High-density pulmonary lesions: Review in chest imaging.

High-density pulmonary lesions are frequently seen in chest imaging, and it is important to identify their different causes. Radiologists must be able to distinguish between common and rare conditions in order to provide the best diagnosis and treatment. This article provides an overview of the various causes and imaging features of high-density lesions in the lungs. The lesions are classified into various categories, such as pulmonary nodules, inflammatory conditions, deposition diseases, contrast-related lesions, and thoracic devices. A clear understanding of these categories can help radiologists accurately diagnose and manage high-density pulmonary lesions encountered in practice.

An Adult Case of Medulloblastoma with Multiple Lung Metastatic Lesions-Case Report and Literature Review.

Medulloblastoma (MB) cerebelli is a common brain tumor of the childhood. MB commonly spreads through cerebrospinal fluid; however, there are several reported cases of extracranial spread. The most common sites of extracranial metastasis are bones and bone marrow followed by peritoneum, liver, and lungs. Here, we report a case of pulmonary metastatic lesions of adult cerebellar MB that were discovered 1 year after the primary surgical treatment. We also tried to highlight similar reported cases in the literature.

Lipid-coated gold nanorods for photoimmunotherapy of primary breast cancer and the prevention of metastasis.

Nanomedicines hold promise for the treatment of various diseases. However, treating cancer metastasis remains highly challenging. In this study, we synthesized gold nanorods (AuNRs) containing (α-GC), an immune stimulator, for the treatment of primary cancer, metastasis, and recurrence of the cancer. Therefore, the AuNR were coated with lipid bilayers loaded with α-GC (α-LA). Upon irradiation with 808 nm light, α-LA showed a temperature increase. Intra-tumoral injection of α-LA in mice and local irradiation of the 4T1 breast cancer tumor effectively eliminated tumor growth. We found that the presence of α-GC in α-LA activated dendritic cells and T cells in the spleen, which completely blocked the development of lung metastasis. In mice injected with α-LA for primary breast cancer treatment, we observed antigen-specific T cell responses and increased cytotoxicity against 4T1 cells. We conclude that α-LA is promising for the treatment of both primary breast cancer and its metastasis.

Antibody and siRNA Nanocarriers to Suppress Wnt Signaling, Tumor Growth, and Lung Metastasis in Triple-Negative Breast Cancer.

The paucity of targeted therapies for triple-negative breast cancer (TNBC) causes patients with this aggressive disease to suffer a poor clinical prognosis. A promising target for therapeutic intervention is the Wnt signaling pathway, which is activated in TNBC cells when extracellular Wnt ligands bind overexpressed Frizzled7 (FZD7) transmembrane receptors. This stabilizes intracellular ß-catenin proteins that in turn promote transcription of oncogenes that drive tumor growth and metastasis. To suppress Wnt signaling in TNBC cells, we developed therapeutic nanoparticles (NPs) functionalized with FZD7 antibodies and ß-catenin small interfering RNAs (siRNAs). The antibodies enable TNBC cell-specific binding and inhibit Wnt signaling by locking FZD7 receptors in a ligand unresponsive state, while the siRNAs suppress ß-catenin through RNA interference. Compared to NPs coated with antibodies or siRNAs individually, NPs coated with both agents more potently reduce the expression of several Wnt related genes in TNBC cells, leading to greater inhibition of cell proliferation, migration, and spheroid formation. In two murine models of metastatic TNBC, the dual antibody/siRNA nanocarriers outperformed controls in terms of inhibiting tumor growth, metastasis, and recurrence. These findings demonstrate suppressing Wnt signaling at both the receptor and mRNA levels via antibody/siRNA nanocarriers is a promising approach to combat TNBC.

FeSA­Ir/Metallene Nanozymes Induce Sequential Ferroptosis­Pyroptosis for Multi­Immunogenic Responses Against Lung Metastasis.

