Lung Melanoma Research Articles

Investigating orbital foreign device-associated malignancies: a scoping review

BackgroundWhile prosthesis-associated malignancies have been acknowledged, awareness among surgeons and patients in the ophthalmologic field remains limited, despite the frequent occurrence of prosthesis-related surgeries. We aim to address this gap through a scoping review of malignancies following ophthalmologic surgeries involving various foreign device/prosthesis/implants.MethodsFollowing PRISMA guidelines, we conducted a review using PubMed and Embase for studies on cancer and ophthalmic prostheses/implants. The final selection of articles for the ophthalmology aspect underwent rigorous investigation.ResultsWe analyzed 30 studies, identifying 41 cases of malignancies following interventions involving orbital foreign devices. Foreign devices linked to malignancies included scleral shells, orbital implants, scleral buckles, encircling bands, and gold plates. Ocular surface squamous neoplasm was most common, with 29 cases. Other malignancies observed were pleomorphic sarcoma, synovial sarcoma, marginal zone B-cell lymphoma, sebaceous carcinoma, malignant melanoma, adenocarcinoma, and metastatic lung adenocarcinoma. These malignancies varied in characteristics and demographics, with some showing metastasis or local invasion. The median time to tumor development was 40 years.ConclusionsThis study highlights a spectrum of malignancies following orbital foreign device procedures and suggests a potential association between different types of orbital foreign devices and malignancies. Future studies, including well-designed epidemiologic studies and scientific experiments, are warranted to elucidate the causal relationship.

Selective expression and significance of ACKR2 in lung aerocytes

BackgroundACKR2 is an atypical chemokine receptor that plays a significant role in regulating inflammation by binding to inflammatory CC chemokines and facilitating their degradation. Previous findings suggest that the genetic...

(E)-1-(3-(3-Hydroxy-4-Methoxyphenyl)-1-(3,4,5-Trimethoxyphenyl)allyl)-1H-1,2,4-Triazole and Related Compounds: Their Synthesis and Biological Evaluation as Novel Antimitotic Agents Targeting Breast Cancer.

Background/Objectives: The synthesis of (E)-1-(1,3-diphenylallyl)-1H-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. Methods: A panel of 29 compounds was synthesized and examined by a preliminary screening in estrogen receptor (ER) and progesterone receptor (PR)-positive MCF-7 breast cancer cells together with cell cycle analysis and tubulin polymerization inhibition. Results: (E)-5-(3-(1H-1,2,4-triazol-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)-2-methoxyphenol 22b was identified as a potent antiproliferative compound with an IC50 value of 0.39 mM in MCF-7 breast cancer cells, 0.77 mM in triple-negative MDA-MB-231 breast cancer cells, and 0.37 mM in leukemia HL-60 cells. In addition, compound 22b demonstrated potent activity in the sub-micromolar range against the NCI 60 cancer cell line panel including prostate, melanoma, colon, leukemia, and non-small cell lung cancers. G2/M phase cell cycle arrest and the induction of apoptosis in MCF-7 cells together with inhibition of tubulin polymerization were demonstrated. Immunofluorescence studies confirmed that compound 22b targeted tubulin in MCF-7 cells, while computational docking studies predicted binding conformations for 22b in the colchicine binding site of tubulin. Compound 22b also selectively inhibited aromatase. Conclusions: Based on the results obtained, these novel compounds are suitable candidates for further investigation as antiproliferative microtubule-targeting agents for breast cancer.

Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma

ObjectiveCancer patients aged ≥80 years present unique characteristics affecting response to immune checkpoint inhibitors (ICIs), with unidentified molecular differences. This study aimed to explore potential biomarkers of response to ICI...

Differential diagnosis in immune checkpoint inhibitors neurotoxicity.

Neurologic symptoms seen in patients receiving immune checkpoint inhibitors (ICI) may not be entirely caused by immunotoxicity. We aim to highlight these confounding conditions through clinical cases to encourage early recognition and management. We describe a series of seven cases from our institution that were treated with ICI and presented with Neurologic symptoms and were diagnosed with superimposed conditions beyond immunotoxicity. A total of 7 cases are described that include acute motor axonal neuropathy with vitamin B12 deficiency, lumbosacral radiculopathy with Wernicke's, Herpes simplex virus (HSV) encephalitis reactivation, central nervous system vasculitis with renal vasculitis, myositis with fasciitis, myositis with fixed clinical deficit at resolution, and synovitis with accompanying carpal tunnel syndrome. Primary cancer site included lung adenocarcinoma (2/7), melanoma (4/7), and oropharyngeal squamous cell carcinoma (1/7). All patients had received treatment with more than one ICI. Median number of cycles prior to neurotoxicity was 3 cycles. Neurologic symptoms seen in patients receiving ICI may include other causes beyond immunotoxicity.

