Cell Lung Carcinoma Research Articles

Nutrients, Phytochemicals, and In Vitro Biological Activities of Goldenberry (Physalis peruviana L.) Fruit and Calyx

This study provides a comprehensive characterization of Physalis peruviana L., covering the nutritional composition of the fruit and the phytochemical profiles and in vitro bioactive properties of berry and calyx extracts. The fresh fruit stood out as a source of dietary fiber (5.16 g/100 g) and is low in fat (0.49 g/100 g). A 100-g serving also contained notable amounts of ascorbic acid (32.0 mg), tocopherols (2.34 mg), potassium (253 mg), phosphorus (45 mg), and magnesium (20 mg). HPLC-DAD-ESI/MS analysis tentatively identified five physalin derivatives and one withanolide in the fruit extract, which showed significant antiproliferative activity against human colorectal adenocarcinoma (Caco-2) and non-small-cell lung carcinoma (NCI-H460) cells. The calyx extracts contained three phenolic acids and four flavonoids, demonstrating high antioxidant activity through physiologically relevant cell-based assays, the ability to inhibit advanced glycation end products (AGEs) formation and nitric oxide production, and also antiproliferative properties. These findings highlight goldenberry as a nutrient-dense fruit rich in vitamins and functional compounds with potential health benefits, supporting its recognition as a “superfruit”. Furthermore, the fruit calyx emerged as a valuable source of bioactive secondary metabolites with potential applications in food and pharmaceutical industries and related sectors.

Strengthening Effect of Thalidomide Combined with an Anti-PD1 Antibody on Enhancing Immunity for Lung Cancer Therapy.

Combining immune checkpoint inhibitors and antiangiogenic agents offers a promising strategy to counteract the cooperative promotion of solid tumor growth by immune checkpoints and intratumoral angiogenesis. We investigated the potential of thalidomide (THD) and anti-PD-1 antibody (PD-1 mAb) in suppressing tumor growth, enhancing immunity, and inhibiting angiogenesis. THD exhibited regulatory effects on PD-1 in CD4+ T cells and PD-L1 in cancer cells, along with tumor growth inhibition in A549 and Lewis lung carcinoma (LLC) cell lines. Combined with PD-1 mAb, THD increased intracellular IL-2 and IFN-γ expression in CD4+ T cells, enhanced granzyme (Gzm-B) expression in peripheral blood mononuclear cells (PBMCs), and reduced TNF-α expression in CD4+ T cells. In C57BL/6 mice, THD plus PD-1 mAb decreased LLC-derived lung tumor weight and volume, boosted CD8+ T cell infiltration in tumors, and reduced CD34+ intratumoral microvessel density. This study highlights THD's role in modifying the tumor microenvironment to enhance PD-1 mAb efficacy, proposing a clinically feasible approach for improving PD-1 mAb treatment outcomes.

Hydromethanolic extracts of Morus alba L. (Mulberry) young and ripe fruit induces apoptosis in lung carcinoma cells (A549)

Abstract The study investigates the potential of Morus alba L. (mulberry) young and ripe fruit extracts against lung cancer cells. Cancer ranking as the second leading cause of global mortality, it is essential to investigate natural compounds like phytochemicals for therapeutic benefits. The research investigates presence of phytochemicals and antioxidant activity of both young (MAF-Y) and ripe (MAF-R) mulberry fruit extracts. Results revealed presence of various secondary metabolites, particularly high phenolic content and antioxidant properties in MAF-R. Both extracts demonstrated significant cytotoxicity against lung adenocarcinoma cells (A549), with IC50 18.4 ± 3.01µg/ml (MAF-R) and 29.41 ±3.6 µg/ml (MAF-Y). Moreover, the extracts effectively inhibited cell migration. Treatment of extracts elevated reactive oxygen species (ROS) production which resulted in disruption of mitochondrial membrane potential, and induced the process of apoptosis in lung carcinoma cells. This was evidenced through various assays including differential staining and DNA fragmentation analysis. These findings underscore the potential of mulberry fruit extracts as promising candidates for cancer prevention and treatment due to their antioxidant properties, cytotoxic effects, and ability to induce apoptosis in lung cancer cells.

Red and NIR light-triggered enhancement of anticancer and antibacterial activities of dinuclear Co(II)-catecholate complexes.