For cancer metastasis inhibition, the combining of nanozymes with immune checkpoint blockade (ICB) therapy remains the major challenge in controllable reactive oxygen species (ROS) generation for creating effective immunogenicity. Herein, new nanozymes with light-controlled ROS production in terms of quantity and variety are developed by conjugating supramolecular-wrapped Fe single atom on iridium metallene with lattice-strained nanoislands (FeSA-Ir@PF NSs). The Fenton-like catalysis of FeSA-Ir@PF NSs effectively produced •OH radicals in dark, which induced ferroptosis and apoptosis of cancer cells. While under second near-infrared (NIR-II) light irradiation, FeSA-Ir@PF NSs showed ultrahigh photothermal conversion efficiency (𝜂, 75.29%), cooperative robust •OH generation, photocatalytic O2 and 1O2 generation, and caused significant pyroptosis of cancer cells. The controllable ROS generation, sequential cancer cells ferroptosis and pyroptosis, led 99.1% primary tumor inhibition and multi-immunogenic responses in vivo. Most importantly, the inhibition of cancer lung metastasis is completely achieved by FeSA-Ir@PF NSs with immune checkpoint inhibitors, as demonstrated in different mice lung metastasis models, including circulating tumor cells (CTCs) model. This work provided new inspiration for developing nanozymes for cancer treatments and metastasis inhibition.

Rare manifestation of pulmonary benign metastasizing leiomyoma: Respiratory failure.

We report a case of a 42-year-old woman diagnosed with pulmonary benign metastasizing leiomyomatosis with a random nodular pattern on image and with a rare clinical condition progressing with respiratory failure and severe hypoxemia. This study is relevant due to the rarity of the tomographic pattern and the patient's clinical presentation. There is no treatment guideline for this comorbidity, which further increases the importance of publishing case reports in the literature.

Nanotechnology for the theranostic opportunity of breast cancer lung metastasis: recent advancements and future challenges.

Lung metastasis of breast cancer is rapidly becoming a thorny problem in the treatment of patients with breast cancer and an obstacle to long-term survival. The main challenges of treatment are the absence of therapeutic targets and drug resistance, which promotes the development of nanotechnology in the diagnosis and treatment process. Taking advantage of the controllability and targeting of nanotechnology, drug-targeted delivery, controlled sustained release, multi-drug combination, improved drug efficacy, and reduced side effects can be realized in the process of the diagnosis and treatment of metastatic breast cancer (MBC). Several nanotechnology-based theranostic strategies have been investigated in breast cancer lung metastases (BCLM): targeted drug delivery, imaging analysis, immunotherapy, gene therapy, and multi-modality combined therapy, and some clinical applications are in the research phase. In this review, we present current nanotechnology-based diagnosis and treatment approaches for patients of incurable breast cancer with lung metastases, and we hope to be able to summarize more effective and promising nano-drug diagnosis and treatment systems that aim to improve the survival of patients with advanced MBC. We describe nanoplatform-based experimental studies and clinical trials targeting the tumor and the tumor microenvironment (TME) for BCLM to obtain more targeted treatment and in the future treatment steps for patients to provide a pioneering strategy.

Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway.

The spreading of cancer cells from the primary tumor site to other parts of the body, known as metastasis, is the leading cause of cancer recurrence and mortality in patients with triple-negative breast cancer (TNBC). Overexpression of epidermal growth factor receptor (EGFR) is observed in approximately 70% of TNBC patients. EGFR is crucial for promoting tumor metastasis and associated with poor prognosis. Therefore, it is vital to identify effective therapeutic strategies targeting EGFR inhibition. Ononin, an isoflavonoid found in various plants, such as clover and soybeans, has been shown to have anticancer properties in several cancers. In the present study, we aimed to investigate the effects of ononin on TNBC lung metastasis and the associated molecular pathways. We used various assays, including cell viability, colony formation, Transwell, wound healing, ELISA, Western blotting, and staining techniques, to achieve this objective. The results demonstrated that ononin effectively suppressed cellular proliferation and induced apoptosis, as evidenced by the cell viability assay, colony formation assay, and expression of apoptosis markers, and reduced the metastatic capabilities of TNBC cells. These effects were achieved through the direct suppression of cell adhesion, invasiveness and motility. Furthermore, in TNBC xenograft lung metastatic models, ononin treatment significantly reduced tumor growth and lung metastasis. Additionally, ononin reversed the epithelial-mesenchymal transition (EMT) by downregulating the expression of EMT markers and matrix metalloproteinases, as confirmed by Western blot analysis. Furthermore, ononin treatment reduced EGFR phosphorylation and suppressed the PI3K, Akt, and mTOR signaling pathways, which was further confirmed using EGFR agonists or inhibitors. Importantly, ononin treatment did not exert any toxic effects on liver or kidney function. In conclusion, our findings suggest that ononin is a safe and potentially therapeutic treatment for TNBC metastasis that targets the EGFR-mediated PI3K/Akt/mTOR pathway. Further studies are warranted to validate its efficacy and explore its potential clinical applications.

Establishment of humanised xenograft models as in vivo study for lung metastasis of osteosarcoma.

