Non-small Cell Lung Carcinoma Research Articles

Spatial proteomic profiling of tumor and stromal compartments in non-small-cell lung cancer identifies signatures associated with overall survival.

Non-small-cell lung carcinoma (NSCLC) is the most prevalent and lethal form of lung cancer. The need for biomarker-informed stratification of targeted therapies has underpinned the need to uncover the underlying properties of the tumor microenvironment (TME) through high-plex quantitative assays. In this study, we profiled resected NSCLC tissues from 102 patients by targeted spatial proteomics of 78 proteins across tumor, immune activation, immune cell typing, immune-oncology, drug targets, cell death and PI3K/AKT modules to identify the tumor and stromal signatures associated with overall survival (OS). Survival analysis revealed that stromal CD56 (HR = 0.384, P = 0.06) and tumoral TIM3 (HR = 0.703, P = 0.05) were associated with better survival in univariate Cox models. In contrast, after adjusting for stage, BCLXL (HR = 2.093, P = 0.02) and cleaved caspase 9 (HR = 1.575, P = 0.1) negatively influenced survival. Delta testing indicated the protective effect of TIM-3 (HR = 0.614, P = 0.04) on OS. In multivariate analysis, CD56 (HR = 0.172, P = 0.001) was associated with better survival in the stroma, while B7.H3 (HR = 1.72, P = 0.008) was linked to poorer survival in the tumor. Deciphering the TME using high-plex spatially resolved methods is giving us new insights into compartmentalised tumor and stromal protein signatures associated with clinical endpoints in NSCLC.

Deciphering fibroblast-induced drug resistance in non-small cell lung carcinoma through patient-derived organoids in agarose microwells.

Patient-derived organoids (PDOs) serve as invaluable 3D tumor models, retaining the histological complexity and genetic heterogeneity found in primary tumors. However, the limitation of small sample volumes and the lack of tailored platforms have hindered the research using PDOs. Within the tumor microenvironment, cancer-associated fibroblasts play a pivotal role in influencing drug sensitivity. In this study, we introduce an agarose microwell platform designed for PDO-based tumor and tumor microenvironment models, enabling rapid drug screening and resistance studies with small sample volumes. These microwells, constructed using 3D printing molds, feature a U-shaped bottom and 200 μm diameter. We successfully generated co-culture spheroids of non-small cell lung carcinoma (NSCLC) cells, including NCI-H358 or A549, and NSCLC PDOs F231 or F671 with fibroblast cell line, WI-38. Our results demonstrate the production of uniformly-sized spheroids (coefficient of variation <30%), high viability (>80% after 1 week), and fibroblast-induced drug resistance. The PDOs maintained their viability (>81% after 2 weeks) and continued to proliferate. Notably, when exposed to adagrasib, a KRASG12C inhibitor, we observed reduced cytotoxicity in KRASG12C-mutant spheroids when co-cultured with fibroblasts or their supernatant. The fibroblast supernatant sustained proliferative signals in tumor models. Taking into account the physical features, viability, and drug resistance acquired through supernatants from the fibroblasts, our platform emerges as a suitable platform for in vitro tumor modeling and the evaluation of drug efficacy using patient-derived tissues.

AZIN1-centric dynamic network biomarker of tipping point in non-small cell lung cancer metastasis

Detection of the tipping point of metastasis of non-small cell lung carcinoma is crucial so that it does not lead to irreversible damage. In contrast to the single biomarker approach, identification of dynamic network biomarkers (DNB) which represent the dynamic change in the expression during disease progression is being increasingly used to study of tipping point in different cancers. In our study, stage-wise gene expression data from a lung cancer database with in silico dynamic network method revealed AZIN1 centric network of seven dynamically interacting genes (AZIN1, PGAM1, CNOT9, HMGCR, EIF3H, DNTTIP1, and ST7). These are involved in purine ribonucleoside monophosphate and purine ribonucleoside triphosphate metabolic pathways. Drastic changes in their gene expressions were observed at 2A and 2B transition stage indicating it to be a tipping point for metastasis. Further, in vitro gene expression studies in NCI-460 cells confirmed the interaction of networking genes. Silencing AZIN1 expression diminished DNTTIP1 and PGAM1 expression almost completely while significantly affecting other genes; further confirming a novel interaction of these genes in non-small cell lung carcinoma (NSCLC). Therefore, AZIN1 centric network of seven genes could serve as an important predictive DNB for the tipping point before NSCLC metastasis.

The influence of magnesium and manganese cations on the chemical and bioactive properties of purple and green basil.

