Datasets:

Gaborandi

/

Lung_Cancer_pubmed_abstracts

like 1

Risk factors associated with cisplatin-induced ototoxicity in Japanese patients with solid tumors.

Cisplatin, a first-generation platinum agent, is used for managing various cancers and is associated with dose-dependent side effects of hearing impairment and tinnitus. However, the safety of high-dose cisplatin in hearing impairment, has not been fully investigated in Japan. We performed pure-tone threshold audiometry before and every 3-4 weeks after chemotherapy for patients receiving cisplatin-containing chemotherapy between April 2015 and October 2017 at Kobe Minimally Invasive Cancer Center. Hearing impairment was evaluated prospectively using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. We enrolled 100 patients and analyzed 96 patients for whom post-chemotherapy audiometry could be performed. The median patient age was 65 years, and most patients were male (75). The cancer types were as follows esophageal, 36 head and neck, 35 lung, 23 and gastric, 2. Cisplatin monotherapy and combination therapy were administered to 33 and 63 patients, respectively. A single cisplatin dose was 60-100 mgm No patient discontinued treatment owing to hearing impairment. The total cisplatin dose was considered related to post-treatment hearing impairment frequency in Japanese patients. However, routine audiometric monitoring is recommended during high-dose cisplatin-based chemotherapy.

Traditional Herbal Medicine A Potential Therapeutic Approach for Adjuvant Treatment of Non-small Cell Lung Cancer in the Future.

Lung carcinoma is the primary reason for cancer-associated mortality, and it exhibits the highest mortality and incidence in developed and developing countries. Non-small cell lung cancer (NSCLC) and SCLC are the 2 main types of lung cancer, with NSCLC contributing to 85% of all lung carcinoma cases. Conventional treatment mainly involves surgery, chemoradiotherapy, and immunotherapy, but has a dismal prognosis for many patients. Therefore, identifying an effective adjuvant therapy is urgent. Historically, traditional herbal medicine has been an essential part of complementary and alternative medicine, due to its numerous targets, few side effects and substantial therapeutic benefits. In China and other East Asian countries, traditional herbal medicine is increasingly popular, and is highly accepted by patients as a clinical adjuvant therapy. Numerous studies have reported that herbal extracts and prescription medications are effective at combating tumors. It emphasizes that, by mainly regulating the P13KAKT signaling pathway, the Wnt signaling pathway, and the NF-κB signaling pathway, herbal medicine induces apoptosis and inhibits the proliferation and migration of tumor cells. The present review discusses the anti-NSCLC mechanisms of herbal medicines and provides options for future adjuvant therapy in patients with NSCLC.

Multi-center experience in an optimized right upper lobectomy surgical procedure in China.

This multi-center study was aimed at retrospectively evaluating the feasibility, safety, clinical outcomes, and surgical learning curve of an optimized procedure for right upper lobectomy (RUL), which is challenging because of the anatomical structures and features of this lobe. This study included 45 RUL cases of robot-assisted thoracoscopy (RATS) in a pilot cohort and 187 RUL cases of video-assisted thoracoscopy (VATS) in three cohorts. A total of 121 and 111 patients underwent traditional and optimized RUL, respectively. The optimized surgical procedure was performed to consecutively transect the superior arterial trunk and bronchus, and finally disconnect the pulmonary vein and posterior ascending artery with interlobar fissures. Clinical and radiological data were reviewed retrospectively. Optimized RUL can be performed successfully by RATS or VATS. The optimized procedure yielded better clinical outcomes than the traditional procedure, including shorter operation times, less blood loss, fewer complications, shorter hospital times, lower costs, and a lower likelihood of postoperative intermedius bronchial kinking. Additionally, for calcified interlobar lymph nodes, the optimized VATS group was less likely to be converted to thoracotomy than the traditional group. The skills required to perform optimized VATS RUL can be gained by surgeons after 12 to 15 cases. The two RUL procedures in the pilot cohort showed similar disease-free survival. The optimized RUL was safe, economical, and feasible, with a short learning curve and satisfactory disease-free survival.

CPSF4 promotes tumor-initiating phenotype by enhancing VEGFNRP2TAZ signaling in lung cancer.

Lung cancer is the leading cause of malignant tumor-related deaths worldwide. The presence of tumor-initiating cells in lung cancer leads to tumor recurrence, metastasis, and resistance to conventional treatment. Cleavage and polyadenylation specificity factor 4 (CPSF4) activation in tumor cells contributes to the poor prognosis of lung cancer. However, the precise biological functions and molecular mechanisms of CPSF4 in the regulation of tumor-initiating cells remain unclear. We demonstrated that CPSF4 promotes tumor-initiating phenotype and confers chemoresistance to paclitaxel both in vitro and in vivo. Mechanistically, we showed that CPSF4 binds to the promoters of vascular endothelial growth factor (VEGF) and neuropilin-2 (NRP2) and activated their transcription. In addition, we showed that CPSF4VEGFNRP2-mediated tumor-initiating phenotype and chemoresistance through TAZ induction. Furthermore, analysis of clinical data revealed that lung cancer patients with high CPSF4 expression exhibit high expression levels of VEGF, NRP2, and TAZ and that expression of these proteins are positively correlated with poor prognosis. Importantly, selective inhibition of VEGF, NRP2, or TAZ markedly suppressed CPSF4-mediated tumor-initiating phenotype and chemoresistance. Our findings reveal the mechanism of CPSF4 modulating tumor-initiating phenotype and chemoresistance in lung cancer and indicate that the CPSF4-VEGF-NRP2-TAZ signaling pathway may be a prognosis marker and therapeutic target in lung cancer.

The effect of Moringa oleifera leaf extracts against urethane-induced lung cancer in rat model.

Lung cancer is one of the most common malignancies in the world, and chemotherapy can have unfavorable side effects. The aim of the present study is to evaluate the therapeutic anticancer role of Moringa oleifera leaf extracts (MLE) in urethane-induced lung cancer in adult male albino rats as compared to standard chemotherapy. Rats were categorized into four groups (10 ratsgroup), including negative control rats, urethane lung cancer model rats, MLE-treated lung cancer rats, and cisplatin-treated rats. Estimation of lung index, some biochemical markers of oxidative stress, quantitative real-time polymerase chain reaction (qRT-PCR), and histopathology and transmission electron microscopy were performed. The lung index was significantly increased about one-fold in urethane lung cancer model rats, but it decreased after MLE treatment. Also, MLE was able to improve the induced changes in glutathione, superoxide dismutase, and malondialdehyde concentration to be 3.8 ± 0.4 mgg, 900.6 ± 58 Ug, and 172 ± 24 nmolg, respectively. Additionally, after MLE treatment, the expression of EGFR-mRNA increased by about 50%. Our light and electron microscopic examination revealed that urethane group showed abnormally distributed excessive collagen fibers and the development of papillary adenocarcinoma from hyperplastic Clara cells in the lumen of terminal bronchiole with bronchiolar wall thickening, alveolar collapse, and inflammation. MLE group has moderate amount of collagen fiber and absence of tumor mass and provided more or less restoration of normal lung histology. Moreover, MLE was able to ameliorate the induced changes in mucin and PCNA positive cells in the lung by 10.8 ± 2.3%. Collectively, the current study showed that MLE could be used as anticancer agents alleviating changes associated with lung cancer in a urethane-induced lung cancer bearing rats thereby representing alternative options to toxic chemotherapy.

Artificial intelligence-based diagnosis of asbestosis analysis of a database with applicants for asbestosis state aid.

In many countries, workers who developed asbestosis due to their occupation are eligible for government support. Based on the results of clinical examination, a team of pulmonologists determine the eligibility of patients to these programs. In this Dutch cohort study, we aim to demonstrate the potential role of an artificial intelligence (AI)-based system for automated, standardized, and cost-effective evaluation of applications for asbestosis patients. A dataset of n 523 suspected asbestosis casesapplications from across the Netherlands was retrospectively collected. Each caseapplication was reviewed, and based on the criteria, a panel of three pulmonologists would determine eligibility for government support. An AI system is proposed, which uses thoracic CT images as input, and predicts the assessment of the clinical panel. Alongside imaging, we evaluated the added value of lung function parameters. The proposed AI algorithm reached an AUC of 0.87 (p < 0.001) in the prediction of accepted versus rejected applications. Diffusion capacity (DLCO) also showed comparable predictive value (AUC 0.85, p < 0.001), with little correlation between the two parameters (r-squared 0.22, p < 0.001). The combination of the imaging AI score and DLCO achieved superior performance (AUC 0.95, p < 0.001). Interobserver variability between pulmonologists on the panel was estimated at alpha 0.65 (Krippendorffs alpha). We developed an AI system to support the clinical decision-making process for the application to the government support for asbestosis. A multicenter prospective validation study is currently ongoing to examine the added value and reliability of this system alongside the clinic panel. • Artificial intelligence can detect imaging patterns of asbestosis in CT scans in a cohort of patients applying for state aid. • Combining the AI prediction with the diffusing lung function parameter reaches the highest diagnostic performance. • Specific cases with fibrosis but no asbestosis were correctly classified, suggesting robustness of the AI system, which is currently under prospective validation.

CT texture analysis and node-RADS CT score of mediastinal lymph nodes - diagnostic performance in lung cancer patients.

Texture analysis derived from computed tomography (CT) can provide clinically relevant imaging biomarkers. Node-RADS is a recently proposed classification to categorize lymph nodes in radiological images. The present study sought to investigate the diagnostic abilities of CT texture analysis and Node-RADS to discriminate benign from malignant mediastinal lymph nodes in patients with lung cancer. Ninety-one patients (n 32 females, 35%) with a mean age of 64.8 ± 10.8 years were included in this retrospective study. Texture analysis was performed using the free available Mazda software. All lymph nodes were scored accordingly to the Node-RADS classification. All primary tumors and all investigated mediastinal lymph nodes were histopathologically confirmed during clinical workup. In discrimination analysis, Node-RADS score showed statistically significant differences between N0 and N1-3 (p < 0.001). Multiple texture features were different between benign and malignant lymph nodes S(1,0)AngScMom, S(1,0)SumEntrp, S(1,0)Entropy, S(0,1)SumAverg. Correlation analysis revealed positive associations between the texture features with Node-RADS score S(4,0)Entropy (r 0.72, p < 0.001), S(3,0) Entropy (r 0.72, p < 0.001), S(2,2)Entropy (r 0.72, p < 0.001). Several texture features and Node-RADS derived from CT were associated with the malignancy of mediastinal lymph nodes and might therefore be helpful for discrimination purposes. Both of the two quantitative assessments could be translated and used in clinical routine.

Antibody responses to second doses of COVID-19 vaccination in lung cancer patients undergoing treatment.

Several reports have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection tends to have more severe outcomes in cancer patients. Although vaccination reduces the risk of severe disease, data on antibody titers achieved by vaccination is scarce in cancer patients. We collected 79 blood samples (69 lung cancer patients and 10 control individuals) and conducted an anti-SARS-CoV-2 antibody assay to compare the antibody titer achieved with current treatment. Sixty-eight patients (86%) received the BNT162 mRNA vaccine and 11 (14%) received the mRNA-1273 vaccine. They were categorized according to the current treatment control individuals without cancer (cohort A), lung cancer patients who were treated with cytotoxic chemotherapy (cohort B), immunotherapy (cohort C), combination of cytotoxic chemotherapy and immunotherapy (cohort D), tyrosine kinase inhibitors (cohort E), and radiation therapy (cohort F). Among 69 lung cancer patients (cohort B-F), 57 (83%) had adenocarcinoma, and 66 (96%) had advanced-stage cancer. In the anti-SARS-CoV-2 antibody assay, the antibody titer was significantly lower in lung cancer patients than in control individuals (p 0.01). The median antibody titers were 161 AUml in control individuals and 59.9 AUml in lung cancer patients. Antibody titers after the second vaccination were lower in cancer patients than those in healthy individuals. Our findings provide essential information for understanding the benefits and necessity of additional vaccination to prevent SARS-CoV-2 infection in lung cancer patients.

A CT-Based Radiomics Nomogram Combined with Clinic-Radiological Characteristics for Preoperative Prediction of the Novel IASLC Grading of Invasive Pulmonary Adenocarcinoma.

The novel International Association for the Study of Lung Cancer (IASLC) grading system of invasive lung adenocarcinoma (ADC) demonstrated a remarkable prognostic effect and enabled numerous patients to benefit from adjuvant chemotherapy. We sought to build a CT-based nomogram for preoperative prediction of the IASLC grading. This work retrospectively analyzed the CT images and clinical data of 303 patients with pathologically confirmed invasive ADC. The histological subtypes and radiological characteristics of the patients were re-evaluated. Radiomics features were extracted, and the optimal subset of features was established by ANOVA, spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses identified the independent clinical and radiological variables. Finally, multivariate logistic regression analysis incorporated clinical, radiological, and optimal radiomics features into the nomogram. Receiver operating characteristic (ROC) curve, and accuracy were applied to assess the models performance. Decision curve analysis (DCA), and calibration curve were applied to assess the clinical usefulness. Nine selected CT image features were used to develop the radiomics model. The accuracy, precision, sensitivity, and specificity of the radiomics model outperformed the clinic-radiological model in the training and testing sets. Integrating Radscore with independent radiological characteristics showed higher prediction performance than clinic-radiological characteristics alone in the training (AUC, 0.915 vs. 0.882 DeLong, p < 0.05) and testing (AUC, 0.838 vs. 0.782 DeLong, p < 0.05) sets. Good calibration and decision curve analysis demonstrated the clinical usefulness of the nomogram. Radiomics features effectively predict high-grade ADC. The combined nomogram may facilitate selecting patients who benefit from adjuvant treatment.

Long-term outcomes and prognostic factors of patients with lung metastases from differentiated thyroid cancer after radioiodine therapy in Japan.

Long-term survival in patients with differentiated thyroid cancer (DTC) and lung metastasis remains unexplored in Japan. This study aimed to investigate the long-term survival and prognostic factors of radioiodine therapy (RIT) in a University Hospital setting. This retrospective study included 62 patients with lung metastases from DTC who received RIT between March 2005 and December 2016. According to the

Co-crystal nanoarchitectonics as an emerging strategy in attenuating cancer Fundamentals and applications.

Cancer ranks as the second foremost cause of death in various corners of the globe. The clinical uses of assorted anticancer therapeutics have been limited owing to the poor physicochemical attributes, pharmacokinetic performance, and lethal toxicities. Various sorts of co-crystals or nano co-crystals or co-crystals-laden nanocarriers have presented great promise in targeting cancer via improved physicochemical attributes, pharmacokinetic performance, and reduced toxicities. These systems have also demonstrated the controlled cargo release and passive targeting via enhanced permeation and retention (EPR) effect. In addition, regional delivery of co-crystals via inhalation and transdermal route displayed remarkable potential in targeting lung and skin cancer effectively. However, more research is required on the use of co-crystals in cancer and their commercialization. The present review mainly emphasizes co-crystals as emerging avenues in the treatment of various cancers by modulating the physicochemical and pharmacokinetic attributes of approved anticancer therapeutics. The worth of co-crystals in cancer treatment, computational paths in the co-crystals screening, diverse experimental techniques of co-crystals fabrication, and sorts of co-crystals and their noteworthy applications in targeting cancer are also discussed. Besides, the game changer approaches like nano co-crystals and co-crystals-laden nanocarriers, and co-crystals in regional delivery in cancer are also explained with reported case studies. Furthermore, regulatory directives for pharmaceutical co-crystals and their scale-up, and challenges are also highlighted with concluding remarks and future initiatives. In essence, co-crystals and nano co-crystals emerge to be a promising strategy in overwhelming cancers through improving anticancer efficacy, safety, patient compliance, and reducing the cost.

Co-exposure to urban particulate matter and aircraft noise adversely impacts the cerebro-pulmonary-cardiovascular axis in mice.

