deep convolutional neural network, generating the segmentation of metastatic lesions in EBUS-TBNA WSIs. To the best of the authors knowledge, this is the first research on fully automated enlarged mediastinal lymph node analysis using EBUS-TBNA cytological WSIs. We evaluated the robustness of the proposed framework on a dataset of 122 WSIs, and the proposed method achieved a high precision of 93.4%, sensitivity of 89.8%, DSC of 82.2%, and IoU of 83.2% for the first experiment (37.7% training and 62.3% testing) and a high precision of 91.8 ± 1.2, sensitivity of 96.3 ± 0.8, DSC of 94.0 ± 1.0, and IoU of 88.7 ± 1.8 for the second experiment using a three-fold cross-validation, respectively. Furthermore, the proposed method significantly outperformed the three state-of-the-art baseline models, including U-Net, SegNet, and FCN, in terms of precision, sensitivity, DSC, and Jaccard index, based on Fishers least significant difference (LSD) test (plt0.001). For a computational time comparison on a WSI, the proposed method was 2.5 times faster than U-Net, 2.3 times faster than SegNet, and 3.4 times faster than FCN, using a single GeForce GTX 1080 Ti, respectively. With its high precision and sensitivity, the proposed method demonstrated that it manifested the potential to reduce the workload of pathologists in their routine clinical practice.

Analysis of the Causes of Solitary Pulmonary Nodule Misdiagnosed as Lung Cancer by Using Artificial Intelligence A Retrospective Study at a Single Center.

Artificial intelligence (AI) adopting deep learning technology has been widely used in the med-ical imaging domain in recent years. It realized the automatic judgment of benign and malig-nant solitary pulmonary nodules (SPNs) and even replaced the work of doctors to some extent. However, misdiagnoses can occur in certain cases. Only by determining the causes can AI play a larger role. A total of 21 Coronavirus disease 2019 (COVID-19) patients were diagnosed with SPN by CT imaging. Their Clinical data, including general condition, imaging features, AI re-ports, and outcomes were included in this retrospective study. Although they were confirmed COVID-19 by testing reverse transcription-polymerase chain reaction (RT-PCR) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), their CT imaging data were misjudged by AI to be high-risk nodules for lung cancer. Imaging characteristics included burr sign (76.2%), lobulated sign (61.9%), pleural indentation (42.9%), smooth edges (23.8%), and cavity (14.3%). The accuracy of AI was different from that of radiologists in judging the nature of be-nign SPNs (

Different Uptake of

An 82-year-old man with a history of colon cancer was found with multiple lymphadenopathies and a pulmonary mass. Fluorine-18 fluorodeoxyglucose positron emission tomographycomputed tomography (

Challenges and Opportunities of Deep Learning for Cough-Based COVID-19 Diagnosis A Scoping Review.

In the past two years, medical researchers and data scientists worldwide have focused their efforts on containing the pandemic of coronavirus disease 2019 (COVID-19). Deep learning models have been proven to be capable of efficient medical diagnosis and prognosis in cancer, common lung diseases, and COVID-19. On the other hand, artificial neural networks have demonstrated their potential in pattern recognition and classification in various domains, including healthcare. This literature review aims to report the state of research on developing neural network models to diagnose COVID-19 from cough sounds to create a cost-efficient and accessible testing tool in the fight against the pandemic. A total of 35 papers were included in this review following a screening of the 161 outputs of the literature search. We extracted information from articles on data resources, model structures, and evaluation metrics and then explored the scope of experimental studies and methodologies and analyzed their outcomes and limitations. We found that cough is a biomarker, and its associated information can determine an individuals health status. Convolutional neural networks were predominantly used, suggesting they are particularly suitable for feature extraction and classification. The reported accuracy values ranged from 73.1% to 98.5%. Moreover, the dataset sizes ranged from 16 to over 30,000 cough audio samples. Although deep learning is a promising prospect in identifying COVID-19, we identified a gap in the literature on research conducted over large and diversified data sets.