Humanised xenograft models and cancer cell lines are widely used for preclinical drug evaluation, biological studies, and targeted therapy strategies in cancer research. A humanised mouse model is a laboratory mouse that has been genetically modified to contain specific human genes, cells, or tissues. By introducing human-specific elements into rodents, researchers can create a more accurate representation of human physiological and pathological processes. Lacking an appropriate animal model for osteosarcoma (OS), hindered understanding of underlying mechanisms in OS metastasis progression. Markedly, metastasis influences the prognosis and treatment of osteosarcoma. Gaining insight into the mechanisms and occurrences of metastasis could potentially facilitate oncologists in improving therapies. Hence, it is important to develop a lung metastatic OS model to study the basic biology of its progression. This study has established a tumour-bearing mouse model using HOS-143B cell line which was injected into male NOD.SCID gamma (NSG) mice at two locations; intramuscularly (hind leg) and subcutaneously (back) respectively. The primary and metastatic tumour size was monitored by palpating the area of tumour induced and quantified using digital calliper. H&E staining was performed by pathologist to confirm metastasis. Our results showed that mice injected with 1 million cancer cells were unable to produce tumours. Meanwhile, mice injected with three million cancer cells showed tumour development and lung metastasis after 25 days of cancer cell inoculation. In conclusion, this study has successfully established a lung metastatic OS mouse model that could be useful for biological studies of OS. These findings imply that this model is essential for safety and efficacy before clinical trials, accelerate the translation from basic research to therapeutic applications.

Wedelolactone suppresses breast cancer growth and metastasis via regulating TGF-ß1/Smad signaling pathway.

OBJECTIVE: Breast cancer is a malignant tumor with high invasion and metastasis. TGF-ß1-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of breast cancer. Wedelolactone (Wed) is extracted from herbal medicine Ecliptae Herba, which is reported to have antineoplastic activity. Here, we aimed to elucidate the efficacy and mechanism of Wed against breast cancer. METHODS: The effects of Wed on migration and invasion of 4T1 were detected. The expression of EMT-related markers was detected by Western blot and qPCR. The 4T1 orthotopic murine breast cancer model was established to evaluate the therapeutic effect of Wed on the growth and metastasis of breast cancer through TGF-ß1/Smad pathway. RESULTS: Wed inhibited the proliferation, migration and invasion of 4T1. It exhibited concentration-dependent inhibition of p-Smad2/3. Wed also reversed the expression of EMT-markers induced by TGF-ß1. In addition, Wed suppressed the growth and metastasis of breast cancer in mice. It also affected p-Smad3 expression as well as EMT-related genes, suggesting that its anti-breast cancer effect may be related to the TGF-ß1/Smad pathway. CONCLUSION: Wed reverses EMT by regulating TGF-ß1/Smad pathway, potentially serving as a therapeutic agent for breast cancer. Wed is expected to be a potential drug to inhibit TGF-ß1/Smad pathway-related diseases.

A Two-Pronged Delivery Strategy Disrupting Positive Feedback Loop of Neutrophil Extracellular Traps for Metastasis Suppression.

Neutrophil extracellular traps (NETs) severely affect tumor metastasis through a self-perpetuating feedback loop involving two key steps: (1) mitochondrial aerobic respiration-induced hypoxia promotes NET formation and (2) NETs enhance mitochondrial metabolism to exacerbate hypoxia. Herein, we propose a two-pronged approach with the activity of NET-degrading and mitochondrion-damaging by simultaneously targeting drugs to NETs and tumor mitochondria of this loop. In addition to specifically recognizing and eliminating extant NETs, the NET-targeting nanoparticle also reduces NET-induced mitochondrial biogenesis, thus inhibiting the initial step of the feedback loop and mitigating extant NETs' impact on tumor metastasis. Simultaneously, the mitochondrion-targeting system intercepts mitochondrial metabolism and alleviates tumor hypoxia, inhibiting neutrophil infiltration and subsequent NET formation, which reduces the source of NETs and disrupts another step of the self-amplifying feedback loop. Together, the combination significantly reduces the formation of NET-tumor cell clusters by disrupting the interaction between NETs and tumor mitochondria, thereby impeding the metastatic cascade including tumor invasion, hematogenous spread, and distant colonization. This work represents an innovative attempt to disrupt the feedback loop in tumor metastasis, offering a promising therapeutic approach restraining NET-assisted metastasis.

Profilin 2 isoform expression is associated with lung metastasis of colorectal cancer according to a comprehensive gene expression study using a mouse model.

