Search Results (10,443)

Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), glycerol-developed vesicles, as innovative nanovesicles for successful ITZ pulmonary drug delivery. Methods: The glycerosomes were functionalized with hyaluronic acid (HA-GLY) to potentiate the anticancer efficacy of ITZ and extend its local bio-fate. ITZ-HA-GLY were fabricated using soybean phosphatidylcholine, tween 80, HA, and sonication time via a thin-film hydration approach according to a 24 full factorial design. The impact of formulation parameters on ITZ-HA-GLY physicochemical properties, as well as the optimal formulation option, was evaluated using Design-Expert^®. Sulphorhodamine-B (SRB) colorimetric cytotoxicity assay of the optimized ITZ-HA-GLY versus ITZ suspension was explored in the human A549 cell line. The in vivo pharmacokinetics and bio-distribution examined subsequent to intratracheal administrations of ITZ suspension, and ITZ-HA-GLY were scrutinized in rats. Results: The optimized ITZ-HA-GLY unveiled vesicles of size 210.23 ± 6.43 nm, zeta potential of 41.06 ± 2.62 mV, and entrapment efficiency of 73.65 ± 1.76%. Additionally, ITZ-HA-GLY manifested a far lower IC50 of 13.03 ± 0.2 µg/mL on the A549 cell line than that of ITZ suspension (28.14 ± 1.6 µg/mL). Additionally, the biodistribution analysis revealed a higher concentration of ITZ-HA-GLY within the lung tissues by 3.64-fold as compared to ITZ suspension. Furthermore, the mean resistance time of ITZ-HA-GLY declined more slowly with 14 h as compared to ITZ suspension, confirming the accumulation of ITZ inside the lungs and their promising usage as a target for the treatment of lung disease. Conclusions: These data indicate that the improved ITZ-HA-GLY demonstrates significant promise and represents an exciting prospect in intratracheal delivery systems for lung cancer treatment, meriting further investigation. Full article

Despite its potential against several carcinomas, the pharmacological efficacy of silibinin (SLB) is hampered by poor solubility, absorption, and oral bioavailability. To face these issues, we developed polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) coated with hydrophilic polyethene oxide (PEO) for controlled and targeted SLB delivery. NPs were produced at two different SLB loadings and presented a spherical shape with smooth surfaces and stable size in water and cell culture medium. The encapsulation efficiencies were found to be >84%, and thermal analysis revealed that the SLB was present in an amorphous state within the NPs. In vitro SLB release experiments revealed that at the lowest SLB loading, desorption of the active molecule from the surface or nanoporosities of the NPs mainly dictates release. In contrast, at the highest SLB loading, diffusion primarily regulates release, with negligible contributions from other mechanisms. Cell experiments showed that, compared with the free drug, SLB loaded in the produced NPs significantly increased the bioactivity against H1299, H1975, and H358 cells. Full article

Lung cancer, both non-small cell and small cell, harbors a high propensity for spreading to the central nervous system. Radiation therapy remains the backbone of the management of brain metastases. Recent advances in stereotactic radiosurgery have expanded its indications and ongoing studies seek to elucidate optimal fractionation and coordination with systemic therapies, especially targeted inhibitors with intracranial efficacy. Efforts in whole-brain radiotherapy aim to preserve neurocognition and to investigate the need for prophylactic cranial irradiation. As novel combinatorial strategies are tested and prognostic/predictive biomarkers are identified and tested, the management of brain metastases in lung cancer will become increasingly personalized to optimally balance intracranial efficacy with preserving neurocognitive function and patient values. Full article

Thoracic surgery is deeply intertwined with the principles of physics, which govern the tools and techniques used in various procedures. A thorough understanding of these principles is essential for the safe and effective use of surgical technology, advancing surgical techniques, and developing new medical devices. This manuscript provides a comprehensive overview of crucial physical principles relevant to thoracic surgery, such as radiosterilization, electrosurgery, fluid dynamics, endoscopic techniques, diffusion principles, and laser technologies. This manuscript aims to enhance thoracic surgeons’ understanding of how physics underpins their practice by elucidating the connections between these principles and their medical applications. This multidisciplinary approach seeks to improve surgical outcomes by fostering a deeper appreciation of the fundamental science behind thoracic surgery, thereby encouraging innovation and the safe, effective use of advanced surgical technologies. Full article

