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The successful pulmonary metastasis of malignant cancer cells depends on the survival of circulating tumor cells in a distant and hostile microenvironment. The formation of a pre-metastatic niche (PMN) creates a supportive environment for subsequent metastasis. Circular RNAs (circRNAs) are increasingly acknowledged as crucial elements in the mechanisms of metastasis due to their stable structures and functions, making them promising early metastasis detection markers. However, the specific expression patterns and roles of circRNAs in the lungs before metastasis remain largely unexplored. Our research aims to chart the circRNA expression profile and assess their impact on the lung PMN. We developed a lung PMN model and employed comprehensive RNA sequencing to analyze the differences in circRNA expression between normal and premetastatic lungs. We identified 38 significantly different circRNAs, primarily involved in metabolism, apoptosis, and inflammation pathways. We then focused on one specific circRNA, circ:chr4:150406196 -- 150406664 (circRERE-PMN), which exhibited a significant change in expression and was prevalent in myeloid-derived suppressor cells (MDSCs), alveolar epithelial cells, and macrophages within the pre-metastatic lung environment. CircRERE-PMN was found to potentially regulate apoptosis and the expression of cytokines and chemokines through its interaction with the downstream target HUR in alveolar epithelial cells. Overall, our study highlights the crucial role of circRNAs in the formation of lung PMNs, supporting their potential as diagnostic or therapeutic targets for lung metastasis. [ABSTRACT FROM AUTHOR]

Purpose: To construct and validate nomograms for predicting lung metastasis probability in patients with malignant primary osseous spinal neoplasms (MPOSN) at initial diagnosis and predicting cancer-specific survival (CSS) in the lung metastasis subgroup. Methods: A total of 1,298 patients with spinal primary osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma were retrospectively collected. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic analysis were used to identify the predictors for lung metastasis. LASSO and multivariate Cox analysis were used to identify the prognostic factors for 3- and 5-year CSS in the lung metastasis subgroup. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) were used to estimate the accuracy and net benefits of nomograms. Results: Histologic type, grade, lymph node involvement, tumor size, tumor extension, and other site metastasis were identified as predictors for lung metastasis. The area under the curve (AUC) for the training and validating cohorts were 0.825 and 0.827, respectively. Age, histologic type, surgery at primary site, and grade were identified as the prognostic factors for the CSS. The AUC for the 3- and 5-year CSS were 0.790 and 0.740, respectively. Calibration curves revealed good agreements, and the Hosmer and Lemeshow test identified the models to be well fitted. DCA curves demonstrated that nomograms were clinically useful. Conclusion: The nomograms constructed and validated by us could provide clinicians with a rapid and user-friendly tool to predict lung metastasis probability in patients with MPOSN at initial diagnosis and make a personalized CSS evaluation for the lung metastasis subgroup. [ABSTRACT FROM AUTHOR]

Simple Summary: We retrospectively evaluated the clinical outcomes of lung metastasectomy in 147 patients with pulmonary metastases from primary liver tumors at three medical centers. Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. These findings can guide thoracic surgeons in patient selection and predicting surgical outcomes. Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary metastasectomies at three medical centers between February 2007 and December 2020. All patients were pathologically confirmed to have lung metastases from liver cancer. Among the 147 patients, 110, 17, and 20 initially underwent surgical resection, radiofrequency ablation, and transcatheter arterial embolization, respectively. The 5-year overall survival (OS) in the study cohort was 22%. Univariate analysis revealed four factors associated with better OS: surgical resection as the initial primary liver tumor treatment (p = 0.004), a disease-free interval exceeding 12 months after the initial liver surgery (p = 0.036), a lower Model for End-Stage Liver Disease (MELD)-Na score (≤20) for liver cirrhosis (p = 0.044), and the absence of local liver tumor recurrence at the time of pulmonary metastasectomy (p = 0.004). Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. Our findings can assist thoracic surgeons in selecting suitable patients for surgery and predicting surgical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma is among the most frequent cutaneous tumors. Over the years, the understanding and diagnostic sensitivity has increased due to the introduction and improved knowledge of dermoscopy, as well as of more recent noninvasive technologies, such as reflectance confocal microscopy and line-field confocal optical coherence. Imaging plays a central role in the staging of the disease; however, its role in the follow-up, as well as the choice of the best technique in each patient, is still not fully clarified. Cutaneous squamous cell carcinoma (SCC) is the second most frequent skin cancer, accounting for approximately 20% of all cutaneous malignancies, and with an increasing incidence due to the progressive increment of the average age of life. The diagnosis is usually firstly suspected based on clinical manifestations; however, dermoscopic features may improve diagnostic sensitivity in cases of an uncertain diagnosis and may guide the biopsy, which should be performed to histopathologically prove the tumor. New diagnostic strategies may improve the sensitivity of the cutaneous SCC, such as reflectance confocal microscopy and line-field confocal optical coherence, for which increasing data have been recently published. Imaging has a central role in the staging of the diseases, while its exact role, as well as the choice of the best techniques, during the follow-up are not fully clarified. The aim of this literature review is to describe diagnostic clinical and instrumental tools of cutaneous SCC, with an insight into the role of imaging in the diagnosis and follow-up of cutaneous SCC. [ABSTRACT FROM AUTHOR]

Neoadjuvant intratumoral (IT) therapy could amplify the weak responses to checkpoint blockade therapy observed in breast cancer (BC). In this study, we administered neoadjuvant IT anti-canine PD-1 therapy (IT acPD-1) alone or combined with IT cowpea mosaic virus therapy (IT CPMV/acPD-1) to companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. CMC patients treated weekly with acPD-1 (n = 3) or CPMV/acPD-1 (n = 3) for four weeks or with CPMV/acPD-1 (n = 3 patients not candidates for surgery) for up to 11 weeks did not experience immune-related adverse events. We found that acPD-1 and CPMV/acPD-1 injections resulted in tumor control and a reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of treated dogs. In two metastatic CMC patients, CPMV/acPD-1 treatments resulted in the control and reduction of established lung metastases. CPMV/acPD-1 treatments were associated with altered gene expression related to TLR1–4 signaling and complement pathways. These novel therapies could be effective for CMC patients. Owing to the extensive similarities between CMC and human BC, IT CPMV combined with approved anti-PD-1 therapies could be a novel and effective immunotherapy to treat local BC and suppress metastatic BC. [ABSTRACT FROM AUTHOR]

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. Schematic illustration of α-LA-mediated photo-immunotherapy for treatment of primary tumor and prevention of metastatic lung cancer. [Display omitted] • For PTT, AuNRs were coated with lipid film comprising α-galactosylceramide (α-LA). • α-LA with 808 nm laser irradiation eliminated orthotopic 4 T1 breast cancer by PTT. • α-LA also prevented recurrence of lung metastatic 4 T1 cancer. • Anti-metastatic effect of a-LA was mediated by cancer antigen-specific immunity. [ABSTRACT FROM AUTHOR]