The Role of Metastasectomies and Immunotherapy in the Management of Melanoma Lung Metastases: An Analysis of the National Cancer Database.

Patients with metastatic melanoma to the lung typically have poor outcomes. Although a pulmonary metastasectomy for selected patients has been shown to improve survival, the role of surgical resection following the introduction of immunotherapy for metastatic melanoma is unknown. The objective of this study was to determine predictors of survival for patients with melanoma metastatic to the lung in the era of immunotherapy. In this retrospective study, data from the National Cancer Database were abstracted for patients with melanoma lung metastases. The overall survival was evaluated using Kaplan-Meier and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. Patients with concomitant metastases to organs other than the lung were excluded from the study. A total of 625 patients with lung metastases at the time of a skin melanoma diagnosis were identified. A total of 280 patients underwent a pulmonary metastasectomy, 267 received immunotherapy, and 78 were treated with both a metastasectomy and immunotherapy. During a median follow-up time of 34.6 months [IQR: 14.2, 75.9], a metastasectomy was found to offer significantly improved survival compared to immunotherapy alone. No difference was noted between a metastasectomy and a combination of a metastasectomy and immunotherapy in the adjusted Cox proportional hazard model. When statistical models were adjusted for risk factors, a metastasectomy maintained a significant survival advantage compared to immunotherapy. The addition of immunotherapy to the treatment of patients treated with a pulmonary metastasectomy did not improve survival. Our findings support the role of surgery for patients with pulmonary metastatic melanoma.

REV7: a small but mighty regulator of genome maintenance and cancer development.

REV7, also known as MAD2B, MAD2L2, and FANCV, is a HORMA-domain family protein crucial to multiple genome stability pathways. REV7's canonical role is as a member of polymerase ζ, a specialized translesion synthesis polymerase essential for DNA damage tolerance. REV7 also ensures accurate cell cycle progression and prevents premature mitotic progression by sequestering an anaphase-promoting complex/cyclosome activator. Additionally, REV7 supports genome integrity by directing double-strand break repair pathway choice as part of the recently characterized mammalian shieldin complex. Given that genome instability is a hallmark of cancer, it is unsurprising that REV7, with its numerous genome maintenance roles, is implicated in multiple malignancies, including ovarian cancer, glioma, breast cancer, malignant melanoma, and small-cell lung cancer. Moreover, high REV7 expression is associated with poor prognoses and treatment resistance in these and other cancers. Promisingly, early studies indicate that REV7 suppression enhances sensitivity to chemotherapeutics, including cisplatin. This review aims to provide a comprehensive overview of REV7's myriad roles in genome maintenance and other functions as well as offer an updated summary of its connections to cancer and treatment resistance.

Design and in vitro anticancer assessment of a click chemistry-derived dinuclear copper artificial metallo-nuclease.

Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6=bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres-central for enhancing AMN activity-to bind DNA, via two phenanthroline ligands separated by an aliphatic linker. DNA-binding experiments, involving circular dichroism spectroscopy, agarose gel electrophoresis and fluorescence quenching, revealed a preference for binding with adenine-thymine-rich DNA. The oxidative cleavage mechanism of Cu2-BPL-C6 was then elucidated using in vitro molecular and biophysical assays, including in-liquid atomic force microscopy analysis, revealing potent DNA cleavage mediated via superoxide and hydrogen peroxide oxidative pathways. Single-molecule analysis with peripheral blood mononuclear cells identified upregulated single-strand DNA lesions in Cu2-BPL-C6-treated cells. Using specific base excision repair (BER) enzymes, we showedthat Endo IV selectively repairs these lesions indicating that the complex generates apurinic and apyrimidinic adducts. Broad spectrum anticancer evaluation of BPL-C6 was performed by the National Cancer Institute's 60 human cell line screen (NCI-60) and revealed selectivity for certain melanoma, breast, colon and non-small cell lung cancer cell lines.

Potent prophylactic cancer vaccines harnessing surface antigens shared by tumour cells and induced pluripotent stem cells.

