Lung Cancer Mortality Research Articles

Abstract 1068: Plasma metabolite biomarkers for EGFR-mutated non-small cell lung cancer (NSCLC)

Abstract Background: Lung cancer is the leading cause of cancer death. More than half of the patients are diagnosed in the advanced stage for which the 5-year survival is below 10%. Lung cancer screening using low-dose CT scan reduced lung cancer mortality among heavy smokers. However, no standard screening method exists for non-smokers. Up to 35% and 90% of male and female lung cancer patients in Southeast Asia, respectively, do not smoke. Half of NSCLC patients in this region harbor EGFR mutations, which is common in women and non-smokers. Thus, we sought to explore novel biomarkers that help to identify lung cancer patients and those who have EGFR mutation. Metabolic reprogramming is one of the hallmarks of cancer. It leads to changes in metabolite levels in the blood. Hence, we conducted plasma metabolomic analysis to identify potential metabolite biomarkers in lung cancer patients. Methods: Plasma samples were collected from 69 lung cancer patients at Siriraj hospital and 10 healthy individuals during 2018-2022. Plasma metabolites from 29 treatment-naïve EGFR-mutated NSCLC patients, 30 treatment-naïve EGFR-wild-type NSCLC patients, 10 treatment-resistant EGFR T790M-mutated NSCLC patients, and 10 healthy individuals were profiled using GC-MS and untargeted LC-MS with Metlin database matching. EGFR mutation was detected from plasma ctDNA using real-time PCR. Negative plasma EGFR mutation results were confirmed with corresponding tumor tissues. Metabolomics data were processed by the metabox R package. Results: Among 114 candidate metabolites that passed the variable importance in projection (VIP) cutoff of 1.5, the top ten metabolites that differentiate NSCLC patients with EGFR mutation from those without were shown in Table 1. Many of them can also separate between NSCLC patients and healthy individuals. Table 1. ROC curve analysis Discriminant metabolites (Mutated EGFR vs Wild-type EGFR NSCLC) AUC Accuracy Sensitivity Specificity PG(a-13:0/i-12:0) 0.8000 0.7833 0.8333 0.7333 Nervonic ceramide 0.7736 0.6772 0.7259 0.6333 Valine 0.7678 0.7298 0.7259 0.7333 L-Histidinol 0.7644 0.7281 0.7222 0.7333 Leucine 0.7563 0.7632 0.7259 0.8000 Tryptophan 0.7425 0.6289 0.5593 0.7000 8-methylcaffeine 0.6793 0.6096 0.6222 0.6000 Formic acid 0.6759 0.6447 0.5889 0.7000 PC(20:0/24:0) 0.6506 0.6614 0.8259 0.5000 Sucrose 0.6471 0.6596 0.7593 0.5667 Discriminant metabolites (NSCLC patients vs Healthy individuals) AUC Accuracy Sensitivity Specificity Tryptophan 0.9986 0.9867 1.0000 0.9848 PC(20:0/24:0) 0.8609 0.9505 0.6111 1.0000 L-Histidinol 0.8572 0.9625 0.7778 0.9861 Formic acid 0.6696 0.9262 0.6667 0.9704 Conclusions: Plasma L-Histidinol, tryptophan, PC(20:0/24:0), and formic acid are potential metabolite biomarkers for NSCLC patients harboring EGFR mutation. Citation Format: Lucksamon Thamlikitkul, Siriphan Manocheewa, Suphitcha Limjiasahapong, Kwanjeera Wanichthanarak, Atikorn Panya, Naravat Poungvarin, Yotsawat Pomyen, Sakda Khoomrung. Plasma metabolite biomarkers for EGFR-mutated non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1068.

Screening approaches for lung cancer by blood-based biomarkers: Challenges and opportunities.