Pulmonary metastasectomy has been clarified in improving long-term survival in most primary malignancies with pulmonary metastasis, while the role of additional lymph node dissection remained controversial. We aimed to investigate the prognosis of lymph node involvement and identify the role of lymph node dissection during pulmonary metastasectomy in a real-world cohort. We identified patients diagnosed with pulmonary metastases with ≤3 cm in size and received pulmonary metastasectomy between 2004 and 2017 in the Surveillance, Epidemiology, and End Results database. We compared the survival via Kaplan–Meier analysis and propensity score matching method, and the multivariable analysis was conducted by cox regression analysis. A total of 3452 patients were included, of which 2268(65.7%) received lymph node dissection, and the incidence of node-positive was 11.3%(256/2268). In total, the median overall survival was 62.8 months(interquartile range, 28.6–118.9 months), and the lymph node involvement was referred to an impaired survival compared to node-negative diseases(5-year overall survival rate, 58.0% versus 38.6%), with comparable survival between N1 and N2 diseases(P = 0.774). Lymph node dissection was associated with improved survival(HR = 0.80; 95%CI, 0.71–0.90; P < 0.001), and the survival benefits remained regardless of age, sex, the number of metastases, and surgical procedures, even in those with node-negative diseases. At least eight LNDs might lead to a significant improvement in survival, and additional survival benefits might be limited with additional dissected lymph nodes. Lymph node involvement was associated with impaired survival, and lymph node dissection during pulmonary metastasectomy could improve long-term survival and more accurate staging. [ABSTRACT FROM AUTHOR]

Introduction: Limited studies are available on the topic of lung metastasis in sacral chordoma. The primary objective of this study was to investigate the prevalence, characteristics, associated factors, and prognosis of lung metastasis in sacral chordoma. Methods: A total of 221 cases with primary sacral chordoma, all of whom underwent surgical resection at our center, were included in this study. Comprehensive demographic information, imaging findings, and oncological evaluations were collected and thoroughly analyzed. The diagnosis of lung metastasis in the majority of cases was established through radiographic examinations. Results: The prevalence of lung metastasis in the cohort was 19.5%, with the lung emerging as the predominant site of distant metastasis. Recurrent chordoma cases exhibited a significantly higher lung metastasis rate in comparison to newly diagnosed chordoma cases (33.33% and 12.76%, p=0.0005). Patients with lung metastasis had a larger tumor size, a higher proportion of previous sacral chordoma surgeries and a greater likelihood of postoperative recurrence. Associated factors of lung metastasis were tumor size, postoperative recurrence and radiotherapy. Patients with lung metastasis exhibited decreased median overall survival (91 vs. 144 months for those without lung metastasis, p<0.05) and recurrence-free survival (27 vs. 68 months, p<0.001) times. Discussion: Lung is the most common site of distant metastasis in sacral chordoma with an incidence rate nearly 20%. Larger tumor size and postoperative recurrence are risk factors for lung metastasis while radiotherapy is a protective factor. Occurrence of lung metastasis in sacral chordoma is a negative prognostic factor. [ABSTRACT FROM AUTHOR]

T lymphocytes play a central role in immunotherapy, utilizing physical interactions to actively inhibit the development of metastases. However, tumor immune privilege and heterogeneity pose challenges by protecting against immune attacks and limiting immune cell infiltration into tumors, particularly in invasive metastatic clusters. Here, a tumor penetrating magnetic particles (TUP) containing the cascade‐responsive cell membrane‐mimetic copolymer (zwitterionic 2‐methacryloyloxyethyl phosphorylcholine‐co‐3‐hydroxypyridin‐4‐one, PH) and cuproptosis molecules (elesclomol‐copper, EsCu) for programming T cell infiltration is developed. The intravenously injected TUP accumulates at the tumor via the charge conversion of PH and hyperthermia effects of TUP. In metastatic clusters, ES and Cu, triggered by intracellular environments and hyperthermia, are readily released. ES and Cu simultaneously induce cuproptosis of cancer cells and stimulate immune responses. This process destroys self‐defense mechanisms and exacerbates cytotoxicity. The therapies facilitate the release of tumor‐associated antigens, including neoantigens and damage‐associated molecular patterns. Following this, the 3‐hydroxypyridin‐4‐one groups on TUP act as antigen reservoirs, transporting autologous tumor‐associated antigens to dendritic cells, thereby inducing prolonged immune activation. TUP acts as an antigen reservoir in copper apoptosis‐mediated lung metastasis, promoting the accumulation of immune cells in metastatic clusters and effectively preventing the progression of metastatic tumors. [ABSTRACT FROM AUTHOR]

Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1‐deficient mice are resistant to metastasis and further protected by combined immune‐checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF‐β1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK‐target cell responses, which is dysregulated and hijacked by tumors during metastatic progression. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer is a malignant tumor with high invasion and metastasis. TGF-β1-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-β1/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-β1. 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-β1/Smad pathway. Conclusion: Wed reverses EMT by regulating TGF-β1/Smad pathway, potentially serving as a therapeutic agent for breast cancer. Wed is expected to be a potential drug to inhibit TGF-β1/Smad pathway-related diseases. [ABSTRACT FROM AUTHOR]

Due to the insufficient Cu+ accumulation, Cu+ efflux mechanism, and highly immunosuppressive tumor microenvironment (TME) in lung metastasis, the cuproptosis efficacy is limited. Herein, an inhalable nanodevice (CLDCu) is constructed to successfully overcome the drawbacks of cuproptosis. CLDCu consists of a Cu2+-chitosan shell and low molecular weight heparin-tocopherol succinate (LMWH-TOS, LT) core with disulfiram (DSF) loading. The prepared CLDCu can be inhaled and accumulate in large amounts in lung lesions (63.6%) with 56.5 times higher than intravenous injection. Within tumor cells, the mild acidity triggers the co-release of DSF and Cu2+, thus generating bis(diethyldithiocarbamate)-copper (CuET) to block Cu+ efflux protein ATP7B and forming toxic Cu+, leading to enhanced cuproptosis. Meanwhile, the released chitosan cooperates with CLDCu-induced cuproptosis to activate stimulator of interferon genes (STING) pathway, which significantly potentiates dendritic cells (DCs) maturation, as wells as evokes innate and adaptive immunity. In lung metastatic mice model, CLDCu is found to induce cuproptosis and reverse the immunosuppressive TME by inhalation administration. Moreover, CLDCu combined with anti-programmed cell death protein ligand-1 antibody (aPD-L1) provokes stronger antitumor immunity. Therefore, nanomedicine that combines cuproptosis with STING activation is a novel strategy for tumor immunotherapy. An inhalable nanoformulation (CLDCu) co-delivering disulfiram and Cu2+ was designed to enhance lung metastasis immunotherapy via cuproptosis and cGAS–STING activation. Moreover, CLDCu collaborated with aPD-L1 provoked more powerful antitumor immunity. [Display omitted] [ABSTRACT FROM AUTHOR]