The development of prophylactic cancer vaccines typically involves the selection of combinations of tumour-associated antigens, tumour-specific antigens and neoantigens. Here we show that membranes from induced pluripotent stem cells can serve as a tumour-antigen pool, and that a nanoparticle vaccine consisting of self-assembled commercial adjuvants wrapped by such membranes robustly stimulated innate immunity, evaded antigen-specific tolerance and activated B-cell and T-cell responses, which were mediated by epitopes from the abundant number of antigens shared between the membranes of tumour cells and pluripotent stem cells. In mice, the vaccine elicited systemic antitumour memory T-cell and B-cell responses as well as tumour-specific immune responses after a tumour challenge, and inhibited the progression of melanoma, colon cancer, breast cancer and post-operative lung metastases. Harnessing antigens shared by pluripotent stem cell membranes and tumour membranes may facilitate the development of universal cancer vaccines.

<i>In vivo</i> antitumor effects of bis-benzimidazole derivatives in mouse melanoma and lung cancer models

BACKGROUND: The development of new antitumor agents on the basis of benzimidazoles opens new opportunities for treatment of the malignant tumors, including those refractory to conventional therapies. The benzimidazole derivatives demonstrate wide spectrum of biological activities, specifically antineoplastic effects, and high-level cytotoxicity toward human’s tumor cell lines. The exploration of antineoplastic effects of new synthetic benzimidazole derivatives in in vivo models of tumor growth will help the development of the effective doses and cancer treatment regimens with the use of such compounds. AIM: To assess the antineoplastic effects of the benzimidazole derivatives — monomeric compound MB2Py(Ac) and dimeric compound DB2Py(3) — in the continuous cellular models of Lewis lung carcinoma (LLC) and melanoma B16 in mice. MATERIALS AND METHODS: In vivo assessment of antineoplastic effects was performed in the continuous mouse models of Lewis lung carcinoma (LLC) and B16 melanoma after a single intravenous injection of MB2Py(Ac) and DB2Py(3). Irinotecan was used as a comparator drug. Antitumor effects were measured via standard parameters, such as tumor growth inhibition (TGI%) and tumor growth rate (TGR). RESULTS: The study compounds DB2Py(3) and MB2Py(Ac) used in the study doses and regimen demonstrated mild antitumor effect in the model of murine solid tumors (TGI 50%). In melanoma B16 model, the maximum tumor growth inhibition was 15% and 38.5%, respectively, for MB2Py(Ac) and DB2Py(3). In the lung carcinoma model, the mild effect was observed, e.g. 8% for MB2Py(Ac) and 23.4% for DB2Py(3). The effect of the comparator drug, irinotecan, was more expressive, although short-term. In particular, TGI achieved 52.5% for melanoma B16 and 34.5% for Lewis lung carcinoma (LLC). In general, melanoma B16 was more sensitive to the effects of both bis-benzimidazoles and irinotecan, compared to the lung carcinoma LLC. CONCLUSION: This study shows that the dimeric compound DB2Py(3) was the most promising among three study substances in the models of melanoma and lung carcinoma in mice. Nevertheless, its high toxicity imposes the necessity of further optimization for the clinical use. The substance MB2Py(Ac) demonstrated lowest efficacy, although it may be also explored in the modified treatment regimens.

Phytochemical Study and In Vitro Antioxidant Activity of Helianthemum cinereum Along with Antitumor Activity of the Isolated trans-Tiliroside and Luteolin 4'-O-β-Xyloside.

Twelve compounds (1-12), kaempferol (1), luteolin (2), luteolin 4'-O-β-xyloside (3), luteolin 4'-O-β-glucoside (4), quercetin 4'-O-β-xyloside (5), kaempferol-3-O-[6″-O-(E)-p-coumaroyl]-β-D-glucoside (trans-tiliroside) (6), protocatechuic acid (7), gallic acid (8), methyl gallate (9), ethyl gallate (10), shikimic acid-3-O-gallate (11), and 3,3',4'-tri-O-methyl-ellagic acid 4-sulfate (12), were isolated and identified from the aerial parts of Helianthemum cinereum (Cav.) Pers (synonym: Helianthemum rubellum C. Presl. All compounds were isolated by applying different chromatographic procedures, such as silica gel, RP-18 and Sephadex LH-20 columns. The structures were elucidated by extensive spectroscopic methods, mainly nuclear magnetic resonance NMR 1D and 2D, and mass spectrometry, as well as by comparison with the reported spectroscopic data. The two organic extracts, ethyl acetate (EtOAc) and butanol (BuOH), were evaluated for their potent phenolic and flavonoid contents using the Folin-Ciocalteu and aluminum chloride colorimetric methods. Furthermore, the antioxidant activity of the two extracts was determined using the DPPH, FRAP, and ABTS methods. Pure trans-tiliroside (6), the main isolated compound, and luteolin 4'-O-β-xyloside (3) were evaluated for their antitumor activity against the lung cancer (A549), melanoma (A375) and pancreatic cancer (Mia PaCa-2 and Panc-1) cell lines by MTT assay.