Computed Tomography-Guided Localization and Extended Segmentectomy for Non-Small Cell Lung Cancer.

Lung cancer is one of the most devastating cancers. Low-dose computed tomography (LDCT) can detect lung cancer at an early stage of the disease when a minimally invasive surgical procedure using video-assisted thoracoscopic surgery is the best strategy. Herein, we discuss the treatment of deep lung tumors between segments or lesions located near the margin of a segment. This was a retrospective study conducted from January 2013 to January 2020 using the National Taiwan University Hospital data bank. We included early-stage non-small cell lung cancer (NSCLC) patients who underwent lung surgery and screened out those who received CT-guided localization for extended segmentectomy. Outcome measurements were safety margin, complication rate, and postoperative course. During the study period, 68 patients with early-stage NSCLC received CT-guided localization followed by extended segmentectomy. The mean surgery time was 92.1 ± 30.3 min, and the mean blood loss was 32.8 mL. Mean drainage time was 2.3 ± 1 days, and the total hospital stay was 4.9 ± 1.1 days. Pathological reports showed tumor-free resection margins gt2 cm. Sixty-one patients had adenocarcinoma at stage IA and two patients at stage IB. One patient had squamous cell carcinoma at stage IA. CT-guided localization followed by extended segmentectomy allows lung volume preservation with clean safety margins and good clinical outcomes.

Alphaviruses in Immunotherapy and Anticancer Therapy.

Alphaviruses have been engineered as expression vectors for vaccine development and gene therapy. Due to the feature of RNA self-replication, alphaviruses can provide exceptional direct cytoplasmic expression of transgenes based on the delivery of recombinant particles, naked or nanoparticle-encapsulated RNA or plasmid-based DNA replicons. Alphavirus vectors have been utilized for the expression of various antigens targeting different types of cancers, and cytotoxic and antitumor genes. The most common alphavirus vectors are based on the Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus, but the oncolytic M1 alphavirus has also been used. Delivery of immunostimulatory cytokine genes has been the basis for immunotherapy demonstrating efficacy in different animal tumor models for brain, breast, cervical, colon, lung, ovarian, pancreatic, prostate and skin cancers. Typically, therapeutic effects including tumor regression, tumor eradication and complete cure as well as protection against tumor challenges have been observed. Alphavirus vectors have also been subjected to clinical evaluations. For example, therapeutic responses in all cervical cancer patients treated with an alphavirus vector expressing the human papilloma virus E6 and E7 envelope proteins have been achieved.

Immunomodulatory Factor TIM3 of Cytolytic Active Genes Affected the Survival and Prognosis of Lung Adenocarcinoma Patients by Multi-Omics Analysis.

Efficacy and Safety of Combined Brain Stereotactic Radiotherapy and Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer with Brain Metastases.

To analyze the outcomes of patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) treated with immunotherapy (IT) and stereotactic radiotherapy (SRT) and to study the impact of the sequence between the two modalities. The authors reviewed the records of 51 patients with 84 BM from NSCLC treated at Institut Curie with IT and SRT. BM were categorized into three groups SRT before IT, concurrent SRT and IT, and SRT after IT. Regional progression-free interval (R-PFI) and overall survival (OS) were estimated using the Kaplan-Meier method. After a median follow-up from SRT of 22.5 months (2.7-47.3), the 1-year and 2-year OS were 69.7% (95%CI 58.0-83.8) and 44.0% 30.6-63.2, respectively. Concerning distant intracranial control, the 1-year and 2-year R-PFI were 40.1% 30.1-53.3 and 35.2% 25.1-49.4, respectively. Moreover, one-year R-PFI in SRT before IT, concurrent SRT and IT, and SRT after IT groups were 24.1%, 49.6%, and 34.2%, respectively ( The concurrent administration of SRT and IT appeared to offer the best locoregional control, without increasing the risk of toxicity, compared to patients treated with SRT before or after IT.