Background: Pancreatic cancer is among the malignancies with the poorest prognosis, largely due to its aggressive nature and resistance to conventional therapies. Case Summary: This report describes the case of a 69-year-old male patient with stage IV primary lung adenocarcinoma presenting with high levels of programmed death-ligand 1 (PD-L1). Simultaneously, abdominal computed tomography (CT) showed a dilated pancreatic duct at the level of the pancreatic head and a hypodense lesion in the uncinate process involving the superior mesenteric artery. Fine-needle aspiration (FNA) of the pancreatic lesions was negative. After three cycles of chemoimmunotherapy, positron emission tomography–computed tomography (PET-CT) showed complete remission of the lung nodules, lymphadenopathy, and pleural thickening, as well as a decrease in the size of the pancreatic lesion. After another six months, a PET-CT scan showed a focal increased uptake in the pancreatic mass in the same location, indicating disease progression. A core biopsy of the pancreatic tumor showed atypical spindle cell morphology with positive staining for vimentin, characteristic of mesenchymal differentiation with no apparent epithelial features. Comprehensive molecular profiling through Caris Molecular Intelligence^® revealed four genes with actionable mutations in the pancreatic tissue, including KRAS (p.G12D) and TP53 (p.R175H). These molecular findings suggested the diagnoses of sarcomatoid carcinoma and conventional pancreatic ductal adenocarcinoma with epithelial–mesenchymal transition. Primary mesenchymal tumors and neuroendocrine neoplasms were excluded because immunohistochemistry was negative for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA), desmin, CD34, signal transducer and activator of transcription 6 (STAT6), S100, HMB45, CD117, discovered on GIST-1 (DOG1), CD56, progesterone, and synaptophysin. However, despite multiple rounds of systemic chemotherapy, immunotherapy, and radiation, his pancreatic disease rapidly deteriorated and metastasized to the liver and bone. Conclusions: Despite multiple lines of treatment, the patient’s condition worsened and he succumbed to his pancreatic malignancy. This study highlights the clinical characteristics, diagnosis, and treatment of rare pancreatic cancer, emphasizing the importance of molecular testing and histopathological biomarkers in personalizing treatment. It also provides insights into promising therapeutic approaches for similar cases with an unusual presentation. Full article

Background: Recent advances in the personalized treatment of non-small cell lung cancer (NSCLC) require representative in vitro model systems that reflect tumor heterogeneity and maintain the characteristic genetic aberrations. We therefore aimed to establish patient-derived NSCLC organoids that offer a reliable platform for further investigations. Methods: NSCLC organoids were cultured between May 2020 and February 2022 from surgically resected NSCLC tissue specimens. After histological and immunohistochemical validation, genetic validation was performed by targeted next-generation sequencing of tissue and organoid specimens using the Oncomine Focus Assay (ThermoFisher Scientific). Results: From 37 resected NSCLC samples, 18 primary organoid cultures were successfully established and expanded during early passages. Upon histomorphological validation, organoids showed complementary characteristics when compared to the resected parental tumor, including adenocarcinoma, squamous cell carcinoma, mucoepidermoid carcinoma, and lung carcinoid differentiation. Among nine parental tumors, traceable genetic alterations were detected, and three corresponding organoids lines retained this mutational profile, including a KRAS p.Gly12Val mutation, KRAS p.Gly12Cys mutation, and RET-fusion. Conclusions: The establishment of primary NSCLC organoids from surgically resected tissue is feasible. Histological, immunohistochemical, and genetic validation is essential to identify representative NSCLC organoids that maintain the characteristics of the parental tumor. Overall, low establishment rates remain a challenge for broad clinical applications. Full article