Lung cancer (LC) is one of the leading causes for cancer-related deaths in the world, accounting for 28% of all cancer deaths in Europe. Screening for lung cancer can enable earlier detection of LC and reduce lung cancer mortality as was demonstrated in several large image-based screening studies such as the NELSON and the NLST. Based on these studies, screening is recommended in the US and in the UK a targeted lung health check program was initiated. In Europe lung cancer screening (LCS) has not been implemented due to limited data on cost-effectiveness in the different health care systems and questions on for example the selection of high-risk individuals, adherence to screening, management of indeterminate nodules, and risk of overdiagnosis. Liquid biomarkers are considered to have a high potential to address these questions by supporting pre- and post- Low Dose CT (LDCT) risk-assessment thereby improving the overall efficacy of LCS. A wide variety of biomarkers, including cfDNA, miRNA, proteins and inflammatory markers have been studied in the context of LCS. Despite the available data, biomarkers are currently not implemented or evaluated in screening studies or screening programs. As a result, it remains an open question which biomarker will actually improve a LCS program and do this against acceptable costs. In this paper we discuss the current status of different promising biomarkers and the challenges and opportunities of blood-based biomarkers in the context of lung cancer screening.

Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study)

Background. We investigated mortality in workers of the world’s largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation.
 Methods. This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers’ complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models.
 Results. A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR=7.64, 95% CI=1.18 to 49.5, to at least 80 fibers per cm3 years and RR=4.56, 95% CI=0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer.
 Conclusion. In this large-scale epidemiological study in the world’s largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.

Dual-branch feature fusion S3D V-Net network for lung nodules segmentation.

Accurate segmentation of lung nodules can help doctors get more accurate results and protocols in early lung cancer diagnosis and treatment planning, so that patients can be better detected and treated at an early stage, and the mortality rate of lung cancer can be reduced. Currently, the improvement of lung nodule segmentation accuracy has been limited by his heterogeneous performance in the lungs, the imbalance between segmentation targets and background pixels, and other factors. We propose a new 2.5D lung nodule segmentation network model for lung nodule segmentation. This network model can well improve the extraction of edge information of lung nodules, and fuses intra-slice and inter-slice features, which makes good use of the three-dimensional structural information of lung nodules and can more effectively improve the accuracy of lung nodule segmentation. Our approach is based on a typical encoding-decoding network structure for improvement. The improved model captures the features of multiple nodules in both 3-D and 2-D CT images, complements the information of the segmentation target's features and enhances the texture features at the edges of the pulmonary nodules through the dual-branch feature fusion module (DFFM) and the reverse attention context module (RACM), and employs central pooling instead of the maximal pooling operation, which is used to preserve the features around the target and to eliminate the edge-irrelevant features, to further improve the performance of the segmentation of the pulmonary nodules. We evaluated this method on a wide range of 1186 nodules from the LUNA16 dataset, and averaging the results of ten cross-validated, the proposed method achieved the mean dice similarity coefficient (mDSC) of 84.57%, the mean overlapping error (mOE) of 18.73% and average processing of a case is about 2.07 s. Moreover, our results were compared with inter-radiologist agreement on the LUNA16 dataset, and the average difference was 0.74%. The experimental results show that our method improves the accuracy of pulmonary nodules segmentation and also takes less time than more 3-D segmentation methods in terms of time.

A pragmatic randomized clinical trial of multilevel interventions to improve adherence to lung cancer screening (The Larch Study): Study protocol

BackgroundIn real-world settings, low adherence to lung cancer screening (LCS) diminishes population-level benefits of reducing lung cancer mortality. We describe the Larch Study protocol, which tests the effectiveness of two patient-centered interventions (Patient Voices Video and Stepped Reminders) designed to address barriers and improve annual LCS adherence. MethodsThe Larch Study is a pragmatic randomized clinical trial conducted within Kaiser Permanente Washington. Eligible patients (target n = 1606) are aged 50–78 years with an index low-dose CT (LDCT) of the chest with negative or benign findings. With a 2 × 2 factorial-design, patients are individually randomized to 1 of 4 arms: video only, reminders only, both video and reminders, or usual care. The Patient Voices video addresses patient education needs by normalizing LCS, reminding patients when LCS is due, and encouraging social support. Stepped Reminders prompts primary care physicians to order patient's repeat screening LDCT and patients to schedule their scan. Intervention delivery is embedded within routine healthcare, facilitated by shared electronic health record components. Primary outcome is adherence to national LCS clinical guidelines, defined as repeat LDCT within 9–15 months. Patient-reported outcomes are measured via survey (knowledge of LCS, perception of stigma) approximately 8 weeks after index LDCT. Our mixed-methods formative evaluation includes process data, collected during the trial, and interviews with trial participants and stakeholders. DiscussionResults will fill an important scientific gap on multilevel interventions to increase annual LCS adherence and provide opportunities for spread and scale to other healthcare settings.Registration: Trial is registered at clinicaltrials.gov (#NCT05747443).