Photoactive complexes of bioessential 3d metals, activable within the phototherapeutic window (650-900 nm), have gained widespread interest due to their therapeutic potential. Herein, we report the synthesis, characterization, and light-enhanced anticancer and antibacterial properties of four new dinuclear Co(II) complexes: [Co(phen)(cat)]2 (Co-1), [Co(dppz)(cat)]2 (Co-2), [Co(phen)(esc)]2 (Co-3), and [Co(dppz)(esc)]2 (Co-4). In these complexes, phen (1,10-phenanthroline) and dppz (dipyrido[3,2-a:2',3'-c]phenazine) act as neutral N,N-donor ligands, while cat2- and esc2- serve as O,O-donor catecholate ligands derived from catechol (1,2-dihydroxybenzene) and esculetin (6,7-dihydroxy coumarin). Their high-spin paramagnetic nature and dimeric identity in solution were confirmed by magnetic susceptibility, UV-visible, emission, and mass spectral data. Co-1-Co-4 exhibited an absorption band within the 600-850 nm range, originating from a charge transfer transition. The electrically neutral complexes demonstrated sufficient solution stability both in the dark and under irradiated conditions. The dppz complexes Co-2 and Co-4 exhibited notable toxicity towards A549 lung carcinoma cells, with potency increasing significantly under brief (5 min) exposure to 660 nm (red) and 808 nm (NIR) laser light (IC50 ∼ 8.9 to 14.9 μM). Notably, their toxicity towards normal NIH-3T3 fibroblast cells was minimal. Cellular assays highlighted that the induced cell death followed an apoptotic pathway, primarily due to mitochondrial damage. Co-2 and Co-4 also demonstrated significant antibacterial potency against Gram-(+) S. aureus and Gram-(-) P. aeruginosa, with effectiveness significantly enhanced upon 808 nm laser irradiation (MIC ∼ 15-142 μM). The increase in the anticancer and antibacterial efficacies was attributed to the generation of cytotoxic singlet oxygen (1O2) species upon red/NIR light exposure. Notably, 808 nm NIR irradiation produced more pronounced effects compared to 660 nm. This study is the first to report on cobalt complexes exhibiting red and NIR light-triggered enhancement of antibacterial and anticancer activities, illuminating the path for the development of long-wavelength absorbing cobalt complexes with enhanced therapeutic efficacy.

The Suppression of Signal Transducer and Activator of Transcription-3 in A549human Lung Carcinoma Cells Induced by Marine Sponge Callyspongia aerizusa.

Lung cancer is recognized as a highly lethal disease, demanding swift and accurate solutions. Previous analysis showed the cytotoxic impact of Callyspongia aerizusa (C. aerizusa) extract containing ergost-22-en-3-one and ergost-7-en3-ol against A549 lung cancer cells, with an IC50 value of 9.38μg/mL. However, the extract did not have cytotoxicity towards Het-1A esophagus epithelial cells. Several reviews also validated the upregulation of pro-apoptotic molecules and the inhibition of anti-apoptotic molecules linked to the caspase-dependent signaling pathway. The objective of this research was to extend the understanding of the effects of C. aerizusa extract on A549 lung carcinoma, examining its influence on various signaling pathways, malignancy, migration, and invasion. PCR was used to measure mRNA expression, targeting PTEN, Akt, mTOR, STAT-3, IL-6, VEGF, and HIF1α. Additionally, Western Blot analysis was adopted to assess PTEN, p-Akt, Akt, p-mTOR, and p-STAT-3 protein expressions. Wound healing and invasion assays were performed to measure the migration and invasion capabilities of A549 cells post-treatment with C. aerizusa extract. The mRNA expression analysis showed an increase in Akt and m-TOR but a decrease in PTEN and STAT-3 after 24hours of treatment with C. aerizusa extract. At the protein level, there was a downregulation of p-Akt, Akt, p-mTOR, and p-STAT-3, while PTEN increased during 24-hour treatment. Wound healing and invasion assay results showed a weakened ability of A549 cells after a 24-hour treatment with C. aerizusa extract. Moreover, IL-6 and HIF-1α mRNA expression levels decreased during 24hours, while VEGF mRNA had a slight decrease compared to untreated cells. In conclusion, the ergosteroids present in marine sponge C. aerizusa extract signified a remarkable reduction in malignancy, migration, and invasion capabilities in A549 lung carcinoma cells. These results suggested their promising candidacy for future anti-angiogenesis in anticancer therapy.

Multi-organelle imaging with dye combinations: targeting the ER, mitochondria, and plasma membrane.