Worldwide, up to 8.8 million excess deathsyear have been attributed to air pollution, mainly due to the exposure to fine particulate matter (PM). Traffic-related noise is an additional contributor to global mortality and morbidity. Both health risk factors substantially contribute to cardiovascular, metabolic and neuropsychiatric sequelae. Studies on the combined exposure are rare and urgently needed because of frequent co-occurrence of both risk factors in urban and industrial settings. To study the synergistic effects of PM and noise, we used an exposure system equipped with aerosol generator and loud-speakers, where C57BL6 mice were acutely exposed for 3d to either ambient PM (NIST particles) andor noise (aircraft landing and take-off events). The combination of both stressors caused endothelial dysfunction, increased blood pressure, oxidative stress and inflammation. An additive impairment of endothelial function was observed in isolated aortic rings and even more pronounced in cerebral and retinal arterioles. The increase in oxidative stress and inflammation markers together with RNA sequencing data indicate that noise particularly affects the brain and PM the lungs. The combination of both stressors has additive adverse effects on the cardiovascular system that are based on PM-induced systemic inflammation and noise-triggered stress hormone signaling. We demonstrate an additive upregulation of ACE-2 in the lung, suggesting that there may be an increased vulnerability to COVID-19 infection. The data warrant further mechanistic studies to characterize the propagation of primary target tissue damage (lung, brain) to remote organs such as aorta and heart by combined noise and PM exposure.

The composition of fusogenic lipid mixtures at the air-water modulates the physicochemical properties changes upon interaction with lysicamine.

Knowing how a bioactive compound interacts with cell membranes is important to understand its effect at the molecular level. In this sense, this work aimed to study the interaction of lysicamine, an alkaloid with action against lung cancer cell lines, with lipid monolayers as cell membrane models. We employed two lipid mixtures the first composed of 35% DOPC, 30% DOPE, 20% sphingomyelin, and 15% cholesterol as healthy cell membranes models (MM1), and the second replacing DOPC with DOPS as cancer cells models (MM2). The interaction of lysicamine with the monolayers was evaluated using tensiometry, Brewster angle microscopy (BAM), and polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). Lysicamine had interfacial effects in both membrane models. For MM 1, it expanded the lipid monolayer and changed the interfacial rheological properties, increasing the in-plane elasticity of the films. PM-IRRAS spectra suggested a higher conformational disorder of the alkyl chains of the lipids. For MM 2, lysicamine also shifted the isotherms to higher areas, expanding the monolayers, but with no significant alteration in their interfacial rheological properties. PM-IRRAS spectra also suggested higher disorder in the orientation of the lipid alkyl chains upon lysicamine incorporation. For both models, BAM did not show alteration in interfacial aggregation upon drug incorporation. In conclusion, changes in some interfacial properties of membrane models caused by lysicamine depend on the monolayer composition, which can be associated with its bioactivity in cellular membranes.

Impact of sex and age on adherence to guidelines in non-small cell lung cancer management.

Age-related disparities in non-small cell lung cancer (NSCLC) treatment are well known, but few studies have assessed the impact of sex on treatment disparities. Disparities in guideline-adherence may explain the superior survival in women with NSCLC. Therefore, we aimed to define patient- and tumor-related factors associated with non-adherence to guidelines in NSCLC management with a special focus on sex and age. Patients with NSCLC who received first-line treatment at the Vaasa Central Hospital between 2016 and 2020 were included in the study. The primary outcome was guideline adherence, defined as adherent, undertreatment, or overtreatment considering performance status. A binary logistic regression model was used to calculate the adjusted odds ratio (aOR) for non-adherence to treatment guidelines depending on patient- and tumor-related factors. 321 patients were included in the study. Non-adherence was highest in ≥75-year-old women (41.3%), followed by ≥75-year-old men (32.6%), <75-year-old men (27.6%) and lowest in women <75-year-old (19.7%) (p 0.035). Non-adherent care consisted more often of undertreatment in <75-year-old men than women (26.0% versus 12.1%) and overtreatment in <75-year-old women than men (7.6% versus 1.6%). Non-adherence was associated with stage III disease (aOR 2.21 95% CI 1.07-4.59), poor pulmonary function (aOR 3.69, 95% CI 1.56-8.71), and Charlson Comorbidity Index 1-2 (aOR 2.09 95% CI 1.09-4.01). Sex- and age-related disparities in guideline adherence were observed in <75-year-old men and in ≥75-year-olds. Stage III NSCLC was associated with non-adherence.

Diagnostic test accuracy of artificial intelligence-based imaging for lung cancer screening A systematic review and meta-analysis.

Lung cancer is the principal cause of cancer-related deaths worldwide. Early detection of lung cancer with screening is indispensable to reduce the high morbidity and mortality rates. Artificial intelligence (AI) is widely utilised in healthcare, including in the assessment of medical images. A growing number of reviews studied the application of AI in lung cancer screening, but no overarching meta-analysis has examined the diagnostic test accuracy (DTA) of AI-based imaging for lung cancer screening. To systematically review the DTA of AI-based imaging for lung cancer screening. PubMed, EMBASE, Cochrane Library, CINAHL, IEEE Xplore, Web of Science, ACM Digital Library, Scopus, PsycINFO, and ProQuest Dissertations and Theses were searched from inception to date. Studies that were published in English and that evaluated the performance of AI-based imaging for lung cancer screening were included. Two independent reviewers screened titles and abstracts and used the Quality Assessment of Diagnostic Accuracy Studies-2 tool to appraise the quality of selected studies. Grading of Recommendations Assessment, Development, and Evaluation to diagnostic tests was used to assess the certainty of evidence. Twenty-six studies with 150,721 imaging data were included. Hierarchical summary receiver-operating characteristic model used for meta-analysis demonstrated that the pooled sensitivity for AI-based imaging for lung cancer screening was 94.6 % (95 % CI 91.4 % to 96.7 %) and specificity was 93.6 % (95 % CI 88.5 % to 96.6 %). Subgroup analyses revealed that similar results were found among different types of AI, region, data source, and year of publication, but the overall quality of evidence was very low. AI-based imaging could effectively detect lung cancer and be incorporated into lung cancer screening programs. Further high-quality DTA studies on large lung cancer screening populations are required to validate AIs role in early lung cancer detection.

EMAS position statement Vitamin D and menopausal health.

There is increasing evidence that vitamin D has widespread tissue effects. In addition to osteoporosis, vitamin D deficiency has been associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However, the effect of vitamin D supplementation on non-skeletal outcomes requires clarification, especially in postmenopausal women. This position statement provides an evidence-based overview of the role of vitamin D in the health of postmenopausal women based on observational and interventional studies. Literature review and consensus of expert opinion. Vitamin D status is determined by measuring serum 25-hydroxyvitamin D levels. Concentrations <20 ngml (<50 nmoll) and <10 ngml (<25 nmoll) are considered to constitute vitamin D deficiency and severe deficiency, respectively. Observational data suggest an association between vitamin D deficiency and adverse health outcomes in postmenopausal women, although they cannot establish causality. The evidence from randomized controlled trials concerning vitamin D supplementation is not robust, since many studies did not consider whether people were deficient at baseline. Moreover, high heterogeneity exists in terms of the population studied, vitamin D dosage, calcium co-administration and duration of intervention. Concerning skeletal health, vitamin D deficiency is associated with low bone mass and an increased risk of fractures. Vitamin D supplementation at maintenance doses of 800-2000 IUday (20-50 μgday), after repletion of vitamin D status with higher weekly or daily doses, may be of benefit only when co-administered with calcium (1000-1200 mgday), especially in the elderly populations and those with severe vitamin D deficiency. Concerning cardiovascular disease, vitamin D deficiency is associated with an increased prevalence of cardiovascular risk factors, mainly metabolic syndrome, type 2 diabetes mellitus and dyslipidemia. Vitamin D deficiency, especially its severe form, is associated with an increased risk of cardiovascular events (coronary heart disease, stroke, mortality), independently of traditional risk factors. Vitamin D supplementation may have a modestly beneficial effect on lipid profile and glucose homeostasis, especially in obese individuals or those ≥60 years old and at doses of ≥2000 IUday (≥50 μgday). However, it has no effect on the incidence of cardiovascular events. Concerning cancer, vitamin D deficiency is associated with increased incidence of and mortality from several types of cancer, such as colorectal, lung and breast cancer. However, the data on other types of gynecological cancer are inconsistent. Vitamin D supplementation has no effect on cancer incidence, although a modest reduction in cancer-related mortality has been observed. Concerning infections, vitamin D deficiency has been associated with acute respiratory tract infections, including coronavirus disease 2019 (COVID-19). Vitamin D supplementation may decrease the risk of acute respiratory tract infections and the severity of COVID-19 (not the risk of infection). Concerning menopausal symptomatology, vitamin D deficiency may have a negative impact on some aspects, such as sleep disturbances, depression, sexual function and joint pains. However, vitamin D supplementation has no effect on these, except for vulvovaginal atrophy, at relatively high doses, i.e., 40,000-60,000 IUweek (1000-1500 IUweek) orally or 1000 IUday (25 μgday) as a vaginal suppository.

Introduction of high-precision stereotactic body radiotherapy of lung tumors at Markusovszky Hospital.

A new, modern computed tomograph simulator was installed in the Oncology Department of the Markusovsky University Teaching Hospital from September 2021. The computed tomography simulator not only makes the work of specialists easier with its automatic contouring tool, but is also able to produce four-dimensional computed tomography scans. This facility is essential for radiotherapy of lung and breast cancer patients. In this paper, we briefly review lung tumors and their treatment options, focusing on radiotherapy requiring high precision. We summarize patient selection criteria, the quality assurance processes for planning and treatment, and the experience gained in treating patients. 5 patients were selected for our study. Their disease met the following criteria 1 nodule, tumor diameter not exceeding 5 cm, patient was inoperable or negated surgery. The planning computed tomography scan was performed with Siemens Somatom go.Sim. At each respiratory phase, the tumor conturs were drawn and then aggregated as an integrated volume and an irradiation plan was prepared on this image. The treatments were performed on a Varian TrueBeam accelerator. Before each treatment, an adjusting CT scan was taken. The higher dose (4 × 12 Gy) treatment caused a reduction in tumor size on the last adjustment scan. Stereotaxic treatment, which is already available in Szombathely, may be a good alternative in the treatment of patients with inoperable lung cancer. The method is not burdensome for patients fewer sessions, short treatment time. In the future, we would like to improve the accelerator with a breath capture system, which will allow even more precise treatment. Orv Hetil. 2022 163(52) 2079-2087. Bevezetés A Markusovszky Egyetemi Oktatókórház Onkoradiológiai Osztályán 2021 szeptemberétől új, modern komputertomográf-szimulátor áll rendelkezésre. A komputertomográf-szimulátor nemcsak megkönnyíti a szakdolgozók munkáját az automata kontúrozóeszközzel, hanem képes négydimenziós komputertomográf-felvételek készítésére is. Ez az opció elengedhetetlen a tüdő- és emlődaganatos betegek sugárkezeléséhez. Célkitűzés A jelen tanulmányban röviden áttekintjük a tüdődaganatok nagy pontosságot igénylő sugárterápiáját. Összefoglaljuk a betegkiválasztás szempontjait, a tervezési és kezelési minőségbiztosítási folyamatokat, illetve a betegek kezelése során szerzett tapasztalatokat. Módszer Kutatásunkba 5 beteget választottunk be. Betegségük az alábbi kritériumoknak felelt meg 1 góc, a tumor átmérője nem haladta meg az 5 centimétert, a beteg nem volt műthető, vagy nem fogadta el a műtétet. A tervezési komputertomográf-felvételt Siemens Somatom go.Sim készülékkel végeztük. Minden légzési fázisban megrajzoltuk a tumor kontúrját, majd ezeket integrált térfogatként összesítettük, és erre készítettük el a besugárzási tervet. A kezeléseket Varian TrueBeam gyorsítón végeztük. Eredmények A tumor mozgását milliméteres nagyságrendű pontossággal tudtuk követni. Minden kezelés előtt beállító komputertomográf-felvétel készült. A nagyobb dózisú (4 × 12 Gy) kezelés az utolsó beállítófelvételen már tumorméret-csökkenést okozott. Megbeszélés A stereotaxiás kezelés, amely már Szombathelyen is elérhető, jó alternatíva lehet a nem műthető tüdődaganatos betegek kezelésében. A módszer a betegek számára nem megterhelő kevesebb alkalom, rövid kezelési idő. Következtetés Jól tudtuk kompenzálni a légzésből adódó eltéréseket. A későbbiekben szeretnénk a gyorsítót fejleszteni légzéskapuzó rendszerrel, amely még pontosabb kezelést tesz lehetővé. Orv Hetil. 2022 163(52) 2079–2087.

Prognosis and incidence of immunological and oncological complications after direct-acting antiviral therapy for chronic hepatitis C.

The long-term comprehensive prognosis of chronic hepatitis C after direct-acting antiviral (DAA) therapy is unclear. This study aimed to investigate the prognosis and incidence of immunological and oncological complications after DAA therapy. The study included a total of 1461 patients who received DAA therapy in our university hospital and affiliated hospitals between September 3, 2014 and September 30, 2018. The incidence rates of total malignancies in overall or female patients after DAA therapy were significantly greater than expected in the corresponding general population. The same was true for lung malignancies. Predictive risk factors associated with the occurrence and recurrence of hepatic malignancies after DAA therapy in patients with sustained virological response were cirrhosis and insulin use, protein induced by vitamin K absence or antagonist-II level, and albumin-bilirubin score, respectively. Eight (0.5%) patients were diagnosed with autoimmune diseases after starting DAA therapy. Importantly, the attending physician considered a possible causal relationship between DAA therapy and these autoimmune diseases in five cases (four rheumatoid arthritis and one membranoproliferative glomerulonephritis). The 5-year overall survival rate was 91.6%. The most frequent primary cause of death was malignancy in 41 (60.2%) patients, including 25 with hepatic malignancies. Lung and colorectal cancers were the next most common. Given that the incidence of total and lung cancers might increase and DAA-related autoimmune diseases might emerge after DAA therapy, we should be alert for the development of these diseases as well as hepatic malignancies.

UHRF1-mediated ferroptosis promotes pulmonary fibrosis via epigenetic repression of GPX4 and FSP1 genes.

Pulmonary fibrosis (PF), as an end-stage clinical phenotype of interstitial lung diseases (ILDs), is frequently initiated after alveolar injury, in which ferroptosis has been identified as a critical event aggravating the pathophysiological progression of this disease. Here in, a comprehensive analysis of two mouse models of pulmonary fibrosis developed in our lab demonstrated that lung damage-induced ferroptosis of alveolar epithelial Type2 cells (AEC2) significantly accumulates during the development of pulmonary fibrosis while ferroptosis suppressor genes GPX4 and FSP1 are dramatically inactivated. Mechanistically, upregulation of de novo methylation regulator Uhrf1 sensitively elevates CpG site methylation levels in promoters of both GPX4 and FSP1 genes and induces the epigenetic repression of both genes, subsequently leading to ferroptosis in chemically interfered AEC2 cells. Meanwhile, specific inhibition of UHRF1 highly arrests the ferroptosis formation and blocks the progression of pulmonary fibrosis in both of our research models. This study first, to our knowledge, identified the involvement of Uhrf1 in mediating the ferroptosis of chemically injured AEC2s via de novo promoter-specific methylation of both GPX4 and FSP1 genes, which consequently accelerates the process of pulmonary fibrosis. The above findings also strongly suggested Uhrf1 as a novel potential target in the treatment of pulmonary fibrosis.

Regulatory T cells infiltrate the tumor-induced tertiary lymphoïd structures and are associated with poor clinical outcome in NSCLC.

