Non-small Cell Lung Carcinoma Research Articles

Circulating Tumor Cell-Free DNA as Prognostic Biomarker in Non-Small Cell Lung Cancer Patients Undergoing Immunotherapy: The CORELAB Experience

The expression level of Programmed Death-Ligand 1 (PD-L1) determined by the immunohistochemical method is currently approved to test the potential efficacy of immune-checkpoint inhibitors and to candidate patients with Non-Small Cell Lung Cancer (NSCLC) for treatment with immunotherapeutic drugs. As part of the CORELAB (New prediCtivebiOmaRkers of activity and Efficacy of immune checkpoint inhibitors in advanced non-small cell Lung cArcinoma) project, aimed at identifying new predictive and prognostic biomarkers in NSCLC patients receiving immunotherapeutic drugs, we investigated the role of circulating tumor DNA (ctDNA) molecular characterization as an additional predictive biomarker. We analyzed plasma ctDNA by targeted Next Generation Sequencing in a subset of 50 patients at different time points. ctDNA content was inversely correlated with the clinical outcome both at a baseline and after 2 months of treatment. OS was significantly higher in patients with ≥50% ctDNA reduction. TP53 and KRAS were the most frequently mutated genes, and patients with KRAS and/or TP53 mutations showed worse outcomes than patients without detectable variants or with mutations in other genes. Fewer common variants were found in BRAF, EGFR, MAP2K1, MET, NRAS, and PIK3CA genes. Our data demonstrated that molecular characterization of ctDNA and also its quantitative evaluation could serve as a dynamic, real-time prognostic, and predictive biomarker, enabling regular molecular monitoring of therapy efficacy in support of other medical examinations.

SMARCA4 Deficiency in Lung Cancer: From Signaling Pathway to Potential Therapeutic Targets.

SMARCA4-deficient lung cancer, including thoracic SMARCA4-deficient undifferentiated tumors and SMARCA4-deficient nonsmall-cell lung carcinomas, is a rare and aggressive disease characterized by rapid progression and poor prognosis. This cancer was identified as a distinct entity with specific morphologic and molecular features in the 2021 WHO Classification of Thoracic Tumors. Molecular alterations in SMARCA4 are specific to this type of lung cancer. Deficiency in SMARCA4 suppresses the SWI/SNF tumor suppressor complex, driving tumor progression. Due to the lack of standardized treatment, most patients succumb to the disease within 6 months. This study provides a detailed analysis of the SMARCA4 pathway and its role in lung cancer. We analyzed potential therapeutic targets and agents to offer insights for the precise and effective treatment of SMARCA4-deficient lung cancer.

Differential Expression of miR-192, miR-221, miR-15 Among the Nodule Tissues of Sarcoidosis and Lung Cancer

Background: Patients with sarcoidosis were found to have a higher risk of lung cancer compared to the general population. Being aware of all possible associations between these two diseases and identification of biomarkers such as miRNA profiles can be helpful in differentiating the mechanisms of these two diseases, which can aid in clinical decision-making. Methods: The aim of the study was to investigate the expression of selected miRNAs (miR-192 miR-221, miR-15) in lymph nodes of patients with pulmonary sarcoidosis, non-small cell lung carcinomas (NSCLC) and control group (n = 30 per groups) by qRT-PCR. Results: Relative expression of miR-221 in sarcoidosis and NSCC patients was higher than in the control group. Furthermore, the relative expression of miR-15 in patients with sarcoidosis and NSCLC tissue was lower than in the control group. Interestingly, miR-192 is differentially expressed in sarcoidosis and NSCLC patients compared to the control group. Conclusions: The obtained results suggest that the studied miRNAs may have potential diagnostic and therapeutic implications, but further research is necessary to fully understand their roles in these diseases.

Synthesis, characterization, and investigation of photochemical and in vitro properties of novel Zn(II) phthalocyanine.