Contemporary trends in utilization of metastasectomy in the era of targeted and immunotherapies.

Metastasectomy is a useful adjunct in the management of metastatic cancer. Widespread adoption of novel targeted and immunotherapies has improved the survival profiles of multiple malignancies, which has potentially altered the role of metastasectomy. This study aimed to characterize trends in metastasectomy across five primary cancers eligible for these therapies. The National Inpatient Sample was used to identify patients who underwent metastasectomy in the United States (2016-2021). Patients with procedure codes for resection of the lung, liver, adrenal gland, brain, or small bowel and concurrent diagnosis codes for secondary malignant neoplasm of that site were included. Subjects were subcategorized by primary malignancy: colorectal cancer, lung cancer, breast cancer, melanoma, or renal cancer. Sample weights were used to produce national estimates, which were incidence adjusted by primary malignancy. Trends in utilization were calculated with average annual percent change (AAPC) and linear regression coefficients. Colorectal cancer was the most frequent indication for metastasectomy (n=57,644 cases), followed by lung cancer (n=55,090 cases), breast cancer (n=12,616 cases), renal cancer (n=8427 cases), and melanoma (n=5658 cases). Utilization of metastasectomy increased over the study period for breast cancer (AAPC, +10.6%; p=.013) and melanoma (AAPC, +8.3%; p=.040) but did not change for lung cancer (AAPC, -1.6%; p=.26), colorectal cancer (AAPC, +0.3%; p=.83), or renal cancer (AAPC, +2.3%; p=.36). Between 2016 and 2021, utilization of metastasectomy increased significantly for melanoma and breast cancer. The role of metastasectomy will likely continue to develop as new treatment protocols improve survival profiles for patients with metastatic disease.

Emerging Therapies for Brain Metastases in NSCLC, Breast Cancer, and Melanoma: A Critical Review.

Advancements in precision medicine have shifted the treatment paradigm of brain metastases (BM) from non-small cell lung cancer (NSCLC), breast cancer, and melanoma, especially through targeted therapies focused on specific molecular drivers. These novel agents have improved outcomes by overcoming challenges posed by the blood-brain barrier (BBB) and resistance mechanisms, enabling more effective treatment of BM. In NSCLC, therapies such as osimertinib have improved efficacy in treating EGFR-mutant BM, with emerging combinations such as amivantamab and lazertinib offering promising alternatives for patients resistant to frontline therapies. In HER2-positive breast cancer, significant advancements with tucatinib and trastuzumab deruxtecan (T-DXd) have transformed the treatment landscape, achieving improved survival and intracranial control in patients with BM. Similarly, in triple-negative breast cancer (TNBC), novel therapies such as sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) offer new hope for managing BM. For melanoma, the combination of immune checkpoint inhibitors such as nivolumab and ipilimumab has proven effective in enhancing survival for patients with BM, both in BRAF-mutant and wild-type cases. Developing targeted therapies penetrating the BBB has revolutionizedBM treatment by targeting key drivers like EGFR, ALK, HER2, and BRAF. Despite improved survival, challenges persist, particularly for patients with resistant genetic alterations. Future research should optimise combination therapies, overcome resistance, and refine treatment sequencing. Continued emphasis on personalized, biomarker-driven approaches offers the potential to further improve outcomes, even for complex cases.

Non-invasive multi-cancer detection using DNA hypomethylation of LINE-1 retrotransposons.

The detection of circulating tumor DNA, which allows non-invasive tumor molecular profiling and disease follow-up, promises optimal and individualized management of patients with cancer. However, detecting small fractions of tumor DNA released when the tumor burden is reduced remains a challenge. We implemented a new highly sensitive strategy to detect base-pair resolution methylation patterns from plasma DNA and assessed the potential of hypomethylation of LINE-1 retrotransposons as a non-invasive multi-cancer detection biomarker. The DIAMOND (Detection of Long Interspersed Nuclear Element Altered Methylation ON plasma DNA) method targets 30-40,000 young L1 scattered throughout the genome, covering about 100,000 CpG sites and is based on a reference-free analysis pipeline. Resulting machine learning-based classifiers showed powerful correct classification rates discriminating healthy and tumor plasmas from 6 types of cancers (colorectal, breast, lung, ovarian, gastric cancers and uveal melanoma including localized stages) in two independent cohorts (AUC = 88% to 100%, N = 747). DIAMOND can also be used to perform copy number alterations (CNA) analysis which improves cancer detection. This should lead to the development of more efficient non-invasive diagnostic tests adapted to all cancer patients, based on the universality of these factors.