Progress in site-specific cancer mortality in Canada over the last 70 years

In Canada, the absolute number of cancer deaths has been steadily increasing, however, age-standardized cancer mortality rates peaked decades ago for most cancers. The objective of this study was to estimate the reduction in deaths for each cancer type under the scenario where peak mortality rates had remained stable in Canada. Data for this study were obtained the Global Cancer Observatory and Statistics Canada. We estimated age-standardized mortality rates (ASMR, per 100,000) from 1950 to 2022, standardized to the 2011 Canadian standard population. We identified peak mortality rates and applied the age-specific mortality rates from the peak year to the age-specific Canadian population estimates for subsequent years (up to 2022) to estimate the number of expected deaths. Avoided cancer deaths were the difference between the observed and expected number of cancer deaths. There have been major reductions in deaths among cancers related to tobacco consumption and other modifiable lifestyle habits (417,561 stomach; 218,244 colorectal; 186,553 lung; 66,281 cervix; 32,732 head and neck; 27,713 bladder; 22,464 leukemia; 20,428 pancreas; 8863 kidney; 3876 esophagus; 290 liver). There have been 201,979 deaths avoided for female-specific cancers (breast, cervix, ovary, uterus). Overall, there has been a 34% reduction in mortality for lung cancer among males and a 9% reduction among females. There has been a significant reduction in cancer mortality in Canada since site-specific cancer mortality rates peaked decades ago for many cancers. This shows the exceptional progress made in cancer control in Canada due to substantial improvements in prevention, screening, and treatment. This study highlights priority areas where more attention and investment are needed to achieve progress.

Efficacy of Definitive Radiotherapy for Patients with Clinical Stage IIIB or IIIC Lung Adenocarcinoma and Epidermal Growth Factor Receptor (EGFR) Mutations Treated Using First- or Second-Generation EGFR Tyrosine Kinase Inhibitors.

The effectiveness of definitive radiotherapy (RT) for patients with clinical stage IIIB or IIIC lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutations who received first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) is unclear. Taiwan Cancer Registry data were used in this retrospective cohort study to identify adult patients diagnosed with EGFR-mutated stage IIIB or IIIC lung adenocarcinoma between 2011 and 2020. Patients treated with first- or second-generation EGFR TKIs were classified into RT and non-RT groups. Propensity score (PS) weighting was applied to balance covariates between groups. The primary outcome was overall survival (OS), and the incidence of lung cancer mortality (ILCM) was considered as a supplementary outcome. Additional supplementary analyses were conducted to assess the robustness of the findings. Among 270 eligible patients, 41 received RT and 229 did not. After a median follow-up of 46 months, PS-weighted analysis showed the PS-weighted hazard ratio of death for the RT group compared to the non-RT group was 0.94 (95% CI: 0.61-1.45, p = 0.78). ILCM rates did not differ significantly between the two groups. Supplementary analyses yielded consistent results. The addition of definitive RT to first- or second-generation EGFR TKI treatment does not significantly improve OS of patients with EGFR-mutated stage IIIB or IIIC lung adenocarcinoma. NCT03521154NCT05167851.