Chronic obstructive pulmonary disease (COPD) is considered as the strongest independent risk factor for lung cancer (LC) development, suggesting an overlapping genetic background in both diseases. A common feature of both diseases is aberrant immunity in respiratory epithelia that is mainly regulated by Toll-like receptors (TLRs), key regulators of innate immunity. The function of the flagellin-sensing TLR5 in airway epithelia and pathophysiology of COPD and LC has remained elusive. We performed case-control genetic association and functional studies on the importance of

Treatment of Brain Metastases The Synergy of Radiotherapy and Immune Checkpoint Inhibitors.

Brain metastases are a devastating sequela of common primary cancers (e.g., lung, breast, and skin) and have limited effective therapeutic options. Previously, systemic chemotherapy failed to demonstrate significant benefit in patients with brain metastases, but in recent decades, targeted therapies and more recently immune checkpoint inhibitors (ICIs) have yielded promising results in preclinical and clinical studies. Furthermore, there is significant interest in harnessing the immunomodulatory effects of radiotherapy (RT) to synergize with ICIs. Herein, we discuss studies evaluating the impact of RT dose and fractionation on the immune response, early studies supporting the synergistic interaction between RT and ICIs, and ongoing clinical trials assessing the benefit of combination therapy in patients with brain metastases.

Inflammatory Cytokine An Attractive Target for Cancer Treatment.

The relationship between inflammation and cancer has attracted attention for a long time. The inflammatory tumor microenvironment consists of inflammatory cells, chemokines, cytokines, and signaling pathways. Among them, inflammatory cytokines play an especially pivotal role in cancer development, prognosis, and treatment. Interleukins, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), interferons, and vascular endothelial growth factor (VEGF) are the representative inflammatory cytokines in various cancers, which may promote or inhibit cancer progression. The pro-inflammatory cytokines are associated with advanced cancer stages, resistance to immunotherapy, and poor prognoses, such as in objective response and disease control rates, and progression-free and overall survival. In this review, we selected colorectal, pancreatic, breast, gastric, lung, and prostate cancers, which are well-reported for an association between cancer and inflammatory cytokines. The related cytokines and their effects on each cancers development and prognosis were summarized. In addition, the treatment strategies targeting inflammatory cytokines in each carcinoma were also described here. By understanding the biological roles of cancer-related inflammatory cytokines, we may modulate the inflammatory tumor microenvironment for potential cancer treatment.

High Tumor Mutation Burden Is Associated with Poor Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy.

This study aimed to determine the association between TMB and treatment outcomes in patients with epidermal growth factor receptor (EGFR)-mutated lung cancer that were treated with tyrosine kinase inhibitors (TKIs). The TMB was assessed using a 409-gene targeted next-generation sequencing panel. We compared the response rate (RR), progression-free survival (PFS), overall survival (OS), and frequency of secondary T790M mutations among the different TMB groups. The median TMB of the study population (n 88) was 3.36megabases. We divided 52 (59%) and 36 (41%) patients into the low and high TMB groups, respectively. A high TMB level was significantly associated with liver metastasis and more advanced stage (all

In Situ Biosynthesis of Reduced Alpha Hematite (α-Fe

In the present study, we utilized

Theabrownin Alleviates Colorectal Tumorigenesis in Murine AOMDSS Model via PI3KAktmTOR Pathway Suppression and Gut Microbiota Modulation.

Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide, yet therapeutic options for CRC often exhibit strong side effects which cause patients well-being to deteriorate. Theabrownin (TB), an antioxidant from Pu-erh tea, has previously been reported to have antitumor effects on non-small-cell lung cancer, osteosarcoma, hepatocellular carcinoma, gliomas, and melanoma. However, the potential antitumor effect of TB on CRC has not previously been investigated in vivo. The present study therefore aimed to investigate the antitumor effect of TB on CRC and the underlying mechanisms. Azoxymethane (AOM)dextran sodium sulphate (DSS) was used to establish CRC tumorigenesis in a wild type mice model. TB was found to significantly reduce the total tumor count and improve crypt length and fibrosis of the colon when compared to the AOMDSS group. Immunohistochemistry staining shows that the expression of the proliferation marker, Ki67 was reduced, while cleaved caspase 3 was increased in the TB group. Furthermore, TB significantly reduced phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and the downstream mechanistic target of rapamycin (mTOR)and cyclin D1 protein expression, which might contribute to cell proliferation suppression and apoptosis enhancement. The 16s rRNA sequencing revealed that TB significantly modulated the gut microbiota composition in AOMDSS mice. TB increased the abundance of short chain fatty acid as well as SCFA-producing

Laminarin Attenuates ROS-Mediated Cell Migration and Invasiveness through Mitochondrial Dysfunction in Pancreatic Cancer Cells.

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously aggressive type of cancer with a high metastasis rate. It is conventionally treated by surgical resection and neoadjuvant chemotherapy. However, continuous chemotherapy leads to relapse in most PDAC patients due to chemical resistance. Therefore, novel anticancer agents need to be identified and developed. The antitumor activities of laminarin extracted from brown algae against hepatocarcinoma, lung, and colon cancer have been established. However, its effects on pancreatic cancer have remained obscure. Our study identified the anticancer effects of laminarin on pancreatic cancer cells and tried to explain its intracellular mechanisms. We assessed the cell viability of PANC-1 and MIA PaCa-2 cells using MTT assay. Hanging drop method was used for the spheroid formation. Flow cytometry was conducted to evaluate the several intracellular alterations including apoptosis, ROS production, mitochondrial membrane potential (MMP), and calcium concentration induced by laminarin. An invasion test was performed to assess the inhibitory effect of laminarin on cell migration and the invasive genes were evaluated by RT-qPCR. Signaling pathway related with anticancer effects of laminarin was analyzed by western blot. We report that inhibiting laminarin increased the proliferation and viability of the representative pancreatic cancer cell lines, MIA PaCa-2 and PANC-1. Laminarin triggered apoptosis and mitochondrial impairment as evidenced by depolarized mitochondrial membranes, disrupted calcium, and suppressed cell migration caused by reactive oxygen species production and related intracellular signaling pathways. Moreover, laminarin showed synergistic effects when combined with 5-FU, a standard anticancer agent for PDAC. The present study is the first to report that laminarin exerts anticancer effect through ROS production in pancreatic cancer cells. Laminarin shows potential to serve as a new anticancer agent for treating PDAC.

Formyl-Peptide Receptor 2 Signaling Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming of Lung Cancer Cells.

Glucose and glutamine play a crucial role in the metabolic reprogramming of cancer cells. Proliferating cells metabolize glucose in the aerobic glycolysis for energy supply, and glucose and glutamine represent the primary sources of carbon atoms for the biosynthesis of nucleotides, amino acids, and lipids. Glutamine is also an important nitrogen donor for the production of nucleotides, amino acids, and nicotinamide. Several membrane receptors strictly control metabolic reprogramming in cancer cells and are considered new potential therapeutic targets. Formyl-peptide receptor 2 (FPR2) belongs to a small family of GPCRs and is implicated in many physiopathological processes. Its stimulation induces, among other things, NADPH oxidase-dependent ROS generation that, in turn, contributes to intracellular signaling. Previously, by phosphoproteomic analysis, we observed that numerous proteins involved in energetic metabolism are uniquely phosphorylated upon FPR2 stimulation. Herein, we investigated the role of FPR2 in cell metabolism, and we observed that the concentrations of several metabolites associated with the pentose phosphate pathway (PPP), tricarboxylic acid cycle, nucleotide synthesis, and glutamine metabolism, were significantly enhanced in FPR2-stimulated cells. In particular, we found that the binding of specific FPR2 agonists (i) promotes NADPH production (ii) activates the non-oxidative phase of PPP (iii) induces the expression of the ASCT2 glutamine transporter (iv) regulates oxidative phosphorylation and (v) induces the de novo synthesis of pyrimidine nucleotides, which requires FPR2-dependent ROS generation.