This research investigated the effects of hydroponic cultivation with enriched concentrations of magnesium (+Mg), manganese (+Mn), a combination of +Mg and +Mn, or decreased concentrations of these minerals (control) on the nutritional, chemical, and bioactive attributes of purple and green basil. While Mn significantly increased the growth of purple basil and affected the composition of essential oil and mineral accumulation, plants treated with Mg showed alterations in nutrient absorption. Protein values were lower, indicating suboptimal protein synthesis, but significant increases were observed in fat, ash, and carbohydrates, suggesting a more nutrient-rich composition due to hydroponic cultivation. Regarding phenolic compounds, green basil showed higher concentrations of rosmarinic acid with +Mg+Mn, while purple basil exhibited lower levels with the addition of +Mn or +Mg+Mn. Antioxidant activities mirrored the phenolic profile, with purple basil displaying superior performance in the thiobarbituric acid-reactive substance (TBARS) test with +Mg treatment, and green basil showing higher activity in the cell antioxidant activity (CAA) test with the +Mg+Mn combination. In microbiological analyses, purple basil was more effective against S. aureus, while green basil performed better against L. monocytogenes. Although none were bactericidal, all treatments showed potential as antimicrobials. Purple basil extracts had significant antiproliferative effects on tumor cell lines, especially non-small cell lung carcinoma (NCI-H460), with synergistic effects observed in gastric adenocarcinoma (AGS) with +Mg+Mn. Additionally, +Mg+Mn demonstrated unique efficacy against colorectal adenocarcinoma (CaCo2) and breast carcinoma (MFC-7 cells), without toxicity to non-tumor a renal epithelial cell line from an African green monkey (VERO) cell, emphasizing the safety of the extracts. Green basil extracts showed no activity against the tumor cell lines analyzed (AGS, Caco2, MFC-7 and NCI-H460); however, they revealed remarkable antiproliferative effects against NCI-H460 cells in the control group. The results are important because they show how mineral treatments, such as the use of magnesium and manganese, influence the nutritional and medicinal properties of purple and green basil leaves. This highlights the relevance of manipulating nutrient solutions to improve plant quality, which is crucial for the production of functional foods and dietary supplements.

Prognostic significance of alpha-2-macrglobulin and low-density lipoprotein receptor-related protein-1 in various cancers.

Cancer is the leading cause of death worldwide. The World Health Organization (WHO) estimates that 10 million fatalities occurred in 2023. Breast cancer (BC) ranked first among malignancies with 2.26 million cases, lung cancer (LC) second with 2.21 million cases, and colon and rectum cancers (CC, CRC) third with 1.93 million cases. These results highlight the importance of investigating novel cancer prognoses and anti-cancer markers. In this study, we investigated the potential effects of alpha-2 macroglobulin and its receptor, LRP1, on the outcomes of breast, lung, and colorectal malignancies. Immunohistochemical staining was used to analyze the expression patterns of A2M and LRP1 in 545 cases of invasive ductal breast carcinoma (IDC) and 51 cases of mastopathies/fibrocystic breast disease (FBD); 256 cases of non-small cell lung carcinomas (NSCLCs) and 45 cases of non-malignant lung tissue (NMLT); and 108 cases of CRC and 25 cases of non-malignant colorectal tissue (NMCT). A2M and LRP1 expression levels were also investigated in breast (MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2), lung (NCI-H1703, NCI-H522, and A549), and colon (LS 180, Caco-2, HT-29, and LoVo) cancer cell lines. Based on our findings, A2M and LRP1 exhibited various expression patterns in the examined malignancies, which were related to one another. Additionally, the stroma of lung and colorectal cancer has increased levels of A2M/LRP1 areas, which explains the significance of the stroma in the development and maintenance of tumor homeostasis. A2M expression was shown to be downregulated in all types of malignancies under study and was positively linked with an increase in cell line aggressiveness. Although more invasive cells had higher levels of A2M expression, an IHC analysis showed the opposite results. This might be because exogenous alpha-2-macroglobulin is present, which has an inhibitory effect on several cancerous enzymes and receptor-dependent signaling pathways. Additionally, siRNA-induced suppression of the transcripts for A2M and LRPP1 revealed their connection, which provides fresh information on the function of the LRP1 receptor in A2M recurrence in cancer. Further studies on different forms of cancer may corroborate the fact that both A2M and LRP1 have high potential as innovative therapeutic agents.

αPD-1 immunotherapy promotes IL-17A production and promotes the formation of acute radiation-induced lung injury.