Metastasis leads to high mortality among cancer patients. It is a complex, multi-step biological process that involves the dissemination of cancer cells from the primary tumor and their systemic spread throughout the body, primarily through the epithelial-mesenchymal transition (EMT) program and immune evasion mechanisms. It presents a challenge in how to comprehensively treat metastatic cancer cells throughout the entire stage of the metastatic cascade using a simple system. Here, we fabricate a nanogel (HNO-NG) by covalently crosslinking a macromolecular nitric oxide (NO) donor with a photothermal IR780 iodide-containing hyaluronic acid derivative via a click reaction. This enables stable storage and tumor-targeted, photothermia-triggered release of NO to combat tumor metastasis throughout all stages. Upon laser irradiation (HNO-NG+L), the surge in NO production within tumor cells impairs the NF-κB/Snail/RKIP signaling loop that promotes the EMT program through S-nitrosylation, thus inhibiting cell dissemination from the primary tumor. On the other hand, it induces immunogenic cell death (ICD) and thereby augments anti-tumor immunity, which is crucial for killing both the primary tumor and systemically distributed tumor cells. Therefore, HNO-NG+L, by fully leveraging EMT reversal, ICD induction, and the lethal effect of NO, achieved impressive eradication of the primary tumor and significant prevention of lung metastasis in a mouse model of orthotropic 4T1 breast tumor that spontaneously metastasizes to the lungs, extending the NO-based therapeutic approach against tumor metastasis. [Display omitted] • Nanogel containing macromolecular NO donor enables double guarantee of NO storage. • HNO-NG + L with photothermia effect mediates spatiotemporal regulation of NO release under reducing conditions. • HNO-NG + L reverses EMT program, inhibiting cell dissemination from the primary tumor. • HNO-NG + L induces ICD, restoring systemic immune surveillance against tumor metastasis. [ABSTRACT FROM AUTHOR]

Herein, a dual‐responsive shape‐transforming charge‐reversal integrated nanomedicine system (DHP@BPP) is developed for the co‐delivery of the photosensitizer pyro pheophorbide‐α (Ppa), anti‐programmed cell death ligand 1 (PD‐L1) peptide (dPPA), and tumor‐associated macrophages (TAMs)‐regulating drug berberrubine (BBR). Hydrophobic Ppa and hydrophilic BBR are linked by matrix metalloproteinase‐2 (MMP‐2) responsive peptide (PMGMRKLVFF) to form BPP. BPP can self‐assemble into spherical nanoparticles with positive charge, which undergo shape transformation to nanofibers upon cleavage by MMP‐2 at tumor sites. The dPPA is conjugated with hexa‐histidine and polyethylene glycol to form DHP, which is then electrostatically adsorbed onto the surface of BPP to form DHP@BPP with negative surface charge. The DHP not only enhances the tumor‐targeting but also induces DHP disassociation and charge reversal of DHP@BPP due to protonation of histidine at the tumor site, thereby increasing tumor penetration while maintaining long blood circulation. Most importantly, through the combination of chemo‐photodynamic‐immunotherapy, it can repolarize TAMs from M2‐type to M1‐type while reducing PD‐L1 expression to reshape the immunosuppressive tumor microenvironment, thereby synergistically enhancing the effect of immunogenic cell death. In conclusion, this study offered a simple but effective idea for the treatment of immunosuppressive cancers through the combination of shape transformation and charge reversal, integrating chemo‐photodynamic‐immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract Purpose To investigate the value of multi-parametric MRI-based radiomics for preoperative prediction of lung metastases from soft tissue sarcoma (STS). Methods In total, 122 patients with clinicopathologically confirmed STS who underwent pretreatment T1-weighted contrast-enhanced (T1-CE) and T2-weighted fat-suppressed (T2FS) MRI scans were enrolled between Jul. 2017 and Mar. 2021. Radiomics signatures were established by calculating and selecting radiomics features from the two sequences. Clinical independent predictors were evaluated by statistical analysis. The radiomics nomogram was constructed from margin and radiomics features by multivariable logistic regression. Finally, the study used receiver operating characteristic (ROC) and calibration curves to evaluate performance of radiomics models. Decision curve analyses (DCA) were performed to evaluate clinical usefulness of the models. Results The margin was considered as an independent predictor (p

Adenoid cystic carcinoma is a rare malignant tumor that primarily occurs in the salivary glands. There are few reports of sublingual gland adenoid cystic carcinoma with lung metastases on which 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) was performed. We report the case of a 57-year-old Japanese woman with an adenoid cystic carcinoma of the sublingual gland with lung metastases in whom the FDG uptake of the lung metastasis was low despite high FDG uptake in the primary lesion. The pathological examination revealed that solid components were more visible and the Ki-67 index was more positive in the primary lesion compared to the metastatic lesion. We speculate that differences in tumor growth ability might have resulted in the differences in FDG uptake. This case demonstrates that significant differences might occur in the FDG uptake between primary and metastatic tumors.

Synovial sarcoma is a rare type of soft tissue sarcoma that typically arises in the lower extremities and rarely in the upper extremities. Here, we present an unusual case of a middle-aged man who complained of dyspnea, dry cough, and chest pain and was found to have a mass-like lesion on the ulnar side of his left wrist during physical examination. The patient also exhibited gynecomastia and had elevated β-human chorionic gonadotropin (βHCG) levels. Subsequent imaging and histopathological analysis of the wrist mass confirmed the diagnosis of synovial sarcoma with disseminated lung metastasis.This article aims to provide a comprehensive overview of the clinical and pathological characteristics of synovial sarcoma, highlight the importance of considering synovial sarcoma as a differential diagnosis in patients with abnormal hormonal assays, and emphasize the need for clinicians to be vigilant about any pathologic lesions existing on the upper extremity to avoid late diagnosis and the development of advanced cancerous diseases.

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. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to evaluate the predictive factors and metastatic time for liver and lung metastasis in locally advanced rectal cancer (RC) patients. Methods: Univariate and multivariate analysis were performed to identify risk factors and prognostic factors for liver metastasis and lung metastasis in RC. Survival probabilities were calculated using the Kaplan–Meier model and compared using the log-rank test between groups. The probability of time-to-event occurrence was calculated using the random survival forest model. Finally, the SEER database was used to verify our findings. Results: Our results indicated that pathological T stage and pathological N stage were independent predictive factors for liver metastasis. Furthermore, CEA level, pathological T stage, and tumor deposit were independent predictive factors for lung metastasis. Based on the results of a multivariate Cox analysis, we categorized patients with liver and lung metastasis into three groups based on their scores. The results revealed that patients with higher scores had a higher probability of experiencing metastasis. For liver metastasis, Groups 1, 2, and 3 all exhibited higher occurrence rates within the first 24 months. However, for lung metastasis, Group 4 showed the highest occurrence rate at the 12th month, while Groups 5 and 6 exhibited the highest occurrence rates at the 15th month. Conclusions: In summary, we developed predictive models to determine the likelihood of liver and lung metastasis in RC patients. It is crucial to implement a more intensive surveillance program for patients with unfavorable risk profiles in order to facilitate early detection of metastasis. [ABSTRACT FROM AUTHOR]

Osteosarcoma, a prevalent primary malignant bone tumor, often presents with lung metastases, severely impacting patient survival rates. Extracellular vesicles, particularly exosomes, play a pivotal role in the formation and progression of osteosarcoma-related pulmonary lesions. However, the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure, with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely unknown. This study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor site. This transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate (MARCKS) expression. Addressing this phenomenon, in this study we employ cationic bovine serum albumin (CBSA) to form nanoparticles (CBSA-anta-194/215) via electrostatic interaction with antagomir-miR-194/215. These nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles (anta-194/215@Exo) targeting osteosarcoma lung metastatic sites. Intervention with bioengineered exosome mimetics (anta-194/215@Exo) not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing mice. These findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS, making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.