Pan-Cancer Analysis and Experimental Validation Identify ACOT7 as a Novel Oncogene and Potential Therapeutic Target in Lung Adenocarcinoma.

Acyl-CoA thioesterase 7 (ACOT7) is of great significance in regulating cell cycle, cell proliferation, and glucose metabolism. The function of ACOT7 in pan-cancer and its capacity as a prognostic indicator in lung adenocarcinoma (LUAD) remains unknown. We intended to perform a comprehensive pan-cancer analysis of ACOT7 and to validate its value in LUAD. The expression levels, prognostic significance, molecular function, signaling pathways, and immune infiltration pattern of ACOT7 in 33 cancers were explored via systematic bioinformatics analysis. Multivariate Cox regression was applied to construct nomograms to predict patients prognoses. Moreover, we conducted in vitro experiments including CCK8, scratch, Transwell, and Matrigel assays to further explore the function of ACOT7 in LUAD. Patients with high ACOT7 expression have notably poorer long-term survival in many cancer types, including LUAD. Further enrichment analyses reveal that ACOT7 is involved in immune cells infiltration and is substantially related to the cancer-immune microenvironment. ACOT7 could influence drug sensitivities, including afatinib, gefitinib, ibrutinib, lapatinib, osimertinib, sapitinib, taselisib, and PLX-4720 (all As an oncogene, ACOT7 is critical in the tumor microenvironment of pan-cancer and might be a novel therapeutic target for LUAD.

Biomimetic Red Blood Cell Membrane-Mediated Nanodrugs Loading Ursolic Acid for Targeting NSCLC Therapy.

As one of the most common cancers worldwide, non-small-cell lung cancer (NSCLC) treatment always fails owing to the tumor microenvironment and resistance. UA, a traditional Chinese medicine, was reported to have antitumor potential in tumor models in vitro and in vivo, but showed impressive results in its potential application for poor water solubility. In this study, a novel biomimetic drug-delivery system based on UA-loaded nanoparticles (UaNPs) with a red blood cell membrane (RBCM) coating was developed. The RBCM-coated UANPs (UMNPs) exhibited improved water solubility, high stability, good biosafety, and efficient tumor accumulation. Importantly, the excellent antitumor efficiency of the UMNPs was confirmed both in vitro and in vivo in cancer models. In addition, we further investigated the antitumor mechanism of UMNPs. The results of Western blotting showed that UMNPs exerted an anticancer effect by inducing the apoptosis and autophagy of NSCLC cells, which makes it superior to free UA. In addition, body weight monitoring, hematoxylin and eosin (HE) analysis, and immunohistochemical (IHC) analysis showed no significant difference between UMNPs and the control group, indicating the safety of UMNPs. Altogether, the preparation of biomimetic UMNPs provides a promising strategy to improve outcomes in NSCLC.

Pure Solid Pattern of Non-Small Cell Lung Cancer and Clustered Circulating Tumor Cells.

There are two solid patterns of non-small cell lung cancer (NSCLC) on computed tomography (CT) pure or mixed with ground-glass opacities (GGOs). They predict the degree of invasiveness, which may suggest the presence of clustered circulating tumor cells (CTCs), a predictor of poor prognosis. In this study, we assessed the implications of the solid patterns on CT and the preoperative clustered CTCs in surgically resected NSCLC. CTCs were detected using a size selection method. The correlation between the presence of preoperative clustered CTCs and the solid pattern and the prognostic implications were evaluated using co-variables from the clinical-pathological findings. Of the 142 cases, pure solid lesions (Group PS) and mixed GGOs (Group G) were observed in 92 (64.8%) and 50 (35.2%) patients, respectively. In Groups PS and G, clustered CTCs were detected in 29 (31.5%) and 1 (2.0%) patient (