Radiotherapy (RT) is essential in the treatment of thoracic neoplasms. Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have significantly improved the clinical management of non-small cell lung carcinoma (NSCLC). This study aimed to investigate the impact of combining anti-PD-1 (αPD-1) immunotherapy with radiotherapy on lung injury. Additionally, it investigates the role and mechanism of interleukin (IL)-17A, a pro-inflammatory cytokine involved in immune regulation, in lung injury arising from this combination treatment. Experiments were conducted using a PD-1 deficient mouse model to simulate acute radiation-induced lung injury. Inbred female BALB/c wild-type (WT) mice and PD-1-/- mice were divided into six groups: WT group, PD-1-/- group, WT_LIR + IgG group, PD-1-/-_LIR + IgG group, WT_LIR + αIL-17A group, and PD-1-/-_LIR + αIL-17A group. The mice were subjected to 8 Gy × 3 irradiation in both lungs. Various methods including histological scoring, immunofluorescence, qPCR, and flow cytometry were employed to analyze the role of IL-17A in lung injury and the effect of PD-1 gene deletion on the severity of radiation-induced lung injury. The PD-1-/-_LIR mice exhibited evident radiation-induced lung injury after receiving 8 Gy × 3 doses in both lungs. The expression level of IL-17A peaked at 2 weeks. Lung injury-related factors IFN-γ, TNF-α, IL-6, and RORγt in the PD-1-/-_LIR groups increased 2 weeks after irradiation. The CD4+ and CD8+ T cells in lung tissue of the PD-1-/-_LIR mice significantly increased. Post αIL-17A administration, the incidence of alveolitis in the treatment group decreased, the expression levels of lung injury-related factors IFN-γ, TNF-α, IL-6, RORγt, TGF-β1, and IL-17A decreased, and the CD4+ and CD8+ T cells in lung tissue significantly declined. Throughout the observation period, the survival rate of the mice in the treatment group was significantly higher than that of the isotype control group (60% vs 0%, P = 0.011). Combining αPD-1 immunotherapy with radiotherapy in mice can induce radiation-induced lung injury, with IL-17A playing a critical role in this process. αIL-17A administration significantly mitigated radiation-induced lung injury caused by the combination of αPD-1 immunotherapy and radiotherapy, improving mouse survival. This finding offers a promising treatment target for lung injury resulting from the combination of αPD-1 immunotherapy and radiotherapy.

Deep Learning Based on Computed Tomography Predicts Response to Chemoimmunotherapy in Lung Squamous Cell Carcinoma.

Non-small-cell lung carcinoma (NSCLC) often carries a dire prognosis. The advent of neoadjuvant chemoimmunotherapy (NCI) has become a promising approach in NSCLC treatment, making the identification of reliable biomarkers for major pathological response (MPR) crucial. This study aimed to devise a deep learning (DL) model to estimate the MPR to NCI in lung squamous cell carcinoma (LUSC) patients and uncover its biological mechanism. We enrolled a cohort of 309 LUSC patients from various medical institutions. A ResNet50 model, trained on contrast-enhanced computed tomography images, was developed, and validated to predict MPR. We examined somatic mutations, genomic data, tumor-infiltrating immune cells, and intra-tumor microorganisms. Post-treatment, 149 (48.22%) patients exhibited MPR. The DL model demonstrated excellent predictive accuracy, evidenced by an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI: 0.98-1.00) and 0.90 (95% CI: 0.81-0.98) in the first and second validation sets, respectively. Multivariate logistic regression analysis identified the DL model score (low vs. high) as an independent predictor of MPR. The prediction of MPR (P-MPR) correlated with mutations in four genes, as well as gene ontology and pathways tied to immune response and antigen processing and presentation. Analysis also highlighted diversity in immune cells within the tumor microenvironment and in peripheral blood. Moreover, the presence of four distinct bacteria varied among intra-tumor microorganisms. Our DL model proved highly effective in predicting MPR in LUSC patients undergoing NCI, significantly advancing our understanding of the biological mechanisms involved.

Effects of methylation and transcription factor YY1 on ID2 expression in non-small cell lung carcinoma cells.