On one hand, regulatory T cells (Tregs) play an immunosuppressive activity in most solid tumors but not all. On the other hand, the organization of tumor-infiltrating immune cells into tertiary lymphoid structures (TLS) is associated with long-term survival in most cancers. Here, we investigated the role of Tregs in the context of Non-Small Cell Lung Cancer (NSCLC)-associated TLS. We observed that Tregs show a similar immune profile in TLS and non-TLS areas. Autologous tumor-infiltrating Tregs inhibit the proliferation and cytokine secretion of CD4

Treatment and Survival Outcomes for Patients with Colorectal Peritoneal Metastases Deemed Ineligible for Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Results of a Retrospective Study.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for selected patients with colorectal peritoneal metastases (PM). This report provides an overview of treatment and survival outcomes for patients deemed ineligible for CRS-HIPEC. Colorectal PM patients referred to a tertiary center from 2014 to 2020 that were ineligible for CRS-HIPEC were included. Patient, tumor, and treatment characteristics were provided. Survival analyses were performed using the Kaplan-Meier method. Of 476 patients referred for CRS-HIPEC, 227 (48%) were deemed ineligible. Median follow-up was 15 months IQR 10-22. Data on follow-up treatment was available for 198 patients, of which 73% received systemic therapy. These patients had a median overall survival (OS) of 17 months IQR 9-25. For patients receiving best supportive care (BSC) median OS was 4 months IQR 2-9. The main reason for ineligibility was extensive PM (42%), with a median OS of 11 months IQR 5-18. Patients deemed ineligible due to (extensive) liver (9%) or lung metastases (8%) showed longer OS (median 22 months, IQR 8-27, and 24 months, IQR 12-29, respectively) than patients with extensive PM (median 11 months, IQR 5-18) or distant lymph node metastases (median 14 months, IQR 4-25). The main reason for CRS-HIPEC ineligibility was extensive PM. The majority of patients received systemic therapy. Patients deemed ineligible due to extra-peritoneal metastases had better survival outcomes than patients deemed ineligible due to extensive PM.

Cyclin G2 in macrophages triggers CTL-mediated antitumor immunity and antiangiogenesis via interferon-gamma.

IFN-γ is a key mediator of tumor immunity that can induce macrophage polarization to suppress tumor growth. Cyclin G2 functions as a tumor suppressor in various cancer cells however, its role in macrophages remains unclear. This study aimed to investigate the role and underlying mechanisms of cyclin G2 in macrophages in vitro and in vivo. Mouse tumor models were used to determine the effect of cyclin G2 in macrophages on tumor growth in vivo following IFN-γ treatment. Immunohistochemistry staining, immunofluorescence staining and flow cytometry were used to evaluate the number of cytotoxic T lymphocytes (CTLs) and blood vessels in the mouse tumors. Moreover, the biological roles of cyclin G2 in macrophages with regard to CTL chemotaxis, cytotoxic function, and vascular endothelial cell tube formation were assessed using in vitro functional experiments. Immunoprecipitation (IP), real-time PCR, and enzyme-linked immunosorbent assays (ELISAs) were conducted to investigate the underlying mechanisms by which cyclin G2 regulates CTLs and vascular endothelial cells. We found that cyclin G2 expression was upregulated in macrophages after IFN-γ treatment. Upregulated cyclin G2 inhibited lung and colon cancer growth by increasing the secretion of its downstream effector CXCL9, which promoted CTL chemotaxis and suppressed vascular endothelial cell tube formation. Moreover, cyclin G2 increased CXCL9 mRNA levels by promoting STAT1 nuclear translocation. In addition, cyclin G2 promoted the activation of the STAT1 signaling pathway, which was dependent on PP2Ac. Cyclin G2 is upregulated by IFN-γ in macrophages, promotes the secretion of CXCL9 to increase CTL chemotaxis and inhibit angiogenesis to suppress tumor growth. Our findings suggest that targeting cyclin G2 could benefit future immunotherapy.

Sotorasib treatment in KRAS G12C-mutated non-small cell lung cancer Experience in the Tours university hospital.

Following the CodeBreak 100 study, since 2021 sotorasib has been available in France, with authorization for early access in treatment of non-small cell lung cancer with a KRAS G12C mutation. Our retrospective observational study was designed to determine the efficacy and safety of sotorasib under real-life conditions in patients treated at the Tours CHRU. Our study of 15 patients showed sotorasib to be effective in 47% of cases, with overall survival of 4 months and median progression-free survival of 5.5 months for responders. Tumor control was achieved in 78 (87%) of patients with PS of 0 or 1 and in 17 (14%) of patients with a PS of 2 or greater. Grade 3 acute hepatitis occurred in 315 patients (20%). While sotorasib is an interesting therapeutic option, with efficacy that seems better in patients in good general condition, it entails a possible risk of drug-induced hepatitis, which remains to be specified in dedicated studies.

Integrated omics profiling and network pharmacology uncovers the prognostic genes and multi-targeted therapeutic bioactives to combat lung cancer.

Non-small cell lung cancer (NSCLC) is the frequent subtype of lung cancer and the currently used treatment methods, diagnosis, and chemoresistance are relatively ineffective. Determining the pharmacological targets from active biomolecules of medicinal plants has become a frontiers era for biomedical research to develop novel therapies. In view of these scenarios, this pilot study, network pharmacology, cheminformatics, integrative omics, molecular docking and in vitro anti-cancer analysis were performed to unveil the multi-targeted treatment mechanisms of novel plant bioactives to treat lung cancer. Bioactive molecules from medicinal plants were compiled from PubChem. Network pharmacology approach revealed that 29 compounds efficiently target the 390 human and lung cancer associated genes. In addition, comparative analysis was performed and identified the 7 bioactive molecules significantly targeting 8 lung cancer genes. The integrative omics analysis discovered unique genes between the lung cancer and normal lung tissues. These genes were further validated through protein-protein interaction, gene ontology, gene functional and pathway enrichment, boxplot and overall survival analyses to understand the function of unique genes and their involvement in cancer signaling pathways. Survival heatmap analyses identified the significant prognostic genes. Docking results revealed that, lupeol and p-coumaric acid displayed high binding affinities with MIF, CCNB1, FABP4. Hence, we selected these two bioactives for in vitro analysis. Furthermore, these selected bioactives were showed concentration dependent cytotoxicity against the lung adenocarcinoma cells (A549). This holistic study has opened up novel avenues and unravels the cancer prognostic genes which could serve as druggable target and bioactives with anti-cancerous efficacy. Further functional validations are prerequisites to deciphering these bioactives as commercial drug candidates.

Reduction of Staphylococcus epidermidis in the mammary tumor microbiota induces antitumor immunity and decreases breast cancer aggressiveness.

The mammary gland hosts a microbiota, which differs between malignant versus normal tissue. We found that aerosolized antibiotics decrease murine mammary tumor growth and strongly limit lung metastasis. Oral absorbable antibiotics also reduced mammary tumors. In ampicillin-treated nodules, the immune microenvironment consisted of an M1 profile and improved T cellmacrophage infiltration. In these tumors, we noted an under-representation of microbial recognition and complement pathways, supported by TLR2TLR7 protein and C3-fragment deposition reduction. By 16S rRNA gene profiling, we observed increased Staphylococcus levels in untreated tumors, among which we isolated Staphylococcus epidermidis, which had potent inflammatory activity and increased Tregs. Conversely, oral ampicillin lowered Staphylococcus epidermidis in mammary tumors and expanded bacteria promoting an M1 phenotype and reducing MDSCs and tumor growth. Ampicillinpaclitaxel combination improved the chemotherapeutic efficacy. Notably, an Amp-like signature, based on genes differentially expressed in murine tumors, identified breast cancer patients with better prognosis and high immune infiltration that correlated with a bacteria response signature. This study highlights the significant influence of mammary tumor microbiota on local immune status and the relevance of its treatment with antibiotics, in combination with breast cancer therapies.

Clinical and technical insights of tumour mutational burden in non-small cell lung cancer.

Despite the durable responses provided by the introduction of checkpoint inhibitors in advanced Non-Small Cell Lung Cancer (NSCLC) without actionable targets in a subset of patients, a large proportion of them will progress after immunotherapy. Programmed Death Ligand 1 (PD-L1) was the first biomarker approved for immunotherapy, although it has multiple limitations, thus the development of novel biomarkers is an urgent need. Tumour Mutational Burden (TMB) is an emerging biomarker defined as the total number of mutations per coding area of tumour genome. Targeted gene panels have emerged as a cost-effective approach to estimate TMB. However, there is still an unmet need to fully standardize sample requirements, panel size, and bioinformatic pipelines to ensure that TMB is calculated appropriately. In addition, researchers are also evaluating TMB calculation in liquid biopsy. In this work, we summarize the relevant advances and the clinical utility of TMB in NSCLC.

A primary small cell neuroendocrine carcinoma (SCNC) of the oral cavity (cheek mucosa) Description of a case report.

Small cell neuroendocrine carcinoma (SCNC) of the oral cavity is a poorly differentiated, high-grade and very aggressive tumor with a poor prognosis. A 64-year-old, Caucasian, smoker man consulted for an ulcero-necrotic, exophytic, lesion of the right retromolar trigone. Haedneck CT scan showed a right tonsillar tumor lesion. The The particularity of this case relies on the rarity of the oral SCNC, its difficult and challenging diagnosis, and the complexity of its management that is not validated by large clinical trials, data being extrapolated from small cell lung cancer. In our case, the patient presenting a locally advanced tumor was treated by a combined radio-chemiotherapy leading to a complete tumor regression. The patients follow up is too short to assess the real benefit of this treatment on overall survival.

T cell-related prognostic risk model and tumor immune environment modulation in lung adenocarcinoma based on single-cell and bulk RNA sequencing.

T cells are present in all stages of tumor formation and play an important role in the tumor microenvironment. We aimed to explore the expression profile of T cell marker genes, constructed a prognostic risk model based on these genes in Lung adenocarcinoma (LUAD), and investigated the link between this risk model and the immunotherapy response. We obtained the single-cell sequencing data of LUAD from the literature, and screened out 6 tissue biopsy samples, including 32,108 cells from patients with non-small cell lung cancer, to identify T cell marker genes in LUAD. Combined with TCGA database, a prognostic risk model based on T-cell marker gene was constructed, and the data from GEO database was used for verification. We also investigated the association between this risk model and immunotherapy response. Based on scRNA-seq data 1839 T-cell marker genes were identified, after which a risk model consisting of 9 gene signatures for prognosis was constructed in combination with the TCGA dataset. This risk model divided patients into high-risk and low-risk groups based on overall survival. The multivariate analysis demonstrated that the risk model was an independent prognostic factor. Analysis of immune profiles showed that high-risk groups presented discriminative immune-cell infiltrations and immune-suppressive states. Risk scores of the model were closely correlated with Linoleic acid metabolism, intestinal immune network for IgA production and drug metabolism cytochrome P450. Our study proposed a novel prognostic risk model based on T cell marker genes for LUAD patients. The survival of LUAD patients as well as treatment outcomes may be accurately predicted by the prognostic risk model, and make the high-risk population present different immune cell infiltration and immunosuppression state.

Developing a primary tumor and lymph node 18F-FDG PETCT-clinical (TLPC) model to predict lymph node metastasis of resectable T2-4 NSCLC.

The goal of this study was to investigate whether the combined PETCT radiomic features of the primary tumor and lymph node could predict lymph node metastasis (LNM) of resectable non-small cell lung cancer (NSCLC) in stage T2-4. This retrospective study included 192 NSCLC patients who underwent tumor and node dissection between August 2016 and December 2017 and underwent The ROC analysis showed that among the three models, the TLPC model had better predictive clinical utility and efficiency in predicting LNM of NSCLC (AUC 0.93, accuracy 85% sensitivity 0.93 specificity 0.75) than both the TPC model (AUC 0.54, accuracy 50% specificity 0.38 sensitivity 0.59) and the LPC model (AUC 0.82, accuracy 70% specificity 0.41 sensitivity 0.92). The TLPC model also exhibited great potential in predicting the N2 stage in NSCLC (AUC 0.94, accuracy 79% specificity 0.64 sensitivity 0.91). The combination of CT and PET radiomic features of the primary tumor and lymph node showed great potential for predicting LNM of resectable T2-4 NSCLC. The TLPC model can non-invasively predict lymph node metastasis in NSCLC, which may be helpful for clinicians to develop more rational therapeutic strategies.

Synergistic Effect of HAD-B1 and Afatinib Against Gefitinib Resistance of Non-Small Cell Lung Cancer.

In epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), acquired resistance to EGFR tyrosine kinase inhibitors (TKI) leads to disease progression. Strategies to overcome the resistance are required in treatment for advanced lung cancer. In this study, we investigated the therapeutic effect of afatinib and HangAmDan-B1 (HAD-B1) co-administration in gefitinib-resistant NSCLC using HCC827-GR, NSCLC cell line with gefitinib resistance, and the HCC827-GR cell implanted mouse model. HAD-B1 consists of 4 herbs,

Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases.

This review aimed to identify preclinical and clinical studies examining the effects of rosmarinic acid (RA), carnosic acid (CaA), rosmanol (RO), carnosol (CA), and ursolic acid (UA) against allergic and immunologic disorders. Various online databases, including PubMed, Science Direct, EMBASE, Web of Sciences, Cochrane trials, and Scopus, were searched from inception until October 2022. Due to the suppression of the nuclear factor-κB (NF-κB) pathway, the main factor in allergic asthma, RA may be a promising candidate for the treatment of asthma. The other ingredients comprising CA and UA reduce the expression of interleukin (IL)-4, IL-5, and IL-13 and improve airway inflammation. Rosemarys anti-cancer effect is mediated by several mechanisms, including DNA fragmentation, apoptosis induction, inhibition of astrocyte-upregulated gene-1 expression, and obstruction of cell cycle progression in the G1 phase. The compounds, essentially found in Rosemary essential oil, prevent smooth muscle contraction through its calcium antagonistic effects, inhibiting acetylcholine (ACH), histamine, and norepinephrine stimulation. Additionally, CA exhibits a substantially greater interaction with the nicotinic ACH receptor than a family of medications that relax the smooth muscles, making it a potent antispasmodic treatment. The components have demonstrated therapeutic effects on the immune, allergy, and respiratory disorders.

Effects of respiratory and cardiac motion on estimating radiation dose to the left ventricle during radiotherapy for lung cancer.

Establish a workflow to evaluate radiotherapy (RT) dose variation induced by respiratory and cardiac motion on the left ventricle (LV) and left ventricular myocardium (LVM). Eight lung cancer patients underwent 4D-CT, expiratory T1-volumetric-interpolated-breath-hold-examination (VIBE), and cine MRI scans in expiration. Treatment plans were designed on the average intensity projection (AIP) datasets from 4D-CTs. RT dose from AIP was transferred onto 4D-CT respiratory phases. About 50% 4D-CT dose was mapped onto T1-VIBE (following registration) and from there onto average cine MRI datasets. Dose from average cine MRI was transferred onto all cardiac phases. Cumulative cardiac dose was estimated by transferring dose from each cardiac phase onto a reference cine phase following deformable image registration. The LV was contoured on each 4D-CT breathing phase and was called clinical LV (cLV) this structure is blurred by cardiac motion. Additionally, LV, LVM, and an American Heart Association (AHA) model were contoured on all cardiac phases. Relative maximummean doses for contoured regions were calculated with respect to each patients maximummean AIP dose. During respiration, relative maximum and mean doses on the cLV ranged from -4.5% to 5.6% and -14.2% to 16.5%, respectively, with significant differences in relative mean doses between inspiration and expiration (P < 0.0145). During cardiac motion at expiration, relative maximum and mean doses on the LV ranged from 1.6% to 59.3%, 0.5% to 27.4%, respectively. Relative mean doses were significantly different between diastole and systole (P 0.0157). No significant differences were noted between systolic, diastolic, or cumulative cardiac doses compared to the expiratory 4D-CT (P > 0.14). Significant differences were observed in AHA segmental doses depending on tumour proximity compared to global LV doses on expiratory 4D-CT (P < 0.0117). In this study, the LV dose was highest during expiration and diastole. Segmental evaluation suggested that future cardiotoxicity evaluations may benefit from regional assessments of dose that account for cardiopulmonary motion.

Circular RNA expression profile identifies circMGEA5 as a novel metastasis-promoting factor and potential biomarker in osteosarcoma.