Multi-organelle imaging allows the visualization of multiple organelles within a single cell, allowing monitoring of the cellular processes in real-time using various fluorescent probes that target specific organelles. However, the limited availability of fluorophores and potential spectral overlap present challenges, and many optimized designs are still in nascency. In this work, we synthesized various sulfonamide-based organic fluorophores that emit in the blue, green, and red regions to target different sub-cellular organelles. By utilizing binary mixtures, we successfully demonstrated multiple imaging of the sub-cellular organelles, such as the endoplasmic reticulum, plasma membrane, and mitochondria in HeLa cells, and dual imaging of the endoplasmic reticulum and mitochondria in A549 lung carcinoma cells with the help of blue and red-emitting fluorophores without any spectral spillover. Additionally, these photostable probes allowed precise cell staining and differentiation, structural features, and live cell dynamics. This approach of utilizing fluorescent mixtures can gain traction for various cellular studies and investigations.

The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

Pulmonary high-grade neuroendocrine carcinoma (NEC) includes small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs. The database included NEC cases diagnosed between January 2011 and December 2019. Eligible cases, with valid survival time and eighth edition TNM stage, were classified as pure SCLC, combined SCLC/non-small cell carcinoma and LCNEC. Survival was calculated by the Kaplan-Meier method, pairwise differences using log-rank test, and prognostic groups by a Cox regression analysis. There were 6181 pure/combined SCLC and 697 LCNEC cases available. For SCLC, survival outcome analyses included 4453 with clinical stage, and 583 with pathologic stage data. The corresponding numbers for LCNEC were 585 and 508. The SCLC data validated the ninth edition classification for lung cancer, including the proposed new subcategories, N2a, single-station ipsilateral mediastinal/subcarinal lymph node involvement, and N2b, involvement of multiple ipsilateral/subcarinal stations. The data also validated the subcategorization of M1c into M1c1 (multiple lesions in a single extrathoracic organ system) and M1c2 (involvement of multiple extrathoracic organ systems). The LCNEC data were insufficient for complete survival analysis, but the available data showed decreasing survival with increasing clinical and pathological stages. The ninth edition TNM classification applies to patients with NEC and is the appropriate standard for use in clinical practice.

Encapsulation of synthesized purpurin-18-N-aminoimide methyl ester in lipid nanovesicles for use as agents in photodynamic cancer therapy.

This study aimed to synthesize purpurin-18-N-aminoimide methyl ester (P18 N AI ME) and encapsulate it into lipid nanovesicles (LNVs) for potential application as photodynamic therapy (PDT) agents in cancer therapy. PDT, a light-induced treatment, offers several advantages over conventional cancer treatments, such as minimal invasiveness and localized action. P18 N AI ME, a chlorine class photosensitizer model drug, was synthesized in an attempt to treat tumor in deeper tissues by interacting long-wavelength light. LNVs were introduced to improve anticancer effect and photostability of P18 N AI ME. LNVs using glycerol monostearate demonstrated smaller particle sizes and more sustained release profiles than those using lauric acid. In photocytotoxicity against HeLa (human cervical carcinoma) and A549 (human lung carcinoma) cell lines, P18 N AI ME-LNVs demonstrated safety under dark conditions and enhanced anticancer effects under light conditions compared to P18 N AI ME alone. The inhibitory concentration values (IC50) were 0.86 μM (P18 N AI ME) and 0.68 μM (LNVs) in HeLa cell line and 0.85 μM (P18 N AI ME) and 0.64 μM (LNVs) in A549 cell line. These findings suggest that P18 N AI ME-LNVs hold promise as PDT agents in cancer therapy.

Pulmonary lysyl oxidase expression and its role in seeding Lewis lung carcinoma cells.