The inhibitor of DNA-binding 2 (ID2) plays a major role in tumor dedifferentiation in non-small cell lung cancer (NSCLC). Studies have indicated an inverse correlation between ID2 expression and NSCLC cell invasiveness. However, the mechanisms through which ID2 activation is regulated are currently unclear. We overexpressed ID2 in H1299 cells and extensively characterized their cellular behaviors. By employing a serial deletion approach combined with a reporter assay, we pinpointed the basal promoter region of ID2. We also examined the DNA methylation status of the ID2 promoter to elucidate the epigenetic mechanisms driving ID2 regulation. Our results revealed that ID2 overexpression effectively inhibited the migration, invasion, proliferation, and colony formation abilities of H1299 cells. The region from -243 to +202 played a major role in driving the transcriptional activity of ID2. Sequence analysis results indicated that the transcription factor Yin Yang 1 (YY1) might be crucial in the regulation of ID2 expression. The ectopically expressed YY1 activated both the expression levels of ID2 and the transcriptional activity of the ID2 promoter, potentially contributing to its repressive activity on cancer cell growth. Furthermore, site-directed mutagenesis and chromatin immunoprecipitation assays revealed that YY1 may target the -120 and -76 sites of the ID2 promoter, thereby activating its transcriptional activity. The ID2 promoter regions were also fully methylated in CL1-5 cells, and the methylation level was correlated with the expression levels of the ID2 promoter. Moreover, the YY1-induced suppression of colony formation was counteracted by ID2 knockdown, which suggests that YY1 represses cell colony growth through the regulation of ID2. Our results indicate that YY1 plays a role in transactivating ID2 expression and might also contribute to the repression of colony growth through the regulation of ID2.

Sintilimab Combined with Nanoparticle Albumin-Bound Paclitaxel-Based Chemotherapy in Severe Locally Advanced or Metastatic Squamous NSCLC Showed Good Efficacy and Safety: A Pilot Retrospective Analysis.

Squamous non-small cell lung carcinoma (sqNSCLC) is associated with a poorer prognosis and limited treatment options. Sintilizumab combined with chemotherapy is used as first-line treatment for advanced sqNSCLC. However, the efficacy and safety of sintilimab combined with nanoparticle albumin-bound paclitaxel-based chemotherapy for severe squamous NSCLC remain to be unknown in clinical studies. Patients with confirmed unresectable stage III/IV sqNSCLC were retrospectively collected between July 1st, 2019, and December 31st. According to performance status (PS) scores, these patients received first-line sintilimab plus nab-PTX-based chemotherapy were divided into severe (PS=2) and non-severe groups (PS=0-1). The treatment regimen was repeated every 3weeks for a maximum of six cycles, or until unacceptable toxicity occurred. The primary endpoint of this study was to assess progression free survival (PFS), with secondary endpoints including the objective response rate (ORR), adverse events (AEs) and disease control rate (DCR). Among 367 patients with unresectable stage III/IV sqNSCLC, 28 male patients, with a median age of 65.5 years, received first-line sintilimab plus nab-PTX-based chemotherapy. These patients were divided into a severe group (11 patients) and a non-severe group (17 patients). The severe group had a significantly higher incidence of chronic obstructive pulmonary disease (COPD) compared to the non-severe group (54.5% vs 11.8%, p = 0.03). The two groups had a similar median number of treatment cycles and safety profiles. Although the severe group showed higher ORR (63.6% vs 47.1%) and DCR (100% vs 76.5%) than the non-severe group, these differences were not statistically significant. Median PFS and Kaplan-Meier curves were also comparable between the groups. Sintilimab combined with nab-PTX-based chemotherapy was effective and well tolerated in a small sample of severe lung squamous cell carcinoma population. This combination may offer a potential treatment option for these patients.

Decoding potential targets and pharmacologic mechanisms of curcumin in treating non-small cell lung carcinoma via bioinformatics and molecular docking.

Emerging evidence demonstrates that curcumin has an inhibitory effect on non-small cell lung cancer (NSCLC), and its targets and mechanism of action need further exploration. The goal of this study was to explore the potential targets and mechanism of curcumin against NSCLC by network pharmacology, bioinformatics, and experimental validation, thereby providing more insight into combination treatment with curcumin for NSCLC in preclinical and clinical research. Curcumin targets against NSCLC were predicted based on HIT2.0, STD, CTD, and DisGeNET, and the core targets were analyzed via protein-protein interaction network construction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking. The gene expression levels of samples in A549 cells, NCI-H460, and curcumin treated groups were detected by real-time quantitative PCR. A total of 67 common targets between curcumin and NSCLC were collected by screening public databases. GO and KEGG analysis suggested that curcumin treatment of NSCLC mainly involves cancer-related pathways, such as PI3K-AKT signaling pathway, Foxo signaling pathway, microRNAs, MAPK signaling pathway, HIF-1 signaling pathway, etc. The targets with the highest degree were identified through the PPI network, namely CASP3, CTNNB1, JUN, IL6, MAPK3, HIF1A, STAT3, AKT1, TP53, CCND1, VEGFA, and EGFR. The results of the in vitro experiments showed that curcumin treatment of NSCLC down-regulated the gene expressions of CCND1, CASP3, HIF1A, IL-6, MAPK3, STAT3, AKT1, and TP53. Our findings revealed that curcumin functions as a potential therapeutic candidate for NSCLC by suppressing multiple signaling pathways and interacting with multiple gene targets.