A new nonperipheral zinc(II) phthalocyanine bearing octa carboxylic acid ethyl ester derivative substituted triazole attached propylmercaptothiobenzylmercapto derivative was synthesized via the tetramerization reaction of phthalonitrile. The photochemical in vitro photodynamic activity of zinc(II) phthalocyanine (ZnPc-I), such as human nonsmall cell lung carcinoma cell lines, was investigated in this study. The singlet oxygen generation property of novel zinc(II) phthalocyanine (ZnPc-I) was also examined due to the significantly high singlet oxygen quantum yield of ZnPc-I (FD = 0.66). The antiproliferative effects of ZnPc-I were also investigated on the A549 and H1299 cell lines, and the results demonstrated that ZnPc-I had a strong antiproliferative effect on both cell lines.

Combination Checkpoint Blockade and Laser Interstitial Thermal Therapy in Radiographically Progressive Non-Small Cell Lung Cancer Brain Metastases

Abstract Background Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment being employed frequently for radiographically progressive brain metastases. Considerable interest exists in combining LITT-mediated in situ vaccination to license immune checkpoint blockade (ICB). No studies have examined the clinical feasibility of this combination in brain metastases. Methods All patients receiving LITT for radiographically progressive non-small cell lung carcinoma (NSCLC) brain metastases at a single center from 2015 – 2023 were retrospectively reviewed. Combination therapy was defined as ICB within 6 weeks of LITT. Clinical data, post-LITT freedom from local progression (FFLP), and overall survival (OS) were collected. Adverse events (AEs) were evaluated according to Common Terminology Criteria. Results Eighteen patients received LITT + ICB to a total of 19 lesions. Median time between therapies was 2.29 weeks (range 0.85 – 5.98). In comparison to NSCLC patients receiving LITT alone or with targeted therapy (LITT only) (n = 25), there was no decrement in procedural outcomes. Patients receiving LITT + ICB discontinued steroids at a median of 11 (4 – 147) days post-LITT vs. 24 (3 – 242) days for patients receiving LITT only (P = 0.62). At study cutoff, the local control rate was 18/19 (94.7%) lesions in the LITT + ICB group and 22/25 (88.0%) in the LITT only group. There were 3 and 5 AEs ≥ Grade 3 in the LITT + ICB and LITT only group, respectively. Conclusions Combination LITT and ICB does not compromise procedural outcomes or time to steroid discontinuation in NSCLC. Prospective studies are needed to assess biomarkers of immune response.

PFKFB3-dependent redox homeostasis and DNA repair support cell survival under EGFR-TKIs in non-small cell lung carcinoma

BackgroundThe efficacy of tyrosine kinase inhibitors (TKIs) targeting the EGFR is limited due to the persistence of drug-tolerant cell populations, leading to therapy resistance. Non-genetic mechanisms, such as metabolic rewiring, play a significant role in driving lung cancer cells into the drug-tolerant state, allowing them to persist under continuous drug treatment.MethodsOur study employed a comprehensive approach to examine the impact of the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) on the adaptivity of lung cancer cells to EGFR TKI therapies. We conducted metabolomics to trace glucose rerouting in response to PFKFB3 inhibition during TKI treatment. Live cell imaging and DCFDA oxidation were used to quantify levels of oxidation stress. Immunocytochemistry and Neutral Comet assay were employed to evaluate DNA integrity in response to therapy-driven oxidative stress.ResultsOur metabolic profiling revealed that PFKFB3 inhibition significantly alters the metabolic profile of TKI-treated cells. It limited glucose utilization in the polyol pathway, glycolysis, and TCA cycle, leading to a depletion of ATP levels. Furthermore, pharmacological inhibition of PFKFB3 overcome TKI-driven redox capacity by diminishing the expression of glutathione peroxidase 4 (GPX4), thereby exacerbating oxidative stress. Our study also unveiled a novel role of PFKFB3 in DNA oxidation and damage by controlling the expression of DNA-glycosylases involved in base excision repair. Consequently, PFKFB3 inhibition improved the cytotoxicity of EGFR-TKIs by facilitating ROS-dependent cell death.ConclusionsOur results suggest that PFKFB3 inhibition reduces glucose utilization and DNA damage repair, limiting the adaptivity of the cells to therapy-driven oxidative stress and DNA integrity insults. Inhibiting PFKFB3 can be an effective strategy to eradicate cancer cells surviving under EGFR TKI therapy before they enter the drug-resistant state. These findings may have potential implications in the development of new therapies for drug-resistant cancer treatment.