Osteosarcoma (OS) is associated with a high incidence of lung metastasis, which leads to a high risk of cancer death. Circular RNA (circRNA), a novel class of noncoding RNA, is emerging as a key player in human cancer. Herein, we explored the role of circMGEA5 in OS metastasis by conducting circRNA expression microarray. CircMGEA5 was significantly upregulated in metastatic OS tissues compared to primary tissues. High circMGEA5 was positively related with shorter overall and disease-free survival time. Knockdown of circMGEA5 suppressed OS cell migration, invasion, and epithelial-mesenchymal transition (EMT). Mechanistically, circMGEA5 acted as a competing endogenous RNA (ceRNA) to directly sponge miR-153-3p and miR-8084, resulting in increasing ZEB1 and Snail expression, respectively, thereby inducing EMT and metastasis. In turn, ZEB1 and Snail were capable to bind to circMGEA5 promoter, activating circMGEA5 transcription, thus forming a positive feedback loop. Furthermore, we established the tail vein injection model and found that circMGEA5 depletion remarkably reduced lung metastasis nodules generated by OS cells. In sum, our findings, for the first time, reveal the metastasis-promoting role of circMGEA5 in OS. Targeting of this newly identified ceRNA axis may be crucial in the development of novel therapies for metastatic OS patients.

Uniportal VATS lobectomy versus thoracotomy lobectomy for NSCLC larger than 5 cm A propensity score-matched study.

The performance of uniportal VATS lobectomy (uVATS) for non-small cell lung cancer (NSCLC) larger than 5 cm is uncertain due to a lack of evidence. Here, we present a retrospective, propensity-score matched cohort study to evaluate the safety and effectiveness of uVATS for patients with locally advanced NSCLC. The data of patients with NSCLC larger than 5 cm diameter who underwent curative resection via uVATS or thoracotomy lobectomy between January 2015 and December 2020 was collected. Propensity-score matching was utilized to control the observable biases. Seventy-two patients underwent uVATS lobectomy, while 38 received thoracotomy lobectomy. No conversion to open surgery or perioperative death occurred. uVATS lobectomy achieved similar total lymph node dissection counts compared to thoracotomy and even yielded a higher amount of lymph node dissection in pTNM stage II patients. The long-term overall and recurrence-free survival rates were also similar between the two groups. Results from the propensity-score matching generated cohort agreed with those from the full cohort. uVATS lobectomy is feasible and effective for curative lobectomy for NSCLC larger than 5 cm in diameter in selected patients. Further validations from well-designed prospective studies are required for uVATS lobectomy for patients with locally advanced NSCLC.

Dose-effect relationship of stereotactic body radiotherapy in non-small cell lung cancer patients.

To establish the dose effect relationship between the dose parameters of stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) and the local tumor control rate. A comprehensive literature search was conducted using PubMed, the Web of Science and the Cochrane databases to determine the articles treated with SBRT in early-stage NSCLC. Original studies with complete prescription dose information, tumor local control rate and other important parameters were screened and reported. Probit model in XLSTAT 2016 was used for regression analysis, and P < 0.05 was set as a statistically significant level. After literature screening, 22 eligible studies were included in probit model regression analysis, involving 1861 patients. There is no significant dose effect relationship between nominal BED For NSCLC treated with SBRT, more attention should be paid to the central dose and average dose of PTV. A set of clear definition in the dose prescription should be established to ensure the effectiveness and comparability of treatment.

Identification of comutation in signaling pathways to predict the clinical outcomes of immunotherapy.

Immune checkpoint blockades (ICBs) have emerged as a promising treatment for cancer. Recently, tumour mutational burden (TMB) and neoantigen load (NAL) have been proposed to be potential biomarkers to predict the efficacy of ICB however, they were limited by difficulties in defining the cut-off values and inconsistent detection platforms. Therefore, it is critical to identify more effective predictive biomarkers for screening patients who will potentially benefit from immunotherapy. In this study, we aimed to identify comutated signaling pathways to predict the clinical outcomes of immunotherapy. Here, we comprehensively analysed the signaling pathway mutation status of 9763 samples across 33 different cancer types from The Cancer Genome Atlas (TCGA) by mapping the somatic mutations to the pathways. We then explored the comutated pathways that were associated with increased TMB and NAL by using receiver operating characteristic (ROC) curve analysis and multiple linear regressions. Our results revealed that comutation of the Spliceosome (Sp) pathway and Hedgehog (He) signaling pathway (defined as SpHe-comut Overall, SpHe-comut

Powered stapling system with gripping surface technology for pulmonary resection of lung cancer real-world clinical effectiveness.

Surgical lung resection involves a critical task of stapled ligation and transection of major vascular structures and tissue, which may lead to bleeding and complications. A newer powered stapling system with Gripping Surface Technology (GST) was introduced to account for tissue movements. This study aimed to examine the real-world effectiveness of GST system on intraoperative and postoperative outcomes of pulmonary resection. A retrospective analysis was conducted using the electronic medical records of Sichuan Provincial Peoples Hospital between July 2020 and March 2021 in China. Patients who underwent their first procedures of single-port lobectomy or multi-port segmentectomy by video-assisted thoracoscopic surgery were identified and grouped as GST group or manual stapler group (manual group) by the stapler types. The intraoperative outcomes such as bleeding rate, blood loss volume, and intervention rate at the staple line (including intraoperative pressure, suture, and electrocoagulation) were documented by trained nurses during the surgery. Propensity score matching was performed between the two groups, controlling forage, BMI, smoking history, history of surgery, complications, and level of complexity of pneumonectomy. A total of 108 matched patients were included in the analysis (54 in the GST group and 54 in the manual group). GST group had lower risks for intraoperative bleeding (22.8% vs 51.9% p 0.003) and intraoperative interventions (31.5% vs 55.6% p 0.02), compared to the manual group. A decrease in the intraoperative blood loss was observed in the GST group, but not statistically significant (134.39 ± 52.82 ml vs 158.11 ± 73.14 ml, p 0.102). The use of NEOVEIL (reinforcement material to prevent air leakage from the staple line) intraoperatively during surgery was significantly lower in the GST group (24.1%) than in the manual group (50%, p 0.01). The GST system was associated with better intraoperative outcomes in clinical practice in China.

Understanding patient barriers and facilitators to uptake of lung screening using low dose computed tomography a mixed methods scoping review of the current literature.

Targeted lung cancer screening is effective in reducing mortality by upwards of twenty percent. However, screening is not universally available and uptake is variable and socially patterned. Understanding screening behaviour is integral to designing a service that serves its population and promotes equitable uptake. We sought to review the literature to identify barriers and facilitators to screening to inform the development of a pilot lung screening study in Scotland. We used Arksey and OMalleys scoping review methodology and PRISMA-ScR framework to identify relevant literature to meet the study aims. Qualitative, quantitative and mixed methods primary studies published between January 2000 and May 2021 were identified and reviewed by two reviewers for inclusion, using a list of search terms developed by the study team and adapted for chosen databases. Twenty-one articles met the final inclusion criteria. Articles were published between 2003 and 2021 and came from high income countries. Following data extraction and synthesis, findings were organised into four categories Awareness of lung screening, Enthusiasm for lung screening, Barriers to lung screening, and Facilitators or ways of promoting uptake of lung screening. Awareness of lung screening was low while enthusiasm was high. Barriers to screening included fear of a cancer diagnosis, low perceived risk of lung cancer as well as practical barriers of cost, travel and time off work. Being health conscious, provider endorsement and seeking reassurance were all identified as facilitators of screening participation. Understanding patient reported barriers and facilitators to lung screening can help inform the implementation of future lung screening pilots and national lung screening programmes.

Characterization of the fatty acid metabolism-related genes in lung adenocarcinoma to guide clinical therapy.

Lung adenocarcinoma (LUAD) is a common cancer with a bad prognosis. Numerous investigations have indicated that the metabolism of fatty acids plays an important role in the occurrence, progression, and treatment of cancer. Consequently, the objective of the current investigation was to elucidate the role and prognostic significance of genes associated with fatty acid metabolism in patients diagnosed with LUAD. The data files were acquired from The Cancer Genome Atlas database and GSE31210 dataset. Univariate Cox and least absolute shrinkage and selection operator regression analyses were conducted to establish a prognostic risk scoring model depending on fatty acid metabolism-associated genes to predict the prognosis of patients with LUAD. pRRophetic algorithm was utilized to evaluate the potential therapeutic agents. Gene set variation analysis combined with cell-type identification based on the estimation of relative subsets of RNA transcript and single-sample gene set enrichment analysis was used to determine the association between immune cell infiltration and risk score. Tumor immune dysfunction and exclusion algorithm was employed to predict immunotherapeutic sensitivity. To forecast the prognosis of patients with LUAD, a risk scoring model based on five genes associated with fatty acid metabolism was developed, including LDHA, ALDOA, CYP4B1, DPEP2, and HPGDS. Using the risk score algorithm, patients were divided into higher- and lower-risk categories. Patients classified as minimal risk showed superior prognosis than those with elevated risk. In addition, individuals in the higher-risk group had a proclivity toward chemoresistance and amenable to immunotherapy. The prognostic risk scoring model aids in estimating the prognosis of LUAD patients. It may also provide new insights into LUAD carcinogenesis and therapeutic strategies.

The multifaceted role of MUC1 in tumor therapy resistance.

Tumor therapeutic resistances are frequently linked to the recurrence and poor prognosis of cancers and have been a key bottleneck in clinical tumor treatment. Mucin1 (MUC1), a heterodimeric transmembrane glycoprotein, exhibits abnormally overexpression in a variety of human tumors and has been confirmed to be related to the formation of therapeutic resistance. In this review, the multifaceted roles of MUC1 in tumor therapy resistance are summarized from aspects of pan-cancer principles shared among therapies and individual mechanisms dependent on different therapies. Concretely, the common mechanisms of therapy resistance across cancers include interfering with gene expression, promoting genome instability, modifying tumor microenvironment, enhancing cancer heterogeneity and stemness, and activating evasion and metastasis. Moreover, the individual mechanisms of therapy resistance in chemotherapy, radiotherapy, and biotherapy are introduced. Last but not least, MUC1-involved therapy resistance in different types of cancers and MUC1-related clinical trials are summarized.

A deep-learning model for transforming the style of tissue images from cryosectioned to formalin-fixed and paraffin-embedded.

Histological artefacts in cryosectioned tissue can hinder rapid diagnostic assessments during surgery. Formalin-fixed and paraffin-embedded (FFPE) tissue provides higher quality slides, but the process for obtaining them is laborious (typically lasting 12-48 h) and hence unsuitable for intra-operative use. Here we report the development and performance of a deep-learning model that improves the quality of cryosectioned whole-slide images by transforming them into the style of whole-slide FFPE tissue within minutes. The model consists of a generative adversarial network incorporating an attention mechanism that rectifies cryosection artefacts and a self-regularization constraint between the cryosectioned and FFPE images for the preservation of clinically relevant features. Transformed FFPE-style images of gliomas and of non-small-cell lung cancers from a dataset independent from that used to train the model improved the rates of accurate tumour subtyping by pathologists.

Could PD-L1 positivity be associated with venous thrombosis in patients with non-small cell lung cancer

The risk of venous thromboembolism (VTE) is increased in non-small cell lung cancer (NSCLC), and defining at-risk patients is important. Thus, we aimed to assess the association between programmed cell death ligand 1 (PD-L1) expression and VTE pulmonary embolism (PE), deep venous thrombosis (DVT) in NSCLC. In this retrospective, observational multicentre study, 369 patients with NSCLC who had PD-L1 immunohistochemistry based on biopsies taken between January 2017 and December 2019, were divided as PD-L1-positive (n 181) and -negative (n 188) groups, and low-positive (n 99) and high-positive (n 82) PD-L1 groups. Among all population, 12.5% of them developed a VTE during a median follow-up of 474 days. The rates of DVT, PE, and PE DVT were 5.7%, 6% and 0.8%, respectively. VTE (15.5% vs. 9.5%) and DVT (3.8% vs. 7.4%) were similar between two groups, while PE was significantly higher in PD‑L1-positive group than those in PD-L1-negative group (11.1% vs 1%, p < 0.001). There were no significant differences between low- and high-positive groups in terms of VTE (14.1% vs. 17%), PE (12.1% vs. 9.8%), and DVT (2% vs. 6.1%). In the multivariate analysis, multiple metastases (Hazard ratio HR 4.02 95% confidence interval Cl 1.18-13.63 p 0.07) and PD-L1 positivity was associated with an increased PE risk (HR 8.39 95% Cl 2.07-34.07 p 0.003). In conclusion, PD-L1 positivity may be of important role in predicting the increased risk of PE in patients with NSCLC and thereby may be used to define patients likely to benefit from thromboprophylaxis.

DNA barcoding and gene expression recording reveal the presence of cancer cells with unique properties during tumor progression.

Tumors comprise diverse cancer cell populations with specific capabilities for adaptation to the tumor microenvironment, resistance to anticancer treatments, and metastatic dissemination. However, whether these populations are pre-existing in cancer cells or stochastically appear during tumor growth remains unclear. Here, we show the heterogeneous behaviors of cancer cells regarding response to anticancer drug treatments, formation of lung metastases, and expression of transcription factors related to cancer stem-like cells using a DNA barcoding and gene expression recording system. B16F10 cells maintained clonal diversity after treatment with HVJ-E, a UV-irradiated Sendai virus, and the anticancer drug dacarbazine. PBS treatment of the primary tumor and intravenous injection of B16F10 cells resulted in metastases formed from clones of multiple cell lineages. Conversely, BL6 and 4T1 cells developed spontaneous lung metastases by a small number of clones. Notably, an identical clone of 4T1 cells developed lung metastases in different mice, suggesting the existence of cells with high metastatic potential. Cas9-based transcription recording analysis in a human prostate cancer cell line revealed that specific cells express POU5F1 in response to an anticancer drug and sphere formation. Our findings provide insights into the diversity of cancer cells during tumor progression.

Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies.

Meta-analysis of whole genome sequencingwhole exome sequencing (WGSWES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGSWES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of the Trans Omics for Precision Medicine (TOPMed) Program, we show that MetaSTAAR performs rare variant meta-analysis at scale and produces results comparable to using pooled data. Additionally, we identified several conditionally significant rare variant associations with lipid traits. We further demonstrate that MetaSTAAR is scalable to biobank-scale cohorts through meta-analysis of TOPMed WGS data and UK Biobank WES data of 200,000 samples.

Leukocyte CH25H is a potential diagnostic and prognostic marker for lung adenocarcinoma.

Metastasis, a major challenge during the treatment of lung cancer, causes deterioration in patient health outcomes. Thus, to address this problem, this study aimed to explore the role and contribution of Cholesterol 25-Hydroxylase (CH25H) as a potential diagnostic and prognostic marker in lung cancer. Online public databases were used to analyze the expression level, prognostic value, gene-pathway enrichment, and immune infiltration of CH25H in lung cancer patients. The Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to analyze and detect the CH25H expression levels in leukocytes from lung cancer patients. The expression level of CH25H was significantly reduced in lung adenocarcinoma (LUAD), which is associated with a higher disease stage, but not in lung squamous cell carcinoma (LUSC). Kaplan-Meier survival analysis indicated that LUAD patients with low CH25H expression had a worse prognosis. Mechanistically, our results showed that in LUAD, CH25H may be a regulatory factor affecting the immune cell infiltration level, and the resultant tumor development. Experimental data showed that low expression of CH25H in leukocytes was significantly associated with LUAD metastasis (P < 0.01). Our study suggests that CH25H may function as a prognostic and risk stratification biomarker for LUAD.

Accelerating tobacco control at the national level with the Smoke-free Generation movement in the Netherlands.