Clinical Effects of Enhanced Recovery after Surgery in Perioperative Period Patients with Video-Assisted Thoracoscopic Lobectomy.

Enhanced recovery after surgery (ERAS) guidelines provide significant benefits for patients after surgery. Care bundles combine various evidence-based treatments and care measures for managing refractory clinical diseases. Therefore, we aimed to evaluate the ERAS measures and care bundles to reduce post-operative complications associated with video-assisted thoracic surgery (VATS) lobectomy and promote patients' recovery. As a retrospective study, this study included 120 non-small cell lung carcinoma patients, who were divided into a control group and an observation group according to the post-operative care methods of the patients in the medical record system. Among them, sixty patients, admitted from January 2018 to January 2019, were included in the control group, and 60 patients, admitted from January 2022 to January 2023, were included in the observation group. The control group received routine care (non-ERAS group), and the observation group followed the bundles of care strategy based on ERAS guidelines (ERAS group). Data collected included baseline characteristics, clinical parameters, and post-operative parameters of patients in the ERAS and non-ERAS groups. The clinical data of all patients came from the hospital medical record system. There were no significant differences in gender, age, tumor node metastasis (TNM) stages, smoking, and drinking between the ERAS and non-ERAS groups (p > 0.05). Similarly, no significant differences were observed in Cardiac Ejection fraction (≥50%), forced expiratory volume in 1 sec % (FEV1%) forced vital capacity (FVC), Lymphocyte, Neutrophils (%), and Tumor diameter between the ERAS and non-ERAS groups (p > 0.05). In contrast, significant differences were found in FVC, FEV1%, diffusing capacity of the lungs for carbon monoxide single breath (DLCO SB), Albumin, C-reactive protein, Leukocyte, Monocytes, Lymphocyte (%), Hemoglobin, and Neutrophils between the ERAS and non-ERAS groups (p < 0.05). Furthermore, Receiver Operating Characteristic (ROC) analysis indicated that Leukocytes, DLCO, C-reactive protein (CRP), FEV1%, Monocytes, Lymphocytes (%), Neutrophils (%), and Body Mass Index (BMI) were essential predictors of ERAS. Using cutoff values of Leukocytes >12.5, FEV1% >112.9, Monocytes >16.8 (109/L), and Neutrophils >11.6, patients undergoing VATS lobectomy were more likely to experience a quick recover. When ERAS measures integrated bundles of care, the extubation time can reduced to less than 5.5 days, the visual analogue scale (VAS) score to less than 3.5, and the post-operative hospital stay to less than 10.5 days. ERAS management measures based on bundles of care can significantly improve the prognosis of patients undergoing VATS lobectomy, reduce post-operative complications, and accelerate safe rehabilitation. Furthermore, they can greatly shorten hospital stays, lower overall healthcare costs, and alleviate social and family burdens. These significant differences may be related to factors such as Leukocytes, FEV1%, Monocytes, and Neutrophils.

Reduced frequency dosing of osimertinib in EGFR-mutant non-small cell lung carcinoma: real world data.

Osimertinib is more efficacious and as safe as first-generation epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors. However, osimertinib is not affordable for most patients in developing nations. Moreover, the minimum biologically effective dose of osimertinib may be less than the approved dose. This was a retrospective observational multicentric study aimed to describe the efficacy (objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS)) and toxicity of osimertinib 80 mg orally administered less frequently than daily (ranging from every other day to once-a-week) in patients with EGFR-mutated non-small cell lung cancer. Between January 2021 and August 2023, we enrolled 22 patients. Six received osimertinib 80 mg once-a-week, nine received 80 mg once-in-3-days and seven received 80 mg on alternate days. Responses included 0 complete responses, 7 (31.8%) partial responses, 9 (40.9%) stable disease and 5 (22.7%) progressive disease. ORR was 31.8%, and DCR was 72.7%. Median PFS was 9.2 months (95% confidence interval (CI) 2.9-15.7), and median OS was 17.8 months (95% CI, 3.2-32.6). In patients who received reduced frequency osimertinib in the second line and beyond, the ORR was 29.4%, DCR was 70.5%, median PFS was 5.9 months (95% CI, 1.1-10.6) and median OS was 17.6 months (95% CI, 2.9-32.2). Grade 3 and higher toxicities were noted in 8 (36.3%) patients. Less frequent dosing of osimertinib may be a valid treatment option, especially in the second line and beyond setting in patients who cannot afford full dose daily osimertinib. This may provide an additional treatment option with a similar toxicity profile as that of standard dose osimertinib.