Background and Objectives: The burdened symptomatology accompanying advanced non-small-cell lung cancer (NSCLC) is associated with poor prognosis and lower quality of life (QoL). Although both chemotherapy and immunotherapy increase survival, they are still associated with reduced functionality due to their toxicity. This study aimed to estimate the QoL and symptom burden of NSCLC patients receiving second-line chemotherapy compared to patients receiving second-line immunotherapy. Materials and Methods: This comparative, prospective study, conducted from January 2020 to December 2021, included 111 NSCLC patients who were divided into two groups: 61 patients receiving second-line chemotherapy and 50 patients receiving second-line immunotherapy. Patients’ QoL and symptom burden were estimated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) (value range 0–100) from treatment cycle 1 to 6. Results: The QoL (mean score > 50) and functionality dimensions (mean score > 50) were moderate to good in both treatment groups, while the symptom burden did not appear to be a serious problem (mean score < 50). From cycle 3 to cycle 5, QoL was significantly better in the immunotherapy group. From cycle 3, the role and social functioning scores were higher in the immunotherapy group, while emotional and cognitive functioning were higher from cycle 2 (p <0.05). The chemotherapy group experienced higher levels of nausea/vomiting, constipation and financial difficulties in all the cycles (p < 0.05). Fatigue and appetite loss were significantly greater from cycle 2 and insomnia was significantly greater from cycle 3. On the contrary, the immunotherapy group experienced higher levels of diarrhea in cycles 5 and 6 (p < 0.05). Conclusions: Although both therapy groups did not report significantly impaired QoL and severe symptoms, it seems that QoL improved in the immunotherapy group, which reported a lower symptom burden compared to the chemotherapy group. Full article

Therapeutic strategies for early-stage non-small cell lung cancer (NSCLC) are advancing, with immune checkpoint inhibitors (ICIs) and targeted therapies making their way into neoadjuvant and adjuvant settings. With recent advances, there was a need for multidisciplinary lung cancer healthcare providers from across Ontario to convene and review recent data from practical and implementation standpoints. The focus was on the following questions: (1) To what extent do patient (e.g., history of smoking) and disease (e.g., histology, tumor burden, nodal involvement) characteristics influence treatment approaches? (2) What are the surgical considerations in early-stage NSCLC? (3) What is the role of radiation therapy in the context of recent evidence? (4) What is the impact of biomarker testing on treatment planning? Ongoing challenges, treatment gaps, outstanding questions, and controversies with the data were assessed through a pre-meeting survey, interactive cases, and polling questions. By reviewing practice patterns across Ontario cancer centers in the context of evolving clinical data, Health Canada indications, and provincial (Cancer Care Ontario [CCO]) funding approvals, physicians treating lung cancer voiced their opinions on how new approaches should be integrated into provincial treatment algorithms. This report summarizes the forum outcomes, including pre-meeting survey and polling question results, as well as agreements on treatment approaches based on specific patient scenarios. Full article

Asbestos is a naturally occurring mineral renowned for its exceptional tensile strength, chemical resistance, and low thermal and electrical conductivity. Due to these properties, it has been widely used in various industries. However, asbestos exposure is strongly linked to severe health conditions, including lung cancer, mesothelioma, and asbestosis. Although over 70 countries have banned asbestos-containing materials, significant health risks persist due to ongoing use and poor management practices in many regions. To mitigate these risks, robust occupational health measures are essential. These include safe removal protocols, comprehensive worker training, proper use of personal protective equipment (PPE), regular exposure monitoring, rigorous compliance checks, and severe penalties for non-compliance. Moreover, effective asbestos waste management and the development of advanced disposal technologies are essential to reducing risks. Public awareness campaigns, regulatory enforcement, and a global ban on asbestos production, use, and export are also necessary, particularly in countries where asbestos is still in use. Lessons from asbestos management in Australia and New Zealand provide valuable insights for nations currently dealing with asbestos issues. This paper reviews current practices in asbestos surveying, removal, and disposal, comparing them to the stringent regulatory frameworks in Australia and New Zealand. It highlights strategies that can be adopted globally to ensure safer management and complete elimination of asbestos. Full article