The Netherlands has moved towards the forefront of tobacco control in Europe, after having implemented important tobacco control measures in 2020 and 2021, which included higher tobacco taxation, plain packaging of tobacco products, a partial point of sale tobacco display ban, smoking ban on school grounds, and other smoking restrictions. We examined the factors contributing to these successes, focussing on the network of tobacco control advocacy organisations and the process of agenda-setting. Crucial determining factors were stricter adherence to Article 5.3 FCTC, which prevents government to consult tobacco industry, and the genesis of a Smoke-free Generation movement in the wider society, initiated by the three main national charities (Lung Foundation Netherlands, Dutch Heart Foundation, Dutch Cancer Society). The Smoke-free Generation concept proved to be a highly attractive unifying strategy for national en local policy makers and Dutch society. As a result, the Dutch government was able to start a process of strengthening tobacco control policy through drafting and implementing a National Prevention Agreement, which aims at a tobacco control endgame goal of less than 5% smokers in 2040. Between 2019 and 2020 smoking rates dropped from 21.7% to 20.2%. The Dutch experience can provide inspiration for countries where tobacco control is still lagging behind. It also illustrates that continued vigilance is needed, since the most recent government change was associated with a hampering of further reduction of the proportion of smokers and a temporary drop in attention to tobacco control from the central government.

27-gene Immuno-Oncology (IO) Score is Associated With Efficacy of Checkpoint Immunotherapy in Advanced NSCLC A Retrospective BC Cancer Study.

Immune checkpoint inhibitors (ICI) are standard of care in advanced non-small cell lung cancer (NSCLC). However, not all patients benefit, even among PD-L1 tumor proportional score (TPS) ≥50%, indicating an unmet need for additional biomarkers such as those assessing the tumor immune microenvironment (TIME). DetermaIO is a 27-gene assay that classifies TIME and has previously demonstrated association with ICI response. FFPE samples were selected from BC Cancer and West Clinic Cancer Center patients with performance status (PS) ≤2 who received at least 2 cycles of ICI monotherapy in the first (1L) or second line (2L). IO scores were generated and analyzed for association with PFS and OS. In the entire cohort (N147), IO score was significantly associated with OS (HR0.68, 95%CI 0.47-0.99, P .042) and PFS (HR0.62, 95%CI 0.43-0.88, P .0069). In 1L treated patients (PD-L1≥50%, N78), IO score was significantly associated with PFS (HR0.55, 95%CI 0.32-0.94, P .028). In exploratory analyses, IO score was associated with benefit in 1L PS2 patients for OS (HR 0.26, 95%CI 0.091-0.74, P .012) and PFS (HR 0.27, 95%CI 0.098-0.72, P .0095) which was confirmed in PFS subgroup analysis in the independent West Cancer Center study (N13 HR0.14, 95%CI 0.027-0.76, P .023). These data confirm the association of DetermaIO with ICI clinical benefit in NSCLC, and expand on previous studies by demonstrating that first line treated PD-L1≥50% patients can further be stratified by IO score to identify efficacy. Exploratory analysis suggested that the IO score identifies benefit in patients with poor PS.

Impact of systemic inflammatory markers in patients with ALK-positive non-small cell lung cancer treated with crizotinib.

To evaluate the prognostic utility of inflammation-based prognostic scores in patients with ALK-positive metastatic or non-resectable non-small-cell lung cancer (NSCLC) treated with crizotinib. A total of 82 patients with ALK-positive metastatic or non-resectable NSCLC who received ALK TKI crizotinib were included. Pre-treatment modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI, and SII on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). The ORR was 77.2%, while 1-year OS and PFS rates were 95.0% and 93.5%, respectively. The univariate analysis revealed significantly higher 1-year PFS (89.4 vs. 64.4%, p0.043) and OS (92.0 vs. 83.3%, p0.01) rates in patients with low (<934.7) vs. high (≥934.7) SII scores. Multivariate analysis revealed that PNI ≥0.09 was a significant determinant of poorer 1-year OS rates (hazard ratio HR 2.46, 95% confidence interval CI 0.88-4.85, p0.035). No significant difference was observed in survival rates according to gender, age, smoking status, prior lines of therapy, or mGPS scores, while higher mGPS scores (odds ratio OR 0.1, 95%CI 0.16-1.04 p0.009) and higher PNI scores (OR 0.16, 95% CI 0.02-0.55 p0.035) were associated with poorer ORR. Our findings indicate the prognostic significance of PNI and SII in terms of survival outcome and the impact of mGPS and PNI on treatment response in patients with ALK-positive NSCLC treated with crizotinib.

Using thoracic ultrasound to detect interstitial lung disease in patients with rheumatoid arthritis a protocol for the diagnostic test accuracy AURORA study.

Pulmonary diseases are significant contributors to morbidity and mortality in patients with rheumatoid arthritis (RA). RA-associated interstitial lung disease (RA-ILD) may be prevalent in up to 30% and clinically evident in 10% of patients with RA. Feasible methods to detect concomitant ILD in RA are warranted. Our objective is to determine the diagnostic accuracy of thoracic ultrasound (TUS) for ILD in patients with RA with respiratory symptoms, by using chest high-resolution CT (HRCT) as the reference standard. Further, we aim to evaluate the diagnostic accuracy for the promising blood biomarkers surfactant protein-D and microfibrillar-associated protein 4 in the detection of ILD in this group of patients. By use of a standardised 14 zone protocol patients suspected of having RA-ILD will undergo TUS as index test performed by a junior resident in rheumatology (BKS), who is certified by the European Respiratory Society in performing TUS assessments. Participants form a consecutive series of up to 80 individuals in total. The anonymised TUS images will be stored and scored by the junior resident as well as two senior rheumatologists, who have received training in TUS, and a TUS-experienced pulmonologist. HRCT will be used as the gold standard for ILD diagnosis (reference standard). The two basic measures for quantifying the diagnostic test accuracy of the TUS test are the sensitivity and specificity in comparison to the HRCT. Data will be collected and stored in the Research Electronic Data Capture database. The study is approved by the Committees on Health Research Ethics and the Danish Data Protection Agency. The project is registered at clinicaltrials.gov (NCT05396469, pre-results) and data will be published in peer-reviewed journals.

Operational Definitions Related to Pediatric Ventilator Liberation.

Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among research and quality improvement efforts, to ensure findings are generalizable, and can be pooled to establish best practices. Can we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches A panel of 26 international experts in pediatric ventilator liberation, two methodologists, and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions that were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions. In eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥ 80% agreement for all 16 definitions in the following areas what constitutes respiratory support (invasive mechanical ventilation and noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28 ventilator-free days, and planned vs rescue use of post-extubation noninvasive respiratory support. We propose that these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability and facilitate comparison.

Development of a high-throughput TR-FRET screening assay for a fast-cycling KRAS mutant.

Mutations in the small GTPase protein KRAS are one of the leading drivers of cancers including lung, pancreatic, and colorectal, as well as a group of developmental disorders termed Rasopathies. Recent breakthroughs in the development of mutant-specific KRAS inhibitors include the FDA approved drug Lumakras (Sotorasib, AMG510) for KRAS G12C-mutated non-small cell lung cancer (NSCLC), and MRTX1133, a promising clinical candidate for the treatment of KRAS G12D-mutated cancers. However, there are currently no FDA approved inhibitors that target KRAS mutations occurring at non-codon 12 positions. Herein, we focused on the KRAS mutant A146T, found in colorectal cancers, that exhibits a fast-cycling nucleotide mechanism as a driver for oncogenic activation. We developed a novel high throughput time-resolved fluorescence resonance energy transfer (TR-FRET) assay that leverages the reduced nucleotide affinity of KRAS A146T. As designed, the assay is capable of detecting small molecules that act to allosterically modulate GDP affinity or directly compete with the bound nucleotide. A pilot screen was completed to demonstrate robust statistics and reproducibility followed by a primary screen using a diversity library totaling over 83,000 compounds. Compounds yielding >50% inhibition of TR-FRET signal were selected as hits for testing in dose-response format. The most promising hit, UNC10104889, was further investigated through a structure activity relationship (SAR)-by-catalog approach in an attempt to improve potency and circumvent solubility liabilities. Overall, we present the TR-FRET platform as a robust assay to screen fast-cycling KRAS mutants enabling future discovery efforts for novel chemical probes and drug candidates.

Lung cancer screening.

Randomised controlled trials, including the National Lung Screening Trial (NLST) and the NELSON trial, have shown reduced mortality with lung cancer screening with low-dose CT compared with chest radiography or no screening. Although research has provided clarity on key issues of lung cancer screening, uncertainty remains about aspects that might be critical to optimise clinical effectiveness and cost-effectiveness. This Review brings together current evidence on lung cancer screening, including an overview of clinical trials, considerations regarding the identification of individuals who benefit from lung cancer screening, management of screen-detected findings, smoking cessation interventions, cost-effectiveness, the role of artificial intelligence and biomarkers, and current challenges, solutions, and opportunities surrounding the implementation of lung cancer screening programmes from an international perspective. Further research into risk models for patient selection, personalised screening intervals, novel biomarkers, integrated cardiovascular disease and chronic obstructive pulmonary disease assessments, smoking cessation interventions, and artificial intelligence for lung nodule detection and risk stratification are key opportunities to increase the efficiency of lung cancer screening and ensure equity of access.

An epithelial-immune circuit amplifies inflammasome and IL-6 responses to SARS-CoV-2.

Elevated levels of cytokines IL-1β and IL-6 are associated with severe COVID-19. Investigating the underlying mechanisms, we find that while primary human airway epithelia (HAE) have functional inflammasomes and support SARS-CoV-2 replication, they are not the source of IL-1β released upon infection. In leukocytes, the SARS-CoV-2 E protein upregulates inflammasome gene transcription via TLR2 to prime, but not activate, inflammasomes. SARS-CoV-2-infected HAE supply a second signal, which includes genomic and mitochondrial DNA, to stimulate leukocyte IL-1β release. Nuclease treatment, STING, and caspase-1 inhibition but not NLRP3 inhibition blocked leukocyte IL-1β release. After release, IL-1β stimulates IL-6 secretion from HAE. Therefore, infection alone does not increase IL-1β secretion by either cell type. Rather, bi-directional interactions between the SARS-CoV-2-infected epithelium and immune bystanders stimulates both IL-1β and IL-6, creating a pro-inflammatory cytokine circuit. Consistent with these observations, patient autopsy lungs show elevated myeloid inflammasome gene signatures in severe COVID-19.

Cancertestis antigen HEMGN correlated with immune infiltration serves as a prognostic biomarker in lung adenocarcinoma.

HEMGN belongs to the Cancertestis antigens (CTAs), which are expressed in various types of human cancers and have received particular attention in cancer immunotherapy. However, the potential function of HEMGN involved in lung cancer and the immune response is not yet elucidated. HEMGN expression in lung adenocarcinoma (LUAD) was estimated via the Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA), The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and Human Protein Atlas databases. The prognostic role of HEMGN was investigated by Gene Expression Profiling Interactive Analysis (GEPIA), PrognoScan, and Kaplan-Meier plotter databases. The associations between HEMGN and clinicopathological parameters were analyzed with UALCAN database. Then, immunohistochemical and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) analysis were performed to further verify the associations in tissue or serum samples. Serum from patients were detected for HEMGN antibody by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect immune cell infiltration in peripheral blood of patients with LUAD. In addition, Gene Set Enrichment Analysis (GSEA) was conducted to investigate the functional role of HEMGN. Furthermore, we obtained the somatic mutation data from the TCGA LUAD dataset and analyzed the mutation profiles with maftools package. Finally, we evaluated the associations between HEMGN and immune infiltration level and the characteristic markers of immune cells in TIMER, GEPIA, and CIBERSORT. The mRNA and protein expressions of HEMGN were significantly decreased in LUAD patients. High HEMGN expression was remarkably associated with better prognosis in LUAD patients. The concentration levels of anti-HEMGN antibody in LUAD were significantly higher than that in healthy individuals and were closely correlated with clinical stage. In addition, HEMGN was involved in distinct typical genomic alterations in LUAD. GSEA demonstrated that HEMGN was significantly connected with immunity and substance metabolism. Notably, HEMGN was significantly related to immune infiltrates, including B cells, CD8 T cells, CD4 T cells, neutrophils, macrophages, dendritic cells (DCs), and various kinds of functional T cells. Furthermore, HEMGN had a significant association with diverse immune gene markers. HEMGN can be considered as a prognostic biomarker of LUAD and is associated with immune infiltration.

A review on the role of LINC00152 in different disorders.

LINC00152 is an important lncRNA in human disorders. It is mainly regarded as a tumor-promoting lncRNA. Mechanistically, LINC00152 serves as a molecular sponge for miR-143a-3p, miR-125a-5p, miR-139, miR-215, miR-193ab-3p, miR-16-5p, miR-206, miR-195, miR-138, miR-185-5p, miR-103, miR-612, miR-150, miR-107, miR-205-5p and miR-153-3p. In addition, it can regulate activity of mTOR, EGFRPI3KAKT, ERKMAPK, Wntβ-Catenin, EGFR, NF-κB, HIF-1 and PTEN. In this review, we provide a concise but comprehensive explanation about the role of LINC00152 in tumor development and progression as well as its role in the pathology of non-malignant conditions with the aim of facilitating the clinical implementation of this lncRNA as a diagnostic or prognostic tumor marker and therapeutic target.

Actionable mutations in non-small cell lung cancer in patients at hospital de Especialidades Eugenio Espejo, Ecuador 2017-2020.

Determine the frequency of actionable mutations in non-small cell lung cancer (NSCLC) and their correlation with overall survival (OS) and the site of metastases. We performed a descriptive cross-sectional study at the Hospital de Especialidades Eugenio Espejo, Ecuador, between 2017 and 2020. Demographic, pathological, and molecular alterations in epidermal growth factor (EGFR), Anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), Programmed death-ligand 1 (PD-L1) expression, and clinical data detailed in patients medical records with metastatic NSCLC were collected and analyzed. Seventy-nine stage IV patients had NSCLC adenocarcinoma histology represents 56 (70.9%). The predominant mutation was in EGFR (22.8%) the most common variant was the deletion of exon 19 (72.2%). The most common metastatic site was in the contralateral lung (22.3%) however, this variable showed no significant correlation to the molecular markers (p0.057). The overall survival (OS) and the status of molecular markers are not statistically significant (p0.27). OS was better for non-mutated EGFR than for mutated EGFR (p0.012). However, the frequency values are unrelated to contralateral lung metastasis or survival. Our frequency mutations are concordant with those found in other studies in Latin America. EGFR was the most common biomarker mutation, and there was a better OS in EGFR non-mutated patient.

Predicting N2 lymph node metastasis in presurgical stage I-II non-small cell lung cancer using multiview radiomics and deep learning method.

Accurate diagnosis of N2 lymph node status of the resectable stage I-II non-small cell lung cancer (NSCLC) before surgery is crucial, while there is lack of corresponding method clinically. To develop and validate a model to quantitively predict the N2 lymph node metastasis in presurgical clinical stage I-II NSCLC using multiview radiomics and deep learning method. In this study, 140 NSCLC patients were enrolled and randomly divided into training and test sets. Univariate and multiple analysis method were used step by step to establish the clinical model Then a multiview radiomics modeling scheme was designed, in which the optimal input feature set was determined by subcategorizing radiomics features (C1 original C2 LoG and C3 wavelet) and comparison of corresponding radiomics model. The minimum-redundancy maximum-relevance (mRMR) selection and the least absolute shrinkage and selection operator (LASSO) algorithm were used for the feature selection and construction of each radiomics model (Rad). Next, an end-to-end ResNet18 architecture and transfer learning techniques were designed to construct a deep learning model (DL). Subsequently, the screened clinical risk factors and constructed Rad and DL models were combined and compared and a nomogram was constructed. Finally, the diagnostic performance of all constructed models were evaluated and compared using receiver operating characteristic curve (ROC) analysis, Delong test, Calibration analysis, Hosmer-Lemeshow test, and decision curves, respectively. Carcinoma embryonic antigen (CEA) level and spiculation were screened to make up the Clinical model, while seven radiomics features in the optimal input feature set C2 C3 were selected to construct the Rad. DL was constructed by training on 1.8 million natural images and small sample data of our N2 lymph node volume of interest (VOI) images. Except for the Clinical model, all other models showed good predictive accuracy and consistency in both training set and test set. DL (area under curve (AUC) 0.83) was better than Rad (AUC 0.76) in predictive accuracy, but their difference was not significant (p 0.45). The combined models showed better diagnostic performance than the model only clinical or image risk factors were used (AUC for Clinical, Rad DL, Rad Clinical, DL Clinical, and Rad DL Clinical were respectively 0.66, 0.86, 0.82, 0.86, and 0.88). Finally, the Rad DL Clinical model with the best diagnostic performance was selected to draw the final nomogram for clinical use. This study proposes a nomogram based on multiview radiomics, deep learning, and clinical features that can be efficiently used to quantitively predict presurgical N2 diseases in patients with clinical stage I-II NSCLC.