PAHPhysRAD: A Digital Imaging and Communications in Medicine Research Tool for Segmentation and Radiomic Feature Extraction.

Segmentation and analysis of organs at risks (OARs) and tumor volumes are integral concepts in the development of radiotherapy treatment plans and prediction of patients' treatment outcomes. To develop a research tool, PAHPhysRAD, that can be used to semi- and fully automate segmentation of OARs. In addition, the proposed software seeks to extract 3214 radiomic features from tumor volumes and user-specified dose-volume parameters. Developed within MATLAB, PAHPhysRAD provides a comprehensive suite of segmentation tools, including manual, semi-automatic, and automatic options. For semi-autosegmentation, meta AI's Segment Anything Model was incorporated using the bounding box methods. Autosegmentation of OARs and tumor volume are implemented through a module that enables the addition of models in Open Neural Network Exchange format. To validate the radiomic feature extraction module in PAHPhysRAD, radiomic features extracted from gross tumor volume of 15 non-small cell lung carcinoma patients were compared against the features extracted from 3D Slicer™. The dose-volume parameters extraction module was validated using the dose volume data extracted from 28 tangential field-based breast treatment planning datasets. The volume receiving ≥20 Gy (V20) for ipsilateral lung and the mean doses received by the heart and ipsilateral lung, were compared against the parameters extracted from Eclipse. The Wilcoxon signed-rank test revealed no significant difference between the majority of the radiomic features derived from PAHPhysRAD and 3D Slicer. The average mean lung and heart doses calculated in Eclipse were 5.51 ± 2.28 Gy and 1.64 ± 1.98 Gy, respectively. Similarly, the average mean lung and heart doses calculated in PAHPhysRAD were 5.45 ± 2.89 Gy and 1.67 ± 2.08 Gy, respectively. The MATLAB-based graphical user interface, PAHPhysRAD, offers a user-friendly platform for viewing and analyzing medical scans with options to extract radiomic features and dose-volume parameters. Its versatility, compatibility, and potential for further development make it an asset in medical image analysis.

Investigating the Hub Genes of Lactic Acid Bacterial Peptides and their association with Anti-Cancer Role

As there is no cure for cancer, hence it becomes one of the top causes of mortality worldwide. Bacterial peptide obtained from probiotic species possesses anti-cancer and anti-bacterial activity and shows specificity towards the prominent target of cancer cells. To find such peptides with anti-cancer activity, a thorough literature review was conducted. Major 9 peptides have been selected as a promising candidate, and their interactions with 9840 possible target genes were retrieved using the STITCH database and the STRING 11.0b database, respectively. In the Cytoscape software version 3.8.2 network analysis, 2465 nodes and 10871 edges were found. Cytoscape version 3.8.1 was used to build, visualize and analyze target-disease and target-pathway networks for anti-cancer peptides to advance current understanding. There were 3127 nodes identified as disease-associated. In total, 271 nodes and 318 edges were discovered, along with 27 distinct genes linked to 243 distinct pathways. The hub genes were found by centrality analysis to comprehend how peptides and highly significant genes interact. Thus, six key hub genes for the peptides—GRB2, APP, COPS5, CDK1, RPS3, and XRCC6—were identified based on topological criteria such as MCC, degree, closeness, betweenness, and radiality. Major genes were discovered to be linked to Neoplasm Metastasis, Neoplasms, Non-Small Cell Lung Carcinoma, and Primary Malignant Neoplasm among the 57 genes. The expression of the disease-related genes and their regulation of the molecular mechanisms causing the disease, together with their transcription factors, have been identified.

Evaluation of the diagnostic yield of lung cancer on various Bronchoscopic modalities

Background: The application of cytological techniques in identifying malignant respiratory tract lesions has been widely praised as a significant achievement. Flexible fiberoptic bronchoscopy has greatly transformed respiratory cytology, making procedures such as bronchial brushings, broncho-alveolar lavage, and bronchial forceps biopsy more convenient, accessible, and popular. Methodology: All the suspected cases of lung cancer from 1st Jan, 2020 - 31st Dec, 2022 fulfilling inclusion criteria who have undergone flexible bronchoscopy in our center have been analyzed and enrolled in the study. Results: Out of 90 patients, 85 were found to be malignant. Squamous cell carcinoma was the most common carcinoma (31.1%) followed by adenocarcinoma (26.7%), non-small Cell Lung Carcinoma (17.8%) and small cell carcinoma (12.2%), majority of the cases were of 6-7th decade of life and were smoker. Sensitivities of Bronchoalveolar Lavage (BAL), Bronchial brush, Endobronchial forceps Biopsy (EBB), Transbronchial Lung Biopsy (TBLB) and Transbronchial Needle Aspiration (TBNA) were found to be 32%, 87%, 83%, 55% and 69% respectively. Diagnostic accuracy of BAL, bronchial brush, EBB, TBLB and TBNA were found to be 36%, 87%, 83%, 55% and 61% respectively. Conclusion: With a greater sensitivity (87%) and diagnostic accuracy (87%), bronchial brushing shows great promise as a convenient cytological technique suitable for screening ambiguous cases and early detection of lung cancer, as it saves the time required for processing biopsy samples.

Kaempferol Promotes Lung Cancer Cell Autophagy

Autophagy is a cellular process involved in the degradation and recycling of cellular components, and it plays a complex role in cancer. In the context of lung cancer, including lung cell cancer, the relationship between autophagy and cancer is multifaceted and can vary depending on the specific circumstances. Wang and colleagues investigated the molecular mechanism by which kaempferol (from Hedyotis diffusa) promotes autophagy in Non-Small Cell Lung Carcinoma (NSCLC) cells. Their results suggest that kaempferol significantly inhibits NSCLC cell proliferation. Kaempferol also caused NSCLC cell death by promoting NSCLC cell autophagy. Their experiments reveal that both protein and mRNA expression of Met was significantly inhibited. They also observed the inhibition of PI3K/AKT/mTOR signaling pathway. These results were validated by the overexpression of Met which resulted in the reversal of kaempferol effects on NSCLC cell viability and cell autophagy. They concluded that Kaempferol exerts its anti-NSCLC effect by promoting NSCLC cell autophagy which involves Met and its downstream PI3K/AKT/mTOR signaling pathway. Phytomedicine. 2023 Dec:121:155090. doi: 10.1016/j.phymed.2023.155090.

MRI imaging pattern of metastasis and tuberculous spondylitis in the spine: serial case report

Background: Tuberculous spondylitis and spinal metastasis manifestations have a similar clinical manifestation. Spinal metastasis prevalence is high in malignant process while tuberculosis is frequent in endemic areas. Back pain, paresthesia, and paralysis are commonly caused by vertebral fractures, soft tissue mass, and spinal canal involvement. The magnetic resonance imaging (MRI) is a useful modality in the pattern differentiation of these diseases. This case series aimed to provide a differentiation between those two diseases using MRI. Case report: In the first case, we presented a 24-year-old female complained of hip pain without history of tuberculosis infection or malignancy. Whole spine MRI showed kyphotic deformity, compression of T9 vertebral body, erosion of anterior aspect T8 and T10 vertebral body, and subligamentous abscess at T7-T12 vertebrae level. Tuberculous infection was proven. The second case was a 39-year-old female complained of leg weakness without complaint of cough or breathing difficulty. Whole spine MRI showed kyphotic thoracic vertebrae, compression T10 vertebral body, destruction of inferior endplate T9 vertebrae, bone marrow changes on thoracic vertebral body, and paravertebral soft tissue mass on anterior T6 to T11 vertebral body. Tuberculosis etiology was proven. The third case was a 51-year-old female that came to the hospital due to waist pain with no history of tuberculosis infection or malignancy. Whole spine MRI revealed T8 and T9 vertebral body compression and bone marrow replacement on cervical, thoracic, and lumbar vertebrae, spinous process of thoracic and lumbar, bilateral posterior rib T4-T5, and soft tissue mass at the posterior T9 vertebrae. In the last case, we presented a 58-year-old male that complianed pain in the back and both legs. Lumbosacral MRI showed compression fracture with signal intensity change on L3 vertebral body, bone marrow replacement on thoracic, lumbar, and sacral vertebrae, expanding to epidural and cause spinal canal stenosis. CT-scan thorax showed lung malignancy proven to be non-small cell lung carcinoma. A spinal biopsy revealed malignant infiltration. Conclusion: Tuberculous spondylitis and metastasis differentiation can be a challenge. Early complaints mostly are back pain, paresthesia, and paralysis. Spine MRI can differentiate the pattern of both diseases and identify the possible etiology.

Antitumor efficacy of synthesized Ag–Au nanocomposite loaded with PEG and ascorbic acid in human lung cancer stem cells

Lung cancer is the leading cause of mortality worldwide of which non-small cell lung carcinoma constitutes majority of the cases. High mortality is attributed to early metastasis, late diagnosis, ineffective treatment and tumor relapse. Chemotherapy and radiotherapy form the mainstay of its treatment. However, their associated side effects involving kidneys, nervous system, gastrointestinal tract, and liver further adds to dismal outcome. These disadvantages of conventional treatment can be circumvented by use of engineered nanoparticles for improved effectiveness with minimal side effects.In this study we have synthesized silver gold nanocomposite (Ag–Au NC) using polyethylene glycol and l-ascorbic acid as surfactant and reducing agent respectively. Synthesized nanocomposite was characterized by ultraviolet–visible absorption, dynamic light scattering, scanning and transmission electron microscopy. Compositional analysis was carried out by energy dispersive X-ray analysis and average pore diameter was estimated using Barrett-Joyner-Halenda method. In-silico molecular docking analysis of the synthesized NC against active regions of epidermal growth factor receptor revealed good binding energy. Subsequently, we investigated the effect of NC on growth and stem cell attributes of A549 lung cancer cells. Results showed that NC was effective in inhibiting A549 cell proliferation, induced DNA damage, G2/M phase arrest and apoptosis. Further, tumor cell migration and spheroid formation were also negatively affected. NC also enhanced reactive oxygen species generation and mitochondrial depolarization. In addition, the effect of NC on putative cancer stem cells in A549 cells was evaluated. We found that Ag–Au NC at IC50 targeted CD44, CD24, CD166, CD133 and CD326 positive cancer stem cells and induced apoptosis. CD166 positive cells were relatively resistance to apoptosis.Together our results demonstrate the anticancer efficacy of Ag–Au NC mediated by a mechanism involving cell cycle arrest and mitochondrial derangement.

Body composition radiomic features as a predictor of survival in patients with non-small cellular lung carcinoma: A multicenter retrospective study

ObjectivesThis study combined two novel approaches in oncology patient outcome predictions—body composition and radiomic features analysis. The aim of this study was to validate whether automatically extracted muscle and adipose tissue radiomic features could be used as a predictor of survival in patients with non-small cell lung cancer. MethodsThe study included 178 patients with non-small cell lung cancer receiving concurrent platinum-based chemoradiotherapy. Abdominal imaging was conducted as a part of whole-body positron emission tomography/computed tomography performed before therapy. Methods used included automated assessment of the volume of interest using densely connected convolutional network classification model - DenseNet121, automated muscle and adipose tissue segmentation using U-net architecture implemented in nnUnet framework, and radiomic features extraction. Acquired body composition radiomic features and clinical data were used for overall and 1-y survival prediction using machine learning classification algorithms. ResultsThe volume of interest detection model achieved the following metric scores: 0.98 accuracy, 0.89 precision, 0.96 recall, and 0.92 F1 score. Automated segmentation achieved a median dice coefficient >0.99 in all segmented regions. We extracted 330 body composition radiomic features for every patient. For overall survival prediction using clinical and radiomic data, the best-performing feature selection and prediction method achieved areas under the curve–receiver operating characteristic (AUC-ROC) of 0.73 (P < 0.05); for 1-y survival prediction AUC-ROC was 0.74 (P < 0.05). ConclusionAutomatically extracted muscle and adipose tissue radiomic features could be used as a predictor of survival in patients with non-small cell lung cancer.

Short Antiangiogenic MMP-2 Peptide-Decorated Conjugated Linoleic Acid-Coated SPIONs for Targeted Paclitaxel Delivery in an A549 Cell Xenograft Mouse Tumor Model.

The design of targeted antiangiogenic nanovectors for the delivery of anticancer drugs presents a viable approach for effective management of nonsmall-cell lung carcinoma (NSCLC). Herein, we report on the fabrication of a targeted delivery nanosystem for paclitaxel (PTX) functionalized with a short antimatrix metalloproteinase 2 (MMP-2) CTT peptide for selective MMP-2 targeting and effective antitumor activity in NSCLC. The fabrication of the targeted nanosystem (CLA-coated PTX-SPIONs@CTT) involved coating of superparamagnetic iron-oxide nanoparticles (SPIONs) with conjugated linoleic acid (CLA) via chemisorption, onto which PTX was adsorbed, and subsequent surface functionalization with carboxylic acid groups for conjugation of the CTT peptide. CLA-coated PTX SPIONs@CTT had a mean particle size of 99.4 nm and a PTX loading efficiency of ∼98.5%. The nanosystem exhibited a site-specific in vitro PTX release and a marked antiproliferative action on lung adenocarcinoma cells. The CTT-functionalized nanosystem significantly inhibited MMP-2 secretion by almost 70% from endothelial cells, indicating specific anti-MMP-2 activity. Treatment of tumor-bearing mice with subcutaneous injection of the CTT-functionalized nanosystem resulted in 69.7% tumor inhibition rate, and the administration of the nanosystem subcutaneously prolonged the half-life of PTX and circulation time in vivo. As such, CLA-coated PTX-SPIONs@CTT presents with potential for application as a targeted nanomedicine in NSCLC management.