Copper promotes tumor growth and metastasis through a variety of mechanisms, most notably as a cofactor within the lysyl oxidase (LOX) family of secreted cuproenzymes. Members of this family, which include LOX and LOX-like enzymes LOXL1-4, catalyze the copper-dependent crosslinking of collagens and elastin within the extracellular matrix (ECM). Elevated LOX expression is associated with higher incidence and worse prognosis in multiple cancers, including colorectal, breast, pancreatic, and head and neck. In this study, we demonstrated that elevated LOX expression correlates with decreased overall survival and shorter median time to first progression in patients with lung cancer. Previous studies have demonstrated that LOX secreted from tumors is critical for pre-metastatic niche formation by promoting ECM remodeling and the recruitment of immune cells and endothelial precursors. Here, we demonstrated that ablation of the LOX gene in Lewis lung carcinoma (LLC) cells diminishes tumor growth and metastasis compared to wild-type LLC cells in a syngeneic mouse model. Although the role of tumor-derived LOX in tumor formation and metastasis is well established, little is known regarding the possible contribution of LOX produced by the parenchymal tissue of metastatic organs. Thus, this report describes our findings that host-derived LOX produced by the lung contributes to the pulmonary metastasis of LLC cells in mice. The suppression of pulmonary lysyl oxidase expression reduces the metastatic potential of Lewis Lung Carcinoma cells in mice, revealing a previously unknown influence of LOX expression in the parenchymal tissue of metastatic target organs on the seeding of tumor cells.

Determinants of Overall and Readmission-Free Survival in Patients with Metastatic Epidural Spinal Cord Compression.

The aim of this study was to assess the surgical outcomes and survival of patients surgically treated for metastatic epidural spinal cord compression (MESCC), with a specific focus on identifying factors that influence overall survival and readmission-free survival. All patients who underwent surgery for spine metastases at our department in the period 2018-2022 were included in the study. A total of 175 patients (n = 71 females, median age 67.15 years) were included. The most common primary tumors were lung carcinoma (n = 31), prostate carcinoma (n = 31), breast carcinoma (n = 28), multiple myeloma (n = 25), and renal cell carcinoma (n = 11). ECOG performance status was 0 (n = 7), 1 (n = 97), 2 (n = 27), 3 (n = 17), and 4 (n = 27). Pathological fractures were present in n = 108 patients. Decompression only was performed in n = 42, additional instrumentation in n = 133, and vertebral body replacement in n = 23. The most common complications were wound healing deficits and hardware failure. Preoperative motor deficits were present in n = 89 patients. Postoperatively, n = 122 improved, n = 43 was unchanged, and n = 10 deteriorated. Mean overall survival (OS) was 239.2 days, with a 30-day mortality rate of 18.3%. Favorable prognostic factors included Tomita score < 7, Frankel score A-C, ECOG 0-1, and Modified Tokuhashi score > 10 (p < 0.01). Factors affecting OS and readmission-free survival (RFS) included prognostic scores, adjuvant therapy, ASA classification, surgical complications, metastasis number, and postoperative improvement. Better prognostic scores, adjuvant therapy, and clinical improvement were associated with longer OS and RFS, while complications or deterioration resulted in worse outcomes. Patients undergoing decompression and/or stabilization for metastatic spinal tumors showed improved outcomes, with favorable prognosis linked to Tomita score < 7, Frankel score A-C, ECOG 0-1, and Modified Tokuhashi score > 10.

EFFECT OF ADHESIVE LLC CELL PRETREATMENT BY OXAMATE ON THE SURVIVAL INDEXES AFTER TRANSITION TO DE-ADHESIVE GROWTH.

The ability to metabolic reprogramming is a distinctive feature of metastatically active tumor cells. A classic example of metabolic reprogramming, characteristic of almost all malignant cells, is aerobic glycolysis. Therefore, inhibition of glycolysis in tumor cells is considered a promising strategy for antitumor therapy. To generate Lewis lung carcinoma (LLC) cell subpopulation after pretreatment by a lactate dehydrogenase (LDH) inhibitor - oxamate in adhesive growth conditions, and then to study the metabolism of this subpopulation in the anchorage-independent growth conditions. LLC cells were cultured without oxamate or with 17 mM oxamate in the adhesive growth conditions with the following transition to the anchorage-independent growth conditions without oxamate. A distribution of LLC cells by cell cycle phases, apoptosis rate, levels of reactive oxygen species (ROS), E-cadherin, and vimentin were determined by flow cytometry. Glucose consumption and lactate production were determined by spectrophotometry. 48-h oxamate treatment in adhesive growth conditions resulted in a 30% decrease of the total number of LLC cells compared to the control. In 72 h after the transfer of both oxamate-treated and control cells into the anchorage-independent growth condition without oxamate, the number of viable cells pretreated with oxamate was reduced by 17% (p < 0.05) compared to the control cells. However, the distribution of cells by cell cycle phases did not differ. In cells pre-treated with oxamate, the rate of glucose consumption decreased by 20% (p < 0.05), ROS generation was reduced by 17%, vimentin expression decreased by 10% while the rate of lactate production was the same in oxamate-pretreated and control cells. The cytostatic effect of oxamate demonstrated in adhesive growth conditions persisted for 72 h in the anchorage-independent growth conditions. The absence of differences in the cell cycle phase distribution and a decrease in the ROS generation may indicate the initial stage of overcoming the cytostatic effect of oxamate after 72 h of culturing LLC cells in anchorage- independent growth conditions.