Matairesinoside, a novel inhibitor of TMEM16A ion channel, loaded with functional hydrogel for lung cancer treatment

The incidence and mortality rates of lung cancer have remained high for several decades, necessitating the discovery of new drugs and the development of effective treatment strategies. This study identified matairesinoside (MTS) as a potent inhibitor of TMEM16A, a novel drug target for lung cancer. Molecular simulation combined with site-directed mutagenesis experiments confirmed the key binding sites of MTS and TMEM16A. Cell experiments demonstrated that MTS significantly inhibited the growth, migration, and invasion of lung cancer cells, while inducing apoptosis. Gene knockdown and overexpression studies further revealed that TMEM16A is the target for MTS in regulating lung cancer cell growth. Western blot analysis elucidated the signaling transduction network involved in MTS-mediated regulation of lung cancer. Building upon these findings, a biodegradable self-healing functional hydrogel was developed to load MTS, aiming to enhance therapeutic efficacy and minimize side effects in vivo. Animal experiments demonstrated that the hydrogel/MTS formulation exhibited satisfactory inhibitory effects on lung cancer and mitigated the side effects associated with direct MTS injection. This study identified MTS as a potential candidate for anti-lung cancer therapy with well-defined pharmacological mechanisms. Moreover, the targeted drug delivery system utilizing the hydrogel/MTS platform offers a promising approach for lung cancer treatment.

Assessing the Global Impact of Ambient Air Pollution on Cancer Incidence and Mortality: A Comprehensive Meta-Analysis.

This study aims to examine the association between exposure to major ambient air pollutants and the incidence and mortality of lung cancer and some nonlung cancers. This meta-analysis used PubMed and EMBASE databases to access published studies that met the eligibility criteria. Primary analysis investigated the association between exposure to air pollutants and cancer incidence and mortality. Study quality was assessed using the Newcastle Ottawa Scale. Meta-analysis was conducted using R software. The meta-analysis included 61 studies, of which 53 were cohort studies and eight were case-control studies. Particulate matter 2.5 mm or less in diameter (PM2.5) was the exposure pollutant in half (55.5%), and lung cancer was the most frequently studied cancer in 59% of the studies. A pooled analysis of exposure reported in cohort and case-control studies and cancer incidence demonstrated a significant relationship (relative risk [RR], 1.04 [95% CI, 1.02 to 1.05]; I2, 88.93%; P < .05). A significant association was observed between exposure to pollutants such as PM2.5 (RR, 1.08 [95% CI, 1.04 to 1.12]; I2, 68.52%) and nitrogen dioxide (NO2) (RR, 1.03 [95% CI, 1.01 to 1.05]; I2, 73.52%) and lung cancer incidence. The relationship between exposure to the air pollutants and cancer mortality demonstrated a significant relationship (RR, 1.08 [95% CI, 1.07 to 1.10]; I2, 94.77%; P < .001). Among the four pollutants, PM2.5 (RR, 1.15 [95% CI, 1.08 to 1.22]; I2, 95.33%) and NO2 (RR, 1.05 [95% CI, 1.02 to 1.08]; I2, 89.98%) were associated with lung cancer mortality. The study confirms the association between air pollution exposure and lung cancer incidence and mortality. The meta-analysis results could contribute to community cancer prevention and diagnosis and help inform stakeholders and policymakers in decision making.

Stereotactic body radiation therapy for clinically diagnosed early‐stage non‐small cell lung cancer: Importance of accurate CT interpretation by experts

AbstractIntroductionThis study evaluated the clinical outcomes of stereotactic body radiotherapy (SBRT) for both pathologically diagnosed (PD) and clinically diagnosed (CD) early‐stage non‐small cell lung cancer (NSCLC) and explored the significance of accurate expert computed tomography (CT) interpretation.MethodsWe retrospectively analyzed 95 patients with early‐stage NSCLC who received SBRT at our institution. Patients were classified into CD and PD groups. Two chest radiologists retrospectively interpreted the pre‐SBRT CT images to determine the tumor subtype and probability of malignancy (PM). Clinical findings, CT features, and treatment outcomes were compared between the two groups. The survival rate of the CD group was analyzed separately according to the PM grade.ResultsMedian overall survival for the CD and PD groups was 6.0 and 5.4 years (P = 0.57), respectively. Median cause‐specific survival was 10.2 years in the CD group and not reached in the PD group (P = 0.76). In the CD group, lung cancer mortality was lower in the low PM group (25% [1 of 4]) than in the high PM group (47.4% [9 of 19]).ConclusionIt may be desirable to evaluate the PM of the nodule using expert CT interpretation to decide whether SBRT is indicated in CD early‐stage NSCLC.