Engineered Human Antibody with Improved Endothelin Receptor Type A Binding Affinity, Developability, and Serum Persistence Exhibits Excellent Antitumor Potency.

Endothelin receptor A (ET

Engineered APOBEC3C Sequencing Enables Bisulfite-Free and Direct Detection of DNA Methylation at a Single-Base Resolution.

DNA methylation (5-methylcytosine, 5mC) is the most important epigenetic modification in mammals. Deciphering the roles of 5mC relies on the quantitative detection of 5mC at the single-base resolution. Bisulfite sequencing (BS-seq) is the most often employed technique for mapping 5mC in DNA. However, bisulfite treatment may cause serious degradation of input DNA due to the harsh reaction conditions. Here, we engineered the human apolipoprotein B mRNA-editing catalytic polypeptide-like 3C (A3C) protein to endow the engineered A3C (eA3C) protein with differential deamination activity toward cytosine and 5mC. By the virtue of the unique property of eA3C, we proposed an engineered A3C sequencing (EAC-seq) method for the bisulfite-free and quantitative mapping of 5mC in DNA at the single-base resolution. In EAC-seq, the eA3C protein can deaminate C but not 5mC, which is employed to differentiate C and 5mC in sequencing. Using the EAC-seq method, we quantitatively detected 5mC in genomic DNA of lung cancer tissue. In contrast to the harsh reaction conditions of BS-seq, which could lead to significant degradation of DNA, the whole procedure of EAC-seq is carried out under mild conditions, thereby preventing DNA damage. Taken together, the EAC-seq approach is bisulfite-free and straightforward, making it an invaluable tool for the quantitative detection of 5mC in limited DNA at the single-base resolution.

Significance of preoperative evaluation of skeletal muscle index and immune-nutritional status for patients with early-stage non-small cell lung cancer.

Sarcopenia involves several mechanisms, including age-related changes, nutritional deficiencies, and inflammation, and is associated with unfavorable clinical outcomes. However, the significance of skeletal muscle index (SMI) and immune-nutritional status for patients with early-stage non-small cell lung cancer (NSCLC) remains unclear. This retrospective study was performed to investigate associations between preoperative SMI based on computed tomography (CT) at the L1 level and immune-nutritional status, and whether these factors correlated with surgical outcomes. We retrospectively investigated 386 patients with stage I-II NSCLC who underwent curative anatomical pulmonary resection. SMI was assessed on CT at the L1 level and patients were divided into low-SMI (n 97) and high-SMI (n 289) groups. We examined the significance of SMI for postoperative outcomes and evaluated correlations between SMI and clinical characteristics, including immune-nutritional status. Low SMI was significantly associated with body mass index and geriatric nutritional risk index. Five-year overall survival rate was significantly lower in the low-SMI group (66.0%) than in the high-SMI group (82.2%, P 0.004). Multivariate analysis revealed SMI (hazard ratio HR 1.850 95% confidence interval CI 1.091-3.135 P 0.022) and prognostic nutritional index (PNI) (HR 2.031 95% CI 1.231-3.352 P 0.006) as independent predictors of overall survival. Low SMI correlated significantly with postoperative complications (P 0.024). Low preoperative SMI based on CT at the L1 level appears associated with poor prognosis and postoperative complications among patients with early-stage NSCLC. PNI is also an independent prognostic factor for surgical outcomes.

Stochastic Fluctuations Drive Non-genetic Evolution of Proliferation in Clonal Cancer Cell Populations.

Evolutionary dynamics allows us to understand many changes happening in a broad variety of biological systems, ranging from individuals to complete ecosystems. It is also behind a number of remarkable organizational changes that happen during the natural history of cancers. These reflect tumour heterogeneity, which is present at all cellular levels, including the genome, proteome and phenome, shaping its development and interrelation with its environment. An intriguing observation in different cohorts of oncological patients is that tumours exhibit an increased proliferation as the disease progresses, while the timescales involved are apparently too short for the fixation of sufficient driver mutations to promote explosive growth. Here, we discuss how phenotypic plasticity, emerging from a single genotype, may play a key role and provide a ground for a continuous acceleration of the proliferation rate of clonal populations with time. We address this question by combining the analysis of real-time growth of non-small-cell lung carcinoma cells (N-H460) together with stochastic and deterministic mathematical models that capture proliferation trait heterogeneity in clonal populations to elucidate the contribution of phenotypic transitions on tumour growth dynamics.

Glucometer Readout for Portable Detection of Heterogeneous Circulating Tumor Cells in Lung Cancer Captured on a Dual Aptamer Functionalized Wrinkled Cellulose Hydrogel Interface.

The rarity of circulating tumor cells (CTCs) poses a great challenge to their clinical application as reliable liquid biopsy markers for cancer diagnosis. Meanwhile, the epithelial-mesenchymal transition (EMT) led to a reduced efficiency in capturing cells with lost or downregulated epithelial cell adhesion molecule (EpCAM) expressions. In this study, we proposed an integrated, highly efficient strategy for heterogeneous CTC capture and portable detection from the blood of non-small-cell lung cancer (NSCLC) patients. First, the cellulose wrinkled hydrogel with excellent biocompatibility and high specific area was employed as the biointerface to capture heterogeneous CTCs with an improved capture efficiency in virtue of dual targeting against epithelial and mesenchymal ones. Meanwhile, the strategy of glucometer readout was introduced for the quantification of captured CTCs on the same hydrogel interface by a detection probe, Au-G-MSN-Apt, which was fabricated via entrapping glucose into the amino group functionalized mesoporous silica nanoparticle (MSN) framework sealed by l-cysteine modified gold nanoparticles (AuNPs) and then linked with dual aptamers of EpCAM and Vimentin. The number of captured CTCs on the hydrogel could be reflected according to the portable glucose meter (PGM) readings. Moreover, it was found that the captured cells maintained a higher viability on the hydrogel and could be in situ recultured without releasing from the substrate. Finally, this integrated strategy was successfully applied to inspect the correlations between the number of heterogeneous CTCs in the blood of NSCLC patients with disease stage and whether there was distant metastasis.

Incorporating higher order network structures to improve miRNA-disease association prediction based on functional modularity.

As microRNAs (miRNAs) are involved in many essential biological processes, their abnormal expressions can serve as biomarkers and prognostic indicators to prevent the development of complex diseases, thus providing accurate early detection and prognostic evaluation. Although a number of computational methods have been proposed to predict miRNA-disease associations (MDAs) for further experimental verification, their performance is limited primarily by the inadequacy of exploiting lower order patterns characterizing known MDAs to identify missing ones from MDA networks. Hence, in this work, we present a novel prediction model, namely HiSCMDA, by incorporating higher order network structures for improved performance of MDA prediction. To this end, HiSCMDA first integrates miRNA similarity network, disease similarity network and MDA network to preserve the advantages of all these networks. After that, it identifies overlapping functional modules from the integrated network by predefining several higher order connectivity patterns of interest. Last, a path-based scoring function is designed to infer potential MDAs based on network paths across related functional modules. HiSCMDA yields the best performance across all datasets and evaluation metrics in the cross-validation and independent validation experiments. Furthermore, in the case studies, 49 and 50 out of the top 50 miRNAs, respectively, predicted for colon neoplasms and lung neoplasms have been validated by well-established databases. Experimental results show that rich higher order organizational structures exposed in the MDA network gain new insight into the MDA prediction based on higher order connectivity patterns.

Hemophagocytic lymphohistiocytosis (HLH) and cytokine release syndrome (CRS) in a patient with oncogene-addicted metastatic non-small cell lung cancer (NSCLC) following combination chemotherapy-immunotherapy.

Immune checkpoint inhibitors (ICIs) are utilized in a variety of clinical settings for the management of patients with metastatic non-small cell lung cancer (mNSCLC). While any organ may be subject to immune-related adverse events (irAEs) as a consequence of ICI therapy, hematological irAEs are uncommon. We describe a scenario involving a patient with oncogene-addicted mNSCLC who experienced the rare, life-threatening complication of hemophagocytic lymphohistiocytosis (HLH) and cytokine release syndrome following the receipt of the IMPower150 regimen (carboplatinpaclitaxelatezolizumabbevacizumab) after progression on initial tyrosine kinase inhibitor therapy. Malignancy-associated HLH, while previously described, is more typically associated with hematological rather than solid cancers and has only very recently been reported among patients receiving ICIs. While identification of hemophagocytosis on bone marrow examination is pathognomonic, this feature is not essential for confirming a diagnosis of HLH. Prompt recognition of suspicious laboratory and clinical features by medical oncologists and engagement with other relevant disciplines is hence critical to ensure optimal management of the condition.

Transcriptomic pan-cancer analysis using rank-based Bayesian inference.

The analysis of whole genomes of pan-cancer data sets provides a challenge for researchers, and we contribute to the literature concerning the identification of robust subgroups with clear biological interpretation. Specifically, we tackle this unsupervised problem via a novel rank-based Bayesian clustering method. The advantages of our method are the integration and quantification of all uncertainties related to both the input data and the model, the probabilistic interpretation of final results to allow straightforward assessment of the stability of clusters leading to reliable conclusions, and the transparent biological interpretation of the identified clusters since each cluster is characterized by its top-ranked genomic features. We applied our method to RNA-seq data from cancer samples from 12 tumor types from the Cancer Genome Atlas. We identified a robust clustering that mostly reflects tissue of origin but also includes pan-cancer clusters. Importantly, we identified three pan-squamous clusters composed of a mix of lung squamous cell carcinoma, head and neck squamous carcinoma, and bladder cancer, with different biological functions over-represented in the top genes that characterize the three clusters. We also found two novel subtypes of kidney cancer that show different prognosis, and we reproduced known subtypes of breast cancer. Taken together, our method allows the identification of robust and biologically meaningful clusters of pan-cancer samples.

Transfer learning supported accurate assessment of multiclass cervix type images.

Cervical cancer predominately affects women compared to lung, breast and endometrial cancer. Premature stage identification and proper treatment of this cancer may lead to 100% survival rate. The cervix type is very prominent in the detailed diagnosis of cervical cancer. High expertise and experienced gynecologist are required for an accurate diagnosis of cervical cancer. To reduce their burden, a model is proposed, based on deep learning that automatically classifies the cervix types. This paper presents Modified Deep Convolutional Neural Networks namely Modified VGG16 (MVGG16), Modified VGG19 (MVGG19), Modified ResNet50 (MRN50), Modified InceptionV3 (MIV3), and Modified InceptionResNetV2 (MIRNV2) for the classification of cervix type images. These modified networks are implemented using a Multiclass Support Vector Machine classifier. The performance metrics are tabulated and compared with pre-trained models. The simulation results show that MIRNV2 achieves the best performance compared to other models with an overall Accuracy of 92.91% and a Kappa score of 0.88. MIRNV2 model also gives better classification accuracy of 96.62% for type 1, 93.58% for type 2, and 95.61% for type 3 cervix images. Hence, this facilitates the application of MIRNV2 as a diagnostic tool to assist the gynecologist in the classification of cervix type images.

Presentations and outcomes among sickle cell disease patients with COVID-19 at a large southern healthcare system.

Compared with the general population, patients with sickle cell disease (SCD) typically have substantially reduced life expectancies. It is unclear whether SCD patients who acquire COVID-19 have higher rates of complications and mortality than the general population. We sought to elucidate COVID-19 presentation and outcomes in patients with SCD. Using retrospective chart review, we evaluated demographic characteristics, presenting symptoms, chest imaging findings, blood transfusion requirements, need for mechanical ventilation or pressor support, medication administration (including remdesivir and dexamethasone), and survival among individuals with SCD hospitalized with COVID-19 from March 2020 to December 2021. Among 72 SCD patients, increased pain was the most common presenting symptom followed by cough, fever, and dyspnea. Thirty-seven (44%) received simple transfusion and 14 (17%) underwent exchange transfusion. Lung imaging findings suggestive of COVID-19 were observed in 27 (37%) patients 21 (29%) patients were treated with remdesivir and 26 (35%) received dexamethasone. Three patients (4%) required mechanical ventilation and pressor support all three died from COVID complications. Pain is the most common presenting symptom in SCD patients with COVID-19. We observed a mortality rate higher than that among the general population among patients who required mechanical ventilation and pressor support.

A retrospective evaluation of the presentation, prognostic factors and outcomes of neuroblastoma in Ugandan children.

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. The complete burden and outcomes in Uganda are unknown. The study was a multicenter retrospective chart review of children aged between 0 to 15 years diagnosed with NB from 2010 to 2020. Demographic, clinical and tumor-related characteristics were extracted for analysis. Kaplan-Meier survival curves and Cox regression models were used to determine the one-year overall survival (OS) and identify prognostic factors. Seventy-five patients were evaluated, with a median age at diagnosis of 48 months (IQR 26-108 months). Fever (74.7%), weight loss (74.7%), high blood pressure (70.3%) and abdominal swellingmass (65.3%) were the most common features at diagnosis. Suprarenal tumors (52%) and stage 4 disease (70.7%) were also common. The one-year OS was 60.0% (95%CI 56.8% 64.3%) with a median survival time of 12.6 months (95% CI 8.1 20.8). The one-year OS for non-metastatic and metastatic disease was 67.3% and 42.6% ( Ugandan children diagnosed with neuroblastoma present with advanced disease.Surgery and radiotherapy are under-utilized in the management of neuroblastoma, but have prognostic value in neuroblastoma outcomes.Children under the age of 12 months are under-diagnosed in Uganda, but those that do present for treatment fare poorer than older age groups.The overall survival is poor but the survival time can be increased with maintenance chemotherapy.

Macrophage renewal modes affect acquired resistance to gefitinib in EGFR‑mutant lung cancer PC‑9 cells.

EGFR tyrosine kinase inhibitors (TKIs) have been successfully used in lung cancer treatment. Nevertheless, tumor cells may develop resistant phenotypes in the tumor microenvironment after a period of treatment with any generation of EGFR TKIs. Macrophages play a pivotal role in carcinogenesis and development. At the same time, macrophages renew continuously, and their polarized phenotype changes dynamically. Although macrophage polarization is generally considered to be involved in secondary resistance, it would be time consuming if renewed macrophages would only protect tumor cells from drug attacks after polarization. It is unclear how dynamic renewal of macrophage contributes to acquired resistance. By using two co‑culture approaches, the present study modeled two types of renewal of macrophages Migrated macrophages (Mm) and locally self‑renewal resident macrophages (Mr). The EGFR‑mutant lung cancer cell line PC‑9 was induced to develop resistance to gefitinib in these co‑culture approaches and without macrophages co‑culture. PC‑9 cells induced in Mm co‑culture recovered fast from gefitinib attack, and formed the gefitinib resistant (GR) subline PC‑9MmGR with the strongest resistant ability. PC‑9MmGR cells exhibited epithelial characteristics, including stable expression of EGFR, phosphorylated EGFR, insulin‑like growth factor 1 receptor, TGF‑βII receptor and E‑cadherin. PC‑9 cells induced in Mr co‑culture and those without co‑culture developed similar weak resistance to gefitinib. TGF‑β secretion was inhibited when PC‑9 cells were in Mr co‑culture, but not in Mm co‑culture. Macrophages were not polarized in either co‑culture type. The present findings suggested that macrophages may affect resistance acquirement by different renewal modes. Mm could promote resistance acquirement by stabilizing tumor cell phenotypes, which would happen before polarization. It would be helpful to monitor the response to EGFR‑TKIs and design novel treatment strategies if macrophages from two renewal modes were distinguished effectively.