Cis-Regulation of an m6A Eraser by an Insertion Variant Associated with Survival of Patients With Non-Small Cell Lung Carcinoma.

N6-methyladenosine (m6A) serves as one of the crucial RNA modifications for genes involved in cancer progression. Here, 7273 expression quantitative trait loci potentially regulating 30 m6A pathway genes are identified from the GTEx database, with 69 single nucleotide polymorphisms significantly associated with survival of non-small cell lung carcinoma (NSCLC) patients (n = 1523) from the ongoing genome-wide association study after false positive probability tests. Notably, the rs151198415 locus, situated in a potential enhancer region, demonstrated a prolonged survival effect with the C>CCACG insertion, which is validated in an independent prospective cohort (n = 237), yielding a pooled hazard ratio of 0.72 (p = 0.007). Mechanistically, the rs151198415 C>CCACG insertion engaged in long-range interaction with the promoter of m6A eraser ALKBH5, promoting ALKBH5 transcription by the creation of an EGR1 binding site. Then, ALKBH5 upregulated FBXL5 expression by m6A demethylation, which is dependent on the ALKBH5 H204 amino acid site and specific m6A sites on FBXL5 mRNA. Finally, the ALKBH5-FBXL5 axis reduces intracellular reactive oxygen species levels, leading to PI3K/AKT and NF-kB pathway inhibition and consequently suppresses NSCLC proliferation and metastasis in vitro and in vivo. Triggered by an insertion variant, this remote cis-regulation of m6A eraser and the downstream molecular events modulate the survival of NSCLC patients.

STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification.

STIL is a regulatory protein essential for centriole biogenesis, and its dysregulation has been implicated in various diseases, including malignancies. However, its role in non-small-cell lung carcinoma (NSCLC) remains unclear. In this study, we examined STIL expression and its potential association with chromosomal numerical abnormalities (CNAs) in NSCLC using The Cancer Genome Atlas (TCGA) dataset, immunohistochemical analysis, and in vitro experiments with NSCLC cell lines designed to overexpress STIL. TCGA data revealed upregulated STIL mRNA expression in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Immunohistochemical analysis of cases from our hospital (LUAD, n = 268; LUSC, n = 98) revealed STIL protein overexpression. To elucidate the functional role of STIL, an inducible STIL-overexpressing H1299 NSCLC cell line was generated. Overexpression of STIL in these cells promoted centrosome amplification, leading to chromosomal instability. Finally, analysis of arm-level chromosomal copy number alterations from the TCGA dataset revealed that elevated STIL mRNA expression was associated with CNAs in both LUAD and LUSC. These findings suggest that STIL overexpression is associated with CNAs in NSCLC, likely through centrosome amplification, which is linked to chromosomal instability and might represent a potential therapeutic target for NSCLC treatment.

PIK3CA Mutations and Co-Mutations in Operated Non-Small Cell Lung Carcinoma.