Abstract Background We aimed to improve the image quality (IQ) of sparse-view computed tomography (CT) images using a U-Net for lung metastasis detection and determine the best tradeoff between number of views, IQ, and diagnostic confidence. Methods CT images from 41 subjects aged 62.8 ± 10.6 years (mean ± standard deviation, 23 men), 34 with lung metastasis, 7 healthy, were retrospectively selected (2016–2018) and forward projected onto 2,048-view sinograms. Six corresponding sparse-view CT data subsets at varying levels of undersampling were reconstructed from sinograms using filtered backprojection with 16, 32, 64, 128, 256, and 512 views. A dual-frame U-Net was trained and evaluated for each subsampling level on 8,658 images from 22 diseased subjects. A representative image per scan was selected from 19 subjects (12 diseased, 7 healthy) for a single-blinded multireader study. These slices, for all levels of subsampling, with and without U-Net postprocessing, were presented to three readers. IQ and diagnostic confidence were ranked using predefined scales. Subjective nodule segmentation was evaluated using sensitivity and Dice similarity coefficient (DSC); clustered Wilcoxon signed-rank test was used. Results The 64-projection sparse-view images resulted in 0.89 sensitivity and 0.81 DSC, while their counterparts, postprocessed with the U-Net, had improved metrics (0.94 sensitivity and 0.85 DSC) (p = 0.400). Fewer views led to insufficient IQ for diagnosis. For increased views, no substantial discrepancies were noted between sparse-view and postprocessed images. Conclusions Projection views can be reduced from 2,048 to 64 while maintaining IQ and the confidence of the radiologists on a satisfactory level. Relevance statement Our reader study demonstrates the benefit of U-Net postprocessing for regular CT screenings of patients with lung metastasis to increase the IQ and diagnostic confidence while reducing the dose. Key points • Sparse-projection-view streak artifacts reduce the quality and usability of sparse-view CT images. • U-Net-based postprocessing removes sparse-view artifacts while maintaining diagnostically accurate IQ. • Postprocessed sparse-view CTs drastically increase radiologists’ confidence in diagnosing lung metastasis. Graphical Abstract

Abstract To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Nuclear accumulation of YAP/TAZ promotes tumorigenesis in several cancers, including melanoma. Although the mechanisms underlying the nuclear retention of YAP are known, those underlying the retention of TAZ remain unclear. Our study investigates a novel acetylation/deacetylation switch in TAZ, governing its subcellular localization in melanoma tumorigenesis. Methods: Immunoprecipitation/Western blot assessed TAZ protein interactions and acetylation. SIRT5 activity was quantified with enzyme-linked immunosorbent assay. Immunofluorescence indicated TAZ nuclear localization. TEAD transcriptional activity was measured through luciferase reporter assays. ChIP detected TAZ binding to the CTGF promoter. Transwell and wound healing assays quantified melanoma cell invasiveness and migration. Metastasis was evaluated using a mouse model via tail vein injections. Clinical relevance was explored via immunohistochemical staining of patient tumors. Results: CBP facilitated TAZ acetylation at K54 in response to epidermal growth factor stimulation, while SIRT5 mediated deacetylation. Acetylation correlated with phosphorylation, regulating TAZ's binding with LATS2 or TEAD. TAZ K54 acetylation enhanced its S89 phosphorylation, promoting cytosolic retention via LATS2 interaction. SIRT5-mediated deacetylation enhanced TAZ-TEAD interaction and nuclear retention. Chromatin IP showed SIRT5-deacetylated TAZ recruited to CTGF promoter, boosting transcriptional activity. In a mouse model, SIRT5 overexpression induced melanoma metastasis to lung tissue following the injection of B16F10 melanocytes via the tail vein, and this effect was prevented by verteporfin treatment. Conclusions: Our study revealed a novel mechanism of TAZ nuclear retention regulated by SIRT5-mediated K54 deacetylation and demonstrated the significance of TAZ deacetylation in CTGF expression. This study highlights the potential implications of the SIRT5/TAZ axis for treating metastatic melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: In our paper, we examine various facets of prostate cancer lung metastasis. We explore their clinical manifestations, such as respiratory symptoms and potential complications. Diagnostic modalities, including imaging techniques and biomarker analysis, are scrutinized for accurate identification. Treatment strategies, encompassing surgery, radiation therapy, chemotherapy, and targeted therapies, are discussed for their efficacy. Survival outcomes are assessed to gauge the effectiveness of different interventions. Through comprehensive analysis, we aim to provide insights into managing prostate cancer lung metastasis and enhancing patient care and outcomes. 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. [ABSTRACT FROM AUTHOR]

Purpose: To establish two nomograms to quantify the risk of lung metastasis (LM) in laryngeal carcinoma (LC) and predict the overall survival of LC patients with LM. Methods: Totally 9515 LC patients diagnosed histologically from 2000 to 2019 were collected from the Surveillance, Epidemiology, and End Results database. The independent diagnostic factors for LM in LC patients and prognostic factors for LC patients with LM were identified by logistic and Cox regression analysis, respectively. Nomograms were established based on regression coefficients and evaluated by receiver operating characteristic curve, calibration curves, and decision curve analysis. Results: Patients with supraglottis, higher pathological grade, higher N stage, and distant metastasis (bone, brain, or liver) were more likely to have LM (P < 0.05). Chemotherapy, surgery and radiotherapy were independent factors of the overall survival of LC patients with LM (P < 0.05). The area under curve of diagnostic nomogram were 0.834 and 0.816 in the training and validation cohort respectively. For the prognostic nomogram, the area under curves of 1-, 2-, and 3-years were 0.735, 0.734, and 0.709 in the training cohort and 0.705, 0.803, and 0.809 in the validation cohort. The calibration curves and decision curve analysis indicated good performance of the nomograms. Conclusion: Distant metastasis (bone, brain, or liver) and N stage should be considered for prediction of LM in LC patients. Chemotherapy is the most significant influencing prognostic factor improving the survival of LC patients with LM. Two nomograms may benefit for providing better precautionary measures and treatment decision. [ABSTRACT FROM AUTHOR]