Landscape of circular RNAs in different types of lung cancer and an emerging role in therapeutic resistance (Review).

Lung cancer is one of the most common malignant tumor types and the leading cause of cancer‑associated death worldwide. Different types of lung cancer exhibit differences in terms of pathophysiology and pathogenesis, and also treatment and prognosis. Accumulating evidence has indicated that circular RNAs (circRNAs) are abnormally expressed among different types of lung cancer and confer important biological functions in progression and prognosis. However, studies comparing different circRNAs in lung cancer subtypes are scarce. Furthermore, circRNAs have an important role in drug resistance and are related to clinicopathological features in lung cancer. Summaries of the association of circRNAs with drug resistance are also scarce in the literature. The present study outlined the biological functions of circRNAs and focused on discriminating differential circRNA patterns and mechanisms in three different types of lung cancer. The emerging roles of circRNAs in the resistance to chemotherapy, targeted therapy, radiotherapy and immunotherapy were also highlighted. Understanding these aspects of circRNAs sheds light on novel physiological and pathophysiological processes of lung cancer and suggests the application of circRNAs as biomarkers for diagnosis and prognosis, as well as therapeutic resistance.

Mistletoe lectin inhibits growth of Myc-amplified small-cell lung cancer.

Small-cell lung cancer (SCLC) is the deadliest form of lung cancer but lacks targeted therapies. We studied the effect of the natural product mistletoe lectin (ML) in pre-clinical models of SCLC, focusing on cell lines with amplification of the myc family oncogenes C-myc and N-myc. We found that ML treatment inhibits growth of SCLC cell lines in culture and induces apoptosis. ML treatment also decreases the expression of the amplified myc proteins. Over-expression of either C-myc or N-myc results in enhanced SCLC cell sensitivity to ML. In a mouse xenograft model of SCLC, treatment with ML results in decreased tumor growth over 4 weeks with evidence of increased apoptosis in tumors from treated animals. Overall, our results demonstrate that ML exhibits therapeutic potential in SCLC, that is at least partially dependent on myc protein expression.

Synthesis and In Vitro Cytotoxicity of Novel Halogenated Dihydropyrano3,2-bChromene Derivatives.

Lung and breast cancers are among the most common cancers. In the present work, initially, 6-bromo- and 6-chloro-3-hydroxychromone compounds were prepared. In the next step, a series of 8-bromo- and 8-chloro-dihyropyrano3,2-bchromene derivatives were synthesized by one-pot three component reaction of these two compounds, aromatic aldehydes, and ethyl cyanoacetate in the presence of triethylamine in EtOH at reflux conditions. The synthesized compounds were tested for their in vitro cytotoxic activity against A549 (lung cancer) and MCF-7 (breast cancer) cell lines. It was found that some compounds have high to moderate cytotoxicity, which makes them potential candidates for further studies. This study can be the basis for further studies to design and synthesis potent anticancer compounds and investigating their mechanism of action.

Lobar versus sublobar resection for atypical lung carcinoid An analysis from the National Cancer Database.

There is a knowledge gap regarding lobar versus sublobar resection for atypical carcinoid (AC) of the lung. As such, the authors sought to understand and analyze the outcomes of sublobar resection versus lobectomy in this patient population. A retrospective analysis using the National Cancer Database was performed to compare overall survival (OS) between patients treated with lobectomy and patients treated with sublobar resection for AC of the lung between the years 2004 and 2016. Patient characteristics were compared with χ The database identified 669 patients with T1-T4 and N0-N3 lung ACs that were surgically resected. Unadjusted Kaplan-Meier survival curves did not demonstrate an OS difference between lobectomy and sublobar resection (p .094). After propensity score matching, curves demonstrated a numerical improvement in OS with lobectomy however, it was not statistically significant (p .5). In a subgroup analysis, lobectomy and node-negative disease were associated with the best OS, whereas sublobar resection and node-positive disease were associated with the worst OS (p < .0001). Nodal involvement was associated with worse survival, regardless of surgical treatment (p < .0001). In patients with T1-T4 and N0-N3 ACs of the lung, lobectomy was not associated with an improvement in OS in comparison with sublobar resection.

circPVT1 and PVT1AKT3 show a role in cell proliferation, apoptosis, and tumor subtype-definition in small cell lung cancer.

Small cell lung cancer (SCLC) is treated as a homogeneous disease, although the expression of NEUROD1, ASCL1, POU2F3, and YAP1 identifies distinct molecular subtypes. The MYC oncogene, amplified in SCLC, was recently shown to act as a lineage-specific factor to associate subtypes with histological classes. Indeed, MYC-driven SCLCs show a distinct metabolic profile and drug sensitivity. To disentangle their molecular features, we focused on the co-amplified PVT1, frequently overexpressed and originating circular (circRNA) and chimeric RNAs. We analyzed hsacirc0001821 (circPVT1) and PVT1AKT3 (chimPVT1) as examples of such transcripts, respectively, to unveil their tumorigenic contribution to SCLC. In detail, circPVT1 activated a pro-proliferative and anti-apoptotic program when over-expressed in lung cells, and knockdown of chimPVT1 induced a decrease in cell growth and an increase of apoptosis in SCLC in vitro. Moreover, the investigated PVT1 transcripts underlined a functional connection between MYC and YAP1POU2F3, suggesting that they contribute to the transcriptional landscape associated with MYC amplification. In conclusion, we have uncovered a functional role of circular and chimeric PVT1 transcripts in SCLC these entities may prove useful as novel biomarkers in MYC-amplified tumors.

The Path to Personalized Treatment in KRAS-Mutant Non-Small Cell Lung Cancer A Review of Targeted Therapies and Immunotherapy.

To summarize the targeted therapies and immunotherapy of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant non-small cell lung cancer (NSCLC), and discuss the ongoing clinical trials. KRAS mutations occur in about 30% of patients with NSCLC and are the second most frequent genetic variation in lung cancer. It has been considered undruggable for 40 years until the discovery of a direct inhibitor of KRAS G12C. The promising direct KRAS G12C inhibitors such as sotorasib and MRTX849 have made a breakthrough with promising anti-tumor effects in patients with KRAS G12C-mutant advancedmetastatic NSCLC post one prior line of therapy. Following the success of immune checkpoint inhibitors (ICIs) in NSCLC, many patients harboring KRAS mutations can benefit from ICIs. However, due to disease heterogeneity, the prognosis of patients remains unsatisfactory, leaving room for personalized treatment options, such as new targeted therapies and other therapies. In this review, we aim to dissect the strategies of clinical trials in these tumors, shifting from a few chemotherapy options to targeted and immunotherapy, in the context of molecular selection of KRAS-mutant NSCLC subtypes.

Evodiamine exerts inhibitory roles in non‑small cell lung cancer cell A549 and its sub‑population of stem‑like cells.

Evodiamine (EVO) is one of the main components extracted from

Estimation of the effects PM2.5, NO2, O3 pollutants on the health of Shahrekord residents based on AirQ

Intertwined with modern life, air pollution is not a new phenomenon. Air pollution imposes a significant number of deaths and disease complications on society, and therefore it is very important to determine the extent of its effects on health in any society. This study sought to evaluate the concentration and short-term and long-term excess mortality attributed to PM2.5, NO Hourly concentrations of PM2.5, O The death rates of IHD, COPD, lung cancer and ALRI and stroke related to PM2.5 were 176, 7, 0, 10, 105, respectively. The effect of ozone on respiratory mortality was zero. During the study period in Shahrekord, no respiratory mortality was determined due to ozone and acute lower respiratory tract infection (ALRI). this study is first ever study on health effects of air pollution in shahrekord city. A significant number of deaths due to air pollutants in Shahrekord have been reported. It can be concluded that by designing and implementing strategies and measures to control air pollution, both health effects and economic losses are prevented.

Health effects and known pathology associated with the use of E-cigarettes.

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.

Recovering from COVID-19 lessons learnt from an intensive secondary care follow-up service.

In response to the first COVID-19 surge in 2020, secondary care outpatient services were rapidly reconfigured to provide specialist review for disease sequelae. At our institution, comprising hospitals across three sites in London, we initially implemented a COVID-19 follow-up pathway that was in line with expert opinion at the time but more intensive than initial clinical guidelines suggested. We retrospectively evaluated the resource requirements for this service, which supported 526 patients from April 2020 to October 2020. At the 6-week review, 193403 (47.9%) patients reported persistent breathlessness, 46336 (13.7%) desaturated on exercise testing, 167403 (41.4%) were discharged from COVID-19-related secondary care services and 190403 (47.1%) needed 12-week follow-up. At the 12-week review, 113309 (36.6%) patients reported persistent breathlessness, 30266 (11.3%) desaturated on exercise testing and 150309 (48.5%) were discharged from COVID-19-related secondary care services. Referrals were generated to multiple medical specialties, particularly respiratory subspecialties. Our analysis allowed us to justify rationalising and streamlining provisions for subsequent COVID-19 waves while reassured that opportunities for early intervention were not being missed.

Anti-PD-1 antibodies, a novel treatment option for advanced chemoresistant pulmonary lymphoepithelioma carcinoma.

Pulmonary lymphoepithelioma-like carcinoma (LELC) exhibits a unique immune microenvironment, including high PD-L1 expression and abundant infiltrating-immune cells. However, the availability of PD-1PD-L1 inhibitors in patients with LELC is still not determined. A total of 36 cases of pulmonary LELC treated with PD-1PD-L1 inhibitors were reviewed, including 10 cases from our institute and 26 cases included from the literature. The Kaplan-Meier method and log-rank test were utilized to analyze the survival outcomes of LELC patients receiving immunotherapy, and the factors related to immunotherapy response were further examined. Of the 10 patients from our institute, the median age was 53.5 years, adrenal glands and distant lymph nodes were the most common metastatic sites, and 4 of 8 (50%) patients had a PD-L1 TPS ≥50%. The median progression-free survival and overall survival in patients from our institute and from the literature were 11.6 and 27.3 months, 17.2 months and not reached, respectively. In all 36 patients, the objective response rate was as high as 57.6%. Patients with higher PD-L1 expression were more likely to have a tumor response, but the association of PD-L1 expression with survival time remains to be determined. PD-1PD-L1 inhibitors in patients with pulmonary LELC demonstrated a promising efficacy in retrospective cohorts, and deserve further validation in prospective studies administrating in front-line setting.

Salvage LATTICE radiotherapy for a growing tumour despite conventional radio chemotherapy treatment of lung cancer.

A 40-year-old patient with cT4cN1M0 squamous cell lung cancer of the upper right lobe received preoperative induction chemotherapy. Systemic induction treatment failed to reverse tumour growth with the addition of conventional radiotherapy (RT). A salvage lattice RT boost of 12 Gy was administered immediately to increase the dose to the tumour. Conventional RT was resumed at the planned dose of 60 Gy. The tumour shrank rapidly, and the patient was surged. The postoperative pathology remained ypT0ypN0 status.

Association between site of infection and mortality in patients with cancer with sepsis or septic shock A retrospective cohort study.

Infections are associated with increased mortality in patients with sepsis or septic shock. However, to the best of our knowledge, the influence of the site of infection on patients with cancer remains unclear. The present study aimed to evaluate the association between the site of infection and mortality in patients with cancer and sepsis or septic shock. The present study was conducted in a Lebanon tertiary care centre from July 2010 to April 2015. A total of 176 patients with active cancer presenting to the emergency department with sepsis or sepsis shock were included in the present analysis. Cox regression and Kaplan-Meier analysis of the effect of the site of infection on mortality were performed. The most common site of infection was the lung (37.50%), followed by the urinary tract (26.70%), unknown site (13.63%), gastrointestinal (13.07%) and others (9.10%). The overall mortality rate was 47.73%. Gastrointestinal infection (78.26%) was associated with the highest mortality, followed by pneumonia (62.12%). The urinary tract infection with the lowest mortality rate was the reference group. After adjusting for confounding variables, gastrointestinal infection was associated with the highest in-hospital mortality hazard ratio (HR), 2.64 95% CI, 1.25-5.55, followed by pneumonia (HR, 1.95 95% CI, 1.03-3.68). The association between site of infection and 28-day and 60-day mortality was analysed by Cox regression, as well as by stratified analysis to investigate the association between site of infection and mortality from haematological and solid tumors. Gastrointestinal infection had a higher mortality rate. In conclusion, the site of infection had the same association with mortality in patients with solid and haematological tumours.

The regulatory role of N6-methyladenosine RNA modification in gastric cancer Molecular mechanisms and potential therapeutic targets.

N6-methyladenosinen (m

Awareness of hazards due to tobacco among people aged 15 years and older in Chongqing, China, in 2020 A cross-sectional analysis.

Tobacco smoke contains a large number of harmful substances and carcinogens. Smoking and secondhand smoke cause a variety of cancers and diseases, seriously endangering human health. However, the status and characteristics of the awareness of hazards due to tobacco among people aged ≥15 years in Chongqing, China, are still unknown. A multistage stratified cluster random sampling method was used to select ten districts and counties in Chongqing Municipality, China and a total of 6622 people were investigated between August and October 2020. The chi-squared test was used to analyze the awareness of hazards due to tobacco in various populations after the data had been cleaned and weighted. In 2020, the awareness rates of people aged ≥15 years in Chongqing, China, about a specific disease caused by smoking were lung cancer (77.1%), heart disease (45.1%), stroke (40.1%), and penile erectile dysfunction (24.2%). However, only 22.1% of the respondents knew that smoking could simultaneously lead to all four diseases mentioned above. Adult lung cancer was the disease with the highest awareness rating (72.5%), followed by childrens lung disease (54.2%) and adult heart disease (46.1%). A total of 42.0% of respondents knew that secondhand smoke could cause the three diseases simultaneously. Only 22.0% of those correctly understood the harm of low-tar cigarettes. The logistic regression results showed that education level and occupation were risk factors for lack of awareness of hazards due to tobacco. In contrast, media campaigns on tobacco control were a protective factor. The awareness of hazards due to tobacco among people aged ≥15 years in Chongqing, China, still needs to be improved. More graphic health warning labels and mass media campaigns about the hazards of tobacco should be carried out to raise peoples awareness and warn about the health risks of smoking.

Development and Validation of the Random Forest Model via Combining CT-PET Image Features and Demographic Data for Distant Metastases among Lung Cancer Patients.

The work aimed at developing and validating a random forest model of CT-PET image features combined with demographic data to diagnose distant metastases among lung cancer patients. This study involved lung cancer patients from The Cancer Genome Atlas lung adenocarcinoma (TCGA-LUAD) dataset, the lung PET-CT dataset, the lung squamous cell carcinoma (LSCC) dataset, and the National Cancer Institutes Clinical Proteomic Tumor Analysis Consortium lung adenocarcinoma (CPTAC-LUAD) dataset and collected the information on 178 CT, 178 PET, and the patients age, history of smoking, and gender. We conducted image processing and feature extraction. Finally, 4 computed tomography (CT) image features and 2 positron emission tomography (PET) image features were extracted. Four prediction models based on CT image features, PET image features, and demographic data were developed, and the area under the receiver operating characteristic (ROC) curve was used to evaluate the performance of prediction models. A total of 178 eligible samples were randomly divided into a training set (

Genomic Profiling Identifies Putative Pathogenic Alterations in NSCLC Brain Metastases.