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.

Impact of Brake Wear Particles on Eukaryotic Cell Viability and Associated Oxidative Stress Responses

In this study, the cytotoxic effects of brake wear particles (≥250 nm ceramic/ceramic wear particles (CCWPs) and ≤100 nm ceramic/steel wear particles (CSWPs)) and 100 nm iron (III) oxide ultrafine particles (IOUFPs) on human lung carcinoma (A549) and Chinese hamster ovary (CHO) cells were investigated. Cell viability was determined using the MTT and Calcein AM methods. Oxidative stress was assessed by measuring reactive oxygen species (ROS), intracellular reduced glutathione (GSH), and malondialdehyde (MDA) concentrations under exposure to the above particles in the concentration range of 10–80 µg/mL. The initial assessments of CCWPs and CSWPs on the cell viability were performed after a 4-h exposure but later extended to 24 h to investigate the time-dependent of the cell viability and oxidative stress. MTT and Calcein AM assays indicated that the A549 cells are less susceptible to CCWPs and CSWPs than the CHO cells when exposed for both 4 h and 24 h. This study highlights that oxidative stress induced by CCWPs, CSWPs, and IOUFPs is cell-specific. While CCWPs did not affect glutathione (GSH) levels in the CHO cells, it significantly reduced GSH levels in A549 cells, with the exception of 80 µg/mL. Both CCWPs and CSWPs increased the lipid peroxidation in both cell types; however, the A549 cells demonstrated lower sensitivity to these treatments.

Asteroid Saponins: A Review of Their Bioactivity and Selective Cytotoxicity.

Saponins are a diverse class of secondary metabolites that are often reported to exhibit a variety of pharmacological applications. While research into the elucidation and application of plant and class Holothuroidea-derived saponins (i.e., sea cucumbers) is extensive, the class Asteroidea-derived saponins (i.e., seastars) have been largely overlooked and primarily limited to elucidation. This review provides a comprehensive overview of the cytotoxic activities of asteroid-derived saponins against various cell cultures, for instance, mammalian erythrocytes, multiple microbial strains and cancer cell lines, including melanoma, breast, colon, and lung cancers. Highlighting the distinct structural variations in these saponins, this review examines their selective cytotoxicity and potency, with many demonstrating IC50 values in the low micromolar range. Specific compounds, such as asterosaponins and polyhydroxylated saponins, exhibit noteworthy effects, particularly against melanoma and lung carcinoma cells, while triterpenoid saponins were found to be highly cytotoxic to both erythrocytes and fungal cells. This review also addresses gaps in the research area, including the need for additional in vitro antimicrobial studies, in vivo studies, and further exploration of their mechanisms of action. By consolidating recent findings, we have shed light on the therapeutic potential of asteroid-derived steroidal saponins in developing novel antimicrobial and anticancer agents.

Pentacyclic triterpenoids with cytotoxic activity from the stems of Syzygium jambos (L.) Alston.

Phytochemical investigation of the stems of Syzygium jambos (L.) Alston resulted in the isolation of five new pentacyclic triterpenoids, including three oleananes (1, 2, and 5) and two ursanes (3 and 4), along with 23 known compounds (6-28). Their structures were elucidated by comprehensive spectroscopic analysis and chemical methods. All isolated compounds were evaluated for their cytotoxic activities against two lung carcinoma cell lines, H1975 and HCC827. Among them, compounds 2, 7, 11, 13-16, 18, and 23 exhibited significant cytotoxic activities against H1975 and/or HCC827 cells, with IC50 values below 10 μM. Furthermore, the preliminary structure-activity relationships of these pentacyclic triterpenoids are also discussed.

Consequences of Reprogrammed CD8+ T-Cell Therapy for Lewis Lung Carcinoma Cells and Neovasculogenesis in C57BL/6 Mice.