Purpose: To facilitate patient consultation and assist in clinical decision-making, we developed a predictive model to analyze the overall survival (OS) rate of cervical cancer patients with concurrent lung metastasis for 6 months, 1 year, or 2 years. Methods: We extracted data on patients diagnosed with cervical cancer and concurrent lung metastasis between 2010 and 2020 from the Surveillance, Epidemiology, and End Results (SEER) database. Through a random assignment process, these patients were allocated to either a training cohort or a validation cohort, maintaining a 7:3 ratio. Utilizing both univariate and multivariate Cox regression analyses, we determined the independent prognostic factors influencing OS. To enhance predictive accuracy, we developed a nomogram model incorporating these identified independent prognostic variables. Model effectiveness was subsequently assessed using various metrics, including receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results: We gathered data on 1330 patients diagnosed with cervical cancer with lung metastases. An OS nomogram was developed, accounting for factors such as histological type, presence of metastases in other organs (brain, liver), surgical interventions, radiation therapy, and chemotherapy. The ROC curves, calibration plots, and DCA curves demonstrated the commendable predictive performance of the nomogram in assessing the prognosis of cervical cancer patients with lung metastases in both the training and validation cohorts. Conclusion: By utilizing clinical data from the SEER database, we have effectively devised a nomogram capable of predicting the 6-month, 1-year, and 2-year survival rates of cervical cancer patients with lung metastases. The nomogram boasts high accuracy, offering precise prognostic predictions. Its implementation can guide the formulation of individualized follow-up and treatment plans for enhanced patient care. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma is one of the most lethal bone tumors worldwide. Immune checkpoint blockades have achieved significant success in solid tumors; however, their role in osteosarcoma remains obscure. Therefore, we aim to explore the clinical significance of soluble immune checkpoint-related proteins in osteosarcoma in this study. We identified four soluble immune checkpoint-related proteins as predictors of progress-free survival and lung metastasis-free survival of osteosarcoma patients. Our findings indicated that soluble immune checkpoint-related proteins could be promising biomarkers for the outcomes and immunotherapy of osteosarcoma. Background: The immune checkpoint blockade remains obscure in osteosarcoma (OS). We aim to explore the clinical significance of soluble immune checkpoint (ICK)-related proteins in OS. Methods: We profiled 14 soluble ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CTLA-4) in the plasma of 76 OS patients and matched controls. We evaluated the associations between the biomarkers and the risk of OS using unconditional multivariate logistic regression. The multivariate Cox model was utilized to develop the prediction model of OS. Immune subtypes were established from the identified biomarkers. Transcriptional data from GEO were analyzed to elucidate potential mechanisms. Results: We found that sTIM3, sCD137, sIDO, and sCTLA4 were significantly correlated with OS risk (all p < 0.05). sBTLA, sPDL2, and sCD27 were significantly associated with the risk of lung metastasis, whereas sBTLA and sTIM3 were associated with the risk of disease progression. We also established an immune subtype based on sBTLA, sPD1, sTIM3, and sPDL2. Patients in the sICK-type2 subtype had significantly decreased progression-free survival (PFS) and lung metastasis-free survival (LMFS) than those in the sICK-type1 subtype (log-rank p = 2.8 × 10−2, 1.7 × 10−2, respectively). Interestingly, we found that the trend of LMFS and PFS in the subtypes of corresponding ICK genes' expression was opposite to the results in the blood (log-rank p = 2.6 × 10−4, 9.5 × 10−4, respectively). Conclusion: Four soluble ICK-related proteins were associated with the survival of OS patients. Soluble ICK-related proteins could be promising biomarkers for the outcomes and immunotherapy of OS patients, though more research is warranted. [ABSTRACT FROM AUTHOR]

Cuproptosis shows enormous application prospects in lung metastasis treatment. However, the glycolysis, Cu+ efflux mechanisms, and insufficient lung drug accumulation severely restrict cuproptosis efficacy. Herein, an inhalable poly (2-(N -oxide- N , N -diethylamino)ethyl methacrylate) (OPDEA)-coated copper-based metal–organic framework encapsulating pyruvate dehydrogenase kinase 1 siRNA (siPDK) is constructed for mediating cuproptosis and subsequently promoting lung metastasis immunotherapy, namely OMP. After inhalation, OMP shows highly efficient lung accumulation and long-term retention, ascribing to the OPDEA-mediated pulmonary mucosa penetration. Within tumor cells, OMP is degraded to release Cu2+ under acidic condition, which will be reduced to toxic Cu+ to induce cuproptosis under glutathione (GSH) regulation. Meanwhile, siPDK released from OMP inhibits intracellular glycolysis and adenosine-5ʹ-triphosphate (ATP) production, then blocking the Cu+ efflux protein ATP7B, thereby rendering tumor cells more sensitive to OMP-mediated cuproptosis. Moreover, OMP-mediated cuproptosis triggers immunogenic cell death (ICD) to promote dendritic cells (DCs) maturation and CD8+ T cells infiltration. Notably, OMP-induced cuproptosis up-regulates membrane-associated programmed cell death-ligand 1 (PD-L1) expression and induces soluble PD-L1 secretion, and thus synergizes with anti-PD-L1 antibodies (aPD-L1) to reprogram immunosuppressive tumor microenvironment, finally yielding improved immunotherapy efficacy. Overall, OMP may serve as an efficient inhalable nanoplatform and afford preferable efficacy against lung metastasis through inducing cuproptosis and combining with aPD-L1. A cuproptosis-mediated immunotherapy nanoplatform (OMP) was constructed for lung metastasis treatment by inhalation administration. Moreover, OMP synergized with PD-L1 checkpoint blockade provoked more powerful anti-tumor immunity to suppress lung metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Osteosarcoma, a prevalent primary malignant bone tumor, often presents with lung metastases, severely impacting patient survival rates. Extracellular vesicles, particularly exosomes, play a pivotal role in the formation and progression of osteosarcoma-related pulmonary lesions. However, the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure, with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely unknown. This study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor site. This transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate (MARCKS) expression. Addressing this phenomenon, in this study we employ cationic bovine serum albumin (CBSA) to form nanoparticles (CBSA-anta-194/215) via electrostatic interaction with antagomir-miR-194/215. These nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles (anta-194/215@Exo) targeting osteosarcoma lung metastatic sites. Intervention with bioengineered exosome mimetics (anta-194/215@Exo) not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing mice. These findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS, making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases. Exosomes of pulmonary metastatic osteosarcoma transport the miR-194/215 cluster to primary osteosarcoma, promoting secondary metastasis via the MARCKS/PHLPP/p-AKT/Slug pathway, while disrupting miR-194/215 delivery and hinders the progression of osteosarcoma. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: In the last decade, the understanding of lung neoplasms, particularly rare salivary gland-type tumors (SGT), has deepened significantly. This review intends to spotlight the latest findings, particularly emphasizing the differentiation between primary and metastatic SGTs in the lung. [ABSTRACT FROM AUTHOR]