Background: Understanding PIK3CA mutations and co-mutations in non-small cell lung carcinoma (NSCLC) is critical to developing personalized treatment strategies. Therefore, this study aims to investigate PIK3CA mutations and the accompanying somatic variations in NSCLC. Methods: This retrospective study included 98 patients over 18 years of age who were diagnosed with NSCLC, operated on, and referred to the Molecular Pathology Laboratory between January 2019 and June 2024 for next-generation sequencing panel tests and ALK-ROS1 FISH analysis. Results: All patients were found to carry PIK3CA mutations. Among the 98 NSCLC patients analyzed, 16 (16.33%) were female and 82 (83.67%) were male. The average age of the patients was 64.53 ± 9.63 years, with an age range of 38-84 years, and the majority were 50 years or older. Of the cases, 51 presented the adenocarcinoma subtype, while the remaining 47 showed the squamous cell carcinoma subtype. A smoking history was present in 77 (78.57%) patients, while 21 (21.43%) had no smoking history. The most frequently detected pathogenic or likely pathogenic PIK3CA variations were c.1633G>A p.E545K (32.65%), c.1624G>A p.E542K (11.22%), c.3140A>G p.H1047R (11.22%), c.3140A>T p.H1047L (5.10%), c.1357G>C p.E453Q (4.08%), and c.3143A>G p.H1048R (2.04%). The top 10 mutations that most commonly accompanied PIK3CA variations were KRAS, NF1, TP53, EGFR, PTEN, BRAF, KIT, CDKN2A, SMARCA4, and ATM mutations, respectively. Conclusions:PIK3CA variations, along with other gene variations, may influence cancer progression and thus may play a crucial role in the determination of targeted treatment strategies.

Neoadjuvant Chemotherapy with Low-Dose Nivolumab Leading to Complete Pathological Response in Non-small Cell Lung Carcinoma

Neoadjuvant Chemotherapy with Low-Dose Nivolumab Leading to Complete Pathological Response in Non-small Cell Lung Carcinoma

Exercise against nonsmall-cell lung carcinoma: novel insights

The mechanisms underlying the potential ‘anticancer’ effects of exercise remain poorly understood. Luo et al. recently identified an exercise-induced, muscle-derived extracellular vesicle (EV)-associated miR, miR-29a-3p, as a key player in the potential benefits of exercise against nonsmall-cell lung carcinoma (NSCLC), including extracellular matrix (ECM) inhibition and improved antitumoral immune responses.

Mesoporous Polydopamine Nano-Bowls Demonstrate a High Entrapment Efficiency and pH-Responsive Release of Paclitaxel for Suppressing A549 Lung Cancer Cell Proliferation In Vitro.

Background: The effectiveness of paclitaxel (PTX) in treating non-small-cell lung carcinoma (NSCLC) is restricted by its poor pharmacokinetic profile and side effects. This limitation stems from the lack of a suitable delivery vector to efficiently target cancer cells. Therefore, there is a critical need to develop an efficient carrier for the optimised delivery of PTX in NSCLC therapy. Methods: The present study describes the fabrication of mesoporous polydopamine (mPDA) nano-bowls via an emulsion-induced interfacial anisotropic assembly method, designed for efficient entrapment of PTX and pH-responsive release behaviour. Results: The nano-bowls depicted a typical bowl-like shape, with connecting mesoporous channels and a central hollow cavity, allowing optimal loading of PTX. The fabricated nanocarrier system, mPDA-PTX-nb, had a mean hydrodynamic bowl diameter of 200.4 ± 5.2 nm and a surface charge of -39.2 ± 1.3 mV. The entrapment efficiency of PTX within the nano-bowls was found to be 95.7%, with a corresponding release of 85.1% achieved at the acidic pH 5.9 (simulated tumour microenvironment) at 48 h. Drug release was best fitted to the Peppas-Sahlin model, indicating the involvement of both diffusion and relaxation mechanisms. Treatment with mPDA-PTX-nb significantly suppressed A549 lung cancer cell proliferation at 48 and 72 h, resulting in cell viability of 14.0% and 9.3%, respectively, at the highest concentration (100 µg/mL). Conclusions: These results highlight the potential of mPDA-PTX-nb as an effective nanocarrier for PTX, promoting enhanced anti-proliferative effects in NSCLC therapy.

Is FDG-PET/CT Scan Useful in the Detection of Subcentimeter Mediastinal Lymph Node Involvement in Patients With Lung Carcinoma?