Therapeutic Adenovirus Vaccine Combined Immunization with IL-12 Induces Potent CD8

Hepatocellular carcinoma (HCC) is one of the cancers with the highest morbidity and mortality in the world. However, clinical progress in the treatment of HCC has not shown a satisfactory therapeutic effect. Here, we have developed a novel strategy to treat HCC with an adenovirus (Ad)-based vaccine, which contains a specific antigen glypican-3 (GPC3) and an immunostimulatory cytokine IL-12. In the subcutaneous tumor model, Ad-IL-12GPC3 vaccine was injected into muscles three times to evaluate its therapeutic effect. Compared with the control immunization group, the Ad-IL-12GPC3 immunization group showed a significant tumor growth inhibition effect, which was confirmed by the reduced tumor volume and the increased tumor inhibition. Ad-IL-12GPC3 co-immunization promoted the induction and maturation of CD11c

Tumor Microenvironment CD14

Patients with early-stage lung adenocarcinoma have a high risk of recurrent or metastatic disease despite undergoing curative intent therapy. We hypothesized that increased CD14

Clinical Utility of Rapid On-Site Evaluation of Touch Imprint Cytology during Cryobiopsy for Peripheral Pulmonary Lesions.

Cryobiopsy enables us to obtain larger specimens than conventional forceps biopsy despite the caution regarding complications. This study aimed to evaluate the clinical utility of rapid on-site evaluation of touch imprint cytology (ROSE-TIC) during cryobiopsy of peripheral pulmonary lesions (PPLs). We retrospectively reviewed the data of consecutive patients who underwent cryobiopsy for solid PPLs between June 2020 and December 2021. ROSE-TIC was performed on the first specimen obtained via cryobiopsy and assessed using Diff-Quik staining. The results of ROSE-TIC for each patient were compared with the histological findings of the first cryobiopsy specimen. Sixty-three patients were enrolled in this study. Overall, 57 (90.5%) lesions were ≤30 mm in size and 37 (58.7%) had positive bronchus signs. The radial endobronchial ultrasound findings were located within and adjacent to the lesion in 46.0% and 54.0% of the cases, respectively. The sensitivity, specificity, and positive and negative predictive values of the ROSE results for histological findings of the corresponding specimens were 69.8%, 90.0%, 93.8%, and 58.1%, respectively. The concordance rate was 76.2%. In conclusion, ROSE-TIC, due to its high specificity and positive predictive value, may be a potential tool in deciding whether cryobiopsy sampling could be finished during bronchoscopy.

LncRNA H19 Promotes Lung Adenocarcinoma Progression via Binding to Mutant p53 R175H.

Accumulating data suggest that long non-coding RNA (lncRNA) H19 and p53are closely related to the prognosis of lung cancer. This study aims to analyze the association and interaction betweenH19 and mutant p53 R175H in lung adenocarcinoma (LAC). Mutant-type (Mt) p53 R175H was assessed by using RT-PCR in LAC cells and 100 cases of LAC tissue samples for association with H19 expression. Western blot, RNA-pull down, immunoprecipitation-Western blot and animal experiments were used to evaluate the interaction between H19 and mtp53. Mtp53 R175H and H19 were over-expressed in LAC tissues and cells, while H19 over-expression extended the p53 half-life and enhanced transcriptional activity. Combined with anti-p53, ShH19 can significantly inhibit tumor growth in vivo. H19 over-expression may induce the elevated expression of mtp53 and interact with mtp53, leading to LAC progression. In addition, the high expression of mtp53 R175H is associated with poor overall survival inpatients. The simultaneous inhibition of H19 and mtp53 may provide a novel strategy for the effective control of LAC clinically.