Lung metastasis is the second most common type of metastasis in colorectal cancer. Specific treatments for lung metastasis have not been developed since the underlying mechanisms are poorly understood. The present study aimed to elucidate the molecular basis of lung metastasis in colorectal cancer. In a mouse model, cell lines that were highly metastatic to the lungs were established by injecting colorectal cancer cells through the tail vein and removing them from the lungs. Differential gene expression comparing the transfected cells with their parental cells was investigated using DNA microarrays. The results were functionally interpreted using gene enrichment analysis and validated using reverse transcription-quantitative PCR (RT-qPCR). The isoforms of the identified genes were examined by melting curve analysis. The present study established colorectal cancer cell lines that were highly metastatic to the lungs. DNA microarray experiments revealed that genes (N-cadherin, VE-cadherin, Six4, Akt and VCAM1) involved in motility, proliferation and adhesion were upregulated, and genes (tissue inhibitor of metalloproteinase-3 and PAX6) with tumor-suppressive functions were downregulated in metastatic cells. Profilin 2 (PFN2) expression was upregulated in multiple metastatic cell lines using RT-qPCR. Two PFN2 isoforms were overexpressed in metastatic cells. In vitro and in vivo models were established and genes associated with lung metastasis were identified to overcome the heterogeneity of the disease. Overall, aberrant PFN2 expression is unreported in lung metastasis in colorectal cancer. In the present study, two PFN2 isoforms with differential tissue distribution were upregulated in metastatic cells, suggesting that they promote lung metastasis in colorectal cancer.

Combination of Brucea javanica oil emulsion and Aidi injection associated with the long­term survival of a patient with colon cancer and lung metastases post­chemotherapy: A case report.

Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide. Treatment options for patients with advanced CRC recurrence and metastases remain limited, particularly for those unable to withstand chemotherapy. Bruscea javanica oil emulsion (BJOE) and Aidi injection (ADI) are two plant-derived products that have antitumor effects. The current report presents the case of a patient with colon cancer and resectable lung metastases. Despite the surgical removal of the metastatic lesions, tumor recurrence was not prevented. The patient underwent three chemotherapy regimens following lung metastasis surgery, namely XELOX, single-agent irinotecan and single-agent tegafur-gimeracil-oteracil potassium capsule, but experienced intolerable adverse reactions with each, and disease progression was observed during subsequent follow-up. Nonetheless, the patient achieved a progression-free survival of >5 years under BJOE + ADI treatment and continues to receive BJOE + ADI treatment to date. Although further research is required to understand the effectiveness of this treatment combination, the present case may instill hope in the treatment of future patients.

Lung-intestinal axis, Shuangshen granules attenuate lung metastasis by regulating the intestinal microbiota and related metabolites.

BACKGROUND: Based on the proposed lung-intestinal axis, there is a significant correlation between the microbiota and lung metastasis. Targeting the microbial composition is valuable in modulating the host response to cancer therapeutics. As a traditional Chinese medicine (TCM) formula, Shuangshen granules (SSG) are clinically useful in delaying lung metastasis, but its underlying mechanisms remain unknown. METHODS: The C57BL/6N mice were chosen to establish the Lewis lung cancer models. The broad-spectrum antibiotics (ABX) group was set up to estimate the effect of microbiota composition on metastasis. The therapeutic effects of different doses of SSG in treating lung metastasis were investigated through histopathology, immunohistochemistry, and Western blot analysis methods. Additionally, the phenotype of tumor-associated macrophages (TAMs) in the lung and blood was evaluated by flow cytometry. The fecal microbiota transplantation (FMT) and negative control (ABX plus high dose SSG group) experiments were also designed to assess intestinal microbiota's role in SSG intervention's outcome in lung metastasis. The 16S rRNA amplicon sequencing and Untargeted metabolomic analysis were used to analyze intestinal microbiota and metabolite changes mediated by SSG in tumor-bearing mice with lung metastasis. RESULT: ABX could observably lead to intestinal microbiota dysbiosis and enhance metastasis. SSG showed a significant chemopreventive effect in lung metastasis, reduced metastatic nodules and the expression levels of pre-metastatic niche biomarkers, and enriched the ratio of CD86+F4/80+CD11b+ cells, while FMT delayed metastasis similarly. The analysis of microbiota and metabolites revealed that SSG significantly enriched probiotics in feces, including Akkermansia muciniphila, Lachnoclostridium sp YL32, Limosilactobacillus reuteri, and potential anti-cancer serum metabolites, including Ginsenoside Rb1, Isoquinoline, Betulin and so on. We also investigated the mechanism of SSG protection against lung metastasis and showed that SSG regulated microbiota, improved TAMs polarization, and inhibited the expression of the NF-κB pathway. CONCLUSION: The results presented in our article demonstrated that SSG improved TAMs polarization and inhibited the NF-κB pathway by alleviating intestinal microbiota imbalance and metabolic disorders in tumor-bearing mice, resulting in delayed lung metastasis.