Background/Objectives: Despite recent advances in research, cancer remains a significant public health concern and a leading cause of death. Among all cancer types, lung cancer is the most common cause of cancer-related deaths, with most cases linked to non-small cell lung cancer (NSCLC). Accurate classification of NSCLC subtypes is essential for developing treatment strategies. Medical professionals regard tissue biopsy as the gold standard for the identification of lung cancer subtypes. However, since biopsy images have very high resolutions, manual examination is time-consuming and depends on the pathologist’s expertise. Methods: In this study, we propose a hybrid model to assist pathologists in the classification of NSCLC subtypes from histopathological images. This model processes deep, textural and contextual features obtained by using EfficientNet-B0, local binary pattern (LBP) and vision transformer (ViT) encoder as feature extractors, respectively. In the proposed method, each feature matrix is flattened separately and then combined to form a comprehensive feature vector. The feature vector is given as input to machine learning classifiers to identify the NSCLC subtype. Results: We set up 13 different training scenarios to test 4 different classifiers: support vector machine (SVM), logistic regression (LR), light gradient boosting machine (LightGBM) and extreme gradient boosting (XGBoost). Among these scenarios, we obtained the highest classification accuracy (99.87%) with the combination of EfficientNet-B0 + LBP + ViT Encoder + SVM. The proposed hybrid model significantly enhanced the classification accuracy of NSCLC subtypes. Conclusions: The integration of deep, textural, and contextual features assisted the model in capturing subtle information from the images, thereby reducing the risk of misdiagnosis and facilitating more effective treatment planning. Full article

Lung cancer, the leading cause of cancer-related deaths globally, presents significant challenges in early detection and diagnosis. The effective analysis of pulmonary medical imaging, particularly computed tomography (CT) scans, is critical in this endeavor. Traditional diagnostic methods, which are manual and time-intensive, underscore the need for innovative, efficient, and accurate detection approaches. To address this need, we introduce the Adaptive Range Slice Grouping Network (ARSGNet), a novel deep learning framework that enhances early lung cancer diagnosis through advanced segmentation and classification techniques in CT imaging. ARSGNet synergistically integrates the strengths of EfficientNet and Transformer architectures, leveraging their superior feature extraction and contextual processing capabilities. This hybrid model proficiently handles the complexities of 3D CT images, ensuring precise and reliable lung nodule detection. The algorithm processes CT scans using short slice grouping (SSG) and long slice grouping (LSG) techniques to extract critical features from each slice, culminating in the generation of nodule probabilities and the identification of potential nodular regions. Incorporating shapley additive explanations (SHAP) analysis further enhances model interpretability by highlighting the contributory features. Our extensive experimentation demonstrated a significant improvement in diagnostic accuracy, with training accuracy increasing from 0.9126 to 0.9817. This advancement not only reflects the model’s efficient learning curve but also its high proficiency in accurately classifying a majority of training samples. Given its high accuracy, interpretability, and consistent reduction in training loss, ARSGNet holds substantial potential as a groundbreaking tool for early lung cancer detection and diagnosis. Full article

Lung cancer remains a leading cause of cancer-related mortality worldwide. Although surgical treatment is a primary approach, residual cancer cells and surgery-induced pathophysiological changes may promote cancer recurrence and metastasis. Anesthetic agents and techniques have recently been shown to potentially impact these processes by modulating surgical stress responses, immune function, inflammatory pathways, and the tumor microenvironment. Anesthetics can influence immune-modulating cytokines, induce pro-inflammatory factors such as HIF-1α, and alter natural-killer cell activity, affecting cancer cell survival and spread. Preclinical studies suggest volatile anesthetics may promote tumor progression by triggering pro-inflammatory signaling, while propofol shows potential antitumor properties through immune-preserving effects and reductions in IL-6 and other inflammatory markers. Additionally, opioids are known to suppress immune responses and stimulate pathways that may support cancer cell proliferation, whereas regional anesthesia may reduce these risks by decreasing the need for systemic opioids and volatile agents. Despite these findings, clinical data remain inconclusive, with studies showing mixed outcomes across patient populations. Current clinical trials, including comparisons of volatile agents with propofol-based total intravenous anesthesia, aim to provide clarity but highlight the need for further investigation. Large-scale, well-designed studies are essential to validate the true impact of anesthetic choice on cancer recurrence and to optimize perioperative strategies that support long-term oncologic outcomes for lung cancer patients. Full article