We studied the effect of reprogrammed CD8+ T cells (rT cells) from the bone marrow of intact mice on tumor cells and neovasculogenesis in mice with orthotopic Lewis lung carcinoma (LLC). Reprogramming of T cells was carried out using a MEK inhibitor and a PD-1 blocker; the targeting of rT cells to tumor cells was achieved by preincubation with LLC cell lysate. It was shown that the antitumor effect of rT cells was based on apoptosis of tumor cells. In addition, cell therapy reduced the number of endothelial cells (CD45-CD309+) and angiogenic cell precursors (CD45-CD117+CD309+), mesenchymal stem cells (CD45-CD31-CD34-CD44+), myeloid (CD45+CD34+CD31-) and non-myeloid (CD45+CD34-CD31-) fibrocytes, and leukocytes (CD45+) in the lungs and increased their number in the blood. Thus, rT cells impaired the recruitment of neovasculogenic cells to the lung. The antitumor effects of rT cells are superior to those of naive CD8+ T cells. The proposed reprogramming method can be useful in developing effective approaches to the therapy of lung cancer, as it allows obtaining cytotoxic rT cells capable of reducing the activity of neovasculogenesis.

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.

Establishing a new human lung squamous cell carcinoma cell line, OMUL-1, expressing insulin-like growth factor 1 receptor and programmed cell death ligand 1.

Squamous cell carcinoma is the second most prevalent type of non-small cell lung cancer. Analyzing the molecular mechanisms underlying lung carcinoma requires useful tools, such as squamous lung cancer cell lines. A novel new lung squamous cell carcinoma cell line, OMUL-1, was developed from the primary lung cancer of a 74-year-old man. We assessed the characteristics and behavior of OMUL-1 cells were examined, including their growth kinetics, tumorigenicity in mice, histological properties, gene expression profiles using reverse transcription polymerase chain reaction (RT-PCR), and RNA sequencing and invasion assays. OMUL-1-an adherent cell line-resulted in 100% tumor formation when subcutaneously injected into mice. Histological analysis of the subcutaneous tumor using hematoxylin and eosin staining revealed squamous cell carcinoma with characteristics similar to those of the primary tumor (p40 and p63 were positive, and TTF-1 was negative). An invasion assay demonstrated that OMUL-1 had a lower invasion ability compared to that of other developed cell lines. RT-PCR analysis and RNA sequencing indicated that OMUL-1 cells expressed FGFR1, FGFR2, FGFR3, FGFR4, EGFR, HER2, ErbB3, ErbB4, VEGFR3, IGF1R, c-MET, PDGFRa, and PDGFRb. Additionally, picropodophyllin (an IGF1R inhibitor) significantly inhibited the growth of OMUL-1 cells. Immunohistochemistry revealed that IGF1R and PD-L1 were expressed in both the primary and subcutaneous tumors. We developed a novel new squamous cell lung carcinoma cell line, OMUL-1, that expresses IGF1R and PD-L1.

Magnetic Resonance Imaging Assessment of Morphological Changes and Molecular Behavior to Evaluate Treatment Response of Brain Metastatic Lesions After Stereotactic Radiosurgery.

Brain metastases (BMs) are the most common type of intracranial tumors, frequently arising from primary cancers such as lung, breast, melanoma, and renal cell carcinoma. Magnetic resonance imaging (MRI) plays a crucial role in assessing both the morphological and molecular characteristics of BMs, particularly in evaluating treatment response following radiosurgery. However, the interpretation of these imaging changes remains complex, often influencing clinical decision-making. This study aims to evaluate the morphological changes and molecular behavior of BMs postradiosurgery using MRI to assess treatment response. A retrospective review was conducted at a high specialty medical center, including 41 patients with BMs treated with stereotactic radiosurgery (SRS) from 2018 to 2022. Patients had a baseline MRI (pre-SRS) prior to treatment and follow-ups at 2-3 months (MRI-2) and 5-6 months (MRI-3). The response assessment in neuro-oncology brain metastases (RANO-BM)criteria were used, and T1/T2 matching was analyzed for each follow-up. Logistic regression was performed relating the T1/T2 matching and susceptibility areas (susceptibility-weighted imaging (SWI)) for MRI-2 and MRI-3. Cross tables were created regarding treatment response and demographic characteristics according to Pearson's Chi-squared test. The mean age was 56.7 years; 53.7% (n= 22) were female. Primary tumors included lung (29.3%, n= 12), breast (19.5%, n= 8), colon (12.2%, n= 5), and melanoma and kidney tumors (7.3%, n= 3). Post-SRS changes included transitions from solid to cystic lesions, reduced perilesional edema, size reduction, and increased areas of magnetic susceptibility. A mixed pattern (areas of T1/T2 match + mismatch) was noted at lesion margins during follow-ups (MRI-2: 70.7% (n= 29), MRI-3: 68.3% (n= 28)). Most patients exhibited a partial response at MRI-2 (43.9%, n= 18), while at MRI-3, disease progression occurred (43.9%, n= 18) due to an increase in lesion number. Logistic regression linking T1/T2 matching and SWI demonstrated a significantly central-peripheral SWI distribution for T1/T2 match during both follow-ups (MRI-2:p = 0.005, R2: 0.52; MRI-3:p = 0.002, R2: 0.56). SWI distribution was higher when a mixed T1/T2 matching was present. Significant associations were found with systemic treatment and response type at MRI-2 (p =0.001), predominantly showing a partial response for those receiving chemotherapy + targeted therapy. SWI and T1/T2 mismatch are valuable tools reflecting changes in the tumor microenvironment postradiosurgery, aiding in treatment response monitoring. The appearance of susceptibility areas may precede changes in the enhancement of the lesion margin. Short-term follow-ups (2-3 months) are crucial due to prevalent progression, marked primarily by the appearance of new lesions in approximately 50% of patients.