Background Early staging of lung carcinoma (CA) is pivotal in planning the treatment. Lymph node metastasis can be detected by imaging and invasive procedures. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is an emerging noninvasive imaging modality in detecting nodal metastasis. Objective This study aimed to determine the usefulness of the FDG-PET/CT scan in detecting subcentimeter mediastinal lymph node involvement in lung CA patients by taking histopathology as the gold standard. Materials and methods We conducted a retrospective cross-sectional study at a tertiary care cancer hospital in Pakistan over four and half years, from January 2015 to June 2019. Allpatients suffering from non-small cell lung CA (NSCLC) having avid subcentimeter nodes on FDG-PET/CT were included. The findings obtained on FDG-PET/CT were correlated with histopathological findings after endobronchial ultrasound(EBUS). The results were formulated usingIBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States). Results Results showed that 42/380 total lung CA patients had avid subcentimeter lymph nodes obtained on FDG-PET/CT. A total of 22/42 (52.4%) lymph nodes appeared to be benign, and20/42 (47.6%) lesions were malignant on histopathology. FDG-PET/CT sensitivity is calculated to be 95%, specificity is 68%, positive predictive value is 73%, negative predictive value is 94%, and accuracy is 80.9%. Using the receiver operating characteristic (ROC) curve,sensitivity and specificity were seen in nodes of size 7.5 mm and the maximum standardized uptake value (SUV max)of 5.5 as cutoff values as manifested by area under the curve(AUC). Conclusion FDG-PET/CT was proven to have high sensitivity and accuracy but a low specificity rate to detect nodal involvement in lung CA patients. The high false-positive rates are mainly due to increased prevalence of endemic lung infectious disease.

Minimally Invasive Image-Guided Percutaneous Irreversible Electroporation of Adrenal Metastases.

A single-center retrospective study was performed to evaluate the safety and efficacy of minimally invasive irreversible electroporation (IRE) to treat metastatic adrenal tumors. This single-center study, approved by the Institutional Review Board, retrospectively analyzed six patients who underwent image-guided percutaneous IRE for adrenal metastases. Pre-procedural imaging included CT, MRI and/or 18F-FDG PET-CT scans. Primary outcomes measures included technical success, efficacy and safety, while secondary outcome measures were local progression-free survival (LPFS), distant progression-free survival (DPFS) and overall survival (OS). Follow-up scans were scheduled post-procedure, and data analysis employed Excel, SPSS and R. Patients had diverse primary tumor origins including renal cell carcinoma (2/6), colorectal carcinoma (1/6), non-small cell lung carcinoma (1/6), leiomyosarcoma (1/6) and urothelial carcinoma (1/6). Adverse events were minimal, with only one grade 1 complication reported. Tumor characteristics revealed tumors close to critical structures, with a median pre-ablation size of 23mm. Technical success was achieved in all procedures. At first follow-up, one patient had complete response, one patient had partial response of the right adrenal gland and complete response of the left adrenal gland, two patients had partial response and two patients had stable disease. Local tumor progression occurred in two out of seven tumors with a median LPFS of 10.9months, and distant progression was observed in four out of six patients. Percutaneous, minimally invasive IRE shows promise as a safe treatment option for unresectable metastatic adrenal tumors, demonstrating potential effectiveness. However, further studies with larger patient cohorts are needed to confirm its safety and efficacy.

Accessing Promising Passerini Adducts in Anticancer Drug Design.

The 3-component Passerini reaction (3CPR), discovered little more than 100 years ago, has been demonstrated in the last few decades to be a valuable tool for accessing structural diversity and complexity, essential topics to consider in drug discovery programs. Focusing on accessing a fine-tuned family of α-acyloxyamide-oxindole hybrids, we underline herein our latest insights regarding the use of this mild reaction approach to obtain promising anticancer agents. Cheap and commercially available isatin was used as starting material. The library of α-acyloxyamide-oxindole hybrids was tested against six human solid-tumor cell lines; among them, non-small cell lung carcinoma, cervical and colon adenocarcinoma, and breast and pancreas cancer. The most potent compound displayed GI50 values in the range of 1.3-21 µM.

DNA Damage and Inflammatory Response of p53 Null H358 Non-Small Cell Lung Cancer Cells to X-Ray Exposure Under Chronic Hypoxia.