Lung cancer is the leading cause of cancer-related mortality worldwide, primarily driven by genetic mutations. The most common genetic alterations implicated in lung cancer include mutations in TP53, KRAS, KEAP1, NF1, EGFR, NRF2, ATM, ALK, Rb1, BRAF, MET, and ERBB2. Targeted therapies have been developed to inhibit cancer growth by focusing on these specific genetic mutations. However, either the mutations are undruggable or the efficacy of these therapies is often compromised over time due to the emergence of drug resistance, which can occur through additional mutations in the targeted protein or alternative growth signaling pathways. In recent years, immunotherapy has emerged as a promising approach to enhance the effectiveness of cancer treatment by leveraging the body’s immune system. Notable advancements include immune checkpoint inhibitors, monoclonal antibodies targeting cell surface receptors, antibody–drug conjugates, and bispecific antibodies. This review provides an overview of the mechanisms of FDA-approved immunotherapeutic drugs, offering an updated perspective on the current state and future developments in lung cancer therapy. More importantly, the factors that positively and negatively impact the immunotherapy’s efficacy will also be discussed. Full article

Cinobufagin (CB), a bufadienolide, has shown promising potential as an anticancer agent, particularly in combating lung cancer. This systematic review synthesizes preclinical evidence on CB’s effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. We analyzed data from various preclinical studies involving both in vitro cell line models and in vivo animal models. The reviewed studies indicate that CB effectively reduces cell viability, induces apoptosis, and inhibits cell proliferation, migration, and invasion across multiple lung cancer cell lines and xenograft models. Specifically, CB was found to decrease cell viability and increase apoptosis in lung cancer cells by modulating key molecular pathways, including Bcl-2, Bax, cleaved caspases, caveolin-1, FLOT2, Akt, STAT3, and FOXO1. In vivo studies further demonstrated significant inhibition of tumor growth with minimal toxicity. However, limitations include reliance on in vitro models, which may not fully represent in vivo tumor dynamics, and a lack of long-term safety data. The studies also vary in their methodologies and cell line models, which may not accurately encompass all lung cancer subtypes or predict human responses. Despite these limitations, CB’s ability to target specific molecular pathways and its promising results in preclinical models suggest it could be a valuable addition to lung cancer treatment strategies. Our review suggests further clinical trials to validate its efficacy and safety in humans. Future research should explore combination therapies and optimize delivery methods to enhance clinical outcomes. Full article

Introduction: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, despite advances in immune checkpoint inhibitors and targeted therapies. Antibody–drug conjugates (ADCs) represent a promising therapeutic approach by delivering cytotoxic agents specifically to cancer cells, potentially reducing harm to healthy tissues. This study aims to explore the effectiveness and challenges associated with ADCs in NSCLC, with a focus on drug-induced interstitial lung disease (D-ILD). Methods: A comprehensive literature review was conducted across MEDLINE (Ovid), Embase (Elsevier), CENTRAL (Cochrane Library), and other sources up to March 2023, to identify ADCs used in NSCLC treatment and their associated risk of D-ILD. The incidence of ILD was analyzed from clinical trial data, while ADC target expression was examined through RNA and protein levels in normal and tumor lung tissues. Discussion: Our findings highlight the therapeutic potential of ADCs in NSCLC, as evidenced by significant clinical outcomes. However, the occurrence of D-ILD presents a notable challenge, as its incidence was not directly correlated with the expression levels of the target antigens. This suggests that D-ILD may result from factors beyond antigen expression, including the cytotoxic payload and linker characteristics of ADCs. Conclusion: ADCs offer a promising avenue for NSCLC treatment. Nonetheless, the risk of D-ILD necessitates a balanced approach in ADC development, focusing on optimizing linker and payload properties to mitigate this adverse effect. Further research is essential to better understand and manage D-ILD, ensuring the safe and effective use of ADCs in clinical practice. Full article