Background: We aimed to improve the image quality (IQ) of sparse-view computed tomography (CT) images using a U-Net for lung metastasis detection and determine the best tradeoff between number of views, IQ, and diagnostic confidence. Methods: CT images from 41 subjects aged 62.8 ± 10.6 years (mean ± standard deviation, 23 men), 34 with lung metastasis, 7 healthy, were retrospectively selected (2016–2018) and forward projected onto 2,048-view sinograms. Six corresponding sparse-view CT data subsets at varying levels of undersampling were reconstructed from sinograms using filtered backprojection with 16, 32, 64, 128, 256, and 512 views. A dual-frame U-Net was trained and evaluated for each subsampling level on 8,658 images from 22 diseased subjects. A representative image per scan was selected from 19 subjects (12 diseased, 7 healthy) for a single-blinded multireader study. These slices, for all levels of subsampling, with and without U-Net postprocessing, were presented to three readers. IQ and diagnostic confidence were ranked using predefined scales. Subjective nodule segmentation was evaluated using sensitivity and Dice similarity coefficient (DSC); clustered Wilcoxon signed-rank test was used. Results: The 64-projection sparse-view images resulted in 0.89 sensitivity and 0.81 DSC, while their counterparts, postprocessed with the U-Net, had improved metrics (0.94 sensitivity and 0.85 DSC) (p = 0.400). Fewer views led to insufficient IQ for diagnosis. For increased views, no substantial discrepancies were noted between sparse-view and postprocessed images. Conclusions: Projection views can be reduced from 2,048 to 64 while maintaining IQ and the confidence of the radiologists on a satisfactory level. Relevance statement: Our reader study demonstrates the benefit of U-Net postprocessing for regular CT screenings of patients with lung metastasis to increase the IQ and diagnostic confidence while reducing the dose. Key points: • Sparse-projection-view streak artifacts reduce the quality and usability of sparse-view CT images. • U-Net-based postprocessing removes sparse-view artifacts while maintaining diagnostically accurate IQ. • Postprocessed sparse-view CTs drastically increase radiologists' confidence in diagnosing lung metastasis. [ABSTRACT FROM AUTHOR]

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis. [ABSTRACT FROM AUTHOR]

Introduction Breast cancer is a rare disease in males with unknown etiology and variable rate of incidence among different ethnic and geographical groups. Objectives This article studies the clinical profile of male breast cancer in Kashmir Valley of India Materials and Methods This study was a retrospective study conducted at a superspecialty hospital (Government Medical College Srinagar) in the department of medical oncology over a period of 4 years from January 2017 to October 2021. All male patients who presented with a histopathology-proven diagnosis of breast cancer were included and studied. Results A total of 8 male patients with breast cancer were studied. The median age at diagnosis was 55 years. Most of the patients were from rural background. The most common presenting symptom was breast lump followed by ulceration. The most common location of the tumor was retroareolar. Infiltrating ductal carcinoma (100%) was the only subtype present in our patients. Locally advanced disease accounted for most of the cases. Among stage IV patients two had bone as the metastatic site and one patient had in addition lung metastasis. Immunohistochemistry analysis revealed that all patients (100%) were hormone receptor positive with only one patient being triple positive (12.5%). None of the patients had triple negative disease in our study. In our study 6 patients were treated with multimodalities (surgery, chemo, radiation, and targeted agents). Conclusion Male breast cancer is a well-recognized entity and the gender gap of disease need to be abolished. Awareness among masses and training of general practitioners is needed to pick cases at early stage. [ABSTRACT FROM AUTHOR]

Introduction: Gestational trophoblastic neoplasia (GTN) is a highly invasive tumor, mainly spreading to the lungs. However, lung metastasis in GTN is usually not considered as an adverse prognostic factor. Therefore, the aim of this study was to summarize the results of previous studies and evaluate the effects of lung metastasis on the treatment and prognosis of GTN. Material and methods: The study was prospectively registered in PROSPERO (CRD42023372371). Electronic databases including PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and China Biomedical Literature Database were used for a systematical search of relevant studies published up to November 21, 2022. The observational studies reporting the clinical outcomes of GTN patients with and without lung metastasis were selected. The incidences of resistance, relapse, and mortality of GTN patients were extracted and successively grouped based on the presence of lung metastasis. The pooled relative risks (RRs) and 95% confidence interval (95% CI) of the eligible studies were calculated. The qualities of included studies were assessed with the Newcastle‐Ottawa Scale and the certainty of evidence was graded based on the GRADE. The meta‐analysis was performed using Stata 12.0 and GradePro software. Results: Five publications with 3629 GTN patients were included. The meta‐analysis revealed that the GTN with lung metastasis was strongly correlated with first‐line chemoresistance (pooled RR = 1.40, 95% CI: 1.22 to 1.61, p < 0.001), recurrence (pooled RR = 3.03, 95% CI: 1.21 to 7.62, p = 0.018), and disease‐specific death (pooled RR = 22.11, 95% CI: 3.37 to 145.08, p = 0.001). Ethnicity was also an important factor and Caucasian GTN patients with lung metastasis showed a higher risk of recurrence as revealed by the subgroup analysis (pooled RR = 5.10, 95% CI: 2.38 to 10.94, p < 0.001). Conclusions: GTN patients with lung metastasis exhibited a higher risk of chemoresistance, relapse, and disease‐specific death. Patients with lung metastasis among the Caucasian population had a higher risk of recurrence than Asian populations. Therefore, the presence of lung metastases might be considered as a high‐risk factor for prognosis of GTN and deserves more attention in the choice of first‐line chemotherapy regimens and follow‐up. [ABSTRACT FROM AUTHOR]

Objective: Distant metastasis occurs in some patients at the first diagnosis of nasopharyngeal carcinoma (NPC), the prognosis is poor, and there are significant individual differences. This study established a nomogram model of lung metastasis of NPC as a supplement to TNM staging. Methods: The training cohort is used to build the nomogram model, and the validation cohort is used to evaluate the model. The training cohort of 177 patients is from the Surveillance, Epidemiology, and End Results (SEER) database. Factors affecting overall survival (OS) in patients with lung metastasis of NPC analysis by Cox regression analysis and then a nomogram were established. 122 patients from the Affiliated Tumor Hospital of Guangxi Medical University were selected as the external validation cohort. The concordance index (C-index), the area under the curve (AUC), and the calibration curve were used to assess the accuracy of the nomogram and used the decision curve analysis (DCA) curve to measure the clinical benefit capacity of the model. The patients were separated into two groups with different risks, and the "Kaplan-Meier (KM)" survival analysis was used to evaluate the differentiation ability of the model. Results: Age, T-stage, radiation, chemotherapy, and brain metastases can affect the OS in NPC with lung metastasis. A nomogram was developed according to the above five factors. The C-index of the training cohort and the validation cohort were 0.726 (95% CI: 0.692-0.760) and 0.762 (95% CI: 0.733-0.791). The AUC of the nomogram was better than that of the TNM staging. In the training cohort, the nomogram predicted OS AUC values of 0.767, 0.746, and 0.750 at 1, 2, and 3 years, TNM stage of 0.574, 0.596, and 0.640. In the validation cohort, nomogram predictions of OS AUC values of 0.817, 0.857, and 0.791 for 1, 2, and 3 years, TNM stage of 0.575, 0.612, and 0.663. DCA curves suggest that nomogram have better clinical net benefits than TNM staging. The KM survival analysis shows that the nomogram has a reasonable risk stratification ability. Conclusion: This study successfully established a nomogram model of NPC lung metastasis, which can be used as a supplement to TNM staging and provide reference for clinicians. [ABSTRACT FROM AUTHOR]