Brain metastases (BM) severely affect the prognosis and quality of life of patients with NSCLC. Recently, molecularly targeted agents were found to have promising activity against BM in patients with NSCLC whose primary tumors carry druggable mutations. Nevertheless, it remains critical to identify specific pathogenic alterations that drive NSCLC-BM and that can provide novel and more effective therapeutic targets. To identify potentially targetable pathogenic alterations in NSCLC-BM, we profiled somatic copy number alterations (SCNAs) in 51 matched pairs of primary NSCLC and BM samples from 33 patients with lung adenocarcinoma and 18 patients with lung squamous cell carcinoma. In addition, we performed multiregion copy number profiling on 15 BM samples and whole-exome sequencing on 40 of 51 NSCLC-BM pairs. BM consistently had a higher burden of SCNAs compared with the matched primary tumors, and SCNAs were typically homogeneously distributed within BM, suggesting BM do not undergo extensive evolution once formed. By comparing focal SCNAs in matched NSCLC-BM pairs, we identified putative BM-driving alterations affecting multiple cancer genes, including several potentially targetable alterations in genes such as Our study represents the most comprehensive genomic characterization of NSCLC-BM available to date, paving the way to functional studies aimed at assessing the potential of the identified pathogenic alterations as clinical biomarkers and targets.

Red light active Pt(iv)-BODIPY prodrug as a mitochondria and endoplasmic reticulum targeted chemo-PDT agent.

A cisplatin-based platinum(iv) prodrug, Pt(NH

Carcinoid tumors outside the abdomen.

Neuroendocrine tumors (NETs) are epithelial malignancies that can arise from multiple tissues. Gastrointestinal (GI) NETs are the most common in this review of extra-abdominal carcinoid tumors, we focus our discussion on bronchial and thymic carcinoid tumors. Bronchial carcinoid tumors comprise a quarter of all NETs and less than 2% of all lung cancers. Thymic carcinoid tumors are extremely rare, accounting for 5% of thymic tumors. Both bronchial and thymic carcinoid tumors are histologically classified as either typical or atypical based on their mitotic rate (less than 2 or 2-10 mitoses per 10 high-powered fields (HPF), respectively). Both bronchial and thymic carcinoids can present with symptoms of obstruction and potentially carcinoid syndrome. The gold standard of management of bronchial and thymic carcinoid tumors is surgical resection. For patients with advanced disease, first-line systemic therapy is generally somatostatin analog monotherapy with octreotide or lanreotide. In patients with refractory disease, therapy generally involves peptide receptor radioligand therapy, everolimus, or cytotoxic chemotherapy. There are ongoing, prospective trials comparing the mainstays of systemic therapy for these patients, as well as ongoing evaluations of immune checkpoint inhibitors and multi-kinase inhibitors. Prognosis for both bronchial and thymic carcinoid tumors depends on histologic grade, local versus invasive disease, and extent of metastases. Herein we provide a summary of the pathophysiologic and clinical background, the current state of the field in diagnosis and management, and note of key ongoing prospective trials for patients with bronchial and thymic carcinoid tumors.

Heparin Inhibits SARS-CoV-2 Replication in Human Nasal Epithelial Cells.

SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary infection predominantly occurs via the nasal epithelium, but the nasal cell biology of SARS-CoV-2 is not well studied. We hypothesized that prophylactic intranasal administration of heparin may provide strain-agnostic protection for household contacts or those in high-risk settings against SARS-CoV-2 infection. Therefore, we investigated the ability of heparin to inhibit SARS-CoV-2 infection and replication in differentiated human nasal epithelial cells and showed that prolonged exposure to heparin inhibits virus infection. Furthermore, we establish a method for PCR detection of SARS-CoV-2 viral genomes in heparin-treated samples that can be adapted for the detection of viruses in clinical studies.

Response to Omalizumab as an Add-On Therapy in the Treatment of Allergic Asthma in Adult Chinese Patients-A Retrospective Study.

(a) Background Omalizumab is an anti-IgE humanized monoclonal antibody marketed in China for the conventional treatment of poorly controlled moderate-to-severe allergic asthma. Numerous clinical trials have demonstrated the effectiveness of omalizumab, but the data from studies in actual clinical treatment are still relatively limited. (b) Methods Thirty-two patients with moderate-to-severe allergic asthma treated with omalizumab on the basis of ICS-LABA (inhaled corticosteroidslong-acting beta2-agonist) were selected. Clinical characteristics before and after treatment were collected to analyze the relationship between changes in serum total IgE levels and peripheral blood EOS (eosinophil) levels, FEV1 (forced expiratory volume in 1 second), PEF (peak expiratory flow), OCS (oral glucocorticoid) dosage, ATC (asthma control test) score, and the number of acute exacerbations and the treatment response, in order to observe the efficacy of omalizumab in addition to primary therapy, and to investigate whether baseline clinical characteristics such as serum total IgE and EOS levels could predict a treatment response. (c) Results Using the ACT score as an evaluation, 68.75% of patients benefited from omalizumab treatment at the end of 16 weeks. The response group has a reduction in OCS dosage (

Influenza Vaccination Reduces the Risk of Liver Cancer in Patients with Chronic Kidney Disease A Nationwide Population-Based Cohort Study.

Previous studies have indicated that influenza vaccination reduces the development of lung cancer. However, the protective effects of influenza vaccination on primary liver cancer in patients with chronic kidney disease (CKD) are unclear. This cohort study identified 12,985 patients aged at least 55 years who had received a diagnosis of CKD between 1 January 2001 and 31 December 2012 from the National Health Insurance Research Database of Taiwan. The patients were classified according to vaccination status. Propensity score matching was used to reduce selection bias. Cox proportional hazards regression analysis was used to evaluate the correlation between influenza vaccination and primary liver cancer in patients with CKD. The prevalence of primary liver cancer was lower in patients with CKD who had received an influenza vaccine (adjusted hazard ratio 0.45, 95% confidence interval CI 0.35-0.58,

Medical Image Classification Based on Semi-Supervised Generative Adversarial Network and Pseudo-Labelling.

Deep learning has substantially improved the state-of-the-art in object detection and image classification. Deep learning usually requires large-scale labelled datasets to train the models however, due to the restrictions in medical data sharing and accessibility and the expensive labelling cost, the application of deep learning in medical image classification has been dramatically hindered. In this study, we propose a novel method that leverages semi-supervised adversarial learning and pseudo-labelling to incorporate the unlabelled images in model learning. We validate the proposed method on two public databases, including ChestX-ray14 for lung disease classification and BreakHis for breast cancer histopathological image diagnosis. The results show that our method achieved highly effective performance with an accuracy of 93.15% while using only 30% of the labelled samples, which is comparable to the state-of-the-art accuracy for chest X-ray classification it also outperformed the current methods in multi-class breast cancer histopathological image classification with a high accuracy of 96.87%.

IGWO-IVNet3 DL-Based Automatic Diagnosis of Lung Nodules Using an Improved Gray Wolf Optimization and InceptionNet-V3.

Artificial intelligence plays an essential role in diagnosing lung cancer. Lung cancer is notoriously difficult to diagnose until it has progressed to a late stage, making it a leading cause of cancer-related mortality. Lung cancer is fatal if not treated early, making this a significant issue. Initial diagnosis of malignant nodules is often made using chest radiography (X-ray) and computed tomography (CT) scans nevertheless, the possibility of benign nodules leads to wrong choices. In their first phases, benign and malignant nodules seem very similar. Additionally, radiologists have a hard time viewing and categorizing lung abnormalities. Lung cancer screenings performed by radiologists are often performed with the use of computer-aided diagnostic technologies. Computer scientists have presented many methods for identifying lung cancer in recent years. Low-quality images compromise the segmentation process, rendering traditional lung cancer prediction algorithms inaccurate. This article suggests a highly effective strategy for identifying and categorizing lung cancer. Noise in the pictures was reduced using a weighted filter, and the improved Gray Wolf Optimization method was performed before segmentation with watershed modification and dilation operations. We used InceptionNet-V3 to classify lung cancer into three groups, and it performed well compared to prior studies 98.96% accuracy, 94.74% specificity, as well as 100% sensitivity.

Isolation and Characterization of Flavonoid Naringenin and Evaluation of Cytotoxic and Biological Efficacy of Water Lilly (

Despite its limited exploration,

Polysaccharide-Based Nanomedicines Targeting Lung Cancer.

A primary illness that accounts for a significant portion of fatalities worldwide is cancer. Among the main malignancies, lung cancer is recognised as the most chronic kind of cancer around the globe. Radiation treatment, surgery, and chemotherapy are some medical procedures used in the traditional care of lung cancer. However, these methods lack selectivity and damage nearby healthy cells. Several polysaccharide-based nanomaterials have been created to transport chemotherapeutics to reduce harmful and adverse side effects and improve response during anti-tumour reactions. To address these drawbacks, a class of naturally occurring polymers called polysaccharides have special physical, chemical, and biological characteristics. They can interact with the immune system to induce a better immunological response. Furthermore, because of the flexibility of their structures, it is possible to create multifunctional nanocomposites with excellent stability and bioavailability for the delivery of medicines to tumour tissues. This study seeks to present new views on the use of polysaccharide-based chemotherapeutics and to highlight current developments in polysaccharide-based nanomedicines for lung cancer.

Nanoparticle-Mediated Delivery of STAT3 Inhibitors in the Treatment of Lung Cancer.

Lung cancer is a common malignancy worldwide, with high morbidity and mortality. Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor that not only regulates different hallmarks of cancer, such as tumorigenesis, cell proliferation, and metastasis but also regulates the occurrence and maintenance of cancer stem cells (CSCs). Abnormal STAT3 activity has been found in a variety of cancers, including lung cancer, and its phosphorylation level is associated with a poor prognosis of lung cancer. Therefore, the STAT3 pathway may represent a promising therapeutic target for the treatment of lung cancer. To date, various types of STAT3 inhibitors, including natural compounds, small molecules, and gene-based therapies, have been developed through direct and indirect strategies, although most of them are still in the preclinical or early clinical stages. One of the main obstacles to the development of STAT3 inhibitors is the lack of an effective targeted delivery system to improve their bioavailability and tumor targetability, failing to fully demonstrate their anti-tumor effects. In this review, we will summarize the recent advances in STAT3 targeting strategies, as well as the applications of nanoparticle-mediated targeted delivery of STAT3 inhibitors in the treatment of lung cancer.

Co-Delivery System of Curcumin and Colchicine Using Functionalized Mesoporous Silica Nanoparticles Promotes Anticancer and Apoptosis Effects.

Many natural agents have a high anticancer potential, and their combination may be advantageous for improved anticancer effects. Such agents, however, often are not water soluble and do not efficiently target cancer cells, and the kinetics of their action is poorly controlled. One way to overcome these barriers is to combine natural agents with nanoparticles. Our aim in the current study was to fabricate an anticancer nanoformulation for co-delivery of two natural agents, curcumin (CR) and colchicine (CL), with a core-shell structure. Using cancer cell lines, we compared the anticancer efficacy between the combination and a nanoformulation with CL alone. For the single-drug nanoformulation, we used phosphonate groups to functionalize mesoporous silica nanoparticles (MSNs) and loaded the MSNs with CL. Additional loading of this nanoformulation with CR achieved the co-delivery format. To create the structure with a core shell, we selected a chitosan-cellulose mixture conjugated with targeting ligands of folic acid for the coating. For evaluating anticancer and apoptosis effects, we assessed changes in important genes and proteins in apoptosis (p53, caspase-3, Bax, Bcl-2) in several cell lines (MCF-7, breast adenocarcinoma HCT-116, colon carcinoma HOS, human osteosarcoma and A-549, non-small cell lung cancer). Nanoformulations were successfully synthesized and contained 10.9 wt.% for the CL single-delivery version and 18.1 wt.% for the CLCR co-delivery nanoformulation. Anticancer effects depended on treatment, cell line, and concentration. Co-delivery nanoformulations exerted anticancer effects that were significantly superior to those of single delivery or free CL or CR. Anticancer effects by cell line were in the order of HCT-116 gt A549 gt HOS gt MCF-7. The lowest IC50 value was obtained for the nanoformulation consisting of CL and CR coated with a polymeric shell conjugated with FA (equivalent to 4.1 ± 0.05 µgmL). With dual delivery compared with the free agents, we detected strongly increased p53, caspase-3, and Bax expression, but inhibition of Bcl-2, suggesting promotion of apoptosis. Our findings, although preliminary, indicate that the proposed dual delivery nanoformulation consisting of nanocore MSNs loaded with CL and CR and coated with a shell of chitosan-cellulose conjugated folic acid exerted strong anticancer and apoptotic effects with potent antitumor activity against HCT-116 colon cells. The effect bested CL alone. Evaluating and confirming the efficacy of co-delivery nanoformulations will require in vivo studies.

Optimization of the Solvent and In Vivo Administration Route of Auranofin in a Syngeneic Non-Small Cell Lung Cancer and Glioblastoma Mouse Model.

The antineoplastic activity of the thioredoxin reductase 1 (TrxR) inhibitor, auranofin (AF), has already been investigated in various cancer mouse models as a single drug, or in combination with other molecules. However, there are inconsistencies in the literature on the solvent, dose and administration route of AF treatment in vivo. Therefore, we investigated the solvent and administration route of AF in a syngeneic SB28 glioblastoma (GBM) C57BL6J and a 344SQ non-small cell lung cancer 129S2SvPasCrl (129) mouse model. Compared to daily intraperitoneal injections and subcutaneous delivery of AF via osmotic minipumps, oral gavage for 14 days was the most suitable administration route for high doses of AF (10-15 mgkg) in both mouse models, showing no measurable weight loss or signs of toxicity. A solvent comprising 50% DMSO, 40% PEG300 and 10% ethanol improved the solubility of AF for oral administration in mice. In addition, we confirmed that AF was a potent TrxR inhibitor in SB28 GBM tumors at high doses. Taken together, our results and results in the literature indicate the therapeutic value of AF in several in vivo cancer models, and provide relevant information about AFs optimal administration route and solvent in two syngeneic cancer mouse models.

Advances in Tumor Organoids for the Evaluation of Drugs A Bibliographic Review.

Tumor organoids are defined as self-organized three-dimensional assemblies of heterogeneous cell types derived from patient samples that mimic the key histopathological, genetic, and phenotypic characteristics of the original tumor. This technology is proposed as an ideal candidate for the evaluation of possible therapies against cancer, presenting advantages over other models which are currently used. However, there are no reports in the literature that relate the techniques and material development of tumor organoids or that emphasize in the physicochemical and biological properties of materials that intent to biomimicry the tumor extracellular matrix. There is also little information regarding the tools to identify the correspondence of native tumors and tumoral organoids (tumoroids). Moreover, this paper relates the advantages of organoids compared to other models for drug evaluation. A growing interest in tumoral organoids has arisen from 2009 to the present, aimed at standardizing the process of obtaining organoids, which more accurately resemble patient-derived tumor tissue. Likewise, it was found that the characteristics to consider for the development of organoids, and therapeutic responses of them, are cell morphology, physiology, the interaction between cells, the composition of the cellular matrix, and the genetic, phenotypic, and epigenetic characteristics. Currently, organoids have been used for the evaluation of drugs for brain, lung, and colon tumors, among others. In the future, tumor organoids will become closer to being considered a better model for studying cancer in clinical practice, as they can accurately mimic the characteristics of tumors, in turn ensuring that the therapeutic response aligns with the clinical response of patients.

Insights into Lipid-Based Delivery Nanosystems of Protein-Tyrosine Kinase Inhibitors for Cancer Therapy.

According to the WHO, cancer caused almost 10 million deaths worldwide in 2020, i.e., almost one in six deaths. Among the most common are breast, lung, colon and rectal and prostate cancers. Although the diagnosis is more perfect and spectrum of available drugs is large, there is a clear trend of an increase in cancer that ends fatally. A major advance in treatment was the introduction of gentler antineoplastics for targeted therapy-tyrosine kinase inhibitors (TKIs). Although they have undoubtedly revolutionized oncology and hematology, they have significant side effects and limited efficacy. In addition to the design of new TKIs with improved pharmacokinetic and safety profiles, and being more resistant to the development of drug resistance, high expectations are placed on the reformulation of TKIs into various drug delivery lipid-based nanosystems. This review provides an insight into the history of chemotherapy, a brief overview of the development of TKIs for the treatment of cancer and their mechanism of action and summarizes the results of the applications of self-nanoemulsifying drug delivery systems, nanoemulsions, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles and nanostructured lipid carriers used as drug delivery systems of TKIs obtained in vitro and in vivo.