Increasing Uptake of Lung Cancer Screening Among Emergency Department Patients: A Pilot Study

BackgroundLung cancer is the leading cause of cancer death in the United States. Lung cancer screening (LCS) decreases lung cancer mortality. Emergency department (ED) patients are at disproportionately high risk for lung cancer. The ED, therefore, is an optimal environment for interventions to promote LCS. ObjectivesDemonstrate the operational feasibility of identifying ED patients in need of LCS, referring them to LCS services, deploying a text message intervention to promote LCS, and conducting follow-up to determine LCS uptake. MethodsWe conducted a randomized clinical trial to determine the feasibility and provide estimates of the preliminary efficacies of 1) basic referral for LCS and 2) basic referral plus a text messaging intervention, grounded in behavioral change theory, to promote uptake of LCS among ED patients. Participants aged 50 to 80, identified as eligible for LCS, were randomized to study arms and followed up at 150 days to assess interval LCS uptake (primary outcome), barriers to screening, and perceptions of the study interventions. ResultsA total of 303 patients were surveyed, with 198 identified as eligible for LCS and subsequently randomized. Results indicated that 24% of participants with follow-up data received LCS (11% of the total randomized sample). Rates of screening at follow-up were similar across study arms. The intervention significantly improved normative perceptions of LCS (p = 0.015; Cohen's d = 0.45). ConclusionThis pilot study demonstrates the feasibility of ED-based interventions to increase uptake of LCS among ED patients. A scalable ED-based intervention that increases LCS uptake could reduce lung cancer mortality.

182P Evolution of lung cancer mortality in Spain: 1980-2022, a joinpoint analysis

182P Evolution of lung cancer mortality in Spain: 1980-2022, a joinpoint analysis

A study on indoor air pollution and its impact on health in urban field practice area: a community-based study

Background: As per the 2022 World Air Quality Report, India holds the eighth position globally for air pollution, with Karnataka in South India experiencing notably poor air quality, leading to 95 deaths per 100,000 population annually. Indoor air pollution poses substantial health risks, contributing to conditions such as pneumonia, stroke, diabetes, lung cancer, and premature mortality. Methods: This study, conducted from April to July 2023 in the urban area of UHTC, Chandabowdi, aimed to assess indoor air pollution's impact. Using simple and systematic random sampling, 128 household members were surveyed through in-person interviews with ethical clearance. Results: Of 128 participants, 44% reported respiratory symptoms, and 94% practiced unsanitary waste disposal. Ventilation issues affected 32.8%, while 75.8% reported neighborhood pollution. LPG was the primary fuel source for 97.7% of households, indicating significant environmental and health concerns. Conclusions: Urgent action is needed to address indoor air pollution's health impacts. Clean technologies, improved building design, and lifestyle changes are essential to mitigate risks. Continuous monitoring and collective efforts are necessary for a healthier and sustainable future.

Ultra-processed food consumption and risk of chronic respiratory diseases mortality among adults: evidence from a prospective cohort study