Hypoxia-induced radioresistance limits therapeutic success in cancer. In addition, p53 mutations are widespread in tumors including non-small cell lung carcinomas (NSCLCs), and they might modify the radiation response of hypoxic tumor cells. We therefore analyzed the DNA damage and inflammatory response in chronically hypoxic (1% O2, 48 h) p53 null H358 NSCLC cells after X-ray exposure. We used the colony-forming ability assay to determine cell survival, γH2AX immunofluorescence microscopy to quantify DNA double-strand breaks (DSBs), flow cytometry of DAPI-stained cells to measure cell cycle distribution, ELISAs to quantify IL-6 and IL-8 secretion in cell culture supernatants, and RNA sequencing to determine gene expression. Chronic hypoxia increased the colony-forming ability and radioresistance of H358 cells. It did not affect the formation or resolution of X-ray-induced DSBs. It reduced the fraction of cells undergoing G2 arrest after X-ray exposure and delayed the onset of G2 arrest. Hypoxia led to an earlier enhancement in cytokines secretion rate after X-irradiation compared to normoxic controls. Gene expression changes were most pronounced after the combined exposure to hypoxia and X-rays and pertained to senescence and different cell death pathways. In conclusion, hypoxia-induced radioresistance is present despite the absence of functional p53. This resistance is related to differences in clonogenicity, cell cycle regulation, cytokine secretion, and gene expression under chronic hypoxia, but not to differences in DNA DSB repair kinetics.

International collaboration of neoadjuvant stereotactic radiosurgery for brain metastases: The INTERNEO individual patient data pooled analysis

Background and PurposeNeoadjuvant stereotactic radiosurgery (NaSRS) is an emerging treatment option for brain metastases (BrM) planned for resection. The aim of this study was to report on the efficacy and safety of NaSRS in an individual patient data pooled analysis. Materials and MethodsPatients undergoing single- and multi-fraction NaSRS for BrM at nine institutions in five countries (Australia, Canada, South Korea, Switzerland and USA) were included. Eligibility criteria included BrM from any primary malignancy and no prior local therapy. The primary endpoint was a composite of local recurrence (LR), any grade radionecrosis (RN), and/or nodular leptomeningeal disease (nLMD). Secondary endpoints included these endpoints and Grade ≥ 2 RN. Endpoints were evaluated using cumulative incidence functions. ResultsNaSRS was delivered to 179 patients with 189 BrM. Median follow-up was 28.4 months. Primary malignancies included non-small cell lung carcinoma (44 %) and melanoma (17 %). The median BrM diameter was 29 mm (IQR 21–36 mm). Single- and multi-fraction NaSRS was utilised in 100 (53 %) and 89 BrM (47 %) respectively. The median single-fraction dose was 18 Gy (IQR 16–20 Gy). Multi-fraction doses included 24 Gy in three fractions (55 %) and 27 Gy in three fractions (25 %). The 12-month incidence for the composite endpoint was 8.0 %. The 12-month incidence of LR was 4.6 %, any grade RN was 3.6 %, Grade ≥ 2 RN was 1.8 % and nLMD was 1.2 %. ConclusionNeoadjuvant SRS results in favourable rates of LR, RN and nLMD. We provide a global experience of this treatment approach with long-term data and the largest cohort of patients undergoing multi-fraction SRS.

Fine-needle aspiration and effusion cytology of thoracic SMARCA4-deficient undifferentiated tumor and SMARCA4-deficient non-small cell lung carcinoma: A multi-institutional experience with 27 patients.