We report a case of invasive metastatic hydatidiform mola on lung with clinical/radiological signs of massive hemothorax, solved with urgent thoracotomy. A 30-year-old woman, nulliparious, was accepted to Gynecologic Clinic because of a planned operation of pelvic tumor. State after endometrial curettage. It is diagnosed as mola hydatidosa. It is evacuated hemorrhagic fluid after pleural punction. Thoracic Computed Tomography (CT)-scan reveals a great massive shadow with right compressive atelectasis of right lung. Urgent right thoracotomy solves massive clots and fresh hemorrhage. In lower right lobe it's seen hemorrhagic tumor with dimension 3 cm × 2 cm and one smaller subpleuraly-1 cm × 1 cm, both excised with wedge resection. Pathological finding revealed invasive hydatidiform mole. Conclusion: Bleeding from metastatic hydatidiform mole from lung should be solving with surgical correction, and corresponding therapy for metastatic disease and careful surveillance of gynecologic problems. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor 2 (HER2)-positive breast cancer with lung metastases resistant to targeted agents is a common therapeutic challenge. Absence of preclinical lung metastasis models that are resistant to multiple anti-HER2 targeted drugs hampers the development of novel therapies. We established a novel HER2-positive breast cancer cell line (L-JIMT-1) with a high propensity to form lung metastases from the parenteral JIMT-1 cell line by injecting JIMT-1 cells into immunodeficient SCID mice. Lung metastases developed in all mice injected with L-JIMT-1 cells, and more rapidly and in greater numbers compared with the parental JIMT-1 cells. L-JIMT-1 cells expressed more epidermal growth factor receptor and HER2 than JIMT-1 cells. L-JIMT-1 cells were resistant to all five tyrosine kinase inhibitors tested in vitro (afatinib, erlotinib, lapatinib, sapitinib, and tucatinib). When we compared JIMT-1 and L-JIMT-1 sensitivity to three HER2-targeting antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and disitamab vedotin (DV) in vitro, JIMT-1 cells were resistant T-DXd, partially sensitive to T-DM1, and sensitive to DV, while L-JIMT-1 cells were resistant to both T-DM1 and T-DXd, but moderately sensitive to DV. In a mouse model, all three ADCs inhibited the growth of L-JIMT-1 lung metastases compared to a vehicle, but DV and T-DXd more strongly than T-DM1, and DV treatment led to the smallest tumor burden. The L-JIMT breast cancer lung metastasis model developed may be useful in the evaluation of anti-cancer agents for multiresistant HER2-positive advanced breast cancer. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) has a high propensity for lung metastasis, which is the leading cause of OS-related death and treatment failure. Intercellular communication between OS cells and distant lung host cells is required for the successful lung metastasis of OS cells to the lung. Before OS cells infiltrate the lung, in situ OS cells secrete extracellular vesicles (EVs) that act as mediators of cell-to-cell communication. In recent years, EVs have been confirmed to act as bridges and key drivers between in situ tumors and metastatic lesions by regulating the formation of a pre-metastatic niche (PMN), defined as a microenvironment suitable for disseminated tumor cell engraftment and colonization, in distant target organs. This review summarizes the current knowledge about the underlying mechanisms of PMN formation induced by OS-derived EVs and the potential roles of EVs as targets or drug carriers in regulating PMN formation in the lung. We also provide an overview of their potential EV-based therapeutic strategies for hindering PMN formation in the context of OS lung metastasis.

Abstract Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1‐deficient mice are resistant to metastasis and further protected by combined immune‐checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF‐β1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK‐target cell responses, which is dysregulated and hijacked by tumors during metastatic progression.

Abstract Purpose To create radiomics signatures based on habitat to assess the instant response in lung metastases of colorectal cancer (CRC) after radiofrequency ablation (RFA). Methods Between August 2016 and June 2019, we retrospectively included 515 lung metastases in 233 CRC patients who received RFA (412 in the training group and 103 in the test group). Multivariable analysis was performed to identify independent risk factors for developing the clinical model. Tumor and ablation regions of interest (ROI) were split into three spatial habitats through K-means clustering and dilated with 5 mm and 10 mm thicknesses. Radiomics signatures of intratumor, peritumor, and habitat were developed using the features extracted from intraoperative CT data. The performance of these signatures was primarily evaluated using the area under the receiver operating characteristics curve (AUC) via the DeLong test, calibration curves through the Hosmer-Lemeshow test, and decision curve analysis. Results A total of 412 out of 515 metastases (80%) achieved complete response. Four clinical variables (cancer antigen 19–9, simultaneous systemic treatment, site of lung metastases, and electrode type) were utilized to construct the clinical model. The Habitat signature was combined with the Peri-5 signature, which achieved a higher AUC than the Peri-10 signature in the test set (0.825 vs. 0.816). The Habitat+Peri-5 signature notably surpassed the clinical and intratumor radiomics signatures (AUC: 0.870 in the test set; both, p

Abstract Background Lung cancer is a leading cause of cancer-related mortality worldwide, and effective therapies are limited. Lung cancer is a leading cause of cancer-related mortality worldwide with limited effective therapy. Sorafenib is a multi-tyrosine kinase inhibitor frequently used to treat numerous types of malignant tumors. However, it has been demonstrated that sorafenib showed moderate antitumor activity and is associated with several side effects in lung cancer, which restricted its clinical application. This study aimed to examine the antitumor effect of the combination treatment of sorafenib and 5-methoxytryptophan (5-MTP) on cell growth and metastasis of Lewis lung carcinoma (LLC) cells. Method The anticancer effect of the combination treatment of sorafenib and 5-MTP was determined through cytotoxicity assay and colony forming assays. The mechanism was elucidated using flow cytometry and western blotting. Wound healing and Transwell assays were conducted to evaluate the impact of the combination treatment on migration and invasion abilities. An in vivo model was employed to analyze the effect of the combination treatment on the tumorigenic ability of LLC cells. Result Our results demonstrated that the sorafenib and 5-MTP combination synergistically reduced viability and proliferation compared to sorafenib or 5-MTP treatment alone. Reduction of cyclin D1 expression was observed in the sorafenib alone or combination treatments, leading to cell cycle arrest. Furthermore, the sorafenib-5-MTP combination significantly increased the inhibitory effect on migration and invasion of LLC cells compared to the single treatments. The combination also significantly downregulated vimentin and MMP9 levels, contributing to the inhibition of metastasis. The reduction of phosphorylated Akt and STAT3 expression may further contribute to the inhibitory effect on proliferation and metastasis. In vivo, the sorafenib-5-MTP combination further reduced tumor growth and metastasis compared to the treatment of sorafenib alone. Conclusions In conclusion, our data indicate that 5-MTP sensitizes the antitumor activity of sorafenib in LLC cells in vitro and in vivo, suggesting that sorafenib-5-MTP has the potential to serve as a therapeutic option for patients with lung cancer.