Lung Metastases in Endometrial Carcinoma: A Deadly Twist.

This case report describes the clinical course of a 73-year-old postmenopausal female presenting with a persistent cough, breathlessness, and hypertension. Upon examination, she exhibited signs of respiratory distress, prompting transfer to the intensive care unit (ICU) where type 1 respiratory failure was diagnosed. Chest imaging revealed bilateral lung opacities, leading to a diagnosis of lung metastasis. Subsequent screening investigations unveiled endometrial carcinoma with atypical respiratory symptoms, highlighting the importance of thorough evaluation. Despite prompt management and biopsy confirmation, the patient's condition rapidly deteriorated, underscoring the aggressive nature of metastatic endometrial carcinoma. This case underscores the necessity of considering atypical presentations and timely intervention in managing such malignancies.

Lung Metastasectomy: Where Do We Stand? Results from an Italian Multicentric Prospective Database.

Background/Objectives: The surgical resection of pulmonary metastases is considered a therapeutic option in selected cases. In light of this, we present the results from a national multicenter prospective registry of lung metastasectomy. Methods: This retrospective analysis involves data collected prospectively and consecutively in a national multicentric Italian database, including patients who underwent lung metastasectomy. The primary endpoints were the analysis of morbidity and overall survival (OS), with secondary endpoints focusing on the analysis of potential risk factors affecting both morbidity and OS. Results: A total 470 lung procedures were performed (4 pneumonectomies, 46 lobectomies/bilobectomies, 13 segmentectomies and 407 wedge resections) on 461 patients (258 men and 203 women, mean age of 63.1 years). The majority of patients had metastases from colorectal cancer (45.8%). In most cases (63.6%), patients had only one lung metastasis. A minimally invasive approach was chosen in 143 cases (30.4%). The mean operative time was 118 min, with no reported deaths. Morbidity most frequently consisted of prolonged air leaking and bleeding, but no re-intervention was required. Statistical analysis revealed that morbidity was significantly affected by operative time and pulmonary comorbidities, while OS was significantly affected by disease-free interval (DFI) > 24 months (p = 0.005), epithelial histology (p = 0.001) and colorectal histology (p = 0.004) during univariate analysis. No significant correlation was found between OS and age, gender, surgical approach, surgical extent, surgical device, the number of resected metastases, lesion diameter, the site of lesions and nodal involvement. Multivariate analysis of OS confirmed that only epithelial histology and DFI were risk-factors, with p-values of 0.041 and 0.031, respectively. Conclusions: Lung metastasectomy appears to be a safe procedure, with acceptable morbidity, even with a minimally invasive approach. However, it remains a local treatment of a systemic disease. Therefore, careful attention should be paid to selecting patients who could truly benefit from surgical intervention.

Prostate Cancer Lung Metastasis: Clinical Insights and Therapeutic Strategies.

Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

Type X collagen knockdown inactivate ITGB1/PI3K/AKT to suppress chronic unpredictable mild stress-stimulated triple-negative breast cancer progression.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, has a poor prognosis and limited access to efficient targeted treatments. Chronic unpredictable mild stress (CUMS) is highly risk factor for TNBC occurrence and development. Type X collagen (COL10A1), a crucial protein component of the extracellular matrix, ranks second among all aberrantly expressed genes in TNBC, and it is significantly up-regulated under CUMS. Nevertheless, the impact of CUMS and COL10A1 on TNBC, along with the underlying mechanisms are still unclear. In this research, we studied the effect of CUMS-induced norepinephrine (NE) elevation on TNBC, and uncovered that it notably enhanced TNBC cell proliferation, migration, and invasion in vitro, and also fostering tumor growth and lung metastasis in vivo. Additionally, our investigation found that COL10A1 directly interacted with integrin subunit beta 1 (ITGB1), then activates the downstream PI3K/AKT signaling pathway, thereby promoting TNBC growth and metastasis, while it was reversed by knocking down of COL10A1 or ITGB1. Our study demonstrated that the TNBC could respond to CUMS, and advocate for COL10A1 as a pivotal therapeutic target in TNBC treatment.