Thoracic switch/sucrose nonfermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4)-deficient (SD) malignancies, including SD undifferentiated tumor (SD-UT) and SD non-small cell lung carcinoma (SD-NSCLC), have been recently described. The cytologic features of these neoplasms in fine-needle aspiration (FNA) and effusion specimens have rarely been reported in the literature. This study aimed to describe and compare the spectrum of cytologic, immunohistochemical, and clinical features ofthese high-grade malignancies recently encountered at the participating institutions. This study documented clinical and imaging characteristics of tumors from 27 patients. Sixteen cytomorphologic features and immunohistochemical findings were compared between SD-UT and SD-NSCLC samples. Twenty three FNAs, two bronchial brushings, and two pleural fluids were evaluated, including 17 SD-UT cases (mean patient age, 70 years) and 10 SD-NSCLC cases (mean patient age, 62 years). Both malignancies presented with large thoracic masses and/or hilar/mediastinal lymphadenopathy. All SD-UT cytologic samples had a discohesive or mixed cohesive-discohesive architecture, and most (13 of 17) showed predominant rhabdoid or mixed rhabdoid-epithelioid features. Most SD-NSCLC cytologic samples (nine of 10) were either cohesive or mixed cohesive-discohesive and had a predominantly epithelioid morphology (eight of 10). Keratins and claudin-4 were negative or focally positive in SD-UT samples, whereas they were diffusely positive in SD-NSCLC samples. Both malignancies were negative for TTF-1 and p40/p63 and showed loss of expression of SMARCA4. Although there is considerable clinical and cytopathologic overlap between SD-UT and SD-NSCLC, some key features allow for their distinction. SD-UT is mostly discohesive with rhabdoid or mixed rhabdoid-epithelioid features, whereas SD-NSCLC often has cohesive epithelioid morphology. The combination of clinical presentation, cytomorphology, and immunohistochemistry is essential for a definitive diagnosis.

NETosis in pulmonary pleomorphic carcinoma

AbstractPulmonary pleomorphic carcinoma (PC) is a rare non‐small‐cell lung carcinoma (NSCLC) with a poor prognosis, characterized by tumor necrosis (TN). NETosis is a form of neutrophil‐specific cell death, which is morphologically characterized by prominent neutrophil infiltration and cell detritus in the necrotic foci. Seventy‐six patients with pulmonary PC who underwent complete resection were enrolled. Tumor necrosis was evaluated using digitally scanned resected specimens. The regions of NETosis were quantified using citrullinated histone H3 (citH3)‐ and myeloperoxidase‐positive regions. We examined the association between the NETosis area and the prognostic outcomes and assessed the correlation between the NETosis area and systemic inflammation. Tumor necrosis was observed in 70 patients (92%). In all the cases, the TN region was accompanied by a citH3‐positive region. The patients with high NETosis area (n = 54) had significantly shorter overall survival than those with low NETosis area (n = 16) (p = 0.013). Furthermore, a high NETosis area was an independent poor prognostic factor in the multivariate analyses. Systemic inflammatory markers, including C‐reactive protein (CRP), CRP‐to‐albumin ratio, and neutrophil‐to‐lymphocyte ratio, were significantly higher in patients with high NETosis area than in those with low NETosis area. Furthermore, the levels of these inflammatory markers were significantly decreased postsurgery. This study shows that in surgically resected pulmonary PC, patients with high NETosis areas have higher systemic inflammation and worse prognosis.

Advancements of CRISPR/Cas9 technology in non-small cell lung cancer research: Applications and current developments

Abstract. Lung cancer is the most aggressive and prevalent malignancies worldwide, contributing significantly to global health challenges with over 1.8 million new cases reported annually. Non-small cell lung carcinoma (NSCLC) accounts for the majority of these cases and is characterized by a poor 5-year survival rate of only 10%. Traditional therapies, including surgery, chemotherapy, and radiotherapy, face limitations such as drug resistance and systemic toxicity. The advent of Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems (CRISPR/Cas) technology has transformed the landscape of gene editing, enabling precise targeting of genes involved in NSCLC pathogenesis. This review explores the therapeutic potential of this technology in NSCLC, focusing on key genes such as AIFM1, ROCK2, TSPAN4, and the PD-1 receptor protein, which play crucial roles in tumor progression and immune evasion. By elucidating the mechanisms through which the genes above help with lung cancer, we highlight how CRISPR/Cas9-mediated interventions can pave the way for innovative and effective treatment strategies. Additionally, we address the current challenges and prospects of implementing CRISPR/Cas9 in clinical settings to enhance the efficacy and specificity of lung cancer therapies, in order to improve patient outcomes and reduce the global burden of this devastating disease.