The Roles of Cytoplasmic Polyadenylation Element Binding Protein 1 in Tumorigenesis.

CPEB1 is an alternative polyadenylation binding protein that promotes or suppresses the expression of related mRNAs and proteins by binding to a highly conserved Cytoplasmic Polyadenylation Element (CPE) in the mRNAs 3'UTR. It is found to express abnormally in multiple tumors and affect tumorigenesis through many pathways. This review summarizes the functions and mechanisms of CPEB1 in a variety of cancers and suggests new directions for future related treatments. A total of 95 articles were eligible for inclusion based on the year, quality of the research, and the strength of association with CPEB1. In this review, current research about how CPEB1 affects the initiation and progression of glioblastoma, breast cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, non-small cell lung cancer, prostate cancer, and melanoma are dissected, and the biomedical functions and mechanisms are summarized. CPEB1 mostly presents as a tumor suppressor for breast cancer, endometrial carcinoma, hepatocellular carcinoma, non-small cell lung cancer, prostate cancer, and melanoma. However, for glioblastoma, gastric cancer, and colorectal cancer, CPEB1 exhibts two opposing properties of tumorigenesis, either promoting or inhibiting it. CPEB1 is likely to serve as a target and dynamic detection index or prognostic indicator for its function of apoptosis, activity, proliferation, migration, invasion, stemness, drug resistance, and even ferroptosis in various cancers.

Immunotherapy or targeted therapy with or without stereotactic radiosurgery for patients with brain metastases from melanoma or non-small cell lung cancer - The ETOP 19-21 USZ-STRIKE study.

Immunotherapy or targeted therapy with or without stereotactic radiosurgery for patients with brain metastases from melanoma or non-small cell lung cancer - The ETOP 19-21 USZ-STRIKE study.

HSD46 Care Pathway of Lung Cancer and Melanoma Patients Treated With Immune Checkpoint Inhibitors (ICI) in Hospital at Home and Administration Costs in France in 2021 and 2022

HSD46 Care Pathway of Lung Cancer and Melanoma Patients Treated With Immune Checkpoint Inhibitors (ICI) in Hospital at Home and Administration Costs in France in 2021 and 2022

PCR218 Health-Related Quality of Life (HRQoL), in Patients With Durable Response to Immune Checkpoint Inhibitors (ICIS) for Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) or Melanoma: QUALICI Study

PCR218 Health-Related Quality of Life (HRQoL), in Patients With Durable Response to Immune Checkpoint Inhibitors (ICIS) for Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) or Melanoma: QUALICI Study

Neoantigen sequestrated autophagosomes as therapeutic cancer vaccines

Neoantigens serve as ideal personalized cancer vaccines because of their high immunogenicity, ability to evade central thymic tolerance, and minimal risk of eliciting autoimmune responses. Herein, we describe a genetically engineered autophagosome-based neoantigen vaccine (APNV) in combination with an immune checkpoint inhibitor (anti-PD-1 antibody) for cancer immunotherapy. The APNV was derived from engineered NIH 3T3 cells, which co-express melanoma neoantigens and autophagosome maker microtubule-associated proteins 1 A/1B light chain 3B (LC3), from which the LC3-labeled neoantigen-autophagosomes were isolated. These purified autophagosomes, in conjunction with vaccine adjuvants high-mobility group box 1 (HMGB1) and granulocyte-macrophage colony-stimulating factor (GM-CSF), were integrated into a hydrogel to create an APNV. The APNV effectively activated dendritic cells both in vitro and in vivo. Moreover, APNV, in combination with checkpoint blockade therapy, significantly hampered post-surgical tumor recurrence in a subcutaneous melanoma tumor model and effectively impeded metastatic progression in a melanoma lung metastasis model. This APNV may be conducive to making personalized therapeutic neoantigen vaccines for cancer immunotherapy.

Traditional Chinese medicine and its components effectively reduce resistance mediated by immune checkpoint inhibitors.

Immunotherapy has become a global focus in cancer treatment and research, with promising results from targeting immune checkpoints in tumors like non-small cell lung cancer, colon cancer, and melanoma. However, resistance to immune checkpoint inhibitors (ICIs) remains a significant challenge. Traditional Chinese medicine (TCM), known for its low toxicity and minimal side effects, shows promise in enhancing cancer treatment when combined with modern therapies. This study reviews recent research on ICIs resistance mechanisms and highlights TCM's potential in overcoming this resistance, aiming to improve ICIs efficacy while minimizing toxicity.