In papillary thyroid carcinoma (PTC) patients with mediastinal lymph nodes (LN) and lung metastases, adding preoperative computed tomography (CT) to ultrasound is useful for planning surgery. We identified risk factors (RFs) for mediastinal lymph node metastasis (MLNM) and lung metastasis in PTC patients. Frequencies of MLNM and lung metastases were compared in 478 patients. Relative risk (RR) was calculated based on RFs. MLNM and lung metastases were detected in 1.2% and 3.3% of patients, respectively. cT3-4, cN1, central LN metastasis, and lateral LN metastasis were RFs for MLNM in all patients (p < 0.05, p < 0.05, p < 0.05, p < 0.01) and older patients (age: ≥55 years) (p < 0.01, p < 0.05, p < 0.05, p < 0.05). cT3-4, cN1, gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs for lung metastasis in all patients (p < 0.01, p < 0.05, p < 0.01, p < 0.01, p < 0.01, respectively). cN1 and gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs in older patients (p < 0.01, p < 0.01, p < 0.05, p < 0.01), while lateral LN metastasis was an RF for lung metastasis in those of

A 50-year-old woman was diagnosed with iron deficiency anemia on general medical examination. Further, contrast-enhanced abdominal CT and magnetic resonance imaging revealed a large hypervascular mass with internal degeneration and necrosis in the retroperitoneal space. She was referred to our hospital for further evaluation and treatment. Because the paraganglioma was most likely as the imaging diagnosis, 123I-MIBG scintigraphy was performed. It revealed the marked abnormal accumulation in the retroperitoneal lesion indicating the paraganglioma and no other abnormal accumulation was noted. Several plasma catecholamines and their urinary metabolites were normal. On the subsequent 18F-FDG PET/CT, high FDG uptake was found in the retroperitoneal lesion (SUVmax=38). FDG uptake was also found in a small nodule at the base of the lower lobe of the right lung (SUVmax= 9.8). Contrast-enhanced imaging revealed a hypervascular nodule at the base of the right lung, suggesting pulmonary metastasis of a paraganglioma. The abdominal lesion and right lung nodule were excised, and retroperitoneal paraganglioma and pulmonary metastasis were diagnosed based on the pathology findings. In this case, 18F-FDG PET/CT was useful in the search for paraganglioma metastasis. We report a relationship between 123I-MIBG accumulation and 18F-FDG uptake in paraganglioma and review the relevant literature.

Abstract Background Risk stratification and personalized care are crucial in managing osteosarcoma due to its complexity and heterogeneity. However, current prognostic prediction using clinical variables has limited accuracy. Thus, this study aimed to explore potential molecular biomarkers to improve prognostic assessment. Methods High-throughput inhibitor screening of 150 compounds with broad targeting properties was performed and indicated a direction towards super-enhancers (SEs). Bulk RNA-seq, scRNA-seq, and immunohistochemistry (IHC) were used to investigate SE-associated gene expression profiles in osteosarcoma cells and patient tissue specimens. Data of 212 osteosarcoma patients who received standard treatment were collected and randomized into training and validation groups for retrospective analysis. Prognostic signatures and nomograms for overall survival (OS) and lung metastasis-free survival (LMFS) were developed using Cox regression analyses. The discriminatory power, calibration, and clinical value of nomograms were evaluated. Results High-throughput inhibitor screening showed that SEs significantly contribute to the oncogenic transcriptional output in osteosarcoma. Based on this finding, focus was given to 10 SE-associated genes with distinct characteristics and potential oncogenic function. With multi-omics approaches, the hyperexpression of these genes was observed in tumor cell subclusters of patient specimens, which were consistently correlated with poor outcomes and rapid metastasis, and the majority of these identified SE-associated genes were confirmed as independent risk factors for poor outcomes. Two molecular signatures were then developed to predict survival and occurrence of lung metastasis: the SE-derived OS-signature (comprising LACTB, CEP55, SRSF3, TCF7L2, and FOXP1) and the SE-derived LMFS-signature (comprising SRSF3, TCF7L2, FOXP1, and APOLD1). Both signatures significantly improved prognostic accuracy beyond conventional clinical factors. Conclusions Oncogenic transcription driven by SEs exhibit strong associations with osteosarcoma outcomes. The SE-derived signatures developed in this study hold promise as prognostic biomarkers for predicting OS and LMFS in patients undergoing standard treatments. Integrative prognostic models that combine conventional clinical factors with these SE-derived signatures demonstrate substantially improved accuracy, and have the potential to facilitate patient counseling and individualized management.

Objective: To establish a mouse model of breast cancer lung metastasis with miR-155 knockout (miR155-/-) mice, and to compare the difference of peripheral blood immune cell typing between miR155-/- mice and C57BL/6J wide-type (WT) mice. Methods: Bioinformatics analysis was used to explore the expression level of miR-155 in breast cancer tissues and peripheral serum, and its relationship with prognosis. Mouse model of lung metastasis of breast cancer was established by tail vein injection; peripheral blood was collected for flow cytometry, and the immune cell typing was analyzed; the lung tissues were collected for immunohisto-chemical detection to observe the tumor metastasis. Results: Percentage of T lymphocytes and monocytes in peripheral blood of miR155-/- mice was significantly decreased compared with WT mice (P<0.05), percentage of myeloid inhibitory cells (MDSCs) was increased significantly (P<0.05), in which the proportion of monocyte subsets (M-MDSC) was significantly decreased (P<0.05), while the proportion of granulocyte subsets (G-MDSC) was significantly increased (P<0.05). In lung metastasis model of breast cancer, percentage of T lymphocytes in peripheral blood of miR155-/- mice was significantly higher compared with WT mice, while percentage of NK cells was decreased significantly (P<0.05), percentage of neutrophil was significantly decreased (P<0.001), proportion of Th cells in T lymphocytes was significantly decreased (P<0.05), proportion of M-MDSCs was significantly decreased (P< 0.01), while proportion of G-MDSCs was significantly increased (P<0.01). Conclusion: Deletion of miR-155 gene leads to significant differences in peripheral immune cell typing, making mice more susceptible to lung metastasis of breast cancer. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop and evaluate the efficacy of a nomogram for predicting lung metastasis in pediatric differentiated thyroid cancer. The SEER database was utilized to collect a dataset consisting of 1,590 patients who were diagnosed between January 2000 and December 2019. This dataset was subsequently utilized for the purpose of constructing a predictive model. The model was constructed utilizing a multivariate logistic regression analysis, incorporating a combination of least absolute shrinkage feature selection and selection operator regression models. The differentiation and calibration of the model were assessed using the C-index, calibration plot, and ROC curve analysis, respectively. Internal validation was performed using a bootstrap validation technique. The results of the study revealed that the nomogram incorporated several predictive variables, namely age, T staging, and positive nodes. The C-index had an excellent calibration value of 0.911 (95 % confidence interval: 0.876–0.946), and a notable C-index value of 0.884 was achieved during interval validation. The area under the ROC curve was determined to be 0.890, indicating its practicality and usefulness in this context. This study has successfully developed a novel nomogram for predicting lung metastasis in children and adolescent patients diagnosed with thyroid cancer. Clinical decision-making can be enhanced by assessing clinicopathological variables that have a significant predictive value for the probability of lung metastasis in this particular population. [ABSTRACT FROM AUTHOR]