PurposeThe purpose of the study was to determine the relationships between ultra-processed food (UPF) consumption and risk of mortality due to chronic respiratory diseases (CRDs) overall, chronic obstructive pulmonary disease (COPD), and lung cancer.MethodsA total of 96,607 participants aged 55 years and over were included from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer trial. Dietary intake was measured using food frequency questionnaire. Cox regression was fitted to estimate the risk of all-cause mortality and mortality due to CRDs overall, COPD and lung cancer associated with UPF intake. Competing risk regression was used to account for deaths from other causes and censoring.ResultsDuring the follow-up of 1,379,655.5 person-years (median 16.8 years), 28,700 all-cause, 4092 CRDs, 2015 lung cancer and 1,536 COPD mortality occurred. A higher intake of UPF increased the risk of mortality from CRDs overall by 10% (HR 1.10; 95% CI 1.01, 1.22) and COPD by 26% (HR 1.26; 95% CI 1.06, 1.49) but not associated with lung cancer mortality risk (HR 0.97; 95% CI 0.84, 1.12). However, the risk of lung cancer increased by 16% (HR 1.16; 95% CI 1.01, 1.34) in the highest UPF intake after multiple imputation. Dose–response relationships existed for CRDs and COPD mortality but not lung cancer.ConclusionUPF consumption was associated with an increased risk of CRD mortality. The association between UPF consumption and lung cancer mortality is inconclusive and only significant when multiple imputation was applied.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.

Fine-particulate air pollution and behaviorally inclusive mortality impacts of China’s winter heating policy, 2013–2018

China’s spatially discontinuous winter heating policy has been used to examine how sustained exposure to air pollution impacts health. This influential literature exploits quasi-experimental cross-sectional variation in atmospheric emissions in a geographically vast and populous nation. Our study introduces an alternative external definition of the winter heating boundary and takes advantage of an unprecedented expansion of pollution and mortality surveillance, covering at least 10 times more sites and finer-grained pollution particle sizes that are more relevant to health standards today. We estimate spatial discontinuities in pollution and mortality that shrink over time, consistent with tighter emissions regulations, higher quality medical care, and increased air quality disclosure to – and defensive behavior by – the public. We find that in 2013–2015 a 10-μg/m3 increase in PM2.5 raised behaviorally inclusive mortality for cardiovascular and respiratory causes by 11% (95% confidence interval = 2–20%) and lung cancer mortality by 20% (95% CI = 4–37%).

PDGFRβ-Antagonistic Affibody-Mediated Tumor-Targeted Tumor Necrosis Factor-Alpha for Enhanced Radiotherapy in Lung Cancer.

The morbidity and mortality of lung cancer are still the highest among all malignant tumors. Radiotherapy plays an important role in clinical treatment of lung cancer. However, the effect of radiotherapy is not ideal due to the radiation resistance of tumor tissues. Abnormalities in tumor vascular structure and function affect blood perfusion, and oxygen transport is impeded, making tumor microenvironment hypoxic. Tumor hypoxia is the major cause of radiotherapy resistance. By promoting tumor vessel normalization and enhancing vascular transport function, tumor hypoxia can be relieved to reduce radiotherapy resistance and increase tumor radiotherapy sensitivity. In our previous study, a pericytes-targeted tumor necrosis factor alpha (named Z-TNFα) was first constructed and produced by genetically fusing the platelet-derived growth factor receptor β (PDGFRβ)-antagonistic affibody (ZPDGFRβ) to the TNFα, and the Z-TNFα induced normalization of tumor vessels and improved the delivery of doxorubicin, enhancing tumor chemotherapy. In this study, the tumor vessel normalization effect of Z-TNFα in lung cancer was further clarified. Moreover, the tumor hypoxia improvement and radiosensitizing effect of Z-TNFα were emphatically explored in vivo. Inspiringly, Z-TNFα specifically accumulated in Lewis lung carcinoma (LLC) tumor graft and relieved tumor hypoxia as well as inhibited HIF-1α expression. As expected, Z-TNFα significantly increased the effect of radiotherapy in mice bearing LLC tumor graft. In conclusion, these results demonstrated that Z-TNFα is also a promising radiosensitizer for lung cancer radiotherapy.

RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation.