Molecular Interactions of the Plant Steroid Hormone Epibrassinolide on Human Drug-Sensitive and Drug-Resistant Small-Cell Lung Carcinoma Cells.

Background: Small-cell lung cancer (SCLC) has a poor prognosis because it is often diagnosed after it has spread and develops multi-drug resistance. Epibrassinolide (EB) is a plant steroid hormone with widespread distribution and physiological effects. In plants, EB-activated gene expression occurs via a GSK-mediated signaling pathway, similar to Wnt-β-catenin signaling in animal cells that is elevated in cancer cells. Methods: This mechanistic parallel prompted investigations of the molecular interactions of EB on drug-sensitive (H69) and multi-drug-resistant (VPA) SCLC cells. Cellular and molecular investigations were performed. Results: Pharmacologic interactions between EB and the Wnt signaling inhibitors IGC-011 and PRI-724 were determined by the combination index method and showed antagonism, indicating that EB acts on the same pathway as these inhibitors. Following incubation of drug-sensitive and drug-resistant SCLC cells with EB, there was a reduction in β-catenin (e.g., 3.8 to 0.7 pg/µg protein), accompanied by a reduction in β-catenin promoter activity, measured by firefly luciferase-coupled promoter element transfection. Cellular β-catenin concentration is regulated by the active form of GSK3β. In Wnt signaling, active GSK3β is converted to inactive pGSK3β, thereby increasing the concentration of β-catenin. After incubation of SCLC cells with EB, there was a reduction in the inactive form (pGSK3β) and a relative increase in the active form (GSK3β). In vitro enzyme assays showed that EB did not inhibit purified GSK3β, but there was non-competitive inhibition when SCLC cell extracts were used as the source of enzyme. This indirect inhibition by EB indicates that it may act on the Wnt pathway by blocking the phosphorylation of GSK3β. The protein levels of three SCLC tumor markers, namely, NSE, CAV1, and MYCL1, were elevated in drug-resistant SCLC cells. EB incubation led to a significant reduction in the levels of the three markers. Two major effects of EB on SCLC cells are the promotion of apoptosis and the reversal of drug resistance. Transcriptional analyses showed that after exposure of SCLC cells to EB, there were increases in the expression of genes encoding apoptotic inducers (e.g., BAX and FAS) and effectors (e.g., CASP3) and reductions in the expression of genes encoding apoptosis inhibitors (e.g., survivin). PGP1 and MRP1, two membrane efflux pumps expressed in SCLC cells, were elevated in drug-resistant cells, but EB incubation did not affect these protein levels. Cellular assays of drug efflux by PGP1 showed an increase in drug-resistant cells, but EB did not alter efflux activity. Following exposure to human liver microsomes, EB was metabolized by NADPH-dependent oxidation and UDPG-dependent glucuronidation, as evidenced by the elimination of EB cytotoxicity against SCLC cells. Conclusions: Taken together, these data indicate that EB, a steroid hormone in plants consumed in the human diet, is pharmacologically active in drug-sensitive and drug-resistant SCLC cells in the Wnt signaling pathway, alters apoptotic gene expression, and is a substrate for microsomal modifications.