Metastasis is the leading cause for the high mortality of lung cancer, however, effective anti-metastatic drugs are still limited. Here it is reported that the RNA-binding protein RBMS1 is positively associated with increased lymph node metastasis in non-small cell lung cancer (NSCLC). Depletion of RBMS1 suppresses cancer cell migration and invasion in vitro and inhibits cancer cell metastasis in vivo. Mechanistically, RBMS1 interacts with YTHDF1 to promote the translation of S100P, thereby accelerating NSCLC cell metastasis. The RRM2 motif of RBMS1 and the YTH domain of YTHDF1 are required for the binding of RBMS1 and YTHDF1. RBMS1 ablation inhibits the translation of S100P and suppresses tumor metastasis. Targeting RBMS1 with NTP, a small molecular chemical inhibitor of RBMS1, attenuates tumor metastasis in a mouse lung metastasis model. Correlation studies in lung cancer patients further validate the clinical relevance of the findings. Collectively, the study provides insight into the molecular mechanism by which RBMS1 promotes NSCLC metastasis and offers a therapeutic strategy for metastatic NSCLC.

Benzene Exposure and Lung Cancer Risk: A Systematic Review and Meta-Analysis of Human Studies.

Lung cancer is a leading cause of death with nearly 1.8 million deaths estimated worldwide in 2020. Although benzene is classified as a human carcinogen (Group 1) on the basis of its association with acute myeloid/non-lymphocytic leukaemia, there is still limited evidence that it may influence lung cancer risk. This study examined the potential link between benzene exposure and risk of lung cancer using a systematic review of epidemiological studies and meta-analysis. We searched through PubMed, Web of Science and Scopus databases up to 10 February 2023 to identify all articles on the association between benzene exposure and lung cancer (incidence or prevalence) and/or mortality. We extracted the risk estimates of the highest and the lowest reported categories of benzene exposure and conducted a meta-analysis using a random-effects model. Heterogeneity and publication bias were analysed using an I2 test and funnel plots asymmetry, respectively. Twenty-one studies were included in the final analysis, with a total of 10,750 lung cancer cases and 2899 lung cancer deaths. Overall, risk estimates of lung cancer prevalence and mortality in association with benzene exposure were 1.20 (n = 14; 95% CI 1.05-1.37) and 1.15 (n = 13; 95% CI 1.02-1.30), respectively. In all cases, heterogeneity was quite large, while no significant publication bias was observed. When only studies that adjusted for smoking habit were selected, the risk for lung cancer increased by up to 34% (n = 9; 95% CI 1.10-1.64). Our data, which show a strong association between benzene exposure and lung cancer risk, may have important public health implications. However, further studies are needed to identify the lung cancer risk associated with benzene exposure considering different smoking conditions.

A Comprehensive Analysis of Risk Assessment of Particulate Matter in Five Health Centers in Akure, Nigeria

This study presents a comprehensive assessment of indoor particulate matter (PM) concentrations, focusing on PM1, PM2.5, and PM10 in five primary health centers (PHCs): Arakale (Urban), the Federal College of Agriculture (FECA) (Urban), Iju (semi-urban), Oba-Ile (semi-urban), and Owode (Rural) within Akure local government areas in Nigeria. The primary novelty of this research lies in its detailed exploration of the toxicity potential of these PM fractions, providing valuable insights into the local air quality and associated health risks. This study assesses the health implications by calculating the toxicity potential (TP), relative risk (RR), excess risk (ER), and attributable fractions (Afs) for cardiopulmonary and lung cancer mortality. The results reveal varying RR values for all-cause mortality, with Arakale showing a slight elevation (RR: 1.061), indicating potential health risks. ER values for cardiopulmonary mortality range from 14.728 ± 7.25 to 19.04 ± 0.38, emphasizing the substantial excess risk associated with long-term PM2.5 exposure. The study also uncovers Afs for cardiopulmonary mortality ranging between 11.03 ± 0.31 and 19.22 ± 0.04, underscoring the significant contribution of PM to cardiovascular and respiratory health risks. Similarly, Afs for lung cancer mortality range from 10.03 ± 0.012 to 17.13 ± 0.10, highlighting the substantial association between PM2.5 exposure and lung cancer risk. These findings underscore the urgent need for targeted air quality management strategies and public health interventions in the studied locations to mitigate the heightened health risks associated with particulate matter pollution. The calculated RR, ER, and AF values offer crucial insights into the complex relationship between PM exposure and adverse health outcomes, providing a foundation for informed decision-